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Pixel reconstruction filters play an important role in physics-based rendering and have been thoroughly studied. In physics-based differentiable rendering, however, the proper treatment of pixel filters remains largely under-explored. We present a new technique to efficiently differentiate pixel reconstruction filters based on the path-space formulation. Specifically, we formulate the pixel boundary integral that models discontinuities in pixel filters and introduce new antithetic sampling methods that support differentiable path sampling methods, such as adjoint particle tracing and bidirectional path tracing. We demonstrate both the need and efficacy of antithetic sampling when estimating this integral, and we evaluate its effectiveness across several differentiable- and inverse-rendering settings.

To increase the in vivo stability of cationic gene carriers and avoid the adverse effects of their positive charge, we synthesized a new shielding material by conjugating low molecular weight polyethylene glycol (PEG) to a hyaluronic acid (HA) core. The HA-PEG conjugate assembled with the positively charged complex, forming a protective layer through electrostatic interactions. DNA/polyetherimide/HA-PEG (DNA/PEI/HA-PEG) nanoparticles had higher stability than both DNA/polyethyleneimine (DNA/PEI) and DNA/PEI/HA complexes. Furthermore, DNA/PEI/HA-PEG nanoparticles also showed a diminished nonspecific response toward serum proteins in vivo. The in vivo transfection efficiency was also enhanced by the low cytotoxicity and the improved stability; therefore, this material might be promising for use in gene delivery applications.

Mass spectrometry identifying EGFR-binding proteins

Leucine-rich repeat-containing G protein–coupled receptors 4, 5, and 6 (LGR4/5/6) play critical roles in development and cancer. The widely accepted mechanism is that these proteins, together with their R-spondin ligands, stabilize Wnt receptors, thus potentiating Wnt signaling. Here we show that LGR4 enhanced breast cancer cell metastasis even when Wnt signaling was deactivated pharmacologically or genetically. Furthermore, LGR4 mutants that cannot potentiate Wnt signaling nevertheless promoted breast cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Multiomic screening identified EGFR as a crucial mediator of LGR4 activity in cancer progression. Mechanistically, LGR4 interacted with EGFR and blocked EGFR ubiquitination and degradation, resulting in persistent EGFR activation. Together, these data uncover a Wnt-independent LGR4–EGFR signaling axis with broad implications for cancer progression and targeted therapy.Significance:This work demonstrates a Wnt-independent mechanism by which LGR4 promotes cancer metastasis.See related commentary by Stevens and Williams, p. 4397

This paper studies the problem of computing an average (or mean) displacement from a set of given spatial displacements using three types of parametric representations: Euler angles and translation vectors, unit quaternions and translation vectors, and dual quaternions. It is shown that the use of Euclidean norm in the space of unit quaternions reduces the problem to that of computing the mean for each quaternion component separately and independently. While the resulting algorithm is simple, a change in the sign of a unit quaternion could lead to an incorrect result. A novel kinematic measure based on dual quaternions is introduced to capture the separation between two spatial displacements. This kinematic measure is used to define the variance of a set of displacements, which is then used to formulate a constrained least squares minimization problem. It is shown that the problem decomposes into that of finding the optimal translation vector and the optimal unit quaternion. The former is simply the centroid of the set of translation vectors and the latter is obtained as the eigenvector corresponding to the least eigenvalue of a 4 × 4 positive definite symmetric matrix. In addition, it is found that the weight factor used in combining rotations and translations in the formulation does not play a role in the final outcome. Examples are provided to show the comparisons of these methods.

Lactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., is a gut symbiont that can colonize many mammals. Since it was first isolated in 1962, a multitude of research has been conducted to investigate its function and unique role in different diseases as an essential probiotic. Among these, the basic functions, beneficial effects, and underlying mechanisms of L. reuteri have been noticed and understood profoundly in intestinal diseases. The origins of L. reuteri strains are diverse, with humans, rats, and piglets being the most common. With numerous L. reuteri strains playing significant roles in different intestinal diseases, DSM 17938 is the most widely used in humans, especially in children. The mechanisms by which L. reuteri improves intestinal disorders include protecting the gut barrier, suppressing inflammation and the immune response, regulating the gut microbiota and its metabolism, and inhibiting oxidative stress. While a growing body of studies focused on L. reuteri, there are still many unknowns concerning its curative effects, clinical safety, and precise mechanisms. In this review, we initially interpreted the basic functions of L. reuteri and its related metabolites. Then, we comprehensively summarized its functions in different intestinal diseases, including inflammatory bowel disease, colorectal cancer, infection-associated bowel diseases, and pediatric intestinal disorders. We also highlighted some important molecules in relation to the underlying mechanisms. In conclusion, L. reuteri has the potential to exert a beneficial impact on intestinal diseases, which should be further explored to obtain better clinical application and therapeutic effects.

Cell lysis is a key step for studying the structure and function of proteins in cells and an important intermediate step in drug screening, cancer diagnosis, and genome analysis. The current cell lysis methods still suffer from limitations, such as the need for large instruments, a long and time-consuming process, a large sample volume, chemical reagent contamination, and their unsuitability for the small amount of bacteria lysis required for point-of-care testing (POCT) devices. Therefore, a fast, chemical-free, portable, and non-invasive device needs to be developed. In the present study, we designed an integrated microfluidic chip to achieve E. coli lysis by applying an alternating current (AC) electric field and investigated the effects of voltage, frequency, and flow rate on the lysis. The results showed that the lysis efficiency of the bacteria was increased with a higher voltage, lower frequency, and lower flow rate. When the voltage was at 10 Vp-p, the lysis efficiency was close to 100%. The study provided a simple, rapid, reagent-free, and high-efficiency cleavage method for biology and biomedical applications involving bacteria lysis.

Traditional algorithm lacks the ability to generalize across different application scenarios and how to set the stopping conditions of network iteration in Stochastic Configuration Network (SCN) is a problem. This paper proposes an event recognition system based on minimum redundancy, maximum relevance (mRMR) and a modified Stochastic Configuration Network (CWCs-SCN) for the fiber Bragg grating (FBG) sensor system. mRMR is used to analyze the importance of 14th time-frequency domain features in different application scenarios. After that, a modified SCN (CWCs-SCN) neural network is used to solve the stopping condition of the network iteration. The experiments demonstrated that the average recognition accuracy of four kind of human intrusion signal can reach to 96.7%, which is better than others traditional methods. In addition, a more compact neural network is obtained compared to SCN. To verify the generalization ability of the proposed model, it is applied to gear fault diagnosis with an accuracy of 96.3%. This imply that the proposed method in this paper has a wide application prospect.

Empathy is essential for human survival and social interaction. Although mindfulness-based interventions (MBIs) have been used to improve empathy in healthy populations, its therapeutic efficacy remains unknown. This study aims to investigate the therapeutic effects of MBIs on empathy in a healthy population and the potential factors affecting the efficacy of MBIs. The literature search focused on PubMed, Embase, Web of Science, Cochrane Library, and CNKI from inception to September 2022. Randomized controlled trials and quasi-experimental studies reporting the effects of using MBIs on empathy in healthy populations were included. A total of 13 studies were included in this review. Results of the meta-analysis showed that MBIs improved empathy (SMD, 0.372, 95% CI, 0.164–0.579, p = 0.001) in the healthy population compared with that in the control group. Moreover, results of the subgroup analysis showed that intervention dose (over 24 h vs. under 24 h), format (online vs. offline), and types (different types) were important factors affecting treatment outcomes. This comprehensive review suggests that MBIs are effective treatment for empathy in healthy population. Future research should markedly focus on large-sample, rigorously designed experiments to explore the long-term effects of MBIs on empathy and to elucidate the underlying mechanisms of MBIs. This study provides a reference for the daily application of MBIs.

The Global Leadership Initiative on Malnutrition (GLIM) has been built to diagnose malnutrition; however, its validity among patients with cirrhosis remains enigmatic. We aimed to investigate the prevalence of malnutrition according to GLIM criteria and compare the differences by using a specific screening tool.We conducted a descriptive cross-sectional study analyzing hospitalized patients. The Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) was chosen as the screening tool. Estimated prevalence was shown with and without the initial screening process. Diverse combinations of phenotypic and etiologic criteria and distinct body mass index (BMI) cutoffs were applied to detect frequency of malnourished patients with cirrhosis.Overall, 363 patients were recruited (median age, 64 years; 51.2% female). The prevalence of malnutrition according to GLIM criteria with and without RFH-NPT screening was 33.3% and 36.4%, respectively. Low BMI and inflammation represented the most prevalent combination resulting in a malnutrition diagnosis (42.4%), followed by low BMI and reduced food intake (39.4%). By contrast, the least prevalence was found when combining reduced muscle mass with inflammation to diagnose malnutrition. Furthermore, the frequency of malnourished and well-nourished participants was not statistically different when using divergent BMI reference values across the study population.GLIM criteria may serve a specific proxy to diagnose malnutrition, along with RFH-NPT screening. Relevant investigation is required to report on the applied combination of phenotypic/etiologic criteria, taking into consideration the marked impact of different models. More attempts are warranted to delineate the prognostic role of GLIM criteria in the context of cirrhosis.

Physics-based differentiable rendering---which focuses on estimating derivatives of radiometric detector responses with respect to arbitrary scene parameters---has a diverse array of applications from solving analysis-by-synthesis problems to training machine-learning pipelines incorporating forward-rendering processes. Unfortunately, existing general-purpose differentiable rendering techniques lack either the generality to handle volumetric light transport or the flexibility to devise Monte Carlo estimators capable of handling complex geometries and light transport effects. In this paper, we bridge this gap by showing how generalized path integrals can be differentiated with respect to arbitrary scene parameters. Specifically, we establish the mathematical formulation of generalized differential path integrals that capture both interfacial and volumetric light transport. Our formulation allows the development of advanced differentiable rendering algorithms capable of efficiently handling challenging geometric discontinuities and light transport phenomena such as volumetric caustics. We validate our method by comparing our derivative estimates to those generated using the finite differences. Further, to demonstrate the effectiveness of our technique, we compare both differentiable rendering and inverse rendering performance with state-of-the-art methods.

Many applications in biomechanics and medical imaging call for the analysis of the kinematic errors in a group of patients statistically using the average displacement and the standard deviations from the average. This paper studies the problem of computing the average displacement from a set of given spatial displacements using three types of parametric representations: Euler angles and translation vectors, unit quaternions and translation vectors, and dual quaternions. It has been shown that the use of Euclidean norm in the space of unit quaternions reduces the problem to that of computing the average for each quaternion component separately and independently. While the resulting algorithm is simple, the change of the sign of a unit quaternion could lead to an incorrect result. A novel kinematic measure based on dual quaternions is introduced to capture the separation between two spatial displacement. This kinematic measure is then used to formulate a constrained least squares minimization problem. It has been shown that the problem decomposes into that of finding the optimal translation vector and the optimal unit quaternion. The former is simply the centroid of the set of given translation vectors and the latter can be obtained as the eigenvector corresponding to the least eigenvalue of a 4 × 4 positive definite symmetric matrix. It is found that the weight factor used in combining rotations and translations in the formulation does not play a role in the final outcome. Examples are provided to show the comparisons of these methods.

Objective The prognostic value of serum ferritin remains elusive in the literature. We aimed to examine the association between serum ferritin and mortality risk in cirrhosis. Methods A total of 257 cirrhotic patients were recruited. The cut-off of serum ferritin was determined by X-tile. The Cox regression and Kaplan-Meier method were used. A 1:1 propensity score matching (PSM) was performed to diminish the impacts of selection bias and possible confounders. Results The difference regarding mortality was mostly significant for serum ferritin >158 ng/mL. Before PSM, serum ferritin >158 ng/mL was an independent predictor of mortality. However, the clinical relevance of high ferritin level for prognostication was blunted after PSM (survival rate: 86.8% vs 96.3%, P = .078). Cox regression indicated that model for end-stage liver disease remains only independent risk factor of 180-day mortality after PSM. Conclusion Serum ferritin may not serve as an independent prognostic indicator of mortality risk in decompensated cirrhotic patients.

Inherent dynamic constraints of distributed generations (DGs) and the correlation between injected variables bring great challenges to distribution network operation. In order to improve the degree of coupling and interconnection coordination between different energy devices, improve the ability of the distribution network to cope with the uncertainty of DGs, achieve low-carbon operation, and improve the environmental friendliness of distribution network operation, this article proposes a robust optimization approach involving risk assessment. The semi-invariant method and scene clustering are used to deal with the uncertainty of DGs and load, thus formulating a robust optimization model for distribution network distribution based on risk indices. To address the time-varying constraints of energy storage systems (ESSs) and gas turbines, a two-stage box-based decomposition model is established. Dynamic constraints are included in the first stage to constrain the operating state and operating domain of the unit and ESSs. In the second stage, the multi-timescale optimization problem is transformed into multiple single-timescale optimization problems, which are solved by the column and constraint generation (C&CG) algorithm to improve the solution efficiency. The feasibility of the comprehensive optimization model based on dynamic reconfiguration and distributed robust optimization (DRO) is demonstrated with the PG&E 69 bus system.

ObjectiveThis research aims to explore the therapeutic effect of cognitive therapeutic exercise (CTE) in proprioception recovery after knee osteoarthritis (KOA) surgery.MethodsIn total, thirty-seven patients recovering from KOA surgery (including 27 patients who had undergone high-tibial osteotomy (HTO) procedure and 10 patients who had received total knee arthroplasty (TKA) treatment were randomly assigned to two groups: 18 patients in the CTE group and 19 patients for the control group (non-CTE). Patients in the CTE group received proprioceptive training as cognitive therapy to facilitate proprioception recovery for up to 4 weeks: 5 days a week and two 10-min sessions a day. Except for cognitive therapeutic exercise, the NCTE group and CTE group had the same treatment protocols. All the interventions began with permission from the surgeon-in-charge. In this research, we applied the joint repositioning training or joint-matching tasks, which is part of the proprioceptive training as a measurement for a proprioceptive training result where patients moved their knee joint from 0° (completely straight knee joint) to produce a presented joint angle, such as 30, 60, and 90° of flexion. Joint-matching task results were recorded before the treatment, at 2 and 4 weeks, postoperatively. The absolute difference between the results of these exercises and the knee flexion angle targets will be measured at each test—pre-rehabilitation (Pre-Reha), 2 weeks post-rehabilitation (2 weeks post-Reha), and 4 weeks post-rehabilitation (4 weeks post-Reha).ResultsThe absolute difference in the CTE group was significantly smaller than that of the control group after 4 weeks of treatment (P < 0.05). After 2 weeks of cognitive therapeutic exercise, the absolute difference between patients' exercises of joint repositioning and the target angle of 30° in the CTE group was smaller than that of the NCTE group (P < 0.01). After 4 weeks of therapy, the joint position sense (JPS) among patients who received cognitive therapeutic exercise when performing joint repositioning at angles of 30 and 60° were better improved than those without receiving proprioceptive training with the absolute difference smaller than those of the control group (P < 0.05).ConclusionThe joint reposition training provided for the CTE group is a painless proprioceptive training practice. This method is simple and effective, making it easy for patients to understand the purpose of training and improve patient engagement. The research showed that after 4 weeks of rehabilitation and physical training, the proprioception sense of both the NCTE and CTE groups improved significantly, and the efficacy of proprioceptive training in the CTE group was better than that of the NCTE group, which provided a new approach to the early proprioception recovery of a patient with KOA after surgery.

Existing deep learning-based methods for detecting fake news are uninterpretable, and they do not use external knowledge related to the news. As a result, the authors of the paper propose a graph matching-based approach combined with external knowledge to detect fake news. The approach focuses on extracting commonsense knowledge from news texts through knowledge extraction, extracting background knowledge related to news content from a commonsense knowledge graph through entity extraction and entity disambiguation, using external knowledge as evidence for news identification, and interpreting the final identification results through such evidence. To achieve the identification of fake news containing commonsense errors, the algorithm uses random walks graph matching and compares the commonsense knowledge embedded in the news content with the relevant external knowledge in the commonsense knowledge graph. The news is then discriminated as true or false based on the results of the comparative analysis. From the experimental results, the method can achieve 91.07%, 85.00%, and 89.47% accuracy, precision, and recall rates, respectively, in the task of identifying fake news containing commonsense errors.

BackgroundMyosteatosis is linked to dismal outcomes in the context of cirrhosis. However, the association of myosteatosis with various body composition abnormalities remains enigmatic. We aimed to clarify the determinants of myosteatosis and its relationship with other body composition profiles and length of hospitalization (LOH).MethodsWe retrospectively analyzed the data of 473 consecutive patients with cirrhosis hospitalized for decompensation. Computed tomography-based segmentation of the cross-sectional area at the third lumbar vertebra was used to evaluate body composition abnormalities. The categories of myosteatosis were built according to our previously outcome-based cutoffs for each gender.ResultsTotally, 83 patients (17.55%) were stratified as myosteatosis, of whom 85.54% had concomitant high visceral adiposity indicative of increased visceral adipose tissue index (VATI). The prevalence of sarcopenia showed no significant difference between the groups with and without myosteatosis. Multivariate analysis showed that advanced age [odds ratio (OR) = 1.097, p < 0.001], higher visceral to subcutaneous ratio of adipose tissue area (VSR; OR = 1.574, p = 0.032), and higher VATI (OR = 1.026, p < 0.001) are independently associated with myosteatosis. Correlation analyses revealed a positive relationship between intramuscular adipose tissue content (IMAC) and VATI (ρ = 0.48, p < 0.001), subcutaneous adipose tissue index (SATI) (ρ = 0.36, p < 0.001), and age (ρ = 0.36, p < 0.001). None of the skeletal muscle or adipose tissue indicators were significantly related to longer LOH.ConclusionHigher VSR, higher VATI, and advanced age are associated with myosteatosis among patients with cirrhosis at the decompensation phase. It is tempting to target divergent adipose tissue depots aimed at timely intervention/prevention of myosteatosis.

Emerging evidence has demonstrated that abnormal body composition may potentiate the development of frailty, whereas little work focuses on the role of divergent adipose tissue. Therefore, we aimed to determine the potential contribution of adipose tissue distribution to multidimensional frailty in decompensated cirrhosis.We conducted a retrospective cohort study. Divergent adipose tissues were assessed by computed tomography-derived subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and total adipose tissue index (TATI), respectively. Frailty was identified by our validated self-reported Frailty Index. Multiple binary logistic models incorporating different covariates were established to assess the relationship between adipose tissue distribution and frailty.The study cohort comprised 245 cirrhotic patients with 45.3% being male. The median Frailty Index, body mass index (BMI) and model for end-stage liver disease (MELD) score were 0.11, 24.3 kg/mIn the context of decompensated cirrhosis, low SATI and concomitant TATI were associated with higher risk of being frail. These findings highlight the importance to further apply tissue-specific tools of body composition in place of crude metric like BMI.

Hepatocellular death is a sensitive parameter for detecting acute liver injury (ALI) of toxic, viral, metabolic, and autoimmune origin. Ferroptosis has recently been implicated in carbon tetrachloride (CCl4)-induced ALI. However, the underpinning mechanism and mechanistic basis remain elusive. In this study, bicyclol, a proprietary hepatoprotectant in China, and ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) were administered in CCl4-injured mice. A panel of ferroptosis-related markers, including mitochondria morphology, reactive oxygen species production, protein adducts in response to lipid peroxidation, and key modulators of ferroptotic process, was determined in vivo. Erastin-treated L-O2 hepatocytes were transfected with glutathione peroxidase 4 (GPx4) or nuclear factor erythroid 2-related factor 2 (Nrf2) siRNA to delineate the pathway of bicyclol against ferroptosis in vitro. As a result, CCl4 led to iron accumulation, excessive reactive oxygen species production, enhanced lipid peroxidation, and characteristic morphological changes in mitochondria, along with a decrease in GPx4 and xCT protein levels in ALI mice liver, all of which were generally observed in ferroptosis. The use of Fer-1 further corroborated that ferroptosis is responsible for liver damage. Bicyclol exerted its hepatoprotection by preventing the aforesaid ferroptotic process. Furthermore, bicyclol alleviated erastin-induced cellular inviability, destruction, and lipid peroxidation in vitro. Knockdown of GPx4 diminished these protective activities against perturbations associated with ferroptosis in L-O2 hepatocytes. Additionally, Nrf2 silencing drastically reduced GPx4 levels, and further impeded the medicinal effects of bicyclol. In summary, positively regulating Nrf2-GPx4 axis by bicyclol can prevent ferroptosis in CCl4-induced ALI in mice.

Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.

In the field of cultural relic protection, the migration of moisture will cause a series of adverse effects, such as disruption and crater eruption. Assessment of water migration status is the key to early warning and prevention of these problems. In an attempt for a solution, the whole process of moisture migration in rammed earth is studied by using the moisture migration initiation criterion based on entropy. We analyzed and compared the entropy change law of the infrared radiation temperature in the two main migration stages, and we made a judgment on whether the moisture state is in the steady equilibrium or in the process of dynamic migration. The results show that the moisture migration status can be identified quickly and in real time by using the moisture migration initiation criterion based on entropy. The results of this study provide a new method for judging the state of moisture migration in geotechnical engineering, especially in the field of cultural relic protection, which has very important practical significance.

Mounting evidence has suggested the clinical significance of body composition abnormalities in the context of cirrhosis. Herein, we aimed to investigate the association between visceral adiposity and malnutrition risk in 176 hospitalized patients with cirrhosis. The adiposity parameters were obtained by computed tomography (CT) as follows: total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR). Malnutrition risk was screened using Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Visceral adiposity was determined given a higher VSR based on our previously established cutoffs. Multivariate analysis implicated that male gender (OR = 2.884, 95% CI: 1.360–6.115, p = 0.006), BMI (OR = 0.879, 95% CI: 0.812–0.951, P = 0.001), albumin (OR = 0.934, 95% CI: 0.882–0.989, P = 0.019), and visceral adiposity (OR = 3.413, 95% CI: 1.344–8.670, P = 0.010) were independent risk factors of malnutrition risk. No significant difference was observed regarding TATI, SATI, and VATI among patients with low or moderate and high risk of malnutrition. In contrast, the proportion of male patients embracing visceral adiposity was higher in high malnutrition risk group compared with that in low or moderate group (47.27 vs. 17.86%, p = 0.009). Moreover, this disparity was of borderline statistical significance in women (19.05 vs. 5.88%, p = 0.061). Assessing adipose tissue distribution might potentiate the estimation of malnutrition risk in cirrhotics. It is pivotal to recognize visceral adiposity and develop targeted therapeutic strategies.

We have clarified that malnutrition risk evaluated by the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) is prevalent in patients with cirrhosis. Mineral elements (zinc, iron, magnesium, copper, manganese, and calcium) are micronutrients essential for versatile physiological processes and cellular bioactivities. However, the association between these trace elements and integral nutritional status is unclear in decompensated cirrhotics. We collected blood samples from hospitalized patients with cirrhosis, and serum trace element concentrations were examined by inductively coupled plasma mass spectrometry. Association of trace element levels with high malnutrition risk was determined by multivariate logistic regression model. Sera from 141 patients with decompensated cirrhosis were analyzed for a total of six trace element concentrations. No significant differences were observed between high and low/moderate RFH-NPT malnutrition risk groups with the exception of zinc. The serum zinc concentrations were significantly decreased in patients at high malnutrition risk when compared to low/moderate subjects (57.9 vs 68.1 μg/dL, P = 0.006). In terms of receiver operating characteristics curve, zinc

Both sleep–wake disturbance and malnutrition are common in cirrhosis and might be associated with similar adverse outcomes, such as impaired health-related quality of life, hepatic encephalopathy, and sarcopenia, but there is no study investigating the relationship between these two. We aimed to explore the relationship between sleep–wake disturbance [estimated by the Pittsburgh Sleep Quality Index (PSQI)] and malnutrition risk [estimated by the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT)]. About 150 patients with cirrhosis were prospectively recruited. The nutritional risk is classified as low (0 points), moderate (1 point), and high (2–7 points) according to the RFH-NPT score. A global PSQI >5 indicated poor sleepers. Furthermore, multivariate linear regression analyses were performed to determine the relationship betweensleep–wakedisturbance and malnutrition. The median PSQI was seven, and RFH-NPT was two in the entire cohort, with 60.67 and 56.67% rated as poor sleep quality and high malnutrition risk, respectively. Patients with cirrhosis with poor sleep quality had significantly higher RFH-NPT score (3 vs. 1,P= 0.007). Our multivariate analyses indicated that male patients (β = 0.279,P< 0.001), ascites (β = 0.210,P= 0.016), and PSQI (β = 0.262,P= 0.001) were independent predictors of malnutrition. In addition, the differences regarding PSQI score were more significant in male patients, as well as those >65 years or with Child-Turcotte-Pugh class A/B (CTP-A/B) or the median model for end-stage liver disease (MELD)

Background: Previous studies have shown that sarcopenia appears to be a significant contributor to physical frailty among outpatients with cirrhosis. However, the evidence is scant regarding the relationship between sarcopenia and multi-dimensional frailty among inpatients. We aimed to investigate the potential contribution of sarcopenia to frailty in hospitalized patients with cirrhosis in a sex-dependent manner. Methods: This cohort enrolled consecutive cirrhotics. Muscle quantity and quality were assessed using the computed tomography-based skeletal muscle index (SMI) and intramuscular adipose tissue content, respectively. Frailty phenotype was clarified by a self-reported Frailty Index. Multiple linear regression determined the association between sarcopenia and frailty phenotype. Results: A total of 202 cirrhotic patients with 48.5% male were included. The median Frailty Index was 0.13, rendering 17.3% subjects as frail. Among the 16 frail men, 68.8% had sarcopenia and 62.5% exhibited myosteatosis. In contrast, among the 19 frail women, 26.3% had sarcopenia and 15.8% exhibited myosteatosis. Frail patients had a significantly lower median SMI (42.80 cm2/m2) compared with those with pre-frailty (48.23 cm2/m2) and with robust status (50.82 cm2/m2) in the male but not the female group. In male patients, multivariate linear regression implicated age (β = 0.330, p Conclusion: Sarcopenia is associated with multi-dimensional frailty in male patients with cirrhosis. It is tempting to incorporate sex-specific intervention with the purpose of mitigating frailty among inpatients.

Circular RNA (circRNA), a novel class of noncoding RNAs, has been used extensively to complement transcriptome remodeling in the central nervous system, although the genomic coverage provided has rarely been studied in intracerebral hemorrhage (ICH) and is limited and fails to provide a detailed picture of the cerebral transcriptome landscape. Here, we described sequencing-based transcriptome profiling, providing comprehensive analysis of cerebral circRNA, messenger RNA (mRNA) and microRNA (miRNA) expression in ICH rats. In the study, male Sprague–Dawley rats were subjected to ICH, and next-generation sequencing of RNAs isolated from non-hemorrhagic (Sham) and hemorrhagic (ICH) rat brain samples collected 7 (early phase) and 28 (chronic phase) days after insults, was conducted. Bioinformatics analysis was performed to determine miRNA binding sites and gene ontology of circRNAs, target genes of miRNAs, as well as biological functions of mRNAs, altered after ICH. These analyses revealed different expression profiles of circRNAs, mRNAs and miRNAs in day-7 and day-28 ICH groups, respectively, compared with the Sham. In addition, the expression signature of circRNAs was more sensitive to disease progression than that of mRNAs or miRNAs. Further analysis suggested two temporally specific circRNA-miRNA-mRNA networks based on the competitive endogenous RNA theory, which had profound impacts on brain activities after ICH. In summary, these results suggested an important role for circRNAs in the pathogenesis of ICH and in reverse remodeling based on self-protection support, providing deep insights into diverse possibilities for ICH therapy through targeting circRNAs.

There are few effective preventive or therapeutic strategies to mitigate the effects of catastrophic intracerebral hemorrhage (ICH) in humans. Heme oxygenase is the rate-limiting enzyme in heme metabolism; heme oxygenase-2 (HO-2) is a constitutively expressed heme oxygenase. We explored the involvement of HO-2 in a collagenase-induced mouse model of ICH in C57BL/6 wild-type and HO-2 knockout mice. We assessed oxidative stress injury, blood-brain barrier permeability, neuronal damage, late-stage angiogenesis, and hematoma clearance using immunofluorescence, Western blot, MRI, and special staining methods. Our results show that HO-2 reduces brain injury volume and brain edema, alleviates cytotoxic injury, affects vascular function in the early stage of ICH, and improves hematoma absorbance and angiogenesis in the late stage of ICH in this model. Thus, we found that HO-2 has a protective effect on brain injury after ICH.

BACKGROUND Liver cirrhosis is characterized by immune dysfunction, contributing to malnutrition. We previously revealed neutrophil-to-lymphocyte ratio (NLR) as an indicator of disordered immune system. Herein we aimed to (1) determine the optimal NLR cutoff that best predicts malnutrition risk and (2) clarify the association between NLR and nutrition status. METHODS A total of 135 hospitalized patients with cirrhosis were included. Immune dysfunction was evaluated by levels of serum C-reactive protein (CRP), NLR, and other parameters. Malnutrition was screened by a risk score referring to the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Receiver operating characteristic (ROC) curve was implemented to determine the best NLR cutoff that predicts malnutrition risk. Correlation between NLR and indicators of hepatic and physical function (handgrip strength) were also examined. Multivariable logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS ROC curve revealed that the optimum cutoff to predict malnutrition risk was NLR > 4.2, with a sensitivity of 47.2%, specificity of 81.0%, negative predictive value of 58.0%, and positive predictive value of 74.5%, respectively. Patients with NLR > 4.2 exhibited a higher RFH-NPT score, serum platelet-to-lymphocyte ratio, and CRP. A positive correlation was found between NLR values and Child-Turcotte-Pugh (r = 0.22; P = .010), model for end-stage liver disease (r = 0.36; P < .001), and RFH-NPT scores (r = 0.31; P < .001). NLR was a risk factor for malnutrition independently of alcoholic liver disease and presence of ascites. CONCLUSIONS Immune dysfunction measured by NLR was associated with malnutrition risk estimated by RFH-NPT in cirrhosis.

Bicyclol, an innovative chemical drug with proprietary intellectual property rights in China, is based on derivative of traditional Chinese medicine (TCM) Schisandra chinensis (Wuweizi) of North. Mounting data has proved that bicyclol has therapeutic potential in various pathological conditions in liver. In this narrative review, we provide the first summary of pharmacological activities, pharmacokinetic characteristics and toxicity of bicyclol, and discuss future research perspectives. Our results imply that bicyclol has a wide spectrum of pharmacological properties, including anti-viral, anti-inflammatory, immuno-regulatory, anti-oxidative, antisteatotic, anti-fibrotic, antitumor, cell death regulatory effects and modulation of heat shock proteins. Pharmacokinetic studies have indicated that bicyclol is the main substrate of CYP3A/2E1. Additionally, no obvious drug interactions have been found when bicyclol is administered simultaneously with other prescriptions. Furthermore, the results of chronic toxicity have strongly addressed that bicyclol has no noticeable toxic effects on all biochemical indices and pathological examinations of the main organs. In view of good pharmacological actions and safety, bicyclol is anticipated to be a potential candidate for various liver diseases, including acute liver injury, fulminant hepatitis, non-alcoholic fatty liver disease, fibrosis and hepatocellular carcinoma. Further studies are therefore required to delineate its molecular mechanisms and targets to confer this well-designed drug a far greater potency. We hope that bicyclol-based therapeutics for liver diseases might be broadly used in clinical practice worldwide.

This objective of this paper is to develop a dual quaternion based method for estimating target volumes in radiation therapy for head and neck cancer. Inaccuracies in radiation targeting are responsible for incidental exposure of healthy adjacent tissues, causing significant morbidity and mortality. This paper focuses on inaccuracies incurred when a tumor is displaced during treatment. To address this problem, the clinical target must be expanded to cover the region through which the tumor might move. The resulting expanded target is known as the Planning Target Volume (PTV). In the current practice, the rotational components of displacements are neglected, producing planning target volumes that either miss the true target motion or are larger than needed to cover the target path. By using the dual quaternion based kinematic formulation, this paper represents and captures both translational and rotational inaccuracies. It then presents a framework for calculating the PTV swept out by the target as it shifts within its range of translations and rotations.

To investigate whether endoscopic treatment is applicable to American patients and explores the predictors of lymph node metastasis (LNM) in early gastric cancer (EGC).Patients with EGC confined to either mucosa (T1a,EGC limited to T1a exhibited a 2.4% incidence of LNM, which increased to 11.1% when the depth invaded T1b.LNM was present at 1.4%, 5.2%, and 5.0% for sizes ≤2, 2-5, and5cm of low-grade T1a EGC, respectively, (Endoscopic treatment may only be suitable for patients in the US population who have low-grade T1a lesions of less than 2 cm in size. Patients with T1a lesions of greater than 2 cm in size, lesions with high-grade, and all T1b lesions may benefit from radical surgical resection with lymphadenectomy.

Scoparone is an active and efficious ingredient of herbal medicine Artemisia capillaris Thunb, which has been used clinically in traditional Chinese medicine formula (e.g. Yin-Chen-Hao decoction) for the treatment of hepatic dysfunction, cholestasis and jaundice for over thousand years. More recently, scoparone has received increasing attention due to its multiple properties. In this comprehensive review, we provide the first summary of the pharmacological effects and pharmacokinetic characteristics of scoparone, and discuss future research prospects. The results implicated that scoparone possesses a wide spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-apoptotic, anti-fibrotic and hypolipidemic properties. Pharmacokinetic studies have addressed that isoscopoletin and scopoletin are major primary metabolites of scoparone. Moreover, hepatic dysfunction might promote bioavailability of scoparone due to limited intrinsic clearance. On the other hand, the bioavailability of multi-component including scoparone in certain TCM formula can also be enhanced by applying this formula at a high dose on account of their interacted effects. In view of good pharmacological actions, scoparone is anticipated to be a potential drug candidate for various liver diseases, such as acute liver injury, fulminant hepatitis, alcohol-induced hepatotoxicity, non-alcoholic fatty liver disease and fibrosis. However, further studies are warranted to clarify its molecular mechanisms and targets, elucidate its toxicity, and identify its interplay with other active ingredients of classical TCM formula in clinical settings.

Differences in microRNA (miRNA) expression after intracerebral hemorrhage (ICH) have been reported in human and animal models, and miRNAs are being investigated as a new treatment for inflammation and oxidative stress after ICH. In this study, we found that microRNA-183-5p expression was decreased in the mouse brain after ICH. To investigate the effect of miRNA-183-5p on injury and repair of brain tissue after ICH, saline, miRNA-183-5p agomir, or miRNA-183-5p antagomir were injected into the lateral ventricles of 8-week-old mice with collagenase-induced ICH. Three days after ICH, mice treated with exogenous miRNA-183-5p showed less brain edema, neurobehavioral defects, inflammation, oxidative stress, and ferrous deposition than control mice. In addition, by alternately treating mice with a heme oxygenase-1 (HO-1) inducer, a HO-1 inhibitor, a nuclear factor erythroid 2-related factor (Nrf2) activator, and Nrf2 knockout, we demonstrated an indirect, HO-1-dependent regulatory relationship between miRNA-183-5p and Nrf2. Our results indicate that miRNA-183-5p and HO-1 are promising therapeutic targets for controlling inflammation and oxidative damage after hemorrhagic stroke.