Long-term outcomes and prognostic factors in dogs with meningoencephalitis of unknown origin and suspected necrotic lesions on magnetic resonance imaging: 37 cases (2007-2020).

OBJECTIVE: To describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in dogs with necrotizing encephalitis (NE). ANIMALS: 37 client-owned dogs clinically diagnosed with NE. METHODS: All dogs underwent MRI and CSF analysis. Cox proportional hazards regression was used to examine factors related to the risk of relapse and death, including signalment, history, diagnostic investigation results, and treatments before the first relapse. RESULTS: The medians of the overall and progression-free survival times were 639 days (IQR, 342 to 1,482 days) and 233 days (IQR, 111 to 775 days), respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months (OR, 3.26; 95% CI, 1.35 to 7.90) was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%. CLINICAL RELEVANCE: This report provides comprehensive follow-up information for dogs with NE, revealing a fair prognosis and low early mortality rate. Seizure is a very common clinical sign with a high recurrence rate.

Biochemical and Genetic Basis of Guanacastane Diterpene Biosynthesis in Basidiomycete Fungi.

Guanacastane diterpenoids with an unusual 5/7/6 tricyclic skeleton mainly produced by basidiomycete fungi represent a structurally intriguing class of natural products. While the chemical synthesis of several members has been achieved, the biochemical and genetic basis of their biosynthesis remain unknown. Herein, we present the identification and characterization of two crucial enzymes in the biosynthesis of guanacastane diterpenoids in Psathyrella candolleana. Heterologous expression reveals that PsaD, a typical class I diterpene synthase, catalyzes the cyclization of geranylgeranyl diphosphate to form a new guanacastane-type diterpene, guanacasta-1,3-diene (7). Moreover, we demonstrate that PsaA, a cytochrome P450 monooxygenase, can catalyze multiple oxidations of 7 to yield guanacastepene U (8). These results provide new opportunities for genome mining and metabolic engineering of guanacastane diterpenoids.

Outcomes in Dogs with Multiple Sites of Cervical Intervertebral Disc Disease Treated with Single Ventral Slot Decompression.

In dogs with acute myelopathy but showing multiple sites of spinal compression from intervertebral disc disease (IVDD) on imaging, one approach is surgical decompression of the single acute disc extrusion while ignoring other previously extruded or protruded discs. However, little is known regarding the outcomes of this approach. This study described the outcomes and investigated prognostic factors in 40 dogs with multiple sites of cervical disc extrusion or protrusion on MRI who underwent ventral slot decompression for the single acute disc. The overall recovery rate was 97.5%. The median recovery time was seven days. The number of affected discs (including disc extrusion and protrusion) and the presence and number of the affected discs causing severe spinal compression did not influence the 30-day outcome. Compared with 23 dogs with single disc extrusion treated surgically, the recovery time and outcomes were similar between the two groups. The total number of affected discs was not associated with recovery time or outcomes. In conclusion, if an acute disc could be identified, ventral slot decompression targeting the single acute disc is a viable management approach for dogs with an acute presentation but diagnosed with multiple sites of spinal cord compression from IVDD.

Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa. PURPOSE: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells. METHODS: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling. RESULTS: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts. CONCLUSIONS: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

Feasibility and Validity of Postural Reaction Tests in the Neurological Examination in Healthy Rabbits.

Neurological examination remains a fundamental step in the care of patients with neurological disorders. However, studies evaluating the feasibility and validity of neurological examination in rabbits are limited. In this study, postural reaction tests or methods commonly performed in dogs and cats were evaluated in clinically healthy rabbits, and we aimed to postulate a simplified examination list according to the results. The feasibility and validity of each test were determined and screened using a cut-off value of 90%. For the remaining tests/methods, the response rates of tests with similar neuroanatomical pathways were compared. Among the 34 healthy rabbits tested, one method of the hopping reaction (holding then lowering the rabbit quickly towards the floor with only the tested limb touching the ground), the hemi-walking test, the wheelbarrowing test, and the righting response yielded a feasibility and validity of over 90%. When comparing tests/methods with similar neuroanatomical pathways, the normal response rate of the hopping reaction was comparable to that of the hemi-walking test. We conclude that in healthy rabbits, hopping reaction tests using the method mentioned above, hemi-walking, wheelbarrowing, and righting responses are likely to be feasible postural reaction tests that yield consistent and normal responses.

MCU Upregulation Overactivates Mitophagy by Promoting VDAC1 Dimerization and Ubiquitination in the Hepatotoxicity of Cadmium.

Cadmium (Cd) is a high-risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd-induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd-induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP-response element binding protein at Ser133(CREBS133 ) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage-dependent anion-selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity.

Multicore Fiber Bending Sensors with High Sensitivity Based on Asymmetric Excitation Scheme.

Bending sensing was realized by constructing a tapered four-core optical fiber (TFCF) sensor. The four-core fiber (FCF) between the fan-in and fan-out couplers was tapered and the diameter became smaller, so that the distance between the four cores arranged in a square became gradually smaller to produce supermodes. The two ends of the TFCF were respectively connected to the fan-in and fan-out couplers so that the individual cores in the FCF could link to the separate single-mode fibers. A broadband light source (superluminescent diodes (SLD)) spanning 1250-1650 nm was injected into any one of the four cores, and the orientation was thus determined. In the tapering process, the remaining three cores gradually approached the excitation core in space to excite several supermodes based on the tri-core structure first, and then transited to the quadruple-core structure. The field distributions of the excited supermodes were asymmetric due to the corner-core excitation scheme, and the interference thus resulted in a higher measurement sensitivity. When the diameter of the TFCF was 7.5 µm and the tapered length was 2.21 mm, the sensitivity of the bending sensor could reach 16.12 nm/m-1.

Aspalathus linearis suppresses cell survival and proliferation of enzalutamide-resistant prostate cancer cells via inhibition of c-Myc and stability of androgen receptor.

Enzalutamide, a nonsteroidal antiandrogen, significantly prolonged the survival of patients with metastatic castration-resistant prostate cancer (CRPC). However, patients receiving enzalutamide frequently develop drug resistance. Rooibos (Aspalathus linearis) is a shrub-like leguminous fynbos plant endemic to the Cedarberg Mountains area in South Africa. We evaluated the possibility of using a pharmaceutical-grade green rooibos extract (GRT, containing 12.78% aspalathin) to suppress the proliferation and survival of enzalutamide-resistant prostate cancer (PCa) cells. Treatment with GRT dose-dependently suppressed the proliferation, survival, and colony formation of enzalutamide-resistant C4-2 MDV3100r cells and PC-3 cells. Non-cancerous human cells were more resistant to GRT treatment. GRT suppressed the expression of proteins involved in phosphoinositide 3-kinase (PI3K)-Akt signaling, androgen receptor (AR), phospho-AR (Ser81), cyclin-dependent kinase 1 (Cdk1), c-Myc and Bcl-2 but increased the expression of apoptotic proteins. Overexpression of c-Myc antagonized the suppressive effects of GRT, while knockdown of c-Myc increased the sensitivity of PCa cells to GRT treatment. Expression level of c-Myc correlated to resistance of PCa cells to GRT treatment. Additionally, immunofluorescence microscopy demonstrated that GRT reduced the abundance of AR proteins both in nucleus and cytoplasm. Treatment with cycloheximide revealed that GRT reduced the stability of AR. GRT suppressed protein expression of AR and AR's downstream target prostate specific antigen (PSA) in C4-2 MDV3100r cells. Interestingly, we observed that AR proteins accumulate in nucleus and PSA expression is activated in the AR-positive enzalutamide-resistant PCa cells even in the absence of androgen. Our results suggested that GRT treatment suppressed the cell proliferation and survival of enzalutamide-resistant PCa cells via inhibition of c-Myc, induction of apoptosis, as well as the suppression of expression, signaling and stability of AR. GRT is a potential adjuvant therapeutic agent for enzalutamide-resistant PCa.

High Sensitivity Fiber Interferometric Strain Sensors Based on Elongated Fiber Abrupt Tapers.

We demonstrate high-sensitivity fiber strain sensors based on an elongated abrupt taper. The fiber abrupt taper, with a tapered diameter ranging from 40-60 µm, was made by using a hydrogen microflame to break the waveguide adiabaticity so as to convert the fundamental mode into cladding modes. The abrupt taper was further uniformly tapered by using a normal moving flame with a torch diameter of 7 mm to elongate the tapered region until the tapered diameter was down to 2.5-5 µm. The excited high-order modes were confined to propagate along the cladding and then recombined at the rear edge of the fiber taper to produce interferences with extinction ratios of up to 16 dB. The tapered region was pulled outwardly to change the optical path difference (OPD) between modes to measure the tensile strain with all the interfering wavelengths blue-shifted. The measured best strain sensitivity was 116.21 pm/µÎµ and the coefficient of determination R2 of linear fitting exhibits high linearity. This strain sensor based on elongated abrupt taper is several times higher than that of most of the fiber strain sensors ever reported.

Assessment of the cutaneous trunci muscle reflex in healthy cats: comparison of results acquired by clinicians and cat owners.

OBJECTIVES: The study aimed to evaluate the cutaneous trunci muscle reflex (CTMR) in healthy cats using methods performed by the clinician and the cat's owner at home. METHODS: A total of 55 healthy cats without neurological abnormalities were included in this study. CTMR evaluation was performed sequentially in each cat using three methods by a clinician: method A, pinch skin with a straight 14 cm Crile haemostat forceps; method B, displace fur with the tip of a pen or haemostat forceps; and method C, poke skin with the tip of a straightened paper clip. The normal response rates for each method were obtained and compared. A 'CTMR performance score' was assigned for each cat, reflecting the presence of a normal CTMR response using one or more of the three methods. An 'owner performance score' was also obtained, reflecting the response of the CTMR when performed at home by the cat owner. The two scores were compared as paired data for each cat. RESULTS: The CTMR was elicited normally in 17 (31%), 27 (49%) and 16 (29%) cats using methods A, B and C, respectively. Method B delivered a significantly higher percentage of normal responses. When comparing the 'CTMR performance score' and 'owner performance score', the percentage of normal responses was 60% and 100%, respectively, which was significantly different. CONCLUSIONS AND RELEVANCE: The overall normal response rate of the CTMR in healthy feline subjects was low when performed by a clinician, regardless of the method applied. Conversely, a high percentage of normal responses was obtained by cat owners performing CTMR at home, potentially indicating the impact of stress on the CTMR performance.

High Sensitivity Strain Sensors Using Four-Core Fibers through a Corner-Core Excitation.

A weakly-coupled multicore fiber can generate supermodes when the multi-cores are closer to enter the evanescent power coupling region. The high sensitivity strain sensors using tapered four-core fibers (FCFs) were demonstrated. The fan-in and fan-out couplers were used to carry out light coupling between singlemode fibers and the individual core of the FCFs. A broadband lightsource from superlumminescent diodes (SLDs) was launched into one of the four cores arranged in a rectangular configuration. When the FCF was substantially tapered, the asymmetric supermodes were produced to generate interferences through this corner-core excitation scheme. During tapering, the supermodes were excited based on a tri-core structure initially and then transited to a rectangular quadruple-core structure gradually to reach the sensitivity of 185.18 pm/µÔ‘ under a tapered diameter of 3 µm. The asymmetric evanescent wave distribution due to the corner-core excitation scheme is helpful to increase the optical path difference (OPD) between supermodes for improving the strain sensitivity.

[Effects of Feedstock Material and Pyrolysis Temperature on Dissolved Organic Matter in Biochars].

The aim of this study was to investigate the effects of feedstock material and pyrolysis temperature on the content and spectral properties of dissolved organic matter(DOM) in biochars. Biochars were produced from the pyrolysis of rice straw and Cunninghamia lanceolata litter at three temperatures(350, 500, and 650℃). The results showed that the pH values of the two biochars with pyrolysis temperature increases were improved from 8.10 and 6.56 to 10.53 and 8.23, respectively. The pyrolysis temperature had no significant effect on the total C content of biochar, but the feedstock material and their interaction had significant effects on the total C content of the biochar(P<0.05). The dissolved organic carbon(DOC) content of the two types of biochar first decreased and then increased with increasing pyrolysis temperature, and the content of DOC of the biochar derived from rice straw was significantly higher than that from Cunninghamia lanceolata litter under the same temperature(P<0.05). The feedstock material had no significant effect on the SUVA254 value of DOM, but temperature and its interactive effect with the feedstock material had a significant effect on the SUVA254 values(P<0.05). Maximum DOC SUVA254 values occurred at 500℃ in the two types of biochar, indicating the highest degree of aromatization. Three-dimensional fluorescence spectra showed that the DOM components of the two types of biochar were dominated by fulvic acid-like and humic acid-like material, which had different responses to pyrolysis temperature. FTIR spectra suggested that the DOM of the biochars had absorption peaks at similar positions, in five regions, and the stretching vibration of aliphatic C-H gradually weakened with an increase in pyrolysis temperature. Therefore, the biochars produced at higher pyrolysis temperatures(500℃ and 650℃) had lower DOC contents but a higher aromatization degree and humification degree, and were more stable, compared to the biochars produced at a lower pyrolysis temperature(350℃).

Lifetime elongation of quantum-dot light-emitting diodes by inhibiting the degradation of hole transport layer.

Developing a colloidal quantum-dot light-emitting device (QDLED) with high efficiency and good reliability is necessarily preliminary for the next-generation high-quality display application. Most QDLED reports are focused on efficiency improvement, but the device operational lifetime issue is less addressed and also the relevant degradation mechanisms. This study achieved a 1.72 times elongation in the operational lifetime and a 9 times improvement in the efficiency of QDLED by inserting a hole-transporting/electron-blocking poly(9-vinylcarbazole) (PVK) layer, which prevented operational degradation on poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-secbutylphenyl))-diphenylamine)] (TFB) hole-transporting layer and also confined the electron in the QD-emitting layer. Although the TFB/PVK HTL structure is a well-known pair to enhance the device performance, its detailed mechanisms were rarely mentioned, especially for relative operational lifetime issues. Herein, a new insight behind operational lifetime elongation of QDLED is disclosed through various fundamental experiments including steady-state photoluminescence, transient electroluminescence and single-carrier only devices. Evidently, other than QD degradation, this study found that the other crucial factor that decreased the device lifetime was TFB-HTL degradation using steady-state photoluminescence and transient electroluminescence analyses. The PVK electron-only device exhibited a stable voltage value when it was driven by fixed current, which also affirmed that PVK has excellent electron-stability characteristics.

Diagnosis of meningeal melanomatosis in a dog using magnetic resonance imaging and cerebrospinal fluid findings.

A 13-year-old spayed female Labrador Retriever was presented with severe progressive tetraparesis. The neuroanatomic localization was the C1-C5 spinal cord segments with brainstem or cranial nerve involvement. Magnetic resonance imaging revealed diffuse T1-weighted and T2-weighted hyperintense lesions with strong contrast enhancement spreading through meninges of the cervical spinal cord and the brain. Few small round areas showing T1-weighted hyperintensity and T2-weighted hypointensity were scattered within the lesions. Cerebrospinal fluid analysis revealed neoplastic round cells and possible melanocytes. Malignant melanoma was suspected. At necropsy, the brain and the entire spinal cord were covered with thick, dark membranous tissue. Based on histopathologic findings, a positive response against Melan-A, and no melanoma identified outside the central nervous system, primary meningeal melanomatosis was diagnosed.

Evaluation of extracellular matrix protein expression and apoptosis in the uterosacral ligaments of patients with or without pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: This study aimed to compare the expression levels of extracellular matrix (ECM) and apoptosis proteins in the uterosacral ligament (USL) of patients with and without pelvic organ prolapse (POP). METHODS: The USL were obtained from patients with POP-Q ≥ III (n = 35) and without POP (n = 20). Immunohistochemistry (IHC) staining and RT-qPCR were conducted to assess the protein and mRNA levels, respectively. The levels of type I collagen (COLI), type III collagen (COLIII), matrix metalloproteinase (MMP)1, MMP2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, estrogen receptor (ER)α, ERß and apoptosis-related gene B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax) in the USL were analyzed. RESULTS: The protein expression and mRNA levels of MMP2 and MMP9, mRNA levels of BAD and BAX, and protein expression of active cleaved-Caspase3 were significantly higher in the POP group. There were no evident differences in COLIII, MMP1 or ERß expression at either the mRNA or protein level or in TIMP1, TIMP2 or Caspase3 by IHC between the two groups. However, obvious decreases in COLI and ERα were evident at both the mRNA and protein levels in the POP group, and the mRNA levels of TIMP1 and TIMP2 were also decreased compared to those of the control group. CONCLUSION: ECM in the USL tissues of POP patients is remodeled compared with non-POP patients and is characterized by decreased synthesis and increased degradation of collagen; moreover, the levels of the main proteins involved in apoptosis are increased in POP tissue.

Respiratory pattern intervention can quickly improve the oral feeding of pre-term infants with suck-swallow-breath coordination disorder / 中华物理医学与康复杂志

Objective:To investigate the effect of a breathing pattern intervention (RPI) on the oral feeding of pre-term infants with suck-swallow-breath (SSwB) coordination disorder.Methods:Sixty pre-term infants with SSwB coordination disorder were divided into an observation group ( n=30) and a control group ( n=30) using a random number table. Both groups were given routine feeding training, including oral exercise intervention, non-nutritive sucking training, and swallowing induction training during nursing, while the observation group was additionally provided with 15 minutes of breathing pattern training once a day, including breathing pattern observation, resistive breathing training prior to eating and passive breathing pattern intervention during eating. Before and after the 7-day intervention, the Pre-term Infant Oral Feeding Readiness Assessment (PIOFRA) was used to evaluate each subject′s oral feeding ability. Rate of transfer (RT), proficiency (PRO), minimum oxygen partial pressure (SaO 2) and SaO 2 fluctuations were also recorded during the feeding process. Results:After 1 week of the intervention, significant improvement was observed in both groups. In the observation group the average RT (2.76±0.36ml/min), PRO, minimum SaO 2, the number of SaO 2 fluctuations, and PIOFRA score (33.28±0.58) were all significantly better than the control group′s averages. Conclusion:Breathing pattern intervention based on routine feeding training can enhance breathing coordination during swallowing and ultimately improve the oral feeding of pre-term infants with SSwB coordination disorders in a relatively short period of time.

Effects of ginsenoside Re on intestinal mucosa of mice with severe acute pancreatitis and its regulation mechanism / 解剖学报

Objective To explore the effect and mechanism of ginsenoside Re on the intestinal mucosa of severe acute pancreatitis (SAP) mice by regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/ STAT3) pathway. Methods Totally 48 mice were divided into : control group, SAP group, SAP + ginsenoside Re group and SAP + ginsenoside Re + LY2784544 group (n = 12). The mice were intraperitoneally injected with caerulein solution (after fasting for 12 hours, 100 μg/kg, 6 times, injection interval 60 minutes) to establish SAP models. Mice in the SAP+ ginsenoside Re group were intraperitoneally injected with ginsenoside Re (4 mg/kg, 1 time a day for 7 consecutive days). Intraperitoneal injection of 12.7 mg/kg LY2784544 was used to inhibit the JAK2/STAT3 pathway. Pancreatic and intestinal mucosal injury were detected in each group. The wet to dry weight ratio of pancreas, serum amylase and inflammatory factor levels were detected in each group. The intestinal mucosal barrier function was analyzed by detecting the levels of D-lactic acid and fluorescein isothiocyanate dextran (FITC-D). The damage of pancreatic tissue and intestinal mucosa tissue was observed by HE staining. Western blotting was used to detect the levels of apoptotic proteins Bax and Bcl-2 in the intestinal mucosa. The JAK2/STAT3 pathway expression levels in pancreatic tissue and intestinal mucosa tissue were detected by Realtime PCR and Western blotting. Results The pancreatic index, serum amylase, interieukin 6 (IL-6) and tumor necrosis factor a (TNF-a), FITC-D, D-lactic acid, Bax protein levels, JAK2 and STAT3 mRNA and protein levels in the SAP group were significantly higher than those in the control group, while Bcl-2 protein was significantly lower than that in the control group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re group was significantly higher than that of SAP group, and other indexes were significantly lower than those in SAP group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re+ LY2784544 group was significantly higher than that of SAP + ginsenoside Re group, and other indexes were significantly lower than those in the SAP+ginsenoside Re group (P<0.05). Conclusion Ginsenoside Re may reduce the pancreatic injury in SAP model mice by inhibiting the JAK/STAT pathway to alleviate the inflammatory response, and may protect the small intestinal mucosal barrier by alleviating pancreatitis and inhibiting the intestinal mucosal JAK/STAT pathway to inhibit cell apoptosis.

Psathyrins: Antibacterial Diterpenoids from Psathyrella candolleana.

Two skeletally novel tetracyclic diterpenoids, psathyrins A (1) and B (2), have been characterized from cultures of the basidiomycete Psathyrella candolleana. Their structures including absolute configurations were established by means of spectroscopic methods, as well as ECD calculations. They possess a novel 5/5/4/6-fuesd ring system, for which the biosynthetic pathway is proposed. Compounds 1 and 2 inhibited the growth of Staphylococcus aureus and Salmonella enterica.

Sesquiterpenoids from Cultures of the Basidiomycetes Irpex lacteus.

Eight previously undescribed sesquiterpenoids, tremutins A-H (1-8), together with three known ones (9-11), were isolated from cultures of the basidiomycetes Irpex lacteus. Structures of the new compounds together with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single-crystal X-ray diffractions and equivalent circulating density calculations. Compounds 1 and 2 possess an unusual 6/7-fused ring system that might be derived from a tremulane framework. Compounds 3-7 and 9-11 are tremulane sesquiterpenoids of which 4 and 5 are the first tremulane examples with a 1,2-epoxy moiety to be reported. Compounds 6, 7, 10, and 11 possess weak activities to several human cancer cell lines. Compound 8 shows a weak inhibitory effect on NO production with a half maximal inhibitory concentration (IC50) value of 22.7 µM. Compound 1 inhibits the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with an IC50 value of 22.4 µM, while 2 inhibits concanavalin A (Con A)-induced T cell proliferation and LPS-induced B lymphocyte cell proliferation with IC50 values of 16.7 and 13.6 µM, respectively.