bluuebunny/crossref_metadata_2025 huggingface dataset:
Extra virgin olive oil extract rich in secoiridoids induces an anti-inflammatory profile in peripheral blood mononuclear cells from obese children
Authors: De Santis Stefania , Crupi Pasquale , Piacente Laura , Mestice Anna , Colabufo Nicola Antonio , Amodio Loredana , Pontrelli Paola , Gesualdo Loreto , Moschetta Antonio , Clodoveo Maria Lisa , Faienza Maria Felicia , Corbo Filomena
Published: October 2022

Obesity represents an important public health challenge of the twenty first century reaching epidemic proportions worldwide; this is especially true for the pediatric population. In this context, bioactive compounds from foods are crucial to counteract chronic inflammation as a typical feature of obesity. In particular, extra virgin olive oil (EVOO) is one of the most important functional foods exerting, among others, an anti-inflammatory activity not only due to its major (monounsaturated fatty acids) but also to its minor (phenolics) components, as reported in the last years. However, only a limited number of studies were performed on pediatric population, and even fewer are those focusing on EVOO phenolics that investigate the correlation of the chemical characterization with the biological function. Thus, starting from our in vitro data identifying an EVOO chemical profile characterized by a high content of secoiridoids correlating with an anti-inflammatory effect, we studied the ability of an EVOO extract with the same chemical profile to retain this function ex vivo. Specifically, peripheral blood mononuclear cells (PBMCs) collected from obese children were treated with EVOO and olive oil extracts, characterized by a low polyphenol content, to study the ability of secoiridoids to dampen the inflammatory response. A reduction of pro-inflammatory CD14+CD16+ monocytes was detected by cytofluorimetric analysis when PBMCs were treated with EVOO as compared to olive oil extracts. According to this, a down modulation of CCL2 and CCL4 chemokines involved in the recruitment of inflammatory cells, was reported in the supernatants of EVOO relative to olive oil extracts treated PBMCs. Moreover, a high-throughput gene expression analysis revealed that PBMCs molecular profile from obese children is greatly modulated after the treatment with EVOO extract in terms of metabolic and inflammatory pathways. Importantly, some of the significantly modulated genes were involved in the pathways promoting the development of severe obesity. Overall, our ex vivo data demonstrated the ability of EVOO to reduce the inflammatory milieu of PBMCs from obese children both at protein and molecular levels. Of note, a good correlation between the EVOO chemical profile and the biological modulations in terms of anti-inflammatory activity was reported.
A time-restricted feeding intervention in children and adolescents with obesity: The TRansForm study protocol
Authors: Molina-Giraldo Paula , Murillo Serafin , Meis Laura , Sans Oscar , Amat-Bou Montse , Llobet Marina , Jimenez-Chillaron Josep C. , Ramon-Krauel Marta , Lerin Carles
Published: October 2022

Obesity during childhood is of special concern as adiposity is typically tracked into adult life and it constitutes a major risk factor for future obesity and associated metabolic disorders. Recent studies indicate that time-restricted feeding (TRF) interventions may provide a promising strategy for obesity treatment. However, TRF interventions have only been tested in adult subjects. This study aims to determine both short- and long-term effects of a TRF intervention in children and adolescents with obesity. We will also investigate potential mechanisms mediating the response to the intervention, including the circadian rhythm and the gut microbiota composition. We have designed a randomized-controlled parallel-group clinical study in which children and adolescents (age range 8–18 year-old) with obesity will be subjected to time-restricted eating or no time restrictions for 2 months. Follow-up visits will allow for long-term effect assessments. We will measure anthropometric (BMI, body composition) and metabolic parameters (glucose and lipid metabolism), indicators of the circadian rhythm, and gut microbiota composition will be analyzed. This study will (1) determine safety and effectiveness of the TRF intervention in children and adolescents; (2) assess its long-term effects; and (3) evaluate potential mechanisms involved in the response to the intervention.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [NCT05174871].
Brown fat-associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein
Authors: Aita Sayuri , Matsushita Mami , Yoneshiro Takeshi , Hatano Takuya , Kameya Toshimitsu , Ohkubo Iwao , Saito Masayuki
Published: October 2022

The increase of whole-body energy expenditure seen after a single meal ingestion, referred to as diet-induced thermogenesis (DIT), substantially varies depending on the meal’s macronutrient composition. Brown adipose tissue (BAT), a site of non-shivering thermogenesis, was reported to be involved in DIT. To examine the effects of meal composition on BAT-associated DIT in humans, healthy male participants underwent fluorodeoxyglucose–positron emission tomography to assess BAT activity, and respiratory gas analysis for 2 h after ingestion of a carbohydrate-, protein-, or fat-rich meal (C-meal, P-meal, and F-meal, respectively). The calculated DIT at 2 h was 6.44 ± 2.01%, 3.49 ± 2.00%, and 2.32 ± 0.90% of the ingested energy after the P-meal, C-meal, and F-meal, respectively. The DIT after C-meal ingestion correlated positively with BAT activity (P = 0.011), and was approximately twice greater in the group with high-BAT activity than in the group with low-BAT activity (4.35 ± 1.74% vs. 2.12 ± 1.76%, P < 0.035). Conversely, the DIT after F-meal or P-meal ingestion did not correlate with BAT activity, with no difference between the two groups. Thus, BAT has a significant role in DIT after ingestion of a carbohydrate-rich meal, but hardly after ingestion either protein- or fat-rich meal.
Thoroughly review the recent progresses in improving O/W interfacial properties of proteins through various strategies
Authors: Zhang Haozhen , Zhao Xue , Chen Xing , Xu Xinglian
Published: October 2022

Along with the future food market developing world widely, the personalized nutrition and rational function food design are found to be urgently attracted. Oil in a water (O/W) emulsion system has an excellent ability to maintain nutraceuticals and thus plays a promising role in producing future functional foods. Understanding the interfacial related mechanisms involved are essential for improving the quality of food products. Protein can effectively reduce interfacial tension and stable immiscible phases. The interfacial properties of proteins directly affect the emulsion qualities, which have gradually become a prospective topic. This review will first briefly discuss the interfacial-related fundamental factors of proteins. Next, the paper thoroughly overviewed current physical and chemical strategies tailored to improving the interfacial and emulsion properties of proteins. To be summarized, a higher flexibility could allow protein to be more easily unfolded and adsorbed onto the interface but could also possibly form a softer interfacial film. Several physical strategies, such as thermal, ultrasound and especially high-pressure homogenization are well applied to improve the interfacial properties. The interfacial behavior is also altered by various green chemical strategies, such as pH adjustment, covalent modification, and low molecular weight (LMW) surfactant addition. These strategies upgraded emulsion properties by increasing adsorption load, accelerating diffusion and adsorption rate, associated with lowering interfacial tension, and promoting interfacial protein interactions. Future researches targeted at elucidating interfacial-bulk protein interactions, unraveling interfacial behavior through in silico tools, exploring connection between interfacial-industrial processing properties, and clarifying the interfacial-sensory-digestive relationships of O/W emulsions is needed to develop emulsion applications.
Physical fitness mediates the inverse association between fatness indicators and academic achievement, despite the school vulnerability of adolescents—The Cogni-Action Project
Authors: Gajardo-Araya Guillermo , Hernández-Jaña Sam , Olivares-Arancibia Jorge , Ferrari Gerson , Delgado-Floody Pedro , Cristi-Montero Carlos
Published: October 2022

Objective

This study aims to determine the mediating role of physical fitness in the relationship between fatness indicators and academic achievement, exploring the influence of school vulnerability.

Methods

A total of 1,296 Chilean adolescents (aged 10 to 14 years; 50% girls) participated in this study. The global fitness score (GFS) was obtained by adding the three main components of the ALPHA fitness test: cardiorespiratory fitness (CRF), muscular fitness (MF), and speed/agility fitness (SAF). CRF was evaluated through the 20 m shuttle run test; MF by upper and lower limb strength tests; and SAF by the 4 × 10 shuttle run test. BMIz and WHtR were evaluated as general (unspecific) and central (specific) fatness indicators. Academic achievement was established through grades in math, language, and science and their average scores. Multiple mediation analyses were performed according to two models, adjusted for sex, maturity, and schools (model 1), and in model 2, the school vulnerability index (SVI) was added. The SVI is an important proxy of socioeconomic status at the school level, and it was categorized as high-, mid-, or low-SVI. Mediation percentages were calculated, and confidence intervals (bootstrapping) were used to establish significant findings.

Results

CRF, SAF, and GFS mediate the relationship between fatness indicators and academic achievement, both partially and totally (ranging from 12.7 to 59.2%). However, MF did not show any mediation effect. After controlling for SVI, CRF, and GFS, mediation changed from partial to total in the associations between math and science with WHtR. Although SAF contributed to GFS mediation, CRF seems to have the most significant mediation role for all academic achievements, regardless of SVI and the fat indicator studied.

Conclusion

A higher level of general physical fitness, especially CRF, significantly mediates the detrimental influence of fatness on the academic achievement of schoolchildren. This study suggests that physical fitness plays a relevant role in academic and public health, considering the high prevalence and detrimental influence of obesity and school vulnerability in children and adolescents.
Grape polyphenols decrease circulating branched chain amino acids in overfed adults
Authors: Bartova Simona , Madrid-Gambin Francisco , Fernández Luis , Carayol Jerome , Meugnier Emmanuelle , Segrestin Bérénice , Delage Pauline , Vionnet Nathalie , Boizot Alexia , Laville Martine , Vidal Hubert , Marco Santiago , Hager Jörg , Moco Sofia
Published: October 2022

Introduction and aims

Dietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials.

Methods

Blood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov.

Results

Changes in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.

Conclusion

Administration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.
Meta analysis of indocyanine green fluorescence in patients undergoing laparoscopic colorectal cancer surgery
Authors: Deng Jia , Hu Wenting , Li Yang , Xiong Kai , Yue Tinghui , Lai Xiangquan , Xiao Tianbao
Published: October 2022

This meta-analysis intended to systematically evaluate the clinical implications of indocyanine green fluorescence (ICG) in patients undergoing laparoscopic colorectal surgery. PubMed, MEDLINE, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Medical Information System and China Biomedical Database were synthetically searched for studies published from inception to April 14, 2022. The randomized controlled trials comparing ICG-use with controls were selected. The incidence of anastomotic leakage (AL), lymph node detection, operation duration, intraoperative bleeding, postoperative morbidity, and hospitalization time were evaluated in summary analysis, and calculated the corresponding 95% confidence intervals (CI). Subsequently, in addition to subgroup analyses, studies for heterogeneity, sensitivity, and publication bias were carried out. Consequently, 3453 patients in the enrolled 15 studies were included; 1616 patients were allocated to the experimental group, and 1837 patients were assigned to the control group. The ICG group had a significantly decreased risk of AL (RR: 0.50, 95% CI: 0.37–0.67) and shorter hospitalization time (SMD: -0.31, 95% CI: -0.54–0.08) compared to the control group. Meanwhile, the ICG showed clearly better lymph node detection (SMD: 0.19, 95% CI: 0.02–0.36). However, when the content of operation duration (SMD: -0.07, 95% CI: -0.30–0.15) and intraoperative bleeding (SMD: -0.16, 95% CI: -0.35–0.04) were compared, no statistical significance was found. Furthermore, the pooled analysis of postoperative morbidity was not statistically significant (RR:0.79, 95% CI: 0.58–1.08). The results of the subgroup analysis of AL indicated that there may be regional variations in AL (RR: 0.50, 95% CI: 0.37–0.67) but not in postoperative morbidity (RR: 0.79, 95% CI: 0.58–1.08). In conclusion, the application of ICG in laparoscopic colorectal surgery can effectively reduce the AL, lymph node detection, and hospitalization time. However, more multicenter large-sample randomized controlled trials are required to further confirm its advantages. The meta-analysis was registered in PROSPERO (no. CRD42022288054).
Detection of asymptomatic recurrence following curative surgery improves survival in patients with gastric cancer: A systematic review and meta-analysis
Authors: Pang Hua-Yang , Yan Meng-Hua , Chen Li-Hui , Chen Xiu-Feng , Chen Zhi-Xiong , Zhang Shou-Ru , Sun Hao
Published: October 2022

Background

To date, there is no evidence that intensive follow-up provides survival benefit in gastric cancer patients undergoing curative gastrectomy. The aim of this study is to investigate the efficacy of detection of asymptomatic recurrence using intensive surveillance strategy in long-term survival after curative gastric cancer surgery.

Methods

A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure, Clinical Trials Registry and Google Scholar was performed up to April 2022. The primary outcomes were survival outcomes: overall survival, recurrence-free survival and post-recurrence survival. The secondary endpoints were clinicopathological features, recurrence patterns and treatment after recurrence. The registration number of this protocol is PROSPERO CRD42022327370.

Results

A total of 11 studies including 1898 participants were included. In the pooled analysis, the detection of asymptomatic recurrence was significantly associated with an improved overall survival compared to patients showing symptoms of recurrence (HR=0.67; 95%CI: 0.57-0.79; P<0.001), which was primarily driven by the prolongation of post-recurrence survival (HR=0.51; 95%CI: 0.42-0.61; P<0.001), since there was no significant difference observed in recurrence-free survival (HR=1.12; 95%CI: 0.81-1.55; P=0.48) between the two groups. Meanwhile, male sex and advanced T stage were more frequently observed in the symptomatic recurrence group. Furthermore, patients in the symptomatic recurrence group had a higher proportion of peritoneal relapse but lower proportion of distant lymph node metastasis. Additionally, patients in the symptomatic recurrence group were less likely to receive surgery treatment and post-recurrence chemotherapy.

Conclusion

The detection of asymptomatic recurrence using intensive follow-up was associated with an appreciable improvement in overall survival. However, more robust data from high-quality studies are still required to verify this issue.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327370, identifier CRD42022327370.
Novel small 99mTc-labeled affibody molecular probe for PD-L1 receptor imaging
Authors: Liang Zhigang , Hu Xianwen , Hu Hongyu , Wang Pan , Cai Jiong
Published: October 2022

Objective

The in vivo imaging of programmed death ligand 1 (PD-L1) can monitor changes in PD-L1 expression and guide programmed death 1 (PD-1) or PD-L1-targeted immune checkpoint therapy. A 99mTc-labeled affibody molecular probe targeting the PD-L1 receptor was prepared and evaluated its tracing effect in PD-L1-overexpressing colon cancer.

Methods

The PD-L1 affibody was prepared by genetic recombineering. The 99mTc labeling of the affibody was achieved by sodium glucoheptonate and an SnCl2 labeling system. The labeling rate, radiochemical purity, and stability in vitro were determined by instant thin-layer chromatography; MC38-B7H1 (PD-L1-positive) and MC38 (PD-L1-negative) colon cancer cells were used to evaluate its affinity to PD-L1 by cell-binding experiments. The biodistribution of the 99mTc-labeled affibody molecular probe was then determined in C57BL/6J mice bearing MC38-B7H1 tumors, and tumor targeting was assessed in C57BL/6J mice with MC38-B7H1, MC38 double xenografts.

Result

The nondecayed corrected yield of the 99mTc-PD-L1 affibody molecular probe was 95.95% ± 1.26%, and showed good stability both in phosphate-buffered saline (PBS) and fetal bovine serum within 6 h. The affinity of the 99mTc-PD-L1 affibody molecular probe for cell-binding assays was 10.02 nmol/L. Single photon emission–computed tomography imaging showed a rapid uptake of the tracer in PD-L1-positive tumors and very little tracer retention in PD-L1-negative control tumors. The tracer was significantly retained in the kidneys and bladder, suggesting that it is mainly excreted through the urinary system. Heart, liver, lung, and muscle tissue showed no significant radioactive retention. The biodistribution in vitro also showed significant renal retention, a small amount of uptake in the thyroid and gastrointestinal tract, and rapid blood clearance, and the tumor-to-blood radioactivity uptake ratio peaked 120 min after drug injection.

Conclusion

The 99mTc-PD-L1 affibody molecular probe that we prepared can effectively target to PD-L1-positive tumors imaging in vivo, and clear in blood quickly, with no obvious toxic side effects, which is expected to become a new type of tracer for detecting PD-L1 expression in tumors.
Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials
Authors: Savan N. Anna , Saavedra Paulo Vilar , Halim Alan , Yuzbasiyan-Gurkan Vilma , Wang Ping , Yoo Byunghee , Kiupel Matti , Sempere Lorenzo , Medarova Zdravka , Moore Anna
Published: October 2022

Ninety percent of deaths from cancer are caused by metastasis. miRNAs are critical players in biological processes such as proliferation, metastasis, apoptosis, and self-renewal. We and others have previously demonstrated that miRNA-10b promotes metastatic cell migration and invasion. Importantly, we also showed that miR-10b is a critical driver of metastatic cell viability and proliferation. To treat established metastases by inhibiting miR-10b, we utilized a therapeutic, termed MN-anti-miR10b, composed of anti-miR-10b antagomirs, conjugated to iron oxide nanoparticles, that serve as delivery vehicles to tumor cells in vivo and a magnetic resonance imaging (MRI) reporter. In our previous studies using murine models of metastatic breast cancer, we demonstrated the effectiveness of MN-anti-miR10b in preventing and eliminating existing metastases. With an outlook toward clinical translation of our therapeutic, here we report studies in large animals (companion cats) with spontaneous feline mammary carcinoma (FMC). We first investigated the expression and tissue localization of miR-10b in feline tumors and metastases and showed remarkable similarity to these features in humans. Next, in the first case study involving this therapeutic we intravenously dosed an FMC patient with MN-anti-miR10b and demonstrated its delivery to the metastatic lesions using MRI. We also showed the initial safety profile of the therapeutic and demonstrated significant change in miR-10b expression and its target HOXD10 after dosing. Our results provide support for using companion animals for further MN-anti-miR10b development as a therapy and serve as a guide for future clinical trials in human patients.
Radiomics models based on CT at different phases predicting lymph node metastasis of esophageal squamous cell carcinoma (GASTO-1089)
Authors: Peng Guobo , Zhan Yizhou , Wu Yanxuan , Zeng Chengbing , Wang Siyan , Guo Longjia , Liu Weitong , Luo Limei , Wang Ruoheng , Huang Kang , Huang Baotian , Chen Jianzhou , Chen Chuangzhen
Published: October 2022

Purpose

To investigate the value of radiomics models based on CT at different phases (non-contrast-enhanced and contrast-enhanced images) in predicting lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC).

Methods and materials

Two hundred and seventy-four eligible patients with ESCC were divided into a training set (n =193) and a validation set (n =81). The least absolute shrinkage and selection operator algorithm (LASSO) was used to select radiomics features. The predictive models were constructed with radiomics features and clinical factors through multivariate logistic regression analysis. The predictive performance and clinical application value of the models were evaluated by area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The Delong Test was used to evaluate the differences in AUC among models.

Results

Sixteen and eighteen features were respectively selected from non-contrast-enhanced CT (NECT) and contrast-enhanced CT (CECT) images. The model established using only clinical factors (Model 1) has an AUC value of 0.655 (95%CI 0.552-0.759) with a sensitivity of 0.585, a specificity of 0.725 and an accuracy of 0.654. The models contained clinical factors with radiomics features of NECT or/and CECT (Model 2,3,4) have significantly improved prediction performance. The values of AUC of Model 2,3,4 were 0.766, 0.811 and 0.809, respectively. It also achieved a great AUC of 0.800 in the model built with only radiomics features derived from NECT and CECT (Model 5). DCA suggested the potential clinical benefit of model prediction of LN metastasis of ESCC. A comparison of the receiver operating characteristic (ROC) curves using the Delong test indicated that Models 2, 3, 4, and 5 were superior to Model 1(P< 0.05), and no difference was found among Model 2, 3, 4 and Model 5(P > 0.05).

Conclusion

Radiomics models based on CT at different phases could accurately predict the lymph node metastasis in patients with ESCC, and their predictive efficiency was better than the clinical model based on tumor size criteria. NECT–based radiomics model could be a reasonable option for ESCC patients due to its lower price and availability for renal failure or allergic patients.
Development of D-α-Tocopherol polyethylene glycol 1000 succinate fabricated nanostructural lipid carrier of sorafenib tosylate for metastatic colorectal targeting application: Stability, physical characterization, cytotoxicity, and apoptotic studies against SW48 cells PTEN
Authors: Bhattacharya Sankha , Sharma Satyam , Prajapati Bhupendra G.
Published: October 2022

The study aimed to create D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) nanostructured lipid carriers (NLC) of sorafenib tosylate (ST) as lymphatic delivery systems (LDDS) to fight Metastatic colorectal cancer. Initially, ST-SLN, ST-NLC, and ST-LNE were formulated considering oleic acid (OA), glycerol monolinoleate (GMO), glycerol monolinoleate (GML) as solid lipid and further characterised, and tested for stability. The most stable ST-NLC was fabricated with TPGS to produce ST-TPGS-NLC and evaluated by performing in vitro drug profiling, in vitro cytotoxicity, and apoptotic studies against human female colorectal adenocarcinoma cell lines (SW48 Cells PTEN). Stability studies on three lipidic nanoparticles (ST-SLN, ST-NLC, ST-LEN) showed particle size, polydispersity index, and zeta potential ranging from 165 nm to 298 nm, 0.125 to 0.288, and -31 mV to -16 mV. At 1600 minutes, more than 80% of ST-NLC1 was released, confirming the sustained release pattern of the formulation. ST-NLC and ST-TPGS-NLC have entrapment efficiencies above 50%. Pure ST’s IC50 at 72 hr was 3.45 µg/mL, while 1.56 µg/mL was for ST-TPGS-NLC. The ST-TPGS-NLC reduced the number of livings SW48 Cells PTEN from 91% to 5%, compared to 75% to 8% of pure ST. The ST-TPGS-NLC is a promising LDDS for delivering ST for metastatic colorectal cancer.
Dorsal root ganglion stimulation produces differential effects on action potential propagation across a population of biophysically distinct C-neurons
Authors: Graham Robert D. , Jhand Amolak S. , Lempka Scott F.
Published: October 2022

Dorsal root ganglion stimulation (DRGS) is a neurostimulation therapy used to manage chronic pain that does not respond to conventional therapies. Unfortunately, not all patients receive sufficient pain relief from DRGS, leaving them with few other treatment options. Presently, our understanding of the mechanisms of action of DRGS is incomplete, preventing us from determining why some patients do not receive analgesia from the therapy. One hypothesis suggests that DRGS augments the filtering of action potentials (APs) at the T-junction of nociceptive C-neurons. To test this hypothesis, we utilized a computational modeling approach in which we developed a population of one thousand biophysically distinct C-neuron models which each produced electrophysiological characteristics (e.g., AP height, AP duration) reported in previous experimental studies. We used this population of model C-neurons to study how morphological and electrophysiological characteristics affected the propagation of APs through the T-junction. We found that trains of APs can propagate through the T-junction in the orthodromic direction at a higher frequency than in the antidromic direction due to the decrease in axonal diameter from the peripheral to spinal axon. Including slow outward conductances in the axonal compartments near the T-junction reduced following frequencies to ranges measured experimentally. We next used the population of C-neuron models to investigate how DRGS affected the orthodromic propagation of APs through the T-junction. Our data suggest that suprathreshold DRGS augmented the filtering of APs at the T-junction of some model C-neurons while increasing the activity of other model C-neurons. However, the stimulus pulse amplitudes required to induce activity in C-neurons (i.e., several mA) fell outside the range of stimulation pulse amplitudes used clinically (i.e., typically ≤1 mA). Furthermore, our data suggest that somatic GABA currents activated directly or indirectly by the DRGS pulse may produce diverse effects on orthodromic AP propagation in C-neurons. These data suggest DRGS may produce differential effects across a population of C-neurons and indicate that understanding how inherent biological variability affects a neuron's response to therapeutic electrical stimulation may be helpful in understanding its mechanisms of action.
Laparoscopic surgery versus robot-assisted surgery for choledochal cyst excision: A systematic review and meta-analysis
Authors: Zhang Ke , Zhao Difang , Xie Xiaolong , Wang Wentao , Xiang Bo
Published: October 2022

The aim of this following study is to systematically review and analyze the published data comparing laparoscopic surgery and robotic assisted surgery for choledochal cyst excisions through the metrics of operative time, length of hospital stay and postoperative outcome. PubMed, Web of Science, Embase, Ovid, and the Cochrane Library databases were combed through and data was retrieved from the timespan between January 1995 and October 2021. The primary measures included operative time, intraoperative bleeding, hospital stay, and postoperative complications. Quality and risk of bias were assessed using the Newcastle-Ottawa Quality Assessment Scale. Making use of random-effects models, we pooled the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs). Six studies comprising a total 484 patients who had undergone either laparoscopic surgery [307 (63.43%) patients] or robot-assisted surgery [177 (36.57%) patients] were included in this analysis. Three of the articles involved adults while the other three involved children. All of the studies were published after 2018 and were retrospective case–control studies. Patients undergoing robotic surgery had a shorter hospital stay (MD, 0.95; 95% CI, 0.56 to 1.35; p < 0.00001) and a longer operative time (MD, −57.52; 95% CI, −67.17 to −47.87; p < 0.00001). And there was no significant discrepancy in complications between the two groups. Compared to laparoscopic surgery, robot-assisted surgery is associated with a shorter hospital stay, scores highly in terms of both safety and feasibility, however it also results in a longer operative time. And the two procedures have the same short- and long-term results.
The association of ARRB1 polymorphisms with response to antidepressant treatment in depressed patients
Authors: Chappell Kenneth , Ait Tayeb Abd El Kader , Colle Romain , Bouligand Jérôme , El-Asmar Khalil , Gressier Florence , Trabado Séverine , David Denis Joseph , Feve Bruno , Becquemont Laurent , Corruble Emmanuelle , Verstuyft Céline
Published: October 2022

Introduction: β-arrestin 1, a protein encoded by ARRB1 involved in receptor signaling, is a potential biomarker for the response to antidepressant drug (ATD) treatment in depression. We examined ARRB1 genetic variants for their association with response following ATD treatment in METADAP, a cohort of 6-month ATD-treated depressed patients.

Methods: Patients (n = 388) were assessed at baseline (M0) and after 1 (M1), 3 (M3), and 6 months (M6) of treatment for Hamilton Depression Rating Scale (HDRS) changes, response, and remission. Whole-gene ARRB1 variants identified from high-throughput sequencing were separated by a minor allele frequency (MAF)≥5%. Frequent variants (i.e., MAF≥5%) annotated by RegulomeDB as likely affecting transcription factor binding were analyzed using mixed-effects models. Rare variants (i.e., MAF<5%) were analyzed using a variant set analysis.

Results: The variant set analysis of rare variants was significant in explaining HDRS score changes (T = 878.9; p = 0.0033) and remission (T = -1974.1; p = 0.034). Rare variant counts were significant in explaining response (p = 0.016), remission (p = 0.022), and HDRS scores at M1 (p = 0.0021) and M3 (p=<0.001). rs553664 and rs536852 were significantly associated with the HDRS score (rs553664: p = 0.0055 | rs536852: p = 0.046) and remission (rs553664: p = 0.026 | rs536852: p = 0.012) through their interactions with time. At M6, significantly higher HDRS scores were observed in rs553664 AA homozygotes (13.98 ± 1.06) compared to AG heterozygotes (10.59 ± 0.86; p = 0.014) and in rs536852 GG homozygotes (14.88 ± 1.10) compared to AG heterozygotes (11.26 ± 0.95; p = 0.0061). Significantly lower remitter rates were observed in rs536852 GG homozygotes (8%, n = 56) compared to AG heterozygotes (42%, n = 105) at M6 (p = 0.0018).

Conclusion: Our results suggest ARRB1 variants may influence the response to ATD treatment in depressed patients. Further analysis of functional ARRB1 variants and rare variant burden in other populations would help corroborate our exploratory analysis. β-arrestin 1 and genetic variants of ARRB1 may be useful clinical biomarkers for clinical improvement following ATD treatment in depressed individuals.

Clinical Trial Registration:clinicaltrials.gov; identifier NCT00526383
Identification of a potent dual-function inhibitor for hIMPDH isoforms by computer-aided drug discovery approaches
Authors: Yazdani Meysam , Zamani Javad , Fatemi Seyed Safa-Ali
Published: October 2022

Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme inde novobiosynthesis of purine nucleotides. Due to this important role, it is a great target to drug discovery for a wide range of activities, especially immunosuppressant in heart and kidney transplantation. Both human IMPDH isoforms are expressed in stimulated lymphocytes. In addition to the side effects of existing drugs, previous studies have mainly focused on the type II isoform. In this study, virtual screening and computer-aided approaches were employed to identify potential drugs with simultaneous inhibitory effects on both human IMPDH isoforms. After Re-docking, Double-step docking, and identification of virtual hits based on the PLANTS scoring function, drug-likeness and ADME-Tox assessments of the topmost ligands were performed. Following further evaluation, the best ligand was selected and, in complex with both isoforms, simulated in monomeric and tetrameric forms using molecular dynamics to evaluate its stability and binding pattern. The results showed a potential drug candidate [(S)-N-(3-hydroxy-1-(4-hydroxyphenyl) propyl)-2-(3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide] with a high inhibitory effect on the two human IMPDH isoforms. This drug-like inhibitor could potentially serve as an immunosuppressant to prevent transplant rejection response by inhibiting B- and T-lymphocyte proliferation. In addition, its effect can be evaluated in various therapeutic targets in which IMPDH is known as a therapeutic target, especially in Covid-19 patients.
A time domain anti-jamming processing algorithm for GNSS ranging receiver
Authors: Li Xianghao , Lu Zukun , Chen Feiqiang , Liu Zhe , Yuan Muzi , Ou Gang
Published: October 2022

Traditional anti-jamming algorithms lead to a deviation of the Global Navigation Satellite System receiver’s ranging value, which has become the main obstacle to the improvement of the accuracy of the high-precision ranging receiver. Traditional time-domain anti-jamming (TDAJ) algorithms can cause signal distortion, resulting in ranging bias. This study aims to solve this problem by proposing a design method for adding preprocessing filters in time-domain anti-jamming navigation receivers. In this method, an optimal order filter for adaptively correcting signal distortion is designed according to the time-domain anti-jamming filter coefficients. The experimental results show that the algorithm proposed in this paper can effectively solve the problem of ranging bias caused by the traditional time-domain anti-jamming algorithm. The algorithm can be widely used in dedicated satellite missions that require high positioning accuracy, such as navigation signal monitoring receivers, satellite payload receivers, and precision approach and landing systems for carrier-based aircraft.
Voluntary wheel exercise training affects locomotor muscle, but not the diaphragm in the rat
Authors: Borzykh Anna A. , Gaynullina Dina K. , Shvetsova Anastasia A. , Kiryukhina Oxana O. , Kuzmin Ilya V. , Selivanova Ekaterina K. , Nesterenko Alexey M. , Vinogradova Olga L. , Tarasova Olga S.
Published: October 2022

Introduction: Functional tests and training regimens intensity-controlled by an individual are used in sport practice, clinical rehabilitation, and space medicine. The model of voluntary wheel running in rats can be used to explore molecular mechanisms of such training regimens in humans. Respiratory and locomotor muscles demonstrate diverse adaptations to treadmill exercise, but the effects of voluntary exercise training on these muscle types have not been compared yet. Therefore, this work aimed at the effects of voluntary ET on rat triceps brachii and diaphragm muscles with special attention to reactive oxygen species, which regulate muscle plasticity during exercise.

Methods: Male Wistar rats were distributed into exercise trained (ET) and sedentary (Sed) groups. ET group had free access to running wheels, running activity was continuously recorded and analyzed using the original hardware/software complex. After 8 weeks, muscle protein contents were studied using Western blotting.

Results: ET rats had increased heart ventricular weights but decreased visceral/epididymal fat weights and blood triglyceride level compared to Sed. The training did not change corticosterone, testosterone, and thyroid hormone levels, but decreased TBARS content in the blood. ET rats demonstrated higher contents of OXPHOS complexes in the triceps brachii muscle, but not in the diaphragm. The content of SOD2 increased, and the contents of NOX2 and SOD3 decreased in the triceps brachii muscle of ET rats, while there were no such changes in the diaphragm.

Conclusion: Voluntary wheel running in rats is intensive enough to govern specific adaptations of muscle fibers in locomotor, but not respiratory muscle.
Stable potassium isotopes (41K/39K) track transcellular and paracellular potassium transport in biological systems
Authors: Higgins John A. , Ramos Danielle Santiago , Gili Stefania , Spetea Cornelia , Kanoski Scott , Ha Darren , McDonough Alicia A. , Youn Jang H.
Published: October 2022

As the most abundant cation in archaeal, bacterial, and eukaryotic cells, potassium (K+) is an essential element for life. While much is known about the machinery of transcellular and paracellular K transport–channels, pumps, co-transporters, and tight-junction proteins—many quantitative aspects of K homeostasis in biological systems remain poorly constrained. Here we present measurements of the stable isotope ratios of potassium (41K/39K) in three biological systems (algae, fish, and mammals). When considered in the context of our current understanding of plausible mechanisms of K isotope fractionation and K+ transport in these biological systems, our results provide evidence that the fractionation of K isotopes depends on transport pathway and transmembrane transport machinery. Specifically, we find that passive transport of K+ down its electrochemical potential through channels and pores in tight-junctions at favors 39K, a result which we attribute to a kinetic isotope effect associated with dehydration and/or size selectivity at the channel/pore entrance. In contrast, we find that transport of K+ against its electrochemical gradient via pumps and co-transporters is associated with less/no isotopic fractionation, a result that we attribute to small equilibrium isotope effects that are expressed in pumps/co-transporters due to their slower turnover rate and the relatively long residence time of K+ in the ion pocket. These results indicate that stable K isotopes may be able to provide quantitative constraints on transporter-specific K+ fluxes (e.g., the fraction of K efflux from a tissue by channels vs. co-transporters) and how these fluxes change in different physiological states. In addition, precise determination of K isotope effects associated with K+ transport via channels, pumps, and co-transporters may provide unique constraints on the mechanisms of K transport that could be tested with steered molecular dynamic simulations.
Dynamic gestational week prediction model for pre-eclampsia based on ID3 algorithm
Authors: Li Ziwei , Xu Qi , Sun Ge , Jia Runqing , Yang Lin , Liu Guoli , Hao Dongmei , Zhang Song , Yang Yimin , Li Xuwen , Zhang Xinyu , Lian Cuiting
Published: October 2022

Pre-eclampsia (PE) is a type of hypertensive disorder during pregnancy, which is a serious threat to the life of mother and fetus. It is a placenta-derived disease that results in placental damage and necrosis due to systemic small vessel spasms that cause pathological changes such as ischemia and hypoxia and oxidative stress, which leads to fetal and maternal damage. In this study, four types of risk factors, namely, clinical epidemiology, hemodynamics, basic biochemistry, and biomarkers, were used for the initial selection of model parameters related to PE, and factors that were easily available and clinically recognized as being associated with a higher risk of PE were selected based on hospital medical record data. The model parameters were then further analyzed and screened in two subgroups: early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE). Dynamic gestational week prediction model for PE using decision tree ID3 algorithm in machine learning. Performance of the model was: macro average (precision = 76%, recall = 73%, F1-score = 75%), weighted average (precision = 88%, recall = 89%, F1-score = 89%) and overall accuracy is 86%. In this study, the addition of the dynamic timeline parameter “gestational week” made the model more convenient for clinical application and achieved effective PE subgroup prediction.
Gapless reference genome assembly of Didymella glomerata, a new fungal pathogen of maize causing Didymella leaf blight
Authors: Ma Wendi , Yang Jun , Ding Junqiang , Zhao Wensheng , Peng You-Liang , Bhadauria Vijai
Published: October 2022

Didymella leaf blight (DLB) caused by Didymella glomerata is a new fungal disease of maize (Zea mays), first detected in 2021 in Panjin, Liaoning province of China. Here we report the reference genome assembly of D. glomerata to unravel how the fungal pathogen controls its virulence on maize at the molecular level. A maize-infecting strain Pj-2 of the pathogen was sequenced on the Illumina NovaSeq 6000 and PacBio Sequel II platforms at a 575-fold genomic coverage. The 33.17 Mb gapless genome assembly comprises 32 scaffolds with L/N50 of 11/1.36 Mb, four of which represent full-length chromosomes. The Pj-2 genome is predicted to contain 10,334 protein-coding genes, of which 211, 12 and 134 encode effector candidates, secondary metabolite backbone-forming enzymes and CAZymes, respectively. Some of these genes are potentially implicated in niche adaptation and expansion, such as colonizing new hosts like maize. Phylogenomic analysis of eight strains of six Didymella spp., including three sequenced strains of D. glomerata, reveals that the maize (Pj-2)- and Chrysanthemum (CBS 528.66)-infecting strains of D. glomerata are genetically similar (sharing 92.37% genome with 98.89% identity), whereas Pj-2 shows truncated collinearity with extensive chromosomal rearrangements with the Malus-infecting strain M27-16 of D. glomerata (sharing only 55.01% genome with 88.20% identity). Pj-2 and CBS 528.66 carry four major reciprocal translocations in their genomes, which may enable them to colonize the different hosts. Furthermore, germplasm screening against Pj-2 led to the identification of three sources of DLB resistance in maize, including a tropical inbred line CML496. DLB resistance in the line is attributed to the accumulation of ROS H2O2 in the apoplastic space of the infected cells, which likely restricts the fungal growth and proliferation.
Activation of apoplastic sugar at the transition stage may be essential for axillary bud outgrowth in the grasses
Authors: Kebrom Tesfamichael H. , Doust Andrew N.
Published: October 2022

Shoot branches develop from buds in leaf axils. Once formed from axillary meristems, the buds enter a transition stage before growing into branches. The buds may transition into dormancy if internal and environmental factors limit sucrose supply to the buds. A fundamental question is why sucrose can be limiting at the transition stage for bud outgrowth, whereas new buds continue to be formed. Sucrose is transported to sink tissues through symplastic or apoplastic pathways and a shift from symplastic to apoplastic pathway is common during seed and fruit development. In addition, symplastic connected tissues are stronger sinks than symplastically isolated tissues that rely on sugars effluxed to the apoplast. Recent studies in sorghum, sugarcane, and maize indicate activation of apoplastic sugar in buds that transition to outgrowth but not to dormancy, although the mode of sugar transport during bud formation is still unclear. Since the apoplastic pathway in sorghum buds was specifically activated during bud outgrowth, we posit that sugar for axillary bud formation is most likely supplied through the symplastic pathway. This suggests a key developmental change at the transition stage, which alters the sugar transport pathway of newly-formed buds from symplastic to apoplastic, making the buds a less strong sink for sugars. We suggest therefore that bud outgrowth that relies on overflow of excess sucrose to the apoplast will be more sensitive to internal and environmental factors that enhance the growth of sink tissues and sucrose demand in the parent shoot; whereas bud formation that relies on symplastic sucrose will be less affected by these factors.
Heterozygous frameshift mutation in FaMYB10 is responsible for the natural formation of red and white-fleshed strawberry (Fragaria x ananassa Duch)
Authors: Yuan Huazhao , Cai Weijian , Chen Xiaodong , Pang Fuhua , Wang Jing , Zhao Mizhen
Published: October 2022

During natural evolution and artificial selection, the fruit color of many species has been repeatedly gained or lost and is generally associated with mutations in genes encoding R2R3-MYB transcription factors, especially MYB10. In this study, we show that a heterozygous frameshift mutation (FaMYB10AG-insert/FaMYB10wild) is responsible for the loss of anthocyanins in the flesh of cultivated strawberry. Comparative transcriptomic and metabolomic analyses of red- and white-fleshed strawberry indicated that the low expression level of FaUFGT (flavonol-O-glucosyltransferases) was responsible for the loss of anthocyanins and accumulation of proanthocyanidin in the white-fleshed strawberry and was the crucial gene that encodes enzymes of the anthocyanin biosynthesis pathway. Accordingly, overexpression and silencing of FaUFGT altered anthocyanin content and changed the flesh color of strawberry fruits. Furthermore, whole-genome resequencing analyses identified an AG insertion in the FaMYB10 coding region (FaMYB10AG-insert) of white-fleshed strawberry. Y1H and EMSA assays showed that FaMYB10wild was able to bind to the promoter of the FaUFGT gene, while the FaMYB10AG-insert could not. The skin and flesh color were tightly linked to the number of fully functional FaMYB10 copies in the selfing progeny of white-fleshed strawberry. Our results suggested that heterozygous frameshift mutation of FaMYB10 resulted in the loss of the ability to activate the expression of the FaUFGT gene, was responsible for the natural formation of red and white-fleshed strawberry.