bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome: a pilot randomized trial
Authors: Wen Qing , Fang Song , Liang Yanjing , Tian Yuting , Chen Yiding , Yuan Jun , Chen Qiu
Published: June 2023

Objective

To observe the effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome(PCOS).

Methods

A total of 64 overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomly assigned to metformin(MET) 850 mg twice a day(BID) or combined MET 850 mg BID with beinaglutide (COMB) starting at 0.1mg three times a day(TID)and increasing to 0.2mg TID two weeks later. The main endpoints were changes in anthropometric measurements of obesity. Glucose and lipid metabolic, gonadal profiles, and antral follicle count changes as secondary outcomes were also observed.

Results

60(93.75%) patients completed the study. In terms of lowering weight, body mass index (BMI),waist circumference(WC) and waist to height ratio(WHtR), COMB treatment outperformed MET monotherapy. Subjects in the COMB arm lost weight 4.54±3.16kg compared with a 2.47±3.59kg loss in the MET arm. In the COMB group, BMI,WC and WHtR were reduced significantly compared with that in the MET group, respectively. COMB therapy is also more favorable in the reduction of fasting insulin(FINS), total testosterone(TT), and homeostasis model assessment–insulin resistance(HOMA-IR) when compared to MET therapy. Antral follicle count and ovarian volume were non-significantly changed in both groups.The most frequent side effects in both groups were mild and moderate digestive symptoms. Itching and induration at the injection site were reported with COMB treatment.

Conclusion

Short-term combined treatment with beinaglutide and metformin appears superior to metformin monotherapy in lowering body weight, BMI, WC,WHtR and improving insulin sensitivity and androgen excess in women with PCOS and obesity, with tolerable adverse events.

Clinical trial registration

https://www.chictr.org.cn/listbycreater.aspx, identifier ChiCTR2000033741.
Robustness enhanced capacity estimation method for lithium-ion batteries based on multi-voltage-interval incremental capacity peaks
Authors: Guo Xianli , Xu Binxiang , Zheng Linfeng , Xu Jing
Published: June 2023

Accurate battery capacity estimation can contribute to safe and reliable operations of lithium-ion battery systems. The incremental capacity (IC) based techniques provide promising estimates of battery capacity. However, curve smoothing algorithms are usually required in the IC-based methods, which introduce additional errors and are computationally burdensome. To address this issue, this work proposes a novel approach using multi-voltage-interval IC peaks combined with a back-propagation neural network (BPNN) for battery capacity estimation. Multiple voltage intervals covering relatively narrow and wide values are applied for computing IC curves to enhance the estimation robustness. In particular, there is no need to employ smoothing algorithms. A BPNN is then applied to approximate the correlation between multi-voltage-interval IC peak and capacity. Besides, a five-point moving window technique is proposed to capture multi-voltage-interval IC peaks online effectively. Experimental results show capacity estimates with the majority of relative errors of ±1% and the maximum error of 2%.
Performance evaluation of MODIS and VIIRS satellite AOD products over the Indian subcontinent
Authors: Payra Swagata , Sharma Ajay , Mishra Manoj Kumar , Verma Sunita
Published: June 2023

In the present study, the first systematic performance evaluation of aerosol optical depth (AOD) products retrieved using two satellite sensors i.e., Visible Infrared Imaging Radiometer Suite (VIIRS) and Aqua-Moderate-Resolution Imaging Spectroradiometer (MODIS) is carried out over India. We have used ground-based AOD from AERONET at 550 nm wavelength for inter-comparison with MODIS Aqua version C6.1 (C061) Deep Blue (DB) aerosol product and VIIRS/SNPP collection version 1.1 (V1.1) DB aerosol product over the time span of 7-year (2014–2020) observation periods. For validation, the average value of satellite pixels falling within the box of 50 Km x 50 Km keeping the AERONET station at the center is retrieved. The average daily data from the AERONET sun photometer (2014–2019) were obtained within ±15 min of satellite overpass time. Statistical parameters like correlation coefficient (R), RMSE, MAE, and RMB were calculated. The uncertainty of satellite AOD is evaluated using an envelope of Expected Error (EE = ±0.05 + 0.15 AOD for land). Statistical analysis shows that the MODIS AOD product outperforms VIIRS-retrieved AOD. The AOD retrieved from both sensors yields a high correlation (0.86—Jaipur, 0.79—Kanpur, 0.84—Gandhi College, and 0.74—Pune for MODIS and 0.75—Jaipur, 0.77—Kanpur, 0.49—Gandhi College, and 0.86—Pune for VIIRS) and low MAE (0.12—Jaipur, 0.20—Kanpur, 0.15—Gandhi College, and 0.09—Pune for MODIS and 0.13—Jaipur, 0.13—Kanpur, 0.26—Gandhi College, and 0.10—Pune for VIIRS). Other statistical measures such as RMSE, RMB, and P also suggest similar performance. More than 66% of the total data fall within the range of EE for both the satellite products at each station. Spatial comparison exhibits the same AOD pattern seasonally as well as annually having a minimum bias from −0.3 to +0.3 between MODIS and VIIRS. Slight underestimation and overestimation are observed in all the stations by MODIS, whereas VIIRS continuously underestimates AOD with increase in optical depth, suggesting improvements in the aerosol model and surface reflection in retrieval. Overall, the comparison of ground AERONET AOD reveals better accuracy of MODIS AOD with that of VIIRS satellite datasets over India.
Exploring attitudinal factors influencing modal shift: a latent class analysis of Danish commuters
Authors: Rasmussen L. R. , Agerholm N. , Lahrmann H. , Olesen A. V.
Published: June 2023

Governments advocate for a modal shift from motorized transport modes to active modes. Various political approaches can be adopted to affect travel behavior and patterns. However, interventions spread across the entire population offer limited opportunities to achieve behavioral change. Furthermore, attitude has been shown to cut across demographic characteristics and strongly influence the conducted travel behavior. Therefore, a latent class analysis including significant sociodemographic variables and value-based attitudes concerning factors influencing transport, settlement, and additional priorities was performed. The study objectively identified five classes of Danish commuters with the same preconditions in terms of commuting distance but with clear differences in attitude and transport modes. Each latent class represents a unique combination of characteristics, which indicates the need to design target group-specific interventions to optimize the chances of influencing travel behavior. In particular, a group of malcontented motorists demonstrating a high intention to change exhibit negative feelings toward car travel and thus appear to act in contravention of their attitudes. In contrast, a class of immovable motorists was found, a class of beneficial commuters and finally two cycling dominated classes of passionate cyclists and environmentalist cyclists. Finally, this study has emphasized that similar attitudes can lead to dissimilar behaviors and that the same behavior can be exhibited for various reasons. We deduced how transport mode choice is influenced by various factors, with habit as one of the strongest, as those with strong habits seem disinclined to information about alternatives and call for “harder” policy interventions. The findings emphasize the importance of targeted interventions tailored to specific commuter groups to encourage modal shifts towards sustainable transportation.
Case report: Sex-specific characteristics of epilepsy phenotypes associated with Xp22.31 deletion: a case report and review
Authors: Wu Yi , Wu Dan , Lan Yulong , Lan Shaocong , Li Duo , Zheng Zexin , Wang Hongwu , Ma Lian
Published: June 2023

Deletion in the Xp22.31 region is increasingly suggested to be involved in the etiology of epilepsy. Little is known regarding the genomic and clinical delineations of X-linked epilepsy in the Chinese population or the sex-stratified difference in epilepsy characteristics associated with deletions in the Xp22.31 region. In this study, we reported two siblings with a 1.69 Mb maternally inherited microdeletion at Xp22.31 involving the genes VCX3A, HDHD1, STS, VCX, VCX2, and PNPLA4 presenting with easily controlled focal epilepsy and language delay with mild ichthyosis in a Chinese family with a traceable 4-generation history of skin ichthyosis. Both brain magnetic resonance imaging results were normal, while EEG revealed epileptic abnormalities. We further performed an exhaustive literature search, documenting 25 patients with epilepsy with gene defects in Xp22.31, and summarized the epilepsy heterogeneities between sexes. Males harboring the Xp22.31 deletion mainly manifested with child-onset, easily controlled focal epilepsy accompanied by X-linked ichthyosis; the deletions were mostly X-linked recessive, with copy number variants (CNVs) in the classic region of deletion (863.38 kb–2 Mb). In contrast, epilepsy in females tended to be earlier-onset, and relatively refractory, with pathogenic CNV sizes varying over a larger range (859 kb–56.36 Mb); the alterations were infrequently inherited and almost combined with additional CNVs. A candidate region encompassing STS, HDHD1, and MIR4767 was the likely pathogenic epilepsy-associated region. This study filled in the knowledge gap regarding the genomic and clinical delineations of X-linked recessive epilepsy in the Chinese population and extends the understanding of the sex-specific characteristics of Xp22.31 deletion in regard to epilepsy.
Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model
Authors: Pan Xiaoli , López Acevedo Sheila N. , Cuziol Camille , De Tavernier Evelyn , Fahad Ahmed S. , Longjam Priyobarta S. , Rao Sambasiva P. , Aguilera-Rodríguez David , Rezé Mathilde , Bricault Christine A. , Gutiérrez-González Matías F. , de Souza Matheus Oliveira , DiNapoli Joshua M. , Vigne Emmanuelle , Shahsavarian Melody A. , DeKosky Brandon J.
Published: June 2023

Molecular characterization of antibody immunity and human antibody discovery is mainly carried out using peripheral memory B cells, and occasionally plasmablasts, that express B cell receptors (BCRs) on their cell surface. Despite the importance of plasma cells (PCs) as the dominant source of circulating antibodies in serum, PCs are rarely utilized because they do not express surface BCRs and cannot be analyzed using antigen-based fluorescence-activated cell sorting. Here, we studied the antibodies encoded by the entire mature B cell populations, including PCs, and compared the antibody repertoires of bone marrow and spleen compartments elicited by immunization in a human immunoglobulin transgenic mouse strain. To circumvent prior technical limitations for analysis of plasma cells, we applied single-cell antibody heavy and light chain gene capture from the entire mature B cell repertoires followed by yeast display functional analysis using a cytokine as a model immunogen. We performed affinity-based sorting of antibody yeast display libraries and large-scale next-generation sequencing analyses to follow antibody lineage performance, with experimental validation of 76 monoclonal antibodies against the cytokine antigen that identified three antibodies with exquisite double-digit picomolar binding affinity. We observed that spleen B cell populations generated higher affinity antibodies compared to bone marrow PCs and that antigen-specific splenic B cells had higher average levels of somatic hypermutation. A degree of clonal overlap was also observed between bone marrow and spleen antibody repertoires, indicating common origins of certain clones across lymphoid compartments. These data demonstrate a new capacity to functionally analyze antigen-specific B cell populations of different lymphoid organs, including PCs, for high-affinity antibody discovery and detailed fundamental studies of antibody immunity.
Immunogenic cell death after combined treatment with radiation and ATR inhibitors is dually regulated by apoptotic caspases
Authors: Eek Mariampillai Adrian , Hauge Sissel , Kongsrud Karoline , Syljuåsen Randi G.
Published: June 2023

Introduction

Inhibitors of the ATR kinase act as radiosensitizers through abrogating the G2 checkpoint and reducing DNA repair. Recent studies suggest that ATR inhibitors can also increase radiation-induced antitumor immunity, but the underlying immunomodulating mechanisms remain poorly understood. Moreover, it is poorly known how such immune effects relate to different death pathways such as caspase-dependent apoptosis. Here we address whether ATR inhibition in combination with irradiation may increase the presentation of hallmark factors of immunogenic cell death (ICD), and to what extent caspase activation regulates this response.

Methods

Human lung cancer and osteosarcoma cell lines (SW900, H1975, H460, U2OS) were treated with X-rays and ATR inhibitors (VE822; AZD6738) in the absence and presence of a pan-caspase inhibitor. The ICD hallmarks HMGB1 release, ATP secretion and calreticulin surface-presentation were assessed by immunoblotting of growth medium, the CellTiter-Glo assay and an optimized live-cell flow cytometry assay, respectively. To obtain accurate measurement of small differences in the calreticulin signal by flow cytometry, we included normalization to a barcoded control sample.

Results

Extracellular release of HMGB1 was increased in all the cell lines at 72 hours after the combined treatment with radiation and ATR inhibitors, relative to mock treatment or cells treated with radiation alone. The HMGB1 release correlated largely – but not strictly – with loss of plasma membrane integrity, and was suppressed by addition of the caspase inhibitor. However, one cell line showed HMGB1 release despite caspase inhibition, and in this cell line caspase inhibition induced pMLKL, a marker for necroptosis. ATP secretion occurred already at 48 hours after the co-treatment and did clearly not correlate with loss of plasma membrane integrity. Addition of pan-caspase inhibition further increased the ATP secretion. Surface-presentation of calreticulin was increased at 24-72 hours after irradiation, but not further increased by either ATR or caspase inhibition.

Conclusion

These results show that ATR inhibition can increase the presentation of two out of three ICD hallmark factors from irradiated human cancer cells. Moreover, caspase activation distinctly affects each of the hallmark factors, and therefore likely plays a dual role in tumor immunogenicity by promoting both immunostimulatory and -suppressive effects.
Disruption of the sialic acid/Siglec-9 axis improves antibody-mediated neutrophil cytotoxicity towards tumor cells
Authors: Lustig Marta , Chan Chilam , Jansen J. H. Marco , Bräutigam Maria , Kölling Max A. , Gehlert Carina Lynn , Baumann Niklas , Mester Simone , Foss Stian , Andersen Jan Terje , Bastian Lorenz , Sondermann Peter , Peipp Matthias , Burger Renate , Leusen Jeanette H. W. , Valerius Thomas
Published: June 2023

Upregulation of surface expressed sialoglycans on tumor cells is one of the mechanisms which promote tumor growth and progression. Specifically, the interactions of sialic acids with sialic acid-binding immunoglobulin-like lectins (Siglecs) on lymphoid or myeloid cells transmit inhibitory signals and lead to suppression of anti-tumor responses. Here, we show that neutrophils express among others Siglec-9, and that EGFR and HER2 positive breast tumor cells express ligands for Siglec-9. Treatment of tumor cells with neuraminidases or a sialyl transferase inhibitor significantly reduced binding of a soluble recombinant Siglec-9-Fc fusion protein, while EGFR and HER2 expression remained unchanged. Importantly, the cytotoxic activity of neutrophils driven by therapeutic EGFR or HER2 antibodies in vitro was increased by blocking the sialic acid/Siglec interaction, either by reducing tumor cell sialylation or by a Siglec-9 blocking antibody containing an effector silenced Fc domain. In vivo a short-term xenograft mouse model confirmed the improved therapeutic efficacy of EGFR antibodies against sialic acid depleted, by a sialyltransferase inhibitor, tumor cells compared to untreated cells. Our studies demonstrate that sialic acid/Siglec interactions between tumor cells and myeloid cells can impair antibody dependent tumor cell killing, and that Siglec-9 on polymorphonuclear cells (PMN) is critically involved. Considering that PMN are often a highly abundant cell population in the tumor microenvironment, Siglec-9 constitutes a promising target for myeloid checkpoint blockade to improve antibody-based tumor immunotherapy.
Immune response of DNA vaccinated-gilthead seabream (Sparus aurata) against LCDV-Sa infection: relevance of the inflammatory process
Authors: Leiva-Rebollo Rocio , Gémez-Mata Juan , Castro Dolores , Borrego Juan J. , Labella Alejandro M.
Published: June 2023

Lymphocystis disease is one of the main viral pathologies affecting cultured gilthead seabream (Sparus aurata) in the Mediterranean region. Recently, we have developed a DNA vaccine based on the major capsid protein (MCP) of the Lymphocystis disease virus 3 (LCDV-Sa). The immune response triggered by either LCDV-Sa infection or vaccination have been previously studied and seem to be highly related to the modulation of the inflammatory and the IFN response. However, a comprehensive evaluation of immune-related gene expression in vaccinated fish after viral infection to identify immunogenes involved in vaccine-induced protection have not been carried out to date. The present study aimed to fulfill this objective by analyzing samples of head-kidney, spleen, intestine, and caudal fin from fish using an OpenArray® platform containing targets related to the immune response of gilthead seabream. The results obtained showed an increase of deregulated genes in the hematopoietic organs between vaccinated and non-vaccinated fish. However, in the intestine and fin, the results showed the opposite trend. The global effect of fish vaccination was a significant decrease (p<0.05) of viral replication in groups of fish previously vaccinated, and the expression of the following immune genes related to viral recognition (tlr9), humoral and cellular response (rag1 and cd48), inflammation (csf1r, elam, il1β, and il6), antiviral response (isg15, mx1, mx2, mx3), cell-mediated cytotoxicity (nccrp1), and apoptosis (prf1). The exclusive modulation of the immune response provoked by the vaccination seems to control the progression of the infection in the experimentally challenged gilthead seabream.
Interaction between plants and epiphytic lactic acid bacteria that affect plant silage fermentation
Authors: Chen Lijuan , Wang Yili , Li Xi , MacAdam Jennifer W. , Zhang Yunhua
Published: June 2023

Lactic acid bacteria (LAB) have the ability to ferment water-soluble carbohydrates, resulting in the production of significant amounts of lactic acid. When utilized as additives in silage fermentation and feed, they have been shown to enhance the quality of these products. Epiphytic LAB of plants play a major role in the fermentation of silage plants. Plant species in turn affect the community structure of epiphytic LAB. In recent years, an increasing number of studies have suggested that epiphytic LAB are more effective than exogenous LAB when applied to silage. Inoculating silage plants with epiphytic LAB has attracted extensive attention because of the potential to improve the fermentation quality of silages. This review discusses the interaction of epiphytic LAB with plants during silage fermentation and compares the effects of exogenous and epiphytic LAB on plant fermentation. Overall, this review provides insight into the potential benefits of using epiphytic LAB as an inoculant and proposes a theoretical basis for improving silage quality.
Assessing phenotypic virulence of Salmonella enterica across serovars and sources
Authors: Petrin Sara , Wijnands Lucas , Benincà Elisa , Mughini-Gras Lapo , Delfgou-van Asch Ellen H. M. , Villa Laura , Orsini Massimiliano , Losasso Carmen , Olsen John E. , Barco Lisa
Published: June 2023

Introduction

Whole genome sequencing (WGS) is increasingly used for characterizing foodborne pathogens and it has become a standard typing technique for surveillance and research purposes. WGS data can help assessing microbial risks and defining risk mitigating strategies for foodborne pathogens, including Salmonella enterica.

Methods

To test the hypothesis that (combinations of) different genes can predict the probability of infection [P(inf)] given exposure to a certain pathogen strain, we determined P(inf) based on invasion potential of 87 S. enterica strains belonging to 15 serovars isolated from animals, foodstuffs and human patients, in an in vitro gastrointestinal tract (GIT) model system. These genomes were sequenced with WGS and screened for genes potentially involved in virulence. A random forest (RF) model was applied to assess whether P(inf) of a strain could be predicted based on the presence/absence of those genes. Moreover, the association between P(inf) and biofilm formation in different experimental conditions was assessed.

Results and Discussion

P(inf) values ranged from 6.7E-05 to 5.2E-01, showing variability both among and within serovars. P(inf) values also varied between isolation sources, but no unambiguous pattern was observed in the tested serovars. Interestingly, serovars causing the highest number of human infections did not show better ability to invade cells in the GIT model system, with strains belonging to other serovars displaying even higher infectivity. The RF model did not identify any virulence factor as significant P(inf) predictors. Significant associations of P(inf) with biofilm formation were found in all the different conditions for a limited number of serovars, indicating that the two phenotypes are governed by different mechanisms and that the ability to form biofilm does not correlate with the ability to invade epithelial cells. Other omics techniques therefore seem more promising as alternatives to identify genes associated with P(inf), and different hypotheses, such as gene expression rather than presence/absence, could be tested to explain phenotypic virulence [P(inf)].
Optimizing growth and biomass production of non-Saccharomyces wine yeast starters by overcoming sucrose consumption deficiency
Authors: Torrellas Max , Pietrafesa Rocchina , Ferrer-Pinós Aroa , Capece Angela , Matallana Emilia , Aranda Agustín
Published: June 2023

The use of non-Saccharomyces yeasts as starters in winemaking has increased exponentially in the last years. For instance, non-conventional yeasts have proven useful for the improvement of the organoleptic profile and biocontrol. Active dry yeast starter production has been optimized for Saccharomyces cerevisiae, which may entail problems for the propagation of non-Saccharomyces yeasts. This work shows that the poor growth of Hanseniaspora vineae and Metschnikowia pulcherrima in molasses is related to a deficient sucrose consumption, linked to their low invertase activity. In order to address this issue, simple modifications to the cultivation media based hydrolysis and the reduction of sucrose concentration were performed. We performed biomass propagation simulations at a bench-top and bioreactor scale. The results show that cultivation in a hexose-based media improved biomass production in both species, as it solves their low invertase activity. The reduction in sugar concentration promoted a metabolic shift to a respiratory metabolism, which allowed a higher biomass yield, but did not improve total biomass production, due to the lower sugar availability. To evaluate the technological performance of these adaptations, we performed mixed grape juice fermentations with biomass produced in such conditions of M. pulcherrima and S. cerevisiae. The analysis of wines produced revealed that the different treatments we have tested did not have any negative impact on wine quality, further proving their applicability at an industrial level for the improvement of biomass production.
Pretreatment with Bifidobacterium longum BAA2573 ameliorates dextran sulfate sodium (DSS)-induced colitis by modulating gut microbiota
Authors: Lin Qiong , Hao Wu-Juan , Zhou Ren-Min , Huang Cui-Lan , Wang Xu-Yang , Liu Yan-Shan , Li Xiao-Zhong
Published: June 2023

Objectives

Inflammatory bowel disease (IBD) is a chronic lifelong inflammatory disease. Probiotics such as Bifidobacterium longum are considered to be beneficial to the recovery of intestinal inflammation by interaction with gut microbiota. Our goals were to define the effect of the exclusive use of BAA2573 on dextran sulfate sodium (DSS)-induced colitis, including improvement of symptoms, alleviation of histopathological damage, and modulation of gut microbiota.

Methods

In the present study, we pretreated C57BL/6J mice with Bifidobacterium longum BAA2573, one of the main components in an over-the-counter (OTC) probiotic mixture BIFOTO capsule, before modeling with DSS. 16S rDNA sequencing and liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomic profiling were performed with the collected feces.

Results

We found that pretreatment of Bifidobacterium longum BAA2573 given by gavage significantly improved symptoms and histopathological damage in DSS-induced colitis mice. After the BAA2573 intervention, 57 genera and 39 metabolites were significantly altered. Pathway enrichment analysis demonstrated that starch and sucrose metabolism, vitamin B6 metabolism, and sphingolipid metabolism may contribute to ameliorating colitis. Moreover, we revealed that the gut microbiome and metabolites were interrelated in the BAA2573 intervention group, while Alistipes was the core genus.

Conclusion

Our study demonstrates the impact of BAA2573 on the gut microbiota and reveals a possible novel adjuvant therapy for IBD patients.
Discovery of anti-SARS-CoV-2 secondary metabolites from the heartwood of Pterocarpus santalinus using multi-informative molecular networking
Authors: Wasilewicz Andreas , Zwirchmayr Julia , Kirchweger Benjamin , Bojkova Denisa , Cinatl Jindrich , Rabenau Holger F. , Rollinger Judith M. , Beniddir Mehdi A. , Grienke Ulrike
Published: June 2023

A pigment-depleted extract from the heartwood of Pterocarpus santalinus L. f. (PS-DE) showed promising anti-SARS-CoV-2 activity with an IC50 of 29.9 μg/mL in Caco-2-F03 cells. To determine the potential active constituents within the extract prior to isolation, multi-informative molecular network (MN) was applied. Therefore, the extract was separated by high-performance counter-current chromatography (HPCCC) into 11 fractions which were subsequently tested for anti-SARS-CoV-2 activity and analysed by UPLC-tandem mass spectrometry (MS2). The resulting MN combines the bioactivity data of the fractions with the MS2 data. The MN analysis led to the targeted isolation of seven compounds including one pterocarpan (7) reported for the first time as constituent of P. santalinus and four so far undescribed natural products (NPs) that belong to the compound classes of arylpropanes (9), isoflavanones (10) coumestans (16) and 3-arylcoumarins (17), respectively. In total, 15 constituents from the heartwood of P. santalinus and one synthetic isoflavonoid that is structurally related to the natural metabolites were tested for anti-SARS-CoV-2 activity. Thereby, the two pterocarpans (−)-homopterocarpin (5) and (−)-medicarpin (2), the stilbene (E)-pterostilbene (1) and the isoflavonoid 7-O-methylgenistein (11) showed a distinct antiviral activity with IC50 values of 17.2, 33.4, 34.7, and 37.9 µM, respectively, and no cytotoxic effects against Caco-2-F03 cells (CC50 > 100 µM). In addition, a structure-activity relationship (SAR) was proposed indicating structural requirements of pterocarpans for anti-SARS-CoV-2 activity. The herein presented results support the implementation of multi-informative molecular networks as powerful tool for dereplication and targeted isolation of bioactive NPs.
Investigation of FGF21 mRNA levels and relative mitochondrial DNA copy number levels and their relation in nonalcoholic fatty liver disease: a case-control study
Authors: Houshmand Massoud , Zeinali Vahide , Hosseini Amirhossein , Seifi Atena , Danaei Bardia , Kamfar Sharareh
Published: June 2023

Background: Although the exact mechanisms of nonalcoholic fatty liver disease (NAFLD) are not fully understood, numerous pieces of evidence show that the variations in mitochondrial DNA (mtDNA) level and hepatic Fibroblast growth factor 21 (FGF21) expression may be related to NAFLD susceptibility.

Objectives: The main objective of this study was to determine relative levels of mtDNA copy number and hepatic FGF21 expression in a cohort of Iranian NAFLD patients and evaluate the possible relationship.

Methods: This study included 27 NAFLD patients (10 with nonalcoholic fatty liver (NAFL) and 17 with non-alcoholic steatohepatitis (NASH)) and ten healthy subjects. Total RNA and genomic DNA were extracted from liver tissue samples, and then mtDNA copy number and FGF21 expression levels were assessed by quantitative real-time PCR.

Results: The relative level of hepatic mtDNA copy number was 3.9-fold higher in patients than in controls (p < 0.0001). NAFLD patients showed a 2.9-fold increase in hepatic FGF21 expression compared to controls (p < 0.013). Results showed that hepatic FGF21 expression was positively correlated with BMI, serum ALT, and AST levels (p < 0.05). The level of mitochondrial copy number and hepatic FGF21 expression was not significantly associated with stages of change in hepatic steatosis. Finally, there was a significant correlation between FGF21 expression and mitochondrial copy number in NAFLD patients (p = 0.027).

Conclusion: Our findings suggest a considerable rise of hepatic FGF21 mRNA levels and mtDNA-CN and show a positive correlation between them in the liver tissue of NAFLD patients.
The biomechanical implications of neck position in cervical contusion animal models of SCI
Authors: Obaid Numaira , Morioka Kazuhito , Sinopoulou Eleni , Nout-Lomas Yvette S. , Salegio Ernesto , Bresnahan Jacqueline C. , Beattie Michael S. , Sparrey Carolyn J.
Published: June 2023

Large animal contusion models of spinal cord injury are an essential precursor to developing and evaluating treatment options for human spinal cord injury. Reducing variability in these experiments has been a recent focus as it increases the sensitivity with which treatment effects can be detected while simultaneously decreasing the number of animals required in a study. Here, we conducted a detailed review to explore if head and neck positioning in a cervical contusion model of spinal cord injury could be a factor impacting the biomechanics of a spinal cord injury, and thus, the resulting outcomes. By reviewing existing literature, we found evidence that animal head/neck positioning affects the exposed level of the spinal cord, morphology of the spinal cord, tissue mechanics and as a result the biomechanics of a cervical spinal cord injury. We posited that neck position could be a hidden factor contributing to variability. Our results indicate that neck positioning is an important factor in studying biomechanics, and that reporting these values can improve inter-study consistency and comparability and that further work needs to be done to standardize positioning for cervical spinal cord contusion injury models.
Research progress on the treatment and nursing of sensorineural hearing loss
Authors: Liu Fangfang , Han Baoai , Zhou Xuhong , Huang Shuo , Huang Jing
Published: June 2023

This article provides a comprehensive review of the progress in the treatment and care of sensorineural hearing loss (SNHL), which is a common disease in the field of otolaryngology. In recent years, the incidence of SNHL has been on the rise due to factors such as fast-paced lifestyles, work pressure, and environmental noise pollution, which have a significant impact on the quality of life of patients. Therefore, the study of the treatment and care of SNHL remains a hot topic in the medical community. Despite significant advances in this field, there are still some challenges and limitations. For example, there is currently no single method that can completely cure SNHL, and the effectiveness of treatment may vary significantly among individuals. In addition, due to the complex etiology of SNHL, the prognosis of patients may vary greatly, requiring the development of personalized treatment plans and care strategies. To address these challenges, continuous research is needed to explore new treatment methods and care models to improve the quality of life of patients. In addition, there is a need for health education programs for the general public to raise awareness of SNHL and promote preventive measures to reduce its incidence. The ultimate goal is to ensure the sustainable development of the field of SNHL treatment and care, thus ensuring the health and well-being of affected individuals.
Dietary glycemic index, glycemic load, and renal cancer risk: findings from prostate, lung, colorectal, and ovarian cancer trial
Authors: Qi Honggang , Xia Dan , Xu Xin
Published: June 2023

Background

Dietary glycemic index (GI) or glycemic load (GL) has been associated with the development of many cancers, but the evidence for renal cancer is still limited. The aim of the present study was to investigate the association between GI or GL and renal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial.

Methods

The cohort for our analysis consisted of 101,190 participants. GI and GL were calculated from the FFQ data using previously published reference values. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model after adjusting for most known renal cancer risk factors.

Results

During a median of 12.2 years of follow-up, 443 incident renal cancer cases occurred. Higher dietary GI was significantly associated with a higher risk of renal cancer (HRQ3vsQ1: 1.38; 95% CI: 1.09–1.74; p for trend = 0.008). There was no significant association between dietary GL and renal cancer risk (HRQ3vsQ1 = 1.12, 95% CI = 0.79–1.59, p for trend = 0.591). Spline regression plot revealed a higher risk of renal cancer with a higher GI but not GL. There was no statistical evidence for nonlinearity (p for nonlinearity >0.05).

Conclusion

In summary, findings of this large-scale prospective cohort study suggested that dietary GI may be associated with the risk of renal cancer. If confirmed in other populations and settings, dietary GI could be considered as a modifiable risk factor for renal cancer prevention.
Case Report: Early detection of lung carcinoid in an asymptomatic individual by blood-test initiated PET-CT imaging
Authors: Burg Simon , Smeets Ralf , Gosau Martin , Failing Katja , Grust Audrey Laure Céline
Published: June 2023

We present the case of a 53-year-old woman who was diagnosed with early-stage lung cancer by targeted cancer screening consisting of an immunological biopsy-based blood test followed by radiological imaging. The PanTum Detect blood test detects the biomarkers Apo10/DNaseX and Transketolase-like 1 (TKTL1) in circulating macrophage-like cells from peripheral blood samples to identify asymptomatic individuals with a high risk for malignancy. The elevated blood test values initiated an 18F-FDG PET/CT visualization for further clarification. In this case, imaging indicated a lung carcinoma in the right upper lobe. A biopsy confirmed the presence of a lung carcinoma, which was removed surgically. Histologic examination revealed a typical I A2 carcinoid, which was completely removed, making further therapy obsolete.
Efficacy of inguinal buffered lidocaine and intranasal flunixin meglumine on mitigating physiological and behavioral responses to pain in castrated piglets
Authors: Lopez-Soriano Magdiel , Merenda Victoria Rocha , Anderson Stephanie , Trindade Pedro Henrique Esteves , Leidig Martin S. , Messenger Kristen , Ferreira Juliana Bonin , Pairis-Garcia Monique Danielle
Published: June 2023

Managing castration pain on US sow farms is hindered by the lack of Food and Drug Administration (FDA) approved products for mitigating pain. Previous work assessing flunixin meglumine (FM) efficacy in mitigating castration pain has shown the drug to be effective in pigs, meanwhile, results from previous work evaluating lidocaine efficacy are contradictory. Therefore, the objectives of this study were to determine the efficacy of inguinal buffered lidocaine (BL) and FM in mitigating castration pain in piglets. This study was divided into Part I (physiological response) and Part II (behavioral response). For part I piglets were randomly assigned to the following treatments: T1: (C) Castration plus physiological saline; T2: (S) Sham plus physiological saline; T3: (CL) Castration plus BL; T4: (SL) Sham plus BL; T5: (CF) Castration plus FM; T6: (SF) Sham plus FM; T7: (CLF) Castration plus BL and FM; T8: (SLF) Sham plus BL and FM. Blood was collected 24 h prior to castration, 1 h, and 24 h post castration for cortisol quantification. For Part II another cohort of piglets was enrolled and randomly assign to the following treatments: T1: (C) Castration plus physiological saline and T7: (CLF) Castration plus BL and FM. Behavior scoring was obtained in real-time by observing each piglet for 4-min continuously using Unesp-Botucatu pig acute pain scale (UPAPS) at the following timepoints: 1 h before castration (−1 h), immediately post-castration (0 h), and 3 h post-castration (+3 h). Average cortisol concentrations did not differ at −24 h (P > 0.05) or at 24 h post-castration (P > 0.05) between treatments. At 1 h post-castration, castrated piglets (C and CL) demonstrated greater cortisol concentrations (P < 0.05). Castrated piglets in the CF and CLF group had lower cortisol concentrations compared to C and CL-treated pigs (P < 0.05). For behavioral response, there were no differences between treatments on total UPAPS scores (C and CLF, P > 0.05). Intranasal FM was able to effectively reduce the physiological piglet's response immediately post-castration. Inguinal buffered lidocaine had no effect on the either physiological or behavioral response to pain. Long-term research should focus on refining injection techniques for inguinal BL and consider administration frequency and dosing of intranasal FM to control pain for a longer period post-castration.
PARP-1: a critical regulator in radioprotection and radiotherapy-mechanisms, challenges, and therapeutic opportunities
Authors: Li Wen-Hao , Wang Fei , Song Gui-Yuan , Yu Qing-Hua , Du Rui-Peng , Xu Ping
Published: June 2023

Background: Since its discovery, poly (ADP-ribose) polymerase 1 (PARP-1) has been extensively studied due to its regulatory role in numerous biologically crucial pathways. PARP inhibitors have opened new therapeutic avenues for cancer patients and have gained approval as standalone treatments for certain types of cancer. With continued advancements in the research of PARP inhibitors, we can fully realize their potential as therapeutic targets for various diseases.

Purpose: To assess the current understanding of PARP-1 mechanisms in radioprotection and radiotherapy based on the literature.

Methods: We searched the PubMed database and summarized information on PARP inhibitors, the interaction of PARP-1 with DNA, and the relationships between PARP-1 and p53/ROS, NF-κB/DNA-PK, and caspase3/AIF, respectively.

Results: The enzyme PARP-1 plays a crucial role in repairing DNA damage and modifying proteins. Cells exposed to radiation can experience DNA damage, such as single-, intra-, or inter-strand damage. This damage, associated with replication fork stagnation, triggers DNA repair mechanisms, including those involving PARP-1. The activity of PARP-1 increases 500-fold on DNA binding. Studies on PARP-1-knockdown mice have shown that the protein regulates the response to radiation. A lack of PARP-1 also increases the organism’s sensitivity to radiation injury. PARP-1 has been found positively or negatively regulate the expression of specific genes through its modulation of key transcription factors and other molecules, including NF-κB, p53, Caspase 3, reactive oxygen species (ROS), and apoptosis-inducing factor (AIF).

Conclusion: This review provides a comprehensive analysis of the physiological and pathological roles of PARP-1 and examines the impact of PARP-1 inhibitors under conditions of ionizing radiation exposure. The review also emphasizes the challenges and opportunities for developing PARP-1 inhibitors to improve the clinical outcomes of ionizing radiation damage.
High quality low-dose SPECT reconstruction using CGAN-based transformer network with geometric tight framelet
Authors: Liang Zengguo , Li Si , Ma Xiangyuan , Li Fenghuan , Peng Limei
Published: June 2023

Single-photon emission computed tomography (SPECT) is a widely used diagnostic tool, but radioactive radiation during imaging poses potential health risks to subjects. Accurate low-dose single-photon emission computed tomography reconstruction is crucial in clinical applications of single-photon emission computed tomography. However, it remains a challenging problem due to the high noise and low spatial resolution of the low-dose reconstructed single-photon emission computed tomography images. The aim of the study is to develop a deep learning based framework for high quality low-dose single-photon emission computed tomography reconstruction. In the proposed framework, the conditional generative adversarial network (CGAN) was used as backbone structure and a Residual Attention CSwin Transformer (RACT) block was introduced as the basic building block for the generator of conditional generative adversarial network. The proposed residual attention CSwin transformer block has a dual-branch structure, which integrates the local modeling capability of CNN and the global dependency modeling capability of Transformer to improve the quality of single-photon emission computed tomography reconstructed images. More importantly, a novel loss term based on the geometric tight framelet (GTF) was designed to better suppress noise for the single-photon emission computed tomography reconstructed image while preserving the details of image to the greatest extent. Monte Carlo simulation software SIMIND was used to produce low-dose single-photon emission computed tomography images dataset to evaluate the performance of the proposed method. The simulation results showed that the proposed method can reduce more noise and preserve more details of various situations compared to several recent methods. To further validate the performance of the proposed method, we also verified the generalization ability of the proposed method, which is more adaptable to different noise level scenarios than other methods. Our results indicated that the proposed framework has the potential to reduce the tracer dose required for single-photon emission computed tomography imaging without compromising the quality of the reconstructed images.
An improved approach for rapid filter convergence of GNSS satellite real-time orbit determination
Authors: Zhou Liqin , Fan Lei , Li Zongnan , Fang Xinqi , Shi Chuang
Published: June 2023

Introduction: The real-time precise satellite orbit of Global Navigation Satellite System (GNSS) usually takes a long time to converge to a stable state using the filter method. The ultra-rapid orbit products are helpful to improve convergence speed by introducing them as external constraints. Reasonably determination of stochastic model of the constraint equation from the ultra-rapid products is the key for a better performance of convergence whereas it has not been well solved.

Methods: We propose to establish the stochastic model of the orbit constraint equation by analyzing the differences between the predicted part of the ultra-rapid orbit and the filter orbit after convergence. To improve the orbit accuracy during the convergence, the constant stochastic model of the constraint equation is first determined for each system by averaging the root mean square (RMS) time-series of the differences between predicted orbit from the ultra-rapid products and the SRIF orbit after convergence in different time ranges. Besides, a time-dependent stochastic model of the constraint equation is then determined by analyzing the variation of the RMS time-series. To validate the proposed method, a month of multi-constellation data collected from 80 globally distributed stations is processed using the Square Root Information Filter (SRIF) algorithm.

Results: Orbit results without introducing external orbit constraints show that the convergence time in the radial direction is 13.75, 15.25 and 17.75 h for GPS, Galileo and BDS-3 satellite, respectively. For the scheme of constant stochastic model using the average RMS over 6 h, results show that there is no significant convergence phenomenon for each system in all directions. The one-dimensional (1D) RMS during the constraint period is improved by 86.5%, 84.8%, 96.8% for GPS, Galileo and BDS-3 satellites when compared to the results without introducing external orbit constraints. As for the scheme of time-dependent stochastic model, results show that the quadratic function is suitable for modeling the RMS time-series for each system, and the accuracy of results during the constraint period has a further improvement of 1.3%, 3.7% in 1D direction for GPS, BDS-3 satellites when compared to the constant stochastic model using the average RMS over 6 h. In addition, the orbit accuracy with external orbit constraint is slightly better than those without external orbit constraint after the constraint period.

Discussion: The above results show that when introducing the ultra-rapid product as the external constraint, there is basically no convergence phenomenon for GNSS satellite, while the orbit accuracy for time-dependent stochastic model has further improvement than constant stochastic model. These results indicate that the proposed method can significantly improve the convergence performance without damaging the orbit accuracy after convergence, and time-dependent stochastic model is better than constant stochastic model.
Antioxidant and Anti-atherogenic Properties of Prosopis strombulifera and Tessaria absinthioides Aqueous Extracts: Modulation of NADPH Oxidase-Derived Reactive Oxygen Species
Authors: Quesada Isabel , de Paola Matilde , Alvarez María Soledad , Hapon María Belén , Gamarra-Luques Carlos , Castro Claudia
Published: June 2023

Graphical Abstract

Schematic representation of the effect of P. strombulifera or T. absinthioide decoctions on VSMC and ApoE-KO mice. The combination of antimitogenic effect and antioxidant capacity of the extracts is effective to increase antioxidant status and reduce atheroma development modulating NADPH oxidase expression.