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1.
Respirol Case Rep ; 12(7): e01421, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38938762

ABSTRACT

Pelvic tumours are a rare cause of pleural effusion. We describe an approach to a case of Meigs syndrome with recurrent unilateral pleural effusion. A woman in her 60s' presented with recurrent right-sided pleural effusion, leading to cough and shortness of breath. Thoracentesis yielded exudative pleural fluid with cytology negative for malignancy. Pleuroscopy revealed inflamed pleura, and pleural biopsy was consistent with inflammatory changes. The patient's cancer antigen 125 level was elevated at 256 U/mL. Given the high suspicion of malignancy, a computed tomography scan of the chest, abdomen, and pelvis was performed and revealed ascites and a large left ovarian and uterine mass. The patient underwent a total abdominal hysterectomy and bilateral salphingo oophorectomy after experiencing three additional episodes of pleural effusion. Histological examination revealed the left ovarian mass to be a cellular fibroma and the uterine masses to be leiomyomata. Following the operation, there was no recurrence of pleural effusion.

2.
Environ Sci Technol ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940696

ABSTRACT

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.

3.
Aging (Albany NY) ; 16(11): 9410-9436, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38848145

ABSTRACT

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.


Subject(s)
Apolipoprotein A-V , Class I Phosphatidylinositol 3-Kinases , Colorectal Neoplasms , Drug Resistance, Neoplasm , Mutation , Oxaliplatin , Reactive Oxygen Species , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Apolipoprotein A-V/genetics , Apolipoprotein A-V/metabolism , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Reactive Oxygen Species/metabolism , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Animals , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice , Male , Apoptosis/drug effects , Apoptosis/genetics , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Signal Transduction/drug effects
4.
Exp Cell Res ; 440(1): 114130, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38885805

ABSTRACT

Prostate cancer (PCa) is the most prevalent malignant tumor of the genitourinary system, and metastatic disease has a significant impact on the prognosis of PCa patients. As a result, knowing the processes of PCa development can help patients achieve better outcomes. Here, we investigated the expression and function of ORC6 in PCa. Our findings indicated that ORC6 was elevated in advanced PCa tissues. Patients with PCa who exhibited high levels of ORC6 had a poor prognosis. Following that, we investigated the function of ORC6 in PCa progression using a variety of functional experiments both in vivo and in vitro, and discovered that ORC6 knockdown inhibited PCa cell proliferation, growth, and migration. Furthermore, RNA-seq was employed to examine the molecular mechanism of PCa progression. The results revealed that ORC6 might promote the expression of PLK1, a serine/threonine kinase in PCa cells. We also discovered that ORC6 as a novel miR-361-5p substrate using database analysis, and miR-361-5p was found to lower ORC6 expression. Additionally, RNA immunoprecipitation (RIP) and luciferase reporter tests revealed that the transcription factor E2F1 could regulate ORC6 expression in PCa cells. PLK1 overexpression or miR-361-5p inhibitor treatment effectively removed the inhibitory effects caused by ORC6 silencing. Notably, our data showed that therapeutically targeting the miR-361-5p/ORC6/PLK1 axis may be a viable therapy option for PCa.


Subject(s)
Cell Cycle Proteins , Cell Movement , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , MicroRNAs , Polo-Like Kinase 1 , Prostatic Neoplasms , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Proliferation/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Gene Expression Regulation, Neoplastic/genetics , Cell Movement/genetics , Animals , Cell Line, Tumor , Mice , Origin Recognition Complex/genetics , Origin Recognition Complex/metabolism , Mice, Nude , Prognosis , Mice, Inbred BALB C
5.
Sci Rep ; 14(1): 14404, 2024 06 22.
Article in English | MEDLINE | ID: mdl-38909101

ABSTRACT

This study aimed to develop and validate prediction models to estimate the risk of death and intensive care unit admission in COVID-19 inpatients. All RT-PCR-confirmed adult COVID-19 inpatients admitted to Fujian Provincial Hospital from October 2022 to April 2023 were considered. Elastic Net Regression was used to derive the risk prediction models. Potential risk factors were considered, which included demographic characteristics, clinical symptoms, comorbidities, laboratory results, treatment process, prognosis. A total of 1906 inpatients were included finally by inclusion/exclusion criteria and were divided into derivation and test cohorts in a ratio of 8:2, where 1526 (80%) samples were used to develop prediction models under a repeated cross-validation framework and the remaining 380 (20%) samples were used for performance evaluation. Overall performance, discrimination and calibration were evaluated in the validation set and test cohort and quantified by accuracy, scaled Brier score (SbrS), the area under the ROC curve (AUROC), and Spiegelhalter-Z statistics. The models performed well, with high levels of discrimination (AUROCICU [95%CI]: 0.858 [0.803,0.899]; AUROCdeath [95%CI]: 0.906 [0.850,0.948]); and good calibrations (Spiegelhalter-ZICU: - 0.821 (p-value: 0.412); Spiegelhalter-Zdeath: 0.173) in the test set. We developed and validated prediction models to help clinicians identify high risk patients for death and ICU admission after COVID-19 infection.


Subject(s)
COVID-19 , Hospitalization , Intensive Care Units , Humans , COVID-19/mortality , COVID-19/virology , Male , Female , Middle Aged , Aged , Risk Factors , Adult , SARS-CoV-2/isolation & purification , Hospital Mortality , ROC Curve , Prognosis , Risk Assessment/methods , China/epidemiology
6.
Front Plant Sci ; 15: 1351023, 2024.
Article in English | MEDLINE | ID: mdl-38916035

ABSTRACT

Introduction: The genus Sanicula L. is a taxonomically complicated taxa within Apiaceae, as its high variability in morphology. Although taxonomists have performed several taxonomic revisions for this genus, the interspecific relationships and species boundaries have not been satisfactorily resolved, especially for those endemic to China. This study mainly focused on S. giraldii var. ovicalycina, S. tienmuensis var. pauciflora, and S. orthacantha var. stolonifera and also described two new members of the genus. Methods: We newly sequenced sixteen plastomes from nine Sanicula species. Combined with eleven plastomes previously reported by us and one plastome downloaded, we performed a comprehensively plastid phylogenomics analysis of 21 Sanicula taxa. Results and Discussion: The comparative results showed that 21 Sanicula plastomes in their structure and features were highly conserved and further justified that two new species were indeed members of Sanicula. Nevertheless, eleven mutation hotspot regions were still identified. Phylogenetic analyses based on plastome data and the ITS sequences strongly supported that these three varieties were clearly distant from three type varieties. The results implied that these three varieties should be considered as three independent species, which were further justified by their multiple morphological characters. Therefore, revising these three varieties into three independent species was reasonable and convincing. Moreover, we also identified and described two new Sanicula species (S. hanyuanensis and S. langaoensis) from Sichuan and Shanxi, China, respectively. Based on their distinct morphological characteristics and molecular phylogenetic analysis, two new species were included in Sanicula. In summary, our study impelled the revisions of Sanicula members and improved the taxonomic system of the genus.

7.
J Asthma ; : 1-38, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832793

ABSTRACT

OBJECTIVE: Inappropriate use of short-acting beta2-agonists (SABA) in asthma has been associated with undesired outcomes. This national expert consensus was developed to spread awareness of SABA overuse and provide recommendations on the ways to eliminate SABA overprescription and overreliance in asthma care in Malaysia. DATA SOURCES: This expert consensus was developed by searching the PubMed database, using index terms to identify SABA overuse-related burden and recommendations made in asthma guidelines. Consensus recommendations were made via the Delphi method, involving a Malaysian expert committee comprising 13 healthcare professionals (five pulmonologists, four family medicine specialists, two emergency medicine physicians and two pharmacists). STUDY SELECTIONS: The articles reviewed include randomized controlled trials, systematic reviews, meta-analyses, observational studies, guidelines, and surveys, with abstracts in English and published up until June 2023. Relevant recommendations were also sourced from the verified websites of medical organizations and societies. RESULTS: Eleven consensus statements were developed, each statement achieving a priori agreement level of at least 70%. The statements reflect SABA overreliance in asthma care, as well as recommendations to eliminate SABA overprescription and overreliance in Malaysia. Supporting evidence in literature as well as expert committee discussions leading to the development of the finalized statements were elaborated. CONCLUSION: This national expert consensus discussed the burden of SABA overreliance and made specific recommendations to eliminate SABA overprescription and overreliance in the Malaysian context. This consensus document is anticipated to impart better awareness among Malaysian healthcare providers and contribute to the continuous improvement of asthma care in the country.

8.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): B106-B115, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38856418

ABSTRACT

The evolution of the information transfer capability of an optical system for underwater focused wave mode localized wave (FWMLW) in anisotropic weakly turbulent absorbing seawater is studied. By developing the probability distribution function as well as the detection probability of the vortex modes carried by the FWMLW and the average bit error rate of the FWMLW underwater system, the information capacity of the FWMLW system with a pointing error is modeled. Through a numerical analysis of the effects of turbulent seawater and optical system parameters on the built light intensity, the detection probability, and the information capacity models, we find that the FWMLW system has an optimal delay time determined by the spectrum bandwidth when the spectrum bandwidth is greater than 1. The information capacity of the FWMLW system is higher than that of the X localized wave system under the same turbulent seawater channel condition, and FWMLW is a better optical signal source for vortex mode division multiplexing underwater systems than a Bessel-Gaussian beam.

9.
J Immunol ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856712

ABSTRACT

Bats are the natural reservoir hosts of some viruses, some of which may spill over to humans and cause global-scale pandemics. Different from humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I IFNs (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments about whether bats have a contracted genome locus or constitutively expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lack of pan-bat analysis, the common characteristics of bat IFN-Is have not been revealed yet. In this study, we characterized the IFN-I locus for nine Yangochiroptera bats and three Yinpterochiroptera bats on the basis of their high-quality bat genomes. We also compared the basal expression in six bats and compared the antiviral and antiproliferative activity and the thermostability of representative Rhinolophus bat IFNs. We found a dominance of unconventional IFNω-like responses in the IFN-I system, which is unique to bats. In contrast to IFNα-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFNω-like genes (IFNω or related IFNαω), but with fewer or even no IFNα genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFNω-like gene. Likewise, the highly expressed IFNω-like protein also demonstrated the best antiviral activity, antiproliferative activity, or thermostability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique, to our knowledge, characteristics in the IFN-I system, which provide insights into our understanding of the innate immunity that contributes to a special coexistence between bats and viruses.

10.
Article in English | MEDLINE | ID: mdl-38839543

ABSTRACT

The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines.

12.
Front Nutr ; 11: 1387676, 2024.
Article in English | MEDLINE | ID: mdl-38873559

ABSTRACT

Background: The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function. Methods: We utilized data from the National Health and Nutrition Examination Survey from 2003-2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust adjusted profile score were the primary analytical methods employed. Results: A total of 20,470 participants were included in the study, with 1,257 participants ultimately included in the analysis. In all adjusted logistic regression models, no significant association was found between the intake of artificial sweeteners and CKD risk. Similarly, the summary odds ratios (OR) for each unit change in genetically predicted CKD risk were 2.14 (95% CI: 0.83, 5.21, p = 0.092), 1.41 (95% CI: 0.54, 3.63, p = 0.482), and 1.50 (95% CI: 0.50, 4.52, p = 0.468) for the impact of artificial sweeteners added to cereals, tea, and coffee, respectively. It was only observed that adding artificial sweeteners to coffee was associated with a modest reduction in urinary albumin-to-creatinine ratio (OR = 0.94, 95% CI: -0.108, -0.022, p = 0.003), the effect appeared to be relatively small and may not directly impact the individual level. Conclusion: Our study does not support a causal relationship between artificial sweetener intake and the risk of CKD. However, due to the limitations and potential confounding factors, these findings need to be further validated through larger sample sizes in observational studies and Mendelian randomization analyses.

13.
Orbit ; : 1, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864585
14.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1223-1232, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38886420

ABSTRACT

The radial growth of trees plays a crucial role in determining forest carbon sequestration capacity. Understanding the growth dynamics of trees and their response to environmental factors is essential for predicting forest's carbon sink potential under future climate change. Coniferous forest trees are particularly sensitive to climate change, with growth dynamics responding rapidly to environmental shifts. We collected and analyzed data from 99 papers published between 1975 and 2023, and examined the effects of exogenous factors (such as temperature, water, and photoperiod) and endogenous factors (including tree age and species) on cambial activity and radial growth in conifers. We further explored the mechanisms underlying these effects. The results showed that climate warming had the potential to advance the onset while delayed the end of xylem differentiation stages in conifers in temperate and boreal regions. Water availability played a crucial role in regulating the timing of cambial phenology and wood formation by influencing water potential and cell turgor. Additionally, the photoperiod not only participated in regulating the start and end times of growth, but also influenced the timing of maximum growth rate occurrence. Future climate warming was expected to extend the growing season, leading to increase in growth of conifers in boreal regions and expanding forests to higher altitudes or latitudes. However, changes in precipitation patterns and increased evapotranspiration resulting from temperature increases might advance the end of growing season and reduce growth rate in arid areas. To gain a more comprehensive understanding of the relationship between radial growth and climatic factors, it is necessary to develop process-based models to elucidate the physiological mechanisms underlying wood formation and the response of trees to climatic factors.


Subject(s)
Cambium , Climate Change , Tracheophyta , Cambium/growth & development , Tracheophyta/growth & development , Tracheophyta/physiology , Ecosystem , Carbon Sequestration
15.
Biomed Pharmacother ; 177: 116977, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38901203

ABSTRACT

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

16.
Inorg Chem ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902911

ABSTRACT

Pathogenic bacteria have consistently posed a formidable challenge to human health, creating the critical need for effective antibacterial solutions. In response, enzyme-metal-organic framework (MOF) composites have emerged as a promising class of antibacterial agents. This study focuses on the development of an enzyme-MOF composite based on HZIF-8, incorporating the advantages of simple synthesis, ZIF-8 antibacterial properties, lysozyme hydrolysis, and high biological safety. Through a one-pot method, core-shell nanoparticles (HZIF-8) were synthesized. This structure enables efficient immobilization of lysozyme and lactoferrin within the HZIF-8, resulting in the formation of the lysozyme-lactoferrin@HZIF-8 (LYZ-LF@HZIF-8) composite. Upon exposure to light irradiation, HZIF-8 itself possessed antibacterial properties. Lysozyme initiated the degradation of bacterial peptidoglycan and lactoferrin synergistically enhanced the antibacterial effect of lysozyme. All of the above ultimately contributed to comprehensive antibacterial activity. Antibacterial assessments demonstrated the efficacy of the LYZ-LF@HZIF-8 composite, effectively eradicating Staphylococcus aureus at a cell density of 1.5 × 106 CFU/mL with a low dosage of 200 µg/mL and completely inactivating Escherichia coli at 400 µg/mL with the same cell density. The enzyme-MOF composite exhibited significant and durable antibacterial efficacy, with no apparent cytotoxicity in vitro, thereby unveiling expansive prospects for applications in the medical and food industries.

17.
Langmuir ; 40(25): 13001-13009, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38860838

ABSTRACT

Metal-organic frameworks (MOFs) based on tin (Sn) have shown great potential as materials for lithium storage, thanks to their ability to alleviate volume expansion due to the homogeneous distribution of Sn in a porous matrix framework. However, the weak mechanical strength of the porous Sn-MOF structure has been a major challenge, leading to pulverization during the discharging/charging process. To overcome this issue, we have developed a feasible strategy to strengthen the Sn-MOF mechanical properties by incorporating SiO2/GeO2 nanoparticles during the synthesis process. The resulting composites of Sn-Si and Sn-Ge exhibited high energy density and long-term cycle stability, thanks to their synergistic effect in alloying and conversion reactions. Our density functional theory (DFT) calculations have revealed that the rigid SiO2/GeO2 nanoparticles enhance the Sn-MOF mechanical properties, including Young's and shear moduli, which contribute to the long-term cycle stability of these composites.

18.
PLoS Pathog ; 20(6): e1012260, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38885242

ABSTRACT

Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy.


Subject(s)
Capsid Proteins , Dependovirus , Evolution, Molecular , Selection, Genetic , Dependovirus/genetics , Dependovirus/immunology , Humans , Animals , Capsid Proteins/genetics , Capsid Proteins/immunology , Genetic Variation , Genetic Therapy
19.
Bioact Mater ; 39: 336-353, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38827171

ABSTRACT

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

20.
Clin Nucl Med ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38861378

ABSTRACT

ABSTRACT: A 75-year-old woman with papillary thyroid carcinoma who underwent 131I radioiodine treatment was incidentally found to have an established left cerebral infarct demonstrating 131I uptake on posttherapy whole-body scan. False-positive iodine accumulation can occur in benign processes and other malignancies, necessitating awareness among nuclear medicine physicians to avoid misdiagnosing metastatic disease. SPECT/CT can be utilized to enhance diagnostic accuracy when needed.

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