bluuebunny/crossref_metadata_2025 huggingface dataset:
Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders
Authors: Opelka Bianca , Schmidt Enno , Goletz Stephanie
Published: August 2022

Pemphigoid diseases (PD) are autoimmune skin blistering diseases characterized by autoantibodies directed against proteins of the cutaneous basement membrane zone (BMZ). One of the major antigens is type XVII collagen (BP180), a transmembrane glycoprotein, which is targeted in four PDs: bullous pemphigoid, mucous membrane pemphigoid, linear IgA dermatosis, and pemphigoid gestationis. To date, different epitopes on BP180 have been described to be recognized by PD disease patients’ autoantibodies. Different BP180 epitopes were associated with distinct clinical phenotypes while the underlying mechanisms are not yet fully understood. So far, the main effects of anti-BP180 reactivity are mediated by Fcγ-receptors on immune cells. More precisely, the autoantibody–antigen interaction leads to activation of complement at the BMZ and infiltration of immune cells into the upper dermis and, by the release of specific enzymes and reactive oxygen species, to the degradation of BP180 and other BMZ components, finally manifesting as blisters and erosions. On the other hand, inflammatory responses independent of Fcγ-receptors have also been reported, including the release of proinflammatory cytokines and internalization and depletion of BP180. Autoantibodies against BP180 can also be found in patients with neurological diseases. The assumption that the clinical expression of PD depends on epitope specificity in addition to target antigens, autoantibody isotypes, and antibody glycosylation is supported by the observation that epitopes of PD patients differ from those of PD patients. The aim of the present review is to describe the fine specificities of anti-BP180 autoantibodies in different PDs and highlight the associated clinical differences. Furthermore, the direct effects after binding of the autoantibodies to their target are summarized.
Antiphospholipid antibodies are persistently positive at high titers. Additive value of platelet-bound C4d
Authors: Sciascia Savino , Bloch Rory , O’Malley Tyler , Kammesheidt Anja , Alexander Roberta Vezza
Published: August 2022

Background

Classification criteria for antiphospholipid syndrome (APS) require that antiphospholipid antibody (aPL) positivity is confirmed after at least 12 weeks. We tested the hypothesis that aPL at high titers remain positive while low titers fluctuate over time. As both platelet-bound C4d (PC4d) and aPL are associated with thrombosis in systemic lupus erythematosus (SLE), we also evaluated whether PC4d can aid in APS diagnosis.

Methods

Data from serum or plasma sent to Exagen’s laboratory for routine aPL testing were analyzed. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein-1 antibodies (aB2GP1) were measured by chemiluminescence or ELiA fluorescence enzyme immunoassay; anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) by ELISA; PC4d by flow cytometry. Statistical analysis included descriptive statistics, logistic regression, and Pearson correlation.

Results

More than 80% of positive samples with aCL and aB2GP1 at high titers - but not low titers - were positive at a retest. Non-criteria aPL (aPS/PT) followed a similar trend. aCL and aB2GP1 measured with two different technologies were highly correlated. PC4d and IgG of the three aPL were at best moderately correlated even when only positive aPL samples were analyzed (coefficient: 0.1917 to 0.2649).

Conclusions

High titers aPL are often persistently positive, allowing an earlier diagnosis and risk assessment at the time of the initial screening. Conversely, a retest may be necessary for low titers. The high correlation between two methodologies suggests that these findings are independent of assay platform. The low to moderate correlation between PC4d and aPL might suggest a possible additive value to evaluate association with thrombosis in autoimmune diseases.
Roles, detection, and visualization of neutrophil extracellular traps in acute pancreatitis
Authors: Li Hongxuan , Zhao Lingyu , Wang Yueying , Zhang Meng-Chun , Qiao Cong
Published: August 2022

Neutrophil extracellular traps (NETs) are produced in large quantities at the site of inflammation, and they locally capture and eliminate various pathogens. Thus, NETs quickly control the infection of pathogens in the body and play vital roles in immunity and antibacterial effects. However, evidence is accumulating that NET formation can exacerbate pancreatic tissue damage during acute pancreatitis (AP). In this review, we describe the research progress on NETs in AP and discuss the possibility of NETs as potential therapeutic targets. In addition, since the current detection and visualization methods of NET formation are not uniform and the selection of markers is still controversial, a synopsis of these issues is provided in this review.
Effect of dietary soybean meal on growth performance, apparent digestibility, intestinal digestive enzyme activity and muscle growth-related gene expression of Litopenaeus vannamei
Authors: Peng Kai , Chen Xiaoying , Lu Huijie , Zhao Jichen , Chen Yihong , Li Chaozheng , Li Huo , Huang Wen
Published: August 2022

Soybean meal is one of the major components of aquatic animal diets, whereas little information is available about the evaluation of soybean meal growth suppression mode of action. A 42-day feeding trial was performed to assess the effects of dietary soybean meal on growth performance, apparent digestibility, intestinal digestive enzyme activity, and muscle growth–related gene expression of Litopenaeus vannamei. A total of 600 shrimp were randomly distributed into 20 tanks with 30 shrimp per tank and four tanks per group. The soybean meal was added to the diets at the rate of 20% (T20), 28% (T28), 35% (T35), 42% (T42), and 50% (T50), respectively. Shrimp were fed with apparent satiation three times daily. Results indicated that the final body weight, weight gain rate, specific growth rate, feed intake, intestinesomatic index, dressed weight percentage, and the apparent digestibility coefficients of dry matter, crude protein, crude lipid, and ash were linearly decreased (p < 0.05), but feed coefficient was linearly increased (p < 0.05) as dietary soybean meal increased from 20% to 50%. The intestinal trypsin and amylase activities were decreased (p < 0.05) as dietary soybean meal increased from 20% to 50%, and reached significance at the level of 35%, 42%, and 50%. Shrimp fed with T20 had higher (p < 0.05) intestinal lipase activity than those fed with other diets. The mRNA relative expression of growth hormone, myogenic regulatory factor 5, and target of rapamycin was downregulated (p < 0.05) as dietary soybean meal increased from 20% to 50%. To conclude, dietary soybean meal exceeded 28% significantly inhibited growth performance of L. vannamei, mainly due to the negative impact of soybean meal on digestion and feed utilization and also the inhibition on the muscle growth and related gene expressions.
Progress in Superlubricity Across Different Media and Material Systems—A Review
Authors: Ayyagari Aditya , Alam Kazi Istiaque , Berman Diana , Erdemir Ali
Published: August 2022

Superlubricity is a terminology often used to describe a sliding regime in which the adhesion leading to friction or resistance to sliding literally vanishes. For improved energy security, environmental sustainability, and a decarbonized economy, achieving superlubric sliding surfaces in moving mechanical systems sounds very exciting, since friction adversely impacts the efficiency, durability, and environmental compatibility of many moving mechanical systems used in industrial sectors. Accordingly, scientists and engineers have been exploring new ways to achieve macroscale superlubricity through the use of advanced materials, coatings, and lubricants for many years. As a result of such concerted efforts, recent developments indicate that with the use of the right kinds of solids, liquids, and gases on or in the vicinity of sliding contact interfaces, one can indeed achieve friction coefficients well below 0.01. The friction coefficient below this threshold is commonly termed the superlubric sliding regime. Hopefully, these developments will foster further research in the field of superlubricity and will ultimately give rise to the industrial scale realization of nearly-frictionless mechanical systems consuming far less energy and causing much-reduced greenhouse gas emissions. This will ultimately have a substantial positive impact on the realization of economically and environmentally viable industrial practices supporting a decarbonized energy future. In this paper, we will provide an overview of recent progress in superlubricity research involving solid, liquid, and gaseous media and discuss the prospects for achieving superlubricity in engineering applications leading to greater efficiency, durability, environmental quality, and hence global sustainability.
Bibliometric and visual analysis of intestinal ischemia reperfusion from 2004 to 2022
Authors: Wan Yantong , Dong Peng , Zhu Xiaobing , Lei Yuqiong , Shen Junyi , Liu Weifeng , Liu Kexuan , Zhang Xiyang
Published: August 2022

Background

Intestinal ischemia/reperfusion (I/R) injury is a common tissue-organ damage occurring in surgical practice. This study aims to comprehensively review the collaboration and impact of countries, institutions, authors, subject areas, journals, keywords, and critical literature on intestinal I/R injury from a bibliometric perspective, and to assess the evolution of clustering of knowledge structures and identify hot trends and emerging topics.

Methods

Articles and reviews related to intestinal I/R were retrieved through subject search from Web of Science Core Collection. Bibliometric analyses were conducted on Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).

Results

A total of 1069 articles and reviews were included from 2004 to 2022. The number of articles on intestinal I/R injury gradually plateaued, but the number of citations increased. These publications were mainly from 985 institutions in 46 countries, led by China and the United States. Liu Kx published the most papers, while Chiu Cj had the largest number of co-citations. Analysis of the journals with the most outputs showed that most journals focused on surgical sciences, cell biology, and immunology. Macroscopic sketch and microscopic characterization of the entire knowledge domain were achieved through co-citation analysis. The roles of cell death, exosomes, intestinal flora, and anesthetics in intestinal I/R injury are the current and developing research focuses. The keywords “dexmedetomidine”, “proliferation”, and “ferroptosis” may also become new trends and focus of future research.

Conclusion

This study comprehensively reviews the research on intestinal I/R injury using bibliometric and visualization methods, and will help scholars better understand the dynamic evolution of intestinal I/R injury and provide directions for future research.
Medical terminology-based computing system: a lightweight post-processing solution for out-of-vocabulary multi-word terms
Authors: Saeed Nadia , Naveed Hammad
Published: August 2022

The linguistic rules of medical terminology assist in gaining acquaintance with rare/complex clinical and biomedical terms. The medical language follows a Greek and Latin-inspired nomenclature. This nomenclature aids the stakeholders in simplifying the medical terms and gaining semantic familiarity. However, natural language processing models misrepresent rare and complex biomedical words. In this study, we present MedTCS—a lightweight, post-processing module—to simplify hybridized or compound terms into regular words using medical nomenclature. MedTCS enabled the word-based embedding models to achieve 100% coverage and enabled the BiowordVec model to achieve high correlation scores (0.641 and 0.603 in UMNSRS similarity and relatedness datasets, respectively) that significantly surpass the n-gram and sub-word approaches of FastText and BERT. In the downstream task of named entity recognition (NER), MedTCS enabled the latest clinical embedding model of FastText-OA-All-300d to improve the F1-score from 0.45 to 0.80 on the BC5CDR corpus and from 0.59 to 0.81 on the NCBI-Disease corpus, respectively. Similarly, in the drug indication classification task, our model was able to increase the coverage by 9% and the F1-score by 1%. Our results indicate that incorporating a medical terminology-based module provides distinctive contextual clues to enhance vocabulary as a post-processing step on pre-trained embeddings. We demonstrate that the proposed module enables the word embedding models to generate vectors of out-of-vocabulary words effectively. We expect that our study can be a stepping stone for the use of biomedical knowledge-driven resources in NLP.
Polymorphism in alpha-synuclein oligomers and its implications in toxicity under disease conditions
Authors: Yoo Je Min , Lin Yuxi , Heo Yunseok , Lee Young-Ho
Published: August 2022

The major hallmark of Parkinson’s disease (PD) is represented by the formation of pathological protein plaques largely consisting of α-synuclein (αSN) amyloid fibrils. Nevertheless, the implications of αSN oligomers in neuronal impairments and disease progression are more importantly highlighted than mature fibrils, as they provoke more detrimental damages in neuronal cells and thereby exacerbate α-synucleinopathy. Interestingly, although generation of oligomeric species under disease conditions is likely correlated to cytotoxicity and different cellular damages, αSN oligomers manifest varying toxicity profiles dependent on the specific environments as well as the shapes and conformations the oligomers adopt. As such, this minireview discusses polymorphism in αSN oligomers and the association of the underlying heterogeneity in regard to toxicity under pathological conditions.
Roles of microglial mitophagy in neurological disorders
Authors: Liu Yang , Wang Miao , Hou Xiao-Ou , Hu Li-Fang
Published: August 2022

Microglia are the resident innate immune cells in the central nervous system (CNS) that serve as the first line innate immunity in response to pathogen invasion, ischemia and other pathological stimuli. Once activated, they rapidly release a variety of inflammatory cytokines and phagocytose pathogens or cell debris (termed neuroinflammation), which is beneficial for maintaining brain homeostasis if appropriately activated. However, excessive or uncontrolled neuroinflammation may damage neurons and exacerbate the pathologies in neurological disorders. Microglia are highly dynamic cells, dependent on energy supply from mitochondria. Moreover, dysfunctional mitochondria can serve as a signaling platform to facilitate innate immune responses in microglia. Mitophagy is a means of clearing damaged or redundant mitochondria, playing a critical role in the quality control of mitochondrial homeostasis and turnover. Mounting evidence has shown that mitophagy not only limits the inflammatory response in microglia but also affects their phagocytosis, whereas mitochondria dysfunction and mitophagy defects are associated with aging and neurological disorders. Therefore, targeting microglial mitophagy is a promising therapeutic strategy for neurological disorders. This article reviews and highlights the role and regulation of mitophagy in microglia in neurological conditions, and the research progress in manipulating microglial mitophagy and future directions in this field are also discussed.
A virtual reality time reproduction task for rodents
Authors: Henke Josphine , Flanagin Virginia L. , Thurley Kay
Published: August 2022

Estimates of the duration of time intervals and other magnitudes exhibit characteristic biases that likely result from error minimization strategies. To investigate such phenomena, magnitude reproduction tasks are used with humans and other primates. However, such behavioral tasks do not exist for rodents, one of the most important animal orders for neuroscience. We, therefore, developed a time reproduction task that can be used with rodents. It involves an animal reproducing the duration of a timed visual stimulus by walking along a corridor. The task was implemented in virtual reality, which allowed us to ensure that the animals were actually estimating time. The hallway did not contain prominent spatial cues and movement could be de-correlated from optic flow, such that the animals could not learn a mapping between stimulus duration and covered distance. We tested the reproduction of durations of several seconds in three different stimulus ranges. The gerbils reproduced the durations with a precision similar to experiments on humans. Their time reproductions also exhibited the characteristic biases of magnitude estimation experiments. These results demonstrate that our behavioral paradigm provides a means to study time reproduction in rodents.
A preclinical study of deep brain stimulation in the ventral tegmental area for alleviating positive psychotic-like behaviors in mice
Authors: Lu Chen , Feng Yifan , Li Hongxia , Gao Zilong , Zhu Xiaona , Hu Ji
Published: August 2022

Deep brain stimulation (DBS) is a clinical intervention for the treatment of movement disorders. It has also been applied to the treatment of psychiatric disorders such as depression, anorexia nervosa, obsessive-compulsive disorder, and schizophrenia. Psychiatric disorders including schizophrenia, bipolar disorder, and major depression can lead to psychosis, which can cause patients to lose touch with reality. The ventral tegmental area (VTA), located near the midline of the midbrain, is an important region involved in psychosis. However, the clinical application of electrical stimulation of the VTA to treat psychotic diseases has been limited, and related mechanisms have not been thoroughly studied. In the present study, hyperlocomotion and stereotyped behaviors of the mice were employed to mimic and evaluate the positive-psychotic-like behaviors. We attempted to treat positive psychotic-like behaviors by electrically stimulating the VTA in mice and exploring the neural mechanisms behind behavioral effects. Local field potential recording and in vivo fiber photometry to observe the behavioral effects and changes in neural activities caused by DBS in the VTA of mice. Optogenetic techniques were used to verify the neural mechanisms underlying the behavioral effects induced by DBS. Our results showed that electrical stimulation of the VTA activates local gamma-aminobutyric acid (GABA) neurons, and dopamine (DA) neurons, reduces hyperlocomotion, and relieves stereotyped behaviors induced by MK-801 (dizocilpine) injection. The results of optogenetic manipulation showed that the activation of the VTA GABA neurons, but not DA neurons, is involved in the alleviation of hyperlocomotion and stereotyped behaviors. We visualized changes in the activity of specific types in specific brain areas induced by DBS, and explored the neural mechanism of DBS in alleviating positive psychotic-like behaviors. This preclinical study not only proposes new technical means of exploring the mechanism of DBS, but also provides experimental justification for the clinical treatment of psychotic diseases by electrical stimulation of the VTA.
The value of mobile magnetic resonance imaging in early warning for stroke: A prospective case-control study
Authors: Liu Miaomiao , Li Qingyang , Chen Guoqiang , Su Ning , Zhou Maorong , Liu Xiaolin , Sun Kai
Published: August 2022

Aims

To evaluate the predictive value of mobile magnetic resonance imaging (MRI) in screening stroke.

Methods

This was a prospective case-control study performed on healthy residents over 40 years old in remote rural areas of northern China between May 2019 and May 2020. Multivariate logistic regression and receiver operator characteristic curve (ROC) analysis were used to evaluate the screening model.

Results

A total of 1,224 patients (500 [40.8%] men) enrolled, including 56 patients who suffered from stroke (aged 64.05 ± 7.27). The individuals who developed stroke were significantly older (P < 0.001), had a significantly higher occurrence of heart disease (P = 0.015), diabetes (P = 0.005), dyslipidemia (P = 0.009), and significantly increased waist circumference (P = 0.02), systolic blood pressure (SBP) (P = 0.003), glycosylated hemoglobin (HbA1c) level (P = 0.007), triglyceride (TG) level (P = 0.025), low density lipoprotein cholesterol (LDL-c) level (P = 0.04), and homocysteine (HCY) level (P < 0.001). Multivariate logistic regression analysis showed that age (OR = 1.055, 95% CI: 1.017–1.094, P = 0.004), HCY (OR = 1.029, 95% CI: 1.012–1.047, P = 0.001) and mobile MRI (OR = 4.539, 95% CI: 1.726–11.939, P = 0.002) were independently associated with stroke. The area under the curve (AUC) of the combined model including national screening criteria, mobile MRI results, and stroke risk factors was 0.786 (95% CI: 0.721–0.851), with a sensitivity of 69.6% and specificity of 80.4%.

Conclusion

Mobile MRI can be used as a simple and easy means to screen stroke.
Secondary damage and neuroinflammation in the spinal dorsal horn mediate post-thalamic hemorrhagic stroke pain hypersensitivity: SDF1-CXCR4 signaling mediation
Authors: Liang Ting , Chen Xue-Feng , Yang Yan , Yang Fei , Yu Yang , Yang Fan , Wang Xiao-Liang , Wang Jiang-Lin , Sun Wei , Chen Jun
Published: August 2022

Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.
U(VI), Np(V), Eu(III) sorption on goethite: A wide-ranging multiradionuclide dataset and uncertainty-aware parametrization of surface complexation models
Authors: Romanchuk Anna Yu. , Svitelman Valentina S. , Blinov Peter D. , Larina Alena I. , Nevolin Iurii M. , Egorov Alexander V. , Saveleva Elena A. , Kalmykov Stepan N.
Published: August 2022

Obtaining reliable thermodynamic sorption data is essential for establishing databases that can be used for the numerical safety evaluations of radioactive waste storage and disposal facilities. For this purpose, new experimental data on the sorption of U(VI), Np(V), and Eu(III) onto synthesized goethite in a wide range of experimental conditions were collected. Thermodynamic surface complexation models based on different approaches were developed and parametrized to fit a large dataset, including experimental data from the current work as well as available literature data. The proposed heuristic optimization procedure allowed identifying and comparing different parametrization variants and their uncertainties for considered models. The developed models pass the test on additional Cd(II) and Zn(II) data, simultaneously providing a reliable description of the sorption process for five cations and could probably be extended using the obtained linear free energy relationship.
Preclinical insights into fucoidan as a nutraceutical compound against perfluorooctanoic acid-associated obesity via targeting endoplasmic reticulum stress
Authors: Liu Jiaqi , Guo Chao , Wang Yuqin , Su Min , Huang Wenjun , Lai Keng Po
Published: August 2022

Obesity is a growing global health problem; it has been forecasted that over half of the global population will be obese by 2030. Obesity is complicated with many diseases, such as diabetes and cardiovascular diseases, leading to an economic impact on society. Other than diet, exposure to environmental pollutants is considered a risk factor for obesity. Exposure to perfluorooctanoic acid (PFOA) was found to impair hepatic lipid metabolism, resulting in obesity. In this study, we applied network pharmacology and systematic bioinformatics analysis, such as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, together with molecular docking, to investigate the targets of fucoidan for treating PFOA-associated obesity through the regulation of endoplasmic reticulum stress (ERS). Our results identified ten targets of fucoidan, such as glucosylceramidase beta (GBA), glutathione-disulfide reductase (GSR), melanocortin 4 receptor (MC4R), matrix metallopeptidase (MMP)2, MMP9, nuclear factor kappa B subunit 1 (NFKB1), RELA Proto-Oncogene, NF-KB Subunit (RELA), nuclear receptor subfamily 1 group I member 2 (NR1I2), proliferation-activated receptor delta (PPARD), and cellular retinoic acid binding protein 2 (CRABP2). GO and KEGG enrichment analyses highlighted their involvement in the pathogenesis of obesity, such as lipid and fat metabolisms. More importantly, the gene cluster is responsible for obesity-associated diseases and disorders, such as insulin resistance (IR), non-alcoholic fatty liver disease, and diabetic cardiomyopathy, via the control of signaling pathways. The findings of this report provide evidence that fucoidan is a potential nutraceutical product against PFOA-associated obesity through the regulation of ERS.
Folate-modified erythrocyte membrane nanoparticles loaded with Fe3O4 and artemisinin enhance ferroptosis of tumors by low-intensity focused ultrasound
Authors: Wang Xingyue , Li Peng , Jing Xiangxiang , Zhou Yun , Shao Yongfu , Zheng Min , Wang Junrui , Ran Haitao , Tang Hailin
Published: August 2022

To overcome the challenges of the low efficiency of artemisinin (ART) in anticancer therapy due to its poor water solubility and poor bioavailability, we constructed folate (FA)-modified erythrocyte membrane (EM)-camouflaged poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) (PFH/ART@PLGA/Fe3O4-eFA). Specifically, the inner core of these NPs is mainly composed of phase-changeable perfluorohexane (PFH), magnetic Fe3O4 and ART. In vitro experiments showed that the prepared PFH/ART@PLGA/Fe3O4-eFA was readily taken up by 4T1 cancer cells. PFH/ART@PLGA/Fe3O4-eFA was exposed to low-intensity focused ultrasound (LIFU) irradiation to induce PFH phase transition and NPs collapse, which promoted the release of ART and Fe3O4. After LIFU irradiation, the proportion of dead 4T1 cells, the level of reactive oxygen species (ROS) and the concentration of intracellular Fe2+ ions in the PFH/ART@PLGA/Fe3O4-eFA group were much higher than those in the other group, indicating that the synergistic effect between the intracellular Fe2+ ions and the released ART played a critical role in tumor cell ferroptosis by enhancing ROS generation in vitro. We demonstrated that FA-modified EM NPs could enhance the targeting and accumulation of the NPs at the tumor site in vivo. After LIFU irradiation at 3 W/m2 for 7 min, tumor growth was completely suppressed through FA-modified EM NPs collapse and the release of ART and Fe3O4, which exerted synergistic effects in inducing tumor ferroptosis. Because of these characteristics, these NPs are considered as a promising approach for the delivery of drugs with poor water solubility for efficient cancer therapy.
Long-term outcomes of prostate intensity-modulated radiation therapy incorporating a simultaneous intra-prostatic MRI-directed boost
Authors: Laughlin Brady S. , Silva Alvin C. , Vora Sujay A. , Keole Sameer R. , Wong William W. , Schild Michael H. , Schild Steven E.
Published: August 2022

Purpose/objectives

This retrospective study demonstrates the long-term outcomes of treating prostate cancer using intensity modulated (IMRT) with incorporation of MRI-directed boost.

Materials/methods

From February 2009 to February 2013, 78 men received image-guided IMRT delivering 77.4 Gy in 44 fractions with simultaneously integrated boost to 81–83 Gy to an MRI-identified lesion. Patients with intermediate-risk or high-risk prostate cancer were recommended to receive 6 and 24–36 months of adjuvant hormonal therapy, respectively.

Results

Median follow-up was 113 months (11–147). There were 18 low-risk, 43 intermediate-risk, and 17 high-risk patients per NCCN risk stratification included in this study. Adjuvant hormonal therapy was utilized in 32 patients (41%). The 10-year biochemical control rate for all patients was 77%. The 10-year biochemical control rates for low-risk, intermediate-risk, and high-risk diseases were 94%, 81%, and 88%, respectively (p = 0.35). The 10-year rates of local control, distant control, and survival were 99%, 88%, and 66%, respectively. Of 25 patients who died, only four (5%) died of prostate cancer. On univariate analysis, T-category and pretreatment PSA level were associated with distant failure rate (p = 0.02). There was no grade =3 genitourinary and gastrointestinal toxicities that persisted at the last follow-up.

Conclusions

This study demonstrated the long-term efficacy of using MRI to define an intra-prostatic lesion for SIB to 81–83Gy while treating the entire prostate gland to 77.4 Gy with IMRT. Our study confirms that modern MRI can be used to locally intensify dose to prostate tumors providing high long-term disease control while maintaining favorable long-term toxicity.
Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
Authors: Wang Jin , Hu Yi , Hamidi Habib , Dos Santos Cedric , Zhang Jingyu , Punnoose Elizabeth , Li Wenjin
Published: August 2022

Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, relapsed and refractory MM has not yet been completely cured due to the immune dysfunction in the tumor microenvironment (TME). In this study, we analyzed the transcriptome data from patients with newly diagnosed (ND) and relapsed/refractory (R/R) MM to characterize differences in the TME and further decipher the mechanism of tumor progression in MM. We observed highly expressed cancer testis antigens and immune suppressive cell infiltration, such as Th2 and M2 cells, are associated with MM progression. Furthermore, the TGF-β signature contributes to the worse outcome of patients with R/R MM. Moreover, patients with ND MM could be classified into immune-low and immune-high phenotypes. Immune-high patients with higher IFN-g signatures are associated with MHC-II–mediated CD4+ T-cell response through CIITA stimulation. The baseline TME status could potentially inform new therapeutic choices for the ND MM who are ineligible for autologous stem cell transplantation and may help predict the response to CAR-T for patients with R/R MM. Our study demonstrates how integrating tumor transcriptome and clinical information to characterize MM immune microenvironment and elucidate potential mechanisms of tumor progression and immune evasion, which will provide insights into MM treatment selection.
Hemangioblastoma in the lateral ventricle: An extremely rare case report
Authors: Pan Ruihan , Shi Jianwei , Xu Yang , Bo Fuduo , Luo Zhengxiang , Zhang Yansong
Published: August 2022

Hemangioblastoma (HB) is a benign vascular tumor that accounts for approximately 2% of intracranial neoplasms. HB of the lateral ventricles is extremely rare. Only a few reports are present in the literature. This article reports a 27-year-old male patient who arrived at our hospital because of a progressive headache lasting one month. The brain Magnetic Resonance Imaging (MRI) revealed a solid-cystic mass of 3.5×3.0 cm in size located in the left lateral ventricle, the surgery was performed by applying an interhemispheric approach to single frontal craniotomy with coronal incision to remove the tumor. The postoperative CT and MRI showed the successful complete removal of the tumor and a normal ventricle morphology. The differential diagnosis should be considered in case of intraventricular tumors including HB. Angiography should be performed prior to surgery when HB is suspected.
Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience
Authors: Bimbatti Davide , Dionese Michele , Lai Eleonora , Cavasin Nicolò , Basso Umberto , Mattana Alvise , Pierantoni Francesco , Zagonel Vittorina , Maruzzo Marco
Published: August 2022

Introduction

Immunotherapy with nivolumab (a monoclonal antibody that targets the programmed cell death protein 1, PD1) has become the standard treatment for patients with metastatic renal cell carcinoma (mRCC) after progression to single-agent tyrosine kinase inhibitors. However, the optimal duration of immunotherapy in this setting has not yet been established.

Patients and methods

We retrospectively reviewed all patients treated with nivolumab at our institution from January 2014 to December 2021 and identified those who discontinued treatment for reasons other than disease progression (PD). We then associated progression-free survival (PFS) and overall survival following treatment cessation with baseline clinical data.

Results

Fourteen patients were found to have discontinued treatment. Four patients (28.6%) ceased treatment due to G3/G4 toxicities, whereas the remaining ten (71.4%) opted to discontinue treatment in agreement with their referring clinicians. The median duration of the initial treatment with nivolumab was 21.7 months (7.5-37.3); during treatment, two patients (14.3%) achieved stable disease as the best response, and the remaining twelve (85.7%) a partial response. At a median follow-up time of 24.2 months after treatment discontinuation, 7 patients (50%) were still progression-free. The median PFS from the date of discontinuation was 19.8 months (15.2 - not reached); a radiological objective response according to RECIST and treatment duration of more than 12 months were associated with a longer PFS. Three patients were re-treated with Nivolumab after disease progression, all of whom achieved subsequent radiological stability.

Conclusion

In our experience, the majority of patients who discontinued treatment in the absence of PD were still progression-free more than 18 months after discontinuation. Patients whose initial treatment duration was less than 12 months or who did not achieve a radiological objective response had a greater risk of progression. Immunotherapy rechallenge is safe and seems capable of achieving disease control.
Case report: Reconstruction of distal medial tibial epiphysis using iliac crest apophyseal autograft
Authors: Zhu Chengming , Shi BaoJie , Rai Saroj , Zhong Haobo , Tang Xin
Published: August 2022

Background

Salter-Harris type VI physeal fracture is a rare injury. This case study aims to present a novel method for treating a rare entity of Salter-Harris type Salter-Harris VI physeal injury of the medial malleolus.

Case presentation

A 6-year-old boy with Salter-Harris type VI physeal injury was successfully treated using the two-stage procedure. In the first stage, the patient was treated with intravenous antibiotics, a series of debridement and lavage followed by a skin graft that left a defect in the medial malleolus. In the second stage, an autogenous iliac crest apophyseal graft was transplanted to reconstruct the medial malleolus, and the ankle joint was stabilized by an external fixator. An additional anticipatory Langenskiold procedure was performed for the physeal bar resection. Although the complete radiological development of medial malleolus compared to the contralateral side was not evident at the last follow-up, the functional and cosmetic outcomes were satisfactory.

Conclusion

The reconstruction of medial malleolus using an autologous iliac crest apophyseal graft and stabilization of the ankle joint with an external fixator is a novel reconstruction technique in treating Salter-Harris type VI physeal injury of the medial malleolus. This technique provides satisfactory functional and cosmetic outcomes in such a fracture pattern; however, a further clinical study using a larger sample size is warranted in order to find the definitive outcome of the technique.
Case Report: Fluzoparib for multiple lines of chemotherapy refractory in metastatic cutaneous squamous cell carcinoma with BRCA2 pathogenic mutation
Authors: Sun Xin , Chen Wenjuan , Qu Xiujuan , Chen Ying
Published: August 2022

Background: Poly ADP-ribose polymerase inhibitors (PARPis) are widely used for patients with BRCA1/2 mutations. However, until now, there is no available evidence reported for the efficiency of PARPis in cutaneous squamous cell carcinoma (cSCC).

Case presentation: We presented a case of a 40-year-old man diagnosed with metastatic cSCC, relapsing after multiple lines of chemotherapy. Liquid biopsy detected a BRCA2 pathogenic germline mutation (c.3109C > T), indicating PARPis might be effective for this patient. The patient achieved tumor stability, and progression-free survival was five months without severe adverse effects after taking fluzoparib.

Conclusion: This result confirmed that PARPis were effective for metastatic cSCC patients with germline BRCA2 pathogenic mutations and provided a new treatment option for this group of patients.
The principle of the 3Rs between aspiration and reality
Authors: Vitale Augusto , Ricceri Laura
Published: August 2022

The Principle of the 3Rs is widely recognised as the methodological and ethical backbone of contemporary animal research. Different authors also stress the reciprocal links among the 3Rs, and how these often complement and reinforce each other. We very much agree with this point, but in this contribution we would like to raise some problems related to the application of the “3Rs”. There is an obvious link among “Replacement, “Reduction” and “Refinement”, but it is worth to notice also that each “R” has its own conceptual characteristics, as well as its own level of applicability. For example, a realistic “methodological inertia” has to be expected more in the case of “Replacement” than in the case of “Refinement”. This also leads to a second order of issues, and here we will offer our experience as projects evaluators. The “3Rs” differ also in the possibility to verify how are applied by the proponents of research protocols involving the use of animal models. Sometimes it appears that the application of the Principle still resolves itself in the use of formulaic sentences, from which it is difficult to really understand the reality of the laboratory decisional and procedural processes. However, the demanding characteristics of the “3Rs” can vary greatly, and this is something that has to be considered. We propose that a network, or a virtual platform, of evaluators could help both researchers and evaluators for a more satisfactory understanding and pragmatic application of the Principle of the 3Rs.
Effect of primary lesions in cytoskeleton proteins on red cell membrane stability in patients with hereditary spherocytosis
Authors: Vercellati Cristina , Marcello Anna Paola , Fattizzo Bruno , Zaninoni Anna , Seresini Agostino , Barcellini Wilma , Bianchi Paola , Fermo Elisa
Published: August 2022

We investigated by targeted next generation sequencing the genetic bases of hereditary spherocytosis in 25 patients and compared the molecular results with the biochemical lesion of RBC membrane obtained by SDS-PAGE analysis. The HS diagnosis was based on available guidelines for diagnosis of congenital hemolytic anemia, and patients were selected because of atypical clinical presentation or intra-family variability, or because presented discrepancies between laboratory investigation and biochemical findings. In all patients but 5 we identified pathogenic variants in SPTA1, SPTB, ANK1, SLC4A1, EPB42 genes able to justify the clinical phenotype. Interestingly, a correspondence between the biochemical lesion and the molecular defect was identified in only 11/25 cases, mostly with band 3 deficiency due to SLC4A1 mutations. Most of the mutations in SPTB and ANK1 gene didn’t hesitate in abnormalities of RBC membrane protein; conversely, in two cases the molecular lesion didn’t correspond to the biochemical defect, suggesting that a mutation in a specific cytoskeleton protein may result in a more complex RBC membrane damage or suffering. Finally, in two cases the HS diagnosis was maintained despite absence of both protein defect and molecular lesion, basing on clinical and family history, and on presence of clear laboratory markers of HS. The study revealed complex relationships between the primary molecular lesion and the final effect in the RBC membrane cytoskeleton, and further underlines the concept that there is not a unique approach to the diagnosis of HS.
Genome-wide analysis of HSP20 gene family and expression patterns under heat stress in cucumber (Cucumis sativus L.)
Authors: Huang Junjun , Hai Zhaoxin , Wang Ruoyi , Yu Yuanyuan , Chen Xin , Liang Weihong , Wang Huahua
Published: August 2022

Cucumber is an important vegetable in China, and its yield and cultivation area are among the largest in the world. Excessive temperatures lead to high-temperature disorder in cucumber. Heat shock protein 20 (HSP20), an essential protein in the process of plant growth and development, is a universal protective protein with stress resistance. HSP20 plays crucial roles in plants under stress. In this study, we characterized the HSP20 gene family in cucumber by studying chromosome location, gene duplication, phylogenetic relationships, gene structure, conserved motifs, protein-protein interaction (PPI) network, and cis-regulatory elements. A total of 30 CsHSP20 genes were identified, distributed across 6 chromosomes, and classified into 11 distinct subgroups based on conserved motif composition, gene structure analyses, and phylogenetic relationships. According to the synteny analysis, cucumber had a closer relationship with Arabidopsis and soybean than with rice and maize. Collinearity analysis revealed that gene duplication, including tandem and segmental duplication, occurred as a result of positive selection and purifying selection. Promoter analysis showed that the putative promoters of CsHSP20 genes contained growth, stress, and hormone cis-elements, which were combined with protein-protein interaction networks to reveal their potential function mechanism. We further analyzed the gene expression of CsHSP20 genes under high stress and found that the majority of the CsHSP20 genes were upregulated, suggesting that these genes played a positive role in the heat stress-mediated pathway at the seedling stage. These results provide comprehensive information on the CsHSP20 gene family in cucumber and lay a solid foundation for elucidating the biological functions of CsHSP20. This study also provides valuable information on the regulation mechanism of the CsHSP20 gene family in the high-temperature resistance of cucumber.
Transcriptome analysis provides novel insights into the soil amendments induced response in continuously cropped Codonopsis tangshen
Authors: Zhou Wuxian , Jiang Xiaogang , Tan Xuhui , Li Darong , Wang Hua , You Jinwen , Li Xiaoling , Zhang Meide
Published: August 2022

Codonopsis tangshen Oliv (C. tangshen) is an important Chinese traditional medicinal plant with various health benefits. However, the growth of C. tangshen are seriously affected by continuous cropping, which led to the decrease of the yield and quality. A field experiment was conducted to learn the effects of soil amendments on the growth of C. tangshen under continuous cropping condition, and the biological events which occurred at molecular level were investigated. The results indicated that the content of chlorophyll a (Chl a), chlorophyll b (Chl b), and carotenoid (Car) was significantly higher in SCPM (silicon-calcium-potassium-magnesium fertilizer), SCPMA (SCPM combined with azoxystrobin) and SCPMAOM (SCPM combined with azoxystrobin and organic manure) treatments. Moreover, the yield and the levels of alkaloid, polysaccharide, flavone and total protein in the treatments of SCPM, SCPMA and SCPMAOM were significantly higher than those in the control, and these indexes were all highest in the SCPMAOM treatment. RNA-sequencing (RNA-Seq) is an economical and efficient method to obtain genetic information for species with or without available genome data. In this study, RNA-Seq was performed to understand how continuously cropped C. tangshen responded to the soil amendments at the transcriptome level. The number of differentially expressed genes (DEGs) were as follows: CK vs. SCPM (719 up- and 1456 down-), CK vs. SCPMA (1302 up- and 1748 down-), CK vs. SCPMAOM (1274 up- and 1678 down-). The soil amendments affected the growth of C. tangshen mainly by regulating the genes involved in pathways of ‘photosynthesis,’ ‘plant hormone signal transduction,’ ‘biosynthesis of unsaturated fatty acids,’ ‘phenylpropanoid biosynthesis,’ and ‘starch and sucrose metabolism,’ etc. qRT-PCR was performed to validate the expressions of 10 target genes such as CP26, PsaF, and POX, etc., which verified the reliability of RNA-Seq results. Overall, this study revealed the roles and underlying mechanisms of the soil amendments in regulating the growth of continuously cropped C. tangshen at transcriptome level. These findings are beneficial for improving the continuous cropping tolerance and may be valuable for future genetic improvement of C. tangshen.