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Five brasilane-type sesquiterpenoids, including four previously undescribed compounds named xylaribrasilaids A-D, along with a known analogue, were isolated from the ethyl acetate extracts of solid fermentation from Xylaria nigripes. X. nigripes, a traditional Chinese medicinal fungus utilized for treating various ailments such as insomnia, trauma, and depression, has garnered attention due to its pharmacological potential. Their structures and absolute configurations were elucidated through comprehensive spectroscopic analysis, including NMR, HRESIMS, and experimental ECD data. In vitro bioassays were conducted to assess the neuroprotective activities of these compounds against glutamate-induced damage in PC12 cells. Remarkably, all isolated compounds demonstrated significant enhancements in cell viability while concurrently inhibiting apoptosis. Moreover, they effectively attenuated oxidative stress markers, as evidenced by increased activities of superoxide dismutase and glutathione. Furthermore, these compounds displayed the capacity to mitigate intracellular reactive oxygen species accumulation, highlighting their potential in combating oxidative stress-related neurodegenerative disorders., 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. Published by Elsevier Ltd.)

Two new quinoline alkaloids with an α, β-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds., Competing Interests: Declaration of competing interest 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 B.V.)

Background: In recent years, novel agents have become available to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the impact of such agents on treatment costs has not been formally studied. We present results from 2 independent, retrospective, real-world cohort analyses to determine the cost of disease progression after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)., Materials and Methods: Analyses were conducted using the IQVIA PharMetrics Ⓡ Plus claims database and the Surveillance, Epidemiology, and End Results registry-Medicare-linked database (SEER-Medicare) and included patients ≥18 years and ≥66 years, respectively. "No progression" was defined as no second-line therapy for ≥2 years after the end of first-line R-CHOP and "treated progression" as initiating a second-line therapy within 2 years following the end of first-line R-CHOP. Analyses were adjusted for baseline covariates, and per-patient-per-month (PPPM) costs were compared between progressors and nonprogressors., Results: The IQVIA PharMetrics Plus analysis (January 1, 2010-June 30, 2018) included 871 patients (nonprogressors, n = 725; progressors, n = 146), including 10 patients who received chimeric antigen receptor T-cell therapy (CAR-T). Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,554 vs. $1561, P < .001). The SEER-Medicare analysis (January 1, 2010-December 31, 2017) included 4099 patients (nonprogressors, n = 3389; progressors, n = 710), including 12 patients receiving CAR-T. Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,928 vs. $2902, P < .001)., Conclusion: Treated progression of DLBCL increases adjusted PPPM costs by over $8000 compared with no progression., Competing Interests: Disclosure John M. Burke reports consultancy or advisory role for AbbVie, Adaptive Biotechnologies, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Constellation, Epizyme, Inc., F. Hoffmann-La Roche Ltd, Genentech, Inc., Genmab, Kura, Kymera Therapeutics, Lilly, MorphoSys, Nurix, Seagen, TG Therapeutics, and X4 Pharmaceuticals; speakers bureau for BeiGene and Seagen. Anthony Masaquel, Rongrong Wang, Farah Hossain, Jia Li, Carmen D. Ng are employees of Genentech, Inc., and receive F. Hoffmann-La Roche Ltd. stocks/stock options. Summera Qiheng Zhou is a paid consultant of Genentech, Inc. Matthew Matasar reports stock or other ownership for Merck Sharp & Dohme; honoraria for Genentech, Inc., F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Seattle Genetics, and ImmunoVaccine Technologies; research funding for Genentech, Inc., F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Seattle Genetics, Rocket Medical, and ImmunoVaccine Technologies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Three undescribed methylsuccinic acid derivatives, xylaril acids A-C, and two undescribed enoic acid derivatives, xylaril acids D-E, were isolated from the fungus Xylaria longipes. The structures of the undescribed compounds were deduced by spectroscopic means, including HRESIMS and 1D/2D NMR spectroscopy, as well as ECD calculations. The absolute configuration of xylaril acids A was further determined by single-crystal X-ray diffraction experiments. All the isolated compounds displayed neuroprotective activities against oxygen-glucose deprivation/reperfusion injury in PC12 cells by enhancing cell viability and inhibiting cell apoptosis., 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 Ltd. All rights reserved.)

Background: The impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction., Methods: Patients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed., Results: A total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years., Conclusion: Both sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 μM, the EC 50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 μM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells., 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 Ltd. All rights reserved.)

Antibiotic resistance genes (ARGs) are receiving increasing concerns due to the antibiotic resistance crisis. Nevertheless, little is known about the spatial behavior and sources of extracellular ARGs (eARGs) in the chlorinated drinking water distribution systems (DWDSs). Here, tap water was continuously collected to reveal the occurrence of both eARGs and intracellular ARGs (iARGs) along a chlorinated DWDS. Afterward, the correlation between eARGs, eDNA-releasing communities, and communities of planktonic bacteria was further analyzed. The eARG concentration decreased significantly, whereas the proportion of vanA and bla NDM-1 increased. Further, the diversity of the eDNA-releasing community increased markedly with increasing distance from the drinking water treatment plant (DWTP). Moreover, the dominant eDNA-releasing bacteria shifted from Acinetobacter, Pseudomonas, and Methylobacterium-Methylorubrum in finished water from the DWTP to Bacteroides, Faecalibacterium, Staphylococcus, and Parabacteroides in the DWDS. In terms of eARG source, thirty genera were significantly correlated with seven types of eARGs that resulted from the lysis of dead planktonic bacteria and detached biofilms. Conversely, the iARGs concentration increased, whereas the biodiversity of the planktonic bacteria community decreased in the sampling points along the DWDSs. Our findings provide critical insights into the spatial behavior and sources of eARGs, highlighting the health risks associated with ARGs in DWDSs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was identified to be associated with a novel SFTS virus (SFTSV). Transmission of the disease among humans has been described, but clinical impact factors and transmission mechanisms still need further study. An outbreak of person-to-person transmission of SFTS in a cluster of nine patients that occurred in an SFTS endemic area, Penglai County, Shandong province, China, was investigated. We found that the onset date of all eight secondary SFTS patients ranged from 7 to 13 days after exposure to the corpse of the index patient, and clinical incubation time was mostly focused on 9-10 days (n = 6). The two dead patients, including the index patient and one secondary infected patient, presented unusually high levels of viral load (6 × 10(8-9) copies/mL), low levels of platelets count (<55 × 10(9)/L), and significant increase of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase values in the second week, and died on day 10 or 11 after disease onset. Genetic sequencing revealed 100% homology among virus strains isolated from the index patient and five secondary patients. Risk factors assessment of the person-to-person transmission revealed that the major exposure factor was blood contact without personal protection equipment. Information from this study provided solid references of SFTS incubation time, clinical and laboratory parameters related to SFTS severity and outcome, and biosafety issues for preventing person-to-person transmission or nosocomial infection of SFTSV., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The clinical risk factors of delayed gastric emptying (DGE) in patients after pancreaticoduodenectomy (PD) remains controversial. Herein, we conducted a systematic review to quantify the associations between clinical risk factors and DGE in patients after conventional PD or pylorus preserving pancreaticoduodenectomy (PPPD)., Methods: A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2012 was performed. Cohort, case-control studies, and randomized controlled trials that examined clinical risk factors of DGE were included., Results: Eighteen studies met final inclusion criteria (total n = 3579). From the pooled analyses, preoperative diabetes (OR 1.49, 95% CI, 1.03-2.17), pancreatic fistulas (OR 2.66, 95% CI, 1.65-4.28), and postoperative complications (OR 4.71, 95% CI, 2.61-8.50) were significantly associated with increased risk of DGE; while patients with preoperative biliary drainage (OR 0.68, 95% CI, 0.48-0.97) and antecolic reconstruction (OR 0.17, 95% CI, 0.07-0.41) had decreased risk of DGE development. Gender, malignant pathology, preoperative jaundice, intra-operative transfusion, PD vs. PPPD and early enteral feeding were not significantly associated with DGE development (all P > 0.05)., Conclusions: Our findings demonstrate that preoperative diabetes, pancreatic fistulas, and postoperative complications were clinical risk factors predictive for DGE. Antecolic reconstruction and preoperative biliary drainage result in a reduction in DGE. Knowledge of these risk factors may assist in identification and appropriate referral of patients at risk of DGE., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Advanced treatment of mature landfill leachate from a municipal landfill located in southern China (Jiangmen) was carried out in a full-scale plant using a new process. The combined process has a sequencing batch reactor (SBR) serving as the primary treatment, with polyferric sulfate (PFS) coagulation coupled with a Fenton system as secondary treatment, and a pair of upflow biological aerated filters (UBAFs) in parallel as tertiary treatment. The overall removal efficiency of chemical oxygen demand (COD) in this process was 97.3%, with an effluent COD less than 100 mg/L. Up to 99% ammonia (N-NH3) removal efficiency was achieved in the SBR, with an effluent of less than 3 mg/L, which meets the discharge standard (< or =25 mg/L) with only primary treatment. The total phosphorus (TP) and suspended solids (SS) in the final effluent were reduced to less than 1 mg/L and 10 mg/L, respectively. The experience gained in the operation and maintenance will lead to a more stable performance of this combined process. An economic analysis shows that the overall operating cost of the advanced treatment was $2.70/m(3). This new combination process was proved to be highly compatible and efficient in a small-scale landfill leachate treatment plant and is recommended for small-scale landfill leachate treatment plants.

To evaluate the role of interleukin-6 (IL-6) in arthritis induced by Staphylococcus aureus, a chicken model was developed for study. A total of 120 healthy broilers (8 wk old) were randomly divided into 4 groups. Two groups were injected with 0.35 mL of Staph. aureus (7.1x10(9) cfu/mL) into the right hock joints and the other 2 were injected with 0.35 mL of sterile saline into the same joints. One group of each of the 2 treatment groups was fed levofloxacin at a dose of 5 mg/kg of BW on the third day postinoculation for 4 successive days. Chicken blood samples were obtained on d 0, 1, 4, 7, 14, 21, 28, and 35 postinoculation. Chicken IL-6 (chIL-6) activities and concentrations in serum were quantified by B9 bioassay and human IL-6 ELISA, respectively. The results showed that chIL-6 activities and concentrations were reduced (P<0.05) in the serum of infected broilers treated with levofloxacin compared with birds injected only with Staph. aureus. Levofloxacin treatment had no effect on IL-6 activities and concentrations in uninfected broilers. There was a strong correlation (r=0.91) between serum chIL-6 activities by the B9 bioassay and serum IL-6 concentrations determined by the human IL-6 ELISA. We concluded that chIL-6 is involved in the progression of chicken arthritis induced by Staph. aureus, and that it contributes to disease incidence and mortality.

Sequence analysis of the tyrosinase (TYR) coding region from one albino rhesus monkey (Macaca mulatta) family revealed that the two monkeys with phenotype similar to human TYR-negative oculocutaneous albinism (OCA) were homozygous for a missense mutation (S184TER) in exon 1 at codon 184. The offspring of one of the albino monkey ("Kangkang") are all heterozygous for the S184TER mutation, but the S184TER mutation was not observed in 93 control individuals. We conclude that the point mutation is responsible and sufficient to generate the albino rhesus monkey phenotype. The rough age of the S184TER nonsense mutation may be about 0.8 million years using a rate of 0.16% per million years.