Objective: To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) fa...Objective: To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) family receptor member RET (rearranged during transfection) and its key downstream phosphatidylinositol 3 kinase (PI-3K)/protein kinase B (Akt) pathway in the process. Methods: A total of 220 seven-day-old SD rats (of either sex, from 22 broods) were randomly divided into two groups, one (30 rats) for sham-surgery group and the other (190 rats) for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui (GV 20), Dazhui (GV 14), Quchi (LI 11) and Yongquan (KI 1) acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin (HE) staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Results: EA could ameliorate neurologic damage of the first somatic sensory area (SITr) and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein l展开更多
Objective: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the...Objective: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. Methods: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. Results: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. Conclusions: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.展开更多
Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during t...Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.展开更多
The continuous chemical investigation on the ethyl acetate (EtOAc) soluble fraction of the MeOH extract afforded two new lanostane triterpenoid derivatives including one with a rearranged lanostane skeleton. They we...The continuous chemical investigation on the ethyl acetate (EtOAc) soluble fraction of the MeOH extract afforded two new lanostane triterpenoid derivatives including one with a rearranged lanostane skeleton. They were identified as 3,4-seco-8-(14→13R)abeo-17,13-friedo-9β-lanosta-4(28), 7,14(30),24-tetraen-26,23-olide-23-hydroxy-3-oic acid (1) and 7,14-mariesa- dien-3oL-hydroxy-25-methoxy-26-oic acid (2). Structural determination of these compounds were carried out by the spectral studies especially by the two digital (2D)-NMR and high-resolution MS experiences.展开更多
PCR amplification was used to detect immunoglobulin heavy chain (IgH), T-cell receptor (TCR)Vγ1-Jγ, Vδ2-Dδ 3 rearranged genes in 45 cases of acute lymphoblastic leukemia (ALL) and IgH gene rearrangement in 41 case...PCR amplification was used to detect immunoglobulin heavy chain (IgH), T-cell receptor (TCR)Vγ1-Jγ, Vδ2-Dδ 3 rearranged genes in 45 cases of acute lymphoblastic leukemia (ALL) and IgH gene rearrangement in 41 cases acute nonlymphoblastic leukemia (ANLL). The positive percentage of the IgH, TCR Vγ1-Jγ and Vδ 2-Dδ3 gene rearrangement was found to be 66. 7%, 62.2%, and 35. 6%, respectively in 45 ALL patients. Multiple rearranged IgH gene bands were found in 8 (26. 7% ) out of 30 ALL patients with IgH gene rearrangement. IgH gene rearrangemens were found in 7 (17. 1% ) out of 41 ANLL patients. ALL patients with positive IgH rearranged gene were with B cell and those with positive TCR Vγ1-Jγ gene rearrangements and with negative IgH rearranged gene were with T-ALL,those with positive both IgH and TCR Vδ2-Dδ3 rearranged genes mostly were with preB-ALL. The complete remission (CR) rate was low in ALL patients with multiple rearranged heavy chains and ANLL patients with IgH gene rearrangement, who were more likely to have a clinical relapse, which may be due to clonal evolution. In complete remission (CR) patients, the cytologic relapse fell behind postive PCR results for an average periods of 7. 2 weeks (range 2 to 23 weeks). Using PCR to detect rearranged genes could be helpful in determining the efficacy of chemotherapy, predicting clinical relapse, assisting gene typing and predicting prognosis.展开更多
Objective The distribution of rearranged hopanes in hydrocarbon source rocks is influenced by thermal maturity and original source input, and is also controlled by depositional conditions. Through comparison of lacus...Objective The distribution of rearranged hopanes in hydrocarbon source rocks is influenced by thermal maturity and original source input, and is also controlled by depositional conditions. Through comparison of lacustrine and coal-bearing source rocks, this work attempted to analyze the composition and origin of rearranged hopanes in hydrocarbon source rocks. Taken the source rocks from the Songliao Basin, Ordos Basin and Kuqa Depression as examples, we aimed to investigate the effect of the redox conditions, water salinity and oxygen content of the source-rock depositional environment on the formation of rearranged hopanes to provide theoretical basis for the genesis of rearranged hopanes.展开更多
Objective The Tarim Basin is China's largest ore-bearing interior basin, and contains mainly marine oils. The Kuqa depression, a secondary structural unit within the northem Tarim Basin, is composed of Mesozoic and ...Objective The Tarim Basin is China's largest ore-bearing interior basin, and contains mainly marine oils. The Kuqa depression, a secondary structural unit within the northem Tarim Basin, is composed of Mesozoic and Cenozoic clastic sedimentary rocks dominated by continental oil. Previous research suggests that the crude oils especially condensates in the Kuqa depression are rich in abnormally high abundant rearranged hopanes. On the basis of 41 condensate samples and five oil samples from the Kuqa depression, this work systematically discussed the relationship between biomarker parameters and rearranged hopanes and deeply investigated the influence of depositional environment, original source,展开更多
A phytochemical investigation on Isodon flavidus led to the isolation of flavidanolide A(1),a rearranged diterpenoid featuring a six/seven/five-membered tricyclic skeleton,together with flavidanolide B(2),an uncommon ...A phytochemical investigation on Isodon flavidus led to the isolation of flavidanolide A(1),a rearranged diterpenoid featuring a six/seven/five-membered tricyclic skeleton,together with flavidanolide B(2),an uncommon heterodimeric diterpenoid consisting of a norabietane and a seco-isopimarane monomeric units.Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses.Their plausible biosynthetic routes were also proposed.In the bioassay,flavidanolide B was found to exhibit good inhibitory effect against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in RAW264.7 cells comparable to positive control pyrrolidinedithiocarbamate ammonium(PDTC),which provided evidence for the medicinal value of I.flavidus as a folk medicine for treating inflammatory diseases.展开更多
The rearranged during transfection(RET)gene encodes a protein tyrosine kinase.RET alterations by point mutations and gene fusions were found in diverse cancers.RET fusions allow abnormal expression and activation of t...The rearranged during transfection(RET)gene encodes a protein tyrosine kinase.RET alterations by point mutations and gene fusions were found in diverse cancers.RET fusions allow abnormal expression and activation of the oncogenic kinase,whereas only a few of RET point mutations found in human cancers are known oncogenic drivers.Earlier studies of RET-targeted therapy utilized multi-targeted protein tyrosine kinase inhibitors(TKIs)with RET inhibitor activity.These multi-targeted TKIs often led to high-grade adverse events and were subject to resistance caused by the gatekeeper mutations.Recently,two potent and selective RET TKIs,pralsetinib(BLU-667)and selpercatinib(LOXO-292),were developed.High response rates to these selective RET inhibitors across multiple forms of RET alterations in different types of cancers were observed in clinical trials,demonstrating the RET dependence in human cancers harboring these RET lesions.Pralsetinib and selpercatinib were effective in inhibiting RETV804L/M gatekeeper mutants.However,adaptive mutations that cause resistance to pralsetinib or selpercatinib at the solvent front RETG810 residue have been found,pointing to the need for the development of the next-generation of RET TKIs.展开更多
The Songliao Basin, one of the biggest continental petroliferous basins in eastern China, is a Mesozoic- Cenozoic fault-depressed and fault-subsided basin developed on the Hercynian fold basement. Generally, rearrange...The Songliao Basin, one of the biggest continental petroliferous basins in eastern China, is a Mesozoic- Cenozoic fault-depressed and fault-subsided basin developed on the Hercynian fold basement. Generally, rearranged hopanes are considered to be formed by clay- mediated acidic catalysis under oxic or suboxic environment, whereas high abundance of rearranged hopanes were found in hydrocarbon source rocks and crude oils that are derived from salty environment in the Songliao Basin. This phenomenon rarely happens all over the world.展开更多
Mesoproterozoic marine organic-rich rocks are widely distributed in the North China Craton,include the Gaoyuzhuang(GYZ),the Hongshuizhuang(HSZ),and the Xiamaling(XML)formations.According to the T;value and isomerisati...Mesoproterozoic marine organic-rich rocks are widely distributed in the North China Craton,include the Gaoyuzhuang(GYZ),the Hongshuizhuang(HSZ),and the Xiamaling(XML)formations.According to the T;value and isomerisation ratio of C;homohopanes,the XML,HSZ,and GYZ samples were in low mature,mature and high mature stage,respectively.Biomarker distribution in extractable organic matter(EOM)of three Mesoproterozoic organic-rock samples in different maturity were analysed to reveal the organic precursor and preservation pathway of in the Mesoproterozoic Combined with gold-tube pyrolysates of three Mesoproterozoic samples,it could further illuminate the chemical composition of Mesoproterozoic kerogen,given excluding.The results indicated that the three formations were all deposited under reducing condition and their organic precursors mainly were some aquatic organisms.High content of rearranged hopanes was detected in EOM of XML and HSZ samples,whereas they were relatively low in the high mature GYZ sample.Contrast to that in EOM,the relative concentration of rearranged hopanes sharply decreased in the gold-tube pyrolysates of the XML kerogen,then slightly increased but was still significantly lower than the EOM of XML sample,which indicated that catalysis of clay minerals in the early diagenesis only changed the chemical composition of the unstable functional groups of the kerogen during the preservation.Due to the thriving heterotrophic microbes and low sink rate of particulate organic matter during the Mesoproterozoic,primary producers suffered extensive degradation during sinking process,only some resistant biopolymers lacking of lipid compounds survived from heterotrophic degradation,while heterotrophic microbes contained more proportion of organic precursors.Abundant pristane(Pr)and phytane(Ph)were only released in high mature stage because of the protection of the macromolecular structure of resistant biopolymers which prevented biomarkers from being altered by the thermal stress.The absence of 13α(n-alkyl)-tri展开更多
BACKGROUND Fine-needle biopsy is an accurate and cost-efficient tool for the assessment of thyroid nodules.It includes two primary methods:Fine-needle capillary biopsy(FNCB)and fine-needle aspiration biopsy.Needle tra...BACKGROUND Fine-needle biopsy is an accurate and cost-efficient tool for the assessment of thyroid nodules.It includes two primary methods:Fine-needle capillary biopsy(FNCB)and fine-needle aspiration biopsy.Needle tract seeding(NTS)is a rare complication of thyroid fine-needle biopsy mainly caused by fine-needle aspiration biopsy rather than FNCB.Here,we present an extremely rare case of a papillary thyroid carcinoma(PTC)patient with FNCB-derived NTS.CASE SUMMARY We report a 32-year-old woman with PTC who showed subcutaneous NTS 1 year after FNCB and thyroidectomy.NTS was diagnosed based on clinical manifestations,biochemistry indices,and imaging(computed tomography and ultrasound).Pathological identification of PTC metastases consistent with the puncture path is the gold standard for diagnosis.Surgical resection was the main method used to treat the disease.After surgery,thyroid function tests and ultrasound scans were performed every 3-6 mo.To date,no evidence of tumor recurrence has been observed.CONCLUSION FNCB is a safe procedure as NTS is rare,and can be easily removed surgically with no recurrence.Accordingly,NTS should not limit the usefulness of FNCB.展开更多
Objective The distribution characteristics and formation mechanism of rearranged hopanes in hydrocarbon source rocks are affected by various geological conditions.Among these geological conditions,thermal action has a...Objective The distribution characteristics and formation mechanism of rearranged hopanes in hydrocarbon source rocks are affected by various geological conditions.Among these geological conditions,thermal action has an important influence on the formation of rearranged hopanes,which has been however little documented previously.展开更多
The rapid advances in the understanding of oncogenic process and the maturation of affordable precision diagnostic tools have enabled the development of targeted therapeutic agents,such as those targeting BCR-ABL,epit...The rapid advances in the understanding of oncogenic process and the maturation of affordable precision diagnostic tools have enabled the development of targeted therapeutic agents,such as those targeting BCR-ABL,epithelial growth factor receptor L858R,EML4-anaplastic lymphoma kinase,and BRAF V600E,to treat cancers that harbor specific molecular alterations.Traditionally,each targeted drug has been developed for a particular tumor type where such alteration is most frequently found.Recently,the widespread adoption of next generation sequencing has led to an increase in the identification of rare and ultra-rare alterations,and,in some cases,the same rare alterations are found across multiple tumor types.The rarity of these alterations makes clinical trials traditionally designed for specific tumor types infeasible.As a result,tissue-agnostic trials have been developed to study the efficacy of these treatments and increase patient access.This review summarizes current successful cases of tissue-agnostic development,such as drugs targeting tropomyosin receptor kinase fusions,and proposes the next wave of potential tissue-agnostic targets,including fusions of ROS1,anaplastic lymphoma kinase,fibroblast growth factor receptor,and rearranged during transfection.In addition,the advantages and the challenges of such approach are discussed in the context of clinical development and approval.展开更多
The theme in this article is the inequalities of B_valued martingales and the properties of Banach spaces. In utilising the techniques of rearranged functions, we proved that for a martingale f we have ‖M αf‖ Φ...The theme in this article is the inequalities of B_valued martingales and the properties of Banach spaces. In utilising the techniques of rearranged functions, we proved that for a martingale f we have ‖M αf‖ Φ≤C pΦ ‖f # α‖ Φ and the same result for (Mf,S (p) (f)+D ∞), (Mf∧Sf,Mf∧Sf+D ∞). This contains the results in R.L.Long[1], furthermore, some of the inequalities can be used to describe the properties of Banach spaces.展开更多
基金Supported by the 45th China Postdoctoral Science Foundation(No.20090450856)
文摘Objective: To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) family receptor member RET (rearranged during transfection) and its key downstream phosphatidylinositol 3 kinase (PI-3K)/protein kinase B (Akt) pathway in the process. Methods: A total of 220 seven-day-old SD rats (of either sex, from 22 broods) were randomly divided into two groups, one (30 rats) for sham-surgery group and the other (190 rats) for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui (GV 20), Dazhui (GV 14), Quchi (LI 11) and Yongquan (KI 1) acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin (HE) staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Results: EA could ameliorate neurologic damage of the first somatic sensory area (SITr) and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein l
基金supported by the Capital Health Research and Development of Special (No. 2014-2-026)
文摘Objective: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. Methods: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. Results: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. Conclusions: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.
文摘Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.
文摘The continuous chemical investigation on the ethyl acetate (EtOAc) soluble fraction of the MeOH extract afforded two new lanostane triterpenoid derivatives including one with a rearranged lanostane skeleton. They were identified as 3,4-seco-8-(14→13R)abeo-17,13-friedo-9β-lanosta-4(28), 7,14(30),24-tetraen-26,23-olide-23-hydroxy-3-oic acid (1) and 7,14-mariesa- dien-3oL-hydroxy-25-methoxy-26-oic acid (2). Structural determination of these compounds were carried out by the spectral studies especially by the two digital (2D)-NMR and high-resolution MS experiences.
文摘PCR amplification was used to detect immunoglobulin heavy chain (IgH), T-cell receptor (TCR)Vγ1-Jγ, Vδ2-Dδ 3 rearranged genes in 45 cases of acute lymphoblastic leukemia (ALL) and IgH gene rearrangement in 41 cases acute nonlymphoblastic leukemia (ANLL). The positive percentage of the IgH, TCR Vγ1-Jγ and Vδ 2-Dδ3 gene rearrangement was found to be 66. 7%, 62.2%, and 35. 6%, respectively in 45 ALL patients. Multiple rearranged IgH gene bands were found in 8 (26. 7% ) out of 30 ALL patients with IgH gene rearrangement. IgH gene rearrangemens were found in 7 (17. 1% ) out of 41 ANLL patients. ALL patients with positive IgH rearranged gene were with B cell and those with positive TCR Vγ1-Jγ gene rearrangements and with negative IgH rearranged gene were with T-ALL,those with positive both IgH and TCR Vδ2-Dδ3 rearranged genes mostly were with preB-ALL. The complete remission (CR) rate was low in ALL patients with multiple rearranged heavy chains and ANLL patients with IgH gene rearrangement, who were more likely to have a clinical relapse, which may be due to clonal evolution. In complete remission (CR) patients, the cytologic relapse fell behind postive PCR results for an average periods of 7. 2 weeks (range 2 to 23 weeks). Using PCR to detect rearranged genes could be helpful in determining the efficacy of chemotherapy, predicting clinical relapse, assisting gene typing and predicting prognosis.
基金financed by the National Science Foundation of China(grant No.41272170)the National Oil and Gas Major Project(grant No.2016ZX05007-001)
文摘Objective The distribution of rearranged hopanes in hydrocarbon source rocks is influenced by thermal maturity and original source input, and is also controlled by depositional conditions. Through comparison of lacustrine and coal-bearing source rocks, this work attempted to analyze the composition and origin of rearranged hopanes in hydrocarbon source rocks. Taken the source rocks from the Songliao Basin, Ordos Basin and Kuqa Depression as examples, we aimed to investigate the effect of the redox conditions, water salinity and oxygen content of the source-rock depositional environment on the formation of rearranged hopanes to provide theoretical basis for the genesis of rearranged hopanes.
基金financed by the National Science Foundation of China(grant No.41272170)
文摘Objective The Tarim Basin is China's largest ore-bearing interior basin, and contains mainly marine oils. The Kuqa depression, a secondary structural unit within the northem Tarim Basin, is composed of Mesozoic and Cenozoic clastic sedimentary rocks dominated by continental oil. Previous research suggests that the crude oils especially condensates in the Kuqa depression are rich in abnormally high abundant rearranged hopanes. On the basis of 41 condensate samples and five oil samples from the Kuqa depression, this work systematically discussed the relationship between biomarker parameters and rearranged hopanes and deeply investigated the influence of depositional environment, original source,
基金supported by the National Natural Science Foundation of China(No.82204605)the National Natural Science Foundation of China(No.81560709)+3 种基金the Technology Fund of Guizhou Administration of Traditional Chinese Medicine(No.QZYY-2022019)Science and Technology Tip-top Talent Foundation of Universities in Guizhou Province(No.Qian jiao he KY(2021)034)the Research Grant Council of the Hong Kong Special Administrative Region,China(No.HKBU 12102219)the University Grants Committee of the Hong Kong Special Administrative Region,China(UGC Research Matching Grant Scheme,No.RMG2019_1_19)。
文摘A phytochemical investigation on Isodon flavidus led to the isolation of flavidanolide A(1),a rearranged diterpenoid featuring a six/seven/five-membered tricyclic skeleton,together with flavidanolide B(2),an uncommon heterodimeric diterpenoid consisting of a norabietane and a seco-isopimarane monomeric units.Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses.Their plausible biosynthetic routes were also proposed.In the bioassay,flavidanolide B was found to exhibit good inhibitory effect against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in RAW264.7 cells comparable to positive control pyrrolidinedithiocarbamate ammonium(PDTC),which provided evidence for the medicinal value of I.flavidus as a folk medicine for treating inflammatory diseases.
文摘The rearranged during transfection(RET)gene encodes a protein tyrosine kinase.RET alterations by point mutations and gene fusions were found in diverse cancers.RET fusions allow abnormal expression and activation of the oncogenic kinase,whereas only a few of RET point mutations found in human cancers are known oncogenic drivers.Earlier studies of RET-targeted therapy utilized multi-targeted protein tyrosine kinase inhibitors(TKIs)with RET inhibitor activity.These multi-targeted TKIs often led to high-grade adverse events and were subject to resistance caused by the gatekeeper mutations.Recently,two potent and selective RET TKIs,pralsetinib(BLU-667)and selpercatinib(LOXO-292),were developed.High response rates to these selective RET inhibitors across multiple forms of RET alterations in different types of cancers were observed in clinical trials,demonstrating the RET dependence in human cancers harboring these RET lesions.Pralsetinib and selpercatinib were effective in inhibiting RETV804L/M gatekeeper mutants.However,adaptive mutations that cause resistance to pralsetinib or selpercatinib at the solvent front RETG810 residue have been found,pointing to the need for the development of the next-generation of RET TKIs.
基金supported by the National Natural Science Foundation of China(grant No.41272170)
文摘The Songliao Basin, one of the biggest continental petroliferous basins in eastern China, is a Mesozoic- Cenozoic fault-depressed and fault-subsided basin developed on the Hercynian fold basement. Generally, rearranged hopanes are considered to be formed by clay- mediated acidic catalysis under oxic or suboxic environment, whereas high abundance of rearranged hopanes were found in hydrocarbon source rocks and crude oils that are derived from salty environment in the Songliao Basin. This phenomenon rarely happens all over the world.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA14010101)the National Key Research and Development Program of China(2017YFC0603101)+1 种基金the National Natural Science Foundation of China(41973068)the Scientific Research and Technological Development Project of CNPC(2019A-0208)。
文摘Mesoproterozoic marine organic-rich rocks are widely distributed in the North China Craton,include the Gaoyuzhuang(GYZ),the Hongshuizhuang(HSZ),and the Xiamaling(XML)formations.According to the T;value and isomerisation ratio of C;homohopanes,the XML,HSZ,and GYZ samples were in low mature,mature and high mature stage,respectively.Biomarker distribution in extractable organic matter(EOM)of three Mesoproterozoic organic-rock samples in different maturity were analysed to reveal the organic precursor and preservation pathway of in the Mesoproterozoic Combined with gold-tube pyrolysates of three Mesoproterozoic samples,it could further illuminate the chemical composition of Mesoproterozoic kerogen,given excluding.The results indicated that the three formations were all deposited under reducing condition and their organic precursors mainly were some aquatic organisms.High content of rearranged hopanes was detected in EOM of XML and HSZ samples,whereas they were relatively low in the high mature GYZ sample.Contrast to that in EOM,the relative concentration of rearranged hopanes sharply decreased in the gold-tube pyrolysates of the XML kerogen,then slightly increased but was still significantly lower than the EOM of XML sample,which indicated that catalysis of clay minerals in the early diagenesis only changed the chemical composition of the unstable functional groups of the kerogen during the preservation.Due to the thriving heterotrophic microbes and low sink rate of particulate organic matter during the Mesoproterozoic,primary producers suffered extensive degradation during sinking process,only some resistant biopolymers lacking of lipid compounds survived from heterotrophic degradation,while heterotrophic microbes contained more proportion of organic precursors.Abundant pristane(Pr)and phytane(Ph)were only released in high mature stage because of the protection of the macromolecular structure of resistant biopolymers which prevented biomarkers from being altered by the thermal stress.The absence of 13α(n-alkyl)-tri
文摘BACKGROUND Fine-needle biopsy is an accurate and cost-efficient tool for the assessment of thyroid nodules.It includes two primary methods:Fine-needle capillary biopsy(FNCB)and fine-needle aspiration biopsy.Needle tract seeding(NTS)is a rare complication of thyroid fine-needle biopsy mainly caused by fine-needle aspiration biopsy rather than FNCB.Here,we present an extremely rare case of a papillary thyroid carcinoma(PTC)patient with FNCB-derived NTS.CASE SUMMARY We report a 32-year-old woman with PTC who showed subcutaneous NTS 1 year after FNCB and thyroidectomy.NTS was diagnosed based on clinical manifestations,biochemistry indices,and imaging(computed tomography and ultrasound).Pathological identification of PTC metastases consistent with the puncture path is the gold standard for diagnosis.Surgical resection was the main method used to treat the disease.After surgery,thyroid function tests and ultrasound scans were performed every 3-6 mo.To date,no evidence of tumor recurrence has been observed.CONCLUSION FNCB is a safe procedure as NTS is rare,and can be easily removed surgically with no recurrence.Accordingly,NTS should not limit the usefulness of FNCB.
基金supported by the National Natural Science Foundation of China (grant No.41272170)the National Oil and Gas Major Project (grant No.2016ZX05007-001)
文摘Objective The distribution characteristics and formation mechanism of rearranged hopanes in hydrocarbon source rocks are affected by various geological conditions.Among these geological conditions,thermal action has an important influence on the formation of rearranged hopanes,which has been however little documented previously.
基金Li IW and Krishnamurthy N were supported by the Emperor Science Awards,an initiative of Stand Up To Cancer(SU2C),made possible by support from Genentech,Bristol-Myers Squibb Company,and Novartis.
文摘The rapid advances in the understanding of oncogenic process and the maturation of affordable precision diagnostic tools have enabled the development of targeted therapeutic agents,such as those targeting BCR-ABL,epithelial growth factor receptor L858R,EML4-anaplastic lymphoma kinase,and BRAF V600E,to treat cancers that harbor specific molecular alterations.Traditionally,each targeted drug has been developed for a particular tumor type where such alteration is most frequently found.Recently,the widespread adoption of next generation sequencing has led to an increase in the identification of rare and ultra-rare alterations,and,in some cases,the same rare alterations are found across multiple tumor types.The rarity of these alterations makes clinical trials traditionally designed for specific tumor types infeasible.As a result,tissue-agnostic trials have been developed to study the efficacy of these treatments and increase patient access.This review summarizes current successful cases of tissue-agnostic development,such as drugs targeting tropomyosin receptor kinase fusions,and proposes the next wave of potential tissue-agnostic targets,including fusions of ROS1,anaplastic lymphoma kinase,fibroblast growth factor receptor,and rearranged during transfection.In addition,the advantages and the challenges of such approach are discussed in the context of clinical development and approval.
文摘The theme in this article is the inequalities of B_valued martingales and the properties of Banach spaces. In utilising the techniques of rearranged functions, we proved that for a martingale f we have ‖M αf‖ Φ≤C pΦ ‖f # α‖ Φ and the same result for (Mf,S (p) (f)+D ∞), (Mf∧Sf,Mf∧Sf+D ∞). This contains the results in R.L.Long[1], furthermore, some of the inequalities can be used to describe the properties of Banach spaces.