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Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanopartic.es with Radiation Therapy to Boost Immune Response of castration-Resistant Prostate cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdulmottaleb e.Zetrini HoYin Lip Azhar Z.Abbasi Ibrahim Alradwan Taksim Ahmed chunsheng He Jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. Departments of Medical Biophysics and Radiation Oncology University of TorontoM5G 1L7TorontoONCanada.

Despite substantial progress in the treatment of castration-resistant prostate cancer (cRPc), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanopartic.es (PLMDs) to remodel the tumor immune microenvironment (TIMe) by inc.easing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine cRPc cells to radiation, significantly inc.easing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the sec.etion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine cRPc TRAMP-c2 cells. In a syngeneic TRAMP-c2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor cD8+ T cells and M1 macrophages to tumor sites. Taken together, TIMe modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic.efficacy in radioresistant and immunosuppressive solid tumors.

关键词： RAW264.7 alone treatment

No Incidence of Liver cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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chinese Journal of Integrative Medicine 2024年第2期30卷 99-106页

作者： SU Tao FANG Zhi-e GUO Yu-ming WANG chun-yu WANG Jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal Division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China china Military Institute of chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney Diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conduc.ed on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December ***-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of *** primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to ***:A total of 337 patients diagnosed with AAN were included in this *** the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with *** cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary ***:No cases of liver cancer were observed at the end of ***,a high prevalence of urinary cancer was observed in AAN *** a direct causality between AA and Hcc is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

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Bone Research 2024年第1期12卷 180-198页

作者： Morten S.Hansen Kaja Madsen Maria Price Kent Søe Yasunori Omata Mario M.Zaiss caroline M.Gorvin Morten Frost Alexander Rauch Molecular endocrinology Laboratory(KMeB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark clinical cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK centre for Membrane Proteins and Receptors(cOMPARe) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsc.es Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes center Odense Odense University HospitalDK-5000 Odense CDenmark

enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is charac.erized by inc.eased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from cD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac c.est biopsies and bone mineral density *** analyses revealed mutual dependenc.es between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific.expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(c5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating c5AR1 enhanced osteoclast formation,while activating SSTR2 dec.eased the resorptive activity of mature osteoclasts,and activating FFAR4 dec.eased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

Impact of Paenibacillus elgii supernatant on sc.eening bac.erial strains with potential for biotechnological applications

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engineering Microbiology 2024年第3期4卷 1-15页

作者： I.c.cunha-Ferreira c.S.Vizzotto T.D.Frederico J.Peixoto L.S carvalho M.R.Tótola R.H.Krüger Laboratory of enzymology Department of Cellular BiologyUniversity of Brasília(UNB)Brasília70910-900Brazil Laboratory of environmental Sanitation Department of Civil and Environmental EngineeringUniversity of Brasília(UNB)Brasília70910-900Brazil Laboratório de Biotecnologia e Biodiversidade para o Meio Ambiente Universidade Federal de Viçosa(UFV)Viçosa36570-900Brazil

The biotechnological industry faces a crucial demand for novel bioactive compounds,particularly antimicrobial agents,to address the rising challenge of bac.erial resistance to current available *** strate-gies for cultivating naturally occurring microorganisms often limit the discovery of novel antimicrobial *** study presents a protocol for targeted selection of bac.erial strains using the supernatant of Paenibacillus el-gii,which produces abundant signal molecules and antimicrobial *** samples were inoculated in these enric.ed culture media to selectively cultivate bac.eria resistant to the supernatant,indicating their potential to produce similar *** bac.erial strains isolated through this method were assessed for their antibac-terial *** addition,the functional annotation of the genome of one of these strains revealed several gene clusters of biotechnological *** study highlights the effectiveness of using this approach for selective cultivation of microorganisms with potential for biotechnological applications.

关键词： Prospecting Supernatant Antibac.erial activity

Seismic attribute and well-log analysis for channel charac.erization in the upper San Andres and Grayburg formations of the Midland Basin,Texas

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energy Geosc.ence 2024年第2期5卷 263-278页

作者： Sumit Verma esra Yalçın Yılmaz Laura Ortiz Sanguino Justin Yandell Miles A.Henderson Robert c.Trentham Department of Geosc.ences The University of Texas Permian BasinOdessaTXUSA School of Geosc.ences The University of OklahomaNormanOKUSA

The Permian Basin is one of the most prolific,and currently one of the most active,oil and gas basins in the *** Lower Permian strata in the Permian Basin have produced more than 14 billion barrels of oil(BBO),making it the largest volume of hydrocarbon in the *** in the Midland Basin during late Leonardian through early Guadalupian(ca.272-269 Ma)resulted in progradation of shelf edge and ultimately closure of the basin by Middle Permian *** analyzed a merged seismic survey covering parts of the Permian Basin(i.e.,central Basin Platform and Midland Basin)in Andrews,ector,and Midland counties,*** seismic survey and well logs show the presence of gently dipping(ca.1°)clinoforms in the Upper San Andres and Grayburg Formations on the eastern edge of the central Basin Platform and western Midland *** seismic attributes,curvature,and spectral decomposition identify low sinuosity slope channels oriented north-south,but such channels do not appear beyond the *** shelf edge shifts from north to south during deposition of the Upper San Andres and Grayburg *** identify five basinward shifts noted by the migration of the shelf edge toward the basin center and the presence of channel features along the depositional *** petrophysical analysis indicates that channels cut into carbonate rocks and are filled by siliciclastic sediments;this interpretation is supported by the most negative curvature anomalies along the channel axes caused by the differential compaction between the carbonate and siliciclastic *** are a few channels with a northwest-southeast strike,which matc.es the direction of the concho Lineament observed by satellite *** observations are consistent with previous interpretations of the northern Midland Basin closure during Middle-Late Permian time.

关键词： Permian shelf carbonate

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聚合过程

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comparison of Block Design Nonparametric Subset Selection Rules Based on Alternative Scoring Rules

作者： (美)c.e席尔奈希特 I.斯凯斯特唐士培杨新源等译

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Applied Mathematics 2024年第5期15卷 355-389页

作者： Gary c. McDonald Sajidah Alsaeed Department of Mathematics and Statistics Oakland University Rochester MI USA

This artic.e compares the size of selec.ed subsets using nonparametric subset selection rules with two different scoring rules for the observations. The scoring rules are based on the expec.ed values of order statistics of the uniform distribution (yielding rank values) and of the normal distribution (yielding normal score values). The comparison is made using state motor vehic.e traffic fatality rates, published in a 2016 artic.e, with fifty-one states (including Dc as a state) and over a nineteen-year period (1994 through 2012). The earlier study considered four block design selection rules—two for choosing a subset to contain the “best” population (i.e., state with lowest mean fatality rate) and two for the “worst” population (i.e., highest mean rate) with a probability of correct selection chosen to be 0.90. Two selection rules based on normal scores resulted in selec.ed subset sizes substantially smaller than corresponding rules based on ranks (7 vs. 16 and 3 vs. 12). For two other selection rules, the subsets chosen were very close in size (within one). A comparison is also made using state homicide rates, published in a 2022 artic.e, with fifty states and covering eight years. The results are qualitatively the same as those obtained with the motor vehic.e traffic fatality rates.

关键词： Order Statistics Rank Scoring Methods Probability of a correct Selection Subset Size Motor Vehic.e Traffic Fatality Rates Homicide Rates Asymptotic Distributions

On Performance charac.eristics of a Nonparametric Subset Selection Procedure with a Small Randomized Block experimental Design

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Applied Mathematics 2024年第9期15卷 630-650页

作者： Gary c. McDonald Sajidah Alsaeed Department of Mathematics and Statistics Oakland University Rochester MI USA

This artic.e addresses the issue of computing the constant required to implement a specific nonparametric subset selection procedure based on ranks of data arising in a statistical randomized block experimental design. A model of three populations and two blocks is used to compute the probability distribution of the relevant statistic, the maximum of the population rank sums minus the rank sum of the “best” population. calculations are done for populations following a normal distribution, and for populations following a bi-uniform distribution. The least favorable configuration in these cases is shown to arise when all three populations follow identical distributions. The bi-uniform distribution leads to an asymptotic counterexample to the conjecture that the least favorable configuration, i.e., that configuration minimizing the probability of a correct selection, occurs when all populations are identically distributed. These results are consistent with other large-scale simulation studies. All relevant computational R-codes are provided in appendices.

关键词： Rank Statistics Least Favorable configuration Probability of correct Selection Slippage configuration equal Spaced configuration counterexample configuration

Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

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World Journal of Transplantation 2024年第2期14卷 76-87页

作者： Andrés Gómez-De León Yesica A López-Mora Valeria García-Zárate Ana Varela-constantino Sergio U Villegas-De Leon Xitlaly J González-Leal Raúl del Toro-Mijares Anna c Rodríguez-Zúñiga Juan F Barrios-Ruiz Victor Mingura-Ledezma Perla R colunga-Pedraza Olga G cantú-Rodríguez césar H Gutiérrez-Aguirre Luz Tarín-Arzaga elías e González-López David Gómez-Almaguer Hematology Service Universidad Autónoma de Nuevo LeónFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezMonterrey 64460Nuevo LeónMexico Hemato-logy Service Clínica Gómez AlmaguerMonterrey 64710Nuevo LeónMexico Hematology Service Instituto Tecnológico de Estudios Superiores de MonterreyTec SaludEscuela de Medicina Ignacio SantosMonterrey 64710Nuevo LeónMexico

BAcKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly *** observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-poc.et vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHScT)in two of Mexico's largest public and private *** To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in *** In this retrospective cohort study,we included adolescents and adults≥16 years who received a matc.ed sibling or haploidentical transplant from *** were selec.ed without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in *** payment groups were compared:Out-of-poc.et(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo Leon and *** outcomes included overall survival(OS),categorized by residence,referral,and payment *** outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,Kaplan-Meier method,and cox proportional hazard regression *** software included SPSS and R with tidycmprsk *** Our primary outcome was overall *** included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients dia

关键词： Hematopoietic cell transplant Social determinants of health Geography Haploidentical Out-of-poc.et Financial toxicity Survival Health services and outcomes Hematopoietic malignancy Aplastic anemia