A Very Deep Graph Convolutional Network for 13C NMR Chemical Shift Calculations with Density Functional Theory Level Performance for Structure Assignment.

Nuclear magnetic resonance (NMR) chemical shift calculations are powerful tools for structure elucidation and have been extensively employed in both natural product and synthetic chemistry. However, density functional theory (DFT) NMR chemical shift calculations are usually time-consuming, while fast data-driven methods often lack reliability, making it challenging to apply them to computationally intensive tasks with a high requirement on quality. Herein, we have constructed a 54-layer-deep graph convolutional network for 13C NMR chemical shift calculations, which achieved high accuracy with low time-cost and performed competitively with DFT NMR chemical shift calculations on structure assignment benchmarks. Our model utilizes a semiempirical method, GFN2-xTB, and is compatible with a broad variety of organic systems, including those composed of hundreds of atoms or elements ranging from H to Rn. We used this model to resolve the controversial J/K ring junction problem of maitotoxin, which is the largest whole molecule assigned by NMR calculations to date. This model has been developed into user-friendly software, providing a useful tool for routine rapid structure validation and assignation as well as a new approach to elucidate the large structures that were previously unsuitable for NMR calculations.

A preliminary study of proximal realignment combination surgery in the treatment of adolescent habitual patellar dislocation.

OBJECTIVE: A combination of lateral soft tissue release, medial soft tissue contraction, vastus medialis anterior placement, medial patellofemoral ligament reconstruction, and rectus femoris insertion reconstruction are introduced in the treatment of habitual patellar dislocation in adolescents. METHODS: A retrospective analysis was performed on 12 patients (17 knees) with habitual patellar dislocation and unclosed epiphyses who underwent surgical treatment at the First Hospital of Jilin University from May 2017 to November 2021. The Lysholm scores and Q angle were collected preoperatively and at final follow-up and were compared. RESULTS: Twelve patients (4 boys and 8 girls) aged 10-15 years were retrospectively analysed, who followed up for an average of 21 months (5-48 months). The range of motion of the knee joint returned to normal in all patients, and no cases of complications including surgical site infection, joint stiffness, or patellar re-dislocation occurred. The mean Lysholm scores and Q angles improved from 73.9, and 19.6° preoperatively to 91.7, and 13.9° at the final follow-up, respectively. CONCLUSION: The preliminary effect of the combination surgery for habitual patellar dislocation in adolescents was satisfactory.

Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism.

A new biflavonoid, (2''S)-6''-methyl-2'',3''-dihydroochnaflavone (1), along with two known ochnaflavones (2, 3), four known amentoflavones (4-7) and two known robustaflavones (8, 9) were obtained from the 70% EtOH extract of Selaginella trichoclada. The chemical structures of isolated compounds were elucidated by extensive spectroscopic analyses. Overall, compounds 1-9 displayed moderate cytotoxic effects against human breast cancer MCF-7 cell lines. Among them, compounds 2 and 8 exhibited relatively strong cytotoxic effects against MCF-7 cells with an IC50 value of 7.7 and 6.9 µΜ, respectively. The results of RNA-sequencing and KEGG functional enrichment analysis showed that 8 could induce ferroptosis in MCF-7 cells by down-regulating the expression of ferroptosis-related genes including ACSL4, NOXO1, NOXA1, ACSL5, STEAP3, LPCAT3, ATG7 and TP53. Then 8 could inhibit the expression of ACSL4 proteins through molecule docking analysis, which showed a strong interaction of - 11.89 Kcal/mol binding energy. Those results indicate that 8 could be chemotherapy agents to fight drug resistance in breast cancer by down-regulating the expression level of ACSL4 proteins via ferroptosis, which needs to be further certified in vitro.

Synthesis, antifungal activity and 3D-QSAR study of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring.

A series of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of novel antifungal molecules. Structures of all the target compounds were characterized by spectral techniques of UV-vis, FT-IR, 1H-NMR, 13C-NMR, and ESI-MS. The antifungal activity of the target compounds was preliminarily evaluated by agar dilution method. The antifungal bioassay revealed that, at 50 µg/mL, compounds 5h (R = o-F), 5m (R = p-Br), and 5n (R = o-NO2) showed the same antifungal activity of 73.6% against Physalospora piricola, which was comparable than that of the positive control. Furthermore, against Gibberella zeae, compounds 5k (R = m-Cl), 5l (R = m-Br), 5m (R = p-Br), and 5n (R = o-NO2) displayed the same antifungal activity of 75.6%, and compound 5o (R = p-NO2) displayed antifungal activity of 78.8%, which were all better than that of the positive control. The preliminary analysis of 3D-QSAR model was performed to study the effect of molecular structure on biological activity using the comparative molecular field analysis (CoMFA) method. The results showed 3D-QSAR model (r2 = 0.995, q2 = 0.503) was reasonable and effective.

The Common and Different Neural Bases of Distraction and Reinterpretation: A Meta-Analysis of fMRI Studies.

Distraction and reinterpretation have been recognized as two different tactics of emotion regulation. As a tactic of attention deployment, distraction involves shifting attention to neutral information or performing a secondary task to distract attention from emotion stimuli of the primary task. Reinterpretation, a representative tactic of cognitive change, was defined as changing the meaning of a situation to enhance or reduce its emotional impact. Thus, there are significant differences between the two processes. We wondered if the neural mechanisms underlying distraction and reinterpretation are different. Even though their neural correlates have been widely studied with functional magnetic resonance imaging (fMRI), few studies were conducted to compare the two tactics directly. Here we conducted an activation likelihood estimation (ALE) meta-analyses to investigate the common or different neural bases of distraction and reinterpretation. Moreover, we also used the meta-analytic connectivity modeling (MACM) to identify the emotion regulation network of distraction and reinterpretation. Overall, we found that the left dorsal lateral prefrontal cortex (DLPFC) was consistently activated during distraction and reinterpretation, whereas the left amygdala and inferior frontal gyrus/ventrolateral prefrontal cortex (VLPFC) were specifically activated during reinterpretation alone. The results indicate that the neural basis of distraction and reinterpretation are similar but not identical. The MACM results showed that distraction and reinterpretation share a common emotion regulation network, including the bilateral DLPFC, the dorsal medial prefrontal cortex, the inferior parietal lobule, the insula, the left (pre) supplementary motor area, the left middle temporal gyrus, and the right superior temporal gyrus. However, that network may subserve different functions when adopting various emotion regulation strategies. In addition, we suggest that the emotion regulation network of the left VLPFC may be a specific regulatory network for reinterpretation.

Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway.

Breast cancer is one of the major malignant tumors in females, and currently, recurrence and metastasis are the main obstacles preventing effective breast cancer treatment. Biflavonoids of secondary metabolites from plants are excellent anticancer agents to fight sensitive and resistant breast cancer cell lines. In this study, six C-3'-C-6″ biflavonoids, including one new robustaflavone A (1, RF-A) and five known robustaflavone derivatives (2-6), were isolated from Selaginella trichoclada for the first time. We aimed to evaluate the inhibitory effects of compounds 1-6 against human breast cancer MCF-7 cells. Among the six compounds, RF-A showed the strongest activity, decreasing cell viability with an IC50 value of 11.89 µΜ. Furthermore, RF-A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.

Synthesis, Antifungal Activity, 3D-QSAR, and Molecular Docking Study of Novel Menthol-Derived 1,2,4-Triazole-thioether Compounds.

A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 µg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against Physalospora piricola. Compounds 5b (R = o-CH3 Ph), 5i (R = o-Cl Ph), 5v (R = m,p-OCH3 Ph) and 5x (R = α-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Compounds 5v (R = m,p-OCH3 Ph) and 5g (R = o-Cl Ph) held inhibition rates of 82.4% and 86.5% against Cercospora arachidicola and Gibberella zeae, respectively, much better than that of the commercial fungicide chlorothalonil. Compound 5b (R = o-CH3 Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against Colleterichum orbicalare and Fusarium oxysporum f. sp. cucumerinum. Compounds 5m (R = o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against F. oxysporum f. sp. cucumerinu, Bipolaris maydis and C. orbiculare. Furthermore, compound 5b (R = o-CH3 Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against P. piricola, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (r2 = 0.991, q2 = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.

Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Nopol-Derived 1,3,4-Thiadiazole-Thiourea Compounds.

A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. All the target compounds exhibited better antifungal activity against P. piricola, C. arachidicola, and A. solani. Compound 6j (R = m, p-Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds 6c (R = m-Me Ph), 6q (R = i-Pr), and 6i (R = p-Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Moreover, compounds 6h (R = m-Cl Ph) and 6n (R = o-CF3 Ph) held inhibition rates of 80.6% and 79.0% against C. arachidicola and G. zeae, respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against A. solani, analysis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r2 = 0.992, q2 = 0.753) has been established. Furthermore, some intriguing structure-activity relationships were found and are discussed by theoretical calculation.

Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19).

Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with real-time polymerase chain reaction-confirmed COVID-19 who presented between January 12, 2020, and February 6, 2020. Patients with severe respiratory distress and/or oxygen requirement at any time during the disease course were excluded. Repeat chest CT was performed at approximately 4-day intervals. Each of the five lung lobes was visually scored on a scale of 0 to 5, with 0 indicating no involvement and 5 indicating more than 75% involvement. The total CT score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). Results Twenty-one patients (six men and 15 women aged 25-63 years) with confirmed COVID-19 were evaluated. A total of 82 chest CT scans were obtained in these patients, with a mean interval (±standard deviation) of 4 days ± 1 (range, 1-8 days). All patients were discharged after a mean hospitalization period of 17 days ± 4 (range, 11-26 days). Maximum lung involved peaked at approximately 10 days (with a calculated total CT score of 6) from the onset of initial symptoms (R2 = 0.25, P < .001). Based on quartiles of chest CT scans from day 0 to day 26 involvement, four stages of lung CT findings were defined. CT scans obtained in stage 1 (0-4 days) showed ground-glass opacities (18 of 24 scans [75%]), with a mean total CT score of 2 ± 2; scans obtained in stage 2 (5-8 days) showed an increase in both the crazy-paving pattern (nine of 17 scans [53%]) and total CT score (mean, 6 ± 4; P = .002); scans obtained in stage 3 (9-13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020.

Bacillus fungorum sp. nov., a bacterium isolated from spent mushroom substrate.

A facultatively anaerobic, Gram-stain-positive, spore-forming Bacillus strain, 17-SMS-01T, isolated from spent mushroom substrate in the Fangshan District, Beijing, PR China, was initially identified as a Bacillus cereus group species based on 16S rRNA gene sequences. Strain 17-SMS-01T had the highest sequence similarities to Bacillus wiedmannii FSL W8-0169T (99.9 %), Bacillus albus N35-10-2T (99.9 %), Bacillus luti TD41T (99.9 %) and Bacillus proteolyticus TD42T (99.9 %). However, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (DDH) values between strain 17-SMS-01T and the most closely related species were less than the previously proposed cut-off values of 96 % (ANI) and 70 % (DDH) for differentiating species within the genus, suggesting that this strain represents a novel Bacillus group species. The fatty acid profile of strain 17-SMS-01T, which showed a predominance of iso-C15 : 0 and anteiso-C15 : 0, supported the allocation of the strain to the genus Bacillus. The predominant menaquinone was MK-7 (100%). The major polar lipids were diphosphatidylglycerol, phosphatidyl ethanolamine, phosphatidyl glycerol, an unidentified aminophospholiped and unidentified lipids. The DNA G+C content of the novel strain was 35.0 mol%. The results of physiological and biochemical tests also allowed the phenotypic differentiation of strain 17-SMS-01T from the most closely related recognized species. On the basis of the phylogenetic and phenotypic evidence, strain 17-SMS-01T represents a novel Bacillus species, for which the name Bacillus fungorum sp. nov. is proposed. Type strain of the novel species is 17-SMS-01T (=MCCC 1K03483T=KCTC 33949T).

Palhinosides A-H: Flavone Glucosidic Truxinate Esters with Neuroprotective Activities from Palhinhaea cernua.

Palhinosides A-H (1-8), new flavone glucosidic truxinate esters, including ß-truxinate and µ-truxinate forms, were isolated from Palhinhaea cernua. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. The flavone glucoside cyclodimers possess a unique cyclobutane ring in their carbon scaffolds. Compounds 2-7 represent three pairs of stereoisomers (2/3, 4/5, 6/7). The protective effects of 1-8 against the damage of HT-22 cells induced by l-glutamate were evaluated, and compounds 4 and 5 showed better neuroprotective effects than the positive control, Trolox.

Anaerophilus nitritogenes gen. nov., sp. nov., isolated from salt lake sediment in Xinjiang Province, China.

An obligately anaerobic, nitrate-reducing bacterial strain (MJB2T) was isolated from sediments of saline in Xinjiang province of China. Cells were Gram-stain-positive rods and motile by means of flagella and formed endospores. The novel strain MJB2T was able to grow at 15-37 °C (optimum 28-30 °C), pH 5.8-9.4 (optimum 7.8) and with 1.0-7.0% NaCl (optimum 5.0-6.0%, w/v). Sulfate, sulfite, thiosulfate, elemental sulfur, nitrite and Fe(III) were not used as terminal electron acceptors. Oxidase and catalase reactions were positive. H2S was producted from L-cystine. Complex substrates such as beef extract, peptone and yeast extract can be used as sole energy sources. The DNA G+C content was 29.4 mol%. The major cellular fatty acids (> 10%) were C14:0, C16:1 cis 7 and C16:1 cis 9. The main polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, three unidentified amino lipids, one unidentified amino glycolipid, two unidentified glycolipid, one unidentified aminophospholipid and two unidentified lipids. No respiratory quinones were detected. According to phylogenetic analysis based on 16S rRNA gene sequences, strain MJB2T was affiliated to the family Clostridiaceae (order Clostridiales) with highest 16S rRNA gene sequence similarity of 95.3% to Crassaminicella profunda Ra1766HT. Strain MJB2T exhibited 74.9% ANI values to C. profunda Ra1766HT. In silico DNA-DNA relatedness value between strain MJB2T and C. profunda Ra1766HT was 19.5%. The distinct biochemical, chemotaxonomic and phylogenetic differences from the previously described taxa supported that strain MJB2T represents a novel species of a new genus, for which the name Anaerophilus nitritogenes gen. nov., sp. nov. is proposed. The type strain is MJB2T (=KCTC 15800T=MCCC 1K03631T).

Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study.

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×109/L, CRP>77.35mg/L, PCT>0.20µg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.

Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety.

Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.

Requirements of metabolizable protein by Dorper × thin-tailed Han crossbred ewe lambs.

The requirement of net protein (NP) and metabolizable protein (MP) by Dorper crossbred ewe lambs grown from 35 to 50 kg of body weight (BW) was assessed by comparative slaughter experiment. Thirty-five ewe lambs (33.5 ± 0.6 kg BW) of F1 crosses of Dorper × thin-tailed Han sheep were used: 7 lambs were slaughtered as reference animals at the start of the trial, and the remaining 28 lambs were randomly divided into 4 groups of 7 lambs each. Three of the 4 groups were fed a pelleted mixed diet (concentrate/roughage = 44:56, dry matter basis) for ad libitum intake or 65% or 45% of ad libitum intake, and they were all slaughtered when the lambs that were fed ad libitum reached 50 kg BW. The lambs from the fourth group were also fed ad libitum and slaughtered at 43 kg BW as the intermediate group. The intake of MP by the animals of these 4 groups was estimated, and their total body protein and protein retention were measured. The daily requirements of NP and MP for maintenance were 1.52 and 3.98 g/kg BW0.75 , respectively, with a partial efficiency of MP utilization for maintenance of 0.38. The MP requirement for growth ranged from 77.4 to 124.5 g/day for average daily gains from 100 to 250 g BW, and the partial efficiency of MP utilization for growth was 0.66. The Dorper crossbred ewe lambs required more MP for both maintenance and growth in comparison with the recommendations of the US nutritional system.

Synthesis of Bioactive Compounds from 3-Carene (II): Synthesis, Antifungal Activity and 3D-QSAR Study of (Z)- and (E)-3-Caren-5-One Oxime Sulfonates.

A series of novel (Z)- and (E)-3-caren-5-one oxime sulfonates were designed and synthesized in search of potent antifungal agents. The structures of the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, and ESI-MS. The in vitro antifungal activity of the target compounds was preliminarily evaluated against Cercospora arachidicola, Physalospora piricola, Alternaria solani, Rhizoeotnia solani, Bipolaris maydis and Colleterichum orbicalare at 50 µg/mL. The bioassay results indicated that the target compounds exhibited the best antifungal activity against P. piricola, in which compounds 4b, 4f, 4m, 4e, 4j, 4l, 4y, 4d, and 4p had excellent inhibition rates of 100%, 100%, 100%, 92.9%, 92.9%, 92.9%, 92.9%, 85.7%, and 85.7%, respectively, showing much better antifungal activity than that of the commercial fungicide chlorothanil. Both the compounds 4y and 4x displayed outstanding antifungal activity of 100% against B. myadis, and the former also displayed outstanding antifungal activity of 100% against R. solani. In order to design more effective antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r² = 0.990, q² = 0.569) has been established.

[Application of machine learning in the CRISPR/Cas9 system].

The third generation of the CRISPR/Cas9-mediated genome fixed-point editing technology has been widely used in the field of gene editing and gene expression regulation. How to improve the on-target efficiency and specificity of this system, as well as reduce its off-target effects are always the bottleneck in its development. Machine learning provides novel methods to the problems of the CRISPR/Cas9 system, and CRISPR/Cas9-based machine learning has recently become a very hot research topic. In this review, we firstly outline the mechanism of the CRISPR/Cas9 system. Subsequently, we elaborate the current issues of CRISPR/Cas9, including low efficiency and potential off-target effects, and sequence-recognizing limitation from protospacer adjacent motif (PAM). Finally, we summarize the applications of methods within the machine learning framework for optimizing the CRISPR/Cas9 system, such as optimized single-guide RNA (sgRNA) design, CRISPR/Cas9 cleavage efficiency prediction, off-target effects evaluation, gene knock-out as well as high-throughput functional genetic screening and prospects for development.

Trichoderpyrone, a Unique Polyketide Hybrid with a Cyclopentenone-Pyrone Skeleton from the Plant Endophytic Fungus Trichoderma gamsii.

Trichoderpyrone (1), a unique polyketide with a cyclopentenone-pyrone hybrid skeleton, was isolated from the plant endophytic fungus Trichoderma gamsii. The structure of 1 was determined by detailed analysis of NMR data together with comparison of chemical shift values of similar fragments. The relative and absolute configurations were established by NOESY correlations and CD experiment. Trichoderpyrone (1) displayed weak cytotoxic activities against A549, HepG2, and HeLa cancer cell lines. 1 might originate from a hybrid biosynthetic pathway through two nonreduced (NR) polyketide megasynthetases.

Three new isobenzofuranone derivatives from the fruiting bodies of Hericium erinaceus.

Three new isobenzofuranone derivatives erinaceolactones D-F (1-3), together with four known ones (4-7), were isolated from the fruiting bodies of Hericium erinaceus. Their structures were determined on the basis of comprehensive spectroscopic analyses including UV, 1D, 2D NMR and HR-TOF-MS. The absolute configuration of erinaceolactone D (1) and erinaceolactone E (2) were assigned by comparing their specific rotation with those of analogs in literatures. The four known compounds were isomers with each other and were isolated simultaneously for the first time.

Two new isobenzofuranone derivatives from the fruiting bodies of Hericium erinaceus.

Two new isobenzofuranone derivatives erinaceolactones G and H (1 and 2) were isolated from the ethanolic extract of fruiting bodies of Hericium erinaceus. Their structures were characterized on the basis of spectroscopic evidences. Compound 2 was suggested to be racemic by specific rotation, which was resolved by chiral HPLC into enantiomers.