Wheat bran arabinoxylans: Chemical structure, extraction, properties, health benefits, and uses in foods.

Wheat bran (WB) is a well-known and valuable source of dietary fiber. Arabinoxylan (AX) is the primary hemicellulose in WB and can be isolated and used as a functional component in various food products. Typically, AX is extracted from the whole WB using different processes after mechanical treatments. However, WB is composed of different layers, namely, the aleurone layer, pericarp, testa, and hyaline layer. The distribution, structure, and extractability of AX vary within these layers. Modern fractionation technologies, such as debranning and electrostatic separation, can separate the different layers of WB, making it possible to extract AX from each layer separately. Therefore, AX in WB shows potential for broader applications if it can be extracted from the different layers separately. In this review, the distribution and chemical structures of AX in WB layers are first discussed followed by extraction, physicochemical properties, and health benefits of isolated AX from WB. Additionally, the utilization of AX isolated from WB in foods, including cereal foods, packaging film, and the delivery of food ingredients, is reviewed. Future perspectives on challenges and opportunities in the research field of AX isolated from WB are highlighted.

Advancing Integration of Direct C-H Arylation-Derived Star-Shaped Oligomers as Second Acceptors for Ternary Organic Solar Cells.

Organic solar cells (OSCs) could benefit from the ternary bulk heterojunction (BHJ), a method that allows for fine-tuning of light capture, cascade energy levels, and film shape, in order to increase their power conversion efficiency (PCE). In this work, the third components of PM6:Y6 and PM6:BTP-eC9 BHJs are a set of four star-shaped unfused ring electron acceptors (SSUFREAs), i.e., BD-IC, BFD-IC, BD-2FIC, and BFD-2FIC, that are facilely synthesized by direct C-H arylation. The four SSUFREAs all show complete complementary absorption with PM6, Y6, and BTP-eC9, which facilitates light harvesting and exciton collection. When BFD-2FIC is added as a third component, the PCEs of PM6:Y6 and PM6:BTP-eC9 binary BHJs are able to be improved from 15.31% to 16.85%, and from 16.23% to 17.23%, respectively, showing that BFD-2FIC is useful for most effective ternary OSCs in general, and increasing short circuit current (JSC) and better film morphology are two additional benefits. The ternary PM6:Y6:BFD-2FIC exhibits a 9.7% percentage of increase in PCE compared to the PM6:Y6 binary BHJ, which is one of the highest percentage increases among the reported ternary BHJs, showing the huge potential of BFD-2FIC for ternary BHJ OSCs.

High-Performance Four-Channel Tactile Sensor for Measuring the Magnitude and Orientation of Forces.

Flexible sensors have gained popularity in recent years. This study proposes a novel structure of a resistive four-channel tactile sensor capable of distinguishing the magnitude and direction of normal forces acting on its sensing surface. The sensor uses EcoflexTM00-30 as the substrate and EGaIn alloy as the conductive filler, featuring four mutually perpendicular and curved channels to enhance the sensor's dynamic responsiveness. Experiments and simulations show that the sensor has a large dynamic range (31.25-100 mΩ), high precision (deviation of repeated pressing below 0.1%), linearity (R2 above 0.97), fast response/recovery time (0.2 s/0.15 s), and robust stability (with fluctuations below 0.9%). This work uses an underactuated robotic hand equipped with a four-channel tactile sensor to grasp various objects. The sensor data collected effectively predicts the shapes of the objects grasped. Furthermore, the four-channel tactile sensor proposed in this work may be employed in smart wearables, medical diagnostics, and other industries.

Nano­selenium alleviates cadmium-induced blood-brain barrier destruction by restoring the Wnt7A/ß-catenin pathway.

Selenium (Se), a highly beneficial animal feed additive, exhibits remarkable antioxidant and anti-inflammatory properties. Nano­selenium (Nano-Se) is an advanced formulation of Se featuring a specialized drug delivery vehicle, with good bioavailability, higher efficacy, and lower toxicity compared to the traditional form of Se. With the advancement of industry, cadmium (Cd) contamination occurs in different countries and regions and thereby contaminating different food crops, and the degree of pollution is degree increasing year by year. The present investigation entailed the oral administration of CdCl2 and/or Nano-Se to male chickens of the Hy-Line Variety White breed, which are one day old, subsequent to a 7-day adaptive feeding period, for a duration of 90 days. The study aimed to elucidate the potential protective impact of Nano-Se on Cd exposure. The study found that Nano-Se demonstrates potential in mitigating the blood-brain barrier (BBB) dysfunction characterized by impairment of adherens junctions (AJS) and tight junctions (TJS) by inhibiting reactive oxygen species (ROS) overproduction. In addition, the data uncovered that Nano-Se demonstrates a proficient ability in alleviating BBB impairment and inflammatory reactions caused by Cd through the modulation of the Wnt7A/ß-catenin pathway, highlights its potential to maintain brain homeostasis. Hence, this research anticipates that the utilization of Nano-Se effectively mitigate the detrimental impacts associated with Cd exposure on the BBB.

Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown. METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed from January 2019 to June 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs). RESULTS: After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important AEs that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8/9 and arginase-1 expression by MDSCs. At the same time, NK cell-derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with b2m-knockout (KO) tumor mice models. Similarly in syngeneic wild-type and IL-6 KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell-mediated mechanism that drives the development of MDSCs during tumor immune escape.

Changes in the structure and enzyme binding of starches during in vitro enzymatic hydrolysis using mammalian mucosal enzyme mixtures.

Starches are hydrolyzed into monosaccharides by mucosal α-glucosidases in the human small intestine. However, there are few studies assessing the direct digestion of starch by these enzymes. The objective of this study was to investigate the changes in the structure and enzyme binding of starches during in vitro hydrolysis by mammalian mucosal enzymes. Waxy maize (WMS), normal maize (NMS), high-amylose maize (HAMS), waxy potato (WPS), and normal potato (NPS) starches were examined. The order of the digestion rate was different compared with other studies using a mixture of pancreatic α-amylase and amyloglucosidase. NPS was digested more than other starches. WPS was more digestible than WMS. Hydrolyzed starch from NPS, NMS, WPS, WMS, and HAMS after 24 h was 66.4, 64.2, 61.7, 58.7, and 46.2 %, respectively. Notably, a significant change in the morphology, reduced crystallinity, and a decrease in the melting enthalpy of the three starches (NPS, NMS, and WPS) after 24 h of hydrolysis were confirmed by microscopy, X-ray diffraction, and differential scanning calorimetry, respectively. The bound enzyme fraction of NPS, NMS, and WPS increased as hydrolysis progressed. In contrast, HAMS was most resistant to hydrolysis by mucosal α-glucosidases in terms of digestibility, changes in morphology, crystallinity, and thermal properties.

Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions.

BACKGROUND: Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM: To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS: The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS: Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION: Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Synergistically optimized electron and phonon transport in high-performance copper sulfides thermoelectric materials via one-pot modulation.

Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

Unveiling the significance of gastric digestion in gastrointestinal fate of octenylsuccinylated starch-stabilized emulsions.

The importance of gastric digestion in starch-based emulsion is often overshadowed compared to intestinal digestion, despite acknowledging the activity of salivary α-amylase in the stomach. This study aimed to address this gap by investigating the digestion of starch-based emulsions through orogastrointestinal digestion experiments. Our observations revealed the crucial role of salivary α-amylase, which hydrolyzed ∼8 %, ∼56 %, and âˆ¼ 28 % of starch in emulsions stabilized by octenylsuccinylated maize starch (OMS-E), gelatinized OMS (GOMS-E), and retrograded OMS (ROMS-E), respectively, during the gastric phase. Consequently, ∼23 % of the oil in GOMS-E underwent lipolysis during this phase, whereas ∼13 and âˆ¼ 6 % of the oil was lipolyzed in OMS-E and ROMS-E, respectively. These phenomena significantly influenced their small intestinal digestion and the bioaccessibility of encapsulated curcumin. Notably, GOMS-E exhibited ∼28 % lower curcumin bioaccessibility than that of curcumin encapsulated in OMS-E or ROMS-E. This difference was attributed to premature gastric digestion and subsequent encapsulant release in the case of GOMS-E. This understanding can be utilized to manipulate the delivery and digestion of starch-based emulsions. Importantly, our findings highlight the necessity of considering gastric amylolysis and lipolysis when investigating the gastrointestinal fate of starch-based emulsions.

Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

DNA topoisomerase II inhibition potentiates osimertinib's therapeutic efficacy in EGFR-mutant non-small cell lung cancer models.

Development of effective strategies to manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the treatment of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), is urgently needed. This study reports that DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide, synergistically decreased cell survival, with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells; suppressed the growth of osimertinib-resistant tumors; and delayed the emergence of osimertinib-acquired resistance. Mechanistically, osimertinib decreased Topo IIα levels in EGFRm NSCLC cells by facilitating FBXW7-mediated proteasomal degradation, resulting in induction of DNA damage; these effects were lost in osimertinib-resistant cell lines that possess elevated levels of Topo IIα. Increased Topo IIα levels were also detected in the majority of tissue samples from patients with NSCLC after relapse from EGFR tyrosine kinase inhibitor treatment. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their susceptibility to osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.

Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis.

BACKGROUND: Previous studies have emphasized the association between the intake of artificial sweeteners (AS) and type 2 diabetes mellitus (T2DM), but the causative relationship remains ambiguous. METHODS: This study employed univariate Mendelian randomization (MR) analysis to assess the causal link between AS intake from various sources and T2DM. Linkage disequilibrium score (LDSC) regression was used to evaluate the correlation between phenotypes. Multivariate and mediation MR were applied to investigate confounding factors and mediating effects. Data on AS intake from different sources (N = 64,949) were sourced from the UK Biobank, while T2DM data were derived from the DIAbetes Genetics Replication And Meta-analysis.The primary method adopted was inverse variance weighted (IVW), complemented by three validation techniques. Additionally, a series of sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. RESULTS: LDSC analysis unveiled a significant genetic correlation between AS intake from different sources and T2DM (rg range: -0.006 to 0.15, all P < 0.05). After correction by the false discovery rate (FDR), the primary IVW method indicated that AS intake in coffee was a risk factor for T2DM (OR = 1.265, 95% CI: 1.035-1.545, P = 0.021, PFDR = 0.042). Further multivariable and mediation MR analyses pinpointed high density lipoprotein-cholesterol (HDL-C) as mediating a portion of this causal relationship. In reverse MR analysis, significant evidence suggested a positive correlation between T2DM and AS intake in coffee (ß = 0.013, 95% CI: 0.004-0.022, P = 0.004, PFDR = 0.012), cereal (ß = 0.007, 95% CI: 0.002-0.012, P = 0.004, PFDR = 0.012), and tea (ß = 0.009, 95% CI: 0.001-0.017, P = 0.036, PFDR = 0.049). No other causal associations were identified (P > 0.05, PFDR > 0.05). CONCLUSION: The MR analysis has established a causal relationship between AS intake in coffee and T2DM. The mediation by HDL-C emphasizes potential metabolic pathways underpinning these relationships.

Cadmium negatively affects the growth and physiological status and the alleviation effects by exogenous selenium in silage maize (Zea mays L.).

Increasing soil cadmium (Cd) contamination is a serious threat to human food health and safety. In order to reduce Cd uptake and Cd toxicity in silage maize, hydroponic tests were conducted to investigate the effect of exogenous Cd on the toxicity of silage maize in this study. In the study, a combination of Cd (5, 20, 50, 80, and 10 µM) treatments was applied in a hydroponic system. With increasing Cd concentration, Cd significantly inhibited the total root length (RL), root surface area (SA), root volume (RV), root tip number (RT), and branching number (RF) of maize seedlings, which were reduced by 28.1 to 71.3%, 20.2 to 64.9%, 11.2 to 56.5%, 43.7 to 63.4%, and 38.2 to 72.6%, respectively. The excessive Cd accumulation inhibited biomass accumulation and reduced silage maize growth, photosynthesis, and chlorophyll content and activated the antioxidant systems, including increasing lipid peroxidation and stimulating catalase (CAT) and peroxidase (POD), but reduced the activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the root. Besides, selenium (Se) significantly decreased the Cd concentration of the shoot and root by 27.1% and 35.1% under Cd50, respectively. Our results reveal that exogenously applied Cd reduced silage maize growth and impaired photosynthesis. Whereas silage maize can tolerate Cd by increasing the concentration of ascorbate and glutathione and activating the antioxidant defense system, the application of exogenous selenium significantly reduced the content of Cd in silage maize.

OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity.

AIM: To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion (NA-CRAO) via optical coherence tomography angiography (OCTA) and analyze their correlation with visual acuity. METHODS: Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into: A type (mild n=29), B type (moderate n=27) and C type (severe n=6) based on the degree of visual loss, retinal edema, and arterial blood flow delay in fundus fluorescence angiography (FFA). Contralateral healthy eyes were used as the control group. Best-corrected visual acuity (BCVA), slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, OCTA, and FFA were performed. Spearman's correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity. RESULTS: There were no statistically significant differences in age, gender, and intraocular pressure among the three types and the control group (P>0.05). Vessel density in deep capillary plexus (VD-DCP) significantly decreased (P<0.05) in all three types of NA-CRAO patients compared to the control group. Vessel density in superficial vascular plexus (VD-SVP) significantly decreased (P<0.05) in type A patients and choriocapillaris flow area significantly decreased (P<0.05) in type B and type C patients compared to the control group; while outer retinal flow areas significantly increased in the type A (P<0.05) and decreased in type C patients (P<0.05). The retinal thickness significantly increased in type C group (P<0.05). The VD-SVP at fovea in the type A was significantly lower than both of type B and C. The VD-SVP at nasal parafovea in type A and B was significantly lower than type C (P<0.05). The logMAR BCVA of type A was significantly better than that of type B and C groups (P<0.05). Spearman's correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea (r=0.679, P=0.031) and nasal parafovea (r=0.826, P=0.013). CONCLUSION: OCTA is valuable for assessing retinal ischemia, and evaluating visual impairment. Deep retinal vasculature is commonly affected in all NA-CRAO types. VD-SVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.

MAPK/NF-κB signaling mediates atrazine-induced cardiorenal syndrome and antagonism of lycopene.

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways.

Inflammatory Fibroblast-Like Synoviocyte-Derived Exosomes Aggravate Osteoarthritis via Enhancing Macrophage Glycolysis.

The severity of osteoarthritis (OA) and cartilage degeneration is highly associated with synovial inflammation. Although recent investigations have revealed a dysregulated crosstalk between fibroblast-like synoviocytes (FLSs) and macrophages in the pathogenesis of synovitis, limited knowledge is available regarding the involvement of exosomes. Here, increased exosome secretion is observed in FLSs from OA patients. Notably, internalization of inflammatory FLS-derived exosomes (inf-exo) can enhance the M1 polarization of macrophages, which further induces an OA-like phenotype in co-cultured chondrocytes. Intra-articular injection of inf-exo induces synovitis and exacerbates OA progression in murine models. In addition, it is demonstrated that inf-exo stimulation triggers the activation of glycolysis. Inhibition of glycolysis using 2-DG successfully attenuates excessive M1 polarization triggered by inf-exo. Mechanistically, HIF1A is identified as the determinant transcription factor, inhibition of which, both pharmacologically or genetically, relieves macrophage inflammation triggered by inf-exo-induced hyperglycolysis. Furthermore, in vivo administration of an HIF1A inhibitor alleviates experimental OA. The results provide novel insights into the involvement of FLS-derived exosomes in OA pathogenesis, suggesting that inf-exo-induced macrophage dysfunction represents an attractive target for OA therapy.

Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression.

Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-ß-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-ß-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-ß-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid ß (Aß) production through ß-catenin-ß-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αß production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.

Optimizing Levothyroxine Replacement: A Precision Dosage Model for Post-Thyroidectomy Patients.

Background: Thyroidectomy is commonly performed for benign or malignant thyroid tumors, often resulting in hypothyroidism. Levothyroxine (LT4) supplementation is crucial to maintain hormone levels within the normal range and suppress TSH for cancer control. However, determining the optimal dosage remains challenging, leading to uncertain outcomes and potential side effects. Methods: We analyzed clinical examination data from 510 total thyroidectomy patients, including demographic information, blood tests, and thyroid function. Using R, we applied data preprocessing techniques and identified 274 samples with 98 variables. Principal Component Analysis, correlation analysis, and regression analysis were conducted to identify factors associated with optimal LT4 dosage. Results: The analysis revealed that only eight variables significantly influenced the final satisfactory dosage of LT4 in tablets: Benign0/Malignant1 (benign or malignant), BQB (electrophoretic albumin ratio), TP (total protein), FDP (fibrin degradation products), TRAB_1 (thyroid-stimulating hormone receptor antibody), PT (prothrombin time), MONO# (monocyte count), and HCV0C (hepatitis C antibody). The resulting predictive model was: . Conclusion: Parameters such as benign/malignant status, TRAB_1, and BQB ratio during medication can serve as observational indicators for postoperative LT4 dosage. The calculated linear model can predict the LT4 dosage for patients after thyroidectomy, leading to improved treatment effectiveness and conserving medical resources.