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Based on recent advancements of reproducing kernels in several complex variables, the theory of rational approximation for weighted Bergman spaces on tube domains over cones is developed. By verifying the boundary vanishing property, the existence of optimal parameters and the corresponding orthogonal functions are obtained. [ABSTRACT FROM AUTHOR]

Background: Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery. Methods: Patients admitted to a teaching hospital in the North-West of England between 2010–2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge. Results: Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010–2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010–2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid. Conclusions: In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13–22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations. [ABSTRACT FROM AUTHOR]

Herein, the Laplace transform representations for functions of weighted holomorphic Bergman spaces on the tube domains are developed. Then a weighted version of the edge-of-the-wedge theorem is derived as a byproduct of the main results. [ABSTRACT FROM AUTHOR]

A notable issue, the proper description of mass and charge distributions of fission fragments within non-adiabatic descriptions of fission dynamics, is investigated by performing double particle number projection on the outcomes of time-dependent Hartree–Fock (TDHF) simulation. The induced fission process of the benchmark nucleus 240 Pu is studied. In the three-dimensional Cartesian coordinate without any symmetry restrictions, we get the static fission pathway from the two-dimensional potential energy surface, and then the fission dynamics from saddle to scission point are obtained using TDHF. We show that the charge numbers of primary heavy fragments from TDHF simulation strongly depend on the deformations of initial configurations via the two asymmetric fission channels, which can be distinguished according to the dynamical fission trajectories. The charge distribution of fission fragments is well reproduced using the double particle number projection technique. After applying the Gaussian kernel estimation based on the distribution from the double particle number projection technique, the mass distribution is also consistent with the experimental results. Besides, the results of the total kinetic energy of fission fragments are reasonably consistent with the experiments. [ABSTRACT FROM AUTHOR]

The shrub and patch size of moss crusts can significantly affect plant and soil nutrients. The effects and relationships of shrubs and moss crusts on soil multifunctionality are unclear. This study aimed to understand the spatial heterogeneity of soil multifunctionality in moss crust patches and shrubs. Soil organic carbon, nutrient, and enzyme activities under moss crust patches were measured. Interestingly, the soil polyphenol oxidase (PPO) and peroxidase (POD) activities, carbon‐related soil multifunctionality index (C‐SMF), nitrogen‐related soil multifunctionality index (N‐SMF), phosphorus‐related soil multifunctionality index (P‐SMF), and soil multifunctionality index (SMF) increased with increasing patch size in moss crusts. The patch size of moss crusts had no significant effect on the C‐SMF, N‐SMF, P‐SMF, and SMF under the shrub. The soil C‐SMF, N‐SMF, P‐SMF, and SMF under shrubs were significantly higher than that in exposed areas (EAs). The soil PPO, POD, N‐SMF, P‐SMF, and SMF under dead shrubs were significantly higher than those under living shrubs and in EAs. Evaluation and composition analysis of C‐SMF, N‐SMF, and P‐SMF indicated that moss crust promotes the increase of P‐SMF, and that shrub promotes the increase of C‐SMF and N‐SMF. Moss crust patches mainly affected phosphorus functionality, increasing phosphorus cycling. Shrub promotes soil carbon and nitrogen functionality. This study elucidates the effect of moss crust patch size on soil multifunctionality influenced by shrub growth in desert ecosystems and provides further new insights into the soil processes and functions. Results are beneficial for the comprehensive utilization of fertile islands and its enhancement of beneficial ecological functions, such as maintaining soil nutrition, quality, health, and vegetation restoration, and lay a foundation for future research on nutrient absorption and utilization between mosses and shrubs. Core Ideas: The patch size effect of moss crusts is a positive in soil multifunctionality and is influenced by microhabitats.Moss crust patches mainly affected phosphorus functionality, increasing phosphorus cycling.Shrub patches mainly affected soil carbon and nitrogen functionality. [ABSTRACT FROM AUTHOR]

Objective To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). Methods Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. Conclusion The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic. [ABSTRACT FROM AUTHOR]

Phosphorus is a limiting factor for eutrophication while also an important nonrenewable resource. Adsorption is one of the most efficient phosphorus pollution control technologies and phosphorus recovery can be promisingly achieved after desorption. The use of iron oxides as adsorbents to remove phosphorus has been extensively studied, due to merits of high adsorption capacity, high selectivity, as well as environmental benign. However, their effectiveness and feasibility in practical applications are still challenged. This review summarized the current achievements of using iron oxides and their modified products to remove phosphorus from wastewater. Phosphorus removal mechanisms and strategies for improving the performance of different types of iron oxide-based adsorbents were summarized. Moreover, the potential methods of phosphorus desorption and subsequent recovery were summarized. Finally, the future challenges on the practical application of iron oxides in phosphorus recovery from wastewater were discussed. This review might provide guidance for the development and application of adsorption-based phosphorus recovery technology. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). METHODS: Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. RESULTS: From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation. [ABSTRACT FROM AUTHOR]

Maintenance planning of two‐component systems has been extensively studied in recent decades. In the literature, most studies assume that the failure cause of a two‐component system is self‐announcing. In some real applications, the failure cause is masked, and a diagnosis with professional equipment is needed to reveal the failed component. This study investigates a preventive replacement policy of a two‐component series system considering masked causes of failure. When an unexpected failure occurs, we can carry out a diagnosis to reveal the failed component and replace it subsequently, or we can directly replace the whole system without diagnosis. Meanwhile, when we carry out a preventive replacement on a component, the other component can be replaced opportunistically. We formulate the problem as a semi‐Markov decision process, and prove the existence of the stationary optimal policy. The optimal preventive replacement age thresholds for each component and the corresponding optimal maintenance actions upon each failure are jointly obtained to minimize the long‐term average maintenance cost per time unit. A comprehensive numerical study is provided to illustrate the effectiveness of our proposed model. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To explore the technical and clinical evaluation of ultrasound-derived fat fraction (UDFF) measurement in adult patients in whom fatty liver was suspected. MATERIALS AND METHODS: In this prospective study, 41 participants were initially enrolled in our hospital between October 2022 and December 2022 and received UDFF assessment using Siemens ACUSON Sequoia system equipped with DAX transducer. UDFF measurement was performed three times to obtain UDFF values from each imaging location (V hepatic segment and VIII hepatic segment) per participant, and the depth (skin-to-capsule distance) was automatically measured. The echogenicity of liver tissue in B mode ultrasound (BMUS) was compared to the normal kidney tissue, and fatty liver was graded as mild (Grade 1), moderate (Grade 2), and severe (Grade 3). The median of the acquired overall median UDFF values was used for statistical analysis. All ultrasound examinations were performed by one of two radiologists (with 20 and 10 years of liver ultrasound imaging experience). RESULTS: Finally, UDFF measurement was successfully performed on 38 participants to obtain valid values, including 21 men with a median age of 40.0 years (interquartile range [IQR]: 23.0 – 58.5) and 17 women with a median age of 60.0 years (IQR: 29.5 – 67.0). Fatty liver was diagnosed by BMUS features in 47.4% (18/38) participants. Among all participants, the median UDFF value was 7.0% (IQR: 4.0 – 15.6). A significant difference in UDFF values was found between participants with fatty liver and without fatty liver (U = 7.0, P < 0.001), and UDFF values elevated as the grade of the fatty liver increased (P < 0.001). The median UDFF values from the three UDFF measurements obtained during each ultrasound examination showed excellent agreement (ICC = 0.882 [95% confidence interval: 0.833 – 0.919]). The Spearman correlation of UDFF values in different depths was moderate, with a rs value of 0.546 (P < 0.001). No significant differences in UDFF values were found between V hepatic segment and VIII hepatic segment (U = 684.5, P = 0.697). CONCLUSIONS: UDFF provides a novel non-invasive imaging tool for hepatic steatosis assessment with excellent feasibility. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, the hallmark of cancer, is accountable for about 90% of cancer-related deaths. Long noncoding RNA (lncRNA), a subset of the noncoding RNAs, has exhibited involvement in various processes, including immune evasion, cell proliferation, migration, and invasion, across multiple human diseases, notably cancer. The objective of our study was to identify a metastasis-associated lncRNA in lung cancer and elucidate the underlying mechanisms. Our findings indicate that Linc01703, which is notably downregulated in metastatic lung cancer cells, effectively suppresses lung cancer metastasis in vivo. Interestingly, Linc01703 does not directly impact the proliferation and invasion capabilities of lung cancer cells but rather inhibits cancer metastasis by promoting the secretion of CD81+ exosomes through the Rab27a/SYTL1/CD81 transport complexes. Consequently, our observations provide new insights into the potential clinical application of CD81+ exosome-based cancer therapy. Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+ exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+ exosomes through the formation of the Rab27a/SYTL1/CD81 complex. [ABSTRACT FROM AUTHOR]

Encephalitis affects people across the lifespan, has high rates of mortality and morbidity, and results in significant neurological sequelae with long-term consequences to quality of life and wider society. The true incidence is currently unknown due to inaccurate reporting systems. The disease burden of encephalitis is unequally distributed across the globe being highest in low- and middle-income countries where resources are limited. Here countries often lack diagnostic testing, with poor access to essential treatments and neurological services, and limited surveillance and vaccination programs. Many types of encephalitis are vaccine preventable, whereas others are treatable with early diagnosis and appropriate management. In this viewpoint, we provide a narrative review of key aspects of diagnosis, surveillance, treatment, and prevention of encephalitis and highlight priorities for public health, clinical management, and research, to reduce the disease burden. [ABSTRACT FROM AUTHOR]

Aims: This study aims to comprehensively examine the shear behavior of rooted soil mixtures at both macroscopic and microscopic levels. Method: The research utilizes the discrete element method (DEM) to investigate the shear behavior of rooted soil mixtures through two-dimensional biaxial tests conducted under the membrane boundary condition. The samples were meticulously prepared, with variations in both the volume fraction of roots and soils. The roots were modeled as multiple bonded rigid blocks, enabling them to undergo deformation when subjected to external forces. Results: From a macroscopic perspective, the rooted samples display deviatoric stress and volumetric strain curves that illustraY. Huangte the stress-strain relationship during shearing. On a microscopic level, the coordination number (representing the contact number per particle) of the rooted soil samples, along with the anisotropy of contact force orientations, serves as valuable descriptors of the evolving microstructures during shearing. Furthermore, the formation of shear bands exhibits variations depending on the content of roots within the samples. Conclusions: The study findings demonstrate that the macroscopic behavior of rooted soils is influenced by multiple factors, including the volume fraction of the mixtures, stiffness, and aspect ratio of soil particles and roots. These findings highlight the intricate and interdependent nature of the mechanical properties within the root-soil mixture. Additionally, it is observed that a higher volume fraction of roots results in a more complex formation of shear bands, further indicating that the mechanical response of the root-soil mixture is significantly influenced by the presence of roots. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a major complication of pregnancy. GDM is associated with a higher risk of adverse pregnancy outcomes (APO). The purpose of this study was to assess the association between third-trimester platelet to lymphocyte ratio (PLR) and high-sensitivity C-reactive protein (hsCRP) concentration and the risk of APO in GDM pregnant women. This study selected 406 non-elderly gestational diabetes patients diagnosed in the Renmin Hospital of Wuhan University from May 2021 to February 2023 as the research objects. According to the presence or absence of APO, they were divided into an APO group (n = 171) and a non-APO group (n = 235). Logistic regression model to evaluate the correlation between PLR and hsCRP and APO in women with GDM; Restricted cubic spline analyses was used to explore nonlinear correlations between PLR or hsCRP and the risk of APO; ROC curve analysis of the diagnostic performance of PLR and hsCRP for APO in women with GDM. APO occurred in 171 of the 406 included participants. Compared with the non-APO group, patients in the APO group had higher PLR and hsCRP levels. The incidence of APO was positively associated with PLR and the hsCRP level in each logistic regression model (P < 0.05). After adjusting for all the risk factors included in this study, restricted cubic spline analyses found that the PLR and the hsCRP level were positively associated with the risk of APO. The levels of PLR and hsCRP in the third trimester are related to the occurrence of APO in women with GDM, and high levels of PLR and hsCRP may indicate the occurrence of APO. [ABSTRACT FROM AUTHOR]

We present a new design for an interfacial dilational rheometer that can generate oscillatory dilational strain on a planar air–liquid interface. The strain is generated by a pneumatic mechanism involving a deformable film, which forms a circular barrier that can contract or expand under different pressures. The interfacial stress is measured using a Wilhelmy rod. We carefully examine and demonstrate the effects of potential sources of measurement error, including inertia, drag, buoyancy, flow from the bulk phase, and surface waves. The design avoids mixed deformations present in other instruments and is currently capable of accurate measurements at frequencies up to ∼0.1 Hz and dilational strains below 0.001, with potential for higher frequencies after further theoretical development. We demonstrate the integration of the interfacial dilational rheometer with a Langmuir trough by measuring the compression isotherm of an insoluble surfactant, stearic acid. Furthermore, we verify the capability of the interfacial dilational rheometer to perform frequency and amplitude sweeps and present the storage and loss moduli for a water-soluble surfactant, sodium dodecylbenzenesulfonate, at different concentrations. [ABSTRACT FROM AUTHOR]

Low-carbohydrate (LC) diets are popular among general and athletic populations attempting to lose body mass. This study investigated the effect of a 7-day LC or moderate-carbohydrate (MC) calorie–restricted diet followed by 18-h recovery on body composition and taekwondo-specific performance. In this randomised cross-over study, 12 male taekwondo athletes consumed an LC (10% of carbohydrate, 41% of protein, 49% of fat, and 15.8 ± 0.4 kcal/kg/day) or an isocaloric MC diet (60% of carbohydrate, 30% of protein, and 10% of fat) for 7 days. The participants then consumed a carbohydrate-rich recovery dinner (39.2 ± 3.1 kcal/kg) followed by breakfast (6.2 ± 0.4 kcal/kg) in both the trials. Three repeated sprint ability (RSA) tests were conducted after breakfast. The taekwondo-specific reaction battery was administered before the first RSA test and after each RSA test. The participants experienced similar magnitudes of significant loss of body mass in the LC (−2.4 ± 1.7%) and MC (−2.3 ± 1.7%) trials. Fat mass and fat percentage significantly decreased in the MC trial but remained unchanged in the LC trial after body mass loss. Fat free mass was maintained in both the trials. The average and peak power in the RSA tests and the premotor reaction time were similar between the trials. The participants experienced significantly higher fatigue in the LC trial. In conclusion, both the diets can help athletes rapidly lose body mass while maintaining performance as long as an adequate amount of carbohydrate is consumed during the recovery period. [ABSTRACT FROM AUTHOR]

Introduction: Older adults are more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher risk of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. Methods: This study included 4,428 individuals from Waves 8 (2016−2017) and 9 (2018−2019) of the English Longitudinal Study of Ageing (ELSA) who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19-related outcomes were examined using multivariable logistic regression. Results: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR = 1.87, 95% CI = 1.42−2.46) but not of COVID-19-related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR = 1.56, 95% CI = 1.24−1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR = 1.46, 95% CI = 1.23−1.74), lung diseases (OR = 1.40, 95% CI = 1.17−1.69), psychiatric conditions (OR = 1.40, 95% CI = 1.16−1.68), retinopathy/eye diseases (OR = 1.39, 95% CI = 1.18−1.64), and arthritis (OR = 1.27, 95% CI = 1.09−1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. Conclusion: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and hospitalisations, highlighting the vulnerability of those with CVD and other complex comorbidities. These findings facilitate crucial new evidence that should be considered for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak. [ABSTRACT FROM AUTHOR]

To achieve high charge density for the triboelectric polymer is a crucial task for fabricating triboelectric nanogenerators (TENGs). This work has developed a quenching polarization (QP) method to create ultrahigh and long‐persistent triboelectric charge on the triboelectric polymer with weak dipole polarity. The Ethylene chlorotrifluoroethylene copolymer (ECTFE) film can reach a charge density of 391 µC m−2 in the vertical contact mode by using this QP treatment, which is 200% higher than the result achieved by the most widely used method of corona polarization. The mechanism of the improvement through QP on the triboelectric properties is studied on the basis of the polarization induced grain refinement and interfacial trapping. The QP‐treated ECTFE can maintain ultra‐high charge density for both solid‐solid and solid‐liquid TENG. More interestingly, the charge induced by QP treatment is so persistent that it produces a recoverable discharging phenomenon for solid‐liquid TENG, which has never been observed before. This QP method provides a different approach for fabricating high‐performance triboelectric materials, while the QP‐induced changes in crystallization and tribo‐charge density can help to complete the physical understanding of the electrification mechanism of triboelectric polymer. [ABSTRACT FROM AUTHOR]

Inconel 718 alloy has high strength and work-hardening characteristics that make the material difficult to machine, and the morphology accuracy is difficult to guarantee. The microstructure of the alloy surface can improve the wettability of the material and affect the functional application of the alloy. In this study, a new process for machining square micropillars on the surface of Inconel 718 alloy using laser vertical cross-scanning technique is proposed—laser-belt machining. The microstructure, roughness, wettability, and chemical composition of Inconel 718 alloy surface were characterized. The results show that the morphological features can be effectively ensured by increasing the laser frequency, increasing the laser scanning pitch and decreasing the laser power. In addition, the capillary forces, nanoparticles, and roughness generated by the square micropillars under the effect of material ablation, thermodynamic processes, and oxidation reactions that make the alloy material surface with better wettability. Compared with other processes, this process has a contact angle of 4.7° under specific processing parameters, achieving a wettability transition from hydrophilic to superhydrophilic (contact angle less than 5°). This study provides guidance on the morphological accuracy and wettability analysis of microstructure surfaces using composite processing technology and provides a new idea for the rapid preparation of microstructure. [ABSTRACT FROM AUTHOR]

Background & Aims: Genome‐wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome‐wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents. Approach & Results: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population‐based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1H‐MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p <.05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1‐SD unit: 2.17, p = 9.7E‐10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76–0.81). Combining the GRS with clinical measures (waist‐to‐height ratio [WHtR] SDS, ALT, and HOMA‐IR) increased the AUC up to 0.86 (95% CI 0.84–0.88). Conclusions: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification. [ABSTRACT FROM AUTHOR]

Glycyrrhiza inflata Batalin is a medicinal licorice species that has been widely used by humans for centuries. Licochalcone A (LCA) is a characteristic flavonoid that accumulates in G. inflata roots with high economical value. However, the biosynthetic pathway and regulatory network of its accumulation remain largely unknown. Here we found that a histone deacetylase (HDAC) inhibitor nicotinamide (NIC) could enhance the accumulation of LCA and total flavonoids in G. inflata seedlings. GiSRT2, a NIC-targeted HDAC was functionally analyzed and its RNAi transgenic hairy roots accumulated much more LCA and total flavonoids than its OE lines and the controls, indicating a negative regulatory role of GiSRT2 in the accumulation of LCA and total flavonoids. Co-analysis of transcriptome and metabolome of RNAi-GiSRT2 lines revealed potential mechanisms in this process. An O-methyltransferase gene, GiLMT1 was up-regulated in RNAi-GiSRT2 lines and the encoded enzyme catalyzed an intermediate step in LCA biosynthesis pathway. Transgenic hairy roots of GiLMT1 proved that GiLMT1 is required for LCA accumulation. Together, this work highlights the critical role of GiSRT2 in the regulation of flavonoid biosynthesis and identifies GiLMT1 as a candidate gene for the biosynthesis of LCA with synthetic biology approaches. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between Dex and nuclear receptor 77 (Nur77). Methods: We investigated the effects of dexmedetomidine on lipopolysaccharide (LPS)‐induced inflammation in RAW264.7 cells and organ injury in the cecal ligation and puncture (CLP) mouse model. Additionally, we examined the relationship between dexmedetomidine and Nur77. The expression levels of Nur77 in RAW264.7 cells were analyzed under various types of stimulation using quantitative reverse transcription polymerase chain reaction and western blot analysis. Inflammatory cytokine levels in the cells were evaluated using enzyme‐linked immunoassay. Organ injuries were assessed by examining tissue histology and pathology of the lung, liver, and kidney. Results: Dexmedetomidine increased the expression of Nur77 and IL‐10, and downregulated inflammatory cytokines (IL‐1β and TNF‐α) in LPS‐treated RAW264.7 cells. The effect of dexmedetomidine on inhibiting inflammation in LPS‐treated RAW264.7 cells was promoted by overexpressing Nur77, while it was reversed by downregulating Nur77. Additionally, dexmedetomidine promoted the expression of Nur77 in the lung and CLP‐induced pathological changes in the lung, liver, and kidney. Activation of Nur77 with the agonist Cytosporone B (CsnB) significantly suppressed the production of IL‐1β and TNF‐α in LPS‐treated RAW264.7 cells. In contrast, knockdown of Nur77 augmented IL‐1β and TNF‐α production in LPS‐treated RAW264.7 cells. Conclusion: Dexmedetomidine can attenuate inflammation and organ injury, at least partially, via upregulating Nur77 in sepsis. [ABSTRACT FROM AUTHOR]

Replacing liquid electrolyte (LE) with gel polymer electrolyte (GPE) can significantly improve the safety and long-term stability of lithium-ion batteries. However, the traditional pure polymethyl methacrylate (PMMA)-based GPE after immersion in the electrolyte has the problem of poor mechanical properties and easy damage. In this article, PMMA was used as the matrix, and low-density polyethylene particles were mixed to prepare a kind of structure-enhanced and heat-resistant GPE by phase inversion method. The prepared GPE has high ionic conductivity at room temperature. It can slow down the temperature rise of the battery by reducing the ionic conductivity at high temperatures, thereby improving the safe application performance of the battery. In addition, the symmetrical battery made of this material can maintain ultra-low overvoltage and run stably for at least 800 h in the overpotential test when the current density is 1 mA cm−2. This study provides new insights for the preparation of high-temperature safety GPE. [ABSTRACT FROM AUTHOR]

Background: Survival prediction is important in cancer patients receiving hospice care. Palliative prognostic index (PPI) and palliative prognostic (PaP) scores have been used to predict survival in cancer patients. However, cancer primary site with metastatic status, enteral feeding tubes, Foley catheter, tracheostomy, and treatment interventions are not considered in aforementioned tools. The study aimed to investigate the cancer features and potential clinical factors other than PPI and PaP to predict patient survival. Methods: We conducted a retrospective study for cancer patients admitted to a hospice ward between January 2021 and December 2021. We examined the correlation of PPI and PaP scores with survival time since hospice ward admission. Multiple linear regression was used to test the potential clinical factors other than PPI and PaP for predicting survival. Results: A total of 160 patients were enrolled. The correlation coefficients for PPI and PaP scores with survival time were -0.305 and -0.352 (both p < 0.001), but the predictabilities were only marginal at 0.087 and 0.118, respectively. In multiple regression, liver metastasis was an independent poor prognostic factor as adjusted by PPI (β = -8.495, p = 0.013) or PaP score (β = -7.139, p = 0.034), while feeding gastrostomy or jejunostomy were found to prolong survival as adjusted by PPI (β = 24.461, p < 0.001) or PaP score (β = 27.419, p < 0.001). Conclusions: Association between PPI and PaP with patient survival in cancer patients at their terminal stages is low. The presence of liver metastases is a poor survival factor independent of PPI and PaP score. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) therapy can improve the survival of cancer patients with a high tumor mutation burden (TMB-H) or deficiency in DNA mismatch repair (dMMR) in their tumors. However, most cancer patients without TMB-H and dMMR do not benefit from ICB therapy. The inhibition of ATM can increase DNA damage and activate the interferon response, thus modulating the tumor immune microenvironment (TIME) and the efficacy of ICB therapy. In this study, we showed that ATM inhibition activated interferon signaling and induced interferon-stimulated genes (ISGs) in cisplatin-resistant and parent cancer cells. The ISGs induced by ATM inhibition were correlated with survival in cancer patients who received ICB therapy. In oral cancer, high expressions of ISG15, IFI27, and OASL were associated with low expressions of ATM, the activation of inflamed immune pathways, and increased tumor-infiltrating scores of CD8+ T, natural killer, and dendritic cells. The high expressions of ISG15, IFI27, and OASL were also correlated with complete remission in patients with cervical cancer treated with cisplatin. These results suggest that ATM inhibition can induce the interferon response and inflamed TIME, which may benefit ICB therapy. [ABSTRACT FROM AUTHOR]

Background: Skill integration is vital in students' mastery development and is especially prominent in developing code tracing skills which are foundational to programming, an increasingly important area in the current STEM education. However, instructional design to support skill integration in learning technologies has been limited. Objectives: The current work presents the development and empirical evaluation of instructional design targeting students' difficulties in code tracing particularly in integrating component skills in the Trace Table Tutor (T3), an intelligent tutoring system. Methods: Beyond the instructional features of active learning, step‐level support, and individualized problem selection of intelligent tutoring systems (ITS), the instructional design of T3 (e.g., hints, problem types, problem selection) was optimized to target skill integration based on a domain model where integrative skills were represented as combinations of component skills. We conducted an experimental study in a university‐level introductory Python programming course and obtained three findings. Results and Conclusions: First, the instructional features of the ITS technology support effective learning of code tracing, as evidenced by significant learning gains (medium‐to‐large effect sizes). Second, performance data supports the existence of integrative skills beyond component skills. Third, an instructional design focused on integrative skills yields learning benefits beyond a design without such focus, such as improving performance efficiency (medium‐to‐large effect sizes). Major Takeaways: Our work demonstrates the value of designing for skill integration in learning technologies and the effectiveness of the ITS technology for computing education, as well as provides general implications for designing learning technologies to foster robust learning. Lay Description: What is currently known about the subject matter?: Skill integration is vital in students' mastery development, and is especially prominent in developing coding tracing skills.Coding tracing skills are foundational to programming, an increasingly important area in the current STEM education, yet many novice students struggle with code tracing.Instructional design to support skill integration in learning technologies has been limited.One of the most effective technologies for skill mastery, intelligent tutoring systems (ITS), is underused or only used in a partial form in programming education. What our paper adds to this?: We present the development and empirical evaluation of instructional design targeting students' difficulties in code tracing particularly in integrating component skills in an ITS, the Trace Table Tutor.The instructional features of the ITS technology (e.g., active learning, step‐level support, individualized problem selection) support effective learning of code tracing.Students' performance data supports the existence of integrative skills beyond component skills.An instructional design that provides deliberate practice and focused practice on integrative skills yields learning benefits beyond a design without such features. The implications of study findings for practitioners: Designing for skill integration is valuable and should receive more attention in designing learning technologies to foster robust learning.The instructional features of full‐scale ITSs are effective in supporting learning and merit further application in learning technologies in computing education. [ABSTRACT FROM AUTHOR]

Paraphlomis caloneura, a new species from Guangxi Zhuang Autonomous Region, China, is described and illustrated. Molecular phylogenetic analyses based on two nuclear ribosomal DNA regions (ITS and ETS) and three plastid DNA markers (rpl32-trnL, rps16, and trnL-trnF) revealed that the new species is sister to P. hirsutissima. Both species are found in the limestone forests and are geographically close to each other, but P. caloneura can be easily distinguished from P. hirsutissima by its oblong or ovate-oblong and adaxially densely hispid laminas with broadly cuneate to cordate bases, densely hispid petioles, and slightly 2-lobed margins of upper corolla lips. [ABSTRACT FROM AUTHOR]

[Display omitted] Modifying surfaces with concentrated polymer brushes (CPBs) is an effective way to reduce friction of tribo-pairs lubricated with liquids. We investigate the hypothesis that colloids grafted with CPBs (hybrid colloids) can deposit onto tribo-substrates by varying the solvent quality with respect to the polymer, in order to obtain ultra-low coefficients of friction (CoFs), so-called superlubricity. Hybrid colloids are synthesized and characterized, and a dynamic light scattering compares their swellings in aqueous solutions of glycerol or polyethylene glycol. A mini-traction machine with viscoelastic tribo-pairs is used for lubrication experiments. Adsorption of colloids and film structures are tested using a quartz crystal microbalance and an atomic force microscope. The solvent controls whether hybrid colloids spontaneously adsorb to the substrate under quiescent conditions or require contact forces to enable (tribo-)deposition. In both cases, the friction in the boundary-mixed lubrication regimes is lower upon increasing the degree of swelling of CPBs and upon increasing coverage of deposited colloids. The greatest lubrication enhancement and surface coverage occur for the spontaneously adsorbed colloids, with ultra-low CoFs of order 10-3 over a large range of speeds. The results demonstrate the potential for hybrid colloids to be used as solvent dispersible "friction modifier additives". [ABSTRACT FROM AUTHOR]

Simple Summary: Although upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy in Western countries, recurrence and distant metastasis are common even after definitive surgery. Many prognostic factors have been identified from previous studies, allowing clinicians to better stratify risk to select patients for perioperative systemic therapy; however, the applicability of adjuvant chemotherapy for patients with stage II UTUC after radical surgery remains unclear. In this study, we found that patients with primary tumor location at ureter or renal pelvis plus synchronous ureter had more frequent disease relapse and worse long-term oncological outcomes than other patients. Male sex, older age, history of previous bladder cancer, and positive surgical margins remain important unfavorable prognostic factors for recurrence and survival. Additional treatment and closer surveillance in patients with these negative prognostic factors are warranted despite complete pathological removal of the tumor. Background: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. Methods: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan–Meier analyses for survival curves. Results: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan–Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Conclusions: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor. [ABSTRACT FROM AUTHOR]

Introduction: Aortic dissection (AD) is a life-threatening disease. However, the effectiveness of different strategies of antihypertensive therapies in non-operated AD patients is still unclear. Materials and methods: Patients were classified into five groups (groups 0–4) based on the number of classes of antihypertensive drugs, including β-blockers, renin-angiotensin system (RAS) agents (angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and the renin-inhibitors), calcium channel blockers (CCBs), and other antihypertensive drugs, were prescribed within 90 days after discharge. The primary endpoint was a composite outcome of re-hospitalization associated with AD, referral for aortic surgery, and all-cause death. Results: A total of 3932 non-operated AD patients were included in our study. The most prescribed antihypertensive drugs were CCBs, followed by β-blockers and ARBs. Within group 1, compared to other antihypertensive drugs, patients using RAS agents (aHR, 0.58; p = 0.005) had a significantly lower risk of occurrence of the outcome. Within group 2, the risk of composite outcomes was lower in patients using β-blockers + CCBs (aHR, 0.60; p = 0.004) or CCBs + RAS agents (aHR, 0.60; p = 0.006) than in those using RAS agents + others. Conclusion: For non-operated AD patients, RAS agents, β-blockers, or CCBs should be given in a different strategy of combinations to reduce the hazard of AD-related complications compared to other agents. [ABSTRACT FROM AUTHOR]

Metabolic activation of indirect-acting carcinogens in target organs is a recognized mechanism of carcinogenesis. This study aimed to determine the role of benzo[a]pyrene (BaP) metabolism enzymes lipoxygenase (LOX), cytochrome P4501A1 (CYP1A1), and prostaglandin synthetase (PGS) in the cytotoxicity and DNA damage induced by BaP in the human tracheobronchial epithelial cells (HBECs) using RNA interference strategy and metabolic enzyme inhibitors. Our results showed that in three epithelial cell lines (HBE, HTR-8/SVneo, and HaCat), BaP significantly upregulated 5-LOX protein expression. 15-LOX-2 expression also increased with increasing BaP concentration, but the change was less pronounced than that of 5-LOX. BaP caused significant cytotoxicity, DNA strand breaks, and 8-hydroxy-2'-deoxyguanosine formation in HBE, which was inhibited by 5-LOXshRNA, a specific inhibitor of 5-LOX (AA861), the CYP1A1 inhibitor α-naphthoflavone, and the PGS inhibitor naproxen. The protective effects of 5-LOXshRNA were stronger than AA861, naproxen and α-naphthoflavone. We conclude that BaP may be activated more by 5-LOX than by CYP1A1 and PGS to produce cytotoxicity and DNA damage in HBE. [ABSTRACT FROM AUTHOR]

As a traditional Tibetan medicine in China, Meconopsis grandis Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in Meconopsis grandis Prain and its pharmacodynamic mechanisms have scarcely been reported. We isolated a meroterpenoid named D1399 from Meconopsis grandis Prain endophytic fungi with strong antitumor activity. The structure analysis showed that D1399 is an alkaloid containing a 13-membered macrocyclic structure. The IC50 of D1399 for human lung cancer cells' viability ranged from 0.88 to 2.45 μM. Furthermore, we utilized TUNEL assay and western blotting to investigate the antitumor effectiveness of D1399. The results have shown that D1399 induced the apoptosis of lung cancer cells on the extrinsic and intrinsic pathways by boosting ROS generation and repressing AKT activity. In the mouse xenograft model, the average tumor weight with 30 mg·kg−1 D1399 treatment exhibited 73.19% inhibition compared with the untreated control, without affecting body weight loss. Above all, for the first time, our study provides a possible mechanism for the antitumor activity of D1399 in vitro and in vivo as a natural product from Tibetan medicine with Meconopsis grandis Prain, which may be a potentially promising antitumor drug candidate. [ABSTRACT FROM AUTHOR]

The roots of Sophora flavescens have a long history of use in Chinese medicine for the treatment of various medical conditions. Flavonoids from the ethyl acetate extract of S. flavescens have shown anti-inflammatory, anticancer, and antidiabetic properties. The objective of this study was to evaluate the toxicological profile of a flavonoid-rich extract of S. flavescens (SFEA). We conducted acute and sub-chronic oral toxicity studies of SFEA in Kunming (KM) mice and Sprague-Dawley (SD) rats. Acute oral administration of 9.0 g/kg SFEA did not result in mortality, clinical signs of toxicity, or abnormal changes in the body weight or food consumption patterns. No significant changes in hematological, blood biochemical, or histopathological parameters were observed. A 13-week sub-chronic toxicity study was conducted in SD rats; the rats were orally administrated with various doses of SFEA (in mg/kg): 0 (control), 40, 80, 400, 800, and 1200. Mortality, clinical signs, or treatment-related changes in body weight, food consumption, hematological parameters, blood biochemical parameters, organ weights, or histopathological parameters were not observed. We found that SFEA is practically nontoxic to KM mice at a dose of 9.0 g/kg and that the no-observed-adverse-effect-level (NOAEL) of SFEA in SD rats is greater than 1200 mg/kg. [ABSTRACT FROM AUTHOR]

Background: Dietary magnesium intake inversely correlated to risk of death in general population. However, it is relatively unknown whether the beneficial effect remains significant in individuals with diabetes. Our study purpose is to evaluate the association of dietary magnesium intake with mortality risk in diabetic population. Methods: The study population is recruited from 2003–2014 National Health and Nutrition Examination Survey, totaling 2,045 adults with diabetes being included. Participants were divided based on glycohemoglobin (HbA1c < 7% and ≥ 7%) and daily dietary magnesium intake (≤ and > 250mg/day) ascertained by 24-hour dietary recall interviews. Results: The average age of the study population was 52.9±10.1 years, with 49.1% being male. During a median follow-up of 77.0 months (interquartile range: 45.0–107.0 months), a total of 223 participants died (1.5 per 1000 person-months). Our results showed that individuals with lower dietary magnesium intake (≤250mg/day) had higher risk of all-cause (HR: 1.56, 95% CI: 1.13–2.16) and other-cause (non-cardiovascular and non-cancer) mortality (HR: 1.68, 95% CI: 1.09–2.60), while cardiovascular and cancer-related mortality were similar compared with individuals with magnesium intake > 250mg/day. We also showed that the risk of all-cause (HR: 1.86, 95% CI: 1.33–2.60) and other-cause mortality (HR: 2.03, 95% CI: 1.29–3.19) were higher in individuals with poorly controlled diabetes (HbA1c ≥7.0%) compared with HbA1c <7.0%; however, the association attenuated in the subgroup of higher magnesium intake (>250mg/day). When combining HbA1c and dietary magnesium intake, we showed that individuals with HbA1c ≥ 7% and dietary magnesium intake ≤ 250 mg/day had higher all-cause and other-cause (non-cardiovascular and non-cancer) mortality risk compared with those with HbA1c < 7% and/or dietary magnesium intake > 250 mg/day. Conclusion: Higher magnesium intake may help reduce mortality risk in individuals with diabetes and attenuate mortality risk of poor diabetic control. [ABSTRACT FROM AUTHOR]

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA‐associated acetyl‐tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6‐guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6‐induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF‐κB‐induced CR and subsequently CR‐dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF‐κB‐CR‐Cdc42 cascade collectively dictate GR. [ABSTRACT FROM AUTHOR]

The positional accuracy of multi-leaf collimators (MLC) is important in stereotactic body radiotherapy (SBRT). The aim of this study was to investigate the impact between MLC positional error and dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC). Fifteen patients with NSCLC were selected to design the 360 SBRT-VMAT plans and the 360 SBRT-IMRT error plans. The DICOM files for these treatment plans were imported into a proprietary computer program that introduced delivery errors. Random and systematic MLC position (0.1, 0.2, 0.5, 1.0, 1.5, and 2.0 mm) errors were introduced. The systematic errors were shift errors (caused by gravity), opening errors, and closing errors. The CI, GI, d2cm and generalized equivalent uniform dose (gEUD) were calculated for the original plan and all treatment plans, accounting for the errors. Dose sensitivity was calculated using linear regression for MLC position errors. The random MLC errors were relatively insignificant. MLC shift, opening, and closing errors had a significant effect on the dose distribution of the SBRT plan. VMAT was more significant than IMRT. To ensure that the gEUD variation of PTV is controlled within 2%, the shift error, opening error, and closing error of IMRT should be less than 2.4 mm, 1.15 mm, and 0.97 mm, respectively. For VMAT, the shift error, opening error, and closing error should be less than 0.95 mm, 0.32 mm, and 0.38 mm, respectively. The dose sensitivity results obtained in this study can be used as a guide for patient-based quality assurance efforts. The position error of the MLC system had a significant impact on the gEUD of the SBRT technology. The MLC systematic error has a greater dosimetric impact on the VMAT plan than on the IMRT plan for SBRT, which should be carefully monitored. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated the expression status of CD56 was associated with prognosis in multiple myeloma (MM) patients, the prognostic significance remains controversial. Here, the prognostic value of CD56 is further investigated in MM patients. We systematically searched the databases including PubMed, EMBASE, Web of Science and the Cochrane Library. The hazard ratios (HRs) with their 95% confidence intervals (CIs) were pooled to evaluate the relationship between CD56 and overall survival (OS) and progress-free survival (PFS). A total of 14 studies covering 1365 patients were included in this meta-analysis. The results revealed that CD56 negativity in MM was associated with poorer OS (HR = 1.83, 95% CI = 1.29–2.60, P = 0.001) and PFS (HR = 1.57, 95% CI = 1.27–1.95, P = 0.000). Subgroup analysis further demonstrated that there was an effect of treatment regimen, detection method, survival analysis, study region and the cut-off value of CD56 on CD56 expression. The meta-analysis suggested that CD56 negative patients had a poor prognosis for OS in Asian patients and for PFS in non-Asian patients. Novel drugs didn't show a significant improvement or overcome on the adverse prognosis brought by CD56 negativity. For patients undergone autologous stem-cell transplantation (ASCT), the poor prognosis was overcome by the treatment, which shed a light on the prognostic judgment and individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Serum prealbumin level is slightly higher, whereas albumin is lower in peritoneal dialysis (PD) than hemodialysis (HD) patients. It is unknown whether albumin to prealbumin ratio (APR) is associated with mortality risk among PD patients. This study aimed to evaluate the clinical implications of APR and its prediction value on long-term outcomes of PD patients. Methods: The study population were prevalent PD patients at a tertiary hospital. Based on APR, a total of 220 PD patients were divided into 3 groups: group 1: top tertile, median APR: 121.1; IQR:109.5–131.9 (n = 73, male: 37%; age: 59±13); group 2: middle tertile, median APR: 97.1; IQR 93.5–100.0 (n = 73, male:37%; age: 54±14), and group3: bottom tertile, median APR: 81.3; IQR:76.8–85.0 (n = 74, male:38%; 54±11). Patients were followed up for a maximum of 5 years. Outcome of interest was all-cause mortality. Results: Group 1 was characterized by older age, higher prevalence of diabetes, lower nPCR, higher Davies score and hs-CRP level. APR positively correlated to hs-CRP (β = 0.149, p = 0.045), but negatively correlated to nPCR (β = -0.161, p = 0.034). Hyperprealbuminemia, accounting for 0%, 23.3%, and 82.4% in groups 1,2, and 3, was associated with a lower risk for mortality (HR:0.41, 95%CI = 0.23–0.73). The cumulative survival is significantly lower in group 1 than the other two groups. By multivariable Cox regression, APR (HR:1.02; 95%CI:1.01–1.03) was found to be an independent predictor of long-term mortality. Conclusion: PD patients with high APR are characterized by having more comorbidities and marked malnutrition-inflammation status, and are associated with long-term mortality, whereas hyperprealbuminemia and lower APR are favorable prognostic factors. [ABSTRACT FROM AUTHOR]

STK11 is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). STK11 mutations also lead to dramatic changes in the tumor microenvironment. Studies have shown that strengthening the killing effect of NK cells is vital for effective cancer treatment. Nonetheless, the mechanism of STK11 mutation in modulating the killing effect of NK cells on LUAD cells remains unclear. The expression of STK11, Ki67, and IFN‐γ in tumor tissues was evaluated by immunohistochemistry. The contents of T cells, NK cells, and macrophages were analyzed by immunofluorescence assay. The expression of IL2, IL6, and IFN‐γ was detected by ELISA. STK11 expression in LUAD cell line was evaluated by qRT‐PCR. CCK‐8 and colony formation assay were used to measure proliferative ability of LUAD cells and the viability of NK cells. Flow cytometry was utilized to analyze cell apoptosis and NK cell content. Transwell assay was utilized to measure the chemotactic capability of NK cells. In vivo experiments validated the effect of abnormal expression of STK11 on tumor growth. LUAD patients with STK11 mutation had a high tumor proliferative ability. Forced expression of STK11 could substantially constrain the proliferation of LUAD cells and induce cell apoptosis. In addition, STK11 deletion significantly reduced the infiltration level of NK cells and inhibited the viability and chemotactic ability of NK cells as well as their killing effect on LUAD cells. In vivo animal experiment results demonstrated that STK11 deletion significantly reduced NK cell infiltration and promoted LUAD tumor growth. This study revealed the mechanism of STK11 mutation regulating NK cytotoxicity and promoting tumor development, providing scientific basis for the exploration of STK11‐related LUAD therapeutic targets and theoretical reference for developing new NK cell‐based immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Emotion-related hyperarousal is an important core pathology of poor sleep. Studies investigating the interplay of alexithymia and affective experiences in determining sleep quality have yielded mixed results. To disentangle the inconsistency, this study examined the concurrent predictive power of alexithymia, and negative and positive affect, while incorporating interoceptive sensibility (IS) as a possible moderator. Methods: A sample of 224 (70.10% were female) participants completed the Toronto Alexithymia Scale, Positive and Negative Affect Schedule, Pittsburgh Sleep Quality Index, Multidimensional Assessment of Interoceptive Awareness (MAIA), and Marlowe‐Crowne Social Desirability Scale (for controlling response bias) using paper and pencil. A two-stage cluster analysis of the MAIA was used to capture IS characteristics. Stepwise regression was conducted separately for each IS cluster. Results: A three-group structure for IS characteristics was found. Higher alexithymia was predictive of poor sleep quality in the low IS group, while higher negative affect predicted poor sleep quality in the moderate and high IS groups. Additionally, alexithymia and positive affect were significantly different in the three IS groups, while negative affect and sleep quality were not. Conclusions: Emotion and cognitive arousal may impact sleep quality differently in individuals with different levels of internal focusing ability, depending on physiological versus emotional self-conceptualization. The implications on pathological research, clinical intervention, study limitations and future directions are discussed. [ABSTRACT FROM AUTHOR]

Aiming at realizing efficient microalgae-based CO 2 sequestration from coal-fired power plants, this study investigated the interaction between the mass transfer of SO 2 -contained flue gas and microalgae growth. The results indicate that the CO 2 dissolution in microalgae suspension and the growth of Chlorella vulgaris could be hindered by solution acidification and oxidative molecular species produced in the conversion of bisulfite to sulfate. With the SO 2 concentration increased from 0 to 400 ppm, the pH of the culture medium decreased from 7 to 2, and the SO 4 2− concentration reached 1 g L−1, resulting in a decrement of 18.1% in the CO 2 dissolution rate. Moreover, the Chlorella cells could only maintain their growth within the SO 4 2− concentration of 800 mg L−1 accompanied by a decrement of 58% in maximum biomass concentration. The cultivation collapsed under excessive SO 2 (over 400 ppm) as the plasmolysis and chloroplast decomposition occurred which severely inhibited the microalgal photosynthesis. This work provides a guide to cultivating microalgae using real flue gas. [Display omitted] [ABSTRACT FROM AUTHOR]

Mixed bacterial syngas fermentation is a promising carbon-neutral method for producing acetic acid and ethanol. However, the bacterial community and metabolic pathways were different in the growth and ethanol production stages, whereas the activity of the bacterial community greatly depended on the pH of the culture. In this study, the effect of pH on syngas fermentation performance and microbial community composition under continuous gas supply was investigated. The mixed bacteria grew fastest at a pH of 7, while a constant pH of 6 led to the highest ethanol concentration of 5.15 g L−1, which was 160 % higher than that at pH 7. Based on this, a two-step pH regulation method was proposed in this study to improve the ethanol production. Initially, the culture pH was maintained at 7 to create optimal growth conditions. Once bacterial density stabilized, it was then changed to a pH 6 to promote ethanol production. By doing this, compared with the control group, the maximum ethanol concentration (5.85 g L−1) increased by 148.9 %, the ethanol production rate (2.41 g L−1 d−1) increased by more than 8 times. This two-step pH regulation method ensured a high bacterial density and effectively stimulated ethanol production during syngas fermentation. [Display omitted] [ABSTRACT FROM AUTHOR]

Transcription factors play an important role in regulating the expression of detoxification genes (e.g. P450s) that confer insecticide resistance. Our previous study identified a series of candidate transcription factors (CYP6B7 -fenvalerate association proteins, CAPs) that may be related to fenvalerate-induced expression of CYP6B7 in a field HDTJ strain of H. armigera. Whether these CAPs can mediate the transcript of CYP6B7 induced by fenvalerate in a susceptible HDS strain of H. armigera remains unknown. Further study showed that the expression levels of multiple CAPs were significantly induced by fenvalerate in HDS strain. Knockdown of CAP19 [fatty acid synthase-like (FAS)], CAP22 [polysaccharide biosynthesis domain-containing protein 1 (PBDC1)], CAP24 [5-formyltetrahydrofolate cycloligase (5-FCL)], CAP30 [peptidoglycan recognition protein LB-like (PGRP)] and CAP33 [NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 (NDUFA11)] resulted in significant inhibition of CYP6B7 and some other P450 genes expression; meanwhile, the sensitivity of HDS strain larvae to fenvalerate was significantly increased. In addition, PBDC1, PGRP and NDUFA11, either alone or in combination, could significantly enhance the activity of CYP6B7 promoter in HDS strain, as well as the expression level of CYP6B7 gene in Sf9 cells line. These results suggested that PBDC1, PGRP and NDUFA11 may be involved in the transcript regulation of key detoxifying genes in response to fenvalerate in HDS strain of H. armigera. [Display omitted] • The expression levels of multiple CAPs were significantly induced by fenvalerate. • Knockdown of CAPs could significantly inhibit the expression of CYP6B7. • Knockdown of CAPs significantly increased the sensitivity of larvae to fenvalerate. • CAP22, CAP30 and CAP33 could significantly enhance the activity of CYP6B7 promoter. • Knockdown of CAPs also affected the expression of some other P450s. [ABSTRACT FROM AUTHOR]

Light availability greatly affects microalgal photosynthetic carbon sequestration and biomass production. However, the continuously changing light transmission during microalgal growth poses a significant challenge for enhancing their performance from the light optimization perspective. In this study, the growth-dependent light transmission characteristics in microalgal suspensions were investigated. As microalgae grew, the light saturation regions within the microalgal suspension expanded initially and then contracted, while the light inhibition expanded and the light limitation regions continuously shrank. Although biomass accumulation was relatively slow during the early growth stage (time <50 h) with biomass concentrations below 0.5 g/L, rapid changes in light attenuation occurred. Furthermore, the light-dependent local growth kinetic was developed to predict microalgal growth and CO 2 fixation potential during growth. A contraction of the local microalgal CO 2 fixation and specific growth rate distribution curve towards the incident light source occurred with its growth. Finally, the performance-enhancing effects of light optimization strategies on flat plate photobioreactors were analyzed based on the above model. Microalgal growth potential and CO 2 fixation performance in the flat plate reactor with 2 cm light path could be increased by up to 188% when the growth-based light intensity enhancement strategy was adopted. It could be further increased by approximately 31% when the light was changed from single-sided to double-sided illumination (same light energy input), and the maximum net profit from microalgal cultivation could be enhanced by 60%. In conclusion, this study provides a unique insight into promoting microalgal carbon sequestration and biomass production from the light optimization perspective. [Display omitted] • The growth-dependent light transmission in microalgal suspensions was studied. • Rapid change in light attenuation occurred in the early growth stage within 50 h. • The light saturation regions expanded initially and then shrank as microalgal grew. • The light inhibition/limitation regions expanded/shrank as microalgal grew. • Growth-based light intensity enhancement boosted growth/CO 2 fixation by up to 188%. [ABSTRACT FROM AUTHOR]

Deep Learning (DL) models, such as Long Short-Term Memory (LSTM) and Gated Recurrent Units (GRU), have been widely used to predict the intermittency of wind power; however, the non-linear activation functions and backpropagation mechanisms in DL models increase computational complexity and energy consumption. This paper proposes a prediction model based on Green Learning (GL) to reduce energy consumption. The proposed GL model replaces the feature extraction of activation functions with a hybrid feature extraction approach combining categorical and numerical features. We also employ cluster centroids and quantile regression forest for classification/regression to eliminate the need for backpropagation in optimizing hyperparameters. Using Taiwan as a case study, this paper evaluates the risk of fluctuations in regional wind power generation in 2030. In simulations, the proposed GL model achieved excellent accuracy with energy consumption significantly lower than that of DL models. Our analysis also revealed that by 2030, fluctuations in wind power generation during the winter will exceed 40% of the peak supply capacity in the central region, indicating the need to enhance the resilience of regional power systems. • This is the first study to apply green learning to wind power prediction. • This study discriminated seasonal climate patterns at the regional level. • This study assessed the fluctuation risk under large-scale wind power integration. • The maximum hourly variability in wind power is projected to exceed 6,010 MWh by 2030. • We recommend the continued deployment of regional energy storage systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • The orientation-dependent growth mechanism of Cr-rich oxide precipitate is revealed. • The directed growth is thermodynamically preferred than the isotropic growth. • The outward diffusion of Fe atom leaving vacancies which enhancing the Cr diffusion. • O promotes the aggregation of Cr atoms along the [1 0 0] direction. Advanced characterization techniques and atomic simulations, including density functional theory calculation and molecular dynamics simulation, are performed to reveal the orientation-dependent growth mechanism of Cr-rich oxide precipitates in the internal oxide layer of Fe-9Cr steel under supercritical water environment. A new Fe/Cr/O/H reactive force field is constructed to address the limitations of existing empirical potentials in accurately describing the corrosion mechanism of FeCr alloy. The high-resolution characterization reveals the growth mechanism of needle-like FeCr 2 O 4 precipitates in the <1 0 0> direction of the matrix. Atomic simulation demonstrate that the directed growth is thermodynamically preferred than the isotropic growth. The vacancies generated by the outward diffusion of metal atoms enhancing the diffusion of Cr atoms, and O promote the aggregation of Cr atoms along the <1 0 0> direction. [ABSTRACT FROM AUTHOR]

Background: The potential therapeutic benefit of adjuvant radiotherapy for patients with stage I uterine sarcoma has not been clear. In this study, we aimed to develop a risk scoring model to select the subgroup of patients with stage I uterine sarcoma who might benefit from adjuvant radiotherapy. Methods: Patients with stage I uterine sarcoma from the Surveillance, Epidemiology, and End Results program from 2010 to 2014 were retrospectively included in this analysis. Cox proportional hazards models were performed to identify risk factors. Results: A total of 947 stage I uterine sarcoma patients were included. The 5‐year disease‐specific survival (DSS) of the overall cohort was 75.81%. Multivariate analysis identified stage (p = 0.013), tumor grade (p <0.001) and histology (p = 0.043) as independent prognostic factors for DSS, and these factors were used to generate the risk scoring model. The low‐risk group presented a better DSS than the high‐risk group (95.51% vs. 49.88%, p < 0.001). The addition of radiotherapy to surgery significantly increased the DSS in the high‐risk group compared with surgery alone (78.06% vs. 46.88%, p = 0.022), but no significant survival benefit was observed in the low‐risk group (98.36% vs. 100%, p = 0.766). Conclusions: Our risk scoring model based on stage, tumor grade, and histology predicted the outcome of patients with stage I uterine sarcoma cancer. This system may help to select stage I uterine sarcoma cancer patients who might benefit from adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Oxidized multi-walled carbon nanotube/nano-gold (AuNP-ox-MWCNT) composites with strong electrochemiluminescence (ECL) activity were applied to construct a new ECL immunosensor for the detection of carcinoembryonic antigen (CEA). The immunosensor showed a linear response range of 10–100 ng mL−1 and detection limit of 0.76 ng mL−1 (at a signal-to-noise ratio of 3). The as-developed immunosensor exhibited several advantages, including being simple to fabricate and being label free. The results indicated that ox-MWCNTs as a luminescent material have great application potential in analysis. [ABSTRACT FROM AUTHOR]

The development of PtIV prodrugs which are selectively reduced within cancerous cells into their PtII therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep‐seated or large tumors is limited. To overcome this limitation, herein, the example of PtIV‐functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self‐assemble into nanoparticles was functionalized with PtIV complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer‐targeting peptides. Upon irradiation, the PtIV center is reduced to PtII and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple‐negative breast cancer tumor inside a mouse model. [ABSTRACT FROM AUTHOR]

Die Entwicklung von PtIV‐Prodrugs, die in Krebszellen selektiv in ihre therapeutisch wirksamen PtII‐Spezies reduziert werden, hat in den letzten Jahrzehnten zunehmend an Bedeutung gewonnen. Trotz jüngster Fortschritte in der Forschung werden die meisten untersuchten Verbindungen mit ultraviolettem oder blauem Licht angeregt. Da die Eindringtiefe des Lichts bei diesen Wellenlängen gering ist, ist die Behandlung von tiefsitzenden oder großen Tumoren begrenzt. Um diese Einschränkung zu überwinden, wird hier über ein Beispiel von PtIV‐funktionalisierten Nanopartikeln berichtet, die im NIR‐Bereich bei 808 nm angeregt werden können. Das Polymer‐Grundgerüst, das sich selbst zu Nanopartikeln zusammensetzen kann, wurde mit PtIV‐Komplexen für die Chemotherapie, Photosensibilisatoren für die photodynamische Immuntherapie und Kern‐/Krebs suchenden Peptiden funktionalisiert. Bei der Aussetzung zu Licht wird das PtIV‐Zentrum zu PtII reduziert und die axial koordinierten Liganden freigesetzt, was eine multimodale Behandlung ermöglicht. Die Nanopartikel reichern sich selektiv im Tumorgewebe an und haben in einem Mausmodell einen dreifach‐negativen Brustkrebstumor vernichtet. [ABSTRACT FROM AUTHOR]