Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many pati...Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuva...Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy.Unfortunately,a significant proportion of patients present with locally advanced,unresectable disease.Furthermore,recurrence rates are high even among patients who undergo surgical resection.The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer.Nevertheless,the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies,chemotherapy regimens,and targeted therapies have generated increasing interest its role.In this article,we review the rationale for,current evidence for,and ongoing research efforts in the use of neoadjuvant therapy for ICC.展开更多
Adenosquamous carcinoma of the pancreas(ASCP)is a rare entity. Like adenocarcinoma of the pancreas,overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalc...Adenosquamous carcinoma of the pancreas(ASCP)is a rare entity. Like adenocarcinoma of the pancreas,overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP.Molecular characterization revealed overexpression in MRP1(80%), MGMT(79%), TOP2A(75), RRM1(42%),TOPO1(42%), PTEN(45%), CMET(40%), and C-KIT(10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease.展开更多
The Paleocene mudrocks in Ghana’s Tano Basin have received limited attention despite ongoing efforts to explore hydrocarbon resources.A thorough geochemical analysis is imperative to assess these mudrocks’petroleum ...The Paleocene mudrocks in Ghana’s Tano Basin have received limited attention despite ongoing efforts to explore hydrocarbon resources.A thorough geochemical analysis is imperative to assess these mudrocks’petroleum generation potential and formulate effective exploration strategies.In this study,a comprehensive geochemical analysis was carried out on ten Paleocene rock cuttings extracted from TP-1,a discovery well within the Tano Basin.Various analytical techniques,including total organic carbon(TOC)analysis,Rock–Eval pyrolysis,gas chromatography-mass spectrometry,and isotope ratio-mass spectrometry,were employed to elucidate their hydrocar-bon potential and organic facies.Thefindings in this study were subsequently compared to existing geochemical data on Paleocene source rocks in the South Atlantic marginal basins.The results indicated that the Paleocene samples have TOC content ranging from 0.68 to 2.93 wt%.The prevalent kerogen types identified in these samples were Type Ⅱ and Type Ⅲ.Molecular and isotope data suggest that the organic matter found in the Paleocene mudrocks can be traced back to land plants and lower aquatic organisms.These mudrocks were deposited in a transi-tional environment withfluctuating water salinity,charac-terized by sub-oxic redox conditions.Maturity indices,both bulk and molecular,indicated a spectrum of maturity levels within the Paleocene mudrocks,spanning from immature to marginally mature,with increasing maturity observed with greater depth.In comparison,the organic composition and depositional environments of Paleocene source rocks in the Tano Basin closely resemble those found in the Niger Delta Basin,Douala,and Kribi-Campo Basins,the Kwanza Formation in Angola,and certain Brazilian marginal basins.However,it is worth noting that Paleocene source rocks in some of the basins,such as the Niger Delta and Brazilian marginal basins,exhibit rela-tively higher thermal maturity levels compared to those observed in the current Paleocene samples from the Tano Basin.In concl展开更多
Adult intussusception is rare, highly associated with a malignant lead point, and often requires emergent surgical management. We report the case of a 44-year-old male who presented with generalized abdominal pain and...Adult intussusception is rare, highly associated with a malignant lead point, and often requires emergent surgical management. We report the case of a 44-year-old male who presented with generalized abdominal pain and was found to have early ileocolic intussusception secondary to a large ileocecal mass. Biopsies of the mass and an enlarged cardiophrenic lymph node, as well as pleural fluid cytology were all consistent with Burkitt lymphoma (BL). Curiously, the patient’s abdominal exam was reassuring, and the intussusception and malignant bowel obstruction resolved over 36 hours with conservative management alone. With a Burkitt lymphoma international prognostic index (BL-IPI) score of 2, the patient proceeded to treatment with combination chemoimmunotherapy and attained a complete response after four cycles. There was no bowel perforation or recurrent intussusception throughout treatment. Thus, this report marks the first reported case of adult BL-associated intussusception to resolve with non-invasive management and establishes a precedent for conservative management in select patients.展开更多
Tensions are rising and the risk of regional war looms over the Middle East.Diplomacy has yet to restrain escalation and prospects for peace unfortunately are dim at this time.The regional situation is complex.Israeli...Tensions are rising and the risk of regional war looms over the Middle East.Diplomacy has yet to restrain escalation and prospects for peace unfortunately are dim at this time.The regional situation is complex.Israeli assassinations raise tensions In addition to the devastating Israeli incursion into occupied Gaza that began after the tragic events of October 7 last year,there is also increasing Israeli pressure on the occupied West Bank,continued Israeli assassinations of top-level Hamas and Hezbollah officials,the continuing Israeli air attacks on Lebanon and Syria,and also the Israeli intransigence at the negotiations over a ceasefire in Gaza.展开更多
Distributed acoustic sensing(DAS) is one recently developed seismic acquisition technique that is based on fiber-optic sensing. DAS provides dense spatial spacing that is useful to image shallow structure with surface...Distributed acoustic sensing(DAS) is one recently developed seismic acquisition technique that is based on fiber-optic sensing. DAS provides dense spatial spacing that is useful to image shallow structure with surface waves.To test the feasibility of DAS in shallow structure imaging,the PoroTomo team conducted a DAS experiment with the vibroseis truck T-Rex in Brady’s Hot Springs, Nevada, USA.The Rayleigh waves excited by the vertical mode of the vibroseis truck were analyzed with the Multichannel Analysis of Surface Waves(MASW) method. Phase velocities between5 and 20 Hz were successfully extracted for one segment of cable and were employed to build a shear-wave velocity model for the top 50 meters. The dispersion curves obtained with DAS agree well with the ones extracted from co-located geophones data and from the passive source Noise Correlation Functions(NCF). Comparing to the co-located geophone array, the higher sensor density that DAS arrays provides help reducing aliasing in dispersion analysis, and separating different surface wave modes. This study demonstrates the feasibility and advantage of DAS in imaging shallow structure with surface waves.展开更多
During their summit in San Francisco,California,on November 15,2023,Chinese President Xi Jinping and U.S.President Joe Biden announced continued cooperation on counternarcotics issues,and a crackdown on fentanyl in pa...During their summit in San Francisco,California,on November 15,2023,Chinese President Xi Jinping and U.S.President Joe Biden announced continued cooperation on counternarcotics issues,and a crackdown on fentanyl in particular.Interaction on a wide range of issues is an inevitable part of the mix in bilateral relations.展开更多
The leaders’summit of the United States,Japan,and the Philippines held in Washington,D.C.is billed as“historic.”Manila will join the Washington-led new arrangements targeted at China.
<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarc...<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.展开更多
Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches f...Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration.The fibroblast growth factor(FGF)signalling pathway is critical for the development of maxillofacial bone.Klotho,a type I transmembrane protein,is an important components of FGF receptor complexes.Recent studies have reported the presence of Klotho expression in bone.However,the role of Klotho in cranioskeletal development and repair remains unknown.Here,we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions.Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo.Under conditions of inflammation and trauma-induced bone loss,we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression.More importantly,we show for the first time that Klotho is present in human alveolar bone,with a distinct expression pattern under both normal and pathological conditions.In summary,our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair.Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration.It may also be a target for future therapeutics.展开更多
We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabricatio...We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide.The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract,particularly in asthma.We utilized the unique properties of reduced graphene oxide(rGO);specifically,the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes,thus allowing for highly sensitive electrochemical detection with minimal fouling.Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane(PDMS),which was necessary to analyze small EBC sample volumes.The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode.We characterized the performance of the sensors using standard nitrite/buffer solutions,nitrite spiked into EBC,and clinical EBC samples.The sensor demonstrated a sensitivity of 0.21μAμM^(−1) cm^(−2) in the range of 20–100μM and of 0.1μAμM^(−1) cm^(−2) in the range of 100–1000μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix.To benchmark our platform,we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5μM.This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.展开更多
AIM： To determine the performance of novice readers （4^th year medical students） for detecting capsule endoscopy findings. METHODS： Ten capsule endoscopy cases of small bowel lesions were administered to the reade...AIM： To determine the performance of novice readers （4^th year medical students） for detecting capsule endoscopy findings. METHODS： Ten capsule endoscopy cases of small bowel lesions were administered to the readers. Gold standard findings were pre-defined by gastroenterologists. Ten gold standard ＂targets＂ were identified among the 10 cases. Readers were given a 30-min overview of Rapid Reader software and instructed to mark any potential areas of abnormalities. A software program was developed using SAS to analyze the thumbnailed findings. RESULTS： The overall sensitivity for detecting the gold standard findings was 80%. As a group, at least 5 out of 10 readers detected each gold standard finding per recording. All the gold standard targets were identified when the readers＇ results were combined. Incidental finding/false positive rate ranged between 8.2-59.8 per reader. CONCLUSION： A panel of medical students with minimal endoscopic experience can achieve high sensitivity in detecting lesions on capsule endoscopy. A group of novice readers can pre-screen recordings to thumbnail potential areas of small bowel lesions for further review. These thumbnails must be reviewed to determine the clinical relevance. Further studies are ongoing to assess other cohorts.展开更多
基金Scholarship for Stabilizing Tablent from Hunan Agricultural University (05WD11)Scholarslip for Excellent Youthfrom Hunan Education Department (07B035)
文摘Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy.Unfortunately,a significant proportion of patients present with locally advanced,unresectable disease.Furthermore,recurrence rates are high even among patients who undergo surgical resection.The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer.Nevertheless,the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies,chemotherapy regimens,and targeted therapies have generated increasing interest its role.In this article,we review the rationale for,current evidence for,and ongoing research efforts in the use of neoadjuvant therapy for ICC.
基金Supported by In part the Lee T.Hanley Fund for Pancreatic Cancer Research
文摘Adenosquamous carcinoma of the pancreas(ASCP)is a rare entity. Like adenocarcinoma of the pancreas,overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP.Molecular characterization revealed overexpression in MRP1(80%), MGMT(79%), TOP2A(75), RRM1(42%),TOPO1(42%), PTEN(45%), CMET(40%), and C-KIT(10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease.
基金funded by the State Key Petroleum Lab of Petroleum Resources and Prospecting at China University of Petroleum (Beijing)
文摘The Paleocene mudrocks in Ghana’s Tano Basin have received limited attention despite ongoing efforts to explore hydrocarbon resources.A thorough geochemical analysis is imperative to assess these mudrocks’petroleum generation potential and formulate effective exploration strategies.In this study,a comprehensive geochemical analysis was carried out on ten Paleocene rock cuttings extracted from TP-1,a discovery well within the Tano Basin.Various analytical techniques,including total organic carbon(TOC)analysis,Rock–Eval pyrolysis,gas chromatography-mass spectrometry,and isotope ratio-mass spectrometry,were employed to elucidate their hydrocar-bon potential and organic facies.Thefindings in this study were subsequently compared to existing geochemical data on Paleocene source rocks in the South Atlantic marginal basins.The results indicated that the Paleocene samples have TOC content ranging from 0.68 to 2.93 wt%.The prevalent kerogen types identified in these samples were Type Ⅱ and Type Ⅲ.Molecular and isotope data suggest that the organic matter found in the Paleocene mudrocks can be traced back to land plants and lower aquatic organisms.These mudrocks were deposited in a transi-tional environment withfluctuating water salinity,charac-terized by sub-oxic redox conditions.Maturity indices,both bulk and molecular,indicated a spectrum of maturity levels within the Paleocene mudrocks,spanning from immature to marginally mature,with increasing maturity observed with greater depth.In comparison,the organic composition and depositional environments of Paleocene source rocks in the Tano Basin closely resemble those found in the Niger Delta Basin,Douala,and Kribi-Campo Basins,the Kwanza Formation in Angola,and certain Brazilian marginal basins.However,it is worth noting that Paleocene source rocks in some of the basins,such as the Niger Delta and Brazilian marginal basins,exhibit rela-tively higher thermal maturity levels compared to those observed in the current Paleocene samples from the Tano Basin.In concl
文摘Adult intussusception is rare, highly associated with a malignant lead point, and often requires emergent surgical management. We report the case of a 44-year-old male who presented with generalized abdominal pain and was found to have early ileocolic intussusception secondary to a large ileocecal mass. Biopsies of the mass and an enlarged cardiophrenic lymph node, as well as pleural fluid cytology were all consistent with Burkitt lymphoma (BL). Curiously, the patient’s abdominal exam was reassuring, and the intussusception and malignant bowel obstruction resolved over 36 hours with conservative management alone. With a Burkitt lymphoma international prognostic index (BL-IPI) score of 2, the patient proceeded to treatment with combination chemoimmunotherapy and attained a complete response after four cycles. There was no bowel perforation or recurrent intussusception throughout treatment. Thus, this report marks the first reported case of adult BL-associated intussusception to resolve with non-invasive management and establishes a precedent for conservative management in select patients.
文摘Tensions are rising and the risk of regional war looms over the Middle East.Diplomacy has yet to restrain escalation and prospects for peace unfortunately are dim at this time.The regional situation is complex.Israeli assassinations raise tensions In addition to the devastating Israeli incursion into occupied Gaza that began after the tragic events of October 7 last year,there is also increasing Israeli pressure on the occupied West Bank,continued Israeli assassinations of top-level Hamas and Hezbollah officials,the continuing Israeli air attacks on Lebanon and Syria,and also the Israeli intransigence at the negotiations over a ceasefire in Gaza.
基金partially supported by the Geothermal Technologies Office of the USA Department of Energy (No. DE-EE0006760)the State Key Laboratory of Geodesy and Earth’s Dynamics, Institute of Geodey and Geophysics, Chinese Academy of Sciences (No. SKLGED2019-5-4-E)
文摘Distributed acoustic sensing(DAS) is one recently developed seismic acquisition technique that is based on fiber-optic sensing. DAS provides dense spatial spacing that is useful to image shallow structure with surface waves.To test the feasibility of DAS in shallow structure imaging,the PoroTomo team conducted a DAS experiment with the vibroseis truck T-Rex in Brady’s Hot Springs, Nevada, USA.The Rayleigh waves excited by the vertical mode of the vibroseis truck were analyzed with the Multichannel Analysis of Surface Waves(MASW) method. Phase velocities between5 and 20 Hz were successfully extracted for one segment of cable and were employed to build a shear-wave velocity model for the top 50 meters. The dispersion curves obtained with DAS agree well with the ones extracted from co-located geophones data and from the passive source Noise Correlation Functions(NCF). Comparing to the co-located geophone array, the higher sensor density that DAS arrays provides help reducing aliasing in dispersion analysis, and separating different surface wave modes. This study demonstrates the feasibility and advantage of DAS in imaging shallow structure with surface waves.
文摘During their summit in San Francisco,California,on November 15,2023,Chinese President Xi Jinping and U.S.President Joe Biden announced continued cooperation on counternarcotics issues,and a crackdown on fentanyl in particular.Interaction on a wide range of issues is an inevitable part of the mix in bilateral relations.
文摘The leaders’summit of the United States,Japan,and the Philippines held in Washington,D.C.is billed as“historic.”Manila will join the Washington-led new arrangements targeted at China.
文摘<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.
基金supported by NSFC grants 81800928,81901040,and 82171001the Young Elite Scientist Sponsorship Program by CAST(No.2020QNRC001 and 2018QNR001)+2 种基金the Sichuan Science and Technology Program(No.2019YJ0054)Research Funding from West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2021-1)State Key Laboratory of Oral Diseases Open Funding Grant SKLOD202114.
文摘Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration.The fibroblast growth factor(FGF)signalling pathway is critical for the development of maxillofacial bone.Klotho,a type I transmembrane protein,is an important components of FGF receptor complexes.Recent studies have reported the presence of Klotho expression in bone.However,the role of Klotho in cranioskeletal development and repair remains unknown.Here,we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions.Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo.Under conditions of inflammation and trauma-induced bone loss,we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression.More importantly,we show for the first time that Klotho is present in human alveolar bone,with a distinct expression pattern under both normal and pathological conditions.In summary,our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair.Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration.It may also be a target for future therapeutics.
基金This work was partially funded by the National Institutes of Health NIEHS Center Grant ES005022 and by the Rutgers University Electrical and Computer Engineering Department.
文摘We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide.The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract,particularly in asthma.We utilized the unique properties of reduced graphene oxide(rGO);specifically,the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes,thus allowing for highly sensitive electrochemical detection with minimal fouling.Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane(PDMS),which was necessary to analyze small EBC sample volumes.The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode.We characterized the performance of the sensors using standard nitrite/buffer solutions,nitrite spiked into EBC,and clinical EBC samples.The sensor demonstrated a sensitivity of 0.21μAμM^(−1) cm^(−2) in the range of 20–100μM and of 0.1μAμM^(−1) cm^(−2) in the range of 100–1000μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix.To benchmark our platform,we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5μM.This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.
基金Supported by NIH Clinical Associate Physician(CAP)Award(Dr.Jutabha),American Society for Gastrointestinal Endoscopy Research Award(Dr.Jutabha),American College of Gastroenterology Capsule Endoscopy Research Award(Dr.Jutabha),NIH General Clinical Research
文摘AIM： To determine the performance of novice readers （4^th year medical students） for detecting capsule endoscopy findings. METHODS： Ten capsule endoscopy cases of small bowel lesions were administered to the readers. Gold standard findings were pre-defined by gastroenterologists. Ten gold standard ＂targets＂ were identified among the 10 cases. Readers were given a 30-min overview of Rapid Reader software and instructed to mark any potential areas of abnormalities. A software program was developed using SAS to analyze the thumbnailed findings. RESULTS： The overall sensitivity for detecting the gold standard findings was 80%. As a group, at least 5 out of 10 readers detected each gold standard finding per recording. All the gold standard targets were identified when the readers＇ results were combined. Incidental finding/false positive rate ranged between 8.2-59.8 per reader. CONCLUSION： A panel of medical students with minimal endoscopic experience can achieve high sensitivity in detecting lesions on capsule endoscopy. A group of novice readers can pre-screen recordings to thumbnail potential areas of small bowel lesions for further review. These thumbnails must be reviewed to determine the clinical relevance. Further studies are ongoing to assess other cohorts.
