Deep random forest with ferroelectric analog content addressable memory.

Deep random forest (DRF), which combines deep learning and random forest, exhibits comparable accuracy, interpretability, low memory and computational overhead to deep neural networks (DNNs) in edge intelligence tasks. However, efficient DRF accelerator is lagging behind its DNN counterparts. The key to DRF acceleration lies in realizing the branch-split operation at decision nodes. In this work, we propose implementing DRF through associative searches realized with ferroelectric analog content addressable memory (ACAM). Utilizing only two ferroelectric field effect transistors (FeFETs), the ultra-compact ACAM cell performs energy-efficient branch-split operations by storing decision boundaries as analog polarization states in FeFETs. The DRF accelerator architecture and its model mapping to ACAM arrays are presented. The functionality, characteristics, and scalability of the FeFET ACAM DRF and its robustness against FeFET device non-idealities are validated in experiments and simulations. Evaluations show that the FeFET ACAM DRF accelerator achieves ∼106×/10× and ∼106×/2.5× improvements in energy and latency, respectively, compared to other DRF hardware implementations on state-of-the-art CPU/ReRAM.

Regulating the crystal orientation of vapor-transport-deposited GeSe thin films by a post-annealing treatment.

Recently, GeSe has emerged as a highly promising photovoltaic absorber material due to its excellent optoelectronic properties, nontoxicity, and high stability. Although many advantages make GeSe well suited for thin-film solar cells, the power conversion efficiency of the GeSe thin-film solar cell is still much below the theoretical maximum efficiency. One of the challenges lies in controlling the crystal orientation of GeSe to enhance solar cell performance. The two-step preparation of GeSe thin films has not yet been reported to grow along the [111] orientation. In this work, we study the effect of a post-annealing treatment on the GeSe thin films and the performance of the solar cells. It was found that amorphous GeSe films can be converted into polycrystalline films with different orientations by changing the post-annealing temperature. [111]-oriented and [100]-oriented GeSe thin films were successfully prepared on the same substrate by optimizing the annealing conditions. With the structure of Au/GeSe/CdS/ITO cell devices, PCEs of 0.14% and 0.16% were ultimately achieved.

Heterozygous prothrombin mutations associated thrombophilia.

BACKGROUND: Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis. MATERIAL AND METHODS: We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms. RESULTS: Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both antithrombin inhibition and PC activation reactions. CONCLUSIONS: The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.

Comprehensive assessment of the anti-obesity effects of highland barley total, insoluble, and soluble dietary fiber through multi-omics analysis.

The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus, while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum, respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity.

Bound polyphenols in insoluble dietary fiber of navel orange peel modulate LPS-induced intestinal-like co-culture inflammation through CSF2-mediated NF-κB/JAK-STAT pathway.

Our laboratory previously extracted bound polyphenols (BPP) in insoluble dietary fiber from navel orange peel (NOP-IDF), and the aim of this study was to investigate the anti-inflammatory activity and potential molecular mechanisms of BPP by establishing an LPS-induced intestinal-like Caco-2/RAW264.7 co-culture inflammation model. The results demonstrated that BPP reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the production of pro-inflammatory cytokines, nitric oxide (NO), and reactive oxidative species (ROS) during the inflammatory damage process. Furthermore, BPP alleviated the lipopolysaccharides (LPS)-induced intestinal barrier damage by attenuating the decrease in trans-epithelial electrical resistance (TEER), diamine oxidase (DAO) activity, and intestinal alkaline phosphatase (IAP) activity, as well as the downregulation of ZO-1, Occludin, and Claudin-1 protein expression levels. RNA-seq results on RAW264.7 cells in the co-culture model showed that the NF-κB and JAK-STAT pathways belonged to the most significantly affected signaling pathways in the KEGG analysis, and western blot confirmed that they are essential for the role of BPP in intestinal inflammation. Additionally, overexpression of the granulocyte-macrophage colony-stimulating factor (CSF2) gene triggered abnormal activation of the NF-κB and JAK-STAT pathways and high-level expression of inflammatory factors, while BPP effectively improved this phenomenon. The above results suggested that BPP could inhibit intestinal inflammatory injury and protect intestinal barrier integrity through CSF2-mediated NF-κB and JAK-STAT pathways.

Emerging Trends in Electron Transport Layer Development for Stable and Efficient Perovskite Solar Cells.

Perovskite solar cells (PSCs) stand at the forefront of photovoltaic research, with current efficiencies surpassing 26.1%. This review critically examines the role of electron transport materials (ETMs) in enhancing the performance and longevity of PSCs. It presents an integrated overview of recent advancements in ETMs, like TiO2, ZnO, SnO2, fullerenes, non-fullerene polymers, and small molecules. Critical challenges are regulated grain structure, defect passivation techniques, energy level alignment, and interfacial engineering. Furthermore, the review highlights innovative materials that promise to redefine charge transport in PSCs. A detailed comparison of state-of-the-art ETMs elucidates their effectiveness in different perovskite systems. This review endeavors to inform the strategic enhancement and development of n-type electron transport layers (ETLs), delineating a pathway toward the realization of PSCs with superior efficiency and stability for potential commercial deployment.

Protective effects of EGCG on acrolein-induced Caenorhabditis elegans and its mechanism of life extension.

In this study, it was found that epigallocatechin-3-gallate (EGCG) could extend the lifespan of Caenorhabditis elegans (C. elegans) induced by 100 µM acrolein (ACR) at all test concentrations (300, 400, 500, 600, and 700 µM). Notably, 500 µM EGCG exhibited the most significant mean lifespan extension, increasing it by approximately 32.5%. Furthermore, 500 µM EGCG effectively reduced elevated levels of reactive oxygen species (ROS) and lipofuscin production caused by acrolein. It also bolstered the activity of antioxidant enzymes and mitigated malondialdehyde (MDA) levels compared to the ACR-only group. These effects appeared independent of dietary restrictions. Additionally, qPCR results revealed different changes in the transcription levels of 11 genes associated with antioxidative and anti-aging functions following EGCG treatment. At the expression level, GST-4::GFP, SOD-3::GFP and HSP-16.2::GFP exhibited an initial increase with ACR treatment followed by a decrease with EGCG treatment, while the expression pattern of these three GFPs remained consistent with the enzyme activity and transcription regulation level. EGCG treatment also reduced the nuclear localization of SKN-1 and DAF-16 in the MAPK and IIS pathways that were enhanced by ACR. Moreover, the longevity-promoting effects of EGCG were diminished or absent in 13 longevity gene-deletion mutants. In conclusion, EGCG demonstrates protective effects on ACR-induced C. elegans, with the IIS and MAPK pathways playing a critical role in enhancing resilience to ACR.

A metal-organic framework signaling probe-mediated immunosensor for the economical and rapid determination of enrofloxacin in milk.

Ensuring the safety of animal-derived foods requires the reliable and swift identification of enrofloxacin residues to monitor the presence of antibiotics. In this regard, we synthesized, tuned, and investigated the optical properties of a bimetallic metal-organic framework (Ce/Zr-UiO 66). The investigation was facilitated by employing a polydopamine-coated pipette tip with high adsorption efficiency, serving as an immunoreactive carrier. Subsequently, an immunofunctionalized variant of Ce/Zr-UiO 66, referred to as Ce/Zr-UiO 66@ Bovine serum albumin-enrofloxacin, was developed as an optical probe for the rapid and sensitive identification of enrofloxacin across a variety of samples. The method can accurately detect enrofloxacin at concentrations as low as 0.12 ng/mL, with a determination time of under 15 min; furthermore, it demonstrates exceptional efficacy when applied to food, environmental, and clinical samples. The implementation of this methodology offers a valuable means for cost-effective, rapid, and on-site enrofloxacin determination.

Ameliorative effect of bound polyphenols in mung bean coat dietary fiber on DSS-induced ulcerative colitis in mice: the intestinal barrier and intestinal flora.

The consumption of dietary fiber is beneficial for gut health, but the role of bound polyphenols in dietary fiber has lacked systematic study. The aim of this study is to evaluate the ameliorative effect of mung bean coat dietary fiber (MDF) on DSS-induced ulcerative colitis in mice in the presence and absence of bound polyphenols. Compared to polyphenol-removed MDF (PR-MDF), MDF and formulated-MDF (F-MDF,backfilling polyphenols by the amount of extracted from MDF into PR-MDF) alleviated symptoms such as weight loss and colonic injury in mice with colitis, effectively reduced excessive inflammatory responses, and the bound polyphenols restored the integrity of the intestinal barrier by promoting the expression of tight junction proteins. Additionally, bound polyphenols restored the expression of autophagy-related proteins (mTOR, beclin-1, Atg5 and Atg7) and inhibited the excessive expression of apoptotic-related proteins (Bax, caspase-9, and caspase-3). Furthermore, bound polyphenols could ameliorate the dysregulation of the intestinal microbiota by increasing the abundance of beneficial bacteria and inhibiting the abundance of harmful bacteria. Thus, it can be concluded that the presence of bound polyphenols in MDF plays a key role in the alleviation of DSS-induced ulcerative colitis.

A noncanonical splicing variant c.875-5 T > G in von Willebrand factor causes in-frame exon skipping and type 2A von Willebrand disease.

INTRODUCTION: A novel variant involving noncanonical splicing acceptor site (c.875-5 T > G) in propeptide coding region of von Willebrand factor (VWF) was identified in a patient with type 2A von Willebrand disease (VWD), who co-inherited with a null variant (p.Tyr271*) and presented characteristic discrepancy of plasma level of VWF antigen and activity, and a selective reduction of both intermediate-molecular-weight (IMWMs) and high-molecular-weight VWF multimers (HMWMs). MATERIALS AND METHODS: VWF mRNA transcripts obtained from peripheral leukocytes and platelets of the patients were investigated to analyze the consequence of c.875-5 T > G on splicing. The impact of the variant on expression and multimer assembly was further analyzed by in vitro expression studies in AtT-20 cells. The intracellular processing of VWF mutant and the Weibel-Palade bodies (WPBs) formation was evaluated by immunofluorescence staining and electron microscopy. RESULTS: The mRNA transcript analysis revealed that c.875-5 T > G variant led to exon 8 skipping and an in-frame deletion of 41 amino acids in the D1 domain of VWF (p.Ser292_Glu333delinsLys), yielding a truncated propeptide. Consistent with the patient's laboratory manifestations, the AtT-20 cells transfected with mutant secreted less VWF, with the VWF antigen level in conditioned medium 47 % of wild-type. A slight retention in the endoplasmic reticulum was observed for the mutant. Almost complete loss of IMWMs and HMWMs in the medium and impaired WPBs formation in the cell, indicating truncated VWF propeptide lost its chaperon-like function for VWF multimerization and tubular storage. CONCLUSIONS: The VWF splicing site variant (c.875-5 T > G) causes propeptide truncation, severely compromising VWF multimer assembly and tubular storage.

Effects of improver on the quality of frozen Chinese sweet rice wine dough: Water status, protein structure and flavor properties.

In the study, a sweet wine koji (YQ-5) was successfully selected to make frozen Chinese sweet rice wine dough (F-CD) for flavor enrichment. Subsequently, the effects of single improver (SI: xanthan gum, potassium carbonate, antifreeze protein, diacetyl tartaric esters of monoglycerides and composite improver (XPADG: Four improvers mixed in proportion) on the texture, rheological properties, microstructure, water status, protein secondary structure, volatile flavor substances and sensory properties of F-CD during frozen storage were investigated. The results indicated that XPADG slowed the increase in freezable water and water mobility in the dough, giving dough the most stable rheological properties and minimizing the damage of freezing to the secondary structure and microstructure of proteins. Besides, GC-QTOF/MS analysis showed that XPADG may facilitate the retention of flavoring substances in F-CD after storage for 6 days. Finally, the sensory evaluation showed that XPADG imparted good sensory properties to the product after freezing for 6 days.

[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

Prognostic value of coagulation markers in patients with colorectal caner: A prospective study.

Background and Aims: The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Methods: Thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d-dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan-Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single-factor and multifactor cox regression analysis model. Results: The following indicators (TM, TAT, PIC, t-PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination "TAT + PIC + DD + FDP + Fbg" can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. Conclusion: The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

Disulfiram: A novel repurposed drug for cancer therapy.

ABSTRACT: Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Ferroelectric FET-based context-switching FPGA enabling dynamic reconfiguration for adaptive deep learning machines.

Field programmable gate array (FPGA) is widely used in the acceleration of deep learning applications because of its reconfigurability, flexibility, and fast time-to-market. However, conventional FPGA suffers from the trade-off between chip area and reconfiguration latency, making efficient FPGA accelerations that require switching between multiple configurations still elusive. Here, we propose a ferroelectric field-effect transistor (FeFET)-based context-switching FPGA supporting dynamic reconfiguration to break this trade-off, enabling loading of arbitrary configuration without interrupting the active configuration execution. Leveraging the intrinsic structure and nonvolatility of FeFETs, compact FPGA primitives are proposed and experimentally verified. The evaluation results show our design shows a 63.0%/74.7% reduction in a look-up table (LUT)/connection block (CB) area and 82.7%/53.6% reduction in CB/switch box power consumption with a minimal penalty in the critical path delay (9.6%). Besides, our design yields significant time savings by 78.7 and 20.3% on average for context-switching and dynamic reconfiguration applications, respectively.

Bimetallic nanozyme-bioenzyme hybrid material-mediated ultrasensitive and automatic immunoassay for the detection of aflatoxin B1 in food.

Aflatoxin B1 (AFB1) is one of the most prevalent and dangerous biotoxin in crops and feedstuff, which poses a great threat to human health and also cause significant financial losses. Therefore, there is an urgent need to develop an effective method for AFB1 detection. In this work, we developed an automatic reaction equipment and nanozyme-enhanced immunosorbent assay (Auto-NEISA) for sensitive and accurate detection of AFB1 by combining the highly effective signal probes with a self-designed automated immunoreactive equipment. Wherein, polystyrene (PS) nanoparticles were used as signal carriers for loading a massive in situ-synthesized platinum and palladium bimetallic nanozyme, which could enrich horseradish peroxidase-labeled goat anti-mouse antibody (HRP-Ab2) on the nanozyme surface to form a bimetallic nanozyme-bioenzyme hybrid material for multiple signal amplification. The entire reaction could be automatically completed by the self-developed immunoreactive equipment. The Auto-NEISA method realized the sensitive detection of AFB1 with a wide linear detection range of 10-104 pg/mL, at a low limit of detection (LOD) of 5.52 pg/mL. The LOD was 65-fold lower than that of the enzyme-linked immunosorbent assay (ELISA). Additionally, Auto-NEISA was successfully applied to detect AFB1 in real food samples, demonstrating that it has considerable potential for detecting food contaminants with high accuracy and efficiency.

Postoperative Antiosteoporotic Treatment with Zoledronic Acid Improves Rotator Cuff Healing but Does Not Improve Outcomes in Female Patients with Postmenopausal Osteoporosis: A Prospective, Single-Blinded, Randomized Study.

PURPOSE: To investigate the effect of the antiosteoporotic agent zoledronic acid (ZA) on rotator cuff healing and clinical outcomes in patients with postmenopausal osteoporosis. METHODS: We prospectively enrolled 138 female patients with postmenopausal osteoporosis who were scheduled to undergo arthroscopic rotator cuff repair (ARCR) from March 2020 to March 2021. Patients were randomly allocated to the ZA group (ARCR followed by intravenous ZA infusions at postoperative Day 1 and 1 year later) and the control group (ARCR alone). All patients were followed up for 24 months. Tendon healing was evaluated by ultrasonography at 6 weeks and 24 months after surgery. The American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Rotator Cuff (WORC) index, and Numeric Rating Scale (NRS) for pain were recorded at each follow-up, and the minimal clinically important difference (MCID) was calculated. RESULTS: A total of 124 patients were included in the final analysis, 61 in the ZA group and 63 in the control group. There was no statistically significant difference in participant characteristics between the 2 groups. The ZA group had a significantly higher tendon healing rate than the control group at 2 years after surgery (odds ratio = 5.0; 95% confidence interval [CI], 1.4-18.7; P = .014). Regarding clinical outcomes, 100% of patients exceeded the MCID in both groups, and no significant differences were found at 2 years after surgery between the 2 groups (ASES: 2.5 [95% CI, -2.2 to 7.2; P = .291]; WORC index: 4.5 [95% CI, -0.117 to 9.117; P = .056]; NRS: -0.1 [95% CI, -0.3 to 0.1; P = .394]). CONCLUSIONS: Antiosteoporotic treatment with ZA reduced the retear rate but did not significantly influence the clinical outcomes after ARCR in female patients with postmenopausal osteoporosis. Outcomes of ARCR showed good results in both groups and exceeded the MCID. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Structural characterization and in vitro fermentation properties of polysaccharides from Polygonatum cyrtonema.

Polysaccharides, the major active ingredient and quality control indicator of Polygomatum cyrtonema are in need of elucidation for its in vitro fermentation characteristics. This study aimed to investigate the structural characteristics of the homogeneous Polygomatum cyrtonema polysaccharide (PCP-80 %) and its effects on human intestinal bacteria and short chain fatty acids (SCFAs) production during the in vitro fermentation. The results revealed that PCP-80 % was yielded in 10.44 % and the molecular weight was identified to be 4.1 kDa. PCP-80 % exhibited a smooth, porous, irregular sheet structure and provided good thermal stability. The analysis of Gas chromatograph-mass spectrometer (GC-MS) suggested that PCP-80 % contained six glycosidic bonds, with 2,1-linked-Fruf residues accounted for a largest proportion. Nuclear magnetic resonance (NMR) provided additional evidence that the partial structure of PCP-80 % probably consists of →1)-ß-D-Fruf-(2 â†’ as the main chain, accompanied by side chains dominated by →6)-ß-D-Fruf-(2→. Besides, PCP-80 % promoted the production of SCFAs and increased the relative abundance of beneficial bacteria such as Megamonas, Bifidobacterium and Phascolarctobacterium during in vitro colonic fermentation, which changed the composition of the intestinal microbiota. These findings indicated that Polygomatum cyrtonema polysaccharides were able to modulate the structure and composition of the intestinal bacteria flora and had potential probiotic properties.

A novel GATA1 variant p.G229D causing the defect of procoagulant platelet formation.

INTRODUCTION: GATA1 is one of the master transcription factors in hematopoietic lineages development which is crucial for megakaryocytic differentiation and maturation. Previous studies have shown that distinct GATA1 variants are associated with varying severities of macrothrombocytopenia and platelet dysfunction. OBJECTIVE: To determine the underlying pathological mechanisms of a novel GATA1 variant (c. 686G > A, p. G229D) in a patient with recurrent traumatic muscle hematomas. METHODS: Comprehensive phenotypic analysis of the patient platelets was performed. Procoagulant platelet formation and function were detected using flow cytometry assay and thrombin generation test (TGT), respectively. The ANO6 expression was measured by qPCR and western blot. The intracellular supramaximal calcium flux was detected by Fluo-5N fluorescent assay. RESULTS: The patient displayed mild macrothrombocytopenia with defects of platelet granules, aggregation, and integrin αIIbß3 activation. The percentage of the procoagulant platelet formation of the patient upon the stimulation of thrombin plus collagen was lower than that of the healthy controls (40.9 % vs 49.0 % ± 5.1 %). The patient platelets exhibited a marked reduction of thrombin generation in platelet rich plasma TGT compared to the healthy controls (peak value: ∼70 % of the healthy controls; the endogenous thrombin potential: ∼40 % of the healthy controls). The expression of ANO6 and intracellular calcium flux were impaired, which together with abnormal granules of the patient platelets might contribute to defect of procoagulant platelet function. CONCLUSIONS: The G229D variant could lead to a novel platelet phenotype characterized by defective procoagulant platelet formation and function, which extended the range of GATA1 variants associated platelet disorders.