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Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study., Competing Interests: Declaration of competing interest The authors confirm that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Study Objective: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer., Design: A secondary analysis of databases from three randomized trials with long-term follow-up., Setting: The underlying trials were conducted in 17 tertiary hospitals in China., Patients: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis., Exposures: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models., Measurements: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals., Main Results: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals., Conclusions: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer., Materials and Methods: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab)., Results: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups., Conclusion: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: To examine the possible synergic effect of spindle view-assisted intracytoplasmic sperm injection (SV-ICSI) with assisted oocyte activation (AOA) for low fertilization rate., Materials and Methods: A single-center retrospective study from 2019/09-2023/06, a total of 47 patients, autologous IVF cycle, and low fertilization rate history, including control group (SV-ICSI, 33 patients) and intervention group (AOA-SV-ICSI, 14 patients), comparing fertilization rate, blastocyst formation rate, and clinical pregnancy rate., Results: The blastocyst formation rate was significantly higher (p = 0.020) in the AOA-SV-ICSI group than in the SV-ICSI group. The fertilization rate (P = 0.468) and clinical pregnancy rate (p = 0.057) were non-significant between groups., Conclusion: The AOA-SV-ICSI group's blastocyst formation rate significantly improved in patients with previous low fertilization rates, which might help them obtain more useable embryos for further embryo implantation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest/no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Research Question: Can spermatozoa penetrate maturing metaphase I (MI) oocytes, and render subsequent development following conventional IVF in a mouse model?, Design: ICR mice were used in this study. Metaphase II (MII) cumulus-oocyte complexes (COC) harvested 15 h after injection of human chorionic gonadotrophin (HCG) were used for IVF as the control group (Group 1). In the treatment group (Group 2), maturing MI COC harvested 7 h after HCG injection were used for IVF. Fertilization, pronuclear formation, cleavage, blastocyst formation, DNA methylation status, chromosome number and live birth rates were used to evaluate the developmental dynamics and competency of maturing MI oocytes following conventional IVF., Results: Maturing MI COC were fertilized using conventional IVF, and sperm penetration at MI-telophase I triggered oocyte activation. Most embryos resulting from fertilized MI oocytes developed to blastocyst stage during preimplantation development, albeit a substantial proportion of them were triploids due to the absence of the second meiotic division. Some of the embryos derived from fertilization of maturing oocytes were able to implant and gave rise to full-term development., Conclusion: Maturing MI COC from follicles before ovulation could be used for mouse IVF, and fertilized MI oocytes had high potential for development. Healthy offspring can be generated from maturing MI COC following conventional IVF. MI COC may represent a valuable source of 'usable' biomaterial in assisted reproduction. However, many embryos derived from MI COC via IVF have abnormal chromosome numbers in the mouse model. The implications of these findings for human IVF remain to be investigated., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pyrolysis is an effective method for treating of livestock and poultry manure developed in recent years. It can completely decompose pathogens and antibiotics, stabilize heavy metals, and enrich phosphorus (P) in biochar. To elucidate the P migration mechanism under different pig manure pyrolysis temperatures, sequential fractionation, solution 31 P nuclear magnetic resonance, X-ray photoelectron spectroscopy, X-ray diffraction, and K-edge X-ray absorption near-edge structure techniques were used to analyze the P species in pig manure biochar (PMB). The results indicated that most of the organic P in the pig manure was converted to inorganic P during pyrolysis. Moreover, the transformation to different P groups pathways was clarified. The phase transition from amorphous to crystalline calcium phosphate was promoted when the temperature was above 600 °C. The content of P extracted by hydrochloric acid, which was the long-term available P for plant uptake, increased significantly. PMB pyrolyzed at 600 °C can be used as a highly effective substitute for P source. It provides the necessary P species (e.g. water-soluble P.) and metal elements for the growth of water spinach plants, and which are slow-release comparing with the Hogland nutrient solution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antiviral treatment for COVID-19 is considered an effective tool in reducing the rate of severe cases and deaths. As of June 2023, a total of six small molecule antiviral drugs have been conditionally approved for marketing by the National Medical Products Administration (NMPA) within China. In this study, a method of HPLC-MS/MS was established and validated for the determination of six small molecule antiviral drugs in plasma using Lamivudine as an internal standard. The chromatographic separation was performed using gradient elution with an ACE 3 C 18 -PFP column (3.0 mm × 150 mm, 3 μm), and the mobile phase consisted of deionized water and acetonitrile/water (90:10, v/v), both with 10 mmol/L of ammonium acetate and 0.1 % ammonium hydroxide added. Quantitative analysis of the six small molecule drugs was carried out through selective reaction monitoring based on the positive ion spray ionization mode. The method exhibited excellent precision, accuracy, recovery, and linearity, and it was used to determine the pharmacokinetic characteristics in rats. Our work not only established a bioanalytical method for six small molecule antiviral drugs but also provided scientific references for clinical pharmacokinetic studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Six pairs of enantiomeric dilignans, (+)/(-)-magdiligols A-F, have been isolated from an ethanolic extract of the barks of Magnolia officinalis var. biloba. Their chemical structures were elucidated by extensive spectroscopic analyses, NMR calculation with DP4+ analysis, and the electronic circular dichroism spectra calculation. (+)/(-)-1-3 possessed a dihydrobenzopyran ring, while a propyl chain of 1 was linked via ether bond. (+)/(-)-Magdiligols D and E ((+)/(-)-4 and 5) were dilignans possessing a furan ring. (+)-Magdiligol B ((+)/(-)-2), (+)/(-)-magdiligol C ((+)/(-)-3), and racemes 2, 3, and 5 showed potential hepatoprotective effects against APAP-induced HepG2 cell damage, increased the cell viability from 65.4% to 72.7, 78.7.76.6, 73.9, 77.9 and 73.2%, via decreasing the level of the live enzymes ALH and LDH consistently. (+)/(-)-Magdiligols B-D ((+)/(-)-2-4) and (+)/(-)-magdiligol F ((+)/(-)-6) exhibited significant antioxidative activity. (+)/(-)-Magdiligols B-C ((+)/(-)-2 and 3), (-)-magdiligol D ((-)-4), and (+)-magdiligol E ((+)-5) displayed significant PTP1B inhibitory activity with IC 50 values 1.41-3.42 μM. (+)/(-)-Magdiligol B ((+)/(-)-2), and its raceme (2) demonstrated α-glucosidase inhibitory activity with the IC 50 values 1.47, 2.88 and 1.85 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

LSM1 is part of the cytoplasmic protein complex Lsm1-7-Pat1 and is likely involved in pre-mRNA degradation by aiding U4/U6 snRNP formation. More research is needed to uncover LSM1's potential in breast cancer (BRCA) clinical pathology, the tumor immune microenvironment, and precision oncology. We discovered LSM1 as a diagnostic marker for advanced BRCA with poor survival, using a multi-omics approach. We studied LSM1 expression across BRCA regions and its link to immune cells through various methods, including spatial transcriptomics and single-cell RNA-sequencing. We also examined how silencing LSM1 affects mitochondrial function and energy metabolism in the tumor environment. These findings were confirmed using 54 BRCA patient biopsies and tissue microarrays. Immunofluorescence and bioinformatics assessed LSM1's connection to clinicopathological features and prognosis. This study uncovers gene patterns linked to breast cancer, with LSM1 linked to macrophage energy processes. Silencing LSM1 in breast cancer cells disrupts mitochondria and energy metabolism. Spatial analysis aligns with previous results, showing LSM1's connection to macrophages. Biopsies confirm LSM1 elevation in advanced breast cancer with increased macrophage presence. To summarize, LSM1 changes may drive BRCA progression, making it a potential diagnostic and prognostic marker. It also influences energy metabolism and the tumor's immune environment during metastasis, showing promise for precision medicine and drug screening in BRCA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Objective: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer., Design: A long-term follow-up of patients enrolled in a randomized trial., Setting: The initial trial was performed in a tertiary care hospital in Beijing, China., Participants: Patients aged 60 years or older who were scheduled for major noncardiac surgery., Intervention: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 μg/kg over 10 min, followed by a continuous infusion of 0.5 μg/kg/h until 1 h before end of surgery) or placebo during anesthesia., Measurements: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis., Results: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients., Conclusions: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals., Competing Interests: Declaration of Competing Interest Dr. Dong-Xin Wang is supported by National Natural Science Foundation of China (Major Program No. 82293644). Drs. Dong-Liang Mu and Dong-Xin Wang are supported by National Key R&D Program of China (2018YFC2001800). All other authors declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Six new oligostilbenes, carastilphenols A-E (1-5) and (-)-hopeachinol B (6), with three reported oligostilbenes were obtained from the stems of Caragana sinica. The structures of compounds 1-6 were determined by comprehensive spectroscopy analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Thus, natural tetrastilbenes were determined as absolute configuration for the first time. Also, we did several pharmacological essays. In the antiviral tests, compounds 2, 4 and 6 showed moderate anti-coxsackie virus B3 type (CVB3) effect on Vero cells activities in vitro with IC 50 values of 19.2 ∼ 69.3 μM; and compounds 3 and 4 showed different levels of anti-respiratory syncytial virus (RSV) effect on Hep2 cells activities in vitro with IC 50 values of 23.1 and 33.3 μM, respectively. As for hypoglycemic activity, compounds 6-9 (10 μM) showed the inhibition of α-glucosidase in vitro with IC 50 values of 0.1 ∼ 0.4 μM; and compound 7 showed significant inhibition (88.8%, 10 μM) of protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 1.1 μM in vitro., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In modern poultry husbandry, storing fertilized eggs is a common measure to cope with the variable demands of the market and the maximum hatching capacity of the hatchery. However, this measure is harmful to the hatchability of eggs and the quality of newly hatched birds. Knowledge about the effects of storing fertilized eggs on the performance of goslings is still limited. The objective of this study was to investigate the effects of storing fertilized eggs on egg quality, hatchability, gosling quality, hatching weight, post-hatching growth performance, and amino acid profile in albumen and newly hatched goslings' serum. A total of 1,080 fertilized goose eggs (Jilin White goose) with a similar egg weight (126.56 ± 0.66 g) were used in this study. All eggs were distributed into 3 groups with 24 replicates per group and 15 eggs per replicate. The differences between groups were the storage duration of eggs (0, 7, or 14 d). We found that the Haugh unit, yolk weight, and eggshell weight decreased linearly, whereas the albumen pH increased linearly, with storage duration. Prolonging storage duration had negative effects on hatchability, hatching weight, post-hatching growth performance parameters, and gosling quality in a time-dependent manner. The analysis of the amino acid profile in albumen and newly-hatched goslings' serum showed that the amino acid content increased linearly with storage duration. Additionally, eggs stored for 14 d had the worst performance for all measured parameters. Therefore, we concluded that the storage of fertilized eggs negatively affects egg quality and post-hatching gosling quality. To produce high-quality goslings, it is necessary to shorten the storage duration for fertilized eggs., Competing Interests: DISCLOSURES The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: The association between preoperative cognitive impairment, postoperative pain, and postoperative delirium in older patients after noncardiac surgery is not known., Methods: This was a secondary analysis of datasets from three previous studies. Patients aged ≥55 yr who underwent elective noncardiac surgery were enrolled. Preoperative cognitive impairment was defined as Mini-Mental State Examination <27. Pain intensity with movement was assessed using an 11-point numeric rating scale at 12-h intervals during the first 72 h after surgery; time-weighted average (TWA) pain score was calculated. Primary outcome was the occurrence of delirium within the first 5 postoperative days. Mediation analysis was used to investigate the relationships between cognitive impairment, pain score, and delirium., Results: A total of 1497 patients were included. Prevalence of preoperative cognitive impairment was 40.3% (603/1497). Patients with cognitive impairment suffered higher TWA pain score within 72 h (4 [3-5] vs 3 [2-5], P=0.004) and more delirium within 5 days (12.9% [78/603] vs 4.9% [44/894], P<0.001) when compared with those without. Total and direct associations between cognitive impairment and delirium were (adjusted β) 8.3% (95% confidence interval [CI], 4.8-12.0%; P<0.001) and 7.8% (95% CI, 4.4-12.0%; P<0.001), respectively. A significant indirect association with acute pain was observed between cognitive impairment and delirium (adjusted β=0.4%; 95% CI, 0.1-1.0%; P=0.006), accounting for 4.9% of the total effect., Conclusions: The association between preoperative cognitive impairment and delirium is significantly mediated by acute pain in patients after noncardiac surgery. Considering the small effect size, clinical significance of this mediation effect requires further investigation., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

This study was conducted to investigate the development patterns of small intestine, intestinal morphology, disaccharidase activities, and sugar transporter gene expression in goslings during pre- and post-hatching periods. Small intestine was sampled on embryonic d 23 and 27, day of hatch, and d 1, 4, and 7 post-hatching. A total of 18 eggs with the breed of Jilin White geese were selected at each sampling timepoint for measuring relevant parameters. Three eggs were considered as a group, with 6 groups in each sampling timepoint. Rapid development of small intestine was observed around the hatching, of which jejunum and ileum had relatively higher development rates. Villus surface area from three intestinal segments started to increase on embryonic d 27, and kept relatively stable during day of hatch to d 1 post-hatching, and following increased till d 7 post-hatching. A high priority of villi enrichment was observed in duodenum and jejunum. The activity of disaccharidase increased before hatching and kept relatively high-level post-hatching, of which the activity of disaccharidase was highest in jejunum. The expression of sugar transporter gene increased prior to hatching and then decreased post-hatching, of which jejunum and duodenum were sites with high sugar transporter gene expression. Rapid development in intestinal morphology, disaccharidase activities, and sugar transporter gene expression around the hatching indicated that goslings have high potential to digest and/or assimilate carbohydrates during its early-life, which provided a preparation for further digestion of exogenous feed. This study provided a profile of development patterns for intestinal morphology, disaccharidase activities, and sugar transporter gene expression in goslings, which was beneficial to understanding the characteristics of nutrient absorption during the early-life of goslings., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The fibular myocutaneous flap is a classic flap used to reconstruct oral and maxillofacial defects. This study aimed to evaluate the effectiveness of high-frequency color Doppler ultrasound in detecting the blood vessels in the fibular myocutaneous flap, analyze the influence of variations in the peroneal vessels and perforating peroneal arteries on the surgical design, and explore the value of this technology in preoperatively assessing the blood vessels of the fibular myocutaneous flap., Methods: Twenty-five patients with mandibular disease or defect underwent preoperative evaluation of the blood vessels of the calf by high-frequency color Doppler ultrasound. The inner diameter and peak systolic velocity (PSV) of the peroneal arteries and veins and the perforating peroneal arteries were compared between different groups. The consistency between the perforating peroneal arteries marked by ultrasonography and the intraoperative findings was analyzed., Results: The initial segment of the peroneal artery had a larger inner diameter (p<0.001) and lower PSV (p<0.05) than the middle segment. The perforating peroneal arteries were mainly distributed in the middle of the fibula. The inner diameter of the perforating peroneal artery was larger in men than in women (p<0.05). In comparison with surgical exploration as the gold standard, high-frequency color Doppler ultrasound results showed good consistency (Kappa=0.684, 95% CI: 0.512-0.856, p<0.001), with a sensitivity of 89.36%, specificity of 78.57%, and accuracy of 85.33%., Conclusion: High-frequency color Doppler ultrasound can detect, quantitatively evaluate, and accurately mark the peroneal artery and vein and perforating peroneal artery before fibular myocutaneous flap transplantation., Competing Interests: Competing Interests There are no conflicts of interest to declare. The authors have declared that no competing interests exist., (Copyright © 2022. Published by Elsevier Ltd.)

The trophodynamics of toxic trace metals is significant for assessing the threat of toxic trace metals to the aquatic ecosystem and human safety. However, due to the difficulty of accurately calculating the trophic positions of freshwater aquatic organisms in the food web, the comprehensive process of trophodynamics of toxic trace metals in freshwater ecosystems was still rarely known. By integrating the compound-specific nitrogen stable isotopic analysis of amino acids (CSIA-AAs) and the Bayesian stable isotope mixing model (SIMM) as a novel approach, the present study investigated the trophodynamics of five toxic trace metals (Zn, As, Cr, Cu, and Hg) in the food web of the YangZong Lake, a plateau freshwater lake that was once heavily polluted by arsenic in Yunnan Province, China. The results revealed that Hg tended to be efficiently biomagnified in the food web with a trophic magnification factor of 1.75; As, Cr, and Cu were biodiluted significantly, while Zn showed no biomagnification or biodilution trends. The dietary health risk assessment indicated the potential health risk of toxic trace metals for the local residents of long-term fish consumption. The present work highlights the accuracy and reliability of the novel CSIA-AAS+SIMM approach in the calculation of the trophic positions of freshwater organisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Identifying patients at risk for mortality from COVID-19 is crucial to triage, clinical decision-making, and the allocation of scarce hospital resources. The 4C Mortality Score effectively predicts COVID-19 mortality, but it has not been validated in a United States (U.S.) population. The purpose of this study is to determine whether the 4C Mortality Score accurately predicts COVID-19 mortality in an urban U.S. adult inpatient population., Methods: This retrospective cohort study included adult patients admitted to a single-center, tertiary care hospital (Philadelphia, PA) with a positive SARS-CoV-2 PCR from 3/01/2020 to 6/06/2020. Variables were extracted through a combination of automated export and manual chart review. The outcome of interest was mortality during hospital admission or within 30 days of discharge., Results: This study included 426 patients; mean age was 64.4 years, 43.4% were female, and 54.5% self-identified as Black or African American. All-cause mortality was observed in 71 patients (16.7%). The area under the receiver operator characteristic curve of the 4C Mortality Score was 0.85 (95% confidence interval, 0.79-0.89)., Conclusions: Clinicians may use the 4C Mortality Score in an urban, majority Black, U.S. inpatient population. The derivation and validation cohorts were treated in the pre-vaccine era so the 4C Score may over-predict mortality in current patient populations. With stubbornly high inpatient mortality rates, however, the 4C Score remains one of the best tools available to date to inform thoughtful triage and treatment allocation., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Tetrabromobisphenol A (TBBPA), a hazardous and persistent flame retardant, has been widely detected in the natural aquatic system. The acceleration of reductive debromination (rate-limiting process) is vital during the decomposition and detoxification of TBBPA. This study achieved superior TBBPA electrochemical reductive debromination performance by nano Pd doped Ni foam electrode (4.8 times higher than Ni foam electrode). The optimal TBBPA reductive debromination performance was obtained under -1.2 V of cathode potential, 1.2 wt% of Pd loading, 10 mg L -1 of TBBPA and 100 mM of Na 2 SO 4 as the electrolyte solution. UPLC-QTOF-MS verified that Br atoms in TBBPA were removed sequentially to form bisphenol A as the major product. Most TBBPA was reductively debrominated by atomic H* through indirect hydrodebromination, evidenced by the atomic H* quenching test. The higher solution conductivity and appropriate TBBPA concentration would contribute to the debromination efficiency. Excessive H 2 generation whether by over negative potential or H atom richness electrolyte largely disturbed the reaction process and restricted the debromination. The improved generation of reductant (H*) ads Pd was the most significant, while excessive Pd loading would make aggregation and limit the debromination efficiency. The study confirmed the optimization strategies of conditions for Pd/Ni foam electrode and revealed the related function mechanism for stimulating TBBPA electrochemical reduction, giving suggestions for the efficient removal of TBBPA in the aquatic environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Four unknown meroterpenoids named as psidials D-G (1-4) together with 5 known compounds (5-9) had been obtained from the leaves of Psidium guajava. Their absolute structures were elucidated by spectral and calculated methods. Psidials DF (1-3) represented unknown carbon skeleton of the 3,5-diformylbenzyl phloroglucinol-coupled sesquiterpenoid. The possible biosynthetic pathway for 1-3 was postulated. In the bioactivity assay, psidial F (3) was found to possess anti-inflammatory and anticoagulant activities., (Copyright © 2022. Published by Elsevier B.V.)

Haemonchus contortus is the most prevalent and pathogenic gastrointestinal nematode infecting sheep and goats. The two CSIRO sheep resource flocks, the Haemonchus-selected flock (HSF) and Trichostrongylus-selected flock (TSF) were developed for research on host resistance or susceptibility to gastrointestinal nematode infection. A recent study focused on the gene expression differences between resistant and susceptible sheep within each flock, with lymphatic and gastrointestinal tissues. To identify features in the host transcriptome and understand the molecular differences underlying host resistance to H. contortus between flocks with different selective breeding and genetic backgrounds, we compared the abomasal transcriptomic responses of the resistant or susceptible animals between HSF and TSF flocks. A total of 11 and 903 differentially expressed genes were identified in the innate infection treatment in HSF and TSF flocks between resistant and susceptible sheep respectively, while 52 and 485 genes were identified to be differentially expressed in the acquired infection treatment, respectively. Among them, 294 genes had significantly different gene expression levels between HSF and TSF flock animals within the susceptible sheep by both the innate and acquired infections. Moreover, similar expression patterns of the 294 genes were observed, with 273 genes more highly expressed in HSF and 21 more highly expressed in the TSF within the abomasal transcriptome of the susceptible animals. Gene ontology enrichment of the differentially expressed genes identified in this study predicted the likely differing function between the two flock's susceptible lines in response to H. contortus infection. Nineteen pathways were significantly enriched in both the innate and adaptive immune responses in susceptible animals, which indicated that these pathways likely contribute to the host resistance development to H. contortus infection in susceptible sheep. Biological networks built for the set of genes differentially abundant in susceptible animals identified hub genes of PRKG1, PRKACB, PRKACA, and ITGB1 for the innate immune response, and CALM2, MYL1, COL1A1, ITGB1 and ITGB3 for the adaptive immune response, respectively. Our results offered a quantitative snapshot of host transcriptomic changes induced by H. contortus infection between flocks with different selective breeding and genetic backgrounds and provided novel insights into molecular mechanisms of host resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Poor ovarian responder (POR) poses a significant challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in POR. The current study attempts to investigate the clinical benefits of DHEA in POR and the possible mechanism of DHEA on cumulus cells (CCs)., Materials and Methods: A total of 60 women who underwent IVF treatment participated, including 22 normal ovarian responders (NORs) and 38 PORs. PORs were assigned to receive DHEA supplementation (n = 18) or not (n = 20) before IVF cycles. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of mitochondrial dynamics relataed genes were measured., Results: Supplementation of DHEA in POR reduced mitochondrial fission in CCs and decreased the expression of PGAM5 in CCs., Conclusion: The benefit of DHEA supplementation on IVF outcomes in POR is significant, and this effect may be mediated in part through improved mitochondrial dynamics in CC., Competing Interests: Declaration of competing interest The author declares that has no conflict of interest regarding the publication of this paper., (Copyright © 2022. Published by Elsevier B.V.)

Research Question: What is the impact of high serum anti-Müllerian hormone (AMH) concentrations on fertilization and embryo development among infertile women undergoing treatment with assisted reproductive technology (ART)?, Design: Retrospective study of 1036 infertile women undergoing ART; women were divided into three groups according to serum AMH concentrations: AMH <1.1 ng/ml, 1.1-5.0 ng/ml and >5.0 ng/ml. The fertilization and embryo development rates of patients with different AMH concentrations and after stratification according to age were compared., Results: Women with high AMH concentrations were younger and had higher testosterone concentrations (0.4 ± 0.13 versus 0.3 ± 0.12 versus 0.3 ± 0.08 µg/dl, P < 0.001) than women with low AMH concentrations. However, analysis of the embryo development rate showed negative outcomes for women with high AMH concentrations, including a poor fertilization rate (76.3 ± 17.36 versus 82.1 ± 19.15 versus 82.4 ± 25.38, P = 0.003), and poor day 3 embryo development rate (55.6 ± 23.88 versus 62.6 ± 26.52 versus 62.8 ± 32.65, P = 0.014). Multivariate linear regression analysis showed significantly negative correlations of the AMH concentrations with the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.006). Subgroup analysis showed that age 30 years or younger had a significant negative correlation with AMH and the embryo development rate, including the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.037)., Conclusion: These results suggest that high serum AMH concentrations, contributing to a hyperandrogenic environment and leading to decreased oocyte developmental competence, may have a negative impact on fertilization and the early stage of embryo development in women undergoing treatment with ART., (Copyright © 2021. Published by Elsevier Ltd.)

Tetrabromobisphenol A (TBBPA) has aroused widespread pollution in industrial wastewater. Microbial fuel cell (MFC) was proved powerful in organics degradation and simultaneous resource recovery during wastewater treatment. However, the TBBPA biotransformation potential, pathway and the related molecular mechanism remain poorly understood. In this study, the enhanced degradation and detoxification performance of TBBPA in MFC anode was confirmed, evidenced by the shorter degradation period (2.3 times shorter) and less generation of bisphenol A. UPLC-QTOF-MS analysis verified TBBPA metabolism went through reductive debromination, hydrolytic debromination, oxidative ring cleavage and o-methylation. Accompanied with those biochemical processes, the metabolites underwent dynamic changes. The distinctly decreased abundance and fewer interactions with other functional genera for the potential reductive dehalogenators (Pseudomonas, etc.) possibly led to the suppressed reductive debromination (5.1%) in the closed bioanode. Otherwise, the more abundant potential function bacteria with more collaborated interrelations, including hydrolytic dehalogenators (Acinetobacter, etc.), aromatics degrading bacteria (Geobacter, Holophaga, etc.) and electroactive bacteria (Geobacter, Desulfovibrio, etc.) made great sense to the enhanced hydrolytic debromination and detoxification of TBBPA. This study revealed that MFC anode was beneficial to TBBPA degradation and provided theoretical support for the decomposition and transformation of micro-pollutants in the municipal sewage treatment coupled with MFC process., (Copyright © 2021. Published by Elsevier B.V.)

Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a six-member ring, and connect to each other by C-4-O-C-13' bonds. Bisbakuchiols (7-9) had a pyran ring by linkage of C-8-O-C-12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC 50 values of 0.69 and 0.73 μM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from -6.9 to -7.1 kcal/mol., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Liberal oxygen therapy might increase the mortality rate of patients. Non-rebreathing masks (NRM) are a high-flow, non-invasive oxygen device that can provide oxygen concentration up to 95%. This study aimed to determine the impact of using NRM in patients with respiratory failure., Methods: This retrospective cohort study was conducted in four medical institutions in Taiwan from January 2010 to December 2016. The association between mortality and NRM use before receiving ventilator support in patients with respiratory failure in the emergency department was analyzed. Patients were divided into the NRM treatment and no NRM treatment groups. A 1:4 propensity score matching was conducted. Regarding the duration of NRM use, treatments were grouped as 0 h, 0-1 h, 1-2 h, and >2 h., Results: A total of 18,749 patients were included, with 1074 using NRM. After propensity score matching, 1028 patients using NRM (0-1 h: 508, 1-2 h: 193, and >2 h: 327) and 4112 patients not using NRM were analyzed. The 30-day mortality rates were 29.1%, 28.5%, 27.5%, and 35.5% in the 0 h, 0-1 h, 1-2 h, and >2 h treatment groups, respectively. Patients with respiratory failure due to pulmonary disease using NRM over 2 h had a higher mortality rate than patients not using NRM (hazard ratio: 1.3, 95% CI: 1.01-1.66)., Conclusions: Prolonged use of NRM in patients with respiratory failure due to pulmonary disease possibly increases mortality., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Although being as an important chemical material in industry, hydrazine (N 2 H 4 ) is highly toxic to the humans and animals. The development of sensitive methods for the detection of hydrazine is meaningful. Herein, we develop a new organic-inorganic hybrid nanoprobe for the detection of N 2 H 4 based on luminescent resonance energy transfer (LRET) process. The nanoprobe contains N 2 H 4 -responsive NIR cyanine dye (CQM1) and α-cyclodextrin (CD) anchored on the surface of lanthanide-doped upconversion nanophosphors (UCNPs). In the presence of hydrazine, the hybrid materials (CQM1-UCNPs) showed the a large ratiometric luminescent signal change with high sensitivity and selectivity. More importantly, by taking advantage of ratiometric Upconversion luminescent (UCL) signal and the features of NIR emission/excitation, the nanoprobe was successfully applied for visualization of hydrazine in living cells for the first time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In our screening program for new biologically active secondary metabolites, nine new polycyclic polyprenyled acylphloroglucinols, hyperscabins D-L, together with three known compounds, were obtained from the aerial parts of Hypericum scabrum. The chemical structures of 1-9 were characterized by extensive spectroscopic analyses, nuclear magnetic resonance calculation with DP4+ probability analysis, and the electronic circular dichroism spectra were calculated. Compound 1 was an unusual prenylated acylphloroglucinol decorated with a 5-oxaspiro [4,5] deca-1,9-dione skeleton. Compound 2 was a newly identified spirocyclic polyprenylated acylphloroglucinol possessing a rare 5,5-spiroketal segment. Compounds 3, 8, and 10 (10 μM) exhibited pronounced hepatoprotective activity against d-galactosamine-induced WB-F344 cell damage in vitro assays. All test compounds (1, 3, and 7-12) demonstrated potential inhibitory effects at 10 μM against noradrenalinet ([ 3 H]-NE) reuptake in rat brain synaptosome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Radiotherapy has become a basic treatment modality for head and neck cancer. However, radiotherapy results in inevitable side effects, particularly radiation sialadenitis, that significantly impairs quality of life. A previous study indicated that nerve growth factor (NGF) has a radio-protective effect, but the mechanism was not determined in salivary glands. In this study, we explored the functional role and mechanism regarding how NGF protects salivary glands against IR-induced damage., Main Methods: Human salivary gland (HSG) cells and C57BL/6 mice were selected to establish an IR-induced salivary gland damage model in vitro and in vivo. Recombinant NGF protein and NGF siRNA and over-expression plasmids were applied to manipulate NGF expression in vitro. AAV-NGF was retrogradely perfused into the submandibular gland (SMG) through the SMG duct to manipulate NGF expression in vitro. Small-molecule inhibitors and siRNAs were applied to inhibit AKT and JNK. Western blotting, quantitative PCR, flow cytometry and histology assays were performed to analyse the functional role and mechanism of NGF., Key Findings: Our study demonstrated that NGF expression was upregulated following radiotherapy both in human HSG cells and mouse SMG tissues. NGF could reduce IR-induced HSG cell apoptosis, and AAV-mediated gene therapy could restore the salivary flow rate and protect the salivary gland against IR-induced apoptosis in vivo. Mechanistically, NGF protects salivary glands from IR-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation., Significance: The current study findings indicated that the modulation of the NGF pathway might prevent IR-induced salivary hypo-function., (Copyright © 2020. Published by Elsevier Inc.)

The barks of Magnolia officinalis var. biloba, Magnoliae cortex, have been used as traditional Chinese medicines for several centuries. In this study, phytochemical investigation of M. officinalis var. biloba bark extract afforded five pairs of novel enantiomeric oligomeric neolignans, (±)-mooligomers A-E (1-5). (±)-1 and (±)-2 were two diastereomeric pairs of enantiomers with six C6-C3 subunits, and (±)-4 was a pair of previously unreported tetrameric neolignans bearing eight C6-C3 subunits. (±)-5 is the first example of a naturally occurring trilignan featuring an eight-membered ring with a magnolol moiety. The absolute configurations of (±)-1-(±)-5 were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopy and electronic circular dichroism (ECD) calculations. Among the compounds tested for their PTP1B inhibitory activities, (±)-2, (±)-4 and (±)-5 displayed significant PTP1B inhibitory activities with IC 50 values of 0.14-2.10 μM. Furthermore, a Molecular docking simulation of PTP1B and active compounds [(±)-2, (±)-4 and (±)-5] exhibited that these active compounds possess low binding affinities ranging from - 5.9 to - 7.7 kcal/mol., (Copyright © 2020. Published by Elsevier Inc.)

This study was conducted to determine the effect of feeding frequency on growth performance, carcass traits, and apparent nutrient digestibility in geese from 28 to 70 D of age. In experiment 1, a total of 240 geese were distributed in a completely randomized design into 4 treatments and 6 replicates of 10 birds each. The treatments were free access to the feeder (ad libitum) and access to the feeder 3, 4, and 5 times daily. Geese fed 3 times daily had a lower (P < 0.05) BW, ADG, and ADFI and a higher (P = 0.064) feed conversion ratio (FCR) from 28 to 41 D of age compared with the other groups. Geese fed 4 times daily had a higher (P < 0.05) ADG and ADFI and a lower (P < 0.05) FCR from 42 to 55 D of age compared with ad libitum fed geese. Geese fed 3 times daily had a higher (P < 0.05) ADG from 56 to 69 D of age than geese fed ad libitum and 4 times daily. No differences (P > 0.05) in BW, ADFI, ADG, and FCR were observed between ad libitum and feeding frequency groups from 28 to 69 D of age. Carcass traits and gastrointestinal development were not affected (P > 0.05) by feeding frequency. In experiment 2, the apparent nutrient digestibility in geese from 71 to 77 D of age fed using different feeding frequencies was determined using the total fecal collection method. Feeding frequency did not affect (P > 0.05) the apparent digestibility of DM, CP, crude ash, calcium, phosphorous, or ether extract in geese. Our study demonstrates for the first time that compensatory growth can be gained by enhancing feed intake when a lower feeding frequency is imposed on geese. Both ad libitum feeding and fixed feeding frequency for 3 to 5 times daily are suitable for geese from 28 to 70 D of age to achieve optimum production., (Copyright © 2020. Published by Elsevier Inc.)

Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Biochar-mineral (bentonite/calcite) composite (BC-CM) prepared at different temperatures were tested under varied conditions for effective removal of lead (Pb) from aqueous solution. With increasing pyrolysis temperature, increased surface area, pore volume, bentonite decomposition and less or no decomposition of calcite occurred. Bentonite-biochar (BCS) and calcite-biochar (CCS) prepared at 700 °C were found most suitable for efficient removal of Pb (99.9%). Bentonite and calcite acted as catalyst and contributed to changes in yield, pH, texture, functional groups, minerals and carbonization that facilitated efficient Pb removal by BCS 700 and CCS 700. Pb concentration, pH, dose of BCS and CCS, and contact time were further optimized using response surface methodology (RSM) for maximizing removal percentage (R%) of Pb and adsorption capacity (qt). Both BCS 700 and CCS 700 showed similar effects (positive/negative) of factors on R% and qt. Under optimized conditions, 0.21 g of BCS 700 effectively removed 99.2% of 431 mg/L in 3.6 h at solution pH of 4.2, while 0.07 g CCS 700 removed 97.06% of 232 mg/L in 3.5 h at 5.5 pH. Removal of Pb onto both BCS and CCS was by monolayer adsorption with maximum adsorption capacity of 500 mg/g. Rapid Pb removal was observed within 2 h of contact time (CCS 700 > BCS 700) and equilibrium was achieved within 10 h. BCS 700 followed first order and CCS 700 followed second order kinetic model. Electrostatic attraction between Pb ions and mineral groups present in BCS 700 and CCS 700 also played important role in Pb removal. This study clearly demonstrated that composite of biochar with bentonite or calcite under optimized conditions significantly improved Pb removal and adsorption capacity that can be further utilized for larger scale applications., Competing Interests: Declaration of competing interest All authors have read and approved its content and ‘No Conflict’ of interest by all authors exists in the submission of this manuscript., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antivenom reactions are a common complication of snake antivenom. This study aimed to identify predicators of antivenom reaction and the involvement of antivenom skin test in antivenom reaction development. This retrospective cohort study was conducted in six medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2006 to December 2016. The association between antivenom reaction and patient demographics, type and dose of antivenom, and skin test results was analyzed. The study enrolled 799 patients, including 219 who developed antivenom reactions. Compared to patients receiving both freeze-dried hemorrhagic (FH) and freeze-dried neurotoxic (FN) antivenom, those administered a single type had a lower antivenom reaction risk (adjusted odds ratios [aORs]: 0.5 and 0.4, 95% confidence interval [CI]: 0.35-0.74 and 0.24-0.69, FH and FN respectively). Patients administered a higher antivenom dose (≥ 5 vials) had higher antivenom reaction risk (aOR: 1.8, 95% CI: 1.23-2.76). A positive skin test result was also associated with antivenom reaction (aOR: 16.7, 95% CI: 5.42-51.22). The skin test showed high specificity (98.5%, 95% CI: 97.49%-99.83%) but low sensitivity (17.5%, 95% CI: 10.74%-24.18%). The antivenom skin test should be abolished because of the extremely low sensitivity and possible misinterpretation of results because of the limitation of this examination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Three pairs of new germacranolides, (+)/(-)-chlogermacrones A-C, along with two known analogues were obtained from the roots of Chloranthus henryi. Spectroscopic techniques and single-crystal X-ray crystallographic analyses were used for the structure elucidation of the compounds. All of the isolated compounds were tested for their neuroprotective effects on H 2 O 2 damaged PC12 cells, compounds 3 and 5 increased cell viability from 43.4 ± 1.3% to 99.6 ± 8.7 and 68.1 ± 4.8% at 10 μM, respectively., Competing Interests: Declaration of Competing Interest The authors declare no compete in financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sleep deprivation (SD) has detrimental effects on the physiological function of the brain. However, the underlying mechanism remains elusive. In the present study, we investigated the expression of candidate plasticity-related gene 15 (cpg15), a neurotrophic gene, and its potential role in SD using a REM-SD mouse model. Immunofluorescent and Western blot analysis revealed that the expression of cpg15 protein decreased in the hippocampus, ventral group of the dorsal thalamus (VENT), and somatosensory area of cerebral cortex (SSP) after 24-72 h of REM-SD, and the oxidative stress in these brain regions was increased in parallel, as indicated by the ratio of glutathione (GSH) to its oxidative product (GSSG). Over-expression of cpg15 in thalamus, hippocampus, and cerebral cortex mediated by AAV reduced the oxidative stress in these regions, indicating that the decrease of cpg15 might be a cause that augments oxidative stress in the sleep deprived mouse brain. Collectively, the results imply that cpg15 may play a protective function in the SD-subjected mouse brain via an anti-oxidative function. To our knowledge, this is the first time to provide evidences in the role of cpg15 against SD-induced oxidative stress in the brain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Compared with intracranial aneurysms (IAs) at other locations, pericallosal artery aneurysms (PAAs) have demonstrated an extremely high risk of rupture. However, owing to their rarity, our understanding of their morphological characteristics has been limited, and whether the morphological characteristics of PAAs contribute to this high rupture risk has remained unexplored. In the present study, we aimed to provide a detailed description of the morphological characteristics of PAAs and investigate the association between its morphology and rupture risk compared with anterior circulation IAs at other locations., Methods: A total of 40 patients with 45 PAAs and 348 patients with 392 anterior circulation IAs at other locations were recruited. The clinical and radiological data for these patients were retrospectively reviewed. The differences in the morphological parameters, including the aneurysm diameter, neck width, height, width, parent artery diameter, inflow angle, aspect ratio (AR), size ratio (SR), and aneurysm diameter/width ratio, between PAAs and other IA groups were compared., Results: Of the 45 PAAs, 22 (48.9%) had ruptured. The proportion of ruptured aneurysms was greater for PAAs than for anterior circulation IAs at other locations. For both ruptured and unruptured anterior circulation IAs, PAAs had the highest AR and SR among all IA groups and had the largest inflow angle., Conclusion: The morphological characteristics of PAAs are unique. Compared with other anterior circulation IAs, PAAs have significantly increased ARs, SRs, and inflow angles, which, ultimately, promote their high propensity toward rupture., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Identification of key components in the chemical and physical milieu for directing osteogenesis is a requirement in the investigation of tissue engineering scaffolds for advancement of bone regeneration. In this study, we engineered different gelatin-based cryogels and studied the effect of nanohydroxyapatite (nHAP) and crosslinking agents on scaffold properties and its osteogenic response towards bone marrow stem cells (BMSCs). The cryogels examined are 5% gelatin and 5% gelatin/2.5% nHAP, crosslinked either with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) or glutaraldehyde (GA). We confirmed that nHAP or the crosslinking agent has no effects on scaffold pore size and porosity. Nonetheless, incorporation of nHAP increased mechanical strength, swelling ratio and degree of crosslinking, but decreased degradation rate. Cryogels crosslinked with EDC showed faster degradation and promoted osteogenic differentiation of BMSCs while those prepared from GA crosslinking promoted proliferation of BMSCs. Furthermore, osteogenic differentiation was always enhanced in the presence of nHAP irrespective of the culture medium (normal or osteogenic) used but osteogenic medium always provide a higher extent of osteogenic differentiation. Employing gelatin/nHAP cryogel crosslinked by EDC in a bioreactor for dynamic culture of BMSCs, cyclic compressive mechanical simulation was found to be beneficial for both cell proliferation and osteogenic differentiation. However, the optimum conditions for osteogenic differentiation and cell proliferation were found at 30% and 60% strain, respectively. We thus demonstrated that osteogenic differentiation of BMSCs could be tuned by taking advantages of chemical cues generated from scaffold chemistry or physical cues generated from dynamic cell culture in vitro. Furthermore, by combining the best cryogel preparation and in vitro cell culture condition for osteogenesis, we successfully employed in vitro cultured cryogel/BMSCs constructs for repair of rabbit critical-sized cranial bone defects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Six new and one known dihydroagarofuran sesquiterpenoids esterified with organic acids were obtained from the leaves of Tripterygium wilfordii. Spectroscopic techniques (UV, IR, MS, NMR, ORD and CD) were used for the structure elucidation of the compounds. The structures of compounds 1 and 2 were confirmed by X-ray single crystallographic analyses. The inhibitory effects on NO production in LPS-induced macrophages of 1-7 were conducted. At 10 μmol/L, compounds 1, 2 and 7 showed moderate inhibitory effects on NO production in LPS-induced macrophages with inhibitory rate at 31.2 ± 3.6, 40.9 ± 4.3, and 66.79 ± 3.1%, respectively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Eight undescribed 9,19-cycloartane type triterpenoid glycosides (cimdalglnoside A-H) and ten known analogues were obtained from the phytochemical research on the roots of Actaea dahurica (syn. Cimicifuga dahurica). All compounds were characterised by spectroscopic experiments, and chemical method. All the compounds isolated were assayed for cytotoxicity to five human cancer cell lines. Cimdalglnoside G showed promising cytotoxicities against Hela, and MCF-7 cell lines with IC 50 values at 7.7 and 12.2 μM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Eight new meroterpenoids with different types of monoterpene units, namely, magmenthanes A-H (1-8), were identified from the bark of Magnolia officinalis var. biloba. Magmenthane A (1) possesses a 1,3-dioxabicyclo [4.3.0 1,5 ] nonane skeleton, 1-5 possess five pairs of enantiomers and 6 possesses a 1,1'-diallyl-biphenyl fragment. The structures of 1-8 were elucidated on the basis of 1D and 2D NMR, HRESIMS and electronic circular dichroism (ECD) calculations. Compounds 5 and 8 displayed significant PTP1B inhibitory activities with IC 50 values of 4.38 and 3.88 μM, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ten undescribed 9,19-cycloartane type triterpenoid glycosides (cimdahxynoside A-J) and five known analogues were obtained from the phytochemical research on the roots of Actaea dahurica (syn. Cimicifuga dahurica). All compounds were characterised by spectroscopic experiments, chemical method and X-ray Single-crystal diffraction analysis. Cimdahxynoside A represented the first X-ray crystallography of 9,19-cycloartane type triterpenoid diglycoside. The cytotoxicity of all compounds were tested against five human cancer cell lines. Cimdahxynoside F showed significant cytotoxicity, with IC 50 values between 6.6 and 9.9 μM., (Copyright © 2019. Published by Elsevier Ltd.)

Phytochemical studies on the leaves of Tripterygium wilfordii led to the isolation of seven new 18(4 → 3)-abeo-abietane lactones, triptergulides E - K (1 - 7). The structure of the new compounds was elucidated on the basis of their spectroscopic analysis, and the absolute configurations of compounds were confirmed by ECD, calculated ECD, and X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Some compounds showed moderate inhibitory activities against NO, IL-6, and TNF-α production in LPS RAW 264.7 macrophage in vitro., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Because of the synergistic effects of drugs and minimal drug dose for cancer therapy, combination chemotherapy is frequently used in the clinic. In this study, hyaluronic acid-modified amine-terminated fourth-generation polyamidoamine dendrimer nanoparticles were synthesized for systemic co-delivery of cisplatin and doxorubicin (HA@PAMAM-Pt-Dox). In vitro data showed that HA@PAMAM-Pt-Dox can enter the cells through the lysosome mediated-pathway in a time-dependent manner. Cell viability studies indicated that HA@PAMAM-Pt-Dox exhibited a higher anticancer activity on MCF-7 and MDA-MB-231 breast cancer cells at a relative low concentration. HA@PAMAM-Pt-Dox not only efficiently inhibited tumor growth but also significantly reduced the toxicity of Dox. Moreover, intravenous administration of HA@PAMAM-Pt-Dox to MDA-MB-231 tumor-bearing BALB/c nude mice resulted in the accumulation of HA@PAMAM-Pt-Dox at the tumor site, thereby significantly inhibiting tumor growth without apparent toxicity. These results suggested that HA@PAMAM-Pt-Dox has great potential to improve the chemotherapeutic efficacy of cisplatin and doxorubicin in breast cancer. STATEMENT OF SIGNIFICANCE: One of the main problems in cancer treatment is the development of drug resistance. To date, it is believed that combination chemotherapy might be an effective strategy for the above problem. However, for two completely different drugs, combination chemotherapy faces huge difficulties including the antagonistic nature of drugs, variations in drugs in terms of solubility, and limited tumor targeting. Recent developments in nanoscience and nanotechnology provide an effective approach for such disadvantages. Considering the advantages of dendrimers such as control of size and molecular weight, bioavailability, and biosafety, we used fourth-generation dendrimers modified by HA as drug vectors by covalently conjugating them with anticancer drugs (cisplatin and doxorubicin) to form a nanodrug delivery system, named HA@PAMAM-Pt-Dox. We observed that the HA@PAMAM-Pt-Dox system can effectively kill breast cancer cells both in vitro and in vivo, which showed a favorable synergistic effect. This strategy can be extended to other drugs, thus providing a highly effective strategy for cancer treatment., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)