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Simple Summary: Cancer cachexia is an underestimated condition with huge impact on survival and quality of life for many cancer patients. Currently, there is no reliable diagnosis for this condition, particularly for cancer cachexia at an early stage. The aim of our study is to develop potential biomarkers that can be used not only for diagnosing cancer cachexia but also evaluating potential anti-cachexia therapy such as anti-Fn14 mAb treatment. We identified several circulating biomarkers for cancer cachexia and confirmed that LCN2 is a promising biomarker for cancer cachexia in humans. These biomarkers could accelerate both diagnosis and clinical trials for cancer cachexia. Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples. [ABSTRACT FROM AUTHOR]

The implementation of turn restrictions represents a critical research challenge in chiplet-based systems, with the objective of achieving deadlock-free communication. Nevertheless, existing methodologies encounter difficulties in terms of computational complexity, which impedes the design process. Moreover, as the scale of the problem increases, the cost of addressing it becomes increasingly untenable. In this paper, we introduce the efficient turn restrictions setting (ETRS) method to reduce the computational cost of implementing turn restrictions for boundary routers in chiplet-based systems. In stage 1, we present a symmetry-based preprocessing algorithm (SBPA). SBPA exploits the symmetry inherent in chiplet topologies by generating multiple sets of identical modes, ensuring that scenarios with the same objective function value are calculated only once per iteration. In stage 2, a heuristic selection algorithm (HSA) for turn restrictions based on NSGA-II is proposed as a means of searching for approximately optimal solutions and of solving the problem quickly. In stage 3, different filtering criteria are introduced to evaluate the Pareto fronts of HSA for making decisions on the placement of boundary routers and their turn restrictions. Evaluation results reveal that the proposed ETRS method surpasses existing solutions in terms of computation efficiency. Moreover, it delivers satisfactory optimal objective values. [ABSTRACT FROM AUTHOR]

• Competitive null models may yield false positives from co-expression. • Self-contained null models may yield false positives from bimodal correlations. • Test statistics interact differently with two types of null models. • Supplementary analyses with various configurations support the findings. Correlating transcriptional profiles with imaging-derived phenotypes has the potential to reveal possible molecular architectures associated with cognitive functions, brain development and disorders. Competitive null models built by resampling genes and self-contained null models built by spinning brain regions, along with varying test statistics, have been used to determine the significance of transcriptional associations. However, there has been no systematic evaluation of their performance in imaging transcriptomics analyses. Here, we evaluated the performance of eight different test statistics (mean, mean absolute value, mean squared value, max mean, median, Kolmogorov-Smirnov (KS), Weighted KS and the number of significant correlations) in both competitive null models and self-contained null models. Simulated brain maps (n = 1,000) and gene sets (n = 500) were used to calculate the probability of significance (Psig) for each statistical test. Our results suggested that competitive null models may result in false positive results driven by co-expression within gene sets. Furthermore, we demonstrated that the self-contained null models may fail to account for distribution characteristics (e.g., bimodality) of correlations between all available genes and brain phenotypes, leading to false positives. These two confounding factors interacted differently with test statistics, resulting in varying outcomes. Specifically, the sign-sensitive test statistics (i.e., mean, median, KS, Weighted KS) were influenced by co-expression bias in the competitive null models, while median and sign-insensitive test statistics were sensitive to the bimodality bias in the self-contained null models. Additionally, KS-based statistics produced conservative results in the self-contained null models, which increased the risk of false negatives. Comprehensive supplementary analyses with various configurations, including realistic scenarios, supported the results. These findings suggest utilizing sign-insensitive test statistics such as mean absolute value, max mean in the competitive null models and the mean as the test statistic for the self-contained null models. Additionally, adopting the confounder-matched (e.g., coexpression-matched) null models as an alternative to standard null models can be a viable strategy. Overall, the present study offers insights into the selection of statistical tests for imaging transcriptomics studies, highlighting areas for further investigation and refinement in the evaluation of novel and commonly used tests. [ABSTRACT FROM AUTHOR]

Purpose: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo.ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies.The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo.[89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.Methods: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo.ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies.The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo.[89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.Results: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo.ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies.The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo.[89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.Conclusion: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo.ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies.The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo.[89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101. [ABSTRACT FROM AUTHOR]

Chiplet integration technology offers enhanced performance and reduced costs by breaking down a large chip into smaller chiplets, which are then interconnected using advanced packaging technology. However, the current chiplet interconnects give priority to correctness concerns rather than load balancing issues. While prioritizing correctness aims to prevent deadlocks, a system that is free of deadlocks can still experience load imbalances that compromise its overall performance. This paper presents the LBDR strategy, which is a load-balanced deadlock-free routing strategy for chiplet systems, and effectively enhances the system performance. Firstly, we develop a novel boundary nodes selection criterion and a heuristic algorithm based node binding mechanism to maintain a balanced load on vertical links for each chiplet's outbound traffic. Secondly, we select turn restrictions at the boundary nodes to ensure that inbound traffic flows evenly into the chiplet, while maintaining a deadlock-free system. Experiments using the Garnet in gem5 simulator show that this strategy outperforms existing methods in terms of load balancing, throughput, and latency, and is applicable to a variety of traffic scenarios. • A binding mechanism is proposed to achieve load balancing of outbound traffic. • The turn restrictions are selected for almost equal opportunities to inbound traffic. • The simulation results demonstrate that this method outperforms existing methods. [ABSTRACT FROM AUTHOR]

Acetone cyanohydrin (ACH), an organic cyanide, is mainly used in the production of methyl methacrylate (MMA), and it also exists in cassava roots, the main calorie source in some tropical countries. ACH can decompose spontaneously or enzymatically into acetone and highly toxic hydrogen cyanide (HCN) and be potentially toxic to its contacts. Given that limited forensic studies and case reports on fatal ACH poisoning are available, herein, we present a report of two fatal cases of ACH poisoning in which the two victims, with postmortem cyanide blood concentrations of 4.22 μg/ml and 4.07 μg/ml, suffered from acute poisoning of ACH due to a traffic accident. Furthermore, a literature review of cyanide poisoning case reports from 2000 to 2020 was carried out, and 28 subjects with cyanide poisoning were presented, including the age, sex, cause of poisoning, autopsy findings and the cyanide concentration in the blood. ACH poisoning lacks specific and reliable autopsy findings for diagnosis, and relevant toxicological studies are necessary. Due to the chemical properties of ACH that allow it to easily decompose, the toxicological analysis of acetone and cyanide in biological samples is essential for the diagnosis of ACH poisoning. [ABSTRACT FROM AUTHOR]

Brain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega‐analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance‐general and substance‐specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence. [ABSTRACT FROM AUTHOR]

Endometritis is a significant contributor to reduced productivity in yaks in Tibet, China. The Cyt-c/Caspase-3 signaling axis plays a crucial role in the mitochondrial pathway that triggers cell apoptosis due to endogenous factors. In this study, we examined the endometrial epithelial tissue of yaks with endometritis using pathological examination, immunohistochemical analysis, TUNEL staining, qRT-PCR, and Western blot. The results indicated significant changes in the apoptotic factors of the Cyt-c/Caspase-3 signaling axis. The expression levels of Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 were significantly increased (P < 0.05), while the expression level of Bcl-2 was significantly decreased. Immunohistochemistry results revealed significant increase in Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 expression in the cytoplasm compared to the healthy group, except for Bcl-2, which showed a significant decrease. Pathological section analysis demonstrated that clinical endometritis in yaks led to structural damage, bleeding, congestion, and inflammatory cell infiltration in the endometrial epithelium. Our study findings indicated that clinical endometritis in yaks can modulate apoptosis of endometrial epithelial cells via the Cyt-c/Caspase-3 signaling pathway, resulting in different levels of damage. This research is pioneering in exploring cell apoptosis induced by clinical endometritis in yaks, offering novel insights and potential strategies for the future prevention and treatment of endometritis in yaks. • The occurrence of yak endometritis is accompanied by cell apoptosis. • The Cyt-c/Caspase-3 signaling axis and its related factors play a significant role in the development of yak endometritis. • This study provides new insights into the relationship between endometritis and apoptosis in yak. [ABSTRACT FROM AUTHOR]

Carbon nanotube fibers (CNTFs) have many similarities with individual aligned carbon nanotubes (ACNTs) in terms of mechanical strength and electrical and thermal conductivity. Unlike ACNTs, CNTFs are macroscopic, easy to operate and maintain strong directionality during processing, so they are much more cost-effective and have potential for economical macroscale applications in the field of electronic skins (E-skins). In this paper, novel flexion-sensitive and stretch-sensitive E-skins based on aligned CNTF (ACNTF) arrays with bridge structures are introduced. During the bending and stretching processes, their bridge positions can be relative sliding and relatively misaligned, resulting in the variation of relative resistance change (ΔR/R 0) of E-skins. By detecting the varying regularity of ΔR/R 0 , the law can be analyzed between the bending angle (θ)/stretching strain (ε) and ΔR/R 0. Furthermore, the characteristics of the prepared E-skins include a simple preparation method, large detection range (0–90 °), high durability (> 1000 cycle) and low production cost, so they have prospective applications in wearable detectors and human–machine interactions. [Display omitted] • Flexion-sensitive and stretch-sensitive E-skins are fabricated based on aligned CNTF arrays with bridge structures. • Bending and stretching detection ranges of the E-skins are 0–90 ° and 0–15%, respectively. • Electronic skins can be widely used in the fields of wearable detectors and human-machine interaction. [ABSTRACT FROM AUTHOR]

Previous studies suggest that individuals with substance use disorder have abnormally large responses to unexpected outcomes (reward prediction errors [RPEs]). However, there is much less information on RPE in individuals at risk of alcohol misuse, prior to neurobiological adaptations that might result from sustained alcohol use. Here, participants (mean age 23.77 years, range 18-32 years) performed the electrophysiological monetary incentive delay task. This task involved responding to a target stimulus following reward incentive cues to win, or avoid losing, the cued reward while brain activity was recorded under 64-channel EEG. The Alcohol Use Disorders Identification Test (AUDIT) was used to quantify at-risk alcohol use, with high (n = 22, mean AUDIT score: 13.82) and low (n = 22, mean AUDIT score: 5.77) alcohol use groups. Trial-by-trial RPEs were estimated using a Rescorla-Wagner reinforcement model based on behavioral data. A single-trial analysis revealed that the feedback-related negativity (FRN) and feedback P3 (fb-P3) event-related potential components were significantly modulated by RPEs. There was increased RPE-related fb-P3 amplitude for those in the high alcohol use group. Next, the mean amplitude of ERPs elicited by positive and negative RPEs were compared between groups. We found that high alcohol use participants had attenuated FRN amplitude in contrast with low alcohol use participants for both positive and negative RPEs but enhanced fb-P3 for both positive and negative RPE. These results, with differences in RPE in an at-risk group, suggest that RPE a potential vulnerability marker for alcohol use disorder. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is an unexpected death caused by a sudden loss of cardiac function, which is currently a global public health problem. Evaluation of the agonal cardiac function of the deceased is a quite important task for the diagnosis of SCD in forensic medicine. Brain natriuretic peptide (BNP) and N‐terminal proBNP (NT‐proBNP) are currently considered as significant biomarkers for the diagnosis of heart failure in both clinical and forensic practices. To investigate the postmortem evaluation roles of postmortem BNP and NT‐proBNP levels for SCD, the present study meta‐analyzed eight related studies from Embase, Cochrane Library, PubMed, China Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data. Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included literature, and the meta‐analysis was performed by RevMan 5.3.5 software. Postmortem NT‐proBNP in pericardial fluid showed higher levels in the SCD group than that of the non‐SCD group with the weighted mean difference = 3665.74, 95% confidence interval: 1812.89–5518.59, and p = 0.0001. However, postmortem levels of BNP in pericardial fluid and NT‐proBNP in serum revealed no statistical difference between SCD and non‐SCD subjects. The results of present meta‐analysis demonstrated that postmortem NT‐proBNP in the pericardial fluid could be used as an ancillary indicator for evaluation of agonal cardiac function in forensic medicine. [ABSTRACT FROM AUTHOR]

Background: The Lieber–DeCarli alcoholic liquid diet is a classical method for establishing animal models of alcoholic cardiomyopathy (ACM). No study has reported whether the AIN‐93 diet, which is widely used as a standard diet for both long‐term and short‐term studies with laboratory animals, could be used to construct the ACM animal model. The present study intended to investigate whether the AIN‐93 diet could be used to establish a mouse ACM model. Methods: Twenty‐four C57BL/6 male mice were randomly divided into 4 equally sized groups. In ethanol (EtOH)‐fed groups, mice were fed a 4%‐EtOH (w/v, 28% of total calories) alcoholic liquid diet of Lieber–DeCarli or the AIN‐93 diet for chronic alcohol exposure for 180 days. In control‐fed groups, mice were fed with non‐EtOH liquid diets with the same calories as EtOH‐fed groups. Morphological observations of the hearts and molecular investigation of the brain natriuretic peptide (BNP) were carried out by echocardiography, hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, real‐time quantitative polymerase chain reaction (qPCR), and enzyme‐linked immunosorbent assay. Results: Echocardiography showed that mice fed with either the 4%‐EtOH Lieber–DeCarli diet or the 4%‐EtOH AIN‐93 diet had dilated ventricles and poor cardiac function. IHC staining of BNP, qPCR of BNP mRNA, and plasma concentration of BNP showed an up‐regulated expression in mice fed with both the 4%‐EtOH Lieber–DeCarli and 4%‐EtOH AIN‐93 diets. Less fatty liver was also observed in mice fed the AIN‐93 alcoholic diet than those fed the Lieber–DeCarli alcoholic diet. Conclusions: The AIN‐93 alcoholic liquid diet can be used to establish ACM animal models, as with the conventional Lieber–DeCarli alcoholic liquid diet. [ABSTRACT FROM AUTHOR]

Abstract In this study, the natural attenuation of naphthalene during riverbank infiltration was examined using batch experiments. The results indicated that, as the grain size and the permeability coefficient decreased, the natural attenuation rate of naphthalene increased, and it was highest in loam (62%) and lowest in coarse sand (20%). The half-life of naphthalene was longest in coarse sand (700 d) and shortest in mild clay (250 d). Facultative anaerobes such as Methylophilaceae accounted for about 70% of the total bacteria and played a major role in naphthalene degradation. A high total organic carbon concentration and large specific surface area can promote natural attenuation of naphthalene. Moreover, the adsorption to riverbank sediment in the hyporheic zone and bioremediation by indigenous microorganisms can effectively eliminate naphthalene during river water infiltration to the riverbank aquifer. Highlights • Adsorption contributes more to naphthalene natural attenuation than biodegradation. • Riverbank sediments can effectively eliminate naphthalene by natural attenuation. • Methylophilaceae played a major role in naphthalene degradation. • Anaerobic environments promote natural attenuation of naphthalene. [ABSTRACT FROM AUTHOR]

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward‐related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity. [ABSTRACT FROM AUTHOR]

Background and Aims: Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)‐derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Here, we establish the robustness and value of SCN for identifying heavy alcohol users in three additional independent studies. Design and Setting: Cross‐sectional and longitudinal studies using data from the Pediatric Imaging, Neurocognition and Genetics (PING) study (n = 400, age range = 14–22 years), the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) (n = 272, age range = 17–22 years) and the Human Connectome Project (HCP) (n = 375, age range = 22–37 years). Cases: Cases were defined based on heavy alcohol use patterns or former alcohol use disorder (AUD) diagnoses: 50, 68 and 61 cases were identified. Controls had none or low alcohol use or absence of AUD: 350, 204 and 314 controls were selected. Measurements Graph theory metrics of segregation and integration were used to summarize SCN. Findings Mirroring our prior findings, and across the three data sets, cases had a lower clustering coefficient [area under the curve (AUC) = −0.029, P = 0.002], lower modularity (AUC = −0.14, P = 0.004), lower average shortest path length (AUC = −0.078, P = 0.017) and higher global efficiency (AUC = 0.007, P = 0.010). Local efficiency differences were marginal (AUC = −0.017, P = 0.052). That is, cases exhibited lower network segregation and higher integration, suggesting that adjacent nodes (i.e. brain regions) were less similar in thickness whereas spatially distant nodes were more similar. Conclusion: Structural covariance network (SCN) differences in the brain appear to constitute an early marker of heavy alcohol use in three new data sets and, more generally, demonstrate the utility of SCN‐derived metrics to detect brain‐related psychopathology. [ABSTRACT FROM AUTHOR]

Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents. [ABSTRACT FROM AUTHOR]

In this study, we collected feces of Tibetan piglets from Nyingchi area for isolation, culture, identification, virulence gene analysis and drug resistance analysis of Escherichia Coli. The results demonstrated a 41.3% isolation rate of Diarrheagenic Escherichia Coli from Tibetan pigs with the main phylogenetic groups: group A (68.6%) and group B2 (15.7%). Typical E.coli accounted for 76.5%. The highest detection rates of porcine virulence genes were E.coli heat-resistant enterotoxin STb (58.82%) and F107 fimbrial subunit (23.53%). The highest detection rates of virulence genes from Tibetan pigs were fimC (80.39%) and ompA (76.47%). A drug sensitivity test showed that Diarrheagenic Escherichia Coli from Tibetan pigs had high drug resistance rates to mezlocillin , doxycycline and gentamicin. This study comprehensively analyzed the species composition, virulence and drug resistance of Diarrheagenic Escherichia Coli from Tibetan pigs, which provided a clearer and more targeted idea for the prevention and treatment of yellow and white dysentery in Tibetan pigs in the future. [ABSTRACT FROM AUTHOR]

Folic acid-modified carboxymethyl chitosan was polymerized withN-3-acrylamidophenylboronic acid monomer to prepare tumor-targeting nanoparticles (NPs). Nanoparticles’ size was characterized by dynamic light scattering, while the micromorphology was observed through transmission electron microscopy (TEM) and scanning electronic microscope (SEM). Doxorubicin was then loaded into prepared nanoparticles. The cellular uptake of these NPs was investigated in monolayer cell model and multicellular spheroids. The results revealed that FA-modified nanoparticles possess excellent ability of accumulation and penetration in 2D and 3D cell models. It was also found that these nanoparticles enhanced drug accumulation in tumor, which finally increased antitumor efficiency in H22 tumor-bearing mice. [ABSTRACT FROM PUBLISHER]

The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5 Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately $2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR’s ability to generate frequency-swept RF waveforms was validated and compared to the scanner’s commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500 kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially-available SDRs. [ABSTRACT FROM AUTHOR]

This study presents a robust motion deblurring method in which an adaptive prediction is used to extract the informative regions for kernel estimation. The prediction not only sharpens the blurry edges, but also adaptively predicts the large scale structure for kernel estimation. It allows to only use the alternating minimisation with a computationally efficient Gaussian prior for both the image and kernel while without employing thoughtful attention such as multi‐scale scheme or kernel refinement. Extensive experiments were carried out to validate the proposed method and to compare it with some previous approaches. The experiment results demonstrated that the approach achieves, if not better than, state‐of‐the‐art results for uniformly blurred images. [ABSTRACT FROM AUTHOR]

Previous studies on insight problem solving using Chinese logogriphs as insight problems only investigated the time- and phase-locked changes of electrocortical responses triggered by Chinese logogriphs, but did not focus on what kind of brain state facilitates individuals to solve insight problems. To investigate this, we focused on participants' alpha activities (8-12 Hz) that closely correlates with insight problem solving and defocused attention while they were solving Chinese logogriphs. Results indicated that in the time window of 800-1400 ms after the presentation of target logogriphs, alpha power over parieto-central electrodes decreased relative to the reference interval in both the successful and unsuccessful logogriphs solving conditions. However, alpha power increased at parieto-occipital electrode sites in successful conditions compared with that in unsuccessful condition. The decrease in alpha activity in both conditions may reflect the cognitive demands in solving the target logogriphs. Furthermore, difference in alpha power between the successful and unsuccessful conditions at parieto-occipital electrode sites is associated with the process of heuristic information. Alpha synchronization observed in the successful condition compared to the unsuccessful condition might reflect a state of defocused attention that facilitates insight problem solving. [ABSTRACT FROM AUTHOR]

Previous studies have provided insights into the representations of original and relative values and the influence of predictability on decision making. However, whether the predictability of outcomes can influence the processing manner of outcomes (i.e. whether the outcomes are processed in terms of original or relative values) is still unknown. To investigate this issue, we had participants perform a monetary decision task which resulted in two outcomes with the same relative values but different original values in either a predictable or unpredictable condition, while recording event-related potentials (ERP). ERP results showed that the outcome processing in the unpredictable condition elicited more positive deflections in the time window of 300–500 ms (P300) than did those in the predictable condition. More importantly, the outcome with high original value elicited a greater P300 component than did that with low original value in the unpredictable condition even though these two outcomes had the same relative values, while in the predictable condition no significant difference was observed between ERPs elicited by the two outcomes even though their original values were different. These results suggest that the outcomes might be processed in terms of relative values in the predictable condition but original values in the unpredictable condition. [ABSTRACT FROM AUTHOR]

This work presents a no-reference sharpness metric for Gaussian blurred image. The metric is based on the notion of relative blur. The key concept is that the judgement on the sharpness closely relates to the degree of convenience for recognizing image objects on a certain scale. Based on this concept, the proposed metric is defined as relative blur with respect to certain object scale using an absolute blur measure. The object scale is characterized by a granularity analysis of image content. And the absolute blur is built on an analysis of edge local gray level distribution. The performance of the metric is tested and compared with some outstanding existing metrics in this field on three widely used databases. The experiment results show that the proposed metric can predict the sharpness of images in varying databases with high accuracy and reliability. [ABSTRACT FROM AUTHOR]

Based on density functional theory and nonequilibrium Green's function method, we investigate the spin polarization and transport ability of hybrid interface states at benzene/Ni surface by introducing the top probe electrode. The results demonstrate that when the top electrode connects the molecule with different sites, the spin polarization of the projected density of states and the interfacial spin density distribution are disturbed in different ways. A contact site induced inversion of the spin polarization is observed at Fermi energy. The transport calculation indicates that the center contact is better to achieve a large tunneling magnetoresistance at low bias, but the edge and top contacts is useful to get a little larger spin polarization of the current. This work points out that the spin polarization and transport property of the hybrid interface states in a molecular junction depends on the way to introduce the second probe electrode, which can be suitable designed to achieve an excellent performance. • The spin polarization of the hybrid interface states depends on the way to introduce the second probe electrode. • A contact site induced inversion of the spin polarization is observed at Fermi energy. • The center contact is better to achieve a large tunneling magnetoresistance at low bias. • The edge and top contacts is useful to get a little larger spin polarization of the current. [ABSTRACT FROM AUTHOR]

Highlights: [•] We describe a Shinnar–Le Roux algorithm to design -selective RF pulses. [•] The algorithm improves the selectivity of -selective pulses. [•] A new pulse form is described that can accurately excite large tip-angles. [•] The pulses’ sensitivity to off-resonance decreases with increasing . [•] The pulses have similar thresholds as BIR-4 pulses, but are more sensitive to off-resonance. [Copyright &y& Elsevier]

This study was ascertained to investigate the adverse effects of pathogenic E. coli on gut microbiota of Tibetan piglets with history of yellow and white dysentery. For this purpose, a total of 18 fecal samples were collected from infected and healthy Tibetan piglets for 16S rRNA gene amplification and sequencing of V3–V4 region. Results showed that Firmicutes , Bacteroidia Fusobacteriota , Proteobacteria and Actinobacteriota were the predominant bacteria in Tibetan piglets at the level of phylum classification. Results on classification at family level showed that Lactobacillus , Bacteroidota , Fusobacteriota and Enterobacteriaceae were the dominant bacteria. Results on classification of bacteria at phylum level compared with normal piglets indicated that Bacteroidota , Actinobacteriota , Euryarchaota and Spirochaetota in fecal microbial community in Tibetan piglets showing yellow dysenteric and diarrhea group were significantly decreased (P ≤ 0.05). Compared with the feces of healthy Tibetan piglets, the abundance of Escherichia-Shigella , Lactobacillus and Enterococcus increased significantly in feces of Tibetan piglets having yellow dysentery and white dysentery. Moreover, results exhibited that the Proteobacteria and Fusobacteriota were significantly increased (P ≤ 0.05) suggesting dominant microbial community. Results revealed that E. coli induced different pathological alterations in intestine including damage to intestinal epithelial cells, infiltration of inflammatory cells, presence of red blood cells in spaces of tissues, hemorrhages and necrosis of intestinal villi in piglets with history of yellow dysentery. This study for the first time reported the composition, characteristics, and differences of the fecal microflora diversity of Tibetan piglets with yellow and white dysentery in Qinghai-Tibet Plateau, which can provide a suitable support for effective control of diarrhoeal disease in these animals. • E. coli induce pathological alterations in intestinal tract of Tabetan piglets. • This study investigate adverse effects of pathogenic E. coli on intestinal flora. • Firmicutes, Bacteroidia Fusobacteriota, Proteobacteria and Actinobacteriota were the predominant bacteria. • This study for the first time reported the fecal microflora diversity in piglets. [ABSTRACT FROM AUTHOR]

Recently, a review article entitled "Diagnostic role of serum tryptase in anaphylactic deaths in forensic medicine: a systematic review and meta-analysis", which was published in I Forensic Science, Medicine, and Pathology i [[1]], has attracted our attention. The retrospective study summarized the diagnostic significance of postmortem serum tryptase in deceased individuals and conducted a systematic review and meta-analysis, which we believe is quite useful. [Extracted from the article]

Cancer cachexia is a common condition in many cancer patients, particularly those with advanced disease. Cancer cachexia patients are generally less tolerant to chemotherapies and radiotherapies, largely limiting their treatment options. While the search for treatments of this condition are ongoing, standards for the efficacy of treatments have yet to be developed. Current diagnostic criteria for cancer cachexia are primarily based on loss of body mass and muscle function. However, these criteria are rather limiting, and in time, when weight loss is noticeable, it may be too late for treatment. Consequently, biomarkers for cancer cachexia would be valuable adjuncts to current diagnostic criteria, and for assessing potential treatments. Using high throughput methods such as "omics approaches", a plethora of potential biomarkers have been identified. This article reviews and summarizes current studies of biomarkers for cancer cachexia. [ABSTRACT FROM AUTHOR]

Data management and analysis are challenging with big Earth observation (EO) data. Expanding upon the rising promises of data cubes for analysis-ready big EO data, we propose a new geospatial infrastructure layered over a data cube to facilitate big EO data management and analysis. Compared to previous work on data cubes, the proposed infrastructure, GeoCube, extends the capacity of data cubes to multi-source big vector and raster data. GeoCube is developed in terms of three major efforts: formalize cube dimensions for multi-source geospatial data, process geospatial data query along these dimensions, and organize cube data for high-performance geoprocessing. This strategy improves EO data cube management and keeps connections with the business intelligence cube, which provides supplementary information for EO data cube processing. The paper highlights the major efforts and key research contributions to online analytical processing for dimension formalization, distributed cube objects for tiles, and artificial intelligence enabled prediction of computational intensity for data cube processing. Case studies with data from Landsat, Gaofen, and OpenStreetMap demonstrate the capabilities and applicability of the proposed infrastructure. [ABSTRACT FROM AUTHOR]

Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson's trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM. [ABSTRACT FROM AUTHOR]

Nutmeg is a traditional spice and medicinal plant with a variety of pharmacological activities. However, nutmeg abuse due to its hallucinogenic characteristics and poisoning cases are frequently reported. Our previous metabolomics study proved the hepatotoxicity of nutmeg and demonstrated that high-dose nutmeg can affect the synthesis and secretion of bile acids and cause oxidative stress. In order to further investigate the hepatotoxicity of nutmeg, normal saline, 1 g/kg, 4 g/kg nutmeg were administrated to male Kunming mice by intragastrical gavage for 7 days. Histopathological investigation of liver tissue, proteomics and biochemical analysis were employed to explore the mechanism of liver damage caused by nutmeg. The results showed that a high-dose (4 g/kg) of nutmeg can cause significant increased level of CYP450s and depletion of antioxidants, resulting in obvious oxidative stress damage and lipid metabolism disorders; but this change was not observed in low-dose group (1 g/kg). In addition, the increased level of malondialdehyde and decreased level of glutathione peroxidase were found after nutmeg exposure. Therefore, the present study reasonably speculates that nutmeg exposure may lead to liver injury through oxidative stress and the degree of this damage is related to the exposure dose. [ABSTRACT FROM AUTHOR]

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD. [ABSTRACT FROM AUTHOR]

Ischemic stroke in rodents is usually induced by intraluminal occlusion of the middle cerebral artery (MCA) via the external carotid artery (ECA) or the common carotid artery (CCA). The latter route requires permanent CCA occlusion after ischemia, and here, we assess its effects on long-term outcomes. Transient occlusion of MCA and CCA was performed at normal body temperature. After 90 min of ischemia, mice were randomized to permanent CCA occlusion or no occlusion (control group). Body weight, and motor and sensory functions, ie, pole test, adhesive tape removal, and elevated plus maze, were evaluated at 24 h, and at 7 and 28 days after stroke. Infarct volume, apoptosis, and activation of astrocytes and microglia were assessed at 4 weeks by an investigator blinded to groups. The Morris water maze test was performed at 3 weeks in the second experiment. One mouse died at 4 days, and the other mice survived with persistent neurologic deficits. CCA-occluded mice exhibited delayed turn on the pole at 24 h and decreased responses to the von Frey filament, and spent more time on the pole at 7 and 28 days than the control group. Infarction, hemispheric atrophy, glial activation, and apoptotic neuronal death were present in all mice, and no intra-group difference was found. However, CCA-occluded mice had a significantly poorer performance in the Morris water maze compared to the control group, which showed an adverse effect of post-ischemia CCA occlusion on cognition. Thus, the model selection should be well considered in preclinical efficacy studies on stroke-induced vascular dementia and stroke with Alzheimer's disease. • CCA occlusion worsens stroke-induced long-term cognitive deficits. • CCA occlusion does not worsen long-term sensorimotor deficits and infarct size. • CCA occlusion does not worsen post-stroke inflammation and apoptosis at 4 weeks. • Transcranial MCA occlusion was used to avoid destroying the carotid artery branches. • MCAO model with CCA filament insertion is not feasible in cognitive function study. [ABSTRACT FROM AUTHOR]

Alcohol use disorder is characterised by disrupted reward learning, underpinned by dysfunctional cortico-striatal reward pathways, although relatively little is known about the biology of reward processing in populations who engage in risky alcohol use. Cues that trigger reward anticipation can be categorized according to their learnt valence (i.e., positive vs. negative outcomes) and motivational salience (i.e., incentive vs. neutral cues). Separating EEG signals associated with these dimensions is challenging because of their inherent collinearity, but the recent application of machine learning methods to single EEG trials affords a solution. Here, the Alcohol Use Disorders Identification Test (AUDIT) was used to quantify risky alcohol use, with participants split into high alcohol (HA) (n = 22, mean AUDIT score: 13.82) and low alcohol (LA) (n = 22, mean AUDIT score: 5.77) groups. We applied machine learning multivariate single-trial classification to the electroencephalography (EEG) data collected during reward anticipation. The LA group demonstrated significant valence discrimination in the early stages of reward anticipation within the cue-P3 time window (400-550 ms), whereas the HA group was insensitive to valence within this time window. Notably, the LA, but not the HA group demonstrated a relationship between single-trial variability in the early valence component and reaction times for gain and loss trials. This study evidences disrupted hypoactive valence sensitivity in the HA group, revealing potential neurophysiological markers for risky drinking behaviours which place individuals at-risk of adverse health events. [ABSTRACT FROM AUTHOR]

• Nutmeg exposure may cause dose- and duration-dependent liver damage. • Inflammatory cell infiltration and hepatocyte necrosis were dose- and duration-related. • Elevated serum AST and ALT levels were related to nutmeg dose and exposure duration. • Nutmeg exposure caused differential levels of metabolites related to liver function. Incidences of abuse and poisoning have been reported for nutmeg, a household spice made from grinding the seed of Myristica fragrans , owing to its hallucinogenic properties. However, there have been no reports on nutmeg hepatotoxicity in relation to dose and duration of exposure. To investigate the hepatotoxicity of different nutmeg exposure durations and doses, male mice were administered daily with normal saline, 1.0 g/kg nutmeg, or 4.0 g/kg nutmeg by intragastrical gavage for either 7 or 14 days (for a total of six treatment groups, n = 6). Body weight of each mouse was monitored daily. Histological analysis of liver tissues was performed using hematoxylin and eosin (H&E) staining to investigate the morphological changes in hepatocytes. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined using enzyme-linked immunosorbent assay (ELISA) to investigate liver function. Metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed between treatment groups for identifying differential metabolites. Mice in the nutmeg exposure groups exhibited slow growth trends, hepatocyte damage, and significantly elevated serum AST and ALT levels associated with nutmeg dose and exposure duration. Metabolomics and KEGG enrichment pathway analyses also revealed differential levels of some metabolites related to liver function upon nutmeg exposure. Therefore, the present study reasonably speculates that nutmeg exposure may cause liver damage and affect liver function depending on the dose and duration. [ABSTRACT FROM AUTHOR]

Rapidly identifying cachexia-inducing factors that directly induce muscle wasting is an existing challenge. We developed two reporter cell lines that allow swift detection of such factors in blood from patients. C2C12 myoblasts were used for the establishment of reporter cells. A luciferase reporter gene, driven by promoters of wasting genes, Muscle RING-finger protein-1 (MuRF1) and Muscle Atrophy F-Box Protein (MAFbx / Atrogin-1) were used for the construction of reporter constructs. Increased expression of these genes in muscle tissue under wasting conditions was shown in vivo and in vitro. We found these reporter cell lines could detect factors associated with cancer cachexia, such as myostatin (Mstn), activin A, and TNF-α. We further investigated the capacity to directly detect a cachectic state using plasma samples from cachectic mice and cancer patients. Activation of the reporter cell lines was observed by the addition of plasma from mice with cancer cachexia and serum samples from patients with pancreatic or colorectal cancer. These results indicate that the reporter cell lines are competent as a tool for screening cachexia-inducing factors and potentially distinguishing a cachectic state induced by cancer. Image 1 • Reporter cell lines were created for detection of cachexia inducing factors in blood. • Differentiated C2C12 myotubes were engineered to express luciferase under muscle wasting promotors, MuRF-1 and Atrogin-1. • These cells lines are able to detect a cachexic state in human and mouse blood samples. • These tools may allow for rapid clinical detection of cachexia in cancer patients. [ABSTRACT FROM AUTHOR]

Background: Cardiac troponin I (cTn I) and cardiac troponin T (cTn T) are currently widely used as diagnostic biomarkers for myocardial injury caused by ischemic heart diseases in clinical and forensic medicine. However, no previous meta-analysis has summarized the diagnostic roles of postmortem cTn I and cTn T. The aim of the present study was to meta-analyze the diagnostic roles of postmortem cTn I and cTn T for cardiac death in forensic medicine, present a systematic review of the previous literature, and determine the postmortem cut-off values of cTn I and cTn T. Methods: We searched multiple databases for the related literature, performed a meta-analysis to investigate the diagnostic roles of postmortem cardiac troponins, and analyzed the receiver operating characteristic (ROC) curve to determine their postmortem cut-off values. Results and Conclusions: The present meta-analysis demonstrated that postmortem cTn I and cTn T levels were increased in pericardial fluid and serum in cardiac death, especially in patients with acute myocardial infarction (AMI). We determined the postmortem cut-off value of cTn I in the pericardial fluid at 86.2 ng/mL, cTn I in serum at 9.5 ng/mL, and cTn T in serum at 8.025 ng/mL. [ABSTRACT FROM AUTHOR]

Currently, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are widely used as diagnostic biomarkers for heart failure (HF) and cardiac dysfunction in clinical medicine. They are also used as postmortem biomarkers reflecting cardiac function of the deceased before death in forensic medicine. Several previous studies have reviewed BNP and NT-proBNP in clinical medicine, however, few articles have reviewed their application in forensic medicine. The present article reviews the biological features, the research and application status, and the future research prospects of BNP and NT-proBNP in both clinical medicine and forensic medicine, thereby providing valuable assistance for clinicians and forensic pathologists. [ABSTRACT FROM AUTHOR]

Soy protein isolate (SPI) was hydrolyzed by compound enzymes to give water soluble low molecular soy protein (SP). SP and folic acid (FA) modified SP was polymerized with N-3- acrylamidophenylboronic acid (APBA) monomer in aqueous solution to give SP nanoparticles (SP NPs) and FA modified nanoparticles (FA-SP NPs), respectively. These NPs display excellent stability in different conditions, and have a uniform spherical shape with a diameter around of 200 nm. Doxorubicin (DOX) was then successfully loaded into SP and FA-SP NPs with a desirable loading content of 13.33% and 16.01%, respectively. The cellular uptake and cytotoxicity of DOX-loaded SP NPs and FA-SP NPs were investigated using the two-dimensional (2D) monolayer cell model and three-dimensional (3D) multicellular spheroids (MCs). In vivo, tumor accumulation and growth inhibitory were then examined using H22 tumor-bearing mice. All these results demonstrated that conjugation of FA can efficiently enhance SP-based NPs' tumor accumulation and antitumor effect. [ABSTRACT FROM AUTHOR]

B cells constitute a major component of infiltrating immune cells in colorectal cancer (CRC). However, the characteristics of B cells and their clinical significance remain unclear. In this study, using single‐cell RNA sequencing and multicolour immunofluorescence staining experiments, we identified five distinct subtypes of B cells with their marker genes, distribution patterns and functional properties in the CRC tumour microenvironment. Meanwhile, we found a higher proportion of IgG plasma cells in tumour sites than that in adjacent normal mucosal tissues. In addition, the CXCL13‐producing CD8+ T cells in the tumour tissues could promote the formation of tertiary lymphoid structure (TLS) B cells, and the CCL28–CCR10 axis is pivotal for IgG plasma cell migration from the periphery of TLSs to the tumour stroma. Finally, we identified four distinct colon immune classes (CICs: A–D) and found that CD20+ B cells within TLSs were enriched in one immune‐inflamed or hot tumour group (CIC D). This B cell‐rich group, which was characterized by strong antigen presentation, IgG plasma cells accumulation, microsatellite instability‐high (MSI‐H) and high tumour mutation burden (TMB‐H), as well as immunosuppressive property in particular, might become a potential predictive biomarker for future immunotherapy. Additionally, in an immunotherapy cohort, patients with the enrichment of B cells and TLSs were demonstrated to obtain significant therapeutic advantages. Together, our findings provide the detailed landscape of infiltrating B cells and their potential clinical significance in CRC. [ABSTRACT FROM AUTHOR]

Artificial Intelligence Machine Learning (AI/ML), in particular Deep Learning (DL), is reorienting and transforming Earth Observation (EO). A consistent data model for delivery of training data will support the FAIR data principles (findable, accessible, interoperable, reusable) and enable Web-based use of training data in a spatial data infrastructure (SDI). Existing training datasets, including open source benchmark datasets, are usually packaged into public or personal repositories and lack discoverability and accessibility. Moreover, there is no unified method to describe the training data. Here we propose a training data model for AI in EO to allow documentation, storage, and sharing of geospatial training data in a distributed infrastructure. We present design rationales, information models, and an encoding method. Several scenarios illustrate the intended uses and benefits for EO DL applications in an open Web environment. The relationship with Open Geospatial Consortium (OGC) standards is also discussed, as is the impact on an AI-ready SDI. [ABSTRACT FROM AUTHOR]

In this paper, we address the distributed resilient fusion filtering (DRFF) problem for a class of nonlinear multi-sensor networked systems (MSNSs) with random sensor delay (RSD) under round-robin protocol (RRP). The RSD is depicted by the Bernoulli random variable with known occurrence probability. In order to relieve the network congestion, the RRP that can deal with information overload issue of the transmission process from sensor to the estimator is utilised. The major objective of this paper is that the resilient fusion filter is designed for nonlinear MSNSs with RSD and RRP in the light of the inverse covariance intersection approach, where the local upper bound regarding the filtering error covariance is obtained and then minimised by suitably exploiting the local filter gain. Finally, a simulation example that can show the validity of the provided DRFF algorithm is presented. [ABSTRACT FROM AUTHOR]

Based on the shape descriptors of image contour, this paper proposes an automatic fault recognition method for Brake-Shoe-Key (BSK) losing of freight train. The method contained two phase, one is the positioning of the feature region, the other is recognition of the feature for the BSK losing. In the position phase, a direction-adaptive grey projection method followed by an enhancing process was put forwarded for the initial positioning of image feature region of the Brake Shoe. And then based on edge information, a threshold-relaxation method was adopted to precisely extract the contour of the Braked Shoe. In the recognition phase, besides some ordinary shape descriptors such as rectangular degree, solidity, compactness, circularity, etc., two new shape descriptors, respectively named as contour smoothness and contour concave–convex were proposed to establish the recognition characters vector. At last, the Support Vector Machine (SVM) was used in the classifier for BSK losing fault recognition. Experiments demonstrated that the proposed algorithm is not sensitive to image noise and performed well on images with complex background and disturbance such as blur, poor illumination, excess exposure, etc. [ABSTRACT FROM AUTHOR]

This paper is concerned with the adaptive event-triggered recursive state estimation (RSE) issue for a class of nonlinear complex dynamical networks (CDNs) with random coupling parameter, missing measurements (MMs) and coding-decoding-based communication mechanism (CDBCM). First of all, a random variable uniformly distributed in a fixed interval is adopted to model the varying topologies. Then, the Bernoulli random sequence with uncertain statistical properties is considered to characterize the phenomenon of MMs subject to the uncertain occurrence probability situation. Furthermore, in order to ensure the security and reliability of the shared network channel, the adaptive event-triggered scheduling strategy (AETSS) and CDBCM are both employed to govern the data transmission thereby enhancing the communication quality. The aim of this paper is to present an RSE scheme for a class of stochastic CDNs such that for all MMs, AETSS and CDBCM, the state estimation error covariance (SEEC) is given the SEEC upper bound (SEECUB) is derived. Then, the state estimator gain matrix (SEGM) is parameterized by means of optimizing the trace of SEECUB. Moreover, the monotonicity of the trace of SEECUB with respect to the available missing probability is clarified detailed. Finally, an illustrative simulation is executed for the purpose of verifying the validity of the proposed RSE scheme. [ABSTRACT FROM AUTHOR]

Simple Summary: Although heart failure is a long-term chronic disease, it can also lead to arrhythmia, triggering cardiac arrest, and eventually death. Our study is a randomized and blinded preclinical assessment of the efficacy of the Mn porphyrin compound, MnTnBuOE-2-PyP5+ (BMX-001), commonly known as a superoxide dismutase mimic, in both mouse and rat models of cardiac arrest and resuscitation. Our study indicates that MnTnBuOE-2-PyP5+ improves survival, neurologic function recovery, and behavioral performance in animals suffering from cardiac arrest. The results support the development of Mn Porphyrin-based therapeutics for the treatment of heart failure and cardiac arrest. Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP5+, Mn(III) ortho meso-tetrakis (N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. Methods Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. Results Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (p < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, p = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (p < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, p = 0.21) and less tubular injury (p < 0.05) relative to vehicle group. Conclusions We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials. [ABSTRACT FROM AUTHOR]

Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study alcohol-induced myocardial injury, myocardial specimens from a previously successfully established mouse model of ACM were subjected to histological, echocardiographic, and proteomic analyses, and validated by real-time quantitative polymerase chain reaction (qPCR). Results of histopathology and echocardiography showed the hypertrophy of cardiomyocytes, the dilation of ventricles, and decreased cardiac function. Proteomic results, available via ProteomeXchange with identifier PXD032949, revealed 56 differentially expressed proteins (DEPs) were identified, which have the potential to be involved in the KEGG pathway related to fatty acid biosynthesis disorders, lipid metabolism disorders, oxidative stress, and, ultimately, in the development of dilated cardiomyopathy (DCM). The present study further elucidates the underlying effects of myocardial injury due to chronic alcohol intake, laying a foundation for further studies to clarify the potential mechanisms of ACM. [ABSTRACT FROM AUTHOR]