Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression.

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

A tabletability change classification system in supporting the tablet formulation design via the roll compaction and dry granulation process.

In this paper, the material library approach was used to uncover the pattern of tabletability change and related risk for tablet formulation design under the roll compaction and dry granulation (RCDG) process. 31 materials were fully characterized using 18 physical parameters and 9 compression behavior classification system (CBCS) parameters. Then, each material was dry granulated and sieved into small granules (125-250 µm) and large granules (630-850 µm), respectively. The compression behavior of granules was characterized by the CBCS descriptors, and were compared with that of ungranulated powders. The relative change of tabletability (CoTr) index was used to establish the tabletability change classification system (TCCS), and all materials were classified into three types, i.e. loss of tabletability (LoT, Type I), unchanged tabletability (Type II) and increase of tabletability (Type III). Results showed that approximately 65% of materials presented LoT, and as the granules size increased, 84% of the materials exhibited LoT. A risk decision tree was innovatively proposed by joint application of the CBCS tabletability categories and the TCCS tabletability change types. It was found that the LoT posed little risk to the tensile strength of the final tablet, when Category 1 or 2A materials, or Category 2B materials with Type II or Type III change of tabletability were used. Formulation risk happened to Category 2C or 3 materials, or Category 2B materials with Type I change of tabletability, particularly when high proportions of these materials were involved in tablet formulation. In addition, the risk assessment results were verified in the material property design space developed from a latent variable model in prediction of tablet tensile strength. Overall, results suggested that a combinational use of CBCS and TCCS could aid the decision making in selecting materials for tablet formulation design via RCDG.

The causal relationship of depression, anxiety, and neuroticism with main indicators of sarcopenia: A Mendelian randomization study.

BACKGROUND: Observational studies have shown the relationship between sarcopenia and psychiatric disorders. However, due to the limitations of traditional research methods, the causal relationship between them has not been accurately concluded. At the same time, considering that sarcopenia is mainly manifested by low muscle strength and low muscle mass, we used Mendelian randomization (MR) analysis in this study to explore the causal relationship of anxiety, depression, and neuroticism with muscle strength and muscle mass, respectively. METHODS: Genetic variants associated with depression were obtained from FinnGen Biobank (Ncase = 33,812, Ncontrol = 271,380), those associated with anxiety were from FinnGen Biobank (Ncase = 21,519, Ncontrol = 307,558), and those associated with neuroticism, including 12 items, were from a large-scale genome-wide association study (N range: 366,301-375,913). Muscle strength was represented by the hand grip strength (HGS), and muscle mass was represented by the appendicular lean mass (ALM) and the body fat percentage. The inverse-variance weighted (IVW) method was used as the primary analysis method, and the Mendelian Randomization Egger (MR-Egger) and the weighted median were used as supplementary methods to test whether the three psychological factors were causally related to these two main indicators of sarcopenia severity. RESULTS: Depression and neuroticism had different degrees of causal influence on muscle mass and strength, which was statistically significant. Specifically, the depression predicted by genes was significantly associated with ALM (beta = -0.043, p = 0.027), low hand grip strength (LHGS, measured for people of 60 years and older) (odds ratio (OR) = 1.129 (1.019-1.251), p = 0.019), right HGS (beta = -0.050, p = 0.001), left HGS (beta = -0.06, p = 0.001), and body fat percentage (beta = 0.035, p = 0.0138). The neuroticism predicted by genes was significantly associated with ALM (beta = -0.073, p = 0.034), LHGS (OR = 1.222 (1.085-1.377), p = 0.001), right HGS (beta = -0.058, p = 0.000), left HGS (beta = -0.080, p < 0.000), and body fat percentage (beta = 0.063, p = 0.008). However, anxiety was only significantly associated with LHGS (OR = 1.215 (1.008-1.465), p = 0.041) but not significantly associated with ALM (beta = 0.033, p = 0.313), right HGS (beta = -0.008, p = 0.678), left HGS (beta = 0.007, p = 0.712), or body fat percentage (beta = 0.022, p = 0.559). CONCLUSION: This study supported the causal association of depression and neuroticism with muscle strength and mass, which are the two main indicators of sarcopenia. At the same time, there was no sufficient evidence for the causal relationship between anxiety and muscle strength or mass. The results of this study pointed to the need to intervene in the mental health of the elderly to prevent sarcopenia or reduce its severity.

Spatiotemporal variations and tradeoff-synergy relations of ecosystem services under ecological water replenishment in Baiyangdian Lake, North China.

Understanding dynamic variations of ecosystem services (ESs) and their tradeoff-synergy relations under ecological water replenishment (EWR) is conducive to the formulation of effective eco-environmental management strategies. In this study, spatiotemporal variations of three leading ESs, namely habitat quality, carbon storage and water yield services influenced by EWR in Baiyangdian Lake, North China from 1991 to 2019, were investigated using the "Integrated Valuation of Ecosystem Services and Tradeoffs" (InVEST) model, and their tradeoff-synergy relations were quantitatively assessed with correlation analysis methods. Our results showed that habitat quality had continuously declined, whereas it got a steady improvement after the year of 2015. Total carbon storage was relatively stable, and the volume of total water yield and precipitation showed the same variation trend. Overall, EWR promoted the maintenance and improvement of ESs. Tradeoff-synergy relations among ESs varied with time and space. Temporally, there was an obvious synergistic relation between habitat quality and carbon storage services. Spatially, these two ESs were synergistic in the southern, central and eastern parts of the lake, while they had a tradeoff relation in the north; and there were no tradeoff-synergy relations between the water yield service and these two services. This study confirmed the importance of zoning management and comprehensive multi-factor management based on spatial and temporal differences of ESs, and can offer a scientific basis for adaptive eco-environmental management strategies for wetland restoration.

A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.

BACKGROUND: Postoperative sleep disorder is common and may cause aggravated postoperative pain, delirium, and poor prognosis. We accessed the effect of intraoperative intravenous dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.  METHODS: This single-center, double-blind, placebo-controlled randomized clinical trial enrolled a total of 110 participants aged 18 years to 65 years who were scheduled to receive endoscopic sinus surgery. Placebo (normal saline) or dexmedetomidine infusion (load dose 0.5 µg kg-1 over 10 min, followed by maintenance dose 0.2 ug kg-1 h-1) during surgery. The primary outcome was postoperative sleep quality. Secondary outcomes were postoperative Ramsay sedation scores, Visual Analog Scale (VAS) scores, serum cortisol, 5-hydroxytryptamine (5-HT) and hypocretin, delirium, and postoperative nausea and vomiting (PONV). RESULTS: Among enrolled 110 patients, 55 were randomized to administer intraoperative dexmedetomidine and placebo. In total, 14 patients (7 in each group) were excluded because of protocol deviations, and 96 patients (48 in each group) were included in the per-protocol analysis. The dexmedetomidine group had a significantly higher sleep efficiency index(SEI) (66.85[3.00] vs 65.38[3.58]), the ratio of rapid eye movement sleep to total sleep(REM)(13.63[1.45] vs 12.38[2.11]) and lower arousal index (AI) (7.20[1.00] vs 8.07[1.29]), higher Ramsay sedation score at post-operation 1 h, 12 h point, lower VAS scores at post-operation 1 h, 12 h, 24 h point, lower cortisol, higher 5-HT and hypocretin in serum than the placebo group. CONCLUSION: In this randomized clinical trial, dexmedetomidine can improve the sleep quality of patients undergoing endoscopic sinus surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative sleep quality in patients with endoscopic sinus surgery. TRIAL REGISTRATION: The study was approved by the Bethune International Peace Hospital Ethics Committee (2021-KY-129) and registered in the Chinese Clinical Trial Registry ( ChiCTR2100051598 , 28/09/2021).

Cancer cells invasion to the gastric bare area adipose tissue: a poor prognostic predictor for gastric cancer.

BACKGROUND: The relationship between gastric bare area adipose tissues invasion (GBAI) confirmed pathologically and the prognosis of gastric cancer (GC) patients is undefined. Till present, there has not been literature investigating this phenomenon. Here, we aimed at analyzing the implication of GBAI in GC. METHODS: The data of 1822 patients who underwent radical surgery between January 2000 and December 2013 at the Sun Yat-sen University Cancer Center were retrieved. Pathologically, tumor deposits (TDs) located > 5 mm from the leading edge of the primary tumor and the lymph nodes (LNs) station number 1, 2, 7, and 9 were considered GBAI. Kaplan-Meier method, log-rank test, and Cox's proportional hazards model were employed to analyze. RESULTS: Two hundred and five (11.3%) patients were pathologically diagnosed with GBAI, which was more commonly found in proximal or linitis lastica than distal GC (P < 0.001). There was significant difference in 5-year survival between patients with and without GBAI for stages IIB, IIIA, IIIB, and IIIC, respectively (P < 0.009 for IIB, IIIA, and IIIB; P = 0.021 for IIIC). Among the 205 GBAI patients, 61 had detailed radiological follow-up data in which 26 (34.7%) were found to have retroperitoneal infiltration, 27 (36.0%) had peritoneal metastasis, 10 (13.3%) had hematogenous metastasis, 16 (21.3%) had lymphatic metastasis, and 16 (21.3%) had others. CONCLUSIONS: GBAI was identified as a predictor of unfavorable prognosis for GC and was more commonly found in the proximal or linitis plastica of the stomach than in distal stomach. Retroperitoneal infiltration was one of the most commonly identified metastatic route for GC associated with GBAI after radical surgery.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

OBJECTIVE: To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. METHOD: Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. RESULT: The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). CONCLUSION: EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.