HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy.

Rationale: Primordial follicles are limited in number and cannot be regenerated, dormant primordial follicles cannot be reversed once they enter a growth state. Therefore, the length of the female reproductive lifespan depends on the orderly progression and selective activation of primordial follicles, the mechanism of which remains unclear. Methods: We used human ovarian cortical biopsy specimens, granulosa cells from diminished ovarian reserve (DOR) patients, Hdac6-overexpressing transgenic mouse model, and RNA sequencing to analyze the crucial roles of histone deacetylase 6 (HDAC6) in fertility preservation and primordial follicle activation. Results: In the present study, we found that HDAC6 was highly expressed in most dormant primordial follicles. The HDAC6 expression was reduced accompanying reproductive senescence in human and mouse ovaries. Overexpression of Hdac6 delayed the rate of primordial follicle activation, thereby prolonging the mouse reproductive lifespan. Short-term inhibition of HDAC6 promoted primordial follicle activation and follicular development in humans and mice. Mechanism studies revealed that HDAC6 directly interacted with NGF, reducing acetylation modification of NGF and thereby accelerating its ubiquitination degradation. Consequently, the reduced NGF protein level maintained the dormancy of primordial follicles. Conclusions: The physiological significance of the high expression of HDAC6 in most primordial follicles is to reduce NGF expression and prevent primordial follicle activation to maintain female fertility. Reduced HDAC6 expression increases NGF expression in primordial follicles, activating their development and contributing to reproduction. Our study provides a clinical reference value for fertility preservation.

The role of the indoleamine 2,3-dioxygenase gene in preventing ovarian transplant rejection in rats.

Indoleamine 2, 3-dioxygenase (IDO) plays important roles in maternal immune tolerance. Female Sprague Dawley rats (9-11 weeks old) were randomly divided into an autoplastic transplantation group (n = 75) and an allograft transplantation group (n = 300) further divided into subgroups of ovarian transplantation, allograft ovarian transplantation, allograft ovarian transplantation with cyclosporine A treatment, allograft ovarian transplantation and transfection with IDO-expressing lentiviruses, and allograft ovarian transplantation and transfection with control lentiviruses. IDO was successfully transfected intothe transplanted ovarian tissue. The survival rate, success rate of ovarian transplantation, period until estrous cycle restoration, and estrogen levels of rats that received IDO-expressing lentiviruseswere significantly different from those of rats that underwent allograft transplantation and with control transfection (all P < 0.05), but not significantly different from those of rats that received autoplastic transplantation (all P > 0.05). The number of ovarian follicles in the transplanted ovarian tissue of rats that received IDO-expressing lentiviruses was also significantly higher. The expression level of IDO protein detected by immunohistochemistry and western blotting was especially high in ovaries that had received IDO-containing lentiviruses. Naturally pregnant rats were found in each group postoperatively. These results indicate that IDO-expressing lentiviruses were successfully transfected into transplanted ovarian tissues of rats and that IDO was stably expressed within a certain time. These findings suggest that the expression level of IDO protein is associated with an enhanced success rate of ovarian tissue transplantation and a short restoration period of endocrine function.

Formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus globulus subsp. maidenii and their ATP-citrate lyase inhibitory activities.

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.

Stem cell therapy for insulin-dependent diabetes: Are we still on the road?

In insulin-dependent diabetes, the islet ß cells do not produce enough insulin and the patients must receive exogenous insulin to control blood sugar. However, there are still many deficiencies in exogenous insulin supplementation. Therefore, the replacement of destroyed functional ß cells with insulin-secreting cells derived from functional stem cells is a good idea as a new therapeutic idea. This review introduces the development schedule of mouse and human embryonic islets. The differences between mouse and human pancreas embryo development were also listed. Accordingly to the different sources of stem cells, the important research achievements on the differentiation of insulin-secreting ß cells of stem cells and the current research status of stem cell therapy for diabetes were reviewed. Stem cell replacement therapy is a promising treatment for diabetes, caused by defective insulin secretion, but there are still many problems to be solved, such as the biosafety and reliability of treatment, the emergence of tumors during treatment, untargeted differentiation and autoimmunity, etc. Therefore, further understanding of stem cell therapy for insulin is needed.

A Signature of Genes Featuring FGF11 Revealed Aberrant Fibroblast Activation and Immune Infiltration Properties in Keloid Tissue.

Keloid is a fibroproliferative disorder in the skin, which manifested with extensive deposition of collagen and extracellular matrix. Its etiology remains a mystery and its recurrence rate remains high despite combinative treatment regimens. Current hypotheses of its pathogenesis centered on the role of inflammatory processes as well as immune infiltration in the microenvironment. However, there are a lot of discrepancies when it comes to the verification of certain well-recognized pathways involved in the dysfunctional fibroblast. Further exploration and characterization are required to reveal the driving force and even leading genes responsible for keloid formation. In this study, we provided supportive evidence of the immunologic nature of keloids distinct from normal fibroblasts and physiological scars by incorporating multiple available expressional profiles in the Gene Expression Omnibus (GEO). Through differential analyses and functional analyses, we identified a set of genes that successfully captures the dissimilarities between keloid lesions and nonlesions. They were differentially regulated in keloid samples and had opposite behavior in exposure to hydrocortisone. A key signature of six genes featuring FGF11 not only was highly correlated with significantly dysregulated fibroblast activation but also reflected various levels of immune cell infiltration. FGF11, in particular, revealed the heterogenous immunologic nature of keloid lesions. This study further supported that aberrant fibroblast was one of the main contributing factors and shed some light on investigating immune properties in future studies.

Vesicular Stomatitis Virus-Based Epstein-Barr Virus Vaccines Elicit Strong Protective Immune Responses.

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.

Development of an LB cloning system and its application in expression of fusion genes in Sphingomonas sp. WG / 生物工程学报

In order to overcome the challenges of insufficient restriction enzyme sites, and construct a fusion-expression vector with flexible fusion direction, we designed an LB cloning system based on the type IIS and type IIT restriction enzymes LguⅠ and BbvCⅠ. The LB cloning system is constructed by inserting the LB fragment (GCTCTTCCTCAGC) into the multiple cloning site region of the broad-host plasmid pBBR1MCS-3 using PCR. The LB fragment contains partially overlapped recognition sites of LguⅠ and BbvCⅠ. Therefore, the same non-palindromic sequence will be generated by these two restriction endonucleases digestion. This feature can be used to quickly and flexibly insert multiple genes into the expression vector in a stepwise and directed way. In order to verify the efficacy of the cloning system, two glycosyltransferase genes welB and welK of Sphingomonas sp. WG were consecutively fused to the LB cloning vector, and the recombinant plasmid was transferred into Sphingomonas sp. WG by triparental mating. The results showed that gene fusion expression has little effect on sphingan titer, but enhanced the viscosity of sphingan. The viscosity of the sphingan produced by recombinant strain Sphingomonas sp. WG/pBBR1MCS-3-LB-welKB was 24.7% higher than that of the wild strain after fermentation for 84 h, which would be beneficial for its application. In conclusion, the application of LB cloning system were verified using Sphingomonas sp. WG. The LB cloning system may provide an efficient tool for fusion expression of target genes.

Ragweed pollen induces allergic conjunctivitis immune tolerance in mice via regulation of the NF-κB signal pathway.

AIM: To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis. METHODS: The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen (RW) and the related cytokines were detected. The mice were divided into 9 groups and the maslinic acid (MA) or PBS were given for different group after modeling. The expression levels of chemokine ligand 5 (CCL5) and P-65 in the conjunctival tissue were analyzed by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The percentage of interleukin-17 (IL-17) and CD4+CD25+ in the splenocyte supernatant was analyzed by flow cytometry. Furthermore, the serum and splenocyte supernatant concentration of total-IgE, interleukin-10 (IL-10), and IL-17 was analyzed by enzyme linked immune response (ELISA). RESULTS: After the model was established, symptoms of conjunctivitis were alleviated, the level of P-65, CCL5, IL-17, and total-IgE was raised, while the expression of IL-10, CD4+CD25+ was decreased. This result fully demonstrated that a typical IL-17/regulatory-T-cells (Treg cells) imbalance and NF-κB activation. When the NF-κB signal pathway was suppressed, it showed that there was a further relief of conjunctivitis in mice. At the same time, the expression of total-IgE, IL-17, and CCL5 was decreased and the expression of anti-inflammatory factor (IL-10, CD4+CD25+) was increased. CONCLUSION: In the state of immune tolerance, symptoms of conjunctivitis in mice are alleviated, the Th-17 cells of allergic conjunctivitis mice are inhibited, and Treg cells activity is enhanced.

Prenatal diagnosis of a fetus with mosaic ring chromosome 13: Case report and review of the literature.

OBJECTIVE: To diagnose the ring chromosome 13 (r(13)) in a fetus, and analyze the genotype-phenotype correlation. CASE REPORT: A 26-year-old woman who was second pregnancy, underwent amniocentesis at 18 weeks of gestation because of the increased nuchal translucency (NT). Prenatal ultrasound showed the NT thickness was 3.5 mm at 12+1 weeks of gestation and nuchal fold (NF) was 6.1 mm at 18 weeks of gestation, and amniotic fluid karyotype analysis revealed mosaic r(13). CMA detected a 16.293 Mb duplication at 13q21.32q31.1 and 31.303 Mb deletion at 13q31.1q34. CONCLUSION: R(13) is a very rare chromosomal abnormality. Cytogenetic examination combined with CMA can provide accurate diagnosis and effective information for genetic counseling.

Clinical Application of Chromosomal Microarray Analysis in Pregnant Women with Advanced Maternal Age and Fetuses with Ultrasonographic Soft Markers.

BACKGROUND In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research. MATERIAL AND METHODS We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA. RESULTS Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P<0.01). More than a half (59.46%, 22/37) of the pregnant women decided to continue their pregnancy despite having a fetus diagnosed with clinically significant CNV. CONCLUSIONS CMA can increase the diagnostic yield of fetal chromosomal abnormality for pregnant women with isolated AMA or/and their fetuses had isolated USG soft markers.

The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.

Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure-activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity at sub-micromolar range, as well as furoquinolinedione derivatives at low micromolar range. The most potent 3-(3,4-dimethoxyphenyl)isoxazolo[4,5-g]quinoline-4,9-dione (70) showed TDP2 inhibitory activity with IC50 of 0.46 ± 0.15 µM. This work will facilitate future efforts for the discovery of isoxazoloquinolinedione TDP2 selective inhibitors.

Silencing of microRNA-3175 represses cell proliferation and invasion in prostate cancer by targeting the potential tumor-suppressor SCN4B.

MicroRNA-3175 (miR-3175) expression is upregulated in prostate cancer, but its roles and the underlying mechanisms in prostate cancer cell growth and invasion need to be elucidated. This study aimed to uncover the roles of miR-3175 in regulating cell growth and migration, as well as the expression of its predicted target gene cardiac sodium channel ß4-subunit gene (SCN4B). Real-time quantitative PCR (RT-qPCR) and/or western blotting techniques were used to measure miR-3175 and SCN4B expression levels in prostate cancer cells. Inhibitor or mimics transfections were used to overexpress or silence miR-3175 in prostate cancer cells. MTT and Edu assays were applied to assess cell viability. Scratch assay and transwell chambers were used to examine cell migration and invasion abilities. The interaction between miR-3175 and SCN4B was determined by means of luciferase gene reporter, RT-qPCR, and western blotting assays. The results showed that miR-3175 expression was increased and SCN4B expression was decreased in prostate cancer cell lines as compared with normal human prostatic epithelial cells. Compared with the control group, knockdown of miR-3175 resulted in strong inhibitions of cell growth, migration, invasion, and N-cadherin expression, together with an increase in E-cadherin expression. In addition, knockdown of miR-3175 dramatically increased the luciferase activity of the luciferase vector of SCN4B, and increased SCN4B expression. Together, this study illustrated that downregulation of miR-3175 repressed the proliferation and invasion of prostate cancer cells, which might be induced by SCN4B downregulation.

Clerodane diterpenoids from Dodonaea viscosa and their inhibitory effects on ATP citrate lyase.

Six undescribed clerodane diterpenoids, dodovisins A-F, together with nine known ones, were isolated from the aerial parts of Dodonaea viscosa (L.) Jacq. Their structures were elucidated by extensive spectroscopic techniques, X-ray crystallographic analysis, and ECD calculation. Dodovisins A and B possess a rare carbon skeleton featuring a bicyclo[6.2.0]decane motif. Dodovisins C-E represent the first clerodane diterpenoids with a 4(5 â†’ 19)-abeo-2,4,10(1)-triene moiety. Dodovisins A, E, and strictic acid showed potent inhibitory activities against ATP citrate lyase.

Epidemiology of Blastocystis infection from 1990 to 2019 in China.

BACKGROUND: Blastocystis is ubiquitous presence in animals and humans worldwide and has a high level genetic diversity. The aim of this study was to conduct a summary of Blastocystis prevalence, subtypes (STs) in humans and animals in China and depict their distribution. METHODS: We searched for the articles related to epidemiology of Blastocystis in humans and animals throughout China which published from January 1, 1990, to July 31, 2019 in the following databases: PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang database. The keywords were Blastocystis and one of the following ones: STs, subtypes, distribution, epidemiology, prevalence, infection, molecular, geographic, intestinal parasites, genetic diversity and characterization. RESULTS: In recent years, various molecular epidemiological studies have been carried out in some provinces/regions of China to identify subtypes of Blastocystis. Infants and young children, school students, hospitalized diarrhea patients, HIV/AIDS patients, tuberculosis patients, and cancer patients as respondents had been included. ST1-ST7 and ST12 were the main subtypes in Chinese population. Moreover, surveys of Blastocystis infection in animal were also conducted in some provinces of China. A variety of animals were investigated including pigs, cattle, sheep, yak, giant panda, and crested ibis (Nipponia nippon) with the main subtypes of ST1-ST8, ST10, ST12-ST14. CONCLUSIONS: In recent years, some provinces/regions in China have conducted various molecular epidemiological studies to identify the Blastocystis subtypes. It is important to focus on new subtypes and mixed subtypes of infection, while increasing data on ribosomal alleles. We encourage the scientific community to start research on humans and surrounding animals (including domestic and wild animals) to better understand the possibility of Blastocystis transmission between humans and animals. We call for action among researchers studying intestinal parasitic diseases (Blastocystis), start drawing the subtype of Blastocystis and increase the subtype related to its clinical symptoms.

Frequency and clinical manifestation of prenatal cytogenetic diagnosis of chromosomal polymorphisms in Northeast China.

OBJECTIVE: To retrospectively analyze the incidence of chromosomal polymorphisms in prenatal cytogenetic diagnostic cases and the effect of the clinical manifestation of these fetuses. MATERIALS AND METHODS: 490 fetuses with chromosomal polymorphisms among 9996 pregnant women who underwent prenatal cytogenetic diagnosis were included in this study and were set as group 1. Other 500 pregnant women, whose fetuses were with normal karyotypes, were randomly selected from the remaining pregnant women and set as group 2. Clinical information and outcomes and maternal serum screening results of group 1 were compared with group 2. RESULTS: The frequency of fetal chromosomal polymorphism was 4.90% (490/9996). The most common variants observed were 1/9/16 qh± (2.27%, 227/9996), followed by inv(9) (0.90%, 90/9996). 94.62% (264/279) of fetal chromosomal variants were inherited from parents. No statistical difference was found in clinical information and outcomes and maternal serum screening results between group 1 and group 2. CONCLUSION: The fetus with chromosomal polymorphism has no impact on serum markers of second trimester screening and does not play an important role for the clinical outcome of the current pregnancy either, whether it is inherited from the parents or a de novo mutation.

Real-world data on the use of secukinumab as treatment for moderate-to-severe psoriasis in Chinese patients.

BACKGROUND: The efficacy and safety of secukinumab, an interleukin-17 inhibitor, as systemic treatment for patients with moderate-to-severe psoriasis have been demonstrated, but real-world data pertaining to this is limited in China. OBJECTIVE: To evaluate the efficacy and safety of secukinumab in clinical practice in Chinese psoriasis patients with or without psoriatic arthritis (PsA) and identify potential baseline factors that affect the response of patients to secukinumab treatment. MATERIALS & METHODS: Data from 81 patients treated with secukinumab for at least 16 weeks were analysed in a retrospective observational study. RESULTS: After 16 weeks of treatment with secukinumab, 91.1%, 73%, and 38.3% of patients achieved a PASI 75 (75% improvement based on the Psoriasis Area and Severity Index), PASI 90, and PASI 100, respectively. A significant improvement in the quality of life of patients was also observed. Notably, baseline factors, such as young age, lower BMI, no scalp involvement and absence of concomitant PsA, were associated with better clinical response to secukinumab. Approximately 42% of patients (34/81) experienced adverse events, of which the most common was pruritus. CONCLUSION: The results demonstrated that secukinumab appears to be an effective treatment alternative for the majority of Chinese plaque psoriasis patients. Baseline factors, including age, BMI, scalp involvement and concomitant presence of PsA, were associated with response to secukinumab.

Indigenization of the median of markers for Down syndrome screening based on statistical analysis of medical big data.

OBJECTIVE: To indigenize the median of Down syndrome (DS) screening markers for first and second trimester, and compare the impact of the indigenized and built-in median data on the efficiency of DS screening. MATERIALS AND METHODS: Data derived from first and Second-trimester screening (FTS and STS) for DS, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Indigenization regression analysis was calculated by using five models to fit statistical the raw data. Multiple of median (MoM) values estimated by using indigenized medians were compared with those calculated by using built-in. RESULTS: This study established a regression equation which is more suitable for the median of each screening marker in the local pregnant women. The changes of median MoM of screening markers were statistically significant after indigenization. For FTS, the detection rate was 100% when the false positive rate was 5%, and the cut-off value was 1/262. On the other hand, for STS, the detection rate of the model with indigenized parameters was 77.42%, which is 16.13% higher than that of built-in parameters. CONCLUSION: For the individual specific risk of pregnancy, when the indigenized parameters was used to calculate, is more accurately and screening effectiveness has been improved. This is a great reference significance for the current prenatal screening whether indigenized data should be used.

Massive-scale biological activity-based modeling identifies novel antiviral leads against SARS-CoV-2

The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of traditional in silico approaches such as QSAR in such efforts in unquestionable, these models fundamentally rely on structural similarity to infer biological activity and are thus prone to becoming trapped in the very nearby chemical spaces of already known ligands. For novel and unprecedented threats such as COVID-19 much faster and efficient paradigms must be devised to accelerate the identification of new chemical classes for rapid drug development. Here we report the development of a new biological activity-based modeling (BABM) approach that builds on the hypothesis that compounds with similar activity patterns tend to share similar targets or mechanisms of action. In BABM, compound activity profiles established on massive scale across multiple assays are used as signatures to predict compound activity in a new assay or against a new target. We first trained and validated this approach by identifying new antiviral lead candidates for Zika and Ebola based on data from ~0.5 million compounds screened against ~2,000 assays. BABM models were then applied to predict ~300 compounds not previously reported to have activity for SARS-CoV-2, which were then tested in a live virus assay with high (>30%) hit rates. The most potent compounds showed antiviral activities in the nanomolar range. These potent confirmed compounds have the potential to be further developed in novel chemical space into new anti-SARS-CoV-2 therapies. These results demonstrate unprecedented ability using BABM to predict novel structures as chemical leads significantly beyond traditional methods, and its application in rapid drug discovery response in a global public health crisis.

Hyperprins A and B, Two Complex Meroterpenoids from Hypericum przewalskii.

Hyperprins A (1) and B (2), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii. Compound 1 possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.03,8.08,12]hexadecane motif. Compound 2 features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1 showed antiproliferation activity against the MV-4-11 cell line, and the p-bromobenzoate derivative of 2 displayed PTP1B inhibition.

A novel cholesterol conjugated fluorescence probe for Cu2+ detection and bioimaging in living cells.

A cholesterol conjugated fluorescence probe T was designed and synthesized. The probe T can be used for recognition of Cu2+ by the absorption spectrum, fluorescence spectrum, and naked eyes respectively in aqueous solution. The cell imaging experiments showed that the probe has good membrane permeability and a huge potentiality for the detection of Cu2+ in living cells.