bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease
Authors: Sargur Madabushi Srideshikan , Fouda Raghda , Ghimire Hemendra , Abdelhamid Amr M. H. , Lim Ji Eun , Vishwasrao Paresh , Kiven Stacy , Brooks Jamison , Zuro Darren , Rosenthal Joseph , Guha Chandan , Gupta Kalpna , Hui Susanta K.
Published: September 2022

Sickle cell disease (SCD) is a serious global health problem, and currently, the only curative option is hematopoietic stem cell transplant (HCT). However, myeloablative total body irradiation (TBI)-based HCT is associated with high mortality/morbidity in SCD patients. Therefore, reduced-intensity (2–4 Gy) total body radiation (TBI) is currently used as a conditioning regimen resulting in mixed chimerism with the rescue of the SCD disease characteristic features. However, donor chimerism gradually reduces in a few years, resulting in a relapse of the SCD features, and organ toxicities remained the primary concern for long-term survivors. Targeted marrow irradiation (TMI) is a novel technique developed to deliver radiation to the desired target while sparing vital organs and is successfully used for HCT in refractory/relapsed patients with leukemia. However, it is unknown if TMI will be an effective treatment for a hematological disorder like SCD without adverse effects seen on TBI. Therefore, we examined preclinical feasibility to determine the tolerated dose escalation, its impact on donor engraftment, and reduction in organ damage using our recently developed TMI in the humanized homozygous Berkley SCD mouse model (SS). We show that dose-escalated TMI (8:2) (8 Gy to the bone marrow and 2 Gy to the rest of the body) is tolerated with reduced organ pathology compared with TBI (4:4)-treated mice. Furthermore, with increased SCD control (AA) mice (25 million) donor BM cells, TMI (8:2)-treated mice show successful long-term engraftment while engraftment failed in TBI (2:2)-treated mice. We further evaluated the benefit of dose-escalated TMI and donor cell engraftment in alleviating SCD features. The donor engraftment in SCD mice completely rescues SCD disease features including recovery in RBCs, hematocrit, platelets, and reduced reticulocytes. Moreover, two-photon microscopy imaging of skull BM of transplanted SCD mice shows reduced vessel density and leakiness compared to untreated control SCD mice, indicating vascular recovery post-BMT.
Contrast-enhanced ultrasound of pancreatic melanoma: A case report and literature review
Authors: Yuan Zhiqiang , Yan Hualin , Ling Wenwu , Luo Yan
Published: September 2022

Melanoma is a malignant tumor that originates from melanocytes, most of which are of cutaneous origin. Most melanomas identified in the pancreas are metastatic, and primary pancreatic melanoma is extremely rare and has rarely been discussed. The correct preoperative diagnosis of pancreatic metastatic melanoma, especially primary melanoma, is challenging. Herein, we report a 43-year-old man who presented to our hospital due to unexplained left abdominal distension and pain. Abdominal ultrasound examination demonstrated multiple space-occupying lesions of the pancreas, and hypoechoic masses partially filled the splenic vein behind the pancreatic body. In the contrast-enhanced ultrasound (CEUS), all of these lesions showed iso-enhancement to slight hypo-enhancement in the arterial phase and hypo-enhancement in the venous phase. Masses in the splenic vein also showed hypo-enhancement. Imaging features suggested that the pancreatic lesions were malignant tumors. The tumor markers carcinoembryonic antigen, carbohydrate antigen 125 and carbohydrate antigen 19-9 were within normal limits. Based on clinical symptoms, imaging findings and incidence of pancreatic tumors, the patient’s clinical diagnosis was pancreatic carcinoma. Surgery was performed for the patient, while postoperative pathology confirmed malignant melanoma of the pancreas. Therefore, it is significant to identify the clinical and imaging manifestations of pancreatic melanoma in order to better manage the disease. Herein, we reported this case and reviewed the literature from 2000 to 2021 on the clinical and imaging features of 26 patients with pancreatic melanoma. It may improve clinicians’ awareness of the clinical and imaging performance of pancreatic melanoma, resulting in improved diagnosis, differential diagnosis, treatment, and outcomes.
Vocal nodules in children: Laryngoscopic morphological classification aids prognostic judgment
Authors: Liu Jia , Cao Wei , Sun Dan-Hua , Wu Lei , Sun Jing , Xu Bin , Fu Yong
Published: September 2022

Objective

Vocal fold nodules (VFNs) are benign lesions, occurring at the junction of the anterior and middle thirds of bilateral vocal cords, for which pediatric prognosis and treatment remains controversial. There is a requirement for a correlation indicator to assess the prognosis by pediatric otolaryngologists.

Materials and methods

Patients with VFNs, who were admitted to the department of otolaryngology, were enrolled. The patient’s gender, age, duration of dysphonia, laryngoscopy results and related diseases [allergic rhinitis, sinusitis, laryngopharyngeal reflux (LPR)] were collected and recovery from dysphonia followed up. Correlations between clinical factors and type of laryngoscopic morphology of VFNs were analyzed.

Results

A total of 432 patients with dysphonia were identified, 208 agreed to undergo laryngoscopy and 194 were diagnosed with VFNs as a result. The modal age of patients with dysphonia was between 3 and 7 years with a male: female ratio of 2.1:1 (294:138) and 116 (26.85%; 116/432) had symptoms of allergic rhinitis. The boy to girl ratio among the 194 children with VFNs was about 2.6:1 (140:54) and modal age was consistent with dysphonia. Vocal nodules were the cause of most phonation disorders (93.27%; 194/208) and those with long duration of dysphonia presented more mature (p = 0.026) and discrete types (p = 0.022). Boys were more likely to have mature (p = 0.050) and discrete nodules (p = 0.008). Dysphonia recovery time was closely related to age (p = 0.000), duration of dysphonia (p = 0.000) and morphology of vocal nodules under laryngoscopy (p = 0.000).

Conclusion

Vocal nodules are the most frequent cause of phonation disorders in children. The morphological classification by endoscopy may help with clinical diagnosis and therapy choice. In the case of the older child with longer duration of dysphonia and the appearance of mature, large, discrete nodules by laryngoscopy, active treatment is recommended, such as drug therapy, voice therapy or surgical treatment.
The possible association between epidemics of hand-foot-and-mouth disease and responsiveness to immunoglobulin therapy in Kawasaki disease
Authors: Shimizu Daisuke , Hoshina Takayuki , Kawamura Masaru , Tomita Yoshie , Hidaka Yasufumi , Kojiro Masumi , Muneuchi Jun , Kamizono Junji , Yamaguchi Kenichiro , Fujino Yoshihisa , Kusuhara Koichi
Published: September 2022

Background

Enterovirus causing hand-foot-mouth disease (HFMD) has been reported to be associated with the development of Kawasaki disease (KD), whereas the involvement of enterovirus in the clinical course of KD is uncertain. The aim of this study is to investigate the association between the clinical course of KD and HFMD epidemics.

Methods

This study included 108 patients who developed KD during HFMD epidemic seasons (July and August) from 2010 to 2014 and who were initially treated with high-dose intravenous immunoglobulin (IVIG). A mean of ≥5.0 HFMD patients reported weekly from each sentinel medical facility was considered to represent a large HFMD epidemic. We compared the clinical characteristics of KD patients in summers of years with and without large HFMD epidemics.

Results

Large HFMD epidemics occurred in 2011 and 2013. The number of KD patients in summer was the highest in 2011. The proportion of patients with resistance to the IVIG therapy in summers of years with the large epidemics (14%) was significantly lower than that in summers of other years (31%, P = 0.030), whereas the proportion of patients with coronary artery abnormalities did not differ to a statistically significant extent. The development of KD during large HFMD epidemics was significantly associated with a lower risk of resistance to the IVIG therapy (incidence rate ratio 0.92, P = 0.049).

Conclusion

Patients developing KD during large HFMD epidemic may have good responsiveness to IVIG. It is important to identify microbes from KD patients to predict responsiveness to IVIG therapy.
Can’t find the antidote: A root cause analysis
Authors: Abu Esba Laila Carolina , Mardawi Ghada , Al Deeb Mohammad
Published: September 2022

Background: In a series of cases that came to be recognized as a national methanol outbreak, an incident of delay in allocation and treatment with the antidote fomepizole is described with aim of sharing a learning experience.

Method: A team of 16 members was formed to conduct a Root Cause Analysis (RCA), which included multiple individual interviews with the stakeholders and inspection visits to the area.

Results: Root causes: The restocking process was unclear and inconsistent and specifically lacked a restocking policy for antidotes, inappropriate labeling and area design, and a sound-alike between fomepizole and omeprazole. Contributing factors included: unsuitable restocking practice and lack of training in using the pharmaceutical electronic inventory system. Corrective actions were recommended and implemented.

Conclusion: Management of antidotes in large healthcare systems requires a team effort to ensure appropriate and timely availability in emergency poisoning cases. This RCA identified important areas for improvement that could be insightful to other institutions in preventing similar vulnerabilities and is unique in describing the details of system improvements that can have a large impact on patient safety.
Comparison of LC-MS/MS and EMIT methods for the precise determination of blood sirolimus in children with vascular anomalies
Authors: Zhao Yue-Tao , Dai Hao-Ran , Li Yue , Zhang Yuan-Yuan , Guo Hong-Li , Ding Xuan-Sheng , Hu Ya-Hui , Chen Feng
Published: September 2022

Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor. The whole blood concentration of SRL is routinely monitored to tailor dosage and prevent toxicity. Currently, the enzyme multiplied immunoassay technique (EMIT) is often applied to perform therapeutic drug monitoring (TDM) of SRL, but the cross-reactivity with various metabolites is of great concern. A more specific method is required, such as liquid chromatography–tandem mass spectrometry (LC-MS/MS). However, no study on the method comparison of the EMIT and LC-MS/MS for the measurement of whole blood SRL concentration in children with vascular anomalies has been reported. This study developed a simple and sensitive LC-MS/MS assay for the determination of SRL. Meanwhile, consistency between LC-MS/MS and the EMIT was evaluated by linear regression and Bland–Altman analysis. Whole blood samples were deproteinized with methanol for erythrocyte lysis, and the resulting solution was injected into the LC-MS/MS system using the positive electrospray ionization mode. The multiple reaction monitoring transitions of m/z 931.7 → 864.6 and m/z 934.7 → 864.6 were used for SRL and SRL-d3 as the internal standards, respectively. The analytes were separated on a C18 column with a gradient mobile phase (0.1 mM formic acid and 0.05 mM ammonium acetate in methanol/ultrapure water). Blood samples collected from children with vascular anomalies undergoing SRL therapy were tested by EMIT and by LC-MS/MS. The linear range of LC-MS/MS was 0.500–50.0 ng/ml and that of the EMIT was 3.50–30.0 ng/ml. A significant positive correlation between the two assays was established with a regression equation described as [EMIT] = 1.281 × [LC−MS/MS] + 2.450 (r = 0.8361). Bland–Altman plots showed a mean concentration overestimation of 4.7 ng/ml [95% CI: (−3.1, 12.6)] and a positive bias of 63.1% [95% CI: (−36.1, 162.3)] generated by the EMIT more than that of by LC-MS/MS. In conclusion, the two methods were closely correlated, indicating that switching between the two methods is feasible. Considering the overestimation nature of the EMIT assay, switching from the EMIT to the LC-MS/MS method deserves close attention and necessary re-evaluation for the target therapeutic reference range, may be required when methods are switched within the same clinical laboratory or results are compared between different laboratories.
Pharmacological effects of berberine on models of ulcerative colitis: A meta-analysis and systematic review of animal studies
Authors: Hu Shuangyuan , Wei Pengfei , Li Wei , Liu Qingsong , Chen Shuanglan , Hu Caiyu , Guo Xiaochuan , Ma Xiao , Zeng Jinhao , Zhang Yi
Published: September 2022

Berberine (BBR) is the main active constituent of the Rhizoma coptidis (Huanglian) and has multiple biological activities. Although current evidence suggests that the BBR has a multi-target effect in ulcerative colitis (UC), its action and mechanism are unclear. The purpose of this meta-analysis was to assess the pharmacological effects and potential mechanisms of BBR in UC models. Studies were searched from four databases (PubMed, Embase, Web of Science, and Cochrane Library) until March 2022. Standardized mean difference (SMD) and 95% confidence intervals (CI) were used for the adjudication of outcomes. Stata 15.0 software was used for statistical analysis. Twenty-eight publications and 29 studies involving 508 animals were included in the meta-analysis. The results showed that BBR reduced disease activity index (DAI) scores, alleviated UC-induced colon length (CL) loss, prevented weight loss, and reduced histological colitis score (HCS). Mechanistically, BBR was found to reduce myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, reduce levels of pro-inflammatory factors interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and mRNA expression of interleukin 17, increase levels of anti-inflammatory factor interleukin 10 (IL-10), and to increase levels of tight junction protein zonula occludens-1 (ZO-1) and occludin, which may involve antioxidant, anti-apoptotic, neuromodulation, anti-fibrotic, anti-inflammatory, barrier protection, and flora regulation aspects. However, additional attention should be paid to these outcomes due to the heterogeneity and methodological quality of the studies.
Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer
Authors: Li Lingling , Liu Tingting , Liu Qingyan , Mu Shuai , Tao Haitao , Yang Xuhui , Li Yao , Xiong Qi , Wang Lijie , Hu Yi
Published: September 2022

Background: Rechallenge of immunotherapy beyond progression (RIBP) has been demonstrably effective in a variety of cancers. Our study aims to investigate the efficacy of RIBP in small-cell lung cancer (SCLC) patients under real-world conditions.

Methods: SCLC patients who experienced progressive disease after receiving programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors combined with chemotherapy from January 2017 to October 2021 were enrolled. The study population was divided into two groups: the RIBP group and the discontinuation of immunotherapy beyond progression (DIBP) group. Inverse propensity score weighting (IPSW) method was used to balance the clinical baseline characteristics. The short-term and long-term efficacy of the two groups was compared.

Results: 100 SCLC patients were included in this study. There were 45 patients in the RIBP group and 55 patients in the DIBP group. The disease control rate (DCR) and the proportion of durable clinical benefit (DCB) were significantly higher in the RIBP group (DCR: 79.7% vs. 55.7%, p = 0.027; DCB: 40.7 vs. 20.7%, p = 0.025) after weighting. The median progressive-free survival (PFS) in the RIBP group was significantly longer than the DIBP group in the total population (mPFS: 4.8 vs. 2.4 months, p = 0.002), while there was no significant difference in overall survival (OS) of the two groups (mOS: 17.4 vs. 8.0 months, p = 0.098). In the weighted first-line initial immunotherapy subgroup, PFS and OS were significantly improved in the RIBP group (mPFS: 4.5 vs. 2.8 months, p = 0.017; mOS: 11.6 vs. 5.4 months, p = 0.028). After weighting, the RIBP group had a significantly longer PFS than the DIBP group in the SD/PD response to the initial immunotherapy subgroup (mPFS: 6.8 vs. 1.8 months, p = 0.026).

Conclusion: Rechallenge of PD-1/PD-L1 inhibitors could bring benefits to SCLC patients, especially in the first-line initial immunotherapy subgroup or SD/PD response to the initial immunotherapy subgroup.
The role of p53 in the alternation of vascular functions
Authors: Chan Gabriel Hoi-Huen , Chan Enoch , Kwok Carsten Tsun-Ka , Leung George Pak-Heng , Lee Simon Ming-Yuen , Seto Sai-Wang
Published: September 2022

Ageing is a risk factor for many degenerative diseases. Cardiovascular diseases (CVDs) are usually big burdens for elderly, caregivers and the health system. During the aging process, normal functions of vascular cells and tissue progressively lost and eventually develop vascular diseases. Endothelial dysfunction, reduced bioavailability of endothelium-derived nitric oxide are usual phenomena observed in patients with cardiovascular diseases. Myriad of studies have been done to investigate to delay the vascular dysfunction or improve the vascular function to prolong the aging process. Tumor suppressor gene p53, also a transcription factor, act as a gatekeeper to regulate a number of genes to maintain normal cell function including but not limited to cell proliferation, cell apoptosis. p53 also crosstalk with other key transcription factors like hypoxia-inducible factor 1 alpha that contribute to the progression of cardiovascular diseases. Therefore, in recent three decades, p53 has drawn scientists’ attention on its effects in vascular function. Though the role of tumor suppressor gene p53 is still not clear in vascular function, it is found to play regulatory roles and may involve in vascular remodeling, atherosclerosis or pulmonary hypertension. p53 may have a divergent role in endothelial and vascular muscle cells in those conditions. In this review, we describe the different effects of p53 in cardiovascular physiology. Further studies on the effects of endothelial cell-specific p53 deficiency on atherosclerotic plaque formation in common animal models are required before the therapeutic potential can be realized.
Optimizing supercontinuum spectro-temporal properties by leveraging machine learning towards multi-photon microscopy
Authors: Hoang Van Thuy , Boussafa Yassin , Sader Lynn , Février Sébastien , Couderc Vincent , Wetzel Benjamin
Published: September 2022

Multi-photon microscopy has played a significant role in biological imaging since it allows to observe living tissues with improved penetration depth and excellent sectioning effect. Multi-photon microscopy relies on multi-photon absorption, enabling the use of different imaging modalities that strongly depends on the properties of the sample structure, the selected fluorophore and the excitation laser. However, versatile and tunable laser excitation for multi-photon absorption is still a challenge, limited by e.g. the narrow bandwidth of typical laser gain medium or by the tunability of wavelength conversion offered by optical parametric oscillators or amplifiers. As an alternative, supercontinuum generation can provide broadband excitations spanning from the ultra-violet to far infrared domains and integrating numerous fluorophore absorption peaks, in turn enabling different imaging modalities or potential multiplexed spectroscopy. Here, we report on the use of machine learning to optimize the spectro-temporal properties of supercontinuum generation in order to selectively enhance multi-photon excitation signals compatible with a variety of fluorophores (or modalities) for multi-photon microscopy. Specifically, we numerically explore how the use of reconfigurable (femtosecond) pulse patterns can be readily exploited to control the nonlinear propagation dynamics and associated spectral broadening occurring in a highly-nonlinear fiber. In this framework, we show that the use of multiple pulses to seed optical fiber propagation can trigger a variety of nonlinear interactions and complex propagation scenarios. This approach, exploiting the temporal dimension as an extended degree of freedom, is used to maximize typical multi-photon excitations at selected wavelengths, here obtained in a versatile and reconfigurable manner suitable for imaging applications. We expect these results to pave the way towards on-demand and real time supercontinuum shaping, with further multi-photon microscopy improvements in terms of spatial 3D resolution, optical toxicity, and wavelength selectivity.
Multi-layer Rotation Memory Model-based correlation filter for visual tracking
Authors: Zhao Yufei , Song Yong , Li Guoqi , Deng Lei , Bai Yashuo , Wu Xiyan
Published: September 2022

Object tracking technology is of great significance in laser image processing. However, occlusion or similar interference during visual object tracking may reduce the tracking precision or even cause tracking failure. Aiming at this issue, we propose a Multi-layer Rotation Memory Model-based Correlation Filter (MRMCF) for visual trackingin this paper. First, we establish a Multi-layer Rotation Memory (MRM) model, in which a set of three rotating concentric rings is used to simulate the three memory spacesand their updating processsimulate the memory spaces. Then we introduce the MRM model into the correlation filter tracking framework, which realizes realizing the dynamic updating of classifier parametersin the correlation filter. When the object is occluded or there is similar interference, the proposed tracker can use the Pre-occ classifier parameters stored in the memory spaces in the MRM model MRM memory spaces to retarget the object, thereby reducing the impact of these factors. The experimental results on the OTB50 dataset show that compared with trackers such as CNN-SVM, MEEM, Struck, etc., the proposed tracker achieves higher accuracy and success rate.
Hydrogen-bond networks for proton couplings in G-Protein coupled receptors
Authors: Bondar Ana-Nicoleta , Alfonso-Prieto Mercedes
Published: September 2022

G-protein signaling pathways mediate communication across cell membranes. The first steps of this communication occur at the cell membrane, where upon receiving an external signal –the binding of an agonist ligand– the membrane-embedded G-Protein Coupled Receptor adopts a conformation recognized by a cytoplasmatic G protein. Whereas specialized GPCRs sense protons from the extracellular milieu, thus acting as pH sensors in specialized cells, accumulating evidence suggests that pH sensitivity might be common to distinct GPCRs. In this perspective article we discuss general principles of protonation-coupled protein conformational dynamics and how these apply to GPCRs. To dissect molecular interactions that might govern the protonation-coupled conformational dynamics of GPCRs, we use graph-based algorithms to compute graphs of hydrogen bond networks. We find that the internal H-bond networks contain sites where structural rearrangements upon protonation change could be transmitted throughout the protein. Proton binding to bulk-exposed clusters of titratable protein sidechains ensures the pH sensing mechanism is robust.
Novel TrueVue series of 3D echocardiography: Revealing the pathological morphology of congenital heart disease
Authors: Sun Feifei , Sun Aijiao , Chen Yixin , Xiao Yangjie , Zhang Xintong , Qiao Wei , Tan Xueying , Liang Yanxiao , Li Dongyu , Yang Shu , Ren Weidong
Published: September 2022

Aims: This study explored the advantages and limitations of novel series of three-dimensional (3D) echocardiographic techniques and summarized their application methods for congenital heart diseases (CHDs).

Method and result: Two-dimensional (2D), traditional 3D echocardiography, and TrueVue plus light and/or Glass novel 3D technologies were performed on 62 patients with CHD, and a clinical survey was designed to judge whether the novel 3D images were more helpful for understanding the cardiac condition and guide treatment than traditional 3D images. TrueVue increased the visual resolution and simulated the true texture of cardiac tissue, significantly improving the display ability of abnormal anatomical structures in CHDs. TrueVue Glass displayed the blood channel and the internal structure of cardiac cavity more intuitively, indicating a new observation aspect not shown by conventional echocardiography. The clinical survey results showed that the new 3D imaging methods effectively increased the diagnostic confidence of echocardiographers, enabled surgeons to better understand the details of lesions, promoted efficient communication, and improved the confidence of both doctors and patients in treatment.

Conclusion: The combined application of TrueVue, TrueVue Light, and TrueVue Glass more closely simulated real anatomical features, showed more comprehensive and subtle blood flow in the lumen, not only increased the visual effect but also provided more useful diagnostic information, improved the accuracy of evaluation and treatment of CHD when compared to traditional imaging techniques, indicating that this combined application has significant clinical value.
Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele
Authors: Flück Martin , Vaughan David , Rittweger Jörn , Giraud Marie-Noëlle
Published: September 2022

Homozygous carriers of the deletion allele in the gene for angiotensin-converting enzyme (ACE-DD) demonstrate an elevated risk to develop inactivity-related type II diabetes and show an overshoot of blood glucose concentration with enduring exercise compared to insertion allele carriers. We hypothesized that ACE-DD genotypes exhibit a perturbed activity of signaling processes governing capillary-dependent glucose uptake in vastus lateralis muscle during exhaustive cycling exercise, which is associated with the aerobic fitness state. 27 healthy, male white Caucasian subjects (26.8 ± 1.1 years; BMI 23.6 +/− 0.6 kg m−2) were characterized for their aerobic fitness based on a threshold of 50 ml O2 min−1 kg−1 and the ACE-I/D genotype. Subjects completed a session of exhaustive one-legged exercise in the fasted state under concomitant measurement of cardiorespiratory function. Capillary blood and biopsies were collected before, and ½ and 8 h after exercise to quantify glucose and lipid metabolism-related compounds (lipoproteins, total cholesterol, ketones) in blood, the phosphorylation of 45 signaling proteins, muscle glycogen and capillaries. Effects of aerobic fitness, ACE-I/D genotype, and exercise were assessed with analysis of variance (ANOVA) under the hypothesis of a dominant effect of the insertion allele. Exertion with one-legged exercise manifested in a reduction of glycogen concentration ½ h after exercise (−0.046 mg glycogen mg−1 protein). Blood glucose concentration rose immediately after exercise in association with the ACE-I/D genotype (ACE-DD: +26%, ACE-ID/II: +6%) and independent of the fitness state (p = 0.452). Variability in total cholesterol was associated with exercise and fitness. In fit subjects, the phosphorylation levels of glucose uptake-regulating kinases [AKT-pT308 (+156%), SRC-pY419, p38α-pT180/T182, HCK-pY411], as well as cytokine/angiotensin 1-7 signaling factors [(STAT5A-pY694, STAT5B-pY699, FYN-pY420, EGFR-pY1086] were higher in angiotensin converting enzyme I-allele carriers than ACE-DD genotypes after exercise. Conversely, the AKT-S473 phosphorylation level (+117%) and angiotensin 2’s blood concentration (+191%) were higher in ACE-DD genotypes. AKT-S473 phosphorylation levels post-exercise correlated to anatomical parameters of muscle performance and metabolic parameters (p < 0.05 and │r│>0.70). The observations identify reciprocal alterations of S473 and T308 phosphorylation of AKT as gatekeeper of a post-translational dysregulation of transcapillary glucose uptake in ACE-DD genotypes which may be targeted in personalized approaches to mitigate type II diabetes.
Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3
Authors: Sidorova-Darmos Elena , Fallah Merrick S. , Logan Richard , Lin Cheng Yu , Eubanks James H.
Published: September 2022

Post-translational modification of mitochondrial proteins represents one mechanism by which the functional activity of mitochondria can be regulated. In the brain, these modifications can influence the functional properties of different neural circuitries. Given that the sirtuin family member Sirt3 represents the primary protein deacetylase enzyme in mitochondria, we tested whether brain mitochondrial proteome acetylation would increase in male or female mice lacking Sirt3. Our results confirm that whole brain mitochondrial proteome acetylation levels are indeed elevated in both sexes of Sirt3-KO mice relative to controls. Consistently, we found the mitochondria of mouse embryonic fibroblast (MEF) cells derived from Sirt3-KO mice were smaller in size, and fewer in number than in wild-type MEFs, and that mitochondrial free calcium levels were elevated within the mitochondria of these cells. As protein acetylation can influence mitochondrial function, and changes in mitochondrial function have been linked to alterations in neural circuit function regulating motor activity and anxiety-like behavior, we tested whether Sirt3-deficient mice would display sensitized responsiveness to the stimulant amphetamine. Both male and female Sirt3-KO mice displayed hyper-locomotion and attenuated anxiety-like behavior in response to a dose of amphetamine that was insufficient to promote any behavioural responses in wild-type mice. Collectively, these results confirm that Sirt3 regulates mitochondrial proteome acetylation levels in brain tissue, and that the absence of Sirt3 increases the sensitivity of neural systems to amphetamine-induced behavioural responses.
Non-invasive prognostic biomarker of lung cancer patients with brain metastases: Recurrence quantification analysis of heart rate variability
Authors: Li Guangqiao , Wu Shuang , Zhao Huan , Guan Weizheng , Zhou Yufu , Shi Bo
Published: September 2022

Background: It has previously been shown that the time-domain characteristic of heart rate variability (HRV) is an independent prognostic factor for lung cancer patients with brain metastasis (LCBM). However, it is unclear whether the nonlinear dynamic features contained in HRV are associated with prognosis in patients with LCBM. Recurrence quantification analysis (RQA) is a common nonlinear method used to characterize the complexity of heartbeat interval time series. This study was aimed to explore the association between HRV RQA parameters and prognosis in LCBM patients.

Methods: Fifty-six LCBM patients from the Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, were enrolled in this study. Five-minute ECG data were collected by a mini-ECG recorder before the first brain radiotherapy, and then heartbeat interval time series were extracted for RQA. The main parameters included the mean diagonal line length (Lmean), maximal diagonal line length (Lmax), percent of recurrence (REC), determinism (DET) and Shannon entropy (ShanEn). Patients were followed up (the average follow-up time was 19.2 months, a total of 37 patients died), and the relationships between the RQA parameters and survival of LCBM patients were evaluated by survival analysis.

Results: The univariate analysis showed that an Lmax of >376 beats portended worse survival in LCBM patients. Multivariate Cox regression analysis revealed that the Lmax was still an independent prognostic factor for patients with LCBM after adjusting for confounders such as the Karnofsky performance status (KPS) (HR = 0.318, 95% CI: 0.151–0.669, p = 0.003).

Conclusion: Reduced heartbeat complexity indicates a shorter survival time in patients with LCBM. As a non-invasive biomarker, RQA has the potential for application in evaluating the prognosis of LCBM patients.
Molecular cytogenetic characterization of a new wheat-Thinopyrum intermedium homoeologous group-6 chromosome disomic substitution line with resistance to leaf rust and stripe rust
Authors: Zhang Xiaojun , Li Jianbo , Ge Yudi , Guan Haixia , Li Guangrong , Zhang Shuwei , Wang Xiaolu , Li Xin , Chang Zhijian , Zhang Peng , Jia Juqing , Liu Cheng
Published: September 2022

Thinopyrum intermedium (JJJsJsStSt, 2n = 6x = 42), a member of tertiary gene pool of hexaploid wheat (Triticum aestivum L., AABBDD, 2n = 6x = 42), provides several beneficial genes for wheat improvement. In this study, line CH51 was developed from the BC1F8 progeny of a partial wheat-Th. intermedium amphiploid TAI8335 (2n = 56) and wheat cultivar (cv.) Jintai 170. Somatic metaphase chromosome counting showed that CH51 had stable 42 chromosomes. Genomic in situ hybridization (GISH) analysis showed that CH51 had 40 wheat chromosomes and two Th. intermedium chromosomes involving translocation between Js- and St-genome chromosomes. Non-denaturing fluorescence in situ hybridization (ND-FISH) analysis revealed that CH51 lacked a pair of wheat chromosome 6B. Wheat 55K SNP array analysis verified that chromosome 6B had the highest percentage of missing SNP loci in both CH51 and Chinese Spring (CS) nullisomic 6B-tetrasomic 6D (CS-N6BT6D) and had the highest percentage of polymorphic SNP loci between CH51 and cv. Jintai 170. We identified that CH51 was a wheat-Th. intermedium T6StS.6JsL (6B) disomic substitution line. Disease resistance assessment showed that CH51 exhibited high levels of resistance to the prevalent Chinese leaf rust and stripe rust races in the field. Therefore, the newly developed line CH51 can be utilized as a potential germplasm in wheat disease resistance breeding.
Characterization of walnut JrWOX11 and its overexpression provide insights into adventitious root formation and development and abiotic stress tolerance
Authors: Chang Yingying , Song Xiaobo , Li Mingjun , Zhang Qixiang , Zhang Pu , Lei Xiashuo , Pei Dong
Published: September 2022

The well-developed root system enables plant survival under various environmental stresses. WUSCHEL-RELATED HOMEOBOX GENE 11 (WOX11) plays a critical role in adventitious root formation and development in rice, Arabidopsis, and easy-to-root tree poplar. However, in difficult-to-root trees, the knowledge of WOX11 during adventitious root formation and development remains scarce. In this study, the JrWOX11 gene was isolated from a difficult-to-root tree walnut and heterologously expressed in the “84K” poplar. The results showed that JrWOX11 contained a similar structure and sequence to the homologous genes in rice, Arabidopsis, and poplar, but had different numbers and types of motifs and cis-elements. JrWOX11 lacked the motif GGAIQY compared to that in easy-to-root trees. In addition, JrWOX11 expression was induced by ABA, PEG, and NaCl treatments. Overexpression of JrWOX11 in poplar promoted root initiation and significantly increased adventitious root (ARs) number, lateral roots (LRs) number, and root hair (RH) length. Furthermore, the aboveground biomass was notably increased under NaCl and PEG treatments in transgenic plants. When NaCl and PEG were removed, the survival rate, aerial shoot development, and de novo root organogenesis were also markedly enhanced in transgenic shoot cuttings. The study provides valuable information on the differences between JrWOX11 and the homologous genes in rice, Arabidopsis, and poplar, and supports the critical role of JrWOX11 in the formation of AR and tolerance to salt and osmotic stresses.
Mepiquat chloride inhibits soybean growth but improves drought resistance
Authors: Wang Xiyue , Zhou Qi , Wang Xin , Song Shuang , Liu Jun , Dong Shoukun
Published: September 2022

Soybeans are an important economic crop. As the most widely used growth regulator globally, the molecular mechanism of mepiquat chloride (DPC) in soybean remains unknown. In this study, RNA sequencing technology combined with ultra-performance liquid chromatography and tandem mass spectrometry were used to analyze the changes in the leaf transcriptome and metabolomics of soybean leaves at the seedling stage under DPC stress. The results showed that differentially expressed genes related to photosynthesis and cell wall synthesis were significantly downregulated at the transcriptional level. In addition, the syntheses of gibberellin, zeatin, brassinolide, and other plant hormones were inhibited in the signal transduction pathway of plant hormones, thereby inhibiting plant growth. In contrast, at the metabolic level, the expression levels of flavonoid differential metabolites were significantly increased, and the proportions of flavonoids in the two varieties were 61.5 and 66%, respectively. The combined analysis of transcriptome and metabolomics showed that the differential expressed genes and metabolites were mainly enriched in the isoflavonoid biosynthesis and flavonoid biosynthesis pathways. Principally, DPC inhibited plant growth but improved drought resistance. Our study is the first to report the molecular mechanism of DPC regulation in soybean, providing useful insights into the rational application of DPC in soybean.
An APETALA2/ethylene responsive factor transcription factor GmCRF4a regulates plant height and auxin biosynthesis in soybean
Authors: Xu Zhiyong , Wang Ruikai , Kong Keke , Begum Naheeda , Almakas Aisha , Liu Jun , Li Hongyu , Liu Bin , Zhao Tuanjie , Zhao Tao
Published: September 2022

Plant height is one of the key agronomic traits affecting soybean yield. The cytokinin response factors (CRFs), as a branch of the APETALA2/ethylene responsive factor (AP2/ERF) super gene family, have been reported to play important roles in regulating plant growth and development. However, their functions in soybean remain unknown. This study characterized a soybean CRF gene named GmCRF4a by comparing the performance of the homozygous Gmcrf4a-1 mutant, GmCRF4a overexpression (OX) and co-silencing (CS) lines. Phenotypic analysis showed that overexpression of GmCRF4a resulted in taller hypocotyls and epicotyls, more main stem nodes, and higher plant height. While down-regulation of GmCRF4a conferred shorter hypocotyls and epicotyls, as well as a reduction in plant height. The histological analysis results demonstrated that GmCRF4a promotes epicotyl elongation primarily by increasing cell length. Furthermore, GmCRF4a is required for the expression of GmYUCs genes to elevate endogenous auxin levels, which may subsequently enhance stem elongation. Taken together, these observations describe a novel regulatory mechanism in soybean, and provide the basis for elucidating the function of GmCRF4a in auxin biosynthesis pathway and plant heigh regulation in plants.
A comprehensive meta-QTL analysis for yield-related traits of durum wheat (Triticum turgidum L. var. durum) grown under different water regimes
Authors: Arriagada Osvin , Gadaleta Agata , Marcotuli Ilaria , Maccaferri Marco , Campana Matteo , Reveco Samantha , Alfaro Christian , Matus Iván , Schwember Andrés R.
Published: September 2022

Abiotic stress strongly affects yield-related traits in durum wheat, in particular drought is one of the main environmental factors that have effect on grain yield and plant architecture. In order to obtain new genotypes well adapted to stress conditions, the highest number of desirable traits needs to be combined in the same genotype. In this context, hundreds of quantitative trait loci (QTL) have been identified for yield-related traits in different genetic backgrounds and environments. Meta-QTL (MQTL) analysis is a useful approach to combine data sets and for creating consensus positions for the QTL detected in independent studies for the reliability of their location and effects. MQTL analysis is a useful method to dissect the genetic architecture of complex traits, which provide an extensive allelic coverage, a higher mapping resolution and allow the identification of putative molecular markers useful for marker-assisted selection (MAS). In the present study, a complete and comprehensive MQTL analysis was carried out to identify genomic regions associated with grain-yield related traits in durum wheat under different water regimes. A total of 724 QTL on all 14 chromosomes (genomes A and B) were collected for the 19 yield-related traits selected, of which 468 were reported under rainfed conditions, and 256 under irrigated conditions. Out of the 590 QTL projected on the consensus map, 421 were grouped into 76 MQTL associated with yield components under both irrigated and rainfed conditions, 12 genomic regions containing stable MQTL on all chromosomes except 1A, 4A, 5A, and 6B. Candidate genes associated to MQTL were identified and an in-silico expression analysis was carried out for 15 genes selected among those that were differentially expressed under drought. These results can be used to increase durum wheat grain yields under different water regimes and to obtain new genotypes adapted to climate change.
Genomic and transcriptomic analyses provide insights into valuable fatty acid biosynthesis and environmental adaptation of yellowhorn
Authors: Liang Qiang , Liu Jian Ning , Fang Hongcheng , Dong Yuhui , Wang Changxi , Bao Yan , Hou Wenrui , Zhou Rui , Ma Xinmei , Gai Shasha , Wang Lichang , Li Shouke , Yang Ke Qiang , Sang Ya Lin
Published: September 2022

Yellowhorn (Xanthoceras sorbifolium) is an oil-bearing tree species growing naturally in poor soil. The kernel of yellowhorn contains valuable fatty acids like nervonic acid. However, the genetic basis underlying the biosynthesis of valued fatty acids and adaptation to harsh environments is mainly unexplored in yellowhorn. Here, we presented a haplotype-resolved chromosome-scale genome assembly of yellowhorn with the size of 490.44 Mb containing scaffold N50 of 34.27 Mb. Comparative genomics, in combination with transcriptome profiling analyses, showed that expansion of gene families like long-chain acyl-CoA synthetase and ankyrins contribute to yellowhorn fatty acid biosynthesis and defense against abiotic stresses, respectively. By integrating genomic and transcriptomic data of yellowhorn, we found that the transcription of 3-ketoacyl-CoA synthase gene XS04G00959 was consistent with the accumulation of nervonic and erucic acid biosynthesis, suggesting its critical regulatory roles in their biosynthesis. Collectively, these results enhance our understanding of the genetic basis underlying the biosynthesis of valuable fatty acids and adaptation to harsh environments in yellowhorn and provide foundations for its genetic improvement.
A systematic review to assess the evidence-based effectiveness, content, and success factors of behavior change interventions for enhancing pro-environmental behavior in individuals
Authors: Rau Henriette , Nicolai Susanne , Stoll-Kleemann Susanne
Published: September 2022

To reduce global greenhouse gas emissions in order to limit global warming to 1.5°C, individuals and households play a key role. Behavior change interventions to promote pro-environmental behavior in individuals are needed to reduce emissions globally. This systematic literature review aims to assess the a) evidence-based effectiveness of such interventions and b) the content of very successful interventions without limiting the results to specific emitting sectors or countries. Based on the “PICOS” mnemonic and PRISMA statement, a search strategy was developed, and eligibility criteria were defined. Three databases (Embase, PsycInfo, and Web of Science) were searched to retrieve and review potential literature. As a result, 54 publications from 2010 to 2021 were included in the analysis. The results show that most interventions only have small positive effects or none at all. A total of 15 very successful interventions focused on the sectors of mobility, energy, and waste and incorporated improved (infra-) structures, education, feedback, enablement or made the sustainable option the default. Six evidence-based recommendations for content, timing, and setting are deducted and given for interventions on enhancing pro-environmental behavior (PEB). In summary, although the various interventions and intervention types to promote PEB differ in their effectiveness, very successful interventions have common elements. Future research should focus on high-/low-impact and high-/low-cost behavior to develop interventions that aim at high-impact but low-cost behavior changes, or avoid low-impact but high-cost behavior.
Investigating user perceptions of commercial virtual assistants: A qualitative study
Authors: Mirghaderi Leilasadat , Sziron Monika , Hildt Elisabeth
Published: September 2022

As commercial virtual assistants become an integrated part of almost every smart device that we use on a daily basis, including but not limited to smartphones, speakers, personal computers, watches, TVs, and TV sticks, there are pressing questions that call for the study of how participants perceive commercial virtual assistants and what relational roles they assign to them. Furthermore, it is crucial to study which characteristics of commercial virtual assistants (both existing ones and those envisioned for the future) are perceived as important for establishing affective interaction with commercial virtual assistants. By conducting 26 interviews and performing content analysis of the interview transcripts, this study investigates how the participants in the study perceive, engage, and interact with a variety of commercial virtual assistants. The results lead to better understanding of whether forms of attachment are established or if some sort of relationship is produced between humans and commercial virtual assistants. Key takeaways from our results indicate that, in their current state, the lack of humanlike characteristics in commercial virtual assistants prevents users from forming an emotional attachment to commercial virtual assistants, but this does not deter them from using anthropomorphic language to describe commercial virtual assistants. Yet, our results reveal that users expect commercial virtual assistants’ attributes to be more humanlike in the future.
Unpacking the effects of personality traits on algorithmic awareness: The mediating role of previous knowledge and moderating role of internet use
Authors: Fang Wei , Jin Jianbin
Published: September 2022

The COVID-19 pandemic has accelerated the integration of algorithms in online platforms to facilitate people’s work and life. Algorithms are increasingly being utilized to tailor the selection and presentation of online content. Users’ awareness of algorithmic curation influences their ability to properly calibrate their reception of online content and interact with it accordingly. However, there has been a lack of research exploring the factors that contribute to users’ algorithmic awareness, especially in the roles of personality traits. In this study, we explore the influence of Big Five personality traits on internet users’ algorithmic awareness of online content and examine the mediating effect of previous knowledge and moderating effect of breadth of internet use in in China during the pandemic era. We adapted the 13-item Algorithmic Media Content Awareness Scale (AMCA-scale) to survey users’ algorithmic awareness of online content in four dimensions. Our data were collected using a survey of a random sample of internet users in China (n= 885). The results of this study supported the moderated mediation model of open-mindedness, previous knowledge, breadth of internet use, and algorithmic awareness. The breadth of internet use was found to be a negative moderator between previous knowledge and algorithmic awareness.