Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability

Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated (6c) and chlorinated (6g) indole moieties led to enhanced anti-hyaluronidase activity (IC50 = 80.3 vs. 9.97 and 9.57 µg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH = 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with anti-hyaluronidase activity

Plant Microbiome and Mycorrhizal Fungi

In this paper, the research results on the synergy between mycorrhizal fungi and plant microorganisms in China and abroad were summarized. The purpose of this paper was to elaborate the effects of the synergy mechanism between mycorrhizal fungi and plant microorganisms on crop growth and stress resistance, soil physical and chemical properties, and soil microbial diversity and to analyze the contribution of the interaction between mycorrhizal fungi and plant microorganisms in agriculture and forestry, so as to provide theoretical basis for the further preparation of composite microbial agents, the healthy and green improvement of crop yield, and the ecological restoration of forestry stress resistance. The main directions of future research in this field were also analyzed

Abnormal Entropy Modulation of the EEG Signal in Patients With Schizophrenia During the Auditory Paired-Stimulus Paradigm

The complexity change in brain activity in schizophrenia is an interesting topic clinically. Schizophrenia patients exhibit abnormal task-related modulation of complexity, following entropy of electroencephalogram (EEG) analysis. However, complexity modulation in schizophrenia patients during the sensory gating (SG) task, remains unknown. In this study, the classical auditory paired-stimulus paradigm was introduced to investigate SG, and EEG data were recorded from 55 normal controls and 61 schizophrenia patients. Fuzzy entropy (FuzzyEn) was used to explore the complexity of brain activity under the conditions of baseline (BL) and the auditory paired-stimulus paradigm (S1 and S2). Generally, schizophrenia patients showed significantly higher FuzzyEn values in the frontal and occipital regions of interest (ROIs). Relative to the BL condition, the normalized values of FuzzyEn of normal controls were decreased greatly in condition S1 and showed less variance in condition S2. Schizophrenia patients showed a smaller decrease in the normalized values in condition S1. Moreover, schizophrenia patients showed significant diminution in the suppression ratios of FuzzyEn, attributed to the higher FuzzyEn values in condition S1. These results suggested that entropy modulation during the process of sensory information and SG was obvious in normal controls and significantly deficient in schizophrenia patients. Additionally, the FuzzyEn values measured in the frontal ROI were positively correlated with positive scores of Positive and Negative Syndrome Scale (PANSS), indicating that frontal entropy was a potential indicator in evaluating the clinical symptoms. However, negative associations were found between the FuzzyEn values of occipital ROIs and general and total scores of PANSS, likely reflecting the compensation effect in visual processing. Thus, our findings provided a deeper understanding of the deficits in sensory information processing and SG, which contribute to cognitive deficits and symptoms in patients with schizophrenia

A new chromosome-scale duck genome shows a major histocompatibility complex with several expanded multigene families

BACKGROUND: The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck's adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC).RESULTS: We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIβ, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model.CONCLUSIONS: These observations supported the hypothesis that duck's adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Realization and application of Large Capacity Chinese Character Disk Operating System (LCCDOS)

In IDL-1120

Behçet's disease with intestinal involvement: a case report and review of the literature

Abstract Background Behçet’s disease (BD) is a chronic systemic disease characterized by vasculitis as the basic pathological change. BD is rare, and gastrointestinal involvement occurs in 3% to 25% of affected patients. This article describes a rare case of intestinal BD along with a literature review of intestinal involvement in BD. Case presentation A 50-year-old Han woman from China presented with a > 6-month history of distending pain in the right upper abdomen. Because of mechanical obstruction secondary to stricture formation from an ileocecal ulcer, she underwent radical right colon resection, and postoperative pathologic examination indicated an ileocecal ulcer. The patient was readmitted to the hospital 6 months postoperatively for recurrence of the same symptoms. Colonoscopy indicated obvious narrowing of the anastomosis with an oval-shaped deep ulcer that could not be passed by the endoscope. Pathologic examination showed acute and chronic inflammation of the anastomotic mucosa and granulation tissue. In addition, gastroscopy showed a 3.0- × 4.0-cm giant ulcer at the junction of the descending bulb along with a sinus tract. Moreover, total gastrointestinal computed tomography angiography showed significant thickening of the intestinal wall near the transverse colon, forming a sinus tract at the junction of the antrum and duodenum with a length of about 1.3 cm and width of about 0.2 cm. Further inquiry regarding the patient’s medical history revealed that she had developed repeated oral ulcers 3 years previously and repeated eye inflammation 5 years previously. Specimens of the right half of the colon removed 6 months previously were sent to Run Run Shaw Hospital Affiliated to Zhejiang University for consultation. The pathologic examination revealed vasculitis in the submucosa and subserosa, and the patient was finally diagnosed with BD. She began treatment with adalimumab, and repeat gastroenteroscopy revealed that the intestinal ulcer had significantly improved. Conclusions An oval-shaped deep intestinal ulcer is a characteristic lesion in patients with BD and may involve the intestinal muscle layer. This case emphasizes that BD is a vasculitis affecting multiple organs and can present with a single, deep, clean-edged intestinal ulcer that penetrates the bowel wall to form a sinus tract. Therefore, careful examination and differential diagnosis should be carried out to prevent a poor prognosis. Adalimumab is effective for patients with intestinal BD