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Abstract Background Adipsin (complement factor D, CFD), as the first described adipokine, is well-known for its regulatory effects in diabetic cardiovascular complications. However, its role in diabetic hind-limb ischemia was not clarified. This study aimed to evaluate the possible therapeutic effect of Adipsin in hind-limb ischemia in type 2 diabetic mice and to elucidate the molecular mechanisms involved. Methods A high-fat diet and streptozotocin (HFD/STZ)-induced diabetic mouse model, and a transgenic mouse model with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg) were employed. Hindlimb ischemia was established by femoral artery ligation, and blood flow recovery was monitored using Laser Doppler perfusion imaging. Molecular mechanisms underlying Adipsin-potentiated angiogenesis were examined using RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses. Results Adipsin expression was upregulated in non-diabetic mice following HLI, while suppressed in diabetic mice, indicating its potential role in ischemic recovery which is impaired in diabetes. Adipsin-Tg mice exhibited significantly improved blood flow recovery, increased capillary density, and enhanced muscle regeneration in comparison with non-transgenic (NTg) diabetic mice. Adipsin facilitated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) under hyperglycemic and hypoxic conditions. Additionally, it enhanced phosphorylation of AKT, ERK, and eNOS pathways both in vivo and in vitro. RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses identified that Adipsin promoted angiogenesis by interacting with SERBP1, which disrupted the binding of SERBP1 to SERPINE1 mRNA, resulting in reduced SERPINE1 expression and the subsequent activation of the VEGFR2 signaling cascade. Conclusions Adipsin promotes angiogenesis and facilitates blood perfusion recovery in diabetic mice with HLI by downregulating SERPINE1 through interaction with SERBP1. These findings elucidate a novel therapeutic potential for Adipsin in the management of PAD in diabetic patients, highlighting its role in enhancing angiogenesis and tissue repair.

Abstract The bidirectional relationship between sleep duration and pain during the COVID-19 pandemic remains poorly understood. This study explores these interactions and the mediating roles of depression and chronic diseases using data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. A cross-sectional analysis was conducted on 15,979 participants aged 45 and older. Sleep duration was self-reported, and pain was assessed using validated anatomical charts. Depression symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and chronic diseases were self-reported. Personal activity during the pandemic was measured using the Personal Activity Score during COVID-19 (PAS-COVID-19). The results showed a significant association between deviations from optimal sleep duration and increased pain frequency. Participants with both shorter and longer sleep durations reported higher pain levels, with depression and chronic diseases acting as significant mediators. However, personal activity did not significantly mediate the association between sleep duration and pain. These findings underscore the complex interplay among sleep duration, pain, depression, and chronic diseases during the COVID-19 pandemic, emphasizing the importance of integrated interventions to manage these interconnected health issues.

Abstract The efficacy of diversion ileostomy followed by radical surgery for locally advanced upper-half rectal cancer remains uncertain. This study seeks to compare the effectiveness of treatment with and without diversion ileostomy in preventing anastomotic leakage (AL) and to identify a subset who may benefit from diversion ileostomy after AL occurs in Chinese patients with stage II and III upper-half rectal cancer. A retrospective study enrolled a total of 809 patients with locally advanced upper-half rectal cancer between 2017 and 2021, with 27.6% (n = 223) treated with diversion ileostomy and 72.4% (n = 586) treated without diversion ileostomy. The Diversion(+) group (n = 172) and Diversion(−) group (n = 172) were compared for perioperative outcomes through 1:1 propensity score matching (PSM). The selection of variables for multivariable logistic regression was determined through bivariate logistic regression analysis. Additionally, optimal cutoff values for risk factors were identified using ROC curve analysis. Within the entire cohort, patients in the Diversion(+) group exhibited a lower distance from the anal verge (DAV) and higher rates of chemoradiotherapy (CRT), diabetes, cN2 stage, mrCRM positivity, EMVI positivity, and CEA elevation compared to those in the Diversion(−) group. Following PSM, a satisfactory balance of baseline variables was achieved between the two groups. There were no statistically significant differences in AL rates (7.0% vs. 5.8%, p = 0.659) or AL grade distribution (Grade A: 0.6% vs. 0%, Grade B: 5.2% vs. 4.1%, Grade C: 1.2% vs. 1.7%, p = 0.691) between the two groups. However, the Diversion(+) group demonstrated a higher incidence of postoperative complications (30.8% vs. 17.4%, p = 0.004), Clavien‒Dindo III–IV complications (2.9% vs. 2.3%, p = 0.013), particularly wound infections (8.1% vs. 1.2%, p = 0.002), and early postoperative inflammatory small bowel obstruction (EPISBO) (8.7% vs. 1.2%, p = 0.001) compared to the Diversion(−) group. Results from multivariate logistic regression analysis revealed that male gender (OR = 2.354, p = 0.014) was the only independent risk factor associated with AL, while the presence of diversion ileostomy (with vs. without, OR = 1.144, p = 0.686) did not show significant associations. In patients with AL, the onset of the AL was observed to occur later in the Diversion(+) group compared to the Diversion(−) group (7.0 ± 3.3 vs. 3.4 ± 1.4 days, p

Abstract Sponsored search plays a major role in the revenue contribution of e-commerce platforms. Advertising systems are designed to maximize platform revenue, but other goals also need to be considered, such as user experience, advertiser utility, and how to achieve the long-term revenue goal. A key component of a sponsored search system is online allocation, which makes real-time decisions to match users’ search requests with relevant ad campaigns to maximize platform revenue within constraints such as campaign budgets. Although much progress has been made, most of the research work on allocation problem has focused on satisfying guaranteed deals for display ads, and those challenges for allocation problems in sponsored search are not properly addressed. In this paper, we develop a framework to solve the large-scale sponsored search ad allocation problem, consisting of two main parts. One is an optimization problem solved offline by a parameter-server based architecture, and the other is an online strategy to alleviate the conflict with the auction mechanism during online service. Comprehensive offline evaluation on real production data and online A/B testing on real production system have been made. The experimental results demonstrate that through better allocating user queries to appropriate ads, the proposed model can significantly increase the platform’s revenue without sacrificing advertisers’ ROI.

Background:. Chemotherapy stands as a recommended approach for all stages of pancreatic cancer. However, its efficacy stratification remains obscure. Genomic sequencing is extensively applied across diverse diseases. This study aims to explore the potential genomic markers in relation to the decision-making of chemotherapy. Methods:. A total of 140 patients with pancreatic cancer were categorized into chemotherapy-first group and adjuvant chemotherapy group. The genomic alterations were detected from the next-generation sequencing using surgical or fine-needle-biopsy specimens. Chemotherapy response was defined according to objective response based on the RECIST criteria (version 1.1). Results:. In the chemotherapy-first group, the patients who harbored higher tumor mutation burden (TMB) levels had significant shorter progress-free survival (PFS) than that with low TMB levels (hazard ratio [HR] = 30.362, P = .002). No independent risk factors were found to be correlated with chemoresistance in patients receiving chemotherapy at first (all P > .05). In the adjuvant chemotherapy group, the increased carbohydrate antigen 125 (CA125) level of more than 35 U/mL potentially elucidated a shorter period of DFS (HR = 3.695, P = .020). Conclusion:. Our study indicated that a high level of TMB may predict earlier tumor progression in pancreatic cancer patients received chemotherapy at first. The elevation of CA125 presents itself as a predictive indicator for postoperative chemotherapy patients’ tumor recurrence, whereas gene mutations remain unrelated to this phenomenon.

Abstract The unmanned aerial vehicle (UAV) city patrol is of great significance in ensuring the safety of residents’ lives and properties, as well as maintaining the normal operation of the city. However, the detection of UAV images faces challenges such as numerous small-scale objects, complex backgrounds, and high requirements for detection speed. In response to these issues, we introduce a Real-time Small Object Detection network in UAV-vision (RTS-Net), tailored for UAV patrols. Initially, we introduce a multiscale feature fusion module (MFFM) designed to augment the expressiveness of features across scales, thereby enhancing the detection of smaller objects. Subsequently, leveraging attention mechanisms, we present the coordinated attention detection module (CADM), which bolsters the detection model’s ability to accurately segregate objects from the background in expansive, complex scenarios. Lastly, a lightweight real-time feature extraction module (RFEM) is crafted to diminish model computational complexity and boost inference speed. On the UAV road patrol image dataset we constructed, our proposed method attains a detection accuracy of 89.9 $$\%$$ % mAP, breaking previous records. It surpasses all prevailing detection methods, particularly for small-scale objects. Simultaneously, it achieves an inference speed of 163.9 FPS. The experimental results show that RTS-Net can satisfy the accurate and efficient detection of ground objects by various different UAV platforms in different complex scenarios.

Abstract Background Under the background of the increasing trend of population aging, the health and quality of life of older adults have become the focus of social concern. As an important part of older adults’ daily life, the design and configuration of the built environment may positively or negatively affect older adults’ health behaviors. Therefore, this study aims to explore the relationship between older adults’ perceived built environments and health behaviors, which is the association between perceived built environments and older adults’ physical activity (PA) and social interactions. This is important for optimizing the community built environment and improving the quality of life of older adults. Methods In this study, a questionnaire was surveyed on 916 Chinese older adults aged 60 and above. The questionnaire was used to collect demographic information and social interaction from the participants, and the Physical Activity Neighborhood Environment Scale (PANES) and the Physical Activity Scale for the Elderly (PASE) were used to assess older adults’ subjective perceptions of the built environment in their neighborhoods and their levels of PA, respectively. In data analysis, ANOVA and chi-square tests were used to compare the significance of differences between groups, and multiple linear regression model were used to estimate the association between older adults’ perceived characteristics of the built environment and their PA and social interaction. Results After controlling for confounders such as gender, age, BMI, and education level, the multiple linear regression model showed that perceived destination accessibility, neighborhood infrastructure, aesthetic qualities, and neighborhood environment indices were significantly correlated with PA (β = 0.083 ~ 0.095, P

In recent years, studies on the degradation of emerging organic contaminants by sulfate radical (SO4−·) based advanced oxidation processes (SR-AOPs) have triggered increasing attention. Metal-loaded biochar (Me-BC) can effectively prevent the agglomeration and leaching of transition metals, and its good physicochemical properties and abundant active sites induce outstanding in activating persulfate (PS) for pollutant degradation, which is of great significance in the field of advanced oxidation. In this paper, we reviewed the preparation method and stability of Me-BC, the effect of metal loading on the physicochemical properties of biochar, the pathways of pollutant degradation by Me-BC-activated PS (including free radical pathways: SO4−·, hydroxyl radical (·OH), superoxide radicals (O2–·); non-free radical pathways: singlet oxygen (1O2), direct electron transfer), and discussed the activation of different active sites (including metal ions, persistent free radicals, oxygen-containing functional groups, defective structures, etc.) in the SR-AOPs system. Finally, the prospect was presented for the current research progress of Me-BC in SR-AOPs technology. HIGHLIGHTS The characteristics of the preparation methods for metal-loaded biochar are summarized.; The effects of metals on the physicochemical properties of biochar are discussed.; The free radical and non-radical pathways for activation of persulfate by metal-loaded biochar are discussed.; The potential mechanisms of metal-loaded biochar catalysts are discussed.; The future blueprint for metal-loaded is described.;

Single-atom catalysts (SACs) exhibit outstanding catalytic activity due to their highly dispersed metal centers. Activating persulfates (PS) with SACs can generate various reactive oxygen species (ROS) to efficiently degrade emerging organic contaminants (EOCs) in aqueous environments, offering unique advantages such as high reaction rates and excellent stability. This technique has been extensively researched and holds enormous potential applications. In this paper, we comprehensively elaborated on the synthesis methods of SACs and their limitations, and factors influencing the catalytic performance of SACs, including metal center characteristics, coordination environment, and types of substrates. We also analyzed practical considerations for application. Subsequently, we discussed the mechanism of SACs activating PS for EOCs degradation, encompassing adsorption processes, radical pathways, and non-radical pathways. Finally, we provide prospects and outline our vision for future research, aiming to guide advancements in applying this technique. HIGHLIGHTS Summarized the synthesis methods of single-atom catalysts and limitations.; Discussed the factors influencing the performance of single-atom catalysts and practical factors.; Elucidated the mechanism of SACs activating PS for EOCs degradation and prospects for the future.;

Abstract Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study in hens with distinct egg production, to detect the hub candidate genes and construct hub molecular networks contributing to egg-laying phenotypic differences. We identifiy three hub candidate genes as egg-laying facilitators: TFPI2, which promotes the GnRH secretion in hypothalamic neuron cells; CAMK2D, which promotes the FSHβ and LHβ secretion in pituitary cells; and OSTN, which promotes granulosa cell proliferation and the synthesis of sex steroid hormones. We reveal key endocrine factors involving egg production by inter-tissue crosstalk analysis, and demonstrate that both a hepatokine, APOA4, and an adipokine, ANGPTL2, could increase egg production by inter-tissue communication with hypothalamic-pituitary-ovarian axis. Together, These results reveal the molecular mechanisms of multi-tissue coordinative regulation of chicken egg-laying performance and provide key insights to avian reproductive regulation.

Background With the gradual deepening of the comprehensive reform of community health services, the prevention and control of single diseases for the entire population in the community is also constantly being optimized, However, there is still a lack of appropriate evaluation methods in the community to reflect its prevention and control effectiveness evaluation. Objective By analyzing and exploring the cost effect of the existing whole-population prevention and control measures of osteoporosis in Fenglin community, from 2016 to 2022, this paper answers the initial results and possible problems of the whole-population prevention and control of single disease in the community. Methods This study conducted a cost-effectiveness analysis on 4 293 community residents who received osteoporosis prevention and treatment in Fenglin community from 2016 to 2022. Divide the research object into three states based on bone density values: healthy, low bone mass, and osteoporosis, and construct a Markov model to analyze the influencing factors of different state transitions. And based on the predicted values of the Markov model combined with quality adjusted life years (QALY) , the increment of quality adjusted life years (QALY) is calculated. All costs invested in prevention and control work from 2016 to 2022 are counted, and the effectiveness of prevention and control is evaluated by the cost/quality adjusted life year increment ratio. Quality adjusted life years (QALY) are obtained by calculating the health utility value and expected life determined through literature search. Results The total cost of osteoporosis prevention and treatment in Fenglin community was 33 814 102.15 yuan. The total quality-adjusted life years of 4 293 community osteoporosis prevention and treatment population were 77 098.288 9 at the first diagnosis, the average per capita was 17.959, and the standard deviation was 9.34. At the second diagnosis, the total quality-adjusted life years were 79 616.936 1, the mean per capita was 18.546, the standard deviation was 9.342, and the difference between the two diagnoses was 2 518.647 2. The incremental cost-effectiveness ratio (ICER) is 2 132.907 0 yuan /QALY, and the incremental cost-effectiveness ratio (ICER) is less than 1 times (66 965.10 yuan) per capita GDP, indicating that the intervention scheme is fully cost-effective. Conclusion This study combined Markov model and quality-adjusted life years (QALY) to make a preliminary evaluation of the prevention and treatment effect of osteoporosis in Fenglin community. The results showed that the intervention program of osteoporosis prevention and treatment in Fenglin community was worth investing, and provided a certain basis for the accurate prevention and treatment decision of osteoporosis in the future.

Background: Both teacher support and math attitudes have been identified as associated with math anxiety in primary school children. However, little is known about how they are interrelated longitudinally. Aims: The study was designed to examine the associations among perceived teacher support, math attitudes, and math anxiety in Chinese primary school students. Sample: The sample included 1802 students (56.16% boys) initially in the third and fourth grades in two public schools in China. Methods: A three-year cross-lagged panel design was conducted to examine the associations among perceived teacher support, math attitudes, and math anxiety. Moreover, a multigroup analysis was used to examine whether the associations varied by gender. Results: There were reciprocal associations over time between math attitudes and math anxiety. Meanwhile, both math attitudes and math anxiety significantly predicted perceived teacher support one year later, but not vice versa. Further, the association between T1 math anxiety and T3 perceived teacher support was mediated by T2 math attitudes; the association between T1 math attitudes and T3 perceived teacher support, on the other hand, was mediated by T2 math anxiety. Moreover, there were no significant gender differences in these associations. Conclusions: Math anxiety and math attitudes objectively affected each other, and both of them significantly predicted later perceived teacher support, but not vice versa. This study demonstrates that children are not merely passive recipients of environmental influences and offers theoretical guidance for intervention practices that aim to reduce the risk of math anxiety.

In this study, five hydrochlorides are used as additives to slow the crystallization rate between SnI2 and AI (A+=MA+, FA+, Cs+) to prepare high-quality perovskite films. This study on film morphology, crystallization and non-radiative recombination demonstrates the effects of organic amine cations with different chain lengths on the quality of thin films. A flexible solar cell device with a lead-free perovskite film doped with PACl is also obtained achieving an efficiency of 5.52 %.

In this study, we prepared a novel three-dimensional boron-doped diamond (BDD) electrode. Subsequently, we systematically conducted an electrochemical oxidation reaction on sulfamethoxazole (SMX) using a BDD anode and a platinum plate (Pt) cathode. The effects of initial concentration, current density, initial pH, and carrier electrolyte on SMX degradation were investigated. The SMX was completely removed after 4 h of electrolysis at a current density of 30 mA/cm2, 0.1 mol sodium sulphate as the supporting electrolyte, and a pH of 7. Additionally, the COD removal rate was 65.6 %, while the energy consumption was 40.1 %. Compared with two-dimensional BDD electrode degradation, the energy saving was 54 %. Density functional theory (DFT) and high-performance liquid chromatography (HPLC) were used to analyse the SMX degradation mechanism. Three possible degradation pathways were proposed: ·OH substitution of the amino group in the aromatic ring, oxidation of the amino group to nitrogen dioxide, and addition of ·OH to the isoxazole ring. The active sites detected in the reaction corresponded closely with the calculated results using DFT. Moreover, ECOSAR toxicity analysis was applied to evaluate the toxicity of the intermediates produced during electrolysis. We discovered that the toxicity of SMX and its intermediates decreased significantly during electrolysis.

Background Previous studies have revealed an underlying connection between abnormal lipid metabolism and albuminuria. We aim to investigate the causal relationship between lipid metabolism disorders and the risk of albuminuria from both a population and genetic perspective.Methods A cross-sectional study was conducted by using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Multivariable-adjusted logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) were employed statistically. Mendelian randomization (MR) analysis was performed to validate the causal relationship between exposure and outcome to mitigate confounding factors and reverse causation interference.Results After adjusting for confounders, HDL levels (1.03-2.07 nmol/L) were associated with a reduced risk of albuminuria. In contrast, elevated cholesterol levels (>6.2 nmol/L) and triglyceride levels (>2.3 nmol/L) were associated with an increased risk of albuminuria. Serum triglyceride concentration emerged as a potential risk factor for albuminuria. In MR analysis, a reduced risk of albuminuria was associated with serum total HDL level (IVW: OR = 0.91, 95% CI = 0.86-0.97, p = 0.002). In contrast, cholesterol esters in medium VLDL (IVW: OR = 1.05, 95% CI = 1.00-1.10, p = 0.032), chylomicrons and extremely large VLDL (IVW: OR = 1.08, 95% CI = 1.03-1.14, p = 0.003), and triglycerides (IVW: OR = 1.14, 95% CI = 1.09-1.19, p

Objective To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids.Materials and methods A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model.Results Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index −0.2) +1×(abdominal wall thickness −5).Conclusions This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

Objective To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids.Materials and methods We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors.Results The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy.Conclusions Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.

Objectives To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence.Materials and methods Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence.Results The median number of fibroids per patient was 3 (interquartile range: 3–4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred.Conclusions USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Objective Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.Methods We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.Results We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62–5.42) for ibuprofen and 2.61 (1.53–4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57–4.57). Global heterogeneity I2 between the studies was low.Conclusions Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

Environmental assessments are critical for ensuring the sustainable development of human civilization. The integration of artificial intelligence (AI) in these assessments has shown great promise, yet the ''black box'' nature of AI models often undermines trust due to the lack of transparency in their decision-making processes, even when these models demonstrate high accuracy. To address this challenge, we evaluated the performance of a transformer model against other AI approaches, utilizing extensive multivariate and spatiotemporal environmental datasets encompassing both natural and anthropogenic indicators. We further explored the application of saliency maps as a novel explainability tool in multi-source AI-driven environmental assessments, enabling the identification of individual indicators' contributions to the model's predictions. We find that the transformer model outperforms others, achieving an accuracy of about 98% and an area under the receiver operating characteristic curve (AUC) of 0.891. Regionally, the environmental assessment values are predominantly classified as level II or III in the central and southwestern study areas, level IV in the northern region, and level V in the western region. Through explainability analysis, we identify that water hardness, total dissolved solids, and arsenic concentrations are the most influential indicators in the model. Our AI-driven environmental assessment model is accurate and explainable, offering actionable insights for targeted environmental management. Furthermore, this study advances the application of AI in environmental science by presenting a robust, explainable model that bridges the gap between machine learning and environmental governance, enhancing both understanding and trust in AI-assisted environmental assessments.

Negatively thermo-responsive 2D membranes, which mimic the stomatal opening/closing of plants, have drawn substantial interest for tunable molecular separation processes. However, these membranes are still restricted significantly on account of low water permeability and poor dynamic tunability of 2D nanochannels under temperature stimulation. Here, we present a biomimetic negatively thermo-responsive MXene membrane by covalently grafting poly (N-isopropylacrylamide) (PNIPAm) onto MXene nanosheets. The uniformly grafted PNIPAm polymer chains can enlarge the interlayer spacings for increasing water permeability while also allowing more tunability of 2D nanochannels for enhancing the capability of gradually separating multiple molecules of different sizes. As expected, the constructed membrane exhibits ultrahigh water permeance of 95.6 L m−2 h−1 bar−1 at 25 °C, which is eight-fold higher than the state-of-the-art negatively thermo-responsive 2D membranes. Moreover, the highly temperature-tunable 2D nanochannels enable the constructed membrane to perform excellent graded molecular sieving for dye- and antibiotic-based ternary mixtures. This strategy provides new perspectives in engineering smart 2D membrane and expands the scope of temperature-responsive membranes, showing promising applications in micro/nanofluidics and molecular separation.

Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners. Methods Twenty patients receiving Invisalign were recruited. The relative intrusion values in the ClinCheck software were recorded as the preset intrusion. The achieved intrusion values were measured through the digital model superimposition. Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values, and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency. Results For the mandibular anterior teeth, the mean intrusion efficiency was 62.2%, with the highest in the central incisors and the lowest in the canines. The intrusion amounts, incisors labial inclinations, and canine attachment types affected the intrusion efficiency. The differences between the preset and achieved values were significant, and the linear relationship existed. The formula of the intrusion overcorrection for the mandibular anterior teeth is “Z=(W-0.110)/0.533-W”. Z represents the overcorrection and W represents the ideal intrusion. Conclusion The preset intrusion values in the treatment protocol could not be fully achieved. Moreover, correction should be designed in cases of mandibular canine intrusion, large amountsof intrusion, orlingually inclined incisors. Compared to the optimized attachments, the vertical rectangular attachments on the mandibular canines could improve the efficiency.

Agricultural non-point source pollution (ANP) had become an important source of water pollution, which seriously restricted the coordinated development of Beijing, Tianjin and Hebei. As the primary agricultural production base in the region of Beijing-Tianjin-Hebei, Hebei had serious ANP. In order to clarify the current status of ANP in Hebei and figure out the main pollution source and areas, ANP load of Hebei from 2000 to 2021 were evaluated by the export coefficient modeling (ECM) and spatial-temporal characteristics were carried out using geographic information system (GIS). In addition, ANP severity and emission characteristics of Hebei in 2021 were evaluated. The results showed that the environmental impact of ANP in southwest area was obviously more serious than that in northeast area of Hebei. Especially, ANP emissions in Hebei showed significant decreasing inflection points in 2007 and 2017, respectively, reaching a minimum by 2021. The TN and TP emissions of ANP in Hebei were 315,026.1 t and 50,323.76 t in 2021, respectively. The contribution of agricultural land, livestock and poultry breeding and rural life to TN and TP emissions were 37%, 34%, 29% and 20%, 61% and 18%, respectively. The ANP pollution mainly came from livestock and poultry breeding in Hebei Province. Based on cluster analysis, cities in Hebei were divided into four types, and the control strategies for ANP environment management were put forward.

Abstract Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE); even combining IR with immune checkpoint inhibitors has shown only anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug, disulfiram (DSF), complexed with copper (DSF/Cu) to induce tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anticancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs relative to spontaneous lung metastasis. In addition, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anticancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral (i.t.) injection of DSF/Cu and IR(12Gy) demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8+ and CD4+ cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, dendritic cells (DC), and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8+ and CD4+ cells abolished the vaccine’s anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anticancer immune response that results in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Objective: To explore the protective effect and underlying mechanism of Rosa roxburghii Tratt polysaccharides on isoproterenol (ISO)-induced myocardial ischemia (MI) in mice. Methods: Forty male C57BL/6 mice were equally and randomly divided into five groups: control, model, propranolol (30 mg/kg), low- and high-dose R. roxburghii Tratt polysaccharides (50 and 100 mg/kg). Mice were pretreated with R. roxburghii Tratt polysaccharides for seven days followed by intraperitoneal injection of isoprenaline (ISO, 10 mL/kg) or physiological saline for seven days. Electrocardiograms were recorded 1 h after the last injection. The mice were anesthetized and hearts were excised to calculate cardiac index. Hematoxylin-eosin (HE) staining was used to evaluate myocardial pathological changes. The area of myocardial infarction was detected by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Serum lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by biochemical kits. The protein expression of NADPH oxidase 2 (NOX2), B-cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), caspase 3, nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH-related protein 1 (Keap1) and heme oxygenase 1 (HO-1) in myocardial tissues were detected by Western blot. Results: Compared with the control group, heart coefficient was significantly increased in the model group and the ST segment of electrocardiogram was significantly elevated. Significantly pathological changes and increased myocardial infarction were found in the myocardial tissue of mice in the model group. Serum MDA and LDH levels were increased (P < 0.001) and SOD activity was inhibited in the model group (P < 0.05). The protein expressions of Nrf2, HO-1 and Bcl2 were significantly down-regulated (P < 0.05 or P < 0.01), while those of Keap1, NOX2, Bax and caspase 3 were significantly up-regulated in the model mice (P < 0.05 or P < 0.01). The ST segment of electrocardiogram was lowered, and myocardial pathological changes were restored in the polysaccharide treatment group compared with the model group. In addition, serum MDA and LDH levels were significantly decreased (P < 0.001) and SOD activity was significantly increased (P < 0.01 or P < 0.001). The protein expressions of Nrf2, HO-1 and Bcl2 were significantly up-regulated (P < 0.05 or P < 0.01), while those of Keap1, NOX2, Bax and caspase 3 were significantly down-regulated (P < 0.05, P < 0.01 or P < 0.001). Conclusion: R. roxburghii Tratt polysaccharides ameliorate ISO-induced myocardial ischemia though reducing oxidative stress, regulating caspase-3, Bax and Bcl2 protein expressions and suppressing myocardial cell apoptosis via the Keap1-Nrf2 signaling pathway.

Abstract Elucidating the expression of microRNAs in developing single cells is critical for functional discovery. Here, we construct scCAMERA (single-cell cartography of microRNA expression based on reporter assay), utilizing promoter-driven fluorescent reporters in conjunction with imaging and lineage tracing. The cartography delineates the transcriptional activity of 54 conserved microRNAs in lineage-resolved single cells throughout C. elegans embryogenesis. The combinatorial expression of microRNAs partitions cells into fine clusters reflecting their function and anatomy. Notably, the expression of individual microRNAs exhibits high cell specificity and divergence among family members. Guided by cellular expression patterns, we identify developmental functions of specific microRNAs, including miR-1 in pharynx development and physiology, miR-232 in excretory canal morphogenesis by repressing NHR-25/NR5A, and a functional synergy between miR-232 and miR-234 in canal development, demonstrating the broad utility of scCAMERA. Furthermore, integrative analysis reveals that tissue-specific fate determinants activate microRNAs to repress protein production from leaky transcripts associated with alternative, especially neuronal, fates, thereby enhancing the fidelity of developmental fate differentiation. Collectively, our study offers rich opportunities for multidimensional expression-informed analysis of microRNA biology in metazoans.

Abstract Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system and leads to incomplete or complete loss of the body’s autonomous motor and sensory functions, seriously endangering human health. Recently, exosomes have been proposed as important substances in cell-to-cell interactions. Mesenchymal stem cell (MSC)-derived exosomes exert good therapeutic effects and play a crucial role in neurological damage repair. However, the detailed mechanisms underlying their effects remain unknown. Herein, we found that compared to SCI rats, those subjected to umbilical cord MSC (UC-MSC)-derived exosomes injection showed an improved motor ability. Nevertheless, the transcriptome of BV2 microglia in different treatment groups indicated that the action pathway of exosomes might be the NF-κB/MAPK pathway. Additionally, exosomes from UC-MSCs could inhibit P38, JNK, ERK, and P65 phosphorylation in BV2 microglia and SCI rat tissues. Moreover, exosomes could inhibit apoptosis and inflammatory reaction and reactive oxygen species (ROS) production of BV2 microglia in vitro and in vivo. In conclusion, UC-MSCs-derived exosomes might protect SCI in rats by inhibiting inflammatory response via the NF-κB/MAPK signaling pathway, representing novel treatment targets or approaches for SCI.

Fe–20Mn–9Al-1.5C–2Ni–3Cr low-density steel is subjected to multi-stage heat treatment (MHT) to improve the toughness while maintaining high strength and ductility. The mechanical properties and fracture behavior of MHT steel are compared with those resulting from single-stage heat treatment (S1000 and S1050) usnig SEM, EBSD, and TEM microstructural characterization. The grain sizes of S1000, S1050 and MHT are 3.17, 3.84, and 7.31 μm, respectively. The proportion of “special” grain boundaries changes from 71.7 % to 68.3 % and finally to 71.2 % (by length). Simultaneously, dissolution of intergranular Cr7C3 precipitates in S1000. The half-size impact energy of MHT is 88.6 % higher than that of S1000, reaching 55.1 J, and the ultimate tensile strength and total elongation are maintained at approximately 1100 MPa and 50 %, respectively. As demonstrated by quantitative analysis, the yield strength is maintained at 910 MPa due to solution, grain boundary, and precipitation strengthening, whereas the increase in toughness is due to the rise in the crack propagation energy. The increased toughness is derived from the combined effect of reducing the number of intergranular precipitates and a high percentage of “special grain boundaries''.

Abstract Fixed frequency beam-scanning leaky-wave antennas have been a focus of attention for many scholars in recent years, and numerous related results have been obtained. However, these antennas suffer from several issues such as small beam-scanning range, low gain, and unsatisfactory impedance matching. To address these problems, this paper proposes a microstrip line (ML) antenna unit based on liquid crystal (LC) materials etched Complementary Split Ring Resonator (CSRR). In a first-of-its-kind approach, the substrate integrated waveguide (SIW) structure and the ML transmission structure are combined to present the SIW-ML transmission structure. The antenna operates in the Ka-band with excellent resonance characteristics at 34.7 GHz, and the S11 parameters are below − 13 dB in the frequency range of 30–40 GHz, indicating outstanding impedance matching. By arranging 56 antenna units, a periodic leaky-wave antenna is created, enabling fixed-frequency beam-scanning at 34.7 GHz. Experimental results show that the antenna can achieve scanning of angles between − 53° and + 60° with a gain of up to 12.63 dB. Once single-beam scanning is achieved, a method combining LC and discrete amplitude weighting technique, as well as multi-beam theory, is proposed for multi-beam study. Experimental results reveal that the designed 56-unit beam-scanning antenna can effectively realize beam scanning in two directions.

Metalens can achieve arbitrary light modulation by controlling the amplitude, phase, and polarization of the incident waves and have been applied across various fields. This paper presents a color router designed based on metalens, capable of effectively separating spectra from visible light to near-infrared light. Traditional design methods for meta-lenses require extensive simulations, making them time-consuming. In this study, we propose a deep learning network capable of forward prediction across a broad wavelength range, combined with a particle swarm optimization algorithm to design metalens efficiently. The simulation results align closely with theoretical predictions. The designed color router can simultaneously meet the theoretical transmission phase of the target spectra, specifically for red, green, blue, and near-infrared light, and focus them into designated areas. Notably, the optical efficiency of this design reaches 40%, significantly surpassing the efficiency of traditional color filters.

Researching infrared adversarial attacks is crucial for ensuring the safe deployment of security-sensitive systems reliant on infrared object detectors. However, current research on infrared adversarial attacks mainly focuses on pedestrian detection tasks. Due to the complex shape and structure of vehicles and the changing working conditions, adversarial attack in infrared vehicle detection pose challenges like difficult multi-angle attack, poor physical transferability, and weak environmental adaptation. This paper proposed Leaf-like Mask Bar Code (LMBC), a novel adversarial attack method for multi-angle physical black-box attack on infrared detectors. Inspired by natural leaf structures, a mask was designed to restrict the adversarial patch contour. Then, adversarial parameters of the patches (angle, sparsity, and position) were optimized using the Genetic Algorithm with Multi-segment (GAM). Moreover, leaf-like structures in physical adversarial patches were constructed using suitable infrared coating materials. deploying them at multiple angles. Experimental results demonstrated LMBC’s efficacy, paralyzing the infrared vehicle detector with an Average Precision (AP) as low as 33.7% and an average Attack Success Rate (ASR) as high as 92.9% across a distance of 2.4m 4.2 m and angles of 0° 360°. Moreover, LMBC’s adversarial patches transferred to mainstream detectors (e.g., Faster RCNN, Yolov3, etc.) and pedestrian detection tasks.

BackgroundThe novel coronavirus disease 2019 as the most pervasive and consequential pandemic in recent years, has exerted significant impacts on human health, including aspects related to body weight. Objectives: This study aims to assess the influence of the lockdown measures implemented during the COVID-19 pandemic on Chinese college students’ Body Mass Index (BMI) through a three-year cohort study.MethodsWe recruited 6156 college students (n = 4,248, 69% male, and n = 1,908, 31% female, with an average age of 18.68 ± 0.86 yr.) from a University in China to participate in this three-year cohort study. All of the subjects took the same physical fitness tests from 2019 to 2021 (pre-lockdown, during lockdown and post-lockdown). Participants’ height and weight data were objectively measured by Tongfang Health Fitness Testing Products 5000 series. A paired t-test was performed in the analysis.ResultsDuring the lockdown, there is 4.2% increase of BMI among the college student (p

Objectives: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. Methods: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. Results: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P

ObjectivesThe safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy.MethodsThe study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy.ResultsThe successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy.ConclusionCompared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

Background:Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis.Methods:Observational study participant data (≥16 years, n = 23,489) from NHANES 2003–2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode.Results:After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094–0.657, p = 0.142).Conclusion:Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

Ammonia (NH3) is a vital chemical for modern human society. It is conventionally produced by the energy‐ and emission‐intensive Haber–Bosch process. Alternatively, sustainable NH3 production from renewable electricity‐driven electrolyzers has emerged as a promising route. Particularly, NH3 synthesis from nitrate (NO3−), a common pollutant in water and soil, by the nitrate reduction reaction (NO3RR) has drawn wide attention. Among various catalysts demonstrated recently, copper (Cu)‐based catalysts have been recognized as attractive candidates due to their availability, good activity, high NH3 selectivity, and facile reaction kinetics. In this review, the recent progress of Cu‐based NO3RR catalysts from the reaction mechanistic fundamentals to various catalyst design strategies, aiming at providing an on‐time summary, is summarized, and perspectives that can guide the rational and on‐demand design of Cu‐ and other earth‐abundant metal‐based catalysts for selective NO3RR toward sustainable NH3 production are elucidated.

BackgroundCutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson’s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.ObjectiveThis study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.MethodsWe performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.ResultsP-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.ConclusionP-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

In this work, the effects of edible alkali additions on the quality of different frozen grain doughs (wheat, buckwheat, corn, and mung bean) were studied, the frozen doughs were prepared by adding different amounts (0%, 1%, 2%, 3%, 4%, 5%) of edible alkali into raw materials, which were based on 100 g of frozen grain dough, respectively. And the doughs were frozen at −30 ℃ for 8 h and freezing at −18°C for 1 d, then thawed at 25 ℃ for 30 min. The water loss rate, water retention rate, pH, textural properties, water distribution were measured, respectively. And changes in the surface network structure and protein structure of the frozen doughs were observed by scanning electron microscopy (SEM). The results showed that the additions of edible alkali were negatively correlated with the water loss rate of frozen doughs, it could significantly (P

ObjectiveTo explore comorbidity pattern, comorbidity burden and economic burden of chronic diseases among inpatients with Parkinson's disease and Parkinsonism in Chengdu city, Sichuan province for effective treatment and management of the patients with the diseases. MethodsBased on disease codes of International Classification of Diseases 10th Revision, we collected 30 436 hospitalization records of Parkinson's disease patients and 3 749 records of Parkinsonism patients for years of 2013 – 2017 from the Information System of Chengdu Medical Insurance Bureau. The comorbidity burden of chronic diseases among the inpatients was evaluated with Charlson Comorbidity Index (CCI). The comorbidity spectrum, comorbidity burden and economic burden of chronic disease among the inpatients with Parkinson's disease and Parkinsonism were described and compared statistically; the influence of CCI on economic burden of the inpatients was analyzed with multivarite linear regression model. ResultsThe ratios of chronic disease comorbidity were 72.23% and 73.26% for 30 436 hospitalizations of Parkinson′s disease patients and 3 740 hospitalizations of inpatients with Parkinsonism during the 5-year period in Chengdu city and there was no significant difference in the ratio between the two groups of hospitalization (χ2 = 1.78, P = 0.182). For hospitalizations of both Parkinson′s disease and Parkinsonism patients, the top three most frequent comorbidity diseases (constituent ratios) were cerebrovascular disease (49.21% and 51.23%), chronic pulmonary disease (19.25% and 20.64%) and diabetes with end-organ damage (15.54% and 16.34%). In terms of multicomorbidity, the most frequent comorbid pattern of two chronic diseases was cerebrovascular disease and chronic pulmonary disease (9.45% and 11.34% for both Parkinson′s disease and Parkinsonism hospitalizations) and that of three chronic diseases was cerebrovascular disease, chronic pulmonary disease, and diabetes with end-organ damage (1.30% and 2.03%); for the 21 983 hospitalizations of Parkinson's disease patients and 2 740 hospitalizations of Parkinsonism patients, the proportions of with 1, 2, 3, 4, and ≥ 5 comorbid chronic diseases were 51.95% and 47.34%, 34.67% and 35.51%, 11.44% and 14.01%, 1.74% and 2.99%, and 0.20% and 0.15%, respectively, with a significant difference in the proportions between the two groups of hospitalization (χ2 = 45.21, P < 0.001). For the hospitalizations of Parkinson′s disease and Parkinsonism patients, the average CCI of 1.39 ± 1.28 and 1.49 ± 1.36 and the average medical expenses per hospitalization were 11 031.75 ± 110.88 and 12 885.81 ± 288.57 (Chinese yuan), with significant differences in the CCI and the average medical expenses between the hospitalizations of the two groups of the inpatients (both P < 0.001). After adjusting for gender, age, hospital grade and length of stay, the results of multivariate linear regression analysis showed no significant difference in the average medical expenses per hospitalization between the hospitalizations of Parkinson′s disease and Parkinsonism patients (β = 0.017, 95% confidence interval [95%CI]: – 0.003 – 0.071); while, the expenses increased with the increment of CCI (β = 0.066, 95%CI: 0.061 – 0.071). ConclusionThe prevalence, disease and the economic burden of comorbidity of chronic diseases were high and cerebrovascular disease, chronic pulmonary disease, and diabetes with end-organ damage were the most common comorbidities among inpatients of Parkinson's disease and Parkinsonism in Chengdu city.