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Circular intuitionistic fuzzy (C-IF) sets are an up-and-coming tool for enforcing indistinct and imprecise information in variable and convoluted decision-making situations. C-IF sets, as opposed to typical intuitionistic fuzzy sets, are better suited for identifying the evaluation data with uncertainty in intricate realistic decision situations. The architecture of the technique for order preference by similarity to ideal solutions (TOPSIS) provides powerful evaluation tools to aid decision-making in intuitionistic fuzzy conditions. To address appraisal issues associated with decision analysis involving extremely convoluted information, this paper propounds a novel C-IF TOPSIS approach in the context of C-IF uncertainty. This research makes three significant contributions. First, based on the three- and four-term operating rules, this research introduces C-IF Minkowski distance measures, which are new generalized representations of distance metrics applicable to C-IF values and C-IF sets. Such general C-IF distance metrics can alleviate the constraints of established C-IF distance measures, provide usage resiliency through parameter settings, and broaden the applicability of metric analysis. Second, unlike existing C-IF TOPSIS methods, this research fully utilizes C-IF information characteristics and extends the core structure of the classic TOPSIS to C-IF contexts. With the newly developed C-IF Minkowski metrics, this study faithfully demonstrates the trade-off evaluation and compromise decision rules in the TOPSIS framework. Third, this research builds on the core strengths of the pioneered C-IF Minkowski distance measures to create innovative C-IF TOPSIS techniques utilizing four different combinations, including displaced and fixed anchoring frameworks, as well as three- and four-term representations. Such a refined C-IF TOPSIS methodology can assist decision-makers in proactively addressing increasingly sophisticated decision-making problems in practical settings. Finally, this research employs two innovative prioritization algorithms to address a site selection issue of large-scale epidemic hospitals to illustrate the superior capabilities of the C-IF TOPSIS methodology over some current related approaches.

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (Hace1) is a crucial mediator of multiple pathological disorders. However, there are few studies regarding the role of Hace1 in myocardial ischemia/reperfusion injury. Here, we studied the functional role of Hace1 on myocardial ischemia/reperfusion injury using hypoxia/reoxygenation (H/R)-injured cardiac cells in vitro. Reduced levels of Hace1 were observed in H/R-exposed cardiac cells. Hace1-overexpressed cardiac cells were resistant to H/R injuries with reduced apoptosis, lowered oxidative stress, and a suppressed inflammatory response. Subsequent analysis revealed that Hace1 overexpression enhanced the activation of nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increased the transcriptional activity of Nrf2 in H/R-exposed cardiac cells. The knockout of kelch-like ECH-associated protein 1 (Keap1) diminished the regulatory role of Hace1 on Nrf2 activation. Additionally, inhibiting Nrf2 reversed Hace1-elicited cardioprotective effects in H/R-injured cardiac cells. In short, these data demonstrated that Hace1 overexpression mitigated myocardial H/R injury by enhancing the Nrf2 pathway via Keap1. This work underlines a possible role of Hace1 in myocardial ischemia/reperfusion injury and suggests Hace1 as a candidate target for exploiting cardioprotective therapy.

Concentration animal feeding operation (CAFO) is an important source of environmental estrogen. However, to the best of our knowledge, the data on estrogen discharge during duck breeding and growth is insufficient. This study used liquid chromatography with tandem mass spectrometry (LC/MS/MS) to analyze the free and conjugated estrogen concentrations in the surface water, outlet water, groundwater, and duck manure/soil mixture at three duck farms in Taiwan. Natural estrogen species included estrone (E1), 17β-estradiol (E2), estriol (E3), estrone-3-sulfate (E1-3S), 17β-estradiol-3-sulfate (E2-3S), estrone-3-glucuronide (E1-3G), and 17β-estradiol-3-glucuronide (E2-3G), whereas synthetic estrogen included 17α-ethynylestradiol (EE2) and diethylstilbestrol (DES). This study showed that the total estrogen concentrations in the surface water and groundwater were 15.4 and 4.5 ng/L, respectively, which constituted 56% and 58%, respectively, conjugated estrogen. From the pond to the outlet water, the total estrogen concentration decreased by 3.9 ng/L (23% loss) in the duck farms. However, the estrogenic potency was slightly reduced from 0.91 to 0.88 E2 equivalent/L, showing a negligible decrease. From the pond to the outlet water, the field results showed that converting the conjugated estrogen into free estrogen in the duck farm-released water increased their environmental hazard. Primarily E1, with an average concentration of 0.9 ± 1.6 ng/g, was present in the duck manure. The estrogen excreted by the ducks in the pond (from surface water to outlet water) was estimated to be 0.18 kg/million head-year. Although the estrogen concentration in the duck farms was low, the environmental impact of CAFO should not be neglected.

The identification of patients at high risk of developing postoperative complications is important to improve surgical safety. We sought to develop an individualized tool to predict post-hepatectomy major complications in hepatitis B virus (HBV)-infected patients with hepatocellular carcinoma (HCC).A multicenter database of patients undergoing hepatectomy for HCC were analyzed; 2/3 and 1/3 of patients were assigned to the training and validation cohorts, respectively. Independent risks of postoperative 30-day major complications (Clavien-Dindo grades III-V) were identified and used to construct a web-based prediction model, which predictive accuracy was assessed using C-index and calibration curves, which was further validated by the validation cohort and compared with conventional scores.Among 2762 patients, 391 (14.2%) developed major complications after hepatectomy. Diabetes mellitus, concurrent hepatitis C virus infection, HCC beyond the Milan criteria, cirrhosis, preoperative HBV-DNA level, albumin-bilirubin (ALBI), and aspartate transaminase to platelet ratio index (APRI) were identified as independent predictors of developing major complications, which were used to construct the online calculator ( http://www.asapcalculate.top/Cal11_en.html ). This model demonstrated good calibration and discrimination, with the C-indexes of 0.752 and 0.743 in the training and validation cohorts, respectively, which were significantly higher than those conventional scores (the training and validation cohorts: 0.565 ~ 0.650 and 0.568 ~ 0.614, all P 0.001).A web-based prediction model was developed to predict the probability of post-hepatectomy major complications in an individual HBV-infected patient with HCC. It can be used easily in the real-world clinical setting to help management-related decision-making and early warning, especially in areas with endemic HBV infection.

This research explores upside and downside jumps in the dynamic processes of three rates: domestic interest rates, foreign interest rates, and exchange rates. To fill the gap between the asymmetric jump in the currency market and the current models, a correlated asymmetric jump model is proposed to capture the co-movement of the correlated jump risks for the three rates and identify the correlated jump risk premia. The likelihood ratio test results show that the new model performs best in 1-, 3-, 6-, and 12-month maturities. The in- and out-of-sample test results indicate that the new model can capture more risk factors with relatively small pricing errors. Finally, the risk factors captured by the new model can explain the exchange rate fluctuations for various economic events.

Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized.Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/mAmong 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P0.05).Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.

The effects of air pollution on sleep and dementia remain unclear. The objective of this study was to investigate the effects of air pollution on cognitive function as mediated by the sleep cycle. A cross-sectional study design was conducted to recruit 4866 subjects on which PSG had been performed. Fifty of them were further given a cognitive function evaluation by the MMSE and CASI as well as brain images by CT and MRI. Associations of 1-year air pollution parameters with sleep parameters, cognitive function, and brain structure were examined. We observed that O3 was associated with a decrease in arousal, an increase in the N1 stage, and a decrease in the N2 stage of sleep. NO2 was associated with an increase in the N1 stage, a decrease in the N2 stage, and an increase in REM. PM2.5 was associated with a decrease in the N1 stage, increases in the N2 and N3 stages, and a decrease in REM. The N1 and N2 stages were associated with cognitive decline, but REM was associated with an increase in cognitive function. The N1 stage was a mediator of the effects of PM2.5 on the concentration domain of the MMSE. O3 was associated with an increase in the pars orbitalis volume of the left brain. NO2 was associated with increases in the rostral middle frontal volume, supramarginal gyrus volume, and transverse temporal volume of the left brain, and the pars opercularis volume of the right brain. PM2.5 was associated with increases in the pars triangularis volume of the left brain and the fusiform thickness of the right brain. In conclusion, we observed that air pollution was associated with cognitive decline by mediating effects on the sleep cycle with changes in the brain structure in controlling executive, learning, and language functions in adults.

A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC.From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence.Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level400 ug/L, tumor size5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS.Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

Background Paeonia ludlowii (Stern & G. Taylor D.Y. Hong) belongs to the peony group of the genus Paeonia in the Paeoniaceae family and is now classified as a “critically endangered species” in China. Reproduction is important for this species, and its low fruiting rate has become a critical factor limiting both the expansion of its wild population and its domestic cultivation. Results In this study, we investigated possible causes of the low fruiting rate and ovule abortion in Paeonia ludlowii. We clarified the characteristics of ovule abortion and the specific time of abortion in Paeonia ludlowii, and used transcriptome sequencing to investigate the mechanism of abortion of ovules in Paeonia ludlowii. Conclusions In this paper, the ovule abortion characteristics of Paeonia ludlowii were systematically studied for the first time and provide a theoretical basis for the optimal breeding and future cultivation of Paeonia ludlowii.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning. The article is an outcome of the #GlobalCollembola community initiative that is voluntarily supported by researchers around the world. Data collection and analysis was supported by the Russian Science Foundation (19-74-00154 to A.P.) and by Deutsche Forschungsgemeinschaft (493345801 to A.P. and 192626868—SFB 990 to S.S.). We acknowledge support by the Open Access Publication Funds of the Göttingen University. The following funding bodies provided support for individual contributors: ARC SRIEAS Grant SR200100005 Securing Antarctica’s Environmental Future to S.L.C., Slovak Scientific Grant Agency VEGA 1/0438/22 to Ľ.K., RFBR 19-516-60002 to N.A.K., Carl Tryggers Stiftelse för Vetenskaplig Forskning and Qatar Petroleum to J.M.A., BIO 27 (2013-2014)-MAGyP and PICTO 2084 (2012)-ANPCyT to V.B., DAAD-19-10 and MSM200962001 to T.C., grant TE, PN-III-P1-1.1-TE-2019-0358 to C.F., NWO grant 821.01.015 to O.F., National Natural Sciences Foundation of China No 41471037 and 41871042 to M.G., BIO 27 (2013-2014), MAGyP; PICT 2084 (2012), FONCyT to D.F.G., NRF South African National Antarctic Programme grant 110734 to M.G., Natural Resources Canada (NRCan), EcoEnergy Innovation Initiative under the Office of Energy Research and Development, and the Natural Sciences and Engineering Research Council of Canada (NSERC) to I.T.H., L.A.V. and L.R., Independent Research Fund Denmark grant no. DFF-4002-00384 to M.H., Estonian Science Foundation G9145 to M.I., SA-France bilateral grant to C.J., SA (NRF)/Russia (RFBR) Joint Science and Technology Research Collaboration project no. 19-516-60002 (FRBR) and no. 118904 (NRF) to M.P. and C.J., European Research Council (ERC), European Union’s Horizon 2020 research and innovation programme (grant agreement no. 677232; to N.E.); iDiv, German Research Foundation (DFG–FZT 118, 202548816) to M.J. and N.E., French National Agency of Research (ANR) (JASSUR research project; ANR-12-VBDU-0011), «Ministère de l’Agriculture et de la Pêche» and «Ministère de l’Education Nationale de la Recherche et de la Technologie» (ACTA programme), «Ministère de l’Aménagement du Territoire et de l’Environnement» (Pnetox programme), EU-funded project, ECOGEN QLK5-CT-2002-01666 (www.ecogen.dk), “Agence de l’Environnement et de la Maîtrise de l'Énergie” (BIOINDICATEUR 2, BIOTECHNOSOL), ANDRA and GISFI (www.gisfi.fr) to S.J., GRR SER-BIODIV (Région Normandie, France) to MCha, ESF9258, B02 to A.K., Fundamental Research Funds for the Central Universities (grant no. 2018CDXYCH0014) to D.L., DFG 316045089 to J.L., Massey University Research Fund grant to M.A.M., DFG SCHE 376/38-2 to M.M.P., grant from the Austria Academy of Science: Heritage_2020-043_Modeling-Museum to P.Q., Slovak Scientific Grant Agency: VEGA Nos. 1/0441/03 and 1/3267/06 to N.R., Higher Education Commission of Pakistan to M.I.R., RSF 21-74-00126 to R.A.S., Austrian Federal Government and European Union (Rural Development 2014-2020) to J.S., АААА-А17-122040600025-2 to A.A.T., Brazilian Council for Scientific and Technological Development—CNPq (grant no. 152717/2016-1) to B.R.W., 309030/2018-8 to D.Z. and 305426/2018-4 to B.C.B., National Natural Science Foundation of China (31970434, 31772491) to N.N.G., Research and Innovation Support Foundation of Santa Catarina (FAPESC) (6.309/2011-6/FAPESC) and the CNPq (563251/2010-7/CNPq) to L.C.I.O.F., O.K.-F., the Latvian Council of Science Grants no. 90.108, 93.140, 96.0110, 01.0344 to E.J., CNPq for the Research Productivity Grant (305939/2018-1) to D.B., FPI-MICINN grant in the project INTERCAPA (CGL2014-56739-R) to P.H, the Natural Sciences and Engineering Research Council of Canada (NSERC) to Z.L., Ministry of Innovation and Technology of Hungary TKP2021-NKTA-43 to D.W. Authors are grateful to Penelope Greenslade for providing the literature on Australian Collembola communities. Authors are grateful to Frans Janssens for providing the global checklist of Collembola.

The passive stiffness and strength of periscapular muscles may affect scapulohumeral control, especially in overhead athletes due to sports-specific training. This study tried to assess the relationship between the passive stiffness and strength of periscapular muscles, scapulohumeral kinematics and neuromuscular control during scaption in swimmers. Ten male adolescent competitive front-crawl swimmers were recruited. The passive stiffness and strength of periscapular muscles were measured in standard postures by a hand-held myotonometer and dynamometer, respectively. Surface electromyography and electromagnetic tracking systems were synchronized to record the muscle activities and scapulohumeral kinematics during scaption. Correlations between the passive stiffness or strength of periscapular muscles and the kinematics or muscle activity were examined by Spearman's rank correlation coefficient. The maximal strength of periscapular muscles correlated positively with the ranges of upward and external rotation of the scapula and negatively with muscle activity during scaption. Passive stiffness of periscapular muscles was associated with the downward rotation of the scapula and triggered an increase in muscle activity. Increased passive stiffness or decreased strength in the periscapular muscles may affect their role in controlling the scapular rotation and contribute to compensation from adjacent muscles. Our findings suggest that when attempting to evaluate scapular behavior, it may be beneficial to examine muscle strength and passive stiffness of periscapular muscles.

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

Digital game-based learning research has received increasing attention in recent years due to advances in technology. A systematic review was conducted to understand the current status and potential of game-based learning (GBL) research in science and mathematics. This study reviewed articles on GBL in science and mathematics education published in the Web of Science (WoS) database from 1991 to 2020. The 146 articles were selected for content and bibliometric analysis. After a systematic analysis of the trends and overviews, we present discussions and insights for the future. The study raised relevant research questions to analyze authors, regions, applied subjects, educational stages, research methods, game types and devices, performance issues, and author keywords. The results revealed that the majority of the published research in this field has been carried out in Taiwan, followed by the United States. GBL is currently applied in mathematics and science to increase learner motivation and engagement and reduce learning anxiety. The results also revealed that higher order thinking skills such as problem solving, group collaboration, and critical thinking, have become an increasingly important focus of research in recent years. The systematic review also found that researchers have been engaged in the field since 1993 and have conducted a large number of studies since 2011. In terms of keywords, game-based learning and interactive learning were the most used keywords in the articles, indicating that they were the most explored topics by researchers, while learning behaviors and competition were relatively new directions to explore. This study analyzed and summarized GBL in science and mathematics education in the hope that it may contribute to future research.

Chemotherapy side effects are minimized, and therapeutic results are enhanced by combination therapy, which is extensively utilized in cancer therapy. MTT experiment showed that compared to the free drugs calreticulin (CRT) and gemcitabine (GEM), GEM-CRT@NPs significantly increased the cytotoxicity of endometrial cancer (Ishikawa cells and KLE cells). These drugs were conjugated to a tri-block copolymeric framework. GEM-CRT@NPs were studied using HR-TEM and DLS analysis to determine particle size and zeta potential. Biochemical staining analyses were also used to investigate the morphological characteristics of endometrial cancer cell lines. After KLE and Ishikawa cancer cells were treated with GEM-CRT@NPs, endometrial cell shape was altered, as evidenced by nuclear fragmentation and nuclear condensation (apoptosis hallmarks). Additionally, the most significant apoptosis ratio to mitochondrial membrane potential indicates that the mitochondrial membrane potential is responsible for the cell's death. Upon treatment with GEM-CRT@NPs, systemic toxicity analysis revealed minimal histological abnormalities and significant blood chemistry alterations, and a near-normal look of the organs. Endometrial cancer treatment may be enhanced with the use of the targeted combination therapeutic system.

Ablation of the upper thoracic sympathetic ganglia that innervates the hands is the most effective and permanent cure of palmar hyperhidrosis. However, this type of sympathectomy causes irreversible neural damage and may result in severe compensatory hyperhidrosis. This experiment is designed to confirm the hypothesis, in which the stimulation of T2 sympathetic chain leads to increased palmar microcirculation, and thus results in treating hyperhidrosis. In this study, we used electric stimulation to induce reversible blockade of the sympathetic ganglion in pigs and investigated its effect on palmar perfusion. An electrode was inserted to the T2 sympathetic ganglion of the pig through three different approaches: open dorsal, thoracoscopic, and fluoroscopy-guided approaches. Electric stimulation was delivered through the electrode using clinically available pulse generators. Palmar microcirculation was evaluated by laser speckle contrast imaging. The T2 sympathetic ganglion of the pig was successfully accessed by all the three approaches, as confirmed by changes in palmar microcirculation during electric stimulation. Similar effects were not observed when the electrode was placed on the T4 sympathetic ganglion or off the sympathetic trunk. We established a large animal model to verify the effect of thoracic sympathetic stimulation. Electric stimulation can be used for sympathetic blockade, as confirmed by increased blood perfusion of the palm. Our work suggests that sympathetic stimulation is a potential solution for palmar hyperhidrosis.

The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer’s disease (AD) in a real-world setting in Taiwan. This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55–95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians’ judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

Pore-forming Gasdermin protein-induced pyroptosis in tumor cells promotes anti-tumor immune response through the release of pro-inflammatory cytokines and immunogenic substances after cell rupture. However, endosomal sorting complexes required for transport (ESCRT) III-mediated cell membrane repair significantly diminishes the tumor cell pyroptosis by repairing and subsequently removing gasdermin pores. Here, we show that blocking calcium influx-triggered ESCRT III-dependent membrane repair through a biodegradable nanoparticle-mediated sustained release of calcium chelator (EI-NP) strongly enhances the intracellularly delivered GSDMD-induced tumor pyroptosis via a bacteria-based delivery system (VNP-GD). An injectable hydrogel and a lyophilized hydrogel-based cell patch are developed for peritumoral administration for treating primary and metastatic tumors, and implantation for treating inoperable tumors respectively. The hydrogels, functioning as the local therapeutic reservoirs, can sustainedly release VNP-GD to effectively trigger tumor pyroptosis and EI-NP to prevent the ESCRT III-induced plasma membrane repair to boost the pyroptosis effects, working synergistically to augment the anti-tumor immune response.

Air pollution exposure has been linked to various diseases, including dementia. However, a novel method for investigating the associations between air pollution exposure and disease is lacking. The objective of this study was to investigate whether long-term exposure to ambient particulate air pollution increases dementia risk using both the traditional Cox model approach and a novel machine learning (ML) with random forest (RF) method. We used health data from a national population-based cohort in Taiwan from 2000 to 2017. We collected the following ambient air pollution data from the Taiwan Environmental Protection Administration (EPA): fine particulate matter (PM2.5) and gaseous pollutants, including sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen oxide (NOx), nitric oxide (NO), and nitrogen dioxide (NO2). Spatiotemporal-estimated air quality data calculated based on a geostatistical approach, namely, the Bayesian maximum entropy method, were collected. Each subject's residential county and township were reviewed monthly and linked to air quality data based on the corresponding township and month of the year for each subject. The Cox model approach and the ML with RF method were used. Increasing the concentration of PM2.5 by one interquartile range (IQR) increased the risk of dementia by approximately 5% (HR = 1.05 with 95% CI = 1.04–1.05). The comparison of the performance of the extended Cox model approach with the RF method showed that the prediction accuracy was approximately 0.7 by the RF method, but the AUC was lower than that of the Cox model approach. This national cohort study over an 18-year period provides supporting evidence that long-term particulate air pollution exposure is associated with increased dementia risk in Taiwan. The ML with RF method appears to be an acceptable approach for exploring associations between air pollutant exposure and disease.

Background Postoperative delirium in elderly patients is a common and costly complication after surgery. Propofol and sevoflurane are commonly used anesthetics during general anesthesia, and the sedative and anti-inflammatory mechanisms of the two medications are different. The aim of this trial is to compare the impact of propofol with sevoflurane on the incidence of postoperative delirium in elderly patients after spine surgery. Methods A single-center randomized controlled trial will be performed at First Affiliated Hospital of Shandong First Medical University, China. A total of 298 participants will be enrolled in the study and randomized to propofol infusion or sevoflurane inhalation groups. The primary outcome is the incidence of delirium within 7 days after surgery. Secondary outcomes include the day of postoperative delirium onset, duration (time from first to last delirium-positive day), and total delirium-positive days among patients who developed delirium; tracheal intubation time in PACU; the length of stay in PACU; the rate of postoperative shivering; the rate of postoperative nausea and vomiting; the rate of emergence agitation; pain severity; QoR40 at the first day after surgery; the length of stay in hospital after surgery; and the incidence of non-delirium complications within 30 days after surgery. Discussion The primary objective of this study is to compare the impact of propofol and sevoflurane on the incidence of postoperative delirium for elderly patients undergoing spine surgery. The results may help inform strategies to the optimal selection of maintenance drugs for general anesthesia in elderly patients undergoing spine surgery. Trial registration ClinicalTrials.govNCT05158998. Registered on 14 December 2021

Background Caves are special natural laboratories for most biota and the cave communities are unique. Establishing population in cave is accompanied with modifications in adaptability for most animals. To date, little is known about the survival mechanisms of soil animals in cave environments, albeit they play vital roles in most terrestrial ecosystems. Here, we investigated whether and how gut microbes would contribute to the adaptation of earthworms by comparing the gut microbiome of two earthworm species from the surface and caves. Results Two dominant earthworm species inhabited caves, i.e., Allolobophora chlorotica and Aporrectodea rosea. Compared with the counterparts on the surface, A. rosea significantly decreased population in the cave, while A. chlorotica didn’t change. Microbial taxonomic and phylogenetic diversities between the earthworm gut and soil environment were asynchronic with functional diversity, with functional gene diversity been always higher in earthworm gut than in soil, but species richness and phylogenetic diversity lower. In addition, earthworm gut microbiome were characterized by higher rrn operon numbers and lower network complexity than soil microbiota. Conclusions Different fitness of the two earthworm species in cave is likely to coincide with gut microbiota, suggesting interactions between host and gut microbiome are essential for soil animals in adapting to new environments. The functional gene diversity provided by gut microbiome is more important than taxonomic or phylogenetic diversity in regulating host adaptability. A stable and high-efficient gut microbiome, including microbiota and metabolism genes, encoded potential functions required by the animal hosts during the processes of adapting to and establishing in the cave environments. Our study also demonstrates how the applications of microbial functional traits analysis may advance our understanding of animal-microbe interactions that may aid animals to survive in extreme ecosystems.

This study focused on understanding the confined crystallization of poly(ethylene oxide) (PEO) in electrospun nanofibers. The effect of thermal treatment on PEO crystallization was also studied. An electrospinning process with a rotating drum collector enabled stretching and aligning of polymer chains, which resulted in the formation of a planar zigzag conformation. The confined environment in nanofibers facilitated an ordered crystal arrangement, resulting in an increase in the degree of crystallinity with a decrease in the fiber diameter. By contrast, large fibers extended solvent evaporation, which resulted in large crystallite sizes. The confined geometry and mechanical force provided by a rotating collector induced the preferred crystal orientation parallel to the fiber axis. Upon thermal annealing, the stretched PEO chains relaxed, resulting in a change from the metastable zigzag conformation to a stable helical conformation. Thermal treatment monotonically increased the melting temperature, degree of crystallinity, and crystallite size of PEO nanofibers regardless of the fiber diameter but did not influence the orientation of the organized crystals. The confinement effect on the chain conformation and crystallization behavior of poly(ethylene oxide) (PEO) in electrospun nanofibers was investigated. The PEO chains in electrospun nanofibers were tightly packed and exhibited a zigzag conformation. Increasing the fiber diameter reduced the packing of polymer chains, resulting in increases in the melting temperature and crystallite size. Thermal treatment relaxed the stretched chains, which induced a change from the metastable zigzag conformation to a stable helical conformation. Additionally, the melting temperature, degree of crystallinity, and crystallite size increased with increasing annealing temperature.

Patients with multiple myeloma (MM) experience substantial cancer/treatment-related symptom burden during maintenance therapy. This is a phase II randomized, double-blinded, placebo-controlled clinical trial to examine the effect of minocycline for symptom reduction by its potential anti-inflammatory effect. Eligible MM patients for maintenance therapy were randomized to receive minocycline (100 mg twice daily) or placebo. The MD Anderson Symptom Inventory for MM (MDASI-MM) was used to assess multiple symptoms weekly during the trial. Clinician-rated toxicities and blood samples were prospectively collected. The effect size, area under the curve (AUC), and t tests were used to determine the symptom burden between treatment groups and identify the 5 most-severe MDASI-MM symptoms. The longitudinal analysis compared the changes in symptom severity and associated inflammatory markers between groups over time. Sixty-nine evaluable MM patients (33 from the intervention group and 36 from the placebo group) were included. No grade 3+ adverse events related to study medication were noted. The AUCs for the 5 worst MDASI-MM symptoms (fatigue, pain, disturbed sleep numbness/tingling, and drowsiness) were not significantly different between two arms. Regardless of group assignment, pain reduction was positively associated with decreased serum levels of soluble tumor necrosis factor-α receptors 1 and 2 during therapy (all P < 0.05). This pPhase II randomized study observed no statistically significant positive signal impact from minocycline on symptom reduction or inflammatory markers during maintenance therapy for MM, although using minocycline was feasible and had a low toxicity profile.

This study aims to extend classic VIKOR technique for multicriteria decision-making (MCDM) problems within Pythagorean fuzzy (PF) scenario. First, judgments from decision makers (DMs) are expressed by PF sets that can describe more uncertain and ambiguous information than available fuzzy sets. Second, PF point operators are applied to denote the risk preference of the DM who may express an attitude toward an emerging science and technology. Third, a new generalized distance measurement formula considering all the characteristics of PF sets is proposed, and some attractive properties of distance measure, which outperforms available distance measures, are proved. Fourth, the novel generalized distance measure is employed to relative distance to identify the optimum and worst PF values and then employed in $$L_{p}$$ -metric VIKOR formula to accurately gain the group utility, individual regret, and compromise index. The novel PF-VIKOR algorithm considering DM’s risk preference and a novel distance measure is described in detail, and a blockchain technology solution selection problem is utilized to validate the feasibility of our technique. Then, the sensitivity analysis is implemented to test stability of our PF-VIKOR technique when the parameters in risk preferences and generalized distance measure are adjusted. Fifth, the comparison among various PF-MCDM techniques is performed to validate superiority and practicability of our presented technique.

This study explores the determinants of Bitcoin’s price from 2010 to 2018. This study applies Generalized Autoregressive Conditional Heteroskedastic model to investigate the Bitcoin datasets. The experimental results find the Bitcoin price has positive relationship to the exchange rates (USD/Euro, USD/GBP, USD/CHF and Euro/GBP), the DAX and the Nikkei 225, while a negative relationship with the Fed funds rate, the FTSE 100, and the USD index. Especially, Bitcoin price is significantly affected by the Fed funds rate, followed by the Euro/GBP rate, the USD/GBP rate and the West Texas Intermediate price. This study also executes the decision tree and support vector machine techniques to predict the trend of Bitcoin price. The machine learning approach could be a more suitable methodology than traditional statistics for predicting the Bitcoin price.

The purpose of this paper is to propose a useful likelihood measure for determining scalar function order relations and developing a novel likelihood-based optimization ordering model for solving multiple criteria group decision making (MCGDM) problems based on Pythagorean fuzzy (PF) sets. This paper scrutinizes PF order relations based on scalar functions to compare sophisticated uncertain information and establish a precedence order. By way of scalar function order relations, this paper utilizes scalar functions that are associated with Pythagorean membership grades and admissible upper approximations to present a novel likelihood measure in PF contexts. With the aid of useful concepts, such as levels of agreement and disagreement and comprehensive performance values, this paper originates a PF likelihood-based optimization ordering model to acquire the optimal group consensus solution for addressing MCGDM problems. Practical applications and several comparative studies are performed to reveal the practicality and strong points of the proposed methodology in tackling real-world MCGDM issues within uncertain environments of PF sets. This paper finds that the new scalar function-based likelihood measure is more flexible and beneficial than the current probability distribution approach. Furthermore, an easy-to-use algorithmic procedure can realize the proposed methodology to efficaciously process sophisticated PF information and improve the understandability of a decision model via a likelihood comparison approach. The originality and main contributions of this work are fourfold: (1) A PF likelihood measure is introduced as a basis for scalar function order relations; (2) the PF likelihood-based optimization ordering model is established for consensus ranking; (3) a predominant procedure is constructed for addressing PF information; and (4) the likelihood-based decision models are enriched under complex uncertainty.

Tachycardia-induced cardiomyopathy (TCM) has been known for decades as a reversible form of non-ischemic cardiomyopathy. However, its mechanism and characteristics remain poorly understood. This retrospective study investigated endomyocardial biopsy (EMB) samples from consecutive patients with TCM and compared them with samples from patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (InCM). A total of 684 patients (18 TCM, 170 DCM, 496 InCM) with recent-onset heart failure and reduced ejection fraction unrelated to valvular or ischemic heart disease were analyzed. In the TCM group, 81% were male, the mean age was 60 ± 13 years, and 94% had heart failure symptoms ≥2 New York Heart Association (NYHA) class. At baseline (BL), 78% had atrial fibrillation/flutter and 12% other forms of tachycardia or frequent extrasystole. The ventricular rate was higher compared to DCM and InCM patients (122 ± 25 versus 78 ± 21; p

Rapid and convenient detection of protein–protein interactions (PPIs) is of great significance for understanding function of protein. For efficiently detecting PPIs, we used the changes of proteins fluorescence localization to design a novel system, fluorescence translocation co-localization (FTCL), based on nuclear localization signal (NLS) in living cells. Depending on the original state of protein localization (both in the cytoplasm, both in the nucleus, one in the nucleus and another in the cytoplasm), two target proteins can be partitioned into the cytoplasm and nucleus by adding a NLS or mutating an existing NLS. Three independent results display that the changes of protein fluorescence co-localization were observed following co-expression of the two target proteins. At the same time, we verified the accuracy of fluorescence co-localization by co-immunoprecipitation. There FTCL system provided a novel detection method for PPIs, regardless of protein localization in the nucleus or cytoplasm. More importantly, this study provides a new strategy for future protein interaction studies through organelle localization (such as mitochondria, Golgi and cytomembrane, etc.).

Some researches have shown the associations between air pollution and hospital-based emergency department visits, while the evidence about the acute effects of air pollution on emergency ambulance dispatches for the whole population is rarely available, especially on an hourly time scale. This paper aimed to investigate the effects of hourly concentrations of ambient air pollution on hourly number of ambulance emergency call-outs (AECOs) in Shenzhen, China. AECO data were collected from Shenzhen Emergency Center from January 2013 to December 2016. A time-stratified case-crossover design with conditional Poisson regression was performed to fit the relationship between hourly air pollution and AECOs. The distributed lag model was applied to determine lag structure of the effects of air pollutants. There were a total of 502,862 AECOs during the study period. The significant detrimental effects of SO2, PM2.5, and PM10 appeared immediately with a following harvesting effect after 5 h and the effects lasted for about 96 h. The cumulative effect estimates of four pollutants over 0–96 h were 13.99% (95% CI 7.52–20.85%), 2.07% (95% CI 0.72–3.43%), 1.20% (95% CI 0.54–1.87%), and 2.46% (95% CI 1.63–3.29%), respectively. We did not observe significant effects of O3. This population-based study quantifies the adverse effects of air pollution on ambulance dispatches and provides evidence of the lag structure of the effects on an hourly time scale.

Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.

Immunosuppressive cells residing in the tumor microenvironment, especially tumor associated macrophages (TAMs), hinder the infiltration and activation of T cells, limiting the anti-cancer outcomes of immune checkpoint blockade. Here, we report a biocompatible alginate-based hydrogel loaded with Pexidartinib (PLX)-encapsulated nanoparticles that gradually release PLX at the tumor site to block colony-stimulating factor 1 receptors (CSF1R) for depleting TAMs. The controlled TAM depletion creates a favorable milieu for facilitating local and systemic delivery of anti-programmed cell death protein 1 (aPD-1) antibody-conjugated platelets to inhibit post-surgery tumor recurrence. The tumor immunosuppressive microenvironment is also reprogrammed by TAM elimination, further promoting the infiltration of T cells into tumor tissues. Moreover, the inflammatory environment after surgery could trigger the activation of platelets to facilitate the release of aPD-1 accompanied with platelet-derived microparticles binding to PD-1 receptors for re-activating T cells. All these results collectively indicate that the immunotherapeutic efficacy against tumor recurrence of both local and systemic administration of aPD-1 antibody-conjugated platelets could be strengthened by local depletion of TAMs through the hydrogel reservoir.

Glutathione (GSH) plays an important role in cells, which is an essential endogenous antioxidant. Here, we have developed a new detection platform to analyze GSH levels. In our system, fluorescent polydopamine (PDA) nanoparticles, as signal indicators, were obtained by oxidation through cobalt oxyhydroxide (CoOOH) nanosheets. When CoOOH was present, CoOOH could quickly oxidize dopamine to fluorescent PDA nanoparticles. However, once GSH existed, CoOOH nanosheets were decomposed into Co2+, and oxidation between CoOOH and dopamine was prevented with weaker fluorescence occurring. Thus, we could realize detection of the GSH concentration according to the decreased fluorescence value of the fluorescent polydopamine. This method provides a fast, simple, high sensitivity and desirable selectivity platform for GSH monitoring.

Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).

This paper extends one of the most extensively used multiple criteria decision analysis (MCDA) methods, the technique for order preference by similarity to ideal solutions (TOPSIS), to adapt to highly complicated uncertain environments based on interval-valued Pythagorean fuzzy (IVPF) sets. In contrast to classical TOPSIS methods, this paper develops a novel concept of Pearson-like IVPF correlation coefficients instead of distance measures to not only construct a useful and effective association measure between two IVPF characteristics but also depict the outranking relationship of IVPF information. Moreover, this paper proposes the (weighted) IVPF correlation-based closeness coefficients to establish a Pearson-like correlation-based TOPSIS model to manage MCDA problems within the IVPF environment. In particular, there is a definite improvement in determining the closeness coefficient required in the TOPSIS procedure. This paper considers anchored judgments with respect to the positive- and negative-ideal IVPF solutions and provides new approach- and avoidance-oriented definitions for the IVPF correlation-based closeness coefficient, which is entirely different from the traditional definition of relative closeness in TOPSIS. Furthermore, this paper proposes a comprehensive IVPF correlation-based closeness index to balance the consequences between ultra-approach orientation and ultra-avoidance orientation and acquire the ultimate compromise solution for decision support and aid. The feasibility and practicability of the developed methodology are illustrated by a practical MCDA problem of rehabilitation treatment for hospitalized patients with acute stroke. The application results, along with experimentations and comparative analyses, demonstrate that the developed methods are rational and effective.

Enhanced green and red upconversion emissions under 980 nm excitation are observed in Ba0.85−xCa0.15TiO3:0.75%Er3+/xIn3+ lead-free ferroelectric ceramics which were synthesized by solid state reaction method. With increasing In3+ ions doping level from x = 0% mol the green and red emission intensities increase and reach the maximum at x = 1.75% mol. The maximum intensity of green emission at 550 nm is 20 times larger than In3+ ions undoped samples, which is unprecedented for Er3+-doped perovskite ferroelectric materials. Based on the ultraviolet-visible-near infrared absorption spectra, the enhancement of the luminescence intensity of the A-site In3+ doped Ba0.85−xCa0.15TiO3:0.75%Er/xIn ceramics is attributed to In3+-doping-induced relative increase in isolate Er3+ and decrease in the clustered-Er3+. The effects of In3+ doping on the crystal structure, dielectric, ferroelectric, piezoelectric properties of the ceramics were also studied and discussed.

Epidemiology studies relying on one address to assign exposures over time share common methodological limitations in failing to account for mobility that may introduce potential exposure misclassification. Using Texas birth certificate and cancer registry data, we identified predictors of residential mobility among mothers of children diagnosed with early childhood leukemia in Texas from 1995 to 2011. We used U.S. Environmental Protection Agency (EPA) National Air Toxics Assessment data to estimate residential levels of benzene and 1,3-butadiene based on addresses at birth and diagnosis and applied mixed-effects ordinal logistic regression models to evaluate differences in exposure classification between the two time periods. In total, 55% of children moved from time of birth to diagnosis, although they generally did not move far (median distance moved was 8 km). Predictors of mobility, at delivery, included younger age, being unmarried and living in neighborhoods with high benzene levels, and, at diagnosis, increasing child’s age and living in neighborhoods with low poverty rates. We observed that the odds of being assigned to a higher exposure quartile at diagnosis relative to the time of birth decreased by 31% for 1,3-butadiene (OR = 0.69, 95% CI 0.59–0.82) and by 12% for benzene (OR = 0.88, 95% CI 0.75, 1.05).

Phenolics are a class of plant secondary metabolites that play important roles in plant growth and environmental adaptation. Glucosylation of phenolics is one of the molecular mechanisms controlling phenolics homeostasis. However, the relevant glucosyltransferases are largely unknown. In this study, a putative family 1 glucosyltransferase gene OsSGT1 was cloned from rice due to its close homology with the previously reported phenolics-related glucosyltransferases UGT84A1-A4, and the phylogenetic relationship of OsSGT1 with homologs from other species was investigated. Recombinant OsSGT1 protein showed strong activity towards phenolics to form their glucose conjugates. This is the first identified natural phenolics-related glucosyltransferase in rice. In addition, the expression patterns of OsSGT1 in different tissues of rice indicated that OsSGT1 was predominantly expressed in the old leaves and dough grains, suggesting that OsSGT1 might be involved in the maturation process of rice by regulating phenolic metabolism, and thus deepened our understanding on the roles of phenolics in rice growth and environmental adaptation.