This paper proposed a new systematic approach-functional evidential reasoning model(FERM) for exploring hazardous chemical operational accidents under uncertainty. First, FERM was introduced to identify various causal...This paper proposed a new systematic approach-functional evidential reasoning model(FERM) for exploring hazardous chemical operational accidents under uncertainty. First, FERM was introduced to identify various causal factors and their performance changes in hazardous chemical operational accidents, along with determining the functional failure link relationships. Subsequently, FERM was employed to elucidate both qualitative and quantitative operational accident information within a unified framework, which could be regarded as the input of information fusion to obtain the fuzzy belief distribution of each cause factor. Finally, the derived risk values of the causal factors were ranked while constructing multi-level accident causation chains to unveil the weak links in system functionality and the primary roots of operational accidents. Using the specific case of the “1·15” major explosion and fire accident at Liaoning Panjin Haoye Chemical Co., Ltd., seven causal factors and their corresponding performance changes were identified. Additionally, five accident causation chains were uncovered based on the fuzzy joint distribution of the functional assessment level(FAL) and reliability distribution(RD),revealing an overall increase in risk along the accident evolution path. The research findings demonstrated that FERM enabled the effective characterization, rational quantification and accurate analysis of the inherent uncertainties in hazardous chemical operational accident risks from a systemic perspective.展开更多
Precipitation plays a pivotal role in wet deposition,significantly affecting aerosol purification.The efficacy of precipitation in removing aerosols depends on its type and the characteristics of the particulates invo...Precipitation plays a pivotal role in wet deposition,significantly affecting aerosol purification.The efficacy of precipitation in removing aerosols depends on its type and the characteristics of the particulates involved.However,further research is necessary to fully understand how precipitation impacts PM_(2.5)components.This study utilized high-temporalresolution data on PM_(2.5),its components and meteorological factors to examine varying responses influenced by precipitation intensity and duration.The findings indicate that increased rainfall intensity and duration enhance PM_(2.5)and its constituents removal efficiency.Specifically,longer precipitation periods significantly improve PM_(2.5)purification,especially with drizzle and light rain.Moreover,there is a direct correlation between preprecipitation PM_(2.5)levels and its scavenging rates,with drizzle potentially exacerbating PM_(2.5)pollution under cleaner conditions(≤35μg/m^(3)).Seasonally,the efficacy of removing PM_(2.5)components varies notably in response to drizzle and light rain.In spring,higher PM_(2.5)levels after drizzlewere primarily due to increased organic carbon concentrations favored by higher relative humidity and lower pH conditions compared to other seasons,conducive to secondary organic aerosol production.Lower wind speeds and higher temperatures further contribute to water-soluble organic carbon accumulation.Daytime and nighttime precipitation exerted differing influences on PM_(2.5)components,particularly in spring where daytime drizzle and light rain significantly increased PM_(2.5)and its constituents,notably NO_(3)-,potentially associated with phase distribution changes between gas and aerosol phases in low-temperature,high-RH conditions compared to nighttime.These results propose a dualimpact mechanism of precipitation on PM_(2.5)and provide scientific basis for designing effective control strategies.展开更多
The management of nitrogenous waste emissions presents significant environmental and health challenges.Efficient and sustainable upcycling strategies are needed to convert waste nitrogen compounds into valuable resour...The management of nitrogenous waste emissions presents significant environmental and health challenges.Efficient and sustainable upcycling strategies are needed to convert waste nitrogen compounds into valuable resources.Electrocatalysis has emerged as a promising solution for waste management,but several challenges remain,including the identification of suitable electrocatalysts and understanding the complex reaction mechanisms.In this review,we focus on the progress in electrocatalytic oxidized nitrogen waste upgrading and utilization,highlighting the application of advanced in situ/operando characterization techniques,including X-ray spectroscopy,scanning electrochemical microscopy and others.These techniques provide valuable insights into the structural and chemical properties of electrocatalysts as well as intermediates during electrochemical reactions,enabling a better understanding of reaction mechanisms and optimization of reaction conditions.The review explores the mechanisms of electrocatalytic upcycling of nitrogenous waste,including nitrate/nitrite reduction,nitric oxide reduction,and carbon dioxide and nitrate co-reduction reactions.Additionally,future research directions and development trends are discussed,offering a relevant guide for the development of sustainable electrocatalytic technologies for waste management and resource recovery.展开更多
Considerable progress has been made in the field of cancer immunotherapy in recent years. This has been made possible in large part by the identification of new immune-based cellular targets and the development of nov...Considerable progress has been made in the field of cancer immunotherapy in recent years. This has been made possible in large part by the identification of new immune-based cellular targets and the development of novel approaches aimed at stimulating the immune system. The role played by the immunosuppressive microenvironment in the development of tumors has been established. The success of checkpoint-inhibiting antibodies and cancer vaccines has marked the beginning of a new era in cancer treatment. This review highlights the clinically relevant principles of cancer immunology and various immunotherapeutic approaches that have either already entered mainstream oncologic practice or are currently in the process of being evaluated in clinical trials. Furthermore, the current barriers to the development of effective immunotherapies and the potential strategies of overcoming them are also discussed.展开更多
Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors ...Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.展开更多
P53正向细胞凋亡调控因子(P53 upregulated modulator of apoptosis,PUMA)是Bcl-2家族唯BH3结构域亚家族成员,位于线粒体内,可被多种损伤因素诱导激活。PUMA通过BH3结构域与Bcl-2样抗凋亡蛋白结合后发挥其促凋亡作用。PUMA抑制剂模拟蛋...P53正向细胞凋亡调控因子(P53 upregulated modulator of apoptosis,PUMA)是Bcl-2家族唯BH3结构域亚家族成员,位于线粒体内,可被多种损伤因素诱导激活。PUMA通过BH3结构域与Bcl-2样抗凋亡蛋白结合后发挥其促凋亡作用。PUMA抑制剂模拟蛋白间的结合作用,阻碍PUMA与Bcl-2样蛋白结合,凋亡被抑制。在体内,依小鼠肝脏缺血、再灌注时间不同,损伤情况各异。损伤较轻时,PUMA表达升高,PUMA抑制剂能够保护肝脏抵抗损伤;当损伤较严重时,PUMA表达升高不明显,PUMA抑制剂的保护作用也不明显。综合上述,在一定程度损伤的条件下,PUMA抑制剂可以有效地保护肝脏,减轻损伤。展开更多
The word "autophagy" is derived from the Greek roots "auto" and "phagy" which mean "self" and "to eat", respectively.As a hot topic and rapidly expanding field in biol...The word "autophagy" is derived from the Greek roots "auto" and "phagy" which mean "self" and "to eat", respectively.As a hot topic and rapidly expanding field in biology and medicine, autophagy is a process by which cytoplasmic components, including soluble macromolecules (such as nucleic acids, proteins, carbohydrates and lipids) and organelles (such as mitochondria, peroxisomes and endoplasmic reticulum) are degraded by lysosomes.There are at least three recognized types of autophagy including chaperone-mediated autophagy, microautophagy, and macroautophagy[1].展开更多
AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the b...AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information.The ABO blood group frequency was compared between these patients and 708842 individual,community-based blood donors who had made donations to Pittsburgh's Central Blood Bank between 1979 and 2009.RESULTS:The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%,odds ratio (OR)=1.43,P=0.004].Conversely,the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%,OR=0.60,P=0.00007).There were limited blood group B (n=38) and AB (n=17) pancreatic cancer patients;the overall P trend value comparing patient to donor blood groups was 0.001.CONCLUSION:The ABO blood group is associated with pancreatic cancer risk.Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group.展开更多
Chinese researchers and physicians are being increasingly recognized for their significant contributions to advancing biomedical research, including cancer research, in China and around the world.To facilitate and str...Chinese researchers and physicians are being increasingly recognized for their significant contributions to advancing biomedical research, including cancer research, in China and around the world.To facilitate and strengthen collaboration among cancer researchers and physicians in the United States and China, the US Chinese Anti-Cancer Association (USCACA) and the US National Foundation for Cancer Research (NFCR) have established the USCACA-NFCR Scholar Exchange and Fellowship Program in basic, translational, and clinical studies.The goal of this joint scholar program is to recognize and reward research excellence by Chinese cancer researchers.Recipients are honored with the USCACA-NFCR Scholar Excellence Award for their achievements in cancer research performed while they were in the United States, as well as contributions to eradicating human cancers after their return to China.展开更多
Recent collaborative,large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced our understanding of this disease.The gene encoding platelet-der...Recent collaborative,large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced our understanding of this disease.The gene encoding platelet-derived growth factor receptor alpha(PDGFR a) was identified as the third of the top 11 amplified genes in clinical GBM specimens.The important roles of PDGFR a signaling during normal brain development also implicate the possible pathologic consequences of PDGFR a over-activation in glioma.Although the initial clinical trials using PDGFR kinase inhibitors have been predominantly disappointing,diagnostic and treatment modalities involving genomic profiling and personalized medicine are expected to improve the therapy targeting PDGFR a signaling.In this review,we discuss the roles of PDGFR a signaling during development of the normal central nervous system(CNS) and in pathologic conditions such as malignant glioma.We further compare various animal models of PDGF-induced gliomagenesis and their potential as a novel platform of pre-clinical drug testing.We then summarize our recent publication and how these findings will likely impact treatments for gliomas driven by PDGFR a overexpression.A better understanding of PDGFR a signaling in glioma and their microenvironment,through the use of human or mouse models,is necessary to design a more effective therapeutic strategy against gliomas harboring the aberrant PDGFR a signaling.展开更多
Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few d...Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. Recent studies have elucidated a key signaling axis, the EGFR-STAT3-Bcl-XL signaling axis, that is aberrantly activated in a majority of HNSCC and contributes to the proliferation and survival of malignant cells. Considerable effort is being placed on developing highly specific inhibitors of different components of this pathway. This review highlights the progress that is being made towards achieving potent inhibition of the EGFR-STAT3-Bcl-XL signaling axis in HNSCC and the promising therapeutic strategies that are currently under development for this disease.展开更多
Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has bee...Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.展开更多
Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review o...Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.展开更多
The development of resistance to chemotherapy, endocrine therapy and anti HER2 agents in breast cancer is an important and common problem that impacts in the management of patients, particularly in the metastatic sett...The development of resistance to chemotherapy, endocrine therapy and anti HER2 agents in breast cancer is an important and common problem that impacts in the management of patients, particularly in the metastatic setting. This resistance has been explained in part by the activation of signal transduction pathways, including the PI3K/AKT/mTOR. The blockade with mTOR inhibitors such as everolimus is a new target agent for therapy that attempts to enhance treatment efficacy and restore tumor sensitivity. In this review article, we present the data about the use of everolimus for the treatment of breast cancer in all tumor phenotypes. Future studies that evaluate biomarkers for treatment response are needed to identify the specific populations that have the highest benefit of this new targeted therapy.展开更多
Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer photo...Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. Methods: CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distribution were determined. For in vitro Pc 4 photodynamic therapy, cells were irradiated at 667 nm at a fluence of 2.5 J/cm<sup>2</sup> at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight hours after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm<sup>2</sup>. Results: The IC<sub>50</sub>s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6 μM and 0.016 μM and >10 μM and 0.026 μM;as spheroids, IC<sub>50</sub>s of Pc 4 photodynamic therapy were, 0.26 μM and 0.01 μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Conclusions: Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.展开更多
Objective.:To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma. Methods.:Forty-seven patients with endometrial cancerwere treated with adjuvant IMRT and HDR brachythe...Objective.:To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma. Methods.:Forty-seven patients with endometrial cancerwere treated with adjuvant IMRT and HDR brachytherapy (HDRB). The external beam dose was between 45 and 50.4 Gy,and all patients received 10Gy in 2 fractions of HDRB to the vaginal cuff. Eight of these patients were treated with extended field to include the paraaortic region. Results.:IMRT dosimetry showed excellent coverage of the planning target volume (PTV) with mean PTV 95,PTV 110 and PTV 120 of 97.8%,8.2%and 0.9%respectively. At a median follow-up of 20 months,four patients have recurred at extra pelvic sites. No patient had pelvic recurrence. The treatment was well tolerated with late toxicities as follows:small bowel grade 1:25%,rectal grade 1:2%and bladder grade 1:13%. One patient had grade 3 small bowel toxicity. The 3-year actuarial rate of grade 2 or greater toxicity,disease-free survival and overall survival rate were 3.3%,84%and 90%,respectively. Conclusions.:The preliminary analysis of IMRT for adjuvant treatment of endometrial carcinoma shows excellent local control and low toxicity. However,longer follow-up and more patients are needed to ascertain whether the benefits of IMRT treatment seen here translate into long-term reductions in toxicities and local recurrence.展开更多
Androgens are intimately associated with prostate cancer development and progression; however, the exact roles of androgens in prostate cancer cells remain unclear. Our research focuses on the identification and
The dysregulation of pathways regulat-ing cellular function is a frequent hall-mark of cancer and the development of specific pathway inhibitors that alter tumor growth and progression are the focus of multiple recent...The dysregulation of pathways regulat-ing cellular function is a frequent hall-mark of cancer and the development of specific pathway inhibitors that alter tumor growth and progression are the focus of multiple recent studies. E3 ubiquitin ligases are a large group of diverse protein enzymes that specifically target proteins for dear- ance, and their importance to normal cel-lular function is illustrated in the many diseases associated with their loss of func- tion or inappropriate targeting. S-phase kinase-associated protein 2 （Skp2） is an F box protein that plays critical roles in cell-cycle progression, senescence, metabolism, and acts as an Skpl-Cullin-l-F box （SCF） ubiquitin ligase substrate recognition fac-tor. Overexpression of Skp2 is associated with poor prognosis and metastasis in many cancers and is a well validated drug target. In a recent report, Chart et al. have iden-tified an Skp2 inhibitor that selectively impairs Skp2 E3 ligase activity using an integrated virtual high-throughput drug screening and experimental validation approach. This Skp2 inhibitor restricts cancer stemness and potentiates sensitivity to chemotherapeutic agents in multiple ani-mal tumor models. These findings identify a new novel small molecule that targets the Skp2 and reduces tumor growth by attenu-ating aerobic glycolysis and inducing cel-lular senescence.展开更多
基金supported by the National Key Research&Development Program of China(2021YFB3301100)the National Natural Science Foundation of China(52004014)the Fundamental Research Funds for the Central Universities(ZY2406).
文摘This paper proposed a new systematic approach-functional evidential reasoning model(FERM) for exploring hazardous chemical operational accidents under uncertainty. First, FERM was introduced to identify various causal factors and their performance changes in hazardous chemical operational accidents, along with determining the functional failure link relationships. Subsequently, FERM was employed to elucidate both qualitative and quantitative operational accident information within a unified framework, which could be regarded as the input of information fusion to obtain the fuzzy belief distribution of each cause factor. Finally, the derived risk values of the causal factors were ranked while constructing multi-level accident causation chains to unveil the weak links in system functionality and the primary roots of operational accidents. Using the specific case of the “1·15” major explosion and fire accident at Liaoning Panjin Haoye Chemical Co., Ltd., seven causal factors and their corresponding performance changes were identified. Additionally, five accident causation chains were uncovered based on the fuzzy joint distribution of the functional assessment level(FAL) and reliability distribution(RD),revealing an overall increase in risk along the accident evolution path. The research findings demonstrated that FERM enabled the effective characterization, rational quantification and accurate analysis of the inherent uncertainties in hazardous chemical operational accident risks from a systemic perspective.
基金supported by the National Natural Science Foundation of China(No.42175124)the Science and Technology Department of Sichuan Province(No.23YFS0383)the Fundamental Research Funds for the Central Universities,China(No.2023CDSN-18).
文摘Precipitation plays a pivotal role in wet deposition,significantly affecting aerosol purification.The efficacy of precipitation in removing aerosols depends on its type and the characteristics of the particulates involved.However,further research is necessary to fully understand how precipitation impacts PM_(2.5)components.This study utilized high-temporalresolution data on PM_(2.5),its components and meteorological factors to examine varying responses influenced by precipitation intensity and duration.The findings indicate that increased rainfall intensity and duration enhance PM_(2.5)and its constituents removal efficiency.Specifically,longer precipitation periods significantly improve PM_(2.5)purification,especially with drizzle and light rain.Moreover,there is a direct correlation between preprecipitation PM_(2.5)levels and its scavenging rates,with drizzle potentially exacerbating PM_(2.5)pollution under cleaner conditions(≤35μg/m^(3)).Seasonally,the efficacy of removing PM_(2.5)components varies notably in response to drizzle and light rain.In spring,higher PM_(2.5)levels after drizzlewere primarily due to increased organic carbon concentrations favored by higher relative humidity and lower pH conditions compared to other seasons,conducive to secondary organic aerosol production.Lower wind speeds and higher temperatures further contribute to water-soluble organic carbon accumulation.Daytime and nighttime precipitation exerted differing influences on PM_(2.5)components,particularly in spring where daytime drizzle and light rain significantly increased PM_(2.5)and its constituents,notably NO_(3)-,potentially associated with phase distribution changes between gas and aerosol phases in low-temperature,high-RH conditions compared to nighttime.These results propose a dualimpact mechanism of precipitation on PM_(2.5)and provide scientific basis for designing effective control strategies.
基金supported by the National Key Research and Development Project(No.2022YFA1505300)National Nature Science Foundation of China(Nos.52202372 and 22304021)Sichuan Science and Technology Program(Nos.2023NSFSC0089 and 2023NSFSC0436).
文摘The management of nitrogenous waste emissions presents significant environmental and health challenges.Efficient and sustainable upcycling strategies are needed to convert waste nitrogen compounds into valuable resources.Electrocatalysis has emerged as a promising solution for waste management,but several challenges remain,including the identification of suitable electrocatalysts and understanding the complex reaction mechanisms.In this review,we focus on the progress in electrocatalytic oxidized nitrogen waste upgrading and utilization,highlighting the application of advanced in situ/operando characterization techniques,including X-ray spectroscopy,scanning electrochemical microscopy and others.These techniques provide valuable insights into the structural and chemical properties of electrocatalysts as well as intermediates during electrochemical reactions,enabling a better understanding of reaction mechanisms and optimization of reaction conditions.The review explores the mechanisms of electrocatalytic upcycling of nitrogenous waste,including nitrate/nitrite reduction,nitric oxide reduction,and carbon dioxide and nitrate co-reduction reactions.Additionally,future research directions and development trends are discussed,offering a relevant guide for the development of sustainable electrocatalytic technologies for waste management and resource recovery.
文摘Considerable progress has been made in the field of cancer immunotherapy in recent years. This has been made possible in large part by the identification of new immune-based cellular targets and the development of novel approaches aimed at stimulating the immune system. The role played by the immunosuppressive microenvironment in the development of tumors has been established. The success of checkpoint-inhibiting antibodies and cancer vaccines has marked the beginning of a new era in cancer treatment. This review highlights the clinically relevant principles of cancer immunology and various immunotherapeutic approaches that have either already entered mainstream oncologic practice or are currently in the process of being evaluated in clinical trials. Furthermore, the current barriers to the development of effective immunotherapies and the potential strategies of overcoming them are also discussed.
文摘Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.
文摘P53正向细胞凋亡调控因子(P53 upregulated modulator of apoptosis,PUMA)是Bcl-2家族唯BH3结构域亚家族成员,位于线粒体内,可被多种损伤因素诱导激活。PUMA通过BH3结构域与Bcl-2样抗凋亡蛋白结合后发挥其促凋亡作用。PUMA抑制剂模拟蛋白间的结合作用,阻碍PUMA与Bcl-2样蛋白结合,凋亡被抑制。在体内,依小鼠肝脏缺血、再灌注时间不同,损伤情况各异。损伤较轻时,PUMA表达升高,PUMA抑制剂能够保护肝脏抵抗损伤;当损伤较严重时,PUMA表达升高不明显,PUMA抑制剂的保护作用也不明显。综合上述,在一定程度损伤的条件下,PUMA抑制剂可以有效地保护肝脏,减轻损伤。
文摘The word "autophagy" is derived from the Greek roots "auto" and "phagy" which mean "self" and "to eat", respectively.As a hot topic and rapidly expanding field in biology and medicine, autophagy is a process by which cytoplasmic components, including soluble macromolecules (such as nucleic acids, proteins, carbohydrates and lipids) and organelles (such as mitochondria, peroxisomes and endoplasmic reticulum) are degraded by lysosomes.There are at least three recognized types of autophagy including chaperone-mediated autophagy, microautophagy, and macroautophagy[1].
基金Supported by The Frieda G.and Saul F.Shapira BRCA Cancer Research Program(Greer JB,Whitcomb DC)the Wayne Fu-saro Pancreatic Cancer Research Fund(Whitcomb DC)the Jack F.Walsh Pancreatic Cancer Foundation(Brand RE)
文摘AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information.The ABO blood group frequency was compared between these patients and 708842 individual,community-based blood donors who had made donations to Pittsburgh's Central Blood Bank between 1979 and 2009.RESULTS:The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%,odds ratio (OR)=1.43,P=0.004].Conversely,the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%,OR=0.60,P=0.00007).There were limited blood group B (n=38) and AB (n=17) pancreatic cancer patients;the overall P trend value comparing patient to donor blood groups was 0.001.CONCLUSION:The ABO blood group is associated with pancreatic cancer risk.Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group.
文摘Chinese researchers and physicians are being increasingly recognized for their significant contributions to advancing biomedical research, including cancer research, in China and around the world.To facilitate and strengthen collaboration among cancer researchers and physicians in the United States and China, the US Chinese Anti-Cancer Association (USCACA) and the US National Foundation for Cancer Research (NFCR) have established the USCACA-NFCR Scholar Exchange and Fellowship Program in basic, translational, and clinical studies.The goal of this joint scholar program is to recognize and reward research excellence by Chinese cancer researchers.Recipients are honored with the USCACA-NFCR Scholar Excellence Award for their achievements in cancer research performed while they were in the United States, as well as contributions to eradicating human cancers after their return to China.
基金supported in part by grants from NIH CA130966the Pennsylvania Department of Health and Innovative Research Scholar Awards of the Hillman Foundation to Shi-Yuan Cheng and Bo Hua James S McDonnell Foundation Researching Award in Brain Cancers to Bo Hu
文摘Recent collaborative,large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced our understanding of this disease.The gene encoding platelet-derived growth factor receptor alpha(PDGFR a) was identified as the third of the top 11 amplified genes in clinical GBM specimens.The important roles of PDGFR a signaling during normal brain development also implicate the possible pathologic consequences of PDGFR a over-activation in glioma.Although the initial clinical trials using PDGFR kinase inhibitors have been predominantly disappointing,diagnostic and treatment modalities involving genomic profiling and personalized medicine are expected to improve the therapy targeting PDGFR a signaling.In this review,we discuss the roles of PDGFR a signaling during development of the normal central nervous system(CNS) and in pathologic conditions such as malignant glioma.We further compare various animal models of PDGF-induced gliomagenesis and their potential as a novel platform of pre-clinical drug testing.We then summarize our recent publication and how these findings will likely impact treatments for gliomas driven by PDGFR a overexpression.A better understanding of PDGFR a signaling in glioma and their microenvironment,through the use of human or mouse models,is necessary to design a more effective therapeutic strategy against gliomas harboring the aberrant PDGFR a signaling.
基金supported by National Institutes ofHealth grants R01 CA137260 and P50 CA097190
文摘Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. Recent studies have elucidated a key signaling axis, the EGFR-STAT3-Bcl-XL signaling axis, that is aberrantly activated in a majority of HNSCC and contributes to the proliferation and survival of malignant cells. Considerable effort is being placed on developing highly specific inhibitors of different components of this pathway. This review highlights the progress that is being made towards achieving potent inhibition of the EGFR-STAT3-Bcl-XL signaling axis in HNSCC and the promising therapeutic strategies that are currently under development for this disease.
文摘Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.
文摘Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.
文摘The development of resistance to chemotherapy, endocrine therapy and anti HER2 agents in breast cancer is an important and common problem that impacts in the management of patients, particularly in the metastatic setting. This resistance has been explained in part by the activation of signal transduction pathways, including the PI3K/AKT/mTOR. The blockade with mTOR inhibitors such as everolimus is a new target agent for therapy that attempts to enhance treatment efficacy and restore tumor sensitivity. In this review article, we present the data about the use of everolimus for the treatment of breast cancer in all tumor phenotypes. Future studies that evaluate biomarkers for treatment response are needed to identify the specific populations that have the highest benefit of this new targeted therapy.
文摘Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. Methods: CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distribution were determined. For in vitro Pc 4 photodynamic therapy, cells were irradiated at 667 nm at a fluence of 2.5 J/cm<sup>2</sup> at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight hours after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm<sup>2</sup>. Results: The IC<sub>50</sub>s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6 μM and 0.016 μM and >10 μM and 0.026 μM;as spheroids, IC<sub>50</sub>s of Pc 4 photodynamic therapy were, 0.26 μM and 0.01 μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Conclusions: Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.
文摘Objective.:To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma. Methods.:Forty-seven patients with endometrial cancerwere treated with adjuvant IMRT and HDR brachytherapy (HDRB). The external beam dose was between 45 and 50.4 Gy,and all patients received 10Gy in 2 fractions of HDRB to the vaginal cuff. Eight of these patients were treated with extended field to include the paraaortic region. Results.:IMRT dosimetry showed excellent coverage of the planning target volume (PTV) with mean PTV 95,PTV 110 and PTV 120 of 97.8%,8.2%and 0.9%respectively. At a median follow-up of 20 months,four patients have recurred at extra pelvic sites. No patient had pelvic recurrence. The treatment was well tolerated with late toxicities as follows:small bowel grade 1:25%,rectal grade 1:2%and bladder grade 1:13%. One patient had grade 3 small bowel toxicity. The 3-year actuarial rate of grade 2 or greater toxicity,disease-free survival and overall survival rate were 3.3%,84%and 90%,respectively. Conclusions.:The preliminary analysis of IMRT for adjuvant treatment of endometrial carcinoma shows excellent local control and low toxicity. However,longer follow-up and more patients are needed to ascertain whether the benefits of IMRT treatment seen here translate into long-term reductions in toxicities and local recurrence.
文摘Androgens are intimately associated with prostate cancer development and progression; however, the exact roles of androgens in prostate cancer cells remain unclear. Our research focuses on the identification and
文摘The dysregulation of pathways regulat-ing cellular function is a frequent hall-mark of cancer and the development of specific pathway inhibitors that alter tumor growth and progression are the focus of multiple recent studies. E3 ubiquitin ligases are a large group of diverse protein enzymes that specifically target proteins for dear- ance, and their importance to normal cel-lular function is illustrated in the many diseases associated with their loss of func- tion or inappropriate targeting. S-phase kinase-associated protein 2 （Skp2） is an F box protein that plays critical roles in cell-cycle progression, senescence, metabolism, and acts as an Skpl-Cullin-l-F box （SCF） ubiquitin ligase substrate recognition fac-tor. Overexpression of Skp2 is associated with poor prognosis and metastasis in many cancers and is a well validated drug target. In a recent report, Chart et al. have iden-tified an Skp2 inhibitor that selectively impairs Skp2 E3 ligase activity using an integrated virtual high-throughput drug screening and experimental validation approach. This Skp2 inhibitor restricts cancer stemness and potentiates sensitivity to chemotherapeutic agents in multiple ani-mal tumor models. These findings identify a new novel small molecule that targets the Skp2 and reduces tumor growth by attenu-ating aerobic glycolysis and inducing cel-lular senescence.
