Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

MOF-polymer composites with well-distributed gold nanoparticles for visual monitoring of homocysteine.

The distribution of gold nanoparticles (AuNPs) on the surface of a metal-organic framework (MOF) plays a crucial role in the catalytic performance of MOF-AuNP composites. This study describes how the physical adsorption (PH@AuNPs-on-U) and chemical modification of AuNPs on the surface of UiO-66-NH2 (U) affect the composites' catalytic efficiency. After 2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VD) linked to poly(N-2-hydroxypropyl methacrylamide) (PH) with U (UVD-PH), UVD-PH@AuNPs composites were constructed with PH as the capping and reducing reagent. The composites exhibited higher peroxidase (POD)-like activity than PH@AuNPs-on-U for oxidising 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The approach demonstrated that the proposed composite-based nanozymes could significantly enhance their catalytic activity and had a highly uniform distribution of PH@AuNPs on the surface of UVD. An assay with the nanozymes for visual detection of homocysteine (Hcy) was developed, displaying a good linear relationship (R2 = 0.998) ranging from 3.34 µM to 30.0 µM and a detection of limit of 0.3 µM. Additionally, the UVD-PH@AuNPs-TMB-H2O2 system successfully monitored serum Hcy after intraperitoneal injection in rats. This study paves a new way for developing MOF-AuNPs with highly uniform surface distribution of polymer@AuNPs to boost its catalytic activity and to detect drugs in real bio-samples.

In situ growth of dual-responsive polymer as coating for open tubular capillary electrochromatographic separation of epimedins.

Recently, open tubular capillary electrochromatography (OT-CEC) has captured considerable interest; its efficient separation capability hinges on the interactions between analytes and polymer coatings. However, in situ growth of stimuli-responsive polymers as coatings has been rarely studied and is crucial for expanding the OT-CEC technique and its application. Herein, following poly(styrene-maleicanhydride) (PSM) chemically bonded onto the inner surface of the capillary, a dual pH/temperature stimuli-responsive block copolymer, P(SMN-COOH), was prepared by in situ polymerizing poly(N-isopropylacrylamide) carboxylic acid terminated [P(N-COOH)] in PSM. An OT-CEC protocol was first explored using the coated capillary for epimedins separation. As a proof of concept, the developed OT-CEC system facilitated hydrogen bonding and tuning the hydrophilic/hydrophobic interactions between the test analytes and the P(SMN-COOH) coating by varying buffer pH and environmental temperature. Four epimedins with similar chemical structures were baseline separated under 40 °C at pH 10.0, exhibiting dramatical improvement in separation efficiency in comparison to its performance under 25 °C at pH 4.0. In addition, the coated capillary showed good repeatability and reusability with relative standard deviations for migration time and peak area between 0.7 and 1.7% and between 2.9 and 4.6%, respectively, and no significant changes after six runs. This work introduces a paradigm for efficient OT-CEC separation of herbal medicines through adjusting the interactions between analytes and smart polymer coatings, addressing polymer coating design and OT-CEC challenges.

Brain region-specific synaptic function of FUS underlies the FTLD-linked behavioural disinhibition.

Synaptic dysfunction is one of the earliest pathological processes that contribute to the development of many neurological disorders, including Alzheimer's disease and frontotemporal lobar degeneration. However, the synaptic function of many disease-causative genes and their contribution to the pathogenesis of the related diseases remain unclear. In this study, we investigated the synaptic role of fused in sarcoma, an RNA-binding protein linked to frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and its potential pathological role in frontotemporal lobar degeneration using pyramidal neuron-specific conditional knockout mice (FuscKO). We found that FUS regulates the expression of many genes associated with synaptic function in a hippocampal subregion-specific manner, concomitant with the frontotemporal lobar degeneration-linked behavioural disinhibition. Electrophysiological study and molecular pathway analyses further reveal that fused in sarcoma differentially regulates synaptic and neuronal properties in the ventral hippocampus and medial prefrontal cortex, respectively. Moreover, fused in sarcoma selectively modulates the ventral hippocampus-prefrontal cortex projection, which is known to mediate the anxiety-like behaviour. Our findings unveil the brain region- and synapse-specific role of fused in sarcoma, whose impairment might lead to the emotional symptoms associated with frontotemporal lobar degeneration.

Effect of psychosocial interventions for depression in adults with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: People with chronic kidney disease (CKD) treated with dialysis are frequently affected by depression. Psychotherapy has been reported to decrease depressive symptoms in various chronic diseases and is a potential treatment option for depression. We aimed to perform a systematic review and meta-analysis to evaluate the effect of psychotherapy on depression in adults with CKD. METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane for published studies up to October 31, 2023. Two investigators independently reviewed the included studies and extracted relevant data. Randomized controlled trials (RCTs) assessing the impact of interventions that provide psychological, emotional, or social support without the use of pharmacological substances on depressive symptoms in people with CKD were included and summarized. Scores on different tools for depressive assessment and quality of life were pooled. RESULTS: A total of 19 RCTs published between 2004 and 2023 were included and analyzed. The weighted mean difference (WMD) for all included studies with regard to depression was - 2.32 (95%CI=-3.83, -0.80, P = 0.003). The WMD for Beck Depression Inventory (BDI) score of depression was - 3.27 (95%CI=-7.81, 1.27, P = 0.158) with significant heterogeneity (I2 = 95.1%). Significant WMD was detected for the Hospital Anxiety and Depression Scale (HADS) tool: WMD=-1.90, 95%CI=-2.91, -0.90, P < 0.001. The WMD for all included studies regarding quality of life was 1.21 (95%CI=-0.51, 2.93, P = 0.168). The WMD for Kidney Disease Quality of Life Short Form (KDQOL-SF) score was 4.55 (95%CI = 0.50, 8.60, P = 0.028). The WMD for SF-36 score was 0.02 (95%CI=-10.33, 10.36, P = 0.998). Significant difference on outcomes of S-PRT scale was observed (WMD = 2.42, 95%CI = 1.07, 3.76, P < 0.001). CONCLUSIONS: Psychosocial interventions probably reduce the depression level among CKD patients. Preliminary evidence suggests that psychosocial interventions might be beneficial for the quality of life in CKD patients. Our results provide medical facilities with an evidence-based basis for establishing psychosocial interventions in kidney care settings.

Resurgence of influenza during COVID-19 in Chongqing, China: A retrospective analysis.

To better understand the trends of influenza and the impact of public health and social measures (PHSMs) implemented during the coronavirus disease 2019 (COVID-19) period in Chongqing, China. Data from the China Influenza Surveillance Information System from January 2017 to June 2022 were extracted. Epidemiological characteristics (influenza-like illness [ILI] and ILI%) and virological characteristics (influenza positive rate and circulating (sub)types) of influenza were described and compared between the pre-COVID-19 period and the COVID-19 period. Our survey showed that the implementation of PHSMs during the COVID-19 period had a positive impact on reducing influenza transmission. However, influenza activity resurged in 2021-2022 as the PHSMs were eased. Children under 5 years old constituted the highest proportion of ILI cases. The overall influenza positive rate was 23.70%, with a higher rate observed during the pre-COVID-19 period (31.55%) compared to the COVID-19 period (13.68%). Influenza virus subtypes co-circulated and the predominant subtype varied each year, with influenza A subtypes predominated in 2018/2019, while influenza B/Victoria lineage dominated in 2020/2021. PHSMs are effective measures to mitigate the spread of influenza. The findings underscore the need for bolstering monitoring systems, advocating influenza vaccination, and implementing practical PHSMs to strengthen prevention and control measures against influenza.

Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: CANT1, as calcium-activated protein nucleotidase 1, is a kind of phosphatase. It is overexpressed in some tumors and related to poor prognosis, but few studies explore its function and carcinogenic mechanism in hepatocellular carcinoma (HCC). METHODS: The expression of CANT1 mRNA and protein was analyzed by the Cancer Genome Atlas (TCGA) database and immunohistochemistry(IHC) staining. The relationship between CANT1 expression and clinicopathology was evaluated by various public databases. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of CANT1 by the area under curve (AUC). Univariate, multivariate Cox regression and Kaplan-Meier curves were applied to evaluate the predictive value of CANT1 on the prognosis of HCC. Methsurv was used to analyze gene changes and DNA methylation, and its impact on prognosis. The enrichment analysis of DEGs associated with CANT1 revealed the biological process of CANT1 based on Gene Set Enrichment Analysis (GSEA). The relationship between immune cell infiltration level and CANT1 expression in HCC was investigated using the single-sample GSEA (ssGSEA) method and the Tumor Immune Estimation Resource (TIMER) database. Finally, the association between CANT1 and immune checkpoints and drug sensitivity was also analyzed. RESULTS: CANT1 was highly expressed in 22 cancers, including HCC, and CANT1 overexpression in HCC was confirmed by IHC. The expression of CANT1 was correlated with clinical features, such as histologic grade. Highly expressed CANT1 caused poor overall survival (OS) of HCC patients. Univariate and multivariate regression analysis suggested that CANT1 was an independent prognostic marker. Of the 31 DNA methylation at CpG sites, three CpG sites were associated with the prognosis of HCC. GSEA indicated that CANT1 was mainly involved in the cell cycle, DNA replication, and etc. Moreover, CANT1 expression was correlated with immune cell infiltration and independently associated with the prognosis of HCC patients. Finally, CANT1 expression was correlated with most immune checkpoints and drug sensitivity. CONCLUSION: CANT1 may be a latent oncogene of HCC, and associated with immune cells and immune checkpoints, which may assist in HCC treatment.

Image Improved Intravoxel Incoherent Motion MRI With Optimized Trigger Delays Based on Strain Curve Analysis to Evaluate Myocardial Microvascular Dysfunction of Exertional Heat Illness.

BACKGROUND: Intravoxel incoherent motion (IVIM) MRI has not been widely used and its role in evaluating exertional heat illness (EHI)-related myocardial involvement remains unknown. PURPOSE: To investigate the feasibility of strain curve-derived trigger delay (TD) IVIM-MRI and its role in assessing myocardial diffusion and microvascular perfusion of EHI patients. STUDY TYPE: Prospective. SUBJECTS: A total of 42 male EHI patients (median age: 21 years) and 22 age- and sex-matched healthy controls (HC). FIELD STRENGTH/SEQUENCE: A 3-T, diffusion-weighted spin-echo echo-planar-imaging sequence. ASSESSMENT: IVIM-MRI was acquired by conventional TD method (group A) or strain curve-based TD method (group B) in random order. IVIM image quality was evaluated on a 3-point Likert scale (1, nondiagnostic; 2, moderate; 3, good). Technical success was defined as image quality score = 3. IVIM-MRI-derived parameters (pseudo diffusion in the capillaries [D*], perfusion fraction [f], and slow apparent diffusion coefficient [D]) were compared between EHI and HC. STATISTICAL TESTS: Student's t-tests, chi-square tests, one-way analysis of variance, receiver operating characteristic (ROC) curve analysis, Pearson's correlation coefficient (r). The statistical significance level was set at P < 0.05. RESULTS: IVIM-MRI image quality score (median [interquartile range]: 3 [2, 3] vs. 2 [1-3]) and technical success rate (61.9%[13/21] vs. 28.6%[6/21]) were significantly improved in group B. EHI patients showed significantly decreased D* (118.1 ± 23.3 × 10-3  mm2 /sec vs. 142.7 ± 42.6 × 10-3  mm2 /sec) and f values (0.42 ± 0.12 vs. 0.51 ± 0.11) and significantly higher D values (3.0 ± 0.9 × 10-3  mm2 /sec vs. 2.5 ± 0.6 × 10-3  mm2 /sec) compared to HC. Relative to D and D*, f showed the most robust efficacy for detecting EHI-related myocardial injury with the highest area under the ROC curve (0.906: 95% confidence interval, 0.799, 0.967) and sensitivity of 88.5% and specificity of 85.6%. CONCLUSION: The strain curve-based TD method significantly improved image quality and technical success rate of IVIM-MRI, and f value may be an effective biomarker to assess myocardial microcirculation abnormalities of EHI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

OBJECTIVES: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). METHODS: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. RESULTS: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042). CONCLUSIONS: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. CLINICAL RELEVANCE STATEMENT: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. KEY POINTS: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Enhancing the catalytic performance of MOF-polymer@AuNP-based nanozymes for colorimetric detection of serum L-cysteine.

The dispersion of gold nanoparticles (AuNPs) on a metal-organic framework (MOF) surface greatly affects the catalytic activity of the material. However, regulating the catalytic performance of AuNP-MOF composite-based nanozymes is a great challenge. Herein, poly(dimethylvinyloxazolinone) (PV) was chemically bonded on the surface of UiO-66-NH2 (U66), followed by modification of pepsin (Pep) on the PV chains. U66-PV-Pep@AuNP composite nanozymes were fabricated after the AuNPs formed in situ with Pep as the capping and reducing reagent. Compared to Pep@AuNPs that were physically adsorbed onto the surface of U66, the U66-PV-Pep@AuNP composites exhibited superior peroxidase (POD)-mimetic activity in the oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. Considering the surface dispersion uniformity and local concentration of Pep@AuNPs on the surface of the U66-PV-Pep@AuNP composites, the principle for improving the catalytic performance of the proposed nanozymes was explored. Furthermore, it was observed that the introduction of L-cysteine (L-Cys) into the U66-PV-Pep@AuNP-TMB-H2O2 system significantly reduced its oxidation activity and faded the color, allowing the development of a highly selective and sensitive colorimetric method for L-Cys detection. The UV-vis absorption intensity of oxTMB showed a good linear relationship with the concentration of L-Cys in the range of 2.5-40.0 µM (R2 = 0.996), with a detection limit of 0.33 µM. The proposed protocol using U66-PV-Pep@AuNP nanozymes was applied to monitor rat serum L-Cys following intraperitoneal injection. This study paves the way for the design and construction of MOF-polymer@AuNP nanozymes for drug detection in real bio-samples.

The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.

BACKGROUND: RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. METHOD: The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. RESULT: The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. CONCLUSION: We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

Effect of Antidiabetic Therapy on Clinical Outcomes of COVID-19 Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: No study has yet systematically evaluated the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate the effect of different antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. METHODS: We comprehensively retrieved the published research which examined the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. The odds ratio (OR) and its 95% confidence interval (95% CI) for clinical outcomes were calculated using the random-effects model, and meta-regression was adopted to evaluate the potential sources of heterogeneity between studies. RESULTS: A total of 54 studies were included in this study. We found that the use of metformin (OR = 0.66, 95% CI: 0.58-0.75), SGLT-2i (OR = 0.80, 95% CI: 0.73-0.88), and GLP-1ra (OR = 0.83, 95% CI: 0.70-0.98) were significantly associated with lower mortality risk in COVID-19 patients with T2D, while insulin use might unexpectedly increase the ICU admission rate (OR = 2.32, 95% CI: 1.34-4.01) and risk of death (OR = 1.52, 95% CI: 1.32-1.75). No statistically significant associations were identified for DPP-4i, SUs, AGIs, and TZDs. CONCLUSION AND RELEVANCE: We demonstrated that the usage of metformin, SGLT-2i, and GLP-1ra could significantly decrease mortality in COVID-19 patients with T2D. The heterogeneity across the studies, baseline characteristics of the included patients, shortage of dosage and the duration of antidiabetic drugs and autonomy of drug selection might limit the objectivity and accuracy of results. Further adequately powered and high-quality randomized controlled trials are warranted for conclusive findings.

Poly(N-2-hydroxypropylmethacrylamide)-capped gold nanoparticles as nanozymes with peroxidase-mimicking performance for the colorimetric monitoring of serum homocysteine.

Recently, nanozymes based on polymer-stabilized gold nanoparticles (AuNPs) have attracted more and more attention on account of their polymer-ligands' multiple functionalization sites. However, the contribution of polymer hydrogen bonding to the catalytic activity of AuNPs has received little attention. This study designed and fabricated poly(N-2-hydroxypropylmethacrylamide)-capped AuNPs (PHPAM@AuNPs) using a hydroxyl-rich polymer as the ligand. The PHPAM@AuNPs exhibited good peroxidase-mimicking activity capable of efficiently oxidizing 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The effect of PHPAM hydrogen bonding on the catalytic activity of PHPAM@AuNPs was investigated. Under peroxidase-mimicking catalysis, homocysteine introduced a notable reduction in oxidation, allowing the creation of a colorimetric method for homocysteine detection with high selectivity and sensitivity. The ultraviolet-visible absorption intensity of oxidized TMB showed a strong linear relationship with homocysteine concentration in the range of 3.0-20.0 µM (R2 = 0.998), with a limit of detection of 0.4 µM. The proposed colorimetric protocol was used to monitor homocysteine in rat serum following intraperitoneal injection. This work provides a new way to refine AuNP-based nanozymes by relying on polymer-ligand hydrogen bonding. It has strong application potential in the analysis of endogenous molecules in real samples.

Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis.

BACKGROUND AND AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising globally. NAFLD patients combined with cholestasis have more obvious liver fibrosis, impaired bile acid (BA), and fatty acid (FA) metabolism and severer liver injury; however, its therapeutic options are limited, and the underlying metabolic mechanisms are understood. Here, we aimed to investigate the effects of farnesoid X receptor (FXR) on BA and FA metabolism in NAFLD combined with cholestasis and related signaling pathways. METHODS: A mouse model of NAFLD combined with cholestasis was established by joint intervention with high-fat diet (HFD) and alpha-naphthylisothiocyanate. The effects of FXR on BA and FA metabolism were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The expression of nuclear hormone receptor, membrane receptor, FA transmembrane transporter, and BA transporter protein in mice were measured by western blot. RESULTS: NAFLD mice combined with cholestasis developed more severe cholestasis and dysregulated BA and FA metabolism. Meanwhile, the expression of FXR protein was decreased in NAFLD mice combined with cholestasis compared to the controls. Fxr-/- mice showed liver injury. HFD aggravated the liver injury with decreased BSEP expression, increased expression of NTCP, LXRα, SREBP-1c, FAS, ACC1, and CD36, and significantly increased BA and FA accumulation. CONCLUSION: All the results suggested that FXR plays a key role in both FA and BA metabolism in NAFLD combined with cholestasis and thus may be a potential target for the treatment of disorders of BA and FA metabolism in NAFLD combined with cholestasis.

Posture planning method for complex feature measurement using a single-line laser scanner.

A single-line laser scanner is commonly utilized for measuring complex surfaces and contours. However, achieving automatic implementation of this scanner poses challenges in terms of designing a measurement posture that considers measurement accuracy, path planning, and the positioning of auxiliary equipment. This ensures non-interference during the measurement process. In this study, we focus on the application of T-SCAN. First, we construct a measurement posture parameter model for T-SCAN and analyze the viewpoint position's coverage of the measurement area. Second, we propose a measurement path planning method based on scanning posture to minimize overlapping areas. Lastly, we present a measurement station planning method based on scanning postures and analyze the transfer error of the measurement targets to establish a unified measurement field. Experimental results demonstrate that, after the posture adjustment process, the average distance deviation between the measurement data and the theoretical model is significantly reduced.

Can a Video a Day Keep Stress Away? A Test of Media Prescriptions.

This research attempts to both replicate initial research on media prescriptions - the assignment of small doses of positively-valenced media for the purposes of reducing perceived stress - and, through the lens of the broaden-and-build theory, shed light on the process through which this effect might emerge. Two longitudinal data sets were collected, one with college students (N = 182) and one with U.S. adults (N = 197), in which participants were assigned to watch either comedic or inspiring media clips every day for 5 days. Findings indicated that both amusement and hope generated by media exposure reduced perceived stress over time. Specifically, inspiring media reduced perceived stress through its effect on felt hope for both samples, whereas comedic media reduced perceived stress via felt amusement for the general adult sample only. Further, as predicted, serial mediation through felt emotion and coping efficacy emerged for amusement in the student sample and for hope in the general sample. Given these data were collected during an inordinately stressful time in both the U.S. and the world with rising rates of COVID-19, a highly contentious political election, and tensions over racial inequity, these findings suggest that media, if harnessed appropriately, could be a useful tool in one's coping arsenal. A call for better understanding of the process through which media prescriptions have effect and their boundary conditions is advanced.

A dual-mode optical assay for iron(II) and gallic acid based on Fenton reaction.

The hydroxyl radicals (·OH) produced by the Fenton reaction of iron(II) and hydrogen peroxide (H2 O2 ) can oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (Ox-TMB), resulting in a decrease in the fluorescence intensity of the reaction system and an increase in ultraviolet absorption. Ox-TMB had a visible absorption peak at 625 nm and a fluorescence peak around 420 nm. When gallic acid (GA) was added to the system, Ox-TMB was reduced to TMB, which made the color of the system disappear and the fluorescence recover. The linear ranges for determination of iron(II) were 0.5-10 µM (fluorometric) and 0.5-20 µM (colorimetric), and the detection limits were 0.25 µM (fluorometric) and 0.28 µM (colorimetric). The linear ranges for determination of GA were 0-80 µM (fluorometric) and 0-60 µM (colorimetric), and the detection limits were 0.31 µM (fluorometric) and 0.8 µM (colorimetric). The results of anti-interference experiments shew that this dual-mode assay had very good selectivity for the determination of iron(II) and GA.

Redox-Responsive Polymer Nanoreactors Based on Methionine Sulfoxide for Monitoring Cell Adhesion.

Expanding the category of redox-responsive monomers suitable for enzymolysis efficiency regulation and application to living biosystems is a prerequisite to complementing the fabrication of stimuli-responsive polymer nanoreactors. However, the development of redox-responsive monomers is severely limited by chemical oxidation and low biocompatibility. This work presents a protocol for overcoming this problem by the self-assembly of redox-responsive polymer nanoreactors containing segments of water-soluble methionine sulfoxide residues and poly(styrene-co-maleic anhydride-l-methionine), and by immobilizing α-l-fucosidase into the nanoreactors. These nanoreactors demonstrate highly selective responses to a mild redox triggered by H2O2 from the initial state (VO) to an oxidation state (VO1), and are reduced by methionine sulfoxide reductase A to mold the VO' state. It resulted in significantly enhanced enzymolysis efficiency and maximal reaction rates 8.1-fold (VO) and 23.3-fold (VO1) higher than those of the free enzyme. Moreover, cell adhesion was evaluated by the highly selective determination of l-fucose on cell surfaces. Using a combination of chemical oxidation and enzymatic reduction, this work achieves reiterative enzymolysis efficiency regulation of polymer nanoreactors, which has great potential for the construction of redox-responsive nanoreactors and for monitoring cell adhesion.

Identification of a hippocampal lncRNA-regulating network in a natural aging rat model.

BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. RESULTS: A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM-receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA-miRNA-mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. CONCLUSIONS: We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.