Molecular Dynamics Simulation Model of Alkali Metal Reduction of Gaseous Halides and Reaction Mechanism Analysis.

The reaction of gaseous hydrogen halides with alkali metals provides a new pathway for producing hydrogen. The structure and reactivity of alkali metals are crucial for the reduction of gaseous halides. However, traditional gas-phase reaction models fail to provide insights into the dynamic processes occurring during alkali metal reactions. In this paper, based on the reaction between Hydrogen fluoride (HF) and alkali metal sodium (Na), we have established a metallic Na slab. HF molecules were randomly inserted above the surface of the Na slab, creating a reaction model for the reduction of HF by metallic Na. The reaction of HF on the Na surface was calculated using first-principles molecular dynamics. The configuration and reaction of the Na surface and HF molecules at different times were judged by analyzing the radial distribution function and mean squared displacement. Na atoms reacted with HF to produce intermediate NaFH, and then the F-H bond broke to form NaF and H. The F-H bond breaking of intermediate NaFH was the key step, and the kinetic parameters of this key step were calculated.

Energy Metabolism Enhance Perylenequinone Biosynthesis in Shiraia sp. Slf14 through Promoting Mitochondrial ROS Accumulation.

Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ titer mutant, Slf14(w). The results indicated that the strain Slf14 exhibited a higher PQ yield, a more vigorous energy metabolism, and a more pronounced oxidation state compared to Slf14(w). Transcriptome analysis consistently revealed that the differences in gene expression between Slf14 and Slf14(w) are primarily associated with genes involved in redox processes and energy metabolism. Additionally, reactive oxygen species (ROS) were shown to play a crucial role in promoting PQ synthesis, as evidenced by the application of ROS-related inhibitors and promoters. Further results demonstrated that mitochondria are significant sources of ROS, which effectively regulate PQ biosynthesis in Shiraia sp. Slf14. In summary, this research revealed a noteworthy finding: the higher energy metabolism of the strain Slf14 is associated with increased intracellular ROS accumulation, which in turn triggers the activation and expression of gene clusters responsible for PQ synthesis.

High energy barrier hydroxyl radical dissociation mechanism of a low shock sensitivity dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) explosive.

As a representative of the new generation of high-energy explosives, TKX-50 has attracted widespread attention due to its remarkably low sensitivity toward shock. However, the reported decomposition barriers of TKX-50 (∼37 kcal mol-1) are comparable to those of commonly used explosives. The mechanism of its low shock sensitivity remains unclear. In this study, using an ab initio molecular dynamics method combined with a multiscale shock simulation technique and transition state calculations (at the B2PLYP-D3/Def2TZVP level), we discovered an unconventional reaction pathway of TKX-50 under shock, and its rate-controlling step is the dissociation of the hydroxyl radical (OH) from the anion ring after proton transfer, followed by ring rupture and the production of H2O and N2. The barrier for this OH dissociation reaction is as high as 51.9 kcal mol-1. In contrast, under thermal stimuli, TKX-50 prefers to open rings directly after proton transfer without losing the OH. The corresponding barrier is 35.4 kcal mol-1, which is in good agreement with previous studies. The reason for the unconventional reaction pathway of TKX-50 under shock may be the suppression of anion ring opening in thermal decomposition by steric hindrance upon shock compression. In addition, the dominant N2 generation pathway under shock releases less energy than pyrolysis which further explains the low shock sensitivity of TKX-50. This study comprehensively elucidates the different reaction mechanisms of TKX-50 under thermal and shock conditions and proposes a crucial reaction pathway leading to its low shock sensitivity. These findings will contribute to the understanding and application of tetrazole anionic energetic salts.

Neural mechanism of non-adaptive cognitive emotion regulation in patients with non-suicidal self-injury.

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.

Plant endophytic fungi exhibit diverse biotransformation pathways of mogrosides and show great potential application in siamenoside I production.

Fungal endophytes, as an untapped resource of glycoside hydrolase biocatalysts, need to be further developed. Mogroside V, the primary active compound in Siraitia grosvenorii fruit, can be converted into other various bioactive mogrosides by selective hydrolysis of glucose residues at C3 and C24 positions. In present study, 20 fungal strains were randomly selected from our endophytic fungal strain library to assess their capability for mogroside V transformation. The results revealed that relatively high rate (30%) endophytic fungal strains exhibited transformative potential. Further analysis indicated that endophytic fungi could produce abundant mogrosides, and the pathways for biotransforming mogroside V showed diverse. Among the given fungal endophytes, Aspergillus sp. S125 almost completely converted mogroside V into the end-products mogroside II A and aglycone within just 2 days of fermentation; Muyocopron sp. A5 produced rich intermediate products, including siamenoside I, and the end-product mogroside II E. Subsequently, we optimized the fermentation conditions for Aspergillus sp. S125 and Muyocopron sp. A5 to evaluate the feasibility of large-scale mogroside V conversion. After optimization, Aspergillus sp. S125 converted 10 g/L of mogroside V into 4.5 g/L of mogroside II A and 3.6 g/L of aglycone after 3 days of fermentation, whereas Muyocopron sp. A5 selectively produced 4.88 g/L of siamenoside I from 7.5 g/L of mogroside V after 36 h of fermentation. This study not only identifies highly effective biocatalytic candidates for mogrosides transformation, but also strongly suggests the potential of plant endophytic fungi as valuable resources for the biocatalysis of natural compounds.

Morphometric similarity differences in drug-naive Parkinson's disease correlate with transcriptomic signatures.

BACKGROUND: Differences in cortical morphology have been reported in individuals with Parkinson's disease (PD). However, the pathophysiological mechanism of transcriptomic vulnerability in local brain regions remains unclear. OBJECTIVE: This study aimed to characterize the morphometric changes of brain regions in early drug-naive PD patients and uncover the brain-wide gene expression correlates. METHODS: The morphometric similarity (MS) network analysis was used to quantify the interregional structural similarity from multiple magnetic resonance imaging anatomical indices measured in each brain region of 170 early drug-naive PD patients and 123 controls. Then, we applied partial least squares regression to determine the relationship between regional changes in MS and spatial transcriptional signatures from the Allen Human Brain Atlas dataset, and identified the specific genes related to MS differences in PD. We further investigated the biological processes by which the PD-related genes were enriched and the cellular characterization of these genes. RESULTS: Our results showed that MS was mainly decreased in cingulate, frontal, and temporal cortical areas and increased in parietal and occipital cortical areas in early drug-naive PD patients. In addition, genes whose expression patterns were associated with regional MS changes in PD were involved in astrocytes, excitatory, and inhibitory neurons and were functionally enriched in neuron-specific biological processes related to trans-synaptic signaling and nervous system development. CONCLUSIONS: These findings advance our understanding of the microscale genetic and cellular mechanisms driving macroscale morphological abnormalities in early drug-naive PD patients and provide potential targets for future therapeutic trials.

Identification and validation of targets of swertiamarin on idiopathic pulmonary fibrosis through bioinformatics and molecular docking-based approach.

BACKGROUND: Swertiamarin is the main hepatoprotective component of Swertiapatens and has anti-inflammatory and antioxidation effects. Our previous study showed that it was a potent inhibitor of idiopathic pulmonary fibrosis (IPF) and can regulate the expressions of α-smooth muscle actin (α-SMA) and epithelial cadherin (E-cadherin), two markers of the TGF-ß/Smad (transforming growth factor beta/suppressor of mothers against decapentaplegic family) signaling pathway. But its targets still need to be investigated. The main purpose of this study is to identify the targets of swertiamarin. METHODS: GEO2R was used to analyze the differentially expressed genes (DEGs) of GSE10667, GSE110147, and GSE71351 datasets from the Gene Expression Omnibus (GEO) database. The DEGs were then enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for their biological functions and annotated terms. The protein-protein interaction (PPI) network was constructed to identify hub genes. The identified hub genes were predicted for their bindings to swertiamarin by molecular docking (MD) and validated by experiments. RESULTS: 76 upregulated and 27 downregulated DEGs were screened out. The DEGs were enriched in the biological function of cellular component (CC) and 7 cancer-related signaling pathways. Three hub genes, i.e., LOX (lysyl oxidase), COL5A2 (collagen type V alpha 2 chain), and CTGF (connective tissue growth factor) were selected, virtually tested for the interactions with swertiamarin by MD, and validated by in vitro experiments. CONCLUSION: LOX, COL5A2, and CTGF were identified as the targets of swertiamarin on IPF.

Individualized antibiotic dosage regimens for patients with augmented renal clearance.

Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%-65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes. Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC. Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research. Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.

Reaction mechanism and electronic properties of host-guest energetic material CL-20/HA under high pressure by quantum-based molecular dynamics simulations.

The novel host-guest material 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20)/hydroxylamine (HA) improves the detonation energy of CL-20 explosives without compromising its safety. However, the reaction mechanism of CL-20/HA under high pressure is not yet fully understood for the complex host-guest structure. A multiscale shock simulation technique by quantum-based molecular dynamics was performed to investigate the reaction mechanism of CL-20/HA under shock with different velocities along different directions, focusing on charge transfer, electronic properties, reaction path and product evolution. The structural changes caused by both insertion of HA and charge overlap between CL-20 and HA are responsible for the electronic changes and gap decrease. Directional charge transfer was observed between CL-20 and HA molecular fragments during shock in all shock loading directions, causing the CL-20 molecular group to become electrically non-neutral. The C-N bond in the CL-20 cage then broke, leading to the release of nitro and nitrous oxide at high temperatures and pressures. The HA molecules or free H atoms from HA could bond with the O atom in the nitro group, leading to the N-O bond cleavage. Some free H atoms could act as an intermediary, connecting two CL-20 molecules and forming dimeric molecules briefly. Compared with the pure CL-20 system, HA can inhibit the reaction of CL-20 in the CL-20/HA system to some extent during the initial shock stage. A further understanding of the chemical reaction mechanism and energy release in dense host-guest materials can be advanced by focusing on the microscopic internal effects of the guest molecule on the host molecule reactions.

Efficacy and mortality of ceftazidime/avibactam-based regimens in carbapenem-resistant Gram-negative bacteria infections: A retrospective multicenter observational study.

OBJECTIVES: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. METHODS: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. RESULTS: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. CONCLUSION: CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.

Remnant Cholesterol as an Independent Predictor of Periodontitis: A Population-Based Study.

Objective: Numerus studies present that remnant cholesterol (RC) as a risk factor participates in the progression of multiple diseases. The aim of this study was to assess the relationship between cholesterol and periodontitis in the US population to find a reliable lipid predictor for periodontitis. Materials and Methods: Clinical data was retrieved from the National Health and Nutrition Examination Survey (NHANES) database between 2009 and 2014. The logistic regression was conducted to examine the corelationship between RC and various clinical features. Meanwhile, the dose-response relationship was measured through restricted cubic spline analysis. And the propensity score matching (PSM) was established to further investigate the potential relationship between RC and periodontitis. Results: A number of 4,829 eligible participants were included in this study. It was found that the increased RC is associated with the higher risk of periodontitis after adjusting the potential confounding factors with the adjusted odds ratios (aOR) of 1.403 (95% confidence intervals (CI): 1.171-1.681, P < 0.001, univariate analysis) and 1.341 (95% CI: 1.105-1.629, P = 0.003, multivariate analysis) in the highest grade. There were significant differences in the relationship between RC and various clinical features including age, gender, body mass index (BMI), race, hypertension, and diabetes mellitus (all P < 0.001). Besides, the calculated thresholds for predicting periodontitis were 19.99 (before propensity score matching (PSM)) and 20.91 (after PSM) mg/dL. Conclusions: In this study, RC was identified to be positively associated with the occurrence of periodontitis, which suggests that RC can be considered as a predictor for periodontitis.

Transcriptional signal and cell specificity of genes related to cortical structural differences of post-traumatic stress disorder.

Due to the diversity of traumatic events, the diagnosis of Post-traumatic Stress Disorder is heterogeneous. The pathogenesis has been explored in the fields of brain imaging and genomics separately, but the results are inconsistent. Previous research evidenced that there existed structural differences between PTSD and healthy controls in multiple brain regions. This study further looked into the differences of brain structure in PTSD at the whole brain level and analyzed the difference-related genomes. The brain structure imaging data of 36 patients and 32 healthy controls were taken as morphological indexes. Partial least squares regression and transcriptome data were used to extract genomes related to structural differences. Additional data sets were used to study transcription characteristics of genome. Morphological differences were found in cingulate gyrus between patients and control group. Differentially expressed genes related to Morphometric similarity networks difference space were also observed. The obtained genes (i.e., RORA, PRKG1 and FKBP5) were proved to be related to the disorder with no significant correlation with other mental illnesses. In the subsequent cell type analysis, astrocytes, excitatory neurons and inhibitory neurons were evidenced to have the most significant correlation with these genes. This study found morphologically different brain regions related to PTSD. The related genome transcription analysis connects the structural differences and molecular mechanisms.

280 mT static magnetic field promotes the growth of postpartum condylar cartilage.

PURPOSE: Functional appliances made of permanent magnets have been used in jaw orthopedic treatment. However, whether the static magnetic field (SMF) generated by permanent magnets promotes the developmental sequence of condylar cartilage and thus promotes the growth of the mandible remains to be studied. The aim of this study was to investigate the effects of 280 mT SMF on postnatal condylar chondrogenesis and endochondral ossification and the roles of FLRT3, FGF2 and BMP2 signaling in this chondrodevelopmental sequences. METHODS: Forty-eight rats were assigned to two groups (control and SMF). The condyles were collected at the specified time points. The histomorphological changes in the condyle were observed by histological staining. The expression of proteins related to the proliferation and differentiation of the condylar cartilage and the changes in subchondral bone microstructure were analyzed by immunohistochemical staining and micro-CT scanning. FLRT3, FGF2, and BMP2 expression was detected by immunofluorescence staining. RESULTS: Under SMF stimulation, the cartilage of young rats grew longitudinally and laterally, and the thickness of the cartilage became thinner as it grew. The SMF promoted the proliferation and differentiation of condylar chondrocytes and endochondral ossification and increased subchondral bone mineral density, and BMP2 signaling was involved. Moreover, under SMF loading, the increased expression of FGF2 and FLRT3 were involved in regulating cartilage morphogenesis and growth. In late development, the decreased expression of FGF2/FLRT3 and the increased expression of BMP2 promoted endochondral ossification. The SMF accelerated this opposite expression trend. CONCLUSION: FGF2/FLRT3 and BMP2 signals are involved in the regulatory effect of SMF exposure on chondrogenesis and endochondral ossification, which provides a theoretical basis for the clinical use of magnetic appliances to promote condylar growth.

Case Report: Therapeutic Strategy With Delayed Debridement for Culture-Negative Invasive Group A Streptococcal Infections Diagnosed by Metagenomic Next-Generation Sequencing.

Streptococcal toxic shock syndrome (STSS) caused by group A streptococcus is a rare condition that rapidly developed to multiple organ failure even death. Therefore, prompt diagnosis, initiate appropriate antibiotics and other supportive treatments are critical. Here we reported a case of STSS caused by group A streptococcus infection. A healthy 39-year-old man presented a sudden pain in the left lower extremity, followed by a high fever (40.0 °C) with dizziness, nausea, and shortness of breath. Twenty-four hours before the visit, the patient showed anuria. The patient was then admitted to the intensive care unit. Blood examination revealed elevated levels of inflammatory markers and creatinine. He suffered from septic shock, dysfunction of coagulation, acute kidney dysfunction, acute respiratory distress syndrome, and acute liver function injury. The diagnosis was obtained through clinical manifestation and metagenomic next-generation sequencing (mNGS) drawn from the pustule and deep soft tissue (lower limb) samples while all bacterial cultures came back negative. The pustule mNGS report detected a total of 132 unique group A streptococcus sequence reads, representing 96.3% of microbial reads while the soft tissue mNGS report identified a total of 142474 unique group A streptococcus sequence reads, representing 100% of microbial reads. The patient was treated with aggressive fluid resuscitation, antibiotics comprising piperacillin/tazobactam and clindamycin, respiratory support, following the delayed surgical debridement. Intravenous immunoglobulin was also used for 5 days. On the 14th day after admission, he was transferred to the general ward for follow-up treatment. Our case highlighted, for the first time, the key role of mNGS in the early diagnosis of culture-negative invasive group A streptococcal infection. The case also suggested that clindamycin combined with beta-lactam antibiotics and adjunction of intravenous immunoglobulin therapy with delayed debridement performed well in the management of unstable STSS patients.

C/MIC > 4: A Potential Instrument to Predict the Efficacy of Meropenem

This prospective study aimed to explore the determinants of meropenem trough concentration (Ctrough) in patients with bacterial pneumonia and to investigate the association between its concentration and efficacy. From January 2019 to December 2019, patients with pulmonary infections were prospectively enrolled from the intensive care unit. Factors affecting the meropenem trough concentration were analyzed, and a multiple linear regression model was constructed. Logistic regression analyses were used to investigate the relationship between Ctrough and clinical efficacy. A total of 64 patients were enrolled, in whom 210 meropenem concentrations were measured. Of the total, 60.9% (39/64) were considered clinically successful after treatment. Ctrough may increase with increased blood urea nitrogen, albumin, and concomitant antifungal use. By contrast, concentration may decrease with increased endogenous creatinine clearance rate. Six variables, including Ctrough/minimum inhibitory concentration (MIC) > 4, were associated with the efficacy of meropenem. There was an independent correlation between Ctrough/MIC > 4 and efficacy after fully adjusting for confounding factors. Based upon renal function indexes, it is possible to predict changes in meropenem concentration and adjust the dosage precisely and individually. Ctrough/MIC > 4 is a potential instrument to predict successful treatment with meropenem.

Endophytic fungi from Dongxiang wild rice (Oryza rufipogon Griff.) show diverse catalytic potential for converting glycyrrhizin.

Endophytic fungi inhabiting niche environments are novel biocatalyst resources that need to be exploited urgently. In this study, 63 endophytic fungi isolated from Dongxiang wild rice (Oryza rufipogon Griff.) were tested to assess their potentials to transform glycyrrhizin (GL) into glycyrrhetinic acid monoglucuronide (GAMG) or glycyrrhetinic acid (GA), of which 12 strains were shown to have ß-d-glucuronidase activity. Based on morphological characteristics and rDNA ITS sequence analysis, the strains S59, L138, L55 and R57 with high GL molar conversion rates (55%, 45%, 65% and 89%) were further identified as Microsphaeropsis arundinis S59, Penicillium rubens L138, Aspergillus flavus L55 and Eupenicillium javanicum R57, respectively. These four strains with four different types of GL conversion processes were identified, i.e., (1) GL → GAMG in M. arundinis S59, (2) GL → GAMG and GA in A. flavus L55, (3) GL → GA in P. rubens L138, and (4) GL → GAMG → GA in E. javanicum R57, in which the bioconversion type (4) is reported for the first time. The study not only provided abundant and diverse ß-d-glucuronidase resources that can be used for GL bioconversion, especially for GAMG biosynthesis from endophytic fungi, but also expanded our knowledge of potential roles of endophytes as new biocatalysts in biotransformation.

Polyketide Derivatives from the Endophytic Fungus Phaeosphaeria sp. LF5 Isolated from Huperzia serrata and Their Acetylcholinesterase Inhibitory Activities.

The secondary metabolites of Phaeosphaeria sp. LF5, an endophytic fungus with acetylcholinesterase (AChE) inhibitory activity isolated from Huperzia serrata, were investigated. Their structures and absolute configurations were elucidated by means of extensive spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses, and calculations of electronic circular dichroism (ECD). A chemical study on the solid-cultured fungus LF5 resulted in 11 polyketide derivatives, which included three previously undescribed derivatives: aspilactonol I (4), 2-(1-hydroxyethyl)-6-methylisonicotinic acid (7), and 6,8-dihydroxy-3-(1'R, 2'R-dihydroxypropyl)-isocoumarin (9), and two new natural-source-derived aspilactonols (G, H) (2, 3). Moreover, the absolute configuration of de-O-methyldiaporthin (11) was identified for the first time. Compounds 4 and 11 exhibited inhibitory activity against AChE with half maximal inhibitory concentration (IC50) values of 6.26 and 21.18 µM, respectively. Aspilactonol I (4) is the first reported furanone AChE inhibitor (AChEI). The results indicated that Phaeosphaeria is a good source of polyketide derivatives. This study identified intriguing lead compounds for further research and development of new AChEIs.

Use of Non-Saccharomyces Yeast Co-Fermentation with Saccharomyces cerevisiae to Improve the Polyphenol and Volatile Aroma Compound Contents in Nanfeng Tangerine Wines.

This study attempted to improve the polyphenol and volatile aroma compound contents in Nanfeng tangerine wines using non-Saccharomyces yeast and Saccharomyces cerevisiae. The effects of fermentation with pure cultures of Candida ethanolica, Hanseniaspora guilliermondii and Hanseniaspora thailandica, as well as in sequential and mixed inoculations (1:1 or 1:100 ratio) with S. cerevisiae in Nanfeng tangerine wines were evaluated. C. ethanolica was found to produce the most polyphenols (138.78 mg/L) during pure fermentation, while H. guilliermondii produced the most volatile aroma compounds (442.34 mg/L). The polyphenol content produced during sequential fermentation with S. cerevisiae and H. guilliermondii (140.24 mg/L) or C. ethanolica (140.21 mg/L) was significantly higher than other co-fermentations. Meanwhile, the volatile aroma compounds were found to be more abundant in S. cerevisiae/H. guilliermondii mixed fermentation (1:1 ratio) (588.35 mg/L) or S. cerevisiae/H. guilliermondii sequential fermentation (549.31 mg/L). Thus, S. cerevisiae/H. guilliermondii sequential fermentation could considerably boost the polyphenol and volatile aroma component contents in Nanfeng tangerine wines. The findings of this study can be used to drive strategies to increase the polyphenol content and sensory quality of tangerine wines and provide a reference for selecting the co-fermentation styles for non-Saccharomyces yeast and S. cerevisiae in fruit wine fermentation.