bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between serum biomarkers and non-alcoholic liver disease: Results of a clinical study of Mediterranean patients with obesity
Authors: De Nucci Sara , Castellana Fabio , Zupo Roberta , Lampignano Luisa , Di Chito Martina , Rinaldi Roberta , Giannuzzi Vito , Cozzolongo Raffaele , Piazzolla Giuseppina , Giannelli Gianluigi , Sardone Rodolfo , De Pergola Giovanni
Published: September 2022

Background

Transient elastography is an ultrasound-based method to detect non-alcoholic fatty liver disease (NAFLD). Despite the simultaneously rising prevalence of fatty liver and metabolic disease, further information about metabolic risk indicators of fatty liver is still necessary.

Methods

A Southern Italian population sample with obesity (N = 87) was cross-sectionally explored for associations among the presence of NAFLD, assessed by FibroScan, and clinical, biochemical and anthropometric parameters. Inclusion criteria were age >18 years, BMI ≥ 25 kg/m2, no ongoing supplemental or drug therapy, including oral contraceptives or osteoporosis medications; exclusion criteria were pregnancy, endocrinological diseases, cardiovascular diseases, neoplasia, renal or hepatic failure, hereditary thrombocytopenia, hepatitis B (HBV) or hepatitis C virus (HCV) infection, and excess alcohol consumption.

Results

The study sample featured a female predominance (67%, N = 60), age range 18–64 years, and 40% prevalence of NAFLD, in accordance with the fibroscan-measured controlled attenuation parameter (CAP) threshold value above 302 dB/m. Males were slightly more frequently affected by NAFLD (51.4% vs. 48.6%, p = 0.01). Insulin levels, insulin resistance (quantified by HOMA-IR), diastolic blood pressure, BMI, visceral adipose tissue (VAT), and waist circumference were significantly higher in the NAFLD subset compared to their counterparts (p < 0.01, p < 0.01, p = 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). Uric acid (p < 0.01) also showed a positive trend in the NAFLD group. Other liver steatosis parameters, measured by stiffness (p < 0.01), fatty liver index (FLI) (p < 0.01) and FibroScan-AST (FAST) (p < 0.01), were also significantly greater in the NAFLD group. In three nested linear regression models built to assess associations between CAP values and serum uric acid levels, a single unit increase in uricemia indicated a CAP increase by 14 dB/m, after adjusting for confounders (coefficient: 14.07, 95% CI 0.6–27.54).

Conclusions

Clinical-metabolic screening for NAFLD cannot ignore uricemia, especially in patients with obesity.
Predictive value of the preoperative prognostic nutritional index for postoperative progression in patients with pancreatic neuroendocrine neoplasms
Authors: Fu Mengfei , Yu Li , Yang Liu , Chen Yang , Chen Xiao , Hu Qinyu , Sun Hui
Published: September 2022

Objective

The preoperative nutritional status of cancer patients is closely related to prognosis. The prognostic nutritional index (PNI) has been shown to predict the prognosis of a variety of tumors, but its study in pancreatic neuroendocrine neoplasms (pNENs) is lacking. The aim of the present study is to investigate the predictive value of the preoperative PNI for postoperative progression in patients with pNENs.

Methods

The medical records of 181 patients with pNENs, who underwent surgery, were retrospectively analyzed. A time-dependent receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value of the preoperative PNI. Correlations between the preoperative PNI and clinicopathological parameters were analyzed using multiple linear regression. A Kaplan-Meier curve was applied to assess the progression-free survival (PFS) rate, which was tested using a log rank. Univariate and multivariate Cox proportional risk regression models were used to analyze the predictive value of the preoperative PNI on prognosis.

Results

The optimal cut-off value of the preoperative PNI was 48.275. The patients were divided into a high PNI group (PNI > 48.275, n = 92) and a low PNI group (PNI ≤ 48.275, n = 89). The proportion of patients with tumor progression after surgery was significantly higher in the low PNI group compared with that in the high PNI group (P = 0.004). The Kaplan-Meier curve showed that the PFS rate after surgery was significantly lower in the low PNI group compared with that in the high PNI group (P = 0.026). The preoperative PNI was an independent predictor of PFS (HR: 2.727, 95% CI: 1.174∼6.333, P = 0.020).

Conclusion

The preoperative PNI has a predictive value for postoperative progression in patients with pNENs.
Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging – from theory to practice
Authors: Luís Carla , Maduro Ana T. , Pereira Paula , Mendes José João , Soares Raquel , Ramalho Renata
Published: September 2022

Aging is a natural physiological process, but one that poses major challenges in an increasingly aging society prone to greater health risks such as diabetes, cardiovascular disease, cancer, frailty, increased susceptibility to infection, and reduced response to vaccine regimens. The loss of capacity for cell regeneration and the surrounding tissue microenvironment itself is conditioned by genetic, metabolic, and even environmental factors, such as nutrition. The senescence of the immune system (immunosenescence) represents a challenge, especially when associated with the presence of age-related chronic inflammation (inflammaging) and affecting the metabolic programming of immune cells (immunometabolism). These aspects are linked to poorer health outcomes and therefore present an opportunity for host-directed interventions aimed at both eliminating senescent cells and curbing the underlying inflammation. Senotherapeutics are a class of drugs and natural products that delay, prevent, or reverse the senescence process – senolytics; or inhibit senescence-associated secretory phenotype – senomorphics. Natural senotherapeutics from food sources – nutritional senotherapeutics – may constitute an interesting way to achieve better age-associated outcomes through personalized nutrition. In this sense, the authors present herein a framework of nutritional senotherapeutics as an intervention targeting immunosenescence and immunometabolism, identifying research gaps in this area, and gathering information on concluded and ongoing clinical trials on this subject. Also, we present future directions and ideation for future clinical possibilities in this field.
The association of Carbohydrate Quality Index with cardiovascular disease risk factors among women with overweight and obesity: A cross-sectional study
Authors: Khosravinia Darya , Shiraseb Farideh , Mirzababaei Atieh , Daneshzad Elnaz , Jamili Shahin , Clark Cain C. T. , Mirzaei Khadijeh
Published: September 2022

Purpose

Diet is one of the most important factors influencing cardiovascular disease (CVD). The negative relationship between carbohydrate intake with lipid profiles and body weight has been previously investigated. However, this is the first study seeking to assess the association of carbohydrate quality index (CQI) with CVD risk factors.

Methods

This cross-sectional study was conducted on 291 Iranian overweight and obese women, with a body mass index (BMI) ranging between 25 and 40 kg/m2, and aged 18–48 years. CQI scores were calculated by using a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Biochemical and anthropometric measures were assessed using standard methods, and bioelectrical impedance was used to measure body composition.

Results

We observed that fruits (P < 0.001), vegetables (P < 0.001), and protein (P = 0.002) intake were higher in participants with a higher score of the CQI. When we adjusted for potential confounders, we observed that the CQI was negatively related to systolic blood pressure (SBP) (β = −6.10; 95% CI = −10.11, −2.10; P = 0.003) and DBP (β = −3.11; 95% CI = −6.15, −0.08; P = 0.04). Also, greater adherence to a high CQI dietary pattern, compared to the reference group, was negatively related to HOMA-IR (β = −0.53; 95% CI = −0.94, −0.12) (P for trend = 0.01), WC (β = −3.18; 95% CI = −6.26, −0.10) (P for trend = 0.04), BMI (β = −1.21; 95% CI = −2.50, 0.07) (P for trend = 0.06), and BF (β = −2.06; 95% CI = −3.82, −0.30) (P for trend = 0.02).

Conclusion

In line with previous studies, the CQI was inversely associated with blood pressure, WC, BMI, and BF. Further prospective and clinical trial studies are suggested to confirm these data.
Co-administration of MDR1 and BCRP or EGFR/PI3K inhibitors overcomes lenvatinib resistance in hepatocellular carcinoma
Authors: Sun Dawei , Liu Juan , Wang Yunfang , Dong Jiahong
Published: September 2022

Lenvatinib is the first-line treatment for hepatocellular carcinoma (HCC), the most common type of primary liver cancer; however, some patients become refractory to lenvatinib. The underlying mechanism of lenvatinib resistance (LR) in patients with advanced HCC remains unclear. We focused on exploring the potential mechanism of LR and novel treatments of lenvatinib-resistant HCC. In particular, we established a Huh7 LR cell line and performed in vitro, bioinformatic, and biochemical assays. Additionally, we used a Huh7-LR cell-derived xenograft mouse model to confirm the results in vivo. Following LR induction, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) transporters were markedly upregulated, and the epidermal growth factor receptor (EGFR), MEK/ERK, and PI3K/AKT pathways were activated. In vitro, the co-administration of elacridar, a dual MDR1 and BCRP inhibitor, with lenvatinib inhibited proliferation and induced apoptosis of LR cells. These effects might be due to inhibiting cancer stem-like cells (CSCs) properties, by decreasing colony formation and downregulating CD133, EpCAM, SOX-9, and c-Myc expression. Moreover, the co-administration of gefitinib, an EGFR inhibitor, with lenvatinib retarded proliferation and induced apoptosis of LR cells. These similar effects might be caused by the inhibition of EGFR-mediated MEK/ERK and PI3K/AKT pathway activation. In vivo, co-administration of lenvatinib with elacridar or gefitinib suppressed tumour growth and angiogenesis. Therefore, inhibiting MDR1 and BCRP transporters or targeting the EGFR/PI3K pathway might overcome LR in HCC. Notably, lenvatinib should be used to treat HCC after LR induction owing to its role in inhibiting tumour proliferation and angiogenesis. Our findings could help develop novel and effective treatment strategies for HCC.
Primary hemostasis in fetal growth restricted neonates studied via PFA-100 in cord blood samples
Authors: Kollia Maria , Iacovidou Nicoletta , Iliodromiti Zoi , Pouliakis Abraham , Sokou Rozeta , Mougiou Vasiliki , Boutsikou Maria , Politou Marianna , Boutsikou Theodora , Valsami Serena
Published: September 2022

Background

Platelet function of fetal growth restricted (FGR) neonates remains a field of debate. Platelet function analyzer (PFA-100) offers a quantitative in vitro assessment of primary, platelet-related hemostasis. Our aim was to examine platelet function using PFA-100 in FGR neonates and associate our results with perinatal parameters.

Methods

PFA-100 was applied on 74 FGR neonates, 48 full-term (>37 weeks' gestation) and 26 preterm neonates (<37 weeks). The control group consisted of 118 healthy neonates. Two closure times (CTs) with COL/EPI and COL/ADP cartridges were determined on cord blood samples for each subject. Statistical analysis was performed by SAS 9.4. The statistical significance level was set at 0.05 and all tests were two-tailed.

Results

COL/EPI CTs were prolonged in FGR (median 132 s, IQR 95–181 s) compared with control neonates (median 112.5 s, IQR 93–145 s), p = 0.04. Median COL/EPI CT for term and preterm FGR neonates was 126 s (IQR 90–157 s) and 137 s (IQR 104–203), respectively (p = 0.001), and COL/ADP CT was 70 s (IQR 62–80 s) for term and 75 s (IQR 68–82 s) for preterm FGR neonates (p = 0.08). Among FGR neonates, COL/EPI CT was related with delivery time (with preterm neonates exhibiting prolonged COL/EPI CTs), p = 0.05. No correlation was proved between both CTs and hematological parameters in FGR neonates.

Conclusion

FGR neonates showed impaired platelet function via PFA-100, with preterm FGR neonates confronting the greatest risk. Prolonged COL/EPI CTs in FGR neonates seemed to be independent of hematological parameters and could warn for closer evaluation during the first days of their lives.
Successful hematopoietic stem cell transplantation for two patients with relapse of intrachromosomal amplification of chromosome 21-positive B-cell precursor acute lymphoblastic leukemia
Authors: Harada Tomoya , Toyoda Hidemi , Tsuboya Naoki , Hanaki Ryo , Amano Keishiro , Hirayama Masahiro
Published: September 2022

In children with relapsed acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. Minimal residual disease (MRD)-based treatment stratification resulted in excellent survival in children with late relapsed B-cell precursor (BCP)-ALL. Chemotherapy alone produced a favorable outcome in patients with negative MRD after induction. The genetic abnormality also plays an important role in determining the prognosis and stratification for treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) is associated with a poor outcome and a high risk for relapse, and there is no standard treatment after relapse. Herein, we present two patients with relapsed iAMP21-positive ALL who were successfully treated by cord blood transplantation (CBT). Although both patients had late bone marrow relapse and favorable MRD response, CBT was performed due to iAMP21 positive. Patients 1 and 2 have been in remission post-CBT for 15 and 45 months, respectively. Patients with relapsed iAMP21-positive ALL may be considered for stem cell transplantation even in late relapses and favorable MRD response.
Vaccination completeness in children with rheumatic diseases: A longitudinal, observational multicenter cohort study in Switzerland
Authors: Welzel Tatjana , Kuemmerle-Deschner Jasmin , Sluka Constantin , Carlomagno Raffaella , Cannizzaro Schneider Elvira , Kaiser Daniela , Hofer Michael , Hentgen Veronique , Woerner Andreas
Published: September 2022

Introduction

Children with pediatric inflammatory rheumatic diseases (PRD) have an increased infection risk. Vaccinations are effective to avoid vaccine-preventable diseases. This study aimed to assess the vaccination completeness in Swiss PRD patients stratified by immunosuppressive treatment (IST).

Materials and methods

This multicenter observational cohort study of PRD patients was performed in Basel, Geneva, Lucerne, Lausanne, and Zurich in PRD patients aged < 18 years included in the Juvenile Inflammatory Rheumatism Cohort. Completeness was assessed for i) the overall vaccination status (Swiss national immunization program (NIP) and specific additional PRD-recommended vaccinations), ii) for all and each vaccination of the NIP at PRD diagnosis and reference date (RefD) and iii) all and each specific additional PRD-recommended vaccination at RefD. Completeness was assessed over the disease course and stratified by IST.

Results

Of 616 eligible patients, 234 children were analyzed. Of these, 147 (63%) were girls. Median age at PRD diagnosis was 6.5 years (IQR 2.9–10.3) and 10.9 years at RefD (6.9–14.3). The median follow-up since PRD diagnosis was 3 years (1.1–5.5). 120/234 children received IST. At RefD, overall vaccination completeness was 3.8% (9/234 children), completeness for the NIP vaccinations was 70.1% (164/234 children; IST 65%, no IST: 75.4%) and for all specific additional PRD-recommended vaccinations was 3.8% (9/234 children; IST 2.5%; no IST 5.3%). Vaccination completeness against pneumococcal disease, hepatitis B virus, and human papilloma virus (HPV) was 50.4, 20, 37.9%, respectively. In 25/35 children with negative varicella zoster virus history vaccination status was complete (IST: 94.4%, no IST: 47%). Annual non-live influenza vaccination was complete in 24.2% of children during IST; adherence decreased over the disease course.

Discussion

This study identified a low overall vaccination completeness in children with PRD. Particularly, the completeness of specific additional PRD-recommended vaccinations was low. If not performed early after PRD diagnosis, vaccination status remained frequently incomplete. Close collaboration between pediatrician and rheumatologist to improve vaccination completeness is essential. Exchange of vaccination records, standardized assessment of specific PRD-recommended vaccinations and those of the NIP, and annual reminder for influenza vaccination are crucial to improve vaccination completeness in this vulnerable pediatric population.
Redo laparoscopic pyeloplasty for recurrent ureteropelvic junction obstruction: Propensity score matched analyses of a high-volume center
Authors: Li Jiayi , Yang Yang , Li Zonghan , Fan Songqiao , Wang Xinyu , Yang Zhenzhen , Liu Pei , Song Hongcheng , Zhang Weiping
Published: September 2022

Purpose

Review the experience of redo laparoscopic pyeloplasty (RLP) in patients with recurrent ureteropelvic junction obstruction (UPJO) in comparison to primary laparoscopic pyeloplasty (PLP) and redo open pyeloplasty (ROP), and determine the feasibility and effectiveness of RLP for recurrent UPJO in children.

Methods

We retrospectively reviewed the clinical data of patients treated with transperitoneal PLP, RLP, and ROP for UPJO from December 2015 to December 2022. The Propensity score matching (PSM) was used to balance confounding variables. RLP patients were 1:4 matched with PLP and 1:3 matched with ROP. The primary outcomes were failure and post-operative complications. Complications were classified according to the Clavien-Dindo grading system.

Results

The study included ten patients who underwent RLP, 43 patients who underwent ROP, and 412 patients who underwent PLP. The follow-up time ranged from 6 to 36 months in the RLP group, 12 to 60 months in the PLP group, and 24 to 54 months in the ROP group. In the RLP group, no failure but three post-operative complications (Clavien grade II) were observed during the follow-up. Compared with the PLP group, the older age, higher weight, larger pre-operative anteroposterior diameter (APD) and APD/cortical thickness (P/C ratio), longer operation time, and post-operative length of stay (LOS) in the RLP group (P < 0.05). After PSM, longer operation time and post-operative LOS were observed in the RLP group (P < 0.05). Compared with the ROP group, the older age, higher weight, and longer post-operative LOS in the RLP group (P < 0.05). After PSM, longer post-operative LOS was observed in the ROP group (P < 0.05). The failure and complication rates were comparable between RLP and PLP or RLP and ROP (P > 0.05).

Conclusions

Our result demonstrated that RLP performed as well as PLP except for a longer operation time. Compared with ROP, RLP has the advantages of a clearer surgical view, sufficient exposure, clearer anatomical landmark position, and minor trauma with a comparable clinical outcome. On experienced hands, RLP for recurrent UPJO after is a safe and effective procedure and should be considered an excellent alternative to the more commonly recommended ROP in select patients.
Effect of head position changes on the depth of tracheal intubation in pediatric patients: A prospective, observational study
Authors: Zhuang Peier , Wang Weikai , Cheng Minghua
Published: September 2022

Purpose

The purpose of this study was to investigate the effect of changing head position on the endotracheal tube (ETT) depth and to assess the risk of inadvertent extubation and bronchial intubation in pediatric patients.

Methods

Subjects aged 4–12 years old with orotracheal intubation undergoing elective surgeries were enrolled. After induction, the distances between “the ETT tip and the trachea carina” (T-C) were measured using a Disposcope flexible endoscope in head neutral position, 45° extension and flexion, 60° right and left rotation. The distance of the ETT tip movement relative to the neutral position (ΔT-C) was calculated after changing the head positions. The direction of the ETT tip displacement and the adverse events including endobronchial intubation, accidental tracheal extubation, hoarseness and sore throat were recorded.

Results

The ETT tip moved toward the carina by 0.5 ± 0.4 cm (P < 0.001) when the head was flexed. After extending the head, the ETT tip moved toward the vocal cord by 0.9 ± 0.4 cm (P < 0.001). Right rotation resulted that the ETT tip moved toward the vocal cord direction by 0.6 ± 0.4 cm (P < 0.001). Moreover, there was no displacement with the head on left rotation (P = 0.126). Subjects with the reinforced ETT had less ETT displacement after changing head position than the taper guard ETT.

Conclusion

The changes of head position can influence the depth of the ETT especially in head extension. We recommend using the reinforced ETT to reduce the ETT displacement in pediatrics to avoid intubation complications.

Clinical trial registration

[www.ClinicalTrials.gov], identifier, [ChiCTR2100042648].
Effects of ilaprazole on the steady-state pharmacodynamics of clopidogrel in healthy volunteers: An open-label randomized crossover study
Authors: Ye Zekang , Chen Pengsheng , Tan Chuchu , Gong Xiaoxuan , Li Ran , Dong Zhou , Ullah Inam , Zhou Chen , Zhou Sufeng , Xie Lijun , Hou Xuemei , Han Zhihui , Gu Qian , Ma Jiazheng , Teng Jianzhen , Tang Yingdan , Zhang Zhuanxia , Hu Haitang , Zhuang Quankun , Chen Juan , Zhu Bei , Shao Feng , Li Chunjian
Published: September 2022

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel.

Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 μmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing.

Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens.

Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant.

Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000031482].
An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell
Authors: Varlı Mücahit , Pham Huong T. , Kim Seong-Min , Taş İsa , Gamage Chathurika D. B. , Zhou Rui , Pulat Sultan , Park So-Yeon , Sesal Nüzhet Cenk , Hur Jae-Seoun , Kang Kyo Bin , Kim Hangun
Published: September 2022

Background: Endolichenic fungi (ELF), which live the inside the lichen thallus, contain many secondary metabolites that show various biological activities. Recent studies show that lichen and ELF secondary metabolites have antioxidant, antibacterial, antifungal, cytotoxic, and anticancer activities.

Purpose: Here, the effects of an ELF extract and its bioactive compounds were investigated on the H1975 cell line focusing on immune checkpoint marker inhibition.

Methods: An ELF was isolated from the host lichen Bryoria fuscescens (Gyelnik) Brodo and D. Hawksw and identified the species as Nemania sp. EL006872. The fungus was cultured on agar medium and acetonic extracts were obtained. Secondary metabolites radianspenes C and D, and dahliane D, were isolated from the crude extract. The biological effects of both the crude extract and the isolated secondary metabolites were evaluated in cell viability, qRT-PCR assays, flow cytometry analysis and western blotting.

Results: The cell viability assay revealed that extracts from Nemania sp. EL006872 and the isolated secondary compounds had low cytotoxicity. The crude extract, radianspenes C and D, and dahliane D, suppressed expression of mRNA encoding PD-L1 and aromatic hydrocarbon receptor (AhR), and surface expression of PD-L1 protein by cells exposed to benzo[a] pyrene. Radianspenes C and D, and dahliane D, reduced expression of AhR, PD-L1, ICOSL, and GITRL proteins by H1975 lung cancer cells, as well as exerting anti-proliferative effects.

Conclusion: Radianspenes C and D, and dahliane D, bioactive compounds isolated from Nemania sp. EL006872 ELF, have the potential for use as immunotherapy and immunoncology treatments.
Dysregulation of dopamine neurotransmission in the nucleus accumbens in immobilization-induced hypersensitivity
Authors: Kishikawa Yuki , Kawahara Yukie , Ohnishi Yoshinori N. , Sotogaku Naoki , Koeda Tomoko , Kawahara Hiroshi , Nishi Akinori
Published: September 2022

Cast immobilization causes sensory hypersensitivity, which is also a symptom of neuropathic pain and chronic pain. However, the mechanisms underlying immobilization-induced hypersensitivity remain unclear. The present study investigated the role of dopamine neurotransmission in the nucleus accumbens shell (NAcSh) of rats with cast immobilization-induced mechanical hypersensitivity using in vivo microdialysis. Cast immobilization of the hind limb decreased the paw withdrawal threshold (PWT). Mechanical stimulation of the cast-immobilized hind limb induced a decrease in dopamine in the NAcSh, and this decrease was associated with the upregulation of presynaptic D2-like receptors. A D2-like receptor antagonist infused into the NAcSh reversed the decrease in PWT in rats with cast immobilization, whereas a D2-like receptor agonist infused into the NAcSh induced a decrease in PWT in control rats. In addition, the expression of the D2 receptor (Drd2) mRNA in the NAcSh was increased by cast immobilization. Importantly, systemic administration of the D2-like receptor antagonist reversed the decrease in PWT in rats with cast immobilization. As dopamine levels regulated by presynaptic D2-like receptors did not correlate with the PWT, it is presumed that the D2-like receptor antagonist or agonist acts on postsynaptic D2-like receptors. These results suggest that immobilization-induced mechanical hypersensitivity is attributable to the upregulation of postsynaptic D2-like receptors in the NAc. Blockade of D2-like receptors in the NAcSh is a potential therapeutic strategy for immobilization-induced hypersensitivity.
A thermodynamically consistent monte carlo cross-bridge model with a trapping mechanism reveals the role of stretch activation in heart pumping
Authors: Yoneda Kazunori , Kanada Ryo , Okada Jun-ichi , Watanabe Masahiro , Sugiura Seiryo , Hisada Toshiaki , Washio Takumi
Published: September 2022

Changes in intracellular calcium concentrations regulate heart beats. However, the decline in the left ventricular pressure during early diastole is much sharper than that of the Ca2+ transient, resulting in a rapid supply of blood to the left ventricle during the diastole. At the tissue level, cardiac muscles have a distinct characteristic, known as stretch activation, similar to the function of insect flight muscles. Stretch activation, which is a delayed increase in force following a rapid muscle length increase, has been thought to be related to autonomous control in these muscles. In this numerical simulation study, we introduced a molecular mechanism of stretch activation and investigated the role of this mechanism in the pumping function of the heart, using the previously developed coupling multiple-step active stiffness integration scheme for a Monte Carlo (MC) cross-bridge model and a bi-ventricular finite element model. In the MC cross-bridge model, we introduced a mechanism for trapping the myosin molecule in its post-power stroke state. We then determined the rate constants of transitions for trapping and escaping in a thermodynamically consistent manner. Based on our numerical analysis, we draw the following conclusions regarding the stretch activation mechanism: (i) the delayed force becomes larger than the original isometric force because the population of trapped myosin molecules and their average force increase after stretching; (ii) the delayed force has a duration of more than a few seconds owing to a fairly small rate constant of escape from the trapped state. For the role of stretch activation in heart pumping, we draw the following conclusions: (iii) for the regions in which the contraction force decreases earlier than the neighboring region in the end-systole phase, the trapped myosin molecules prevent further lengthening of the myocytes, which then prevents further shortening of neighboring myocytes; (iv) as a result, the contraction forces are sustained longer, resulting in a larger blood ejection, and their degeneration is synchronized.
Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise
Authors: Zhao Binyi , Xu Yanping , Chen Yunlin , Cai Ying , Gong Zhiyan , Li Dan , Kuang Hongyu , Liu Xiaozhu , Zhou Hao , Liu Guochun , Yin Yuehui
Published: September 2022

Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFβ) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson’s trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar–Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFβ-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFβ1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.
Activated AMP-activated protein kinase prevents hepatic steatosis, oxidative stress and inflammation in primary chicken hepatocytes
Authors: Yao Yao , Li Longlong , Wang Huihui , Yang Ying , Ma Haitian
Published: September 2022

Fatty liver hemorrhagic syndrome (FLHS) in laying hens, a nutritional metabolic disorder disease, can lead to the decline of laying rate, shortening of laying peak period and increase of mortality, which seriously constrain the sustainable development of layer industry. Until now, there is no effective strategies can prevent and control the occurrence of fatty liver hemorrhagic syndrome in laying hens. The AMP-activated protein kinase (AMPK), a major sensor of cellular energy status, acts a crucial role in regulating lipid metabolism, oxidative stress and inflammatory responses in body. However, the potential molecular mechanisms about AMP-activated protein kinase signal in controlling the occurrence of fatty liver hemorrhagic syndrome are remain unclear. In present study, we found that the phosphorylated AMP-activated protein kinase (Thr172) protein level was markedly reduced in palmitic acid plus oleic acid (PO)-induced primary chicken hepatocytes. Moreover, blocked AMP-activated protein kinase signal by AMP-activated protein kinase inhibitor compound C obviously exacerbated lipid metabolism disorders, oxidative stress and inflammatory response triggered by palmitic acid plus oleic acid in primary chicken hepatocytes. Nevertheless, the lipid metabolism disorders, oxidative stress and inflammatory response challenged by palmitic acid plus oleic acid were obviously alleviated through activation of AMP-activated protein kinase signal with AMP-activated protein kinase activator AICAR in hepatocytes. In addition, we found that the beneficial effects of AMP-activated protein kinase signal in relieving lipid metabolism disorders, oxidative stress and inflammatory response are achieved by activating the nuclear factor erythroid 2-related factor 2 (NRF-2)/kelch-like ECH-associated protein 1 (KEAP1) pathway and inhibiting the NF-κB pathway in PO-stimulated primary chicken hepatocytes. Collectively, our data demonstrated that AMP-activated protein kinase acts as a potential target for the prevention of fatty liver hemorrhagic syndrome occurrence in laying hens.
Histidine kinase inhibitors impair shoot regeneration in Arabidopsis thaliana via cytokinin signaling and SAM patterning determinants
Authors: Lardon Robin , Trinh Hoang Khai , Xu Xiangyu , Vu Lam Dai , Van De Cotte Brigitte , Pernisová Markéta , Vanneste Steffen , De Smet Ive , Geelen Danny
Published: September 2022

Reversible protein phosphorylation is a post-translational modification involved in virtually all plant processes, as it mediates protein activity and signal transduction. Here, we probe dynamic protein phosphorylation during de novo shoot organogenesis in Arabidopsis thaliana. We find that application of three kinase inhibitors in various time intervals has different effects on root explants. Short exposures to the putative histidine (His) kinase inhibitor TCSA during the initial days on shoot induction medium (SIM) are detrimental for regeneration in seven natural accessions. Investigation of cytokinin signaling mutants, as well as reporter lines for hormone responses and shoot markers, suggests that TCSA impedes cytokinin signal transduction via AHK3, AHK4, AHP3, and AHP5. A mass spectrometry-based phosphoproteome analysis further reveals profound deregulation of Ser/Thr/Tyr phosphoproteins regulating protein modification, transcription, vesicle trafficking, organ morphogenesis, and cation transport. Among TCSA-responsive factors are prior candidates with a role in shoot apical meristem patterning, such as AGO1, BAM1, PLL5, FIP37, TOP1ALPHA, and RBR1, as well as proteins involved in polar auxin transport (e.g., PIN1) and brassinosteroid signaling (e.g., BIN2). Putative novel regeneration determinants regulated by TCSA include RD2, AT1G52780, PVA11, and AVT1C, while NAIP2, OPS, ARR1, QKY, and aquaporins exhibit differential phospholevels on control SIM. LC–MS/MS data are available via ProteomeXchange with identifier PXD030754.
LsARF3 mediates thermally induced bolting through promoting the expression of LsCO in lettuce (Lactuca sativa L.)
Authors: Li Yunfeng , Zhu Jiaqi , Feng Yixuan , Li Zhenfeng , Ren Zheng , Liu Ning , Liu Chaojie , Hao Jinghong , Han Yingyan
Published: September 2022

Lettuce (Lactuca sativa L.) is a leafy vegetable whose edible organs usually are leaf or stems, and thus high-temperature induced bolting followed by flower initiation is an undesirable trait in lettuce production. However, the molecular mechanism that controls lettuce bolting and flowering upon thermal treatments is largely unknown. Here, we identified a Lettuce auxin response factor 3 (LsARF3), the expression of which was enhanced by heat and auxin treatments. Interestingly, LsARF3 is preferentially expressed in stem apex, suggesting it might be associated with lettuce bolting. Transgenic lettuce overexpressing LsARF3 displayed early bolting and flowering, whereas knockout of LsARF3 dramatically delayed bolting and flowering in lettuce under normal or high temperature conditions. Furthermore, Exogenous application of IAA failed to rescue the late-bolting and -flowering phenotype of lsarf3 mutants. Several floral integrator genes including LsCO, LsFT, and LsLFY were co-expressed with LsARF3 in the overexpression and knockout lettuce plants. Yeast one-hybrid (Y1H) experiments suggested that LsARF3 could physically interact with the LsCO promoter, which was further confirmed by a dual luciferase assay in tobacco leaves. The results indicated that LsARF3 might directly modulate the expression of LsCO in lettuce. Therefore, these results demonstrate that LsARF3 could promote lettuce bolting in response to the high temperature by directly or indirectly activating the expression of floral genes such as LsCO, which provides new insights into lettuce bolting in the context of ARFs signaling and heat response.
An R2R3-MYB transcription factor VyMYB24, isolated from wild grape Vitis yanshanesis J. X. Chen., regulates the plant development and confers the tolerance to drought
Authors: Zhu Ziguo , Quan Ran , Chen Guangxia , Yu Guanghui , Li Xiujie , Han Zhen , Xu Wenwen , Li Guirong , Shi Jiangli , Li Bo
Published: September 2022

In grapevines, the MYB transcription factors play an important regulatory role in the phenylpropanoid pathway including proanthocyanidin, anthocyanin, and flavonoid biosynthesis. However, the role of MYB in abiotic stresses is not clear. In this study, an R2R3-MYB transcription factor, VyMYB24, was isolated from a high drought-tolerant Chinese wild Vitis species V. yanshanesis. Our findings demonstrated that it was involved in plant development and drought tolerance. VyMYB24 is a nuclear protein and is significantly induced by drought stress. When over-expressed in tobacco, VyMYB24 caused plant dwarfing including plant height, leaf area, flower size, and seed weight. The GA1+3 content in transgenic plants was reduced significantly, and spraying exogenous gibberellin could recover the dwarf phenotype of VyMYB24 transgenic plants, suggesting that VyMYB24 might inhibit plant development by the regulation of gibberellin (GA) metabolism. Under drought stress, the VyMYB24 transgenic plants improved their tolerance to drought with a lower wilting rate, lower relative electrical conductivity, and stronger roots. Compared to wild-type tobacco plants, VyMYB24 transgenic plants accumulated less reactive oxygen, accompanied by increased antioxidant enzyme activity and upregulated gene expression levels of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) genes. In addition, transgenic plants accumulated more proline, and their related synthetic genes NtP5CR and NtP5CS genes were significantly upregulated when exposed to drought. Besides, abiotic stress-responsive genes, NtDREB, NtERD10C, NtERD10D, and NtLEA5, were upregulated significantly in VyMYB24 transgenic plants. These results indicate that VyMYB24 plays a positive regulatory role in response to drought stress and also regulates plant development, which provides new evidence to further explore the molecular mechanism of drought stress of the MYB gene family.
A time-course transcriptome analysis of wax gourd fruit development reveals predominant genes regulating taste and nutrition
Authors: Xue Shudan , Wan Xiaotong , Lu Sen , Zhong Yujuan , Xie Dasen
Published: September 2022

Wax gourd, which belongs to Cucurbitaceae, is an excellent plant resource with the concomitant function of both medicine and foodstuff. Its unique taste and rich nutrition are deeply accepted by consumers. However, the main flavor and nutrients are still unclear, which restricts the quality breeding process of wax gourd. Here, we discovered that monosaccharides, malic acid and citrulline affect the flavor and nutrition of wax gourd and clarified the dynamic accumulation process of these metabolites. To gain insights into the underlying predominant genes regulating accumulation of these metabolites, we performed a time-course transcriptome analysis using RNA-sequencing analysis and compared the expression of screened genes among twenty-four germplasms with different metabolites levels. In addition, the expression abundance among the homologous genes were also analyzed. Finally, a total of 8 genes related to sugar [AGA2 (Bhi03G001926), SUS (Bhi12G001032)], malic acid [MDH (Bhi12G001426, Bhi01G000427), PEPC (Bhi12G000721, Bhi09G002867), ME (Bhi01G002616)] and citrulline [ASS (Bhi02G000401)], respectively were determined. In summary, understanding the core genes influencing taste or nutrition will provide a theoretical basis for fruit quality improvement in wax gourd.
Structure, development, and the salt response of salt bladders in Chenopodium album L.
Authors: Zhang Yigong , Mutailifu Ayibaiheremu , Lan Haiyan
Published: September 2022

Salt bladders are specialized epidermal structures that halophytes use to store and excrete excess salt. However, the cell wall composition during salt bladder development is unclear, and the functions of salt bladders in a few wild plants remain unexplored. Therefore, the present study examined salt bladder development, cell wall composition, and their roles under salt stress by employing bladder-brushed and unbrushed Chenopodium album plants. We found that the bladder cell of C. album was connected to the epidermal cells through a rectangular stalk cell and developed from the shoot tip and the young leaves. The polysaccharides of salt bladder cell wall showed dynamic distribution at different stages of development. Moreover, salt bladders affected Na+ and K+ accumulation, increased reactive oxygen species scavenging, and improved the osmoregulation and photosynthetic efficiency in leaves, subsequently enhancing the salt tolerance of plants. The findings strengthen our knowledge of the physiological mechanisms of the accessory structures in desert plants, which can be used as a reference for further research at the molecular level.
Physiological genetic variation in tomato fruit chilling tolerance during postharvest storage
Authors: David Sivan , Levin Elena , Fallik Elazar , Alkalai-Tuvia Sharon , Foolad Majid R. , Lers Amnon
Published: September 2022

Storage at low temperatures is a common practice to prolong postharvest life of fruit and vegetables with a minimal negative impact on human/environmental health. Storage at low temperatures, however, can be restricted due to produce susceptibility to non-freezing chilling temperatures, when injuries such as physiological disorders and decays may result in unmarketable produce. We have investigated tomato fruit response to postharvest chilling stress in a recombinant inbred line (RIL) population developed from a cross between a chilling-sensitive cultivated tomato (Solanum lycopersicumL.) breeding line and a chilling-tolerant inbred accession of the tomato wild speciesS. pimpinellifoliumL. Screening of the fruit of 148 RILs under cold storage (1.5°C) indicated presence of significant variations in chilling tolerance, manifested by varying degrees of fruit injury. Two extremely contrasting groups of RILs were identified, chilling-tolerant and chilling-sensitive RILs. The RILs in the two groups were further investigated under chilling stress conditions, and several physiological parameters, including weight loss, chlorophyll fluorescence parametersFv/Fm, andPerformance Index(PI), were determined to be efficient markers for identifying response to chilling stress in postharvest fruit. TheFv/Fmvalues reflected the physiological damages endured by the fruit after cold storage, andPIwas a sensitive marker for early changes inphotosystem IIfunction. These two parameters were early indicators of chilling response before occurrence of visible chilling injuries. Antioxidant activities and ascorbic acid content were significantly higher in the chilling-tolerant than the chilling-sensitive lines. Further, the expression of C-repeat/DREB binding factors (CBFs) genes swiftly changed within 1-hr of fruit exposure to the chilling temperature, and theSlCBF1transcript level was generally higher in the chilling-tolerant than chilling-sensitive lines after 2-hr exposure to the low temperature. This research demonstrates the presence of potential genetic variation in fruit chilling tolerance in the tomato RIL population. Further investigation of the RIL population is underway to better understand the genetic, physiological, and biochemical mechanisms involved in postharvest fruit chilling tolerance in tomato.
Economies of scale in constructing plant factories with artificial lighting and the economic viability of crop production
Authors: Zhuang Yunfei , Lu Na , Shimamura Shigeharu , Maruyama Atsushi , Kikuchi Masao , Takagaki Michiko
Published: September 2022

Since the introduction of LED lamps a decade ago, the plant factory with artificial lighting (PFAL) has been expected to be a savior that overcomes the food crisis, brings food safety, and enhances environmental friendliness. Despite such high expectations, the diffusion of commercial crop production in PFALs has been slow. It has been said that the main reason for this is the huge initial investment required to construct PFALs. This situation has attracted studies to access the economic feasibility of the crop production in PFALs. One thing strange in these studies is that they pay little attention to the scale of their PFALs. PFALs are factories so that they would be subject to economies of scale. If so, the scale of PFALs is an important factor that determines the economic feasibility of plant production in PFALs. However, no study has thus far attempted to examine whether economies of scale exist in the construction of PFALs. To fill this gap, this paper tries to examine, based on the data on the investment cost of PFAL construction collected from various countries and regions in the world, whether economies of scale exist in PFAL construction and, if yes, how it affects the economic viability of the plant production in PFALs by searching for the minimum scale that ensures PFAL crop production economically viable. The results show that economies of scale exist in PFAL construction, and that the production of lettuce, PFALs’ most popular crop, is now well on a commercial basis with the technology level of the most advanced PFAL operators, but strawberries has not reached that stage yet. It is also shown that crop production in PFALs is highly sensitive to changes in the yield and the price of the crops: A 30% decline either in the yield or the price of lettuce would easily bring PFALs bankruptcy. It is discussed that the optimum scale of PFALs would depend not only on the economies of scale but also on the transaction costs, such as the costs of searching and keeping a sufficient number of buyers who offer good and stable crop prices.