Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review.

Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients' quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.

Scaling Supercapacitive Swing Adsorption of CO2 Using Bipolar Electrode Stacks.

Supercapacitive swing adsorption (SSA) modules with bipolar stacks having 2, 4, 8, and 12 electrode pairs made from BPL 4 × 6 activated carbon are constructed and tested for carbon dioxide capture applications. Tests are performed with simulated flue gas (15%CO2 /85%N2) at 2, 4, 8, and 12 V, respectively. Reversible adsorption with sorption capacities (≈58 mmol kg-1) and adsorption rates (≈38 µmol kg-1 s-1) are measured for all stacks. The productivity scales with the number of cells in the module, and increases from 70 to 390 mmol h-1 m-2. The energy efficiency and energy consumption improve with increasing number of bipolar electrodes from 67% to 84%, and 142 to 60 kJ mol-1, respectively. Overall, the results show that SSA modules with bipolar electrodes can be scaled without reducing the adsorptive performance, and with improvement of energetic performance.

Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

Flexible Composite Electrolyte Membranes with Fast Ion Transport Channels for Solid-State Lithium Batteries.

Numerous endeavors have been dedicated to the development of composite polymer electrolyte (CPE) membranes for all-solid-state batteries (SSBs). However, insufficient ionic conductivity and mechanical properties still pose great challenges in practical applications. In this study, a flexible composite electrolyte membrane (FCPE) with fast ion transport channels was prepared using a phase conversion process combined with in situ polymerization. The polyvinylidene fluoride-hexafluoro propylene (PVDF-HFP) polymer matrix incorporated with lithium lanthanum zirconate (LLZTO) formed a 3D net-like structure, and the in situ polymerized polyvinyl ethylene carbonate (PVEC) enhanced the interface connection. This 3D network, with multiple rapid pathways for Li+ that effectively control Li+ flux, led to uniform lithium deposition. Moreover, the symmetrical lithium cells that used FCPE exhibited high stability after 1200 h of cycling at 0.1 mA cm-2. Specifically, all-solid-state lithium batteries coupled with LiFePO4 cathodes can stably cycle for over 100 cycles at room temperature with high Coulombic efficiencies. Furthermore, after 100 cycles, the infrared spectrum shows that the structure of FCPE remains stable. This work demonstrates a novel insight for designing a flexible composite electrolyte for highly safe SSBs.

Synthesis of Monodisperse Mesoporous Carbon Spheres/EPDM Rubber Composites and Their Enhancement Mechanical Properties.

Monodisperse mesoporous carbon spheres (MCS) were synthesized and their potential applications in ethylene propylene diene monomer (EPDM) foam were evaluated. The obtained MCS exhibited a high specific surface area ranging from 621-to 735 m2/g along with large pore sizes. It was observed that the incorporation of MCS into EPDM foam rubber significantly enhances its mechanical properties. The prepared MCS-40 rubber composites exhibit the highest tear strength of 210 N/m and tensile strength of 132.72 kPa, surpassing those of other samples. The enhancement mechanism was further investigated by employing computer simulation technology. The pores within the MCS allowed for the infiltration of EPDM molecular chains, thereby strengthening the interaction forces between the filler and matrix. Moreover, a higher specific surface area resulted in greater adsorption of molecular chains onto the surface of these carbon spheres. This research offers novel insights for understanding the enhancement mechanism of monodisperse mesoporous particles/polymer composites (MCS/EPDM) and highlights their potential application in high-performance rubber composites.

The leaching behavior of hazardous element under different leaching procedure utilizing slag-fly ash-based agent: Chromium, antimony, and lead.

Low-carbon cementitious materials based on blast furnace slag (BFS) and municipal solid waste incineration (MSWI) fly ash play a pivotal role in the construction industry by substituting cement clinker. This innovation significantly reduces CO2 emissions and enables the extensive utilization of both industrial solid waste and hazardous urban waste on a large scale. However, the application of MSWI fly ash as a precursor for alkali-activated cementitious materials presents a significant leaching risk of heavy metal during the extended reaction process, posing a critical barrier to the efficient and widespread utilization of these solid waste. Three static leaching methods [horizontal vibration (HV), sulphuric acid & nitric acid (SN), and acetic acid buffer solution (AAB)], along with acid neutralization capacity (ANC) leaching tests, were applied in BFS-fly ash-based cementitious materials (BFCM) to assess the leaching behavior of high-risk elements-Cr, Sb, and Pb-within MSWI fly ash. The A4 matrix (BFS: MSWI fly ash:FGDG = 70:20:10) exhibits a compressive strength of 72.51 MPa at 180 day, with the leaching concentrations of target elements remaining below the standard limit under chemical attack (H+ and OH-). The critical pH determined is 9.2 from the ANC leaching test results. Visual MINTEQ simulation illustrates the occurrence states of Cr, Sb, and Pb as (CrO4)2-, [Sb(OH)6]-, and Pb(OH)3- within the BFCM system, respectively. The "double salt effect", intended to enhance the dissociation degree of BFS, acts as the driving force behind the long-term hydration reaction. It also serves as an assurance in controlling the long-term leaching risk of object elements. The dissociation degree of BFS within A4 matrix increased by 38.71 %, with the relative content of the typical low-solubility double salt "Ettringite" reaching 29 % at 180 d. This study provides novel theoretical and data-driven evidence to investigate the leaching behavior associated with MSWI fly ash and the accomplishment of replacing cement clinker with low-carbon BFCM.

IL-17A is involved in the hyperplasia of blood vessels in local lesions of psoriasis by inhibiting autophagy.

OBJECTIVE: Increased angiogenesis is a pathological feature of psoriasis, but the pathomechanisms of angiogenesis in psoriasis are not clear. Interleukin-17A (IL-17A) is the major effect factor in the pathogenesis of psoriasis. Our results showed that IL-17A can promote angiogenesis and cause endothelial cell inflammation. Autophagy plays an important role not only in regulating inflammation, but also in regulating angiogenesis. Whether angiogenesis in psoriasis is related to autophagy remains unclear. In this study, we treated human umbilical vein endothelial cells (HUVECs) with IL-17A to simulate increased angiogenesis to study whether increased angiogenesis in psoriasis is related to autophagy. METHODS AND RESULTS: Our results showed that treatment of HUVECs with IL-17A significantly increased angiogenesis and expression levels of mRNA for multiple proinflammatory cytokines (CCL20, IL-8, CCL2, IL-6, and IL-1ß) and, while decreasing intracellular levels of nitric oxide (NO) and NO synthase (NOS) activity. Moreover, IL-17A inhibited autophagy as shown that IL-17A significantly increased expression levels of LC3II and p62 proteins. Induction of autophagy ameliorated IL-17A-mediated inflammatory response and inhibited angiogenesis, accompanied by increased p-AMPKα(Thr172) and p-ULK1(Ser555) expression, and decreased p-mTOR(Ser2448) and p-ULK1(Ser757) expression. Furthermore, inhibition of either AMPK or lysosomal acidification completely overrode autophagy-induced changes in angiogenesis and NOS activity. Finally, induction of autophagy decreased apoptosis and caspase-3 activity in IL-17A-treated HUVECs. CONCLUSIONS: These results showed that IL-17A is involved in angiogenesis and inflammatory response by inhibiting autophagy through AMPK signaling pathway, suggesting that autophagy may be a new therapeutic target for psoriasis.

TLR7 enhancing follicular helper T (Tfh) cells response in C57BL/6 mice infected with Plasmodium yoelii NSM TLR7 mediated Tfh cells in P. yoelii infected mice.

Toll-like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll-like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4+ CXCR5+ PD-1+ Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down-regulated expression of functional molecules CD40L, IFN-γ, IL-21 and IL-10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM-infected mice.

Associations between metal(loid) exposure with overweight and obesity and abdominal obesity in the general population: A cross-sectional study in China.

Previous studies have revealed links between metal(loid)s and health problems; however, the link between metal(loid)s and obesity remains controversial. We evaluated the cross-sectional association between metal(loid) exposure in whole blood and obesity among the general population. Vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), thallium (T1), and lead (Pb) were measured in 3029 subjects in Guangdong Province (China) using ICP-MS. The prevalence of overweight and obesity (OWO) and abdominal obesity (AOB) was calculated according to body mass index (BMI) and waist circumference (WC), respectively. Multivariate analysis showed that elevated blood Cu, Cd, and Pb levels were inversely associated with the risk of OWO, and these associations were confirmed by a linear dose-response relationship. Elevated blood Co concentration was associated with a decreased risk of AOB. A quantile g-computation approach showed a significantly negative mixture-effect of 13 metal(loid)s on OWO (OR: 0.96; 95% CI: 0.92, 0.99). Two metals-Ni and Mo-were inversely associated with the risk of OWO but positively associated with AOB. We cross-grouped the two obesity measurement types and found that the extremes of metal content were present in people with AOB only. In conclusion, blood Cu, Mo, Ni, Cd, and Pb were inversely associated with the risk of OWO. The presence of blood Co may be protective, while Ni and Mo exposure might increase the risk of AOB. The association between metal(loid) exposure and obesity warrants further investigation in longitudinal cohort studies.

Hyaluronic Acid-modified Liposomes for Ursolic Acid-targeted Delivery Treat Lung Cancer Based on p53/ARTS-mediated Mitochondrial Apoptosis.

Background: Chemotherapy drugs can cause drug resistance and other problems when treating lung cancer, which leads to treatment failure. Ursolic acid (UA) is used in formulations based on traditional Chinese medicine. UA has excellent anti-tumor effects, but they are limited by solubility and non-specificity to tumor cells. Objectives: To overcome these issues, we created a novel hyaluronic acid (HA)-targeted liposome system for delivering UA (HA-Lipo/UA) to explore the targeting and anti-tumor effects of UA. Methods: We constructed the HA-Lipo/UA delivery system by the thin film hydration method. The uptake and localization of UA were detected by flow cytometry and microscope. Cell proliferation of A549 cells was detected by MTT assays. Apoptosis and reactive oxygen species (ROS) expression of A549 cells were also evaluated after being treated with HA-Lipo/UA. Western blot analysis evaluated the anti-tumor mechanism of HA-Lipo/UA. Results: HA-Lipo/UA exhibited favorable targeting of the cluster of differentiation (CD)44-overexpressing A549 cells. HA-Lipo/UA exhibited significant inhibition of the proliferation of A549 cells and induced their apoptosis compared with the corresponding monotherapies. HA-Lipo/UA induced overexpression of reactive oxygen species and upregulated expression of p53 and apoptosis-related protein in the transforming growth factor-ß signaling (ARTS) pathway, which induced cytochrome-c release, activation of caspase-3, and promoted mitochondrial apoptosis in A549 cells. Conclusions: Taken together, these data suggested that HA-Lipo/UA could be used to target tumor cells.

Association of dietary inflammatory index with all-cause and cardiovascular disease mortality in hyperuricemia population: A cohort study from NHANES 2001 to 2010.

Dietary management is a crucial component of non-pharmacological treatment for hyperuricemia, yet there is a paucity of research on the impact of dietary habits on the survival outcomes of individuals with hyperuricemia. The objective of this study is to examine the association between dietary inflammatory index (DII) and the all-cause and cardiovascular disease (CVD) mortality in individuals with hyperuricemia. This study included 3093 adult participants from National Health and Nutrition Examination Survey (NHANES) 2001 to 2010. Participants were categorized into 4 groups based on quartiles of DII to demonstrate data characteristics, with sample weights considered. The relationship between DII and the risk of hyperuricemia was examined using multivariable logistic regression models. Kaplan-Meier models and Cox proportional hazards models were employed to assess the relationship between DII levels and the all-cause mortality in individuals with hyperuricemia, with the non-linear relationship tested using restricted cubic splines (RCS). Competing risk models were employed to investigate the association between DII levels and the CVD mortality in individuals diagnosed with hyperuricemia. Subgroup and sensitivity analysis were performed to confirm the robustness and reliability of the findings. Among the participants, 47.95% were aged over 60 years. A positive association observed between the highest quartile of DII level and the incidence of hyperuricemia (OR: 1.34, CI [1.13, 1.57]). Elevated DII levels were correlated with increased all-cause mortality (P value < .001) and CVD mortality (P value < .001) in participants. In comparison to the lowest quartile, the highest quartile of DII exhibited a 31% rise in all-cause mortality (HR: 1.31, CI [1.01, 1.68]) and a 50% increase in CVD mortality (HR: 1.50, CI [1.00, 2.26]). No indication of a nonlinear association between DII levels and all-cause mortality (p-non-linear = .43). These findings indicate a positive correlation between the pro-inflammatory diet and the incidence of hyperuricemia. Additionally, a pro-inflammatory diet may elevate the all-cause and CVD mortality in individuals with hyperuricemia.

Association between dietary intakes of B vitamins and nonalcoholic fatty liver disease in postmenopausal women: a cross-sectional study.

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly common globally, particularly among postmenopausal women. Diet plays a fundamental role in the treatment of NAFLD. However, clinical research on the dietary intakes of B vitamins, specifically in postmenopausal women, is scant. Hence, it is imperative to study the impact of B vitamin dietary intake in postmenopausal women. Methods: This study utilized National Health and Nutrition Examination Survey (NHANES) data for 668 postmenopausal women. Logistic regression analysis was conducted to investigate the association of the intakes of B vitamins with hepatic steatosis and liver fibrosis prevalence. The analysis accounted for various covariates and employed restricted cubic spline analysis to examine potential nonlinear relationships. Additionally, interactions among age, diabetes, and B-vitamin intakes, as well as the interaction between folate and vitamin B12 intake, were explored. Results: Higher intakes of folate [0.30 (0.10-0.88)], choline [0.26 (0.07-0.95)], vitamin B1, and vitamin B2 were associated with a reduced risk of hepatic steatosis in postmenopausal women. The associations of niacin (P-nonlinear = 0.0003), vitamin B1 (P-nonlinear = 0.036), and vitamin B2 (P-nonlinear<0.0001) intakes with hepatic steatosis showed a nonlinear pattern. However, no significant associations were observed between the intakes of niacin, vitamin B6 and vitamin B12 and hepatic steatosis. Furthermore, there were no significant associations between B-vitamin intakes and liver fibrosis. No interaction effects were observed. Conclusion: Dietary intakes of folate, choline, vitamin B1, and vitamin B2 may be associated with liver steatosis in postmenopausal women, these results suggest that optimizing the intake of these specific B vitamins may have a protective effect against liver steatosis in postmenopausal women, offering valuable insights into potential dietary strategies to promote their well-being.

Engineered muscle from micro-channeled PEG scaffold with magnetic Fe3O4 fixation towards accelerating esophageal muscle repair.

Engineered scaffolds are used for repairing damaged esophagus to allow the precise alignment and movement of smooth muscle for peristalsis. However, most of these scaffolds focus solely on inducing cell alignment through directional apparatus, often overlooking the promotion of muscle tissue formation and causing reduced esophageal muscle repair effectiveness. To address this issue, we first introduced aligned nano-ferroferric oxide (Fe3O4) assemblies on a micropatterned poly(ethylene glycol) (PEG) hydrogel to form micro-/nano-stripes. Further modification using a gold coating was found to enhance cellular adhesion, orientation and organization within these micro-/nano-stripes, which consequently prevented excessive adhesion of smooth muscle cells (SMCs) to the thin PEG ridges, thereby effectively confining the cells to the Fe3O4-laid channels. This architectural design promotes the alignment of the cytoskeleton and elongation of actin filaments, leading to the organized formation of muscle bundles and a tendency for SMCs to adopt synthetic phenotypes. Muscle patches are harvested from the micro-/nano-stripes and transplanted into a rat esophageal defect model. In vivo experiments demonstrate the exceptional viability of these muscle patches and their ability to accelerate the regeneration of esophageal tissue. Overall, this study presents an efficient strategy for constructing muscle patches with directional alignment and muscle bundle formation of SMCs, holding significant promise for muscle tissue regeneration.

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Recent progress and application of the tetrahedral framework nucleic acid materials on drug delivery.

INTRODUCTION: The application of DNA framework nucleic acid materials in the biomedical field has witnessed continual expansion. Among them, tetrahedral framework nucleic acids (tFNAs) have gained significant traction as the foremost biological vectors due to their superior attributes of editability, low immunogenicity, biocompatibility, and biodegradability. tFNAs have demonstrated promising results in numerous in vitro and in vivo applications. AREAS COVERED: This review summarizes the latest research on tFNAs in drug delivery, including a discussion of the advantages of tFNAs in regulating biological behaviors, and highlights the updated development and advantageous applications of tFNAs-based nanostructures from static design to dynamically responsive design. EXPERT OPINION: tFNAs possess distinct biological regulatory attributes and can be taken up by cells without the requirement of transfection, differentiating them from other biological vectors. tFNAs can be easily physically/chemically modified and seamlessly incorporated with other functional systems. The static design of the tFNAs-based drug delivery system makes it versatile, reproducible, and predictable. Further use of the dynamic response mechanism of DNA to external stimuli makes tFNAs-based drug delivery more effective and specific, improving the uptake and utilization of the payload by the intended target. Dynamic targeting is poised to become the future primary approach for drug delivery.

Pangenome graph layout by Path-Guided Stochastic Gradient Descent.

Motivation: The increasing availability of complete genomes demands for models to study genomic variability within entire populations. Pangenome graphs capture the full genomic similarity and diversity between multiple genomes. In order to understand them, we need to see them. For visualization, we need a human readable graph layout: A graph embedding in low (e.g. two) dimensional depictions. Due to a pangenome graph's potential excessive size, this is a significant challenge. Results: In response, we introduce a novel graph layout algorithm: the Path-Guided Stochastic Gradient Descent (PG-SGD). PG-SGD uses the genomes, represented in the pangenome graph as paths, as an embedded positional system to sample genomic distances between pairs of nodes. This avoids the quadratic cost seen in previous versions of graph drawing by Stochastic Gradient Descent (SGD). We show that our implementation efficiently computes the low dimensional layouts of gigabase-scale pangenome graphs, unveiling their biological features. Availability: We integrated PG-SGD in ODGI which is released as free software under the MIT open source license. Source code is available at https://github.com/pangenome/odgi.

A neutron beam monitor based on ceramic gas electron multiplier with high spatial resolution for low flux measurements.

Neutron scattering instruments play an important role in studying the inner structure of materials. A neutron beam monitor is a detector commonly used in a neutron scattering instrument. The detection efficiency for most neutron beam monitors is quite low (10-4-10-6). However, in some experiments with a low neutron flux, such as small angle neutron scattering (SANS) and inelastic neutron scattering experiments, a neutron beam monitor with a higher detection efficiency (∼1% for thermal neutrons) is required to reduce the duration of the experiment. To meet this requirement, a ceramic gas electron multiplier-based neutron beam monitor equipped with a 1 µm 10B4C neutron converter was developed in this study. Its performance was determined both experimentally and in simulations. The detection efficiency in the wavelength range of 1.8-5.5 Å was measured experimentally and was confirmed by the simulation results. An algorithm based on event selection and position reconstruction was developed to improve the spatial resolution to about 1 mm full-width-half-maximum. The wavelength spectrum was measured in beamline 20 (BL20) and agreed well with the results obtained using a commercial monitor. The maximum counting rate was 1.3 MHz. The non-uniformity over the whole 100 × 100 mm2 active area was determined to be 1.4%. Due to the excellent performance of this monitor, it has been used in several neutron instruments, such as the SANS and the High-Energy Direct-Geometry Inelastic Spectrometer instruments in the China spallation neutron source.

Immunological characteristics of CD103+CD8+ Tc cells in the liver of C57BL/6 mouse infected with plasmodium NSM.

CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were sacrificed on 12-16 days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8+ Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8+ Tc cells significantly decreased after infection. Compared to that of CD103- CD8+ Tc cells, CD103+ CD8+ Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103+CD8+ Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.

A Study on Vascular Regulators as Early Biomarkers of Hand Arm Vibration Syndrome.

OBJECTIVES: Purposes of this study are to study the changes in expression of vascular regulators after vibration exposure and during the onset of vibration-induced white finger (VWF) and to screen for vascular regulatory factors that could be used as early biomarkers of HAVS. METHODS: Using judgmental sampling from a Chinese factory, workers with VWF and hand-transmitted vibration exposure but without VWF were selected for research. Blood samples were taken from all subjects, and the levels of nine of the vascular regulators were measured using ELISA. RESULTS: Receiver operating characteristic curve analysis was performed on nine vascular regulators to assess their diagnostic sensitivity for VWF with the following area under the curve results: PGI 2 = 0.861, ANP = 0.840. CONCLUSIONS: Collectively, PGI 2 and ANP exhibited the most potential for the early diagnosis of HAVS.

Comparison of surface microscopy coil and ankle joint special phased array coil magnetic resonance imaging in assessing preoperative osteochondral lesions of the talus.

Background: Lesion size is a major determinant of treatment strategies and predictor of clinical outcomes for osteochondral lesions of the talus (OLTs). Although magnetic resonance imaging (MRI) has been commonly used in the preoperative evaluation of OLTs, MRI has low reliability and usually overestimates or underestimates lesion size compared with intraoperative assessment. This study aims to determine whether the surface microscopy coil (SMC) can improve the accuracy of assessment of preoperative OLTs compared with conventional coil MRI, ankle joint special phased array coil (ASC). Methods: A total of 43 patients diagnosed with OLTs undertook preoperative MRI examination with both SMC and ASC were included in this prospective study from 2019 to 2022. The diameter of the lesion was measured in sagittal plane and coronal plane at its widest point and then the lesion area was calculated. Then MRI measurements were compared with arthroscopy or open-surgery measurements. Results: The mean lesion area measured with ASC was significantly greater than that measured intraoperatively (95.07±44.60 vs. 52.74±29.86 mm2, P<0.001), while there was no significant difference between lesion area measured in SMC and intraoperatively (55.28±36.06 vs. 52.74±29.86 mm2, P=0.576). Diameter measured in ASC was significantly greater than that measured intraoperatively in both coronal plane (8.95±2.48 vs. 6.67±1.81, P<0.001) and sagittal plane (13.12±3.76 vs. 9.58±3.98, P<0.001). No significant difference between lesion diameter measured in SMC and intraoperatively in both coronal plane (6.44±2.59 vs. 6.67±1.81, P=0.608) or sagittal plane (10.23±3.69 vs. 9.58±3.98, P=0.194). Compared with surgical assessment, 39 of 43 cases were consistent with SMC assessment while only 26 of 43 cases were consistent with ASC assessment (39/43 vs. 26/43, P=0.002). Conclusions: Diameter measured with SMC was much more accurate than ASC MRI. Compared with ASC MRI, the SMC had a much higher concordance rate between preoperative assessment and surgical assessment.