bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Stratification in Oral Cancer: A Novel Approach
Authors: Tu Irene Wen-Hui , Shannon Nicholas Brian , Thankappan Krishnakumar , Balasubramanian Deepak , Pillai Vijay , Shetty Vivek , Rangappa Vidyabhushan , Chandrasekhar Naveen Hedne , Kekatpure Vikram , Kuriakose Moni Abraham , Krishnamurthy Arvind , Mitra Arun , Pattatheyil Arun , Jain Prateek , Iyer Subramania , Subramaniam Narayana , Iyer N. Gopalakrishna
Published: July 2022

Background

Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines.

Methods

Anonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision–recall analysis and the Kaplan–Meier survival analysis.

Results

Low-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials.

Conclusion

Nomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients.
Efficacy and Safety of Capecitabine for Triple-Negative Breast Cancer: A Meta-Analysis
Authors: Xun Xueqiong , Cao Qinguang , Hong Pan , Rai Saroj , Zhou Yeming , Liu Ruikang , Hu Huiyong
Published: July 2022

Background

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited treatment options and poor prognosis. Capecitabine, as a novel adjuvant chemotherapy for TNBCs, remains controversial. Therefore, we conducted this meta-analysis to assess the efficacy and safety of capecitabine for early-stage TNBCs combined with neo-/adjuvant chemotherapy.

Methods

We searched Medline, Embase, Web of Science, and Cochrane databases updated on Mar 18, 2022 for relevant RCTs. In all, 11 RCTs with 5,175 patients were included. We used hazard ratios (HRs) and odds ratios (ORs) to assess the differences between disease-free survival (DFS), overall survival (OS), and adverse events.

Results

Our study demonstrated significance differences in both DFS and OS (DFS: HR=0.77; 95% CI 0.68–0.86; OS: HR=0.73, 95% CI 0.63–0.85). In subgroup analysis, the lower dosage group showed higher DFS (HR=0.79, 95% CI 0.69–0.91), higher frequency (HR=0.72, 95%CI 0.62–0.83), and adjuvant chemotherapy (HR=0.74, 95% CI 0.65–0.84). However, capecitabine was also associated with a higher risk of diarrhea (OR=3.10, 95% CI 2.32–4.15), hand–foot syndrome (OR=25.79, 95% CI 15.32–43.42), and leukopenia (OR=2.08, 95% CI 1.13–3.84).

Conclusion

The addition of capecitabine to early-stage TNBC patients receiving standard adjuvant chemotherapy showed significant DFS and OS improvement with tolerable adverse events. The lower dosage and higher frequency of capecitabine combined with adjuvant chemotherapy demonstrated a better survival outcome.
Case Report: Clinical Characteristics and Outcomes of HIV Positive Patients With Metastatic Prostate Cancer Treated With Immunotherapy: A Case Series and Literature Review
Authors: Idossa Dame , Friedlander Terence , Paller Channing J. , Ryan Charles J. , Borno Hala T.
Published: July 2022

Background

The treatment of metastatic prostate cancer has been revolutionized with the advent of many targeted therapies, including immunotherapy. Pembrolizumab has demonstrated benefit in the treatment of certain patients with docetaxel-refractory metastatic castrate-resistant prostate cancer (mCRPC). However, extrapolation of these data to patients with HIV is limited, as these patients are conventionally excluded from therapeutic clinical trials. This study aims to develop a better understanding of the clinical outcomes of HIV positive patients with prostate cancer treated with immunotherapy. A review of the literature is conducted on the use of immunotherapy in HIV positive patients with prostate cancer, and a summary is presented of two clinical cases from a single institution.

Methods

This is a retrospective case report of 2 patients diagnosed with prostate cancer and HIV who received treatment with pembrolizumab. Quantitative analysis was performed to summarize patient demographics, clinical history, and outcomes.

Results

Two patients with mCRPC and HIV on highly active antiretroviral therapy were identified. Both individuals had biochemical and radiographic response to treatment with pembrolizumab. The duration of response for individual 1 is >31 months and 14 months for individual 2. Neither patient had immune-related adverse events or decreased suppression of their HIV infection. One patient died from disease progression after 14 months of treatment and the other remains on treatment with pembrolizumab to date.

Conclusion

In this small case series, pembrolizumab appears to be a safe and effective treatment option for HIV positive patients with metastatic prostate cancer.
Association of Mu-Opioid Receptor Expression With Long-Term Survival and Perineural Nerve Invasion in Patients Undergoing Surgery for Ovarian Cancer
Authors: Zhang Hao , Qu Mengdi , Sun Caihong , Wang Yanghanzhao , Li Ting , Xu Wei , Sun Zhirong , Zhang Xiaoguang , Guo Kefang , Chen Wankun , Sun Minli , Miao Changhong
Published: July 2022

Background

Opioids are widely used during primary debulking surgery (PDS) for ovarian cancers, and a high mu-opioid receptor (MOR) expression predicts worse cancer outcomes. However, the impact of MOR expression on survival outcomes in ovarian cancers is still not clear.

Methods

A retrospective cohort study was conducted in patients who underwent PDS in ovarian cancer patients. MOR expression was measured in tumor and normal tissue. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included perineural invasion (PNI), intraoperative sufentanil consumption, length of stay (LOS), and verbal numerical rating scale (VNRS) on postoperative day 1 (POD1), POD3, and POD5.

Results

After propensity score matching, a total of 366 patients were finally enrolled in this study. There were no significant differences in OS rates in patients with high versus low levels of MOR (1-year OS: 82.9% versus 83.3%, 3-year: 57.8% versus 59.1%, 5-year: 22.4% versus 23.1%,respectively) in the ovarian cancers. There were no significant differences in DFS between the groups. Intraoperative sufentanil consumption was higher in the MOR high-expression group compared with the MOR low-expression group. Tumors expressing high levels of MOR showed higher rates of PNI. VNRS in the MOR high-expression group was higher on POD1.

Conclusion

MOR is not an independent predictor of worse survival in ovarian cancers but is associated with high rates of perineural invasion.
Prognostic Significance of the Systemic Immune-Inflammation Index in Patients With Cholangiocarcinoma: A Meta-Analysis
Authors: Liu Xue-chun , Jiang Yue-ping , Sun Xue-guo , Zhao Jian-jian , Zhang Ling-yun , Jing Xue
Published: July 2022

Background

The systemic immune-inflammation index (SII) is a significant prognostic factor for neoplastic diseases. However, the prognostic value of SII in patients with cholangiocarcinoma (CCA) remains unclear. This meta-analysis aimed to investigate the prognostic value of preoperative SII in patients with CCA.

Method

We systematically searched for relevant studies in PubMed, Scopus, EMBASE, Web of Science, PROSPERO, and Cochrane Library databases up to March 22, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association between SII and survival outcomes, including overall survival (OS) and recurrence-free survival.

Results

Five studies with 1402 patients were included in this meta-analysis to determine the prognostic value of preoperative SII. The results showed that a higher SII was associated with poor OS in patients with CCA who underwent invasive surgery (HR=1.916; 95% CI, 1.566–2.343; Z=6.329; P<0.001). The results were reliable in the subgroup analysis according to country, age, sample size, SII cutoff values, and treatment methods.

Conclusions

A high preoperative SII appears to be an effective and practical method for monitoring survival in patients with CCA.

Systematic Review Registration

International Platform of Registered Systematic. Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202240015.
Comprehensive Analysis of TRP Channel–Related Genes in Patients With Triple-Negative Breast Cancer for Guiding Prognostic Prediction
Authors: Zhang Haojie , Zhang Xiangsheng , Wang Xiaohong , Sun Hongguang , Hou Changran , Yu Yue , Wang Song , Yin Fangxu , Yang Zhenlin
Published: July 2022

Background

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer. Transient Receptor Potential (TRP) channel superfamily has emerged as a novel and interesting target in a variety of tumors. However, the association of TRP channel–related genes with TNBC is still unclear.

Methods

The The Cancer Genome Atlas (TCGA)-TNBC and GSE58812 datasets were downloaded from the public database. The differentially expressed TRP channel–related genes (DETGs) were screened by limma package, and mutations of the above genes were analyzed. Subsequently, new molecular subtypes in TNBC-based DETGs were explored by consensus clustering analysis. In addition, Lasso–Cox regression analysis was used to divide it into two robust risk subtypes: high-risk group and low-risk group. The accuracy and distinguishing ability of above models were verified by a variety of methods, including Kaplan–Meier survival analysis, ROC analysis, calibration curve, and PCA analysis. Meanwhile, CIBERSORT algorithm was used to excavate status of immune-infiltrating cells in TNBC tissues. Last, we explored the therapeutic effect of drugs and underlying mechanisms of risk subgroups by pRRophetic package and GSEA algorithm, respectively.

Results

A total of 19 DETGs were identified in 115 TNBC and 113 normal samples from TCGA database. In addition, missense mutation and SNP were the most common variant classification. According to Lasso–Cox regression analysis, the risky formula performed best when nine genes were used: TRPM5, TRPV2, HTR2B, HRH1, P2RY2, MAP2K6, NTRK1, ADCY6, and PRKACB. Subsequently, Kaplan–Meier survival analysis, ROC analysis, calibration curve, and Principal Components Analysis (PCA) analysis showed an excellent accuracy for predicting OS using risky formula in each cohort (P < 0.05). Specifically, high-risk group had a shorter OS compared with low-risk group. In addition, T-cell CD4 memory activated and macrophages M1 were enriched in normal tissues, whereas Tregs were increased in tumor tissues. Note that the low-risk group was better therapeutic effect to docetaxel, doxorubicin, cisplatin, paclitaxel, and gemcitabine than the high-risk group (P < 0.05). Last, in vitro assays, Quantitative Real-time PCR (qRT-PCR) indicated that TRPM5 was significantly highly expressed in MDA-MB-231 and MDA-MB-468 cells compared with that in MCF-10A cells (P < 0.01).

Conclusion

We identified a risky formula based on expression of TRP channel–related genes that can predict prognosis, therapeutic effect, and status of tumor microenvironment for patients with TNBC.
Pressure-Volume Relationships in the Spinal Canal and Potential Neurological Complications After Epidural Fluid Injections
Authors: Bosscher Hemmo
Published: July 2022

High-volume fluid injections into the spinal canal may lead to severe neurological complications. But when anatomical or pathological conditions in the spinal canal are unfavorable, even small volume epidural injections can cause dangerously high epidural, subarachnoid, and intracranial pressures or pressure gradients. Data obtained from the scientific literature and direct clinical observation are used to derive a first-order approximation of epidural, subarachnoid, and intracranial pressure responses to epidural fluid injections. Maximum allowable fluid volumes for single or multiple divided fluid injections over time are calculated. In the presence of spinal pathology, 10 ml of fluids may increase epidural pressure to >100 mmHg. Injection speed >4 ml per second may also generate dangerously high intraspinal and intracranial pressures. Intermitted bolus injections provide limited protection, but intraspinal pressures may rise very fast when a critical total injected volume is reached. Potential complications of increased intracranial pressures or large pressure waves include nerve palsies, tinnitus, blindness, stroke, and death. Spinal injections or endoscopy should be performed in an awake responsive patient or with direct cerebrospinal fluid pressure monitoring. A set of guidelines for epidural fluid management is given.
Surveillance of Acute SARS-CoV-2 Infections in Elementary Schools and Daycare Facilities in Bavaria, Germany (09/2020–03/2021)
Authors: Kern Anna , Kuhlmann Pia H. , Matl Stefan , Ege Markus , Maison Nicole , Eckert Jana , von Both Ulrich , Behrends Uta , Anger Melanie , Frühwald Michael C. , Gerstlauer Michael , Woelfle Joachim , Neubert Antje , Melter Michael , Liese Johannes , Goettler David , Sing Andreas , Liebl Bernhard , Hübner Johannes , Klein Christoph ,   the COVID Kids Bavaria Consortium
Published: July 2022

Introduction

Here we report our results of a multi-center, open cohort study (“COVID-Kids-Bavaria”) investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany.

Materials and Methods

Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits.

Results

In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5–438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined.

Discussion

During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.
Frontiers Review: Severe Asthma in Adolescents
Authors: Warraich Sara , Sonnappa Samatha
Published: July 2022

Asthma remains the most prevalent chronic respiratory disease of childhood. Severe asthma accounts for a minority group of patients but with substantial morbidity burden. It may reflect disease which is resistant to treatment or that which is difficult to treat, or a combination of both. The adolescent patient cohort denote a unique group and are the focus of this review. This group of patients embody transitioning priorities and evolving health beliefs, all of which may influence the management and burden of disease. Factors of importance include the influence of physiological parameters such as sex and race, which have confer implications for medical management and non-physiological factors, such as adherence, risk-taking behavior, and vaping. The holistic approach to management of severe asthma within this group of patients must acknowledge the evolving patient independence and desire for autonomy and strive for a collaborative, patient tailored approach. This review will focus on the factors that may pose a challenge to the management of severe adolescent asthma whilst offering suggestions for changes in practice that might harness patient priorities and shared clinical decision-making.
Effect of Threshold Inspiratory Muscle Training on Functional Fitness and Respiratory Muscle Strength Compared to Incentive Spirometry in Children and Adolescents With Obesity: A Randomized Controlled Trial
Authors: Kaeotawee Phatthareeda , Udomittipong Kanokporn , Nimmannit Akarin , Tovichien Prakarn , Palamit Apinya , Charoensitisup Pawinee , Mahoran Khunphon
Published: July 2022

Background

To determine the effect of threshold inspiratory muscle training (IMT) on functional fitness and respiratory muscle strength (RMS) compared to incentive spirometry (IS) in children/adolescents with obesity.

Methods

A total of 60 obese children/adolescents aged 8–15 years were randomized into the threshold IMT group (n= 20), the IS group (n= 20), or the control group (n= 20). The IMT group performed 30 inspiratory breaths with the intensity set at 40% of baseline maximal inspiratory pressure (MIP) twice daily for 8 weeks; the IS group performed 30 breaths with sustained maximum inspiration twice daily for 8 weeks; and, the control group was assigned no training device for 8 weeks. Six-min walk test (6-MWT), RMS, and spirometry were compared between baseline and 8 weeks.

Results

Six-MWT distance (528.5 ± 36.2 vs. 561.5 ± 35.2 m,p= 0.002) and MIP (121.2 ± 26.8 vs. 135.3 ± 32.1%Predicted,p= 0.03) were significantly improved after 8 weeks of IMT training. There was no significant difference in any evaluated pulmonary function parameters between baseline and 8 weeks in the IS or control groups; however, 6-MWT distance demonstrated a trend toward significant improvement in the IS group (526.9 ± 59.1 vs.549.0 ± 50.6 m,p= 0.10). No significant difference among groups was found for any variable relative to change from baseline to post-training.

Conclusion

Eight weeks of threshold IMT training significantly improved both inspiratory muscle strength (MIP) and functional fitness (6-MWT) in children/adolescents with obesity. Eight weeks of IS training yielded a trend toward significantly improved functional fitness.
Chronic Administration of COVID-19 Drugs Fluvoxamine and Lopinavir Shortens Action Potential Duration by Inhibiting the Human Ether‐à‐go‐go–Related Gene and Cav1.2
Authors: Zheng Zequn , Cai Dihui , Fu Yin , Wang Ying , Song Yongfei , Lian Jiangfang
Published: July 2022

Background: Old drugs for new indications in the novel coronavirus disease of 2019 (COVID-19) pandemic have raised concerns regarding cardiotoxicity, especially the development of drug-induced QT prolongation. The acute blocking of the cardiac hERG potassium channel is conventionally thought to be the primary mechanism of QT prolongation induced by COVID-19 drugs fluvoxamine (FLV) and lopinavir (LPV). The chronic impact of these medications on the hERG expression has yet to be determined.

Methods: To investigate the effect of long-term incubation of FLV and LPV on the hERG channel, we used electrophysiological assays and molecular experiments, such as Western blot, RT-qPCR, and immunofluorescence, in HEK-293 cells stably expressing hERG and human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs).

Results: Compared to the acute effects, chronic incubation for FLV and LPV generated much lower half-maximal inhibitory concentration (IC50) values, along with a left-shifted activation curve and retarded channel activation. Inconsistent with the reduction in current, we unexpectedly found that the chronic effects of drugs promoted the maturation of hERG proteins, accompanied by the high expression of Hsp70 and low expression of Hsp90. Targeting Hsp70 using siRNA was able to reverse the effects of these drugs on hERG proteins. In addition, FLV and LPV resulted in a significant reduction of APD90 and triggered the early after-depolarizations (EADs), as well as inhibited the protein level of the L-type voltage–operated calcium channel (L-VOCC) in hiPSC-CMs.

Conclusion: Chronic incubation with FLV and LPV produced more severe channel-blocking effects and contributed to altered channel gating and shortened action potential duration by inhibiting hERG and Cav1.2.
CYP2A6 and GABRA2 Gene Polymorphisms are Associated With Dexmedetomidine Drug Response
Authors: Fang Chao , Ouyang Wen , Zeng Youjie , Pei Qi , Xia Yuhao , Luo Siwan , Chen Minghua
Published: July 2022

Background: Dexmedetomidine is a commonly used clinical sedative; however, the drug response varies among individuals. Thus, the purpose of this study was to explore the association between dexmedetomidine response and gene polymorphisms related to drug-metabolizing enzymes and drug response (CYP2A6, UGT2B10, UGT1A4, ADRA2A, ADRA2B, ADRA2C, GABRA1, GABRB2, and GLRA1).

Methods: This study was a prospective cohort study. A total of 194 female patients aged 18–60 years, American Society of Anesthesiologists (ASA) score I-II, who underwent laparoscopy at the Third Xiangya Hospital of Central South University, were included. The sedative effect was assessed every 2 min using the Ramsay score, and the patient’s heart rate decrease within 20 min was recorded. Peripheral blood was collected from each participant to identify genetic variants in the candidate genes of metabolic and drug effects using the Sequenom MassARRAY® platform. Furthermore, additional peripheral blood samples were collected from the first 99 participants at multiple time points after dexmedetomidine infusion to perform dexmedetomidine pharmacokinetic analysis by Phoenix® WinNonlin 7.0 software.

Results: Carriers of the minor allele (C) of CYP2A6 rs28399433 had lower metabolic enzyme efficiency and higher plasma concentrations of dexmedetomidine. In addition, the participants were divided into dexmedetomidine sensitive or dexmedetomidine tolerant groups based on whether they had a Ramsay score of at least four within 20 min, and CYP2A6 rs28399433 was identified to have a significant influence on the dexmedetomidine sedation sensitivity by logistic regression with Plink software [p = 0.003, OR (95% CI): 0.27 (0.11–0.65)]. C allele carriers were more sensitive to the sedative effects of dexmedetomidine than A allele carriers. GABRA2 rs279847 polymorphism was significantly associated with the degree of the heart rate decrease. In particular, individuals with the GG genotype had a 4-fold higher risk of heart rate abnormality than carriers of the T allele (OR = 4.32, 95% CI: 1.96–9.50, p = 0.00027).

Conclusion:CYP2A6 rs28399433 polymorphism affects the metabolic rate of dexmedetomidine and is associated with susceptibility to the sedative effects of dexmedetomidine; GABRA2 rs279847 polymorphism is significantly associated with the degree of the heart rate decrease.
Significance of Ramped Temperature in the Dynamics of Unsteady Viscoelastic Fluid Subjected to Lorentz Force
Authors: Khan Ilyas
Published: July 2022

Viscoelastic fluids, such as polymers, paints, and DNA suspensions, are almost everywhere and very useful in the industry. This article aims to study the significance of ramped temperature in the dynamics of viscoelastic fluid. Magnetohydrodynamic (MHD) effect is considered in the presence of Lorentz force. The flow is considered in a porous medium using generalized Darcy’s law. Heat transfers through convection, and the fluid near the plate takes heat in a ramped nature. Instead of the classical fluid model which has certain limitations, a generalized model is considered with fractional derivatives of the Atangana–Baleanu type. The well-known technique of Laplace transform was adopted to obtain the solutions which are displayed in various plots with detailed discussion analysis. From the graphical analysis, it is worth noting that the Atangana–Baleanu fractional model shows a good memory effect on the dynamics of the viscoelastic fluid as compared to its classical form.
Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle
Authors: Ojha Krishna Raj , Shin Song Yi , Padgham Samuel , Leon Olmedo Frida , Guo Bohong , Han Gang , Woodman Christopher , Trache Andreea
Published: July 2022

Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin β1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin β1 expression in aging, while soft substrates abolish age-induced differences in overall integrin β1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries.
Research on Methods Decreasing Pesticide Waste Based on Plant Protection Unmanned Aerial Vehicles: A Review
Authors: Hu Heming , Kaizu Yutaka , Huang Jingjing , Furuhashi Kenichi , Zhang Hongduo , Li Ming , Imou Kenji
Published: July 2022

In plant protection, the increasing maturity of unmanned aerial vehicle (UAV) technology has greatly increased efficiency. UAVs can adapt to multiple terrains and do not require specific take-off platforms. They do well, especially in farmland areas with rugged terrain. However, due to the complex flow field at the bottom of a UAV, some of the droplets will not reach the surface of a plant, which causes pesticide waste and environmental pollution. Droplet deposition is a good indicator of the utilization rate of pesticides; therefore, this review describes recent studies on droplet deposition for further method improvement. First, this review introduces the flight altitude, speed, and environmental factors that affect pesticide utilization efficiency and then summarizes methods to improve pesticide utilization efficiency from three aspects: nozzles, electrostatic sprays, and variable spray systems. We also point out the possible direction of algorithm development for a UAV’s precision spray.
Phenotypic Characterization of High Carotenoid Tomato Mutants Generated by the Target-AID Base-Editing Technology
Authors: Hunziker Johan , Nishida Keiji , Kondo Akihiko , Ariizumi Tohru , Ezura Hiroshi
Published: July 2022

Our previous study demonstrated that Target-AID which is the modified CRISPR/Cas9 system enabling base-editing is an efficient tool for targeting multiple genes. Three genes, SlDDB1, SlDET1, and SlCYC-B, responsible for carotenoid accumulation were targeted, and allelic variations were previously obtained by Target-AID. In this research, we characterized the effect of new alleles on plant growth and fruit development, as well as carotenoid accumulation, individually in segregating backcross populations or combined in null self-segregant lines. Only lines carrying homozygous substitutions in the three targeted genes and the segregating backcross population of individual mutations were characterized, resulting in the isolation of two allelic versions for SlDDB1, one associated with SlDET1 and the last one with SlCYC-B. All edited lines showed variations in carotenoid accumulation, with an additive effect for each single mutation. These results suggest that Target-AID base-editing technology is an effective tool for creating new allelic variations in target genes to improve carotenoid accumulation in tomato.
New Insights Into the Activity of Apple Dihydrochalcone Phloretin: Disturbance of Auxin Homeostasis as Physiological Basis of Phloretin Phytotoxic Action
Authors: Smailagić﻿﻿﻿ Dijana , Banjac Nevena , Ninković﻿﻿﻿ Slavica , Savić﻿﻿﻿ Jelena , Ćosić﻿﻿﻿ Tatjana , Pěnčík Aleš , Ćalić﻿﻿﻿ Dušica , Bogdanović﻿﻿﻿ Milica , Trajković﻿﻿﻿ Milena , Stanišić Mariana
Published: July 2022

Apple species are the unique naturally rich source of dihydrochalcones, phenolic compounds with an elusive role in planta, but suggested auto-allelochemical features related to “apple replant disease” (ARD). Our aim was to elucidate the physiological basis of the phytotoxic action of dihydrochalcone phloretin in the model plant Arabidopsis and to promote phloretin as a new prospective eco-friendly phytotoxic compound. Phloretin treatment induced a significant dose-dependent growth retardation and severe morphological abnormalities and agravitropic behavior in Arabidopsis seedlings. Histological examination revealed a reduced starch content in the columella cells and a serious disturbance in root architecture, which resulted in the reduction in length of meristematic and elongation zones. Significantly disturbed auxin metabolome profile in roots with a particularly increased content of IAA accumulated in the lateral parts of the root apex, accompanied by changes in the expression of auxin biosynthetic and transport genes, especially PIN1, PIN3, PIN7, and ABCB1, indicates the role of auxin in physiological basis of phloretin-induced growth retardation. The results reveal a disturbance of auxin homeostasis as the main mechanism of phytotoxic action of phloretin. This mechanism makes phloretin a prospective candidate for an eco-friendly bioherbicide and paves the way for further research of phloretin role in ARD.
Simultaneous Ozone and High Light Treatments Reveal an Important Role for the Chloroplast in Co-ordination of Defense Signaling
Authors: Xu Enjun , Tikkanen Mikko , Seyednasrollah Fatemeh , Kangasjärvi Saijaliisa , Brosché Mikael
Published: July 2022

Plants live in a world of changing environments, where they are continuously challenged by alternating biotic and abiotic stresses. To transfer information from the environment to appropriate protective responses, plants use many different signaling molecules and pathways. Reactive oxygen species (ROS) are critical signaling molecules in the regulation of plant stress responses, both inside and between cells. In natural environments, plants can experience multiple stresses simultaneously. Laboratory studies on stress interaction and crosstalk at regulation of gene expression, imply that plant responses to multiple stresses are distinctly different from single treatments. We analyzed the expression of selected marker genes and reassessed publicly available datasets to find signaling pathways regulated by ozone, which produces apoplastic ROS, and high light treatment, which produces chloroplastic ROS. Genes related to cell death regulation were differentially regulated by ozone versus high light. In a combined ozone + high light treatment, the light treatment enhanced ozone-induced cell death in leaves. The distinct responses from ozone versus high light treatments show that plants can activate stress signaling pathways in a highly precise manner.
Genetic, Phenotypic and Metabolic Diversity of Yeasts From Wheat Flag Leaves
Authors: Gouka Linda , Vogels Caroline , Hansen Lars H. , Raaijmakers Jos M. , Cordovez Viviane
Published: July 2022

The phyllosphere, the aboveground part of a plant, is a harsh environment with diverse abiotic and biotic stresses, including oscillating nutrient availability and temperature as well as exposure to UV radiation. Microbial colonization of this dynamic environment requires specific adaptive traits, including tolerance to fluctuating temperatures, the production of secondary metabolites and pigments to successfully compete with other microorganisms and to withstand abiotic stresses. Here, we isolated 175 yeasts, comprising 15 different genera, from the wheat flag leaf and characterized a selection of these for various adaptive traits such as substrate utilization, tolerance to different temperatures, biofilm formation, and antagonism toward the fungal leaf pathogen Fusarium graminearum. Collectively our results revealed that the wheat flag leaf is a rich resource of taxonomically and phenotypically diverse yeast genera that exhibit various traits that can contribute to survival in the harsh phyllosphere environment.
Genome-Wide Analysis of CqCrRLK1L and CqRALF Gene Families in Chenopodium quinoa and Their Roles in Salt Stress Response
Authors: Jiang Wei , Li Chao , Li Leiting , Li Yali , Wang Zhihao , Yu Feiyu , Yi Feng , Zhang Jianhan , Zhu Jian-Kang , Zhang Heng , Li Yan , Zhao Chunzhao
Published: July 2022

Chenopodium quinoa is a halophyte with exceptional nutritional qualities, and therefore it is potentially an ideal crop to grow in saline soils, not only addressing the problem of land salinization, but also providing nutrient food for the health of humans. Currently, the molecular mechanisms underlying salt tolerance in quinoa are still largely unknown. In Arabidopsis thaliana, Catharanthus roseus receptor-like kinase (CrRLK1Ls) FERONIA (FER) and its ligands rapid alkalinization factors (RALFs) have been reported that participate in the regulation of salt tolerance. Here, we performed a genome-wide analysis and identified 26 CqCrRLK1L and 18 CqRALF family genes in quinoa genome. Transcriptomic profiling of the leaf, root, stamen, and pistil tissues of quinoa reveals that different CqCrRLK1L and CqRALF genes exhibit tissue-specific expression patterns, which is consistent with that observed in other plant species. RNA-seq data show that three CqCrRLK1L genes are highly up-regulated after salt treatment, suggesting that some CqCrRLK1L family genes are transcriptionally responsive to salt stress in quinoa. Biochemical study indicates that CqRALF15, a paralog of Arabidopsis RALF22, is physically associated with CrRLK1L proteins CqFER and AtFER. CqRALF15 and AtRALF22 are functionally conserved in inducing the internalization of AtFER and in triggering root growth inhibition in both quinoa and Arabidopsis. Moreover, overexpression of CqRALF15 in Arabidopsis results in enhanced leaf bleaching under salt stress, indicating that CqRALF15 is involved in salt stress response. Together, our study characterizes CqCrRLK1L and CqRALF family genes in quinoa at genomic, transcriptional, and protein levels, and provides evidence to support their roles in salt stress response.
Grid Search for Lowest Root Mean Squared Error in Predicting Optimal Sensor Location in Protected Cultivation Systems
Authors: Uyeh Daniel Dooyum , Iyiola Olayinka , Mallipeddi Rammohan , Asem-Hiablie Senorpe , Amaizu Maryleen , Ha Yushin , Park Tusan
Published: July 2022

Irregular changes in the internal climates of protected cultivation systems can prevent attainment of optimal yield when the environmental conditions are not adequately monitored and controlled. Key to indoor environment monitoring and control and potentially reducing operational costs are the strategic placement of an optimal number of sensors using a robust method. A multi-objective approach based on supervised machine learning was used to determine the optimal number of sensors and installation positions in a protected cultivation system. Specifically, a gradient boosting algorithm, a form of a tree-based model, was fitted to measured (temperature and humidity) and derived conditions (dew point temperature, humidity ratio, enthalpy, and specific volume). Feature variables were forecasted in a time-series manner. Training and validation data were categorized without randomizing the observations to ensure the features remained time-dependent. Evaluations of the variations in the number and location of sensors by day, week, and month were done to observe the impact of environmental fluctuations on the optimal number and location of placement of sensors. Results showed that less than 32% of the 56 sensors considered in this study were needed to optimally monitor the protected cultivation system’s internal environment with the highest occurring in May. In May, an average change of −0.041% in consecutive RMSE values ranged from the 1st sensor location (0.027°C) to the 17th sensor location (0.013°C). The derived properties better described the ambient condition of the indoor air than the directly measured, leading to a better performing machine learning model. A machine learning model was developed and proposed to determine the optimal sensors number and positions in a protected cultivation system.
Distribution Pattern of N6-Methyladenine DNA Modification in the Seashore Paspalum (Paspalum vaginatum) Genome
Authors: Hao Jiang-Shan , Xing Jian-Feng , Hu Xu , Wang Zhi-Yong , Tang Min-Qiang , Liao Li
Published: July 2022

N6-methyladenine (6mA) DNA modification has been detected in several eukaryotic organisms, in some of them, it plays important role in the regulation process of stress-resistance response. However, the genome-wide distribution patterns and potential functions of 6mA DNA modification in halophyte Seashore paspalum (Paspalum vaginatum) remain largely unknown. Here, we examined the 6mA landscape in the P. vaginatum genome by adopting single molecule real-time sequencing technology and found that 6mA modification sites were broadly distributed across the P. vaginatum genome. We demonstrated distinct 6mA methylation levels and 6mA distribution patterns in different types of transcription genes, which hinted at different epigenetic rules. Furthermore, the moderate 6mA density genes in P. vaginatum functionally correlated with stress resistance, which also maintained a higher transcriptional level. On the other hand, a specific 6mA distribution pattern in the gene body and near TSS was observed in gene groups with higher RNA expression, which maybe implied some kind of regularity between 6mA site distribution and the protein coding genes transcription was possible. Our study provides new insights into the association between 6mA methylation and gene expression, which may also contribute to key agronomic traits in P. vaginatum.
Multiplexed Massively Parallel Sequencing of Plastomes Provides Insights Into the Genetic Diversity, Population Structure, and Phylogeography of Wild and Cultivated Coptis chinensis
Authors: Wang Yiheng , Sun Jiahui , Zhao Zhenyu , Xu Chao , Qiao Ping , Wang Sheng , Wang Mengli , Xu Zegang , Yuan Qingjun , Guo Lanping , Huang Luqi
Published: July 2022

Root rot has been a major problem for cultivated populations ofCoptis chinensisvar.chinensisin recent years.C. chinensisvar.brevisepala, the closest wild relative ofC. chinensisvar.chinensis, has a scattered distribution across southwestern China and is an important wild resource. Genetic diversity is associated with greater evolutionary potential and resilience of species or populations and is important for the breeding and conservation of species. Here, we conducted multiplexed massively parallel sequencing of the plastomes of 227 accessions of wild and cultivatedC. chinensisusing 111 marker pairs to study patterns of genetic diversity, population structure, and phylogeography among wild and cultivatedC. chinensispopulations. Wild and cultivated resources diverged approximately 2.83 Mya. The cultivated resources experienced a severe genetic bottleneck and possess highly mixed germplasm. However, high genetic diversity has been retained in the wild resources, and subpopulations in different locations differed in genotype composition. The significant divergence in the genetic diversity of wild and cultivated resources indicates that they require different conservation strategies. Wild resources requirein situconservation strategies aiming to expand population sizes while maintaining levels of genetic diversity; by contrast, germplasm resource nurseries with genotypes of cultivated resources and planned distribution measures are needed for the conservation of cultivated resources to prevent cultivated populations from undergoing severe genetic bottlenecks. The results of this study provide comprehensive insights into the genetic diversity, population structure, and phylogeography ofC. chinensisand will facilitate future breeding and conservation efforts.
AP1G2 Affects Mitotic Cycles of Female and Male Gametophytes in Arabidopsis
Authors: Zhou Yongmei , Fang Wenqin , Pang Ziqin , Chen Li-Yu , Cai Hanyang , Ain Noor-Ul- , Chang Men-Chi , Ming Ray
Published: July 2022

During sexual reproduction in flowering plants, haploid spores are formed from meiosis of spore mother cells. The spores then undergo mitosis, develop into female and male gametophytes, and give rise to seeds after fertilization. We identified a female sterile mutant ap1g2-4 from EMS mutagenesis, and analyses of two T-DNA insertion mutants, ap1g2-1+/− and ap1g2-3−/−, and detected a partial female and male sterility. The ap1g2 mutant gametophyte development was arrested at one nuclear stage. A complementation test using a genomic sequence of AP1G2 with its native promoter restored the function in the three ap1g2 mutant lines. Transcriptome profiling of ap1g2 ovules revealed that four genes encoding clathrin assembly proteins PICALM5A/B and PICALM9A/B, which were involved in endocytosis, were downregulated, which were confirmed to interact with AP1G2 through yeast two-hybrid assays and BIFC analysis. Our result also demonstrated that RALFL4-8-15-19-26 CML16 and several calcium-dependent protein kinases, including CPK14-16-17, were all downregulated in the ovules of ap1g2-1+/−. Moreover, Ca2+ concentration was low in impaired gametophytes. Therefore, we proposed that through interaction with PICALM5A/B and PICALM9A/B, AP1G2 may mediate gametogenesis accompanied by Ca2+ signaling in Arabidopsis. Our findings revealed a crucial role of AP1G2 in female and male gametogenesis in Arabidopsis and enhanced our understanding of the molecular mechanisms underpinning sexual reproduction in flowering plants.
A Novel Transcriptional Regulator HbERF6 Regulates the HbCIPK2-Coordinated Pathway Conferring Salt Tolerance in Halophytic Hordeum brevisubulatum
Authors: Jiang Ying , Zhang Haiwen , Li Yang , Chang Congcong , Wang Yunxiao , Feng Hao , Li Ruifen
Published: July 2022

Halophytic Hordeum brevisubulatum is a perennial grass which has evolved many distinctive salt-adaptive mechanisms. Our previous studies indicated it could thrive under salt stress through maintaining better K+ and Na+ homeostasis. Stress-responsive HbCIPK2 can phosphorylate K+ channel HbVGKC1 and Na+ transporter HbSOS1L to prevent Na+ accumulation and K+ reduction, hence pathway was not detected in glycophytic plants. In this study, we cloned the inducible promoter of HbCIPK2 by genome-walking, and identified a novel transcriptional regulator HbERF6 through yeast one-hybrid screening. HbERF6 functioned as a transcription factor which can bind to the GCC-box of the HbCIPK2 promoter to activate its expression. HbERF6 transgenic lines in Arabidopsis improved salt tolerance compared with wild type, and especially induced AtCIPK24 (SOS2) expression, resulting in K+/Na+ homeostasis to enhance salt tolerance. All the results confirmed the inducible function of HbERF6 for CIPK genes during salt tolerance. This regulatory network that integrates transcriptional regulation and post-translation modification will unravel a novel salt stress-responsive mechanism, highlighting the value and utilization of the halophytic resource.
Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense
Authors: Wu Liping , Meng Xiaoxi , Huang Huizhen , Liu Yingying , Jiang Weimin , Su Xinglong , Wang Zhaojian , Meng Fei , Wang Longhai , Peng Daiyin , Xing Shihai
Published: July 2022

The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. Here, we conducted proteomics and phosphoproteomics analyses to reveal differences in molecular mechanisms between SPUF and GP. We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. Significant differences between SPUF and GP were observed by mapping the DEPs and phosphorylated proteins to photosynthesis and polysaccharide and alkaloid biosynthesis pathways. Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense.