Interfacial solvation-structure regulation for stable Li metal anode by a desolvation coating technique.

Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.

Realizing high-capacity all-solid-state lithium-sulfur batteries using a low-density inorganic solid-state electrolyte.

Lithium-sulfur all-solid-state batteries using inorganic solid-state electrolytes are considered promising electrochemical energy storage technologies. However, developing positive electrodes with high sulfur content, adequate sulfur utilization, and high mass loading is challenging. Here, to address these concerns, we propose using a liquid-phase-synthesized Li3PS4-2LiBH4 glass-ceramic solid electrolyte with a low density (1.491 g cm-3), small primary particle size (~500 nm) and bulk ionic conductivity of 6.0 mS cm-1 at 25 °C for fabricating lithium-sulfur all-solid-state batteries. When tested in a Swagelok cell configuration with a Li-In negative electrode and a 60 wt% S positive electrode applying an average stack pressure of ~55 MPa, the all-solid-state battery delivered a high discharge capacity of about 1144.6 mAh g-1 at 167.5 mA g-1 and 60 °C. We further demonstrate that the use of the low-density solid electrolyte increases the electrolyte volume ratio in the cathode, reduces inactive bulky sulfur, and improves the content uniformity of the sulfur-based positive electrode, thus providing sufficient ion conduction pathways for battery performance improvement.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.

Neuroprotective effects of a new triterpenoid from edible mushroom on oxidative stress and apoptosis through the BDNF/TrkB/ERK/CREB and Nrf2 signaling pathway in vitro and in vivo.

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties. In this study, 10 secondary metabolites (1-10), including a new lanostane triterpenoid named 2α-hydroxy-inotodiol (2α-HI, 1), were identified from the edible mushroom I. obliquus through high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance spectroscopy (NMR) data analysis. The neuroprotective function of all steroidal metabolites in H2O2-induced SH-SY5Y cells was investigated. The results showed that 2α-HI exhibited the most remarkable neuroprotective activity. In the meantime, 2α-HI significantly ameliorated oxidative stress damage, reactive oxygen species (ROS) accumulation and mitochondrial damage induced by H2O2 in SH-SY5Y cells. The Nrf2 siRNA and inhibitors transfected the SH-SY5Y cells, indicating the Nrf2 and BDNF/TrkB/ERK/CREB pathway mediated the neuroprotective effects of 2α-HI against the H2O2-stimulated oxidative stress and apoptosis. Moreover, the neuroprotection of 2α-HI was preliminarily verified in zebrafish. In conclusion, this research was the first to confirm that 2α-HI could effectively protect SH-SY5Y cells against H2O2-induced oxidative stress and apoptosis via the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Hence, this mushroom could be a potential dietary supplement to ameliorate neurodegenerative diseases.

Triterpenoids and meroterpenoids from the edible Ganoderma resinaceum and their potential anti-inflammatory, antioxidant and anti-apoptosis activities.

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1ß, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H2O2-induced SH-SY5Y cells by activating the Akt/GSK-3ß/Nrf2 signaling pathway. Taken together, these results may provide a stronger theoretical basis for ganoresinoid A from G. resinaceum as nutrition intervention to alleviate neurodegenerative diseases.

Exploring of seasonal dynamics of microbial community in multispecies fermentation of Shanxi mature vinegar.

The constituents of fermentation foods vary seasonally and the microbiota plays a crucial role in metabolites formation. Here, the diversity and succession of microbiota of Shanxi mature vinegar produced with solid-solid fermentation craft have been investigated by Illumina Hiseq sequencing in both summer and winter. Obvious differences were observed in the structure of microbiota between summer and winter, and the bacterial community showed a significant difference (P < 0.05). Alpha diversity analysis showed that the diversity and richness of bacterial community were basically higher than that of fungal community in both summer and winter. For bacterial community, Lactobacillus and Limosilactobacillus were the two major group bacteria in the fermentation process of Shanxi mature vinegar in summer, and they dominated in acetic acid fermentation and alcoholic fermentation stages, respectively. Lactobacillus and Acetobacter were the two major group bacteria during the fermentation of Shanxi mature vinegar in winter. Saccharomyces, Saccharomycopsis, and Issatchenkia were the main yeasts in both seasons, while the dominant mould was Rhizopus in summer and Monascus in winter, respectively. The diversity of yeasts and moulds in winter was far greater than that in summer, especially in alcoholic fermentation stage. Collectively, our work revealed critical insights into effect of seasonal variation on the structure of microbiota of Shanxi mature vinegar, and was relevant in understanding the relationships between environmental change and microbiota.

Structures of ganorbifates C-I, seven previously undescribed lanostanoids from the mushroom Ganoderma orbiforme, and insights of computed biosynthesis with DFT.

Ganorbifates C-I, seven undescribed biosynthetically related polyoxygenated 3,4-seco-27-norlanostanoid congeners, were isolated from the edible mushroom, Ganoderma orbiforme. Ganorbifate C features a unique cyclobutene ring constructed at C19/C11, and both D and E incorporate an unusual cyclopropane ring formed by C-19/C-9 linkage. Their structures, including the absolute configurations, were determined by spectroscopic methods and ECD calculations. The proposed Norrish-Yang cyclization-based key biosynthetic pathway for ganorbifates C-E is revealed by density functional theory (DFT) calculations. The computational studies uncover the formation of both cyclobutene and cyclopropane rings in the isolates and the stereoselectivity centers of these steps are consistent with those in the natural products. All compounds exhibited NO generation inhibition in LPS-induced BV-2 microglial cells, among them ganorbifate C was the most promising one with the IC50 values of 4.37 µM.

Phytochemistry and Pharmacological Activities of the Diterpenoids from the Genus Daphne.

There are abundant natural diterpenoids in the plants of the genus Daphne from the Thymelaeaceae family, featuring a 5/7/6-tricyclic ring system and usually with an orthoester group. So far, a total of 135 diterpenoids has been isolated from the species of the genus Daphne, which could be further classified into three main types according to the substitution pattern of ring A and oxygen-containing functions at ring B. A variety of studies have demonstrated that these compounds exert a wide range of bioactivities both in vitro and in vivo including anticancer, anti-inflammatory, anti-HIV, antifertility, neurotrophic, and cholesterol-lowering effects, which is reviewed herein. Meanwhile, the fascinating structure-activity relationship is also concluded in this review in the hope of providing an easy access to available information for the synthesis and optimization of efficient drugs.

Ganoderterpene A, a New Triterpenoid from Ganoderma lucidum, Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells.

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC50 values in the range 7.15-36.88 µM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 µM, and the structure-activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.

Nephrotic syndrome in syngeneic hematopoietic stem cell transplantation recipients: A case report.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is widely used in the treatment of hematological diseases. However, complications after transplantation, such as acute and chronic graft-vs-host disease (GVHD), still seriously affect the quality of life and even threaten the lives of patients. There is evidence that glomerular diseases can manifest as GVHD. However, GVHD should not occur as a result of syngeneic HSCT. CASE SUMMARY: A 20-year-old male diagnosed with T lymphoblastic lymphoma (stage IIIA, aaIPI 1) in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission. He underwent syngeneic HSCT in June 2014, and had no kidney disease history before the transplant. However, nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT. Renal biopsy was performed, which led to a diagnosis of atypical membranous nephropathy. After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine, the nephrotic syndrome was completely relieved. CONCLUSION: We report a case of delayed nephrotic syndrome after syngeneic HSCT. Antibody-mediated autoimmune glomerular disease may be the underlying mechanism. After treatment with immunosuppressive agents, the nephrotic syndrome was completely relieved but further long-term follow-up is still needed.

Social interactions upregulate hemolymph tryptophan and tyrosine levels in the male lobster cockroach.

In the present study, we found that tryptophan (TRP) and tyrosine (TYR) levels are increased in hemolymph of male Nauphoeta cinerea after social contact with either male or female conspecifics. Hemolymph was collected from individual males before and after the social interactions, and samples were analyzed by HPLC-ECD; analyte identities were confirmed by UPLC/MS. After a male-male first encounter fight, hemolymph TRP and TYR levels were significantly increased in dominants compared with the levels before the encounter. Conversely, TRP and TYR in subordinates were maintained at levels similar to those before the encounter. While after-fight TRP and TYR levels were significantly higher in dominants than subordinates, no significant differences were found in the contestants before the fight. Moreover, contact with an isolated male antenna was sufficient to stimulate attack behavior and increase hemolymph TRP and TYR titers to levels similar to those seen in dominants. After a male-female interaction, two distinct outcomes could be observed. Either hemolymph TRP and TYR levels were increased in successfully mated males, or TRP and TYR levels were unchanged in males that only exhibited premating wing-raising behavior but failed in mating. After contacting the antenna of a socially naïve male with an isolated female antenna, three patterns of behavior and related amino acid response were observed: 1) only premating wing-raising behavior with significant increase of TRP and TYR levels, 2) only attack behavior with significant increase of TRP and TYR levels, and 3) mixed wing-raising and attack behaviors with no significant changes in TRP and TYR levels. The present results show a robust response of hemolymph TRP and TYR to social contact. In light of previously characterized responses in pheromone and juvenile hormone levels, these amine responses suggest that the physiological response of N. cinerea to social contact is multi-dimensional.

Anti-neuroinflammatory polyoxygenated lanostanoids from Chaga mushroom Inonotus obliquus.

Chaga mushroom, Inonotus obliquus, was used as food and nutrient food and traditional herbs in Russia, China and Japan, with anti-inflammatory and anticancer activities. Chemical investigations of the fruiting bodies of Chaga were carried to uncover the bioactive metabolites. As a result, seven undescribed lanostane-type triterpenoids, namely inonotusols H-N, were isolated, and all lanostanoids remarkably inhibited NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Of these, inonotusols I and L presented the most potent inhibitory effects on inducible nitric oxide synthase (iNOS) and NO production without any significant cytotoxicity. Molecular docking studies confirmed the capacity of inonotusols I and L to interact with iNOS protein. Structure-activity relationships were also discussed. These results indicated that the potential anti-inflammatory effects of inonotusols I and L in microglial BV-2 cells may be imparted through suppression of iNOS. These results may support the use of I. obliquus for food and medicinal application.

Phenolic and Steroidal Metabolites from the Cultivated Edible Inonotus hispidus Mushroom and Their Bioactivities.

A chemical study on the fruiting bodies of cultivated edible mushroom Inonotus hispidus resulted in 14 metabolites including three new hispolon congeners, named inonophenols A-B and one new lanostane triterpenoid, named inonoterpene A. These structures were identified by NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) data analysis. All metabolites were assessed for neurotrophic, anti-inflammatory, and antioxidative activities. Among them, inonophenols B and C were the most active in promoting PC-12 cell neurite outgrowth at a concentration of 10 µM. The phenolic derivatives reduced NO generation by lipopolysaccharide (LPS)-induced BV-2 microglial cells by suppressing the expression of toll-like receptor-4 (TLR-4) and the nuclear factor-kappa-B (NF-κB) signaling pathway as well as the inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the phenolics showed antioxidant effects in DPPH scavenging assay with the IC50 values of 9.82-21.43 µM. These findings showed that I. hispidus may be a new source of neurotrophic and protective agents against neurodegenerative disorders.

Photoperiod-dependent release of suppression pheromone in the male lobster cockroach Nauphoeta cinerea.

The complex agonistic repertoire between male lobster cockroaches (Nauphoeta cinerea) makes this species an excellent model for aggression studies. During the establishment of dominance hierarchies, 3-hydroxy-2-butanone (3H-2B) functions as a suppression pheromone, keeping the rivals in a submissive state. In the present study, we evaluated the release of 3H-2B by dominant individuals across four different time phases within the 24-h photoperiod, i.e., early scotophase (ES), late scotophase (LS), early photophase (EP), and late photophase (LP). For each time phase, we collected volatile pheromones during a 60-min first-encounter fight to measure the level of released 3H-2B. Subsequently, the amount of 3H-2B remaining in the sternal glands of dominant and subordinate individuals was measured and compared to socially naïve male controls. Release of 3H-2B was relatively high during ES or LP first-encounter fights, compared to LS or EP encounters. The attack duration and aggressive posture intensity in dominant males were positively correlated with the amount of 3H-2B release in all four phases. A similar statistical distribution was found between the amount of 3H-2B released by dominant males and the amount of 3H-2B in the sternal glands of naïve male sternal during LS, EP, and LP. However, during ES, the statistical distribution of 3H-2B released by the dominant was significantly greater than the distribution of 3H-2B content in socially naïve male sternal glands. The observed phase-dependence of 3H-2B release might be due to variations in 3H-2B biosynthesis or the scotophase-specific behavior of naïve males, wherein an aggressive posture is spontaneously adopted with concomitant 3H-2B release.

The impacts of zanubrutinib on immune cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

Ibrutinib, a first-generation Bruton's tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. Whether zanubrutinib, a second-generation selective BTK inhibitor, has similar effects as ibrutinib remains to be determined. Dynamics of number and immunophenotype of immune cells during zanubrutinib treatment in 25 R/R CLL/SLL patients were examined by flow cytometry and blood routine tests. The expression intensity of programmed death-1 (PD-1) on total CD4+ (P < .01), total CD8+ (P < .01), and T helper cells (P < .05) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on total CD4+ (P = .010) and regulatory T cells (P < .05) reduced after treatment. There were significant differences in expression intensity of CD19 (P < .01), C-X-C chemokine receptor type 5 (CXCR5) (P < .01), and CD49d (P < .05) on B cells before and after treatment. Downregulation of PD-1 on T cells and CXCR5 and CD19 on B cells were observed in nearly all patients after zanubrutinib treatment. Programmed death-ligand 1 expression downregulated, especially in the female, CLL, normal spleen, normal ß2-macroglobulin (ß2-MG) and abnormal lactate dehydrogenase (LDH) subgroups, and CTLA-4 expression on CD4+ T cells tended to decrease in the male, old, CLL, splenomegaly, abnormal ß2-MG, normal LDH, IGHV-mutated and wild-type tumor protein 53 subgroups after zanubrutinib treatment. These findings suggest that zanubrutinib can regulate immunity primarily by improving T cell exhaustion, inhibiting suppressor cells and disrupting CLL cells migration through downregulation of adhesion/homing receptors. Furthermore, favorable changes in cell number and immunophenotype were preferably observed in patients without adverse prognostic factors.

New cyathane diterpenoids with neurotrophic and anti-neuroinflammatory activity from the bird's nest fungus Cyathus africanus.

Eleven new cyathane diterpenoids, designated cyafricanins A-K (1-11), were isolated from the culture broth of the baisidiomycete Cyathus africanus (Nidulariaceae, Bird's nest fungi). Their structures were elucidated by comprehensive analysis of their NMR and HRESIMS data. Cyafricanins A (1) was found to possess an unusual 3,4-seco­carbon skeleton. All compounds were evaluated for their neurotrophic activity in PC-12 cells and anti-neuroinflammatory activity in BV2 microglia cells. All of the diterpenoids showed nerve growth factor induced neurite outgrowth-promoting activity at concentration of 20 µM. Among them, cyafricanin B (2) and cyafricanin G (7) exhibited promising neurotrophic activity, and cyafricanin A (1) showed strong inhibitory effects on both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, molecular docking studies revealed that cyafricanin A (1) showed strong interactions with the iNOs protein in the active cavity.

Winner and loser effects in lobster cockroach contests for social dominance.

In the context of animal aggression, the winner/loser effect is a cross-taxa phenomenon. In the present study, the effect of social contest experience on winning and losing subsequent encounters was investigated in the furious male lobster cockroach, Nauphoeta cinerea. Dominant and subordinate individuals were generated as the result of an encounter between two socially naïve males (SNMs); the winner and loser were designated as 1st encounter dominants and 1st encounter subordinates, respectively. With these dominants and subordinates, three experiments were conducted: (I) the original pair met in a re-encounter, (II) the 1st encounter dominants and subordinates were paired with an inexperienced SNM, (III) the 1st encounter dominants and subordinates were paired with an experienced individual of the same rank. Each experiment was conducted at 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks after the 1st encounter fight. Juvenile hormone (JH) III titer was monitored in all individuals before and after each subsequent encounter. Our results showed that, in the original pairing and in the pairing with SNMs, the probability that a 1st encounter dominant (or subordinate) would win (or lose) the subsequent encounter fit well with the 95% confidence interval of the theoretical criteria proposed by Begin et al. (1969), indicating the existence of the winning/losing effect. However, this effect was inconsistent along the five-week observation period. For all 1st encounter dominants, at each week after the 1st encounter, the before subsequent encounter JH III titers distribution was significantly different from that on the 1st encounter day; the distributions of before subsequent encounter JH III titers could be further clustered into two groups, the higher JH III group and the lower JH III group, which were significantly correlated with subsequent winning and losing, respectively. For the 1st encounter subordinates, the distributions of before subsequent encounter JH III titers were not significantly different from that of SNMs, but the titer distributions were significantly shifted to a higher level compared to the 1st encounter day. Compared with before subsequent encounter, the after subsequent encounter hemolymph JH III level was significantly increased in winners and significantly decreased in losers. From these data, we propose that instability of the winner and loser effects may occur due to physiological costs and recovery; this instability may partly explain why the social hierarchy is unstable in this cockroach species.

Cyathane diterpenoids and drimane sesquiterpenoids with neurotrophic activity from cultures of the fungus Cyathus africanus.

Five terpenoids, including two new cyathane diterpenoids neocyathin S (1) and neocyathin T (2), together with three drimane sesquiterpenoids, one known 3ß,6ß-dihydroxycinnamolide (3), two new ones 3ß,6α-dihydroxycinnamolide (4) and 2-keto-3ß,6ß-dihydroxycinnamolide (5), were isolated from the cultures of the basidiomycete Cyathus africanus. Their structures were established based on extensive spectroscopic methods including 2D NMR (HSQC, 1H‒1H-COSY, HMBC, ROESY) and HRESIMS experiments. The absolute configurations of two pairs of epimers, 1 and 2 as well as 3 and 4, were determined by ECD quantum chemical calculation. All the five compounds enhanced nerve growth factor (NGF)-mediated neurite outgrowth using rat pheochromocytoma (PC12) cells at concentration 10 µM.

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities.

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A-J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal Basidiomycete Cyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K-R (1-8), were isolated from the solid culture of C. africanus cultivated on cooked rice, together with three known congeners (9-11). The structures and the absolute configurations of the new compounds were elucidated through comprehensive NMR and HRESIMS spectroscopic data, electronic circular dichroism (ECD) data, and chemical conversion. Compounds 1 and 2 represent the first reported naturally occurring compounds with 4,9-seco-cyathane carbon skeleton incorporating an unprecedented medium-sized 9/7 fused ring system, while the 3,4-seco-cyathane derivative (3) was isolated from Cyathus species for the first time. All compounds were evaluated for their neurotrophic and anti-neuroinflammatory activity. All the isolates at 1-25 µM displayed differential nerve growth factor (NGF)-induced neurite outgrowth-promoting activity in PC-12 cells, while one of the compounds, allocyathin B2 (11), inhibited NO production in lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. In addition, molecular docking studies showed that compound 11 generated interactions with the inducible nitric oxide synthase (iNOS) protein.

TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia.

OBJECTIVES: Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. METHODS: TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. RESULTS: Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, ß2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). CONCLUSION: Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL.