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Ying Yang,1 Hai-yong Ao,1 Sheng-bing Yang,1 Yu-gang Wang,1 Wen-tao Lin,2 Zhi-feng Yu,1 Ting-ting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 2Department of Orthopedics, Fuzhou Second Hospital, Affiliated Hospital of Xiamen University, Fuzhou, People’s Republic of China Abstract: Titanium-based implants have been widely used in orthopedic surgery; however, failures still occur. Our in vitro study has demonstrated that gentamicin-loaded, 80 nm-diameter nanotubes possessed both antibacterial and osteogenic activities. Thus, the aim of this study was to further investigate the in vivo anti-infection effect of the titanium implants with gentamicin-loaded nanotubes. Thirty-six male Sprague Dawley rats were used to establish an implant-associated infection model. A volume of 50 µL Staphylococcus aureus suspension (1×105 CFU/mL) was injected into the medullary cavity of the left femur, and then the titanium rods without modification (Ti), titanium nanotubes without drug loading (NT), and gentamicin-loaded titanium nanotubes (NT-G) were inserted with phosphate-buffered saline-inoculated Ti rods as a blank control. X-ray images were obtained 1 day, 21 days, and 42 days after surgery; micro-computed tomography, microbiological, and histopathological analyses were used to evaluate the infections at the time of sacrifice. Radiographic signs of bone infection, including osteolysis, periosteal reaction, osteosclerosis, and damaged articular surfaces, were demonstrated in the infected Ti group and were slightly alleviated in the NT group but not observed in the NT-G group. Meanwhile, the radiographic and gross bone pathological scores of the NT-G group were significantly lower than those of the infected Ti group (P

A new steroid named persteroid ( 1 ) and seven known compounds ( 2 - 8 ) were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. The structure of 1 was determined by HRESIMS, NMR, and ECD calculations. Compound 1 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 46.31 ± 0.52 μM. Moreover, compound 1 potently suppressed nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The cytotoxicity and antibacterial activity of all isolates were tested.

Objective: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H 2 S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function., Methods: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H 2 S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala., Results: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H 2 S-induced intestinal and cerebral injury., Conclusion: This experimental data suggests that H 2 S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR., 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 B.V.)

Background: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation., Purpose: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action., Methods: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays., Results: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA., Conclusion: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial competing interest in the subject matter or materials discussed in this manuscript by any of the authors., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC 50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages., 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 Inc.)

Different morphologies and sizes of α-Fe 2 O 3 were prepared by a coprecipitation method using polyvinylpyrrolidone as a dispersant. In the preparation process, homogeneous and dispersed nanoscale FeOOH particles were first obtained by the coprecipitation method, and then the FeOOH particles were calcined at high temperature to form α-Fe 2 O 3 . The growth and aggregation of the α-Fe 2 O 3 particles at different calcination temperatures resulted in α-Fe 2 O 3 powders with diversiform morphologies (nanoscale microsphere, pinecone ellipsoidal, polyhedral, and quasi-spherical structures). By analyzing the SEM images, it was inferred that the polyhedral structure of α-Fe 2 O 3 particles was formed by the accumulation of rhomboid sheet structures and high-temperature growth. In terms of the magnetic properties, the samples belonged to the class of canted antiferromagnetic materials, and the morphology, particle size, and crystallite size of the α-Fe 2 O 3 particles were important factors affecting the coercivity. Among these, when the calcination temperature was increased from 700 °C to 800 °C, the growth rate of the particle size was significantly faster than that of the crystallite size, and the coercivity increased substantially from 1411 Oe to 2688 Oe.

We investigate optical transmission in cavity magnon polaritons and discover a complex multi-window magnetically induced transparency and a bistability with magnetic and optical characteristics. With the regulation of Kerr nonlinear effects and driven fields, a complex multi-window resonant transmission with fast and slow light effects appears, which includes transparency and absorption windows. The magnetically induced transparency and absorption can be explained by the destructive and constructive interference between different excitation pathways. Moreover, we demonstrate the bistability of magnons and photons with a hysteresis loop, where magnetic and optical bistabilities can induce and control each other. Our results pave a new way, to the best of our knowledge, for implementing a room-temperature multiband quantum memory.

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC 50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 μM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC 50 values of 30.2 ± 0.13 μM and 120.6 ± 0.14 μM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations., 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.)

We investigate the transmission of probe fields in a coupled-cavity system with polaritons and propose a theoretical schema for realizing a polariton-based photonic transistor. When probe light passes through such a hybrid optomechanical device, its resonant point with Stokes or anti-Stokes scattered effects, intensity with amplification or attenuation effects, as well as group velocity with slow or fast light effects can be effectively controlled by another pump light. This controlling depends on the exciton-photon coupling and single-photon coupling. We also discover an asymmetric Fano resonance in transparency windows under the strong exciton-photon coupling, which is different from general symmetric optomechanically induced transparency. Our results open up exciting possibilities for designing photonic transistors, which may be useful for implementing polariton integrated circuits.

Background: Perioperative neurocognitive disorders (PND), such as delirium and cognitive impairment, are commonly encountered complications in aged patients. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is aberrantly synthesized from reactive astrocytes following inflammatory stimulation and is implicated in the pathophysiology of neurodegenerative diseases. Additionally, the activation of NOD-like receptor protein 3 (NLRP3) inflammasome is involved in PND. Herein, we aimed to investigate whether the NLRP3-GABA signaling pathway contributes to the pathogenesis of aging mice's PND., Methods: 24-month-old C57BL/6 and astrocyte-specific NLRP3 knockout male mice were used to establish a PND model via tibial fracture surgery. The monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) was intraperitoneally administered once a day for 7 days after the surgery. PND, including impulsive-like behaviors and cognitive impairment, was evaluated by open field test, elevated plus maze, and fear conditioning. Thereafter, pathological changes of neurodegeneration were explored by western blot and immunofluorescence assays., Results: Selegiline administration significantly ameliorated TF-induced impulsive-like behaviors and reduced excessive GABA production in reactive hippocampal astrocytes. Moreover, astrocyte-specific NLRP3 knockout mice reversed TF-induced impulsive-like and cognitive impairment behaviors, decreased GABA levels in reactive astrocytes, ameliorated NLRP3-associated inflammatory responses during the early stage, and restored neuronal degeneration in the hippocampus., Conclusions: Our findings suggest that anesthesia and surgical procedures trigger neuroinflammation and cognitive deficits, which may be due to NLRP3-GABA activation in the hippocampus of aged mice., (© 2023. The Author(s).)

Background: Water shortage caused by global warming seriously affects the yield and quality of vegetable crops. β-carotene, the lipid-soluble natural product with important pharmacological value, is abundant in celery. Transcription factor MYB family extensively disperses in plants and plays regulatory roles in carotenoid metabolism and water scarcity response., Results: Here, the AgMYB5 gene encoding 196 amino acids was amplified from celery cv. 'Jinnanshiqin'. In celery, the expression of AgMYB5 exhibited transactivation activity, tissue specificity, and drought-condition responsiveness. Further analysis proved that ectopic expression of AgMYB5 increased β-carotene content and promoted drought tolerance in transgenic Arabidopsis thaliana. Moreover, AgMYB5 expression promoted β-carotene biosynthesis by triggering the expression of AtCRTISO and AtLCYB, which in turn increased antioxidant enzyme activities, and led to the decreased contents of H 2 O 2 and MDA, and the inhibition of O 2 - generation. Meanwhile, β-carotene accumulation promoted endogenous ABA biosynthesis of transgenic Arabidopsis, which resulted in ABA-induced stomatal closing and delayed water loss. In addition, ectopic expression of AgMYB5 increased expression levels of AtERD1, AtP5CS1, AtRD22, and AtRD29., Conclusions: The findings indicated that AgMYB5 up-regulated β-carotene biosynthesis and drought tolerance of Arabidopsis., (© 2023. The Author(s).)

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

We study the ground-state stability of the trapped one-dimensional Bose-Einstein condensate under a density-dependent gauge field by variational and numerical methods. The competition of density-dependent gauge field and mean-field atomic interaction induces the instability of the ground state, which results in irregular dynamics. The threshold of the gauge field for exciting the instability is obtained analytically and confirmed numerically. When the gauge field is less than the threshold, the system is stable, and the gauge field induces chiral dynamics of the wave packet. When the gauge field is greater than the threshold, the system is unstable, and the ground-state wave packet will be deformed and fragmented. Interestingly, we find that as the gauge field approaches the threshold, strong dipolar and breathing dynamics take place, and strong modes mixing occurs, the instability of the system sets in. In addition, we show that the stability of the system can be well controlled by periodical modulation of the trapping potential. We provide theoretical evidence to understand and control the irregular dynamics associated with chiral superfluid induced by density-dependent gauge field.

Objective: To analyze the status quo of the knowledge and related factors of cancer prevention and treatment among residents in Liaoning Province in 2021. Methods: From August to November 2021, through network sampling method, 17 474 permanent residents aged 15-69 years in Liaoning Province were surveyed. The WeChat public account was used to collect information such as demographic characteristics and core knowledge of cancer prevention and treatment. The Chi-square test was used to compare the difference of the level of the cancer prevention and treatment knowledge among different groups. The multivariate logistic regression model was used to analyze the related factors. Results: Among the 17 474 subjects, 43.1% (7 528) were male and 58.7% (10 262) were urban residents. The overall awareness rate was 72.3%, and the awareness rate of cancer cognition, prevention, early diagnosis and treatment, cancer management and rehabilitation were 71.4%, 67.6%, 72.7%, 83.4% and 63.5%, respectively. The multivariate logistic regression model showed that the residents who were man ( OR : 0.850, 95% CI : 0.781-0.925), in rural areas ( OR : 0.753, 95% CI : 0.694-0.817), 55-59 years old ( OR : 0.851, 95% CI : 0.751-0.963), quitters ( OR : 0.721, 95% CI : 0.640-0.813) and smoker ( OR : 0.724, 95% CI : 0.654-0.801) had lower awareness rates, while the residents who were 35-54 years old ( OR : 1.312, 95% CI : 1.202-1.432), with an educational level of junior high school/senior high school/college degree or above ( OR : 1.834-5.130, 95% CI : 1.575-6.047), technical personnel ( OR : 1.592, 95% CI : 1.367-1.854), civil servant/institution staff ( OR : 1.282, 95% CI : 1.094-1.503), enterprise/business/service staff ( OR : 1.218, 95% CI : 1.071-1.385), retired ( OR : 1.324, 95% CI : 1.114-1.573) and with family history of cancer ( OR : 1.369, 95% CI : 1.266-1.481) had higher awareness rates. Conclusion: The level of the awareness of core knowledge of cancer prevention and treatment among residents in Liaoning Province has met the requirements of the Healthy China Action. Region, gender, education level, age, family history of cancer and smoking are relevant factors.

Thin-film-composite (TFC) nanofiltration membranes have found wide uses in environment remediation and industrial separation. There is a growing trend to avoid the use of organic solvents and toxic chemicals during membrane fabrication. Therefore, the aqueous fabrication of TFC membranes receives considerable interest as a green and sustainable process. However, it remains challenging to construct a defect-free and ultrathin film in a homogeneous aqueous phase without the assistance of an interface. The contra-diffusion process provides a special "interface" to confine the film formation within a narrow space by regulating the competition between precursor diffusion and interfacial reactions. Herein, Fe 3+ /tannic acid (TA) TFC membranes were fabricated by a contra-diffusion process. The effects of fabrication parameters on the Fe 3+ /TA TFC membrane microstructure and performance were also investigated. The negatively charged membrane performs a competitive Na 2 SO 4 rejection of 95.6% with a permeation flux of 44.3 L m -2 h -1 under 0.6 MPa as well as more than 99.5% rejection to several anionic dyes. The as-prepared membranes perform superior nanofiltration performance compared to other reported Fe 3+ /TA-based membranes, owing to the thin and defect-free selective layers by self-regulation. Moreover, the membranes exhibit stable rejection during a long-term nanofiltration test.

Objectives: Wenjing decoction (WJD) was widely used in the treatment for ovulatory disorder infertility (ODI) in China, while its efficacy was not clearly known. In this study, we evaluated the clinical efficacy of WJD by meta-analysis., Methods: Eight electronic databases including Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched for randomized controlled trials (RCTs) published from the inception of each database to July 1, 2021, of which the interventions involve WJD and clomiphene. Outcomes included clinical efficacy rate, pregnancy rate, ovulation rate, dominant follicle diameter, endometrial thickness, estradiol, follicle-stimulating hormone, and luteinizing hormone. Meta-analysis and risk of bias were performed by RevMan 5.3 software., Results: Eleven RCTs including 915 patients, of which 476 in the intervention group and 439 in the control group. Meta-analysis showed that WJD was better than clomiphene for patients with ODI in terms of clinical effective rate (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.08-1.34), pregnancy rate (OR = 1.54, 95% CI: 1.15-2.07), ovulation rate (OR = 1.34, 95% CI: 1.07-1.67), endometrial thickness (mean difference [MD] = 1.50, 95% CI: 0.90-2.10), and dominant follicle diameter (MD = 1.85, 95% CI: 0.68-3.02). The estradiol level (MD = 91.0, 95% CI: 80.3-101.88) in patients taking WJD was significantly higher than those taking clomiphene, while the follicle-stimulating hormone level (MD = -0.93, 95% CI: -1.13 to -0.72) and the luteinizing hormone level (MD = -4.41, 95% CI: -4.80 to -4.03) in patients taking WJD was significantly lower than those taking clomiphene. Our results also indicated that WJD combined with clomiphene was better than clomiphene alone for patients with ODI in terms of pregnancy rate (OR = 1.79, 95% CI: 1.37-2.35)., Conclusions: WJD may be effective in the treatment of patients with ODI. Due to the quality and quantity of literature, RCT with large sample size and high quality need to be performed to verify our conclusion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

An unknown endophytic fungus was isolated from the aquatic plant Hippuris vulgaris in Litang county, Sichuan province, China. Phylogenetic analyses inferred from combined ITS, Sod2, Apn2, and TUB2 sequences revealed that the endophyte is a new species belonging to the Colletotrichum graminicola species complex. Morphological characteristics showed that Colletotrichum litangense is characterized by its falcate, lunate to sublunate conidia, and ellipsoidal, ovoid, or lobed appressoria. Pathogenicity tests on several fruits showed that C. litangense could induce anthracnose lesions. As a result of the phylogenetic, morphological, and pathogenicity analyses, we proposed the name Colletotrichum litangense for the new species., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Macrofungi Ganoderma is a valuable medicinal fungus resource for human health and longevity in China. In this study, ten undescribed compounds including seven lostane-type triterpenoids, ganodaustralic acids A ∼ G (1-7), one pair of meroterpenoid enantiomers, (-)-6'-O-ethyllingzhiol (8) and (+)-6'-O-ethyllingzhiol (9), and one polyhydroxylated sterol, 3-O-acetyl-fomentarol C (10), together with eight known compounds (11-18), were isolated from the fruiting bodies of Ganoderma australe. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and electronic circular dichroism (ECD) calculations. Compounds 4, 8, 9, and 12 showed significant α-glucosidase inhibitory activities with IC 50 values in the range of 4.1-11.7 μM, which were superior to that of positive control acarbose (213 μM). Only compound 7 exhibited weak cytotoxicity against SGC-7901 cells., (Copyright © 2021. Published by Elsevier Inc.)

The family Microthyriaceae is represented by relatively few mycelial cultures and DNA sequences; as a result, the taxonomy and classification of this group of organisms remain poorly understood. During the investigation of the diversity of aquatic hyphomycetes from southern China, several isolates were collected. These isolates were cultured and sequenced and a BLAST search of its LSU sequences against data in GenBank revealed that the closest related taxa are in the genus Microthyrium . Phylogenetic analyses, based on the combined sequence data from the internal transcribed spacers (ITS) and the large subunit (LSU), revealed that these isolates represent eight new taxa in Microthyriaceae, including two new genera, Antidactylaria gen. nov. and Isthmomyces gen. nov. and six new species, Antidactylariaminifimbriata sp. nov. , Isthmomycesoxysporus sp. nov. , I.dissimilis sp. nov. , I.macrosporus sp. nov. , Triscelophorusanisopterioideus sp. nov. and T.sinensis sp. nov . These new taxa are described, illustrated for their morphologies and compared with similar taxa. In addition, two new combinations are proposed in this family., (Min Qiao, Hua Zheng, Ji-Shu Guo, Rafael F. Castañeda-Ruiz, JianPing Xu, Jie Peng, Ke-Qin Zhang, Ze-Fen Yu.)

Exophiala is an important genus, with several species associated with infections in humans and animals. In a survey of soil fungal diversity in Yunnan province, PR China, a novel taxon, Exophiala pseudooligosperma sp. nov., was identified based on combined morphological and molecular phylogenetic features. Morphologically, this species is characterized by having torulose, septate hyphae and swollen, terminal or intercalary conidiogenous cells arising at acute angles from aerial hyphae. Phylogenetic analysis of the combined sequences of the internal transcribed spacer, the small and large nuclear subunit of the rRNA gene and part of the β-tubulin gene confirmed the phylogenetic position of the new species within the genus Exophiala .

Four new indole-diterpenoids, named penerpenes K-N ( 1 - 4 ), along with twelve known ones ( 5 - 16 ), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds ( 4 , 9, and 15 ) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC 50 value of 5.3 μM. Moreover, six compounds ( 5 , 7 , 10 , 12 , 14 , and 15 ) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

Purpose: To determine whether functional vision and visual function improvements after voretigene neparvovec (VN; Luxturna [Spark Therapeutics, Inc]) administration in patients with biallelic RPE65 mutation-associated inherited retinal disease are maintained at 3 to 4 years and to review safety outcomes., Design: Open-label, randomized, controlled phase 3 trial., Participants: Thirty-one individuals were enrolled and randomized 2:1 to intervention (n = 21) or control (n = 10). One participant from each group withdrew before, or at, randomization., Methods: Patients in the original intervention (OI) group received bilateral subretinal VN injections. Delayed intervention (DI) patients served as control participants for 1 year then received VN., Main Outcome Measures: Change from injection baseline in bilateral performance on the multiluminance mobility test (MLMT), a measure of ambulatory navigation, and change from injection baseline in full-field light sensitivity threshold white light, visual field (VF), and visual acuity (VA)., Results: Mean bilateral MLMT change scores at year 4 for OI patients and year 3 for DI patients were 1.7 and 2.4, respectively, with 71% of patients with a year 3 visit able to pass MLMT at the lowest light level. Mean change in full-field light sensitivity threshold white light, averaged over both eyes at year 4 for OI patients and year 3 for DI patients, was -1.90 log 10 (cd.s/m 2 ) and -2.91 log 10 (cd.s/m 2 ), respectively. Mean change in Goldmann kinetic VF III4e sum total degrees, averaged across both eyes, was 197.7 at year 4 for OI patients and 157.9 at year 3 for DI patients. Mean change in VA (Holladay scale), averaged across both eyes, was -0.003 logarithm of the minimum angle of resolution (logMAR) at year 4 for OI patients and -0.06 logMAR at year 3 for DI patients. One OI patient experienced retinal detachment at approximately year 4 that impacted VA for the OI group. No product-related serious adverse events (AEs) occurred, nor did any deleterious immune responses., Conclusions: Improvements in ambulatory navigation, light sensitivity, and VF were consistent in both intervention groups. Overall, improvements were maintained up to 3 to 4 years, with ongoing observation. The safety profile of VN was consistent with vitrectomy and the subretinal injection procedure and was similar between intervention groups, with no product-related serious AEs reported., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

A new species, Colletotrichum menglaense , isolated from air in Mengla, Xishuangbanna, Yunnan Province, China, was characterized and described combining morphological characteristics and multigene phylogenetic analysis. Morphologically, it is characterized by oblong, sometimes slightly constricted, micro-guttulate conidia and simple obovoid to ellipsoidal appressoria. Phylogenetic analysis of the ITS, ACT, CHS, and GAPDH sequences showed that C. menglaense belongs to the C. gloeosporioides complex. The pathogenicity of C. menglaense on fruits of several crop plants, including strawberry, orange, grape, tomato, and blueberry, was tested and confirmed by the re-isolation of C. menglaense .

The stability and superfluidity of the Bose-Einstein condensate in two-leg ladder with magnetic field are studied. The dispersion relation and the phase diagram of the system are obtained. Three phases are revealed: the Meissner phase, the biased ladder (BL) phase, and the vortex phase. The dispersion relation and phase transition of the system strongly depend on the magnitude of atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. Particularly, the change of the energy band structure in the phase transition region is modified significantly by the atomic interaction strength. Furthermore, based on the Bogoliubov theory, the energetic and dynamical stability of the system are invested. The stability phase diagram in the full parameter space is presented, and the dependence of superfluidity on the dispersion relation is illustrated explicitly. The atomic interaction strength can produce dynamical instability in the energetic unstable region and can expand the superfluid region. The results show that the stability of the system can be controlled by the atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. In addition, the excitation spectrums in the Meissner phase, BL phase and vortex phase are further studied. The modulation of the excitation spectrum and the energetic stability of the system by the atomic interaction strength, the rung-to-leg coupling ratio and magnetic flux is discussed. Finally, through the numerical simulation, the dynamical instability of the system is verified by the time evolution of the Bloch wave and rung current. This provides a theoretical basis for controlling the superfluidity of the system.

Context: Financial toxicity is a priority concern faced by cancer patients and oncology providers. A validated instrument is important to measure this toxicity and improve health-related quality of life of patients., Objectives: To assess the validity and responsiveness of the Chinese version of the COmprehensive Score for financial Toxicity (COST) and to measure financial toxicity using the COST instrument in Chinese health care systems., Methods: A longitudinal observational study was performed at three cancer centers from March 2017 to October 2018 for eligible patients. Construct validity was assessed by exploratory and confirmatory factor analysis. The convergent and discriminant validity was tested by examining the correlation coefficient. Responsiveness was tested using the standardized response mean and effect size. Associations between the financial toxicity and variables were assessed by multivariable linear analysis., Results: There were 440 participants at baseline and 268 participants at 6-month follow up. A two-factor solution better represented the Chinese version of COST structure with good internal consistency and test-retest reliability. Convergent validity showed mild to moderate correlations between the domains of COST and the similar domains of Self-Perceived Burden Scale and Quality of Life Discriminant validity showed a low correlation between the COST and the subjective support of Social Support Rate Scale. Sensitivity to change at the sixth month showed effect sizes with global COST scores of 0.3. Multivariable analysis showed that age, household income, and health insurance were significantly associated with financial toxicity., Conclusions: The Chinese version of COST is a valid and clinically responsive instrument. The identified baseline variables can be used to provide evidence for a financial toxicity intervention study., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11β-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 μmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 μmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 μmol·L~(-1).

To aim of the present paper was to introduce a novel fixation technique for the treatment of inferior pole fracture of the patella. We performed a prospective observational study of consecutive cases of inferior pole fracture of the patella that were treated at our institution between January 2018 and June 2019. The patients include three men and one woman, with an average age of 47 years (range: 42-59 years). All patients were treated with the novel rim plating fixation technique for preserving the inferior pole of the patella. During the surgery, a 2.4 mm straight locking compression plate was contoured to adapt to the arc of the lower half of the patella as the rim plate. After reduction of the fracture, the rim plate was fixed to the proximal fragment of the patella through multiple locking screws, against the continuous pull of the patellar tendon. The rim plate encircles and constricts the inferior pole fragments, functioning as a compression and blocking construct. If necessary, an additional anterior tension band or mini locking plate can be used to further prevent anterior displacement of the inferior pole fragments. Under this rigid fixation, motion of the knee and full weight-bearing were encouraged postoperatively. The patients were followed up monthly until 12 months after surgery. The time to achieve 90°pain-free, full range of motion of the knee, and fracture healing, were recorded. Related complications were monitored, including infection, loss of reduction, fixation failure, anterior knee pain, and soft-tissue irritation. The modified Cincinnati knee rating system was used for knee function assessment. The average operative time was 58.8 min (range: 52-63 min). The average blood loss was 59.8 mL (range: 45-71 mL). For all patients, pain-free 90° range of motion was restored in 2-4 weeks, and the full range of motion was restored in 8-11 weeks. All patients achieved bone union in 6-9 weeks with no displacement of the fragments or breakage of the implant. No patient complained of anterior knee pain or soft-tissue irritation. The modified Cincinnati score at 12-month follow up demonstrated excellent outcomes in all four patients. The rim plating technique may be a feasible option for the treatment of the inferior pole fracture of the patella., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Two new compounds named asperpenes D ( 1 ) and E ( 2 ) were isolated from the marine-derived fungus Aspergillus sp. SCS-KFD66. Their structures were determined on the basis of spectroscopic methods. Compound 2 represents the first natural product bearing a 2-substituted-5-oxo-4-phenyl-2,5-dihydrofuran-3-carboxylic acid skeleton. All the compounds were tested for enzyme inhibitory activity against AChE and α-glucosidase and DPPH radical scavenging activity, respectively. [Formula: see text].

During a mycological survey of freshwater hyphomycetes on submerged leaves in southwest China, a new species, Anacraspedodidymum submersum , was isolated. The new species A. submersum is characterized by having monophialidic conidiogenous cells with funnel shaped collarettes and globose or subglobose, aseptate and hyaline conidia. Morphologically, A. submersum is somewhat similar to A. aquaticum and A. hyalosporum in conidiophores and conidiogenous cells, but can be easily distinguished by its subglobose to globose and smaller conidia. Phylogenetic analysis of combined ITS and LSU sequences show that the new species of Anacraspedodidymum clustered together with the genus Thozetella in Chaetosphaeriaceae . A full description, illustrations and a phylogenetic tree showing the position of A. submersum are provided herein.

To determine if Ageratina adenophora can accumulate diverse pathogens from surrounding native plants, we intensively sampled fungal communities, including endophytes, leaf spot pathogens and canopy air fungi, associated with Ag. adenophora as well as native plants in its invasive range. In total, we collected 4542 foliar fungal strains from 10 geographic sites, including 1340 from healthy leaves of Ag. adenophora , 2051 from leaf spots of Ag. adenophora and 1151 from leaf spots of 56 species of native plants and crops. Taxonomically, the common fungal genera included Colletotrichum , Diaporthe , Alternaria , Nemania , Xylaria , Neofusicoccum , Nigrospora , Epicoccum , Gibberella , Pestalotiopsis , Irpex , Schizophyllum and Clonostachys . We also isolated the cultivable fungi from 12 air samples collected from six areas in Yunnan Province, PR China. Among the total of 1255 air fungal isolates, the most common genera were Cladosporium , Trichoderma and Epicoccum . Among them, two new Remotididymella species, Remotididymella ageratinae from leaf spot of Ag. adenophora and Remotididymella anemophila from canopy air of Ag. adenophora were found. The two species showed both asexual and sexual reproductive structures. The conidia of R. ageratinae and R. anemophila are larger than those of R. anthropophila and R. destructiva . The size of ascospores of R. ageratinae and R. anemophila also differ from R. bauhiniae . Phylogenetic analysis of the combined ITS, LSU rRNA, rpb2 and tub2 sequences showed that R. ageratinae and R. anemophila each formed a distinct clade, separated from all species previously described in Remotididymella and confirmed them as new species belonging to Remotididymella . Full descriptions of R. ageratinae and R. anemophila are provided in this study.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

The Bose-Einstein condensates in a finite depth potential well provide an ideal platform to study the quantum escape dynamics. In this paper, the ground state, tunneling, and diffusion dynamics of the spin-orbit coupling (SOC) of Bose-Einstein condensates with two pseudospin components in a shallow trap are studied analytically and numerically. The phase transition between the plane-wave phase and zero-momentum phase of the ground state is obtained. Furthermore, the stability of the ground state is discussed, and the stability diagram in the parameter space is provided. The bound state (in which condensates are stably trapped in the potential well), the quasibound state (in which condensates tunnel through the well), and the unstable state (in which diffusion occurs) are revealed. We find that the finite depth potential well has an important effect on the phase transition of the ground state, and, interestingly, SOC can stabilize the system against the diffusion and manipulate the tunneling and diffusion dynamics. In particular, spatial anisotropic tunneling and diffusion dynamics of the two pseudospin components induced by SOC in quasibound and unstable states are observed. We provide an effective model and method to study and control the quantum tunneling and diffusion dynamics.

The metabolites of the genus Marasmius are diverse, showing good research prospects for finding new bioactive molecules. In order to explore the active metabolites of the fungi Marasmius berteroi , the deep chemical investigation on the bioactive compounds from its cultures was undertaken, which led to the isolation of three new naphthalene compounds dipolynaphthalenes A-B ( 1 , 2 ) and naphthone C ( 3 ), as well as 12 known compounds ( 4 - 15 ). Compounds 1 , 2 , and 4 are dimeric naphthalene compounds. Their structures were elucidated by MS, 1D and 2D NMR spectroscopic data, as well as ECD calculations. Compounds 2 - 4 and 7 exhibited acetylcholinesterase (AChE) inhibitory activities at the concentration of 50 μg/mL with inhibition ratios of 42.74%, 44.63%, 39.50% and 51.49%, respectively. Compounds 5 and 7 , 8 showed weak inhibitory activities towards two tumor cell lines, with IC 50 of 0.10, 0.076 and 0.058 mM (K562) and 0.13, 0.18, and 0.15 mM (SGC-7901), respectively.

Leptographium panxianense and L. puerense are proposed as new taxa based on sequence data and morphological characters. The phylogenetic analyses based on ITS2-partial LSU rDNA region, β-tubulin and elongation factor 1-α genes showed that L. panxianense and L. puerense formed well-supported clades and were closely related to L. yunnanense , L. wushanense and L. conjunctum , and then nested within the L. lundbergii complex. The two species differ in their conidial size and shape. The conidia of L. panxianense are larger than those of L. puerense while the conidial shape of L. puerense is more ovovoid. The optimal growth temperature of both L. panxianense and L. puerense is at 20 °C, which is different from those of L. yunnanense , L. wushanense and L. conjunctum . Comparison of sequence data and morphological characters confirmed the placement of the two undescribed taxa in the genus of Leptographium .

To compare short-term and long-term efficacy after laparoscopic left hepatectomy(LLR) to open left hepatectomy(OLH) for primary left-sided hepatolithiasis. Methods: Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t -test or rank-sum test. Count data were analyzed with χ(2) test or Fisher test. Results: No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P> 0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs .(8.5±2.2)days, t= 4.085, P= 0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs .21.2%, χ(2)=4.374, P= 0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs .27.6%, χ(2)=4.502, P= 0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs . 17.0%, χ(2)=4.029, P= 0.045). OLH (95 % CI : 1.55 to 10.75, P= 0.004) and postoperative complications (95 % CI : 1.29 to 9.52, P= 0.013) were independent risk factors for prolonged hospital stay. OLH (95 % CI : 1.428 to 44.080, P= 0.018) and residual stones (95 % CI : 1.580 to 62.379, P= 0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95 % CI : 1.078 to 24.517, P= 0.040) was an independent risk factor for the recurrence of stones. Conclusion: Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

This study examined over 20 fungal specimens of the Orbiliaceae (Orbiliomycetes) from different regions in China. Our analyses based on morphological traits and the ITS rDNA sequences revealed two new Orbilia species with drechslerella-like asexual morphs. These new species are able to trap nematodes with constricting rings. In addition, Orbilia cf. orientalis is reported as a new cryptic Chinese variant of European collections of O. orientalis . All three species are described and illustrated in detail in this paper. Their phylogenetic relationships with other orbiliaceous species were identified based on their ITS sequences.

The atom-light hybrid interferometer recently attracted much attention in the research of precision metrology for its combination of light and atomic spin wave. With the AC Stark effect and proper design, it can be applied in the scheme of quantum non-demolition (QND) measurement of photon numbers. In this work, we apply the QND criteria to the scheme and theoretically derive its explicit formulas with various losses of the atomic-light hybrid interferometer. With the formulas and actual experiment parameters, we estimate and compare the performance of the vapor-atom-based and cold-atom-based hybrid interferometer in the QND measurement, analyze the influences of different kinds of losses, and provide optimized working parameter ranges of the interferometer.

During a survey of endophytic fungi in plant roots in secondary forests in Yunnan, China, a novel ascomyceteous taxon, Beltrania sinensis , was isolated from Quercus cocciferoides Hand.-Mazz. and Fraxinus malacophylla Hemsl. This novel species is characterized by having oval or obovoid conidiogenous cells with several apical, flat-tipped denticles, and biconic, aseptate, smooth, pale brown conidia with a hyaline to subhyaline equatorial transverse band and apical tubular appendage. Phylogenetic analysis of the combined sequences of the internal transcribed spacer and the LSU rRNA gene confirmed its novel species status within the genus Beltrania . Here, the novel species is described and illustrated, and a taxonomic key to species in the genus Beltrania is provided.

Phalangispora sinensis , an aquatic hyphomycete collected from south-western PR China, is described as a new species. This new species is characterized by having multicellular branched conidia composed of a curved main axis and one or two laterals, with the laterals arising from the third or fourth cell of the base of the main axis. Combined analyses of the LSU, SSU, RPB2 and TEF1 gene sequence data revealed that Phalangispora and another aquatic hyphomycete genus, Setosynnema , belonged to Wiesneriomycetaceae, Tubeufiales, Dothideomycetes, Ascomycota.

During a survey of fungal diversity in a deserted rocky area in Yunnan, PR China, a new species, Memnoniella sinensis , was identified. This new species is characterized by having phialidic conidiogenous cells with conspicuous collarettes, and aseptate, verrucose, ellipsoidal to sometimes ovoid, olivaceous brown to dark brown conidia. Morphologically, M. sinensis is similar to M. dichroa , but can be easily distinguished due to its hyaline conidiophores and smaller conidia. Phylogenetic analysis based on DNA sequences at five loci showed that our strain grouped together with M. dichroa and M. oenanthes . Here, the new species is described and illustrated, and a key to the species of the genus Memnoniella is provided.

In our study, we sequenced the complete mitochondrial genome of Dactylella tenuis and obtained the complete mitochondrial DNA sequence. This mitogenome is a typical circular molecule of 186,056 bp in length, which is rich in AT (73.79%), including 14 protein-coding genes, 24 transfer RNA genes, and 2 ribosomal RNA genes. Phylogenetic analysis showed the evolutionary relationship between D. tenuis and other species of nematode-trapping fungus., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector-based gene therapy for RPE65 mutation-associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2., Design: Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial., Participants: Forty subjects who received 1.5×10 11 vector genomes (vg) of VN per eye in at least 1 eye during the trials, including 11 phase 1 follow-on subjects and 29 phase 3 subjects (20 original intervention [OI] and 9 control/intervention [CI])., Methods: Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects., Main Outcome Measures: End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing., Results: Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 log 10 (cd.s/m 2 ) improvement in light sensitivity at 1 year and subsequent available follow-up visits. The safety profile was consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred., Conclusions: After VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation-associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Chemical investigation on the cultures of the fungus Cordyceps spp., a strain from cell fusion between Cordyceps militaris and Cordyceps cicadae, resulted in the isolation of 13 compounds including 2 new ones named 2-(5-(3-oxobutyl) furan-2-yl) acetic acid (1) and cordycepone (2). Their structures were elucidated from the analysis of 1D/2D NMR and CD data. Among them, compounds 1, 7-9, at a concentration of 50 μg/ml, showed weak inhibitory activity against AChE. Moreover, compounds 6, 9, and 11 showed moderate inhibitory activity against the nematode Panagrellus redivivus with mortality ratio of 79.0, 71.7, and 72.3% at 2.5 mg/ml, respectively.