Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA.

PURPOSE: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. METHODS: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Advance in pathogenesis of sarcoidosis: Triggers and progression.

Sarcoidosis, a multisystemic immune disease, significantly impacts patients' quality of life. The complexity and diversity of its pathogenesis, coupled with limited comprehensive research, had hampered both diagnosis and treatment, resulting in an unsatisfactory prognosis for many patients. In recent years, the research had made surprising progress in the triggers of sarcoidosis (genetic inheritance, infection and environmental factors) and the abnormal regulations on immunity during the formation of granuloma. This review consolidated the latest findings on sarcoidosis research, providing a systematic exploration of advanced studies on triggers, immune-related regulatory mechanisms, and clinical applications. By synthesizing previous discoveries, we aimed to offer valuable insights for future research directions and the development of clinical diagnosis and treatment strategies.

Local thiamet-G delivery by a thermosensitive hydrogel confers ischemic cardiac repair via myeloid M2-like activation in a STAT6 O-GlcNAcylation-dependent manner.

Infarct healing requires a dynamic and orchestrated inflammatory reaction following myocardial infarction (MI). While an uncontrolled excessive inflammatory response exaggerates ischemic injury post-MI, M2-like reparative macrophages may facilitate inflammation regression and promote myocardial healing. However, how protein post-translational modification regulates post-MI cardiac repair and dynamic myeloid activation remains unknown. Here we show that M2-like reparative, but not M1-like inflammatory activation, is enhanced by pharmacologically-induced hyper-O-GlcNAcylation. Mechanistically, myeloid knockdown of O-GlcNAc hydrolase O-GlcNAcase (Oga), which also results in hyper-O-GlcNAcylation, positively regulates M2-like activation in a STAT6-dependent fashion, which is controlled by O-GlcNAcylation of STAT6. Of note, both systemic and local supplementation of thiamet-G (TMG), an Oga inhibitor, effectively facilitates cardiac recovery in mice by elevating the accumulation of M2-like macrophages in infarcted hearts. Our study provides a novel clue for monocyte/macrophage modulating therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.

Simulated microgravity increases CD226+ Lin- CD117- Sca1+ mesenchymal stem cells in mice.

Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+ Lin- CD117- Sca1+ MSCs. The CD226+ MSCs produced higher IL-6, M-CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.

The combination use of inclisiran and statins versus statins alone in the treatment of dyslipidemia in mainland China: a cost-effectiveness analysis.

Objective: Statin is well-established as a classical lipid-lowering drug, and its cost has reduced considerably in the past years. Inclisiran is a new and effective lipid-lowering drug given as a subcutaneous injection at 6-month intervals. This study aims to evaluate the cost-effectiveness of the combination use of inclisiran and statin versus statin alone for dyslipidemia in the mainland China population. Methods: The Markov decision-making model was used, and the clinical data and real-world data were collected at the University of Hong Kong-Shenzhen Hospital (HKU-SZH). Patients with cardiovascular disease (CVD) and blood lipid levels above the target on statin therapy were included as the target population and analyzed for cardiovascular events, future medical expenses, and the calculation made for the total life cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted to evaluate the influence of parameter uncertainty on the base-case analysis results. Results: If inclisiran was priced at Chinese renminbi (RMB) 20,000.00 (USD 2,973.49) per injection, patients in the inclisiran and statin group would incur an incremental cost of RMB 449,233.56 (USD 66,789.60) compared with the statin group, and they would obtain 0.21 more QALYs in their life cycle. The subsequent ICER of RMB 2,127,756.78 (USD 316,343.32)/QALY was significantly higher than the willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China, which was RMB 257,094.00 (USD 38,223.33)/QALY, suggesting that the combined use of inclisiran and statin was not cost-effective. If the price of inclisiran were reduced to RMB 2,500.00 (USD 371.69)/injection, the ICER of patients in the inclisiran and statin group would become RMB 257,790.63 (USD 38,326.91)/QALY, which is slightly lower than the WTP threshold of 3 times the per capita GDP of China, indicating that the combined use of inclisiran and statin would be cost-effective. Conclusion: If inclisiran is priced at RMB 20,000.00 (USD 2,973.49)/injection, then the combined use of inclisiran and statins is not cost-effective compared with statin alone. It will be economical only if the price of inclisiran is reduced by more than 88%.

Subsequent surgical treatment or maintenance immunotherapy in stage III lung cancer patients achieving a favorable response following neoadjuvant immunotherapy: A matched retrospective cohort study from the surgical perspective.

BACKGROUND: Current treatment strategies for advanced non-small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy. METHODS: We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long-term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores. RESULTS: In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1- and 3-year overall survival (OS) and progression-free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long-term prognosis of patients (PFS and OS) but could impact their perioperative experience. CONCLUSION: Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2-4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC.

Structural analysis of polysaccharide from Inonotus obliquus and investigate combined impact on the sex hormones, intestinal microbiota and metabolism in SPF male mice.

The dysregulation of sex hormone levels is associated with metabolic disorders such as obesity. Inonotus obliquus polysaccharide (IOP) exhibits a promising therapeutic effect on conditions like obesity and diabetes, potentially linked to its influence on intestinal microbiota and metabolism. The exact cause and mechanisms that link sex hormones, gut microbiota and metabolism are still unknown. In this research, we examined the molecular weight, monosaccharide composition, and glycosidic bond type of IOP. We found that IOP mostly consists of alpha-structured 6­carbon glucopyranose, with a predominant (1 â†’ 4) linkage to monosaccharides and a uniform distribution. Following this, we administered two different concentrations of IOP to mice through gavage. The results of the enzyme-linked immunosorbent assay (ELISA) demonstrated a significant increase in testosterone (T) levels in the IOP group as compared to the control group. Additionally, the results of tissue immunofluorescence indicated that increased IOP led to a decrease in adiponectin content and an increase in SET protein expression. The study also revealed changes in the intestinal microbiota and metabolic changes in mice through 16S rRNA data and non-targeted LC-MS data, respectively. The study also found that IOP mainly affects pathways linked to glycerophospholipid metabolism. In addition, it has been observed that there is an increase in the number of beneficial bacteria, such as the Eubacterium coprostanoligenes group and g.Lachnospiraceae NK4A136 group, while the levels of metabolites that are linked to obesity or diabetes, such as 1,5-anhydrosorbitol, are reduced. Furthermore, biomarker screening has revealed that the main microorganism responsible for the differences between the three groups is g.Erysipelatoclostridiaceae. In summary, these findings suggest that IOP exerts its therapeutic effects through a synergistic interplay between sex hormones, gut microbiome composition, and metabolic processes.

Validity and responsiveness of EQ-5D-Y in children with haematological malignancies and their caregivers.

The psychometric properties of the EQ-5D-Y have not been widely tested in severely ill children. The aim of this study was to assess and compare the validity and responsiveness of the EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric inpatients with haematological malignancies and caregivers. Respondents completed the interviewer-administered self-complete or proxy version of the EQ-5D-Y-3L and EQ-5D-Y-5L and an overall health assessment twice on different days. Known-groups validity was assessed by comparing patients who differed in overall health and Eastern Cooperative Oncology Group (ECOG) performance. Responsiveness to worsened health was assessed using standardised effect size (SES) for patients with worsened ECOG grade, self-reported rating, or chemotherapy initiation. Ninety-six dyads completed the baseline questionnaires. A smaller proportion of patients reported "no problems" on the EQ-5D-Y-5L compared to EQ-5D-Y-3L for most of the five dimensions. Patients in poor health reported more problems in all dimensions and had higher EQ-5D-Y-5L level sum score, lower EQ VAS and EQ-5D-Y-3L index scores (Cohen's d ES: 0.32-1.38 for patients; 0.50-2.05 for caregivers). There was a mild to good responsiveness to worsened health condition based on ECOG (SES: 0.14-0.61 for patients; 0.40-0.96 for caregivers), suggesting the proxy version was slightly responsive than the self-complete version of both instruments. The results demonstrated validity and responsiveness for both the self-complete and proxy versions of the EQ-5D-Y-3L and EQ-5D-Y-5L. The proxy and 5-level versions of the instrument were more sensitive than the self-complete and 3-level versions in this patient group.

Association between serum uric acid levels and depressive symptoms according to menopausal status.

INTRODUCTION: The menopause-specific relationship between serum uric acid (SUA) and depressive symptoms were not known. We aimed to explore the association between SUA and depressive symptoms stratified by menopausal status. METHODS: This is a cross-sectional study, a total of 4845 females were enrolled from China health and retirement longitudinal study (CHARLS) in China. The Center for Epidemiologic Studies Depression Scale (CESD) were used to measure depressive symptoms. A cut-off score of CES-D ≥ 10 was defined as depression. Multiple regression models were used to assess the relationship between SUA and depression stratified by menopausal status. RESULTS: Overall, SUA was significantly associated with depressive symptoms/depression in post-menopause women (ß = -0.39, 95 % CI: -0.60, -0.17) after adjusted potential confounders. Compared with those whose SUA levels were in the first tertile, participants with their SUA in the second (ß = -0.76, 95 % CI: -1.30, -0.22) and third tertile (ß = -1.24, 95 % CI: -1.80, -0.68) had milder depressive symptoms. However, SUA was not associated with depressive symptoms in pre-menopause women (ß = 0.1, 95 % CI: -0.25, 0.46). An interaction between menopausal status and SUA on depressive symptoms were found in this study (P = 0.02). Similar results were found for depression. LIMITATIONS: Some potential covariates like diet that could affect SUA levels were not considered in this study. CONCLUSIONS: Higher SUA was associated with depressive symptoms/depression in post-menopause women. An interaction between menopausal status and SUA on depressive symptoms were found. SUA was not associated with depressive symptoms/depression in pre-menopause women.

The role of circular RNA in preeclampsia: From pathophysiological mechanism to clinical application.

Preeclampsia (PE) is a common pregnancy-induced hypertension disorder that poses a significant threat to the health of pregnant women and fetuses, and has become a leading cause of maternal, fetal, and neonatal mortality. Currently, the therapy strategy for PE is mainly prevention management and symptomatic treatment, and only delivery can completely terminate PE. Therefore, a deeper understanding of the pathogenesis of PE is needed to make treatment and prevention more effective and targeted. With the deepening of molecular etiology research, circular RNAs (circRNAs) have been found to be widely involved in various processes of PE pathogenesis. As a kind of RNA with a special "head to tail" loop structure, the characteristics of circRNAs enable them to play diverse roles in the pathophysiology of PE, and can also serve as ideal biomarkers for early prediction and monitoring progression of PE. In this review, we summarized the latest research on PE-related circRNAs, trying to elucidate the unique or shared roles of circRNAs in various pathophysiological mechanisms of PE, aiming to provide a whole picture of current research on PE-related circRNAs, and extend a new perspective for the precise screening and targeted therapy of PE.

The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions.

BACKGROUND: Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim of this study was to uncover genes involved in the invasion process, which could also serve as therapeutic targets. For the isolation of invasive GBM cells from non-invasive cells, we used a three-dimensional organotypic co-culture system where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing (ui-RNA Seq), an invasive gene signature was obtained that was exploited in a therapeutic context. METHODS: GFP-labeled tumor cells were sorted from invasive and non-invasive regions within co-cultures. Ui-RNA sequencing analysis was performed to find a gene cluster up-regulated in the invasive compartment. This gene cluster was further analyzed using the Connectivity MAP (CMap) database. This led to the identification of SKF83566, an antagonist of the D1 dopamine receptor (DRD1), as a candidate therapeutic molecule. Knockdown and overexpression experiments were performed to find molecular pathways responsible for the therapeutic effects of SKF83566. Finally, the effects of SKF83566 were validated in orthotopic xenograft models in vivo. RESULTS: Ui-RNA seq analysis of three GSC cell models (P3, BG5 and BG7) yielded a set of 27 differentially expressed genes between invasive and non-invasive cells. Using CMap analysis, SKF83566 was identified as a selective inhibitor targeting both DRD1 and DRD5. In vitro studies demonstrated that SKF83566 inhibited tumor cell proliferation, GSC sphere formation, and invasion. RNA sequencing analysis of SKF83566-treated P3, BG5, BG7, and control cell populations yielded a total of 32 differentially expressed genes, that were predicted to be regulated by c-Myc. Of these, the UHRF1 gene emerged as the most downregulated gene following treatment, and ChIP experiments revealed that c-Myc binds to its promoter region. Finally, SKF83566, or stable DRD1 knockdown, inhibited the growth of orthotopic GSC (BG5) derived xenografts in nude mice. CONCLUSIONS: DRD1 contributes to GBM invasion and progression by regulating c-Myc entry into the nucleus that affects the transcription of the UHRF1 gene. SKF83566 inhibits the transmembrane protein DRD1, and as such represents a candidate small therapeutic molecule for GBMs.

Mean number of DNA breakpoints: illuminating sperm DNA integrity and in vitro fertilization outcomes.

OBJECTIVE: To verify the capacity of the mean number of DNA breakpoints (MDB) for evaluating sperm integrity and its relationship with in vitro fertilization (IVF) outcomes. DESIGN: Retrospective cohort study. SETTING: Reproductive center in a tertiary hospital. PATIENT(S): All men whose female partners underwent IVF from March to October 2022 in the reproductive center. INTERVENTION(S): The MDB and DNA fragmentation index (DFI) were used to assess sperm DNA integrity. The patients were stratified into two groups according to MDB and DFI cutoffs: sperm DNA-normal and sperm DNA-impaired. MAIN OUTCOME MEASURES: Semen parameters: concentration, progressive motility (PR), MDB, and the DFI; IVF outcome measures: two pronuclei (2-PN), fertilization rate, fertilization cleavage rate, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, and implantation rate. RESULTS: Sperm MDB had a higher negative correlation with PR compared with the DFI (r = -0.43; r = -0.37, respectively). Sperm MDB did not have a statistical correlation with sperm concentration, whereas the DFI correlated significantly with concentration (r = -0.17; r = -0.27, respectively). Logistic regression analysis controlling for age and semen concentration demonstrated that an increase in MDB increased the risk of asthenospermia (odds ratio = 1.018, 95% confidence interval [CI] 1.003-1.034). An increasing DFI also increased the risk of asthenospermia (odds ratio = 1.044, 95% CI 1.002-1.087). The MDB showed a stronger clinical relevance with sperm PR than the DFI, as indicated using the area under the curve values (0.754, 95% CI 0.649-0.859 vs. 0.691, 95% CI 0.556-0.825). A threshold of the MDB >0.37 nM was calculated to define sperm DNA-impaired. Comparison of IVF results showed that the high-quality embryo rate (χ2 = 13.00) was significantly lower in the DNA-impaired group than in the DNA-normal group stratified using the MDB, although there were no significant differences in IVF outcomes in DFI-stratified groups. CONCLUSION: The MDB has been verified to correlate closely with semen PR and may serve as a predictive parameter for IVF outcomes. Rigorous prospective studies are required to explore MDB performance and to further validate and reinforce the potential application of MDB as a parameter for male infertility.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Bimolecular versus Trimolecular Reaction Pathways for H2O2 with Hypochlorous Species and Implications for Wastewater Reclamation.

The benchmark advanced oxidation technology (AOT) that uses UV/H2O2 integrated with hypochlorous species exhibits great potential in removing micropollutants and enhancing wastewater treatability for reclamation purposes. Although efforts have been made to study the reactions of H2O2 with hypochlorous species, there exist great discrepancies in the order of reaction kinetics, the rate constants, and the molecule-level mechanisms. This results in an excessive use of hypochlorous reagents and system underperformance during treatment processes. Herein, the titled reaction was investigated systematically through complementary experimental and theoretical approaches. Stopped-flow spectroscopic measurements revealed a combination of bi- and trimolecular reaction kinetics. The bimolecular pathway dominates at low H2O2 concentrations, while the trimolecular pathway dominates at high H2O2 concentrations. Both reactions were simulated using direct dynamics trajectories, and the pathways identified in the trajectories were further validated by high-level quantum chemistry calculations. The theoretical results not only supported the spectroscopic data but also elucidated the molecule-level mechanisms and helped to address the origin of the discrepancies. In addition, the impact of the environmental matrix was evaluated by using two waters with discrete characteristics, namely municipal wastewater and ammonium-rich wastewater. Municipal wastewater had a negligible matrix effect on the reaction kinetics of H2O2 and the hypochlorous species, making it a highly suitable candidate for this integration technique. The obtained in-depth reaction mechanistic insights will enable the development of a viable and economical technology for safe water reuse.

Photoacoustic speckle pattern interferometry for detecting cracks of different sizes.

A system and method for non-destructive detection of cracks of different width and depths based on digital speckle interferometry coupled with pulsed laser excitation is introduced and tested. Based on photoacoustic effect, acoustic waves are induced onto the rear of the samples by pumping a pulsed laser beam on it. The generated mechanical wave propagates from the rear surface of the sample to the front while front surface is monitored by speckle interferometry. In order to acquire information about surface deformation, the front surface is illuminated by continuous wave laser and interference are imaged onto the camera as speckle images. After processing the produced fringe patterns, it indicates the presence and location of the cracks in qualitative way. In this study, the system and method mentioned above are validated by detecting medium density fiberboard with simulated cracks. The fringe patterns from areas with or without defects are compared and discussed. Besides, the system and method to distinguish and predict cracks sizes is proposed and validated.

Influence of grasping postures on skin deformation of hand.

To investigate the influence of different grasping postures on the hand's skin deformation, a handheld 3D EVA SCANNER was used to obtain 3D models of 111 women in five postures, including a straight posture and grasping cylinders with various diameters (4/6/8/10 cm). Skin relaxation strain ratio ([Formula: see text]) and surface area skin relaxation strain ratio ([Formula: see text]) were used as measures of skin deformation between two landmarks and multiple landmarks, respectively. The effects of grasping posture on skin deformation in different directions were analyzed. The results revealed significant variations in skin deformation among different grasping postures, except for the width of middle finger metacarpal and the length of middle finger's proximal phalanx. The [Formula: see text] increased with decreasing grasping object diameter, ranging from 5 to 18% on the coronal axis, and from 4 to 20% on the vertical axis. The overall variation of [Formula: see text] ranged from 5 to 37.5%, following the same trend as [Formula: see text] except for the surface area of tiger's mouth, which exhibited a maximum difference of 10.9% with significant differences. These findings have potential applications in improving the design of hand equipment and understanding hand movement characteristics.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

Analyzing EFL learners' demotivating factors in blended learning context.

In second language and foreign language learning, demotivation in learning is a common occurrence. Almost all previous studies on learners' demotivation focused on traditional classroom learning environment rather than blended learning setting. This paper investigates learner perceptions of demotivating factors for Chinese EFL college students in blended learning context. 272 college sophomores with varied majors from a university in Mid-East China took part in a questionnaire survey. The questionnaire, consisted of 34 4-point Likert type items about learners' demotivation in a blended EFL learning environment, was adapted from Kikuchi's demotivation questionnaire and Xie's LPDS (Learner Perceptions of Demotivator Scale). An exploratory factor analysis was performed to explore the factor structure of the questionnaire items. Then mean scores of items loading on each factor were calculated and independent samples t-test analysis was adopted to examine the differences of demotivating factors between different groups of participants. Five demotivating factors from the questionnaire were extracted. The findings reveal a newly discovered factor: learners' lack of self-discipline in online learning. The paper indicates that there is no significant difference of these five demotivating factors between male and female learners, and between rural and urban learners. Whereas less motivated learners perceive four among the five factors to be more demotivating than more motivated learners.