Encapsulation of luteolin by self-assembled Rha/SSPS/SPI nano complexes: Characterization, stability, and gastrointestinal digestion in vitro.

Luteolin has anti-inflammatory, antioxidant, and anti-tumor functions, but its poor water solubility and stability limit its applications in foods as a functional component. In this study, the nanocomposites loading luteolin (Lut) with soybean protein isolate (SPI), soluble soybean polysaccharide (SSPS) and/or rhamnolipid (Rha) were prepared by layer-by-layer shelf assembly method, and their properties were also evaluated. The results showed that Rha/SPI/Lut had the smallest particle size (206.24 nm) and highest loading ratio (8.03 µg/mg) while Rha/SSPS/SPI/Lut had the highest encapsulation efficiency (82.45 %). Rha interacted with SPI through hydrophobic interactions as the main driving force, while SSPS attached to SPI with only hydrogen bonding. Furthermore, the synergistic effect between Rha and SSPS was observed in Rha/SSPS/SPI/Lut complex, in consequence, it had the best thermal and storage stability, and the slowest release in gastrointestinal digestion. Thus, this approach provided an alternative way for the application of luteolin in functional foods.

Treatment patterns and hospitalizations following rejection, reversal, or payment of the initial once-monthly paliperidone palmitate long-acting injectable antipsychotic claim among patients with schizophrenia or schizoaffective disorder.

BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic approved for the treatment of schizophrenia and schizoaffective disorder (SCA) in adults. OBJECTIVE: To assess treatment patterns and schizophrenia/SCA-related hospitalization following payer rejection, patient reversal, or payment of an initial PP1M claim. METHODS: This was a retrospective cohort study using the IQVIA Formulary Impact Analyzer database linked to the Medical Claims, Hospital Charge Detail Master, and Experian consumer databases. Patients with schizophrenia/SCA and ≥1 PP1M pharmacy claim from January 1, 2018, to February 28, 2022, were identified and stratified into 3 cohorts based on the transaction status of the initial PP1M claim (index date): rejected (payer not approved), reversed (payer approved, patient abandoned), and paid (payer approved, patient filled). Patient characteristics during the 12 months before the index date, subsequent treatment patterns, and schizophrenia/SCA-related hospitalization for patients with >6 months of follow-up were assessed by cohort. RESULTS: The rejected, reversed, and paid cohorts included 1,260, 1,046, and 1,686 patients, respectively. Across these cohorts, the mean ages ranged between 39.2 and 44.5 years; more than half were male (50.8%-51.6%) and White (50.6%-58.3%); 19.8%-24.6% of patients had a Quan-Charlson Comorbidity Index score of ≥2. Rates of prior atypical oral and long-acting injectable antipsychotic use ranged between 76.4%-80.3% and 7.8%-12.7%, respectively. Among patients with ≥6 months of follow-up, 52.2% in the rejected and 53.1% in the reversed cohorts had a subsequent paid PP1M claim during the study period; the median (quartile 1-quartile 3) time to the first paid PP1M claim was 22 (5-74) days for rejection and 11 (1-41) days for reversal. In the rejected and reversed cohorts, 10.2% (n = 111) and 9.8% (n = 90) of patients, respectively, did not receive any paid claim for an antipsychotic after the initial PP1M rejection/reversal. The prevalence of schizophrenia/SCA-related hospitalization during follow-up was similar between patients with a paid (7.4%) and rejected PP1M claim (7.0%; P = 0.689) but higher among patients with a reversed claim (10.8%; P = 0.004). After adjusting for confounders, patients in the reversed cohort were 39% more likely to have a schizophrenia/SCA-related hospitalization than those in the paid cohort (odds ratio = 1.39; 95% CI = 1.03-1.87). CONCLUSIONS: Payer rejection and patient reversal of initial PP1M claims is a form of primary nonadherence and may influence patient trajectory. Data from this study suggest that patient reversal of PP1M may lead to an increased risk of schizophrenia/SCA-related hospitalizations, potentially caused by missed or delayed treatment. Policy initiatives that remove barriers to primary adherence or fulfillment may help improve patients' clinical outcomes.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Efficacy and Safety of CT-guided Percutaneous Cryoablation for Hepatocellular Carcinoma at High-risk Sites.

OBJECTIVE: This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites. MATERIALS AND METHODS: Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease. RESULTS: The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. CONCLUSION: CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment.

Thyroid disrupting effects and the developmental toxicity of hexafluoropropylene oxide oligomer acids in zebrafish during early development.

As perfluorooctanoic acid (PFOA) alternatives, hexafluoropropylene oxide dimeric acid (HFPO-DA) and hexafluoropropylene oxide trimeric acid (HFPO-TA) have been increasingly used and caused considerable water pollution. However, their toxicities to aquatic organisms are still not well known. Therefore, in this study, zebrafish embryos were exposed to PFOA (0, 1.5, 3 and 6 mg/L), HFPO-DA (0, 3, 6 and 12 mg/L) and HFPO-TA (0, 1, 2 and 4 mg/L) to comparatively investigate their thyroid disrupting effects and the developmental toxicity. Results demonstrated that waterborne exposure to PFOA and its two alternatives decreased T4 contents, the heart rate and swirl-escape rate of zebrafish embryos/larvae. The transcription levels of genes related to thyroid hormone regulation (crh), biosynthesis (tpo and tg), function (trα and trß), transport (transthyretin, ttr), and metabolism (dio1, dio2 and ugt1ab), were differently altered after the exposures, which induced the thyroid disrupting effects and decreased the heart rate. In addition, the transcription levels of some genes related to the nervous system development were also significantly affected, which was associated with the thyroid disrupting effects and consequently affected the locomotor activity of zebrafish. Therefore, HFPO-DA and HFPO-TA could not be safe alternatives to PFOA. Further studies to uncover the underlying mechanisms of these adverse effects are warranted.

The machine learning-based model for lateral lymph node metastasis of thyroid medullary carcinoma improved the prediction ability of occult metastasis.

BACKGROUND: For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed. METHODS: From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN0-1a patients. RESULTS: A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN0-1a patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64). CONCLUSIONS: We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN0-1a patients more accurately, then benefit the decision of prophylactic LND.

Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study.

BACKGROUND: Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. METHODS AND RESULTS: This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. CONCLUSIONS: Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.

A critical suppression feedback loop determines soybean photoperiod sensitivity.

Photoperiod sensitivity is crucial for soybean flowering, adaptation, and yield. In soybean, photoperiod sensitivity centers around the evening complex (EC) that regulates the transcriptional level of the core transcription factor E1, thereby regulating flowering. However, little is known about the regulation of the activity of EC. Our study identifies how E2/GIGANTEA (GI) and its homologs modulate photoperiod sensitivity through interactions with the EC. During long days, E2 interacts with the blue-light receptor flavin-binding, kelch repeat, F box 1 (FKF1), leading to the degradation of J/ELF3, an EC component. EC also suppresses E2 expression by binding to its promoter. This interplay forms a photoperiod regulatory loop, maintaining sensitivity to photoperiod. Disruption of this loop leads to losing sensitivity, affecting soybean's adaptability and yield. Understanding this loop's dynamics is vital for molecular breeding to reduce soybean's photoperiod sensitivity and develop cultivars with better adaptability and higher yields, potentially leading to the creation of photoperiod-insensitive varieties for broader agricultural applications.

Identification of the ferroptosis-related prognostic gene signature in mesothelioma.

Mesothelioma, an uncommon yet highly aggressive malignant neoplasm, presents challenges in the effectiveness of current therapeutic approaches. Ferroptosis, a non-apoptotic mechanism of cellular demise, exhibits a substantial association with the progression of diverse cancer forms. It is important to acknowledge that there exists a significant association between ferroptosis and the advancement of various forms of cancer. Nevertheless, the precise role of ferroptosis regulatory factors within the context of mesothelioma remains enigmatic. In our investigation, we initially scrutinized the prognostic significance of 24 ferroptosis regulatory factors in the realm of mesothelioma. Our observations unveiled that heightened expression levels of CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, coupled with reduced DPP4 expression, were indicative of an unfavorable prognosis. Built upon the nine previously discussed prognostic genes, the ferroptosis prognostic model offers a reliable means to forecast mesothelioma patients' survival with a substantial degree of precision. Furthermore, a notable correlation emerged between these prognostic ferroptosis regulators and parameters such as immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression in the context of mesothelioma. Within this cadre of nine ferroptosis regulatory factors with prognostic relevance, FANCD2 exhibited the most pronounced prognostic influence, as elucidated by our analyses. Subsequently, we executed a validation process employing clinical specimens sourced from our institution, thus confirming that heightened FANCD2 expression is a discernible harbinger of an adverse prognosis in the context of mesothelioma. In vitro experiments revealed that knocking down FANCD2 markedly suppressed the proliferation, migration, and ability of mesothelioma cells to attract immune cells. Furthermore, our findings also showed that reducing FANCD2 levels heightened the vulnerability of mesothelioma cells to inducers of ferroptosis. Furthermore, an extensive pan-cancer analysis uncovered a robust association between FANCD2 and the gene expression linked to immune checkpoints, thereby signifying an adverse prognosis across a broad spectrum of cancer types. Additional research is warranted to validate these findings.

The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

Role of protein Post-translational modifications in enterovirus infection.

Enteroviruses (EVs) are the main cause of a number of neurological diseases. Growing evidence has revealed that successful infection with enteroviruses is highly dependent on the host machinery, therefore, host proteins play a pivotal role in viral infections. Both host and viral proteins can undergo post-translational modification (PTM) which can regulate protein activity, stability, solubility and interactions with other proteins; thereby influencing various biological processes, including cell metabolism, metabolic, signaling pathways, cell death, and cancer development. During viral infection, both host and viral proteins regulate the viral life cycle through various PTMs and different mechanisms, including the regulation of host cell entry, viral protein synthesis, genome replication, and the antiviral immune response. Therefore, protein PTMs play important roles in EV infections. Here, we review the role of various host- and virus-associated PTMs during enterovirus infection.

Knockdown of the Expression of Two Trehalase Genes with RNAi Disrupts the Trehalose and Chitin Metabolism Pathways in the Oriental Armyworm, Mythimna separata.

Trehalose is an important carbohydrate substance in insect hemolymph. Chitin is the main component of cuticle and peritrophic matrix in insects. Trehalase (Tre) catalyzes the decomposition of trehalose. Few studies of trehalase in lepidopteran insects have been conducted. Here, the functions of soluble Tre (Tre1) and membrane-bound Tre (Tre2) in the growth and development of Mythimna separata were investigated. We cloned and identified Tre1 and Tre2 cDNA sequences in M. separata. Analysis expression revealed that MsTre1 and MsTre2 were highly expressed in midgut and integument, respectively. The expression of MsTre1 and MsTre2 was highest in the pupal stage. We used RNA interference (RNAi) to inhibit Tre expression in M. separata larvae. Injection of dsMsTre1 or dsMsTre2 resulted in abnormal phenotypes and impeded normal molting. Silencing of MsTre1 and MsTre2 resulted in significant changes in the expression of genes in the trehalose and chitin metabolism pathways, significantly increased the trehalose and glycogen content, and significantly decreased MsTre1 and MsTre2 activity, the glucose content, and the chitin content in midgut and integument. Silencing of MsTre1 slowed larval molting, and the new cuticle was significantly thinner. These results indicate that RNAi of Tre may be useful for control strategies against M. separata.

Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC. METHODS: We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student's t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong's test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models. RESULTS: The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM. CONCLUSIONS: We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.

Characterization of alkaloids and phenolics in Nitraria roborowskii Kom. fruit by UHPLC-triple-TOF-MS/MS and its sucrase and maltase inhibitory effects.

Nitraria roborowskii Kom (NRK), with high economic and ecological value, is mainly distributed in the Qaidam Basin, China. However, research on its chemical components and bioactivities is still rare. In this study, its chemical constituents (52) including 10 ß-carboline alkaloids, nine cyclic peptides, three indole alkaloids, five pyrrole alkaloids, eight phenolic acids and 17 flavonoids were identified tentatively using UPLC-triple-TOF-MS/MS. Notablely, one new ß-carboline alkaloid and five new cyclic peptides were confirmed using MS/MS fragmentation pathways. In addition, experiments in vitro indicated that NRK-C had strong maltase and sucrase inhibitory activities (IC50 of 0.202 and 0.103 mg/mL, respectively). Polysaccharide tolerance experiments confirmed NRK-C (400 mg/kg) was associated with decreased postprandial blood glucose (PBG) in diabetic mice. These results suggested that NRK fruit might be used as a functional ingredient in food products.

Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. AIM OF THE STUDY: Clarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. MATERIALS AND METHODS: A free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. RESULTS: The results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. CONCLUSION: For the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.

Improvement in Microstructure and Properties of 304 Steel Wire Arc Additive Manufacturing by the Micro-Control Deposition Trajectory.

In this study, the GMAW welding torch was controlled by a stepping motor to achieve a periodic swing. By controlling the swing speed, a micro-variable deposition path was obtained, which was called the micro-control deposition trajectory. The influence of the micro-control deposition trajectory on the arc characteristics, microstructure, and mechanical properties of 304 steel wire arc additive manufacturing was studied. The results showed that the micro-control deposition process was affected by the swing arc and the deposition trajectory and that the arc force was dispersed over the whole deposition layer, which effectively reduced the welding heat input. However, the arc centrifugal force increased with the increase in the swing speed, which easily caused instability of the arc and large spatter. Compared with common thin-walled deposition, the deposition width of micro-control thin-walled deposition components was increased. In addition, the swinging arc had a certain stirring effect on the molten pool, which was conducive to the escape of the molten pool gas and refinement of the microstructure. Below, the interface of the deposition layer, the microstructure of the common thin-walled deposition components, and the micro-control thin-walled deposition components were composed of lathy ferrite and austenite. Compared with the common deposition, when the swing speed increased to 800 °/s, the microstructure consisted of vermicular ferrite and austenite. The tensile strength and elongation of the micro-control thin-walled deposition components are higher than those of the common thin-walled deposition components. The tensile fracture mechanism of the common thin-walled deposition components and the micro-control thin-walled deposition components was the ductile fracture mechanism.

Red Cell Distribution Width is Related to Mild Cognitive Impairment: A Cross-Sectional Study of Community Residents.

BACKGROUND AND OBJECTIVE: Previous literature has reported that red cell distribution width (RDW) correlated with Alzheimer's disease (AD), but the correlation with mild cognitive impairment (MCI) was not clear. This study aimed to investigate MCI in the residents aged ≥65 living in the suburban of Shanghai, China. MATERIALS AND METHODS: A total of 550 participants were recruited as MCI (MCI group, 226) and normal (NC group, 284) groups and received blood examination voluntarily. Blood routine indexes were tested by blood tests using Sysmex XT-4000i (Japan). The Chi-square test, t-test, and linear regression analysis were used to find the statistical difference and correlation of data, respectively. RESULTS: Each cognition domain of MCI was found to be impaired, the weight of which, however, was different in integral damage. Most MCI people had impairment of attention among cognitive domains (235, 88.3%). According to the results of the binary logistic regression, the highest weight among impaired cognitive domains was for attention in MCI, and the Wald value of attention was higher than those of others (Wald = 51.83). Additionally, RDW had the greatest negative correlation with attention score (P < 0.05). CONCLUSIONS: Increased RDW may be considered as a biomarker of MCI.

Marginal zone B cells produce 'natural' atheroprotective IgM antibodies in a T cell-dependent manner.

AIMS: The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis. METHODS AND RESULTS: We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr-/- mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet-induced Tfh. CONCLUSION: Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective 'natural' IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.