bluuebunny/crossref_metadata_2025 huggingface dataset:
DSC MRI in the human brain using deoxyhemoglobin and gadolinium—Simulations and validations at 3T
Authors: Schulman Jacob Benjamin , Sayin Ece Su , Manalac Angelica , Poublanc Julien , Sobczyk Olivia , Duffin James , Fisher Joseph A. , Mikulis David , Uludağ Kâmil
Published: February 2023

Introduction

Dynamic susceptibility contrast (DSC) MRI allows clinicians to determine perfusion parameters in the brain, such as cerebral blood flow, cerebral blood volume, and mean transit time. To enable quantification, susceptibility changes can be induced using gadolinium (Gd) or deoxyhemoglobin (dOHb), the latter just recently introduced as a contrast agent in DSC. Previous investigations found that experimental parameters and analysis choices, such as the susceptibility amplitude and partial volume, affect perfusion quantification. However, the accuracy and precision of DSC MRI has not been systematically investigated, particularly in the lower susceptibility range.

Methods

In this study, we compared perfusion values determined using Gd with values determined using a contrast agent with a lower susceptibility—dOHb—under different physiological conditions, such as varying the baseline blood oxygenation and/or magnitude of hypoxic bolus, by utilizing numerical simulations and conducting experiments on healthy subjects at 3T. The simulation framework we developed for DSC incorporates MRI signal contributions from intravascular and extravascular proton spins in arterial, venous, and cerebral tissue voxels. This framework allowed us to model the MRI signal in response to both Gd and dOHb.

Results and discussion

We found, both in the experimental results and simulations, that a reduced intravascular volume of the selected arterial voxel, reduced baseline oxygen saturation, greater susceptibility of applied contrast agent (Gd vs. dOHb), and/or larger magnitude of applied hypoxic bolus reduces the overestimation and increases precision of cerebral blood volume and flow. As well, we found that normalizing tissue to venous rather than arterial signal increases the accuracy of perfusion quantification across experimental paradigms. Furthermore, we found that shortening the bolus duration increases the accuracy and reduces the calculated values of mean transit time. In summary, we experimentally uncovered an array of perfusion quantification dependencies, which agreed with the simulation framework predictions, using a wider range of susceptibility values than previously investigated. We argue for caution when comparing absolute and relative perfusion values within and across subjects obtained from a standard DSC MRI analysis, particularly when employing different experimental paradigms and contrast agents.
Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma
Authors: Lin Jiaji , You Na , Li Xiaolong , Huang Jiayu , Lu Haoxuan , Hu Jianxing , Zhang Jun , Lou Xin
Published: February 2023

Objective

Tinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear.

Methods

Both preoperative (VSpre) and postoperative (VSpost) functional MR images were collected from 32 patients with unilateral VS and matched healthy controls (HCs). Connectome gradients were generated for the identification of altered regions and perturbed gradient distances. Tinnitus measurements were conducted for predictive analysis with neuroimaging–genetic integration analysis.

Results

There were 56.25% of preoperative patients and 65.63% of postoperative patients suffering from ipsilateral tinnitus, respectively. No relevant factors were identified including basic demographics info, hearing performances, tumor features, and surgical approaches. Functional gradient analysis confirmed atypical functional features of visual areas in VSpre were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VSpost vs. HC : P = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus (PFDR = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score (r = −0.30, P = 0.013), THI level (r = −0.31, P = 0.010), and visual analog scale (VAS) rating (r = −0.31, P = 0.0093), which could be used to predict VAS rating in the linear model. Neuropathophysiological features linked to the tinnitus gradient framework were linked to Ribosome dysfunction and oxidative phosphorylation.

Conclusion

Altered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.
A heterogeneous phantom study for investigating the stability of PET images radiomic features with varying reconstruction settings
Authors: Alsyed Emad , Smith Rhodri , Bartley Lee , Marshall Christopher , Spezi Emiliano
Published: February 2023

The purpose of this work was to assess the capability of radiomic features in distinguishing PET image regions with different uptake patterns. Furthermore, we assessed the stability of PET radiomic features with varying image reconstruction settings. An in-house phantom was designed and constructed, consisting of homogenous and heterogenous artificial phantom inserts. Four artificially constructed inserts were placed into a water filled phantom and filled with varying levels of radioactivity to simulate homogeneous and heterogeneous uptake patterns. The phantom was imaged for 80 min. PET images were reconstructed whilst varying reconstruction parameters. The parameters adjusted included, number of ordered subsets, number of iterations, use of time-of-flight and filter cut off. Regions of interest (ROI) were established by segmentation of the phantom inserts from the reconstructed images. In total seventy eight 3D radiomic features for each ROI with unique reconstructed parameters were extracted. The Friedman test was used to determine the statistical power of each radiomic feature in differentiating phantom inserts with different hetero/homogeneous configurations. The Coefficient of Variation (COV) of each feature, with respect to the reconstruction setting was used to determine feature stability. Forty three out of seventy eight radiomic features were found to be stable (COV ≤5%) against all reconstruction settings. To provide any utility, stable features are required to differentiate between regions with different hetro/homogeneity. Of the forty three stable features, fifteen (35%) features showed a statistically significant difference between the artificially constructed inserts. Such features included GLCM (Difference average, Difference entropy, Dissimilarity and Inverse difference), GLRL (Long run emphasis, Grey level non uniformity and Run percentage) and NGTDM (Complexity and Strength). The finding of this work suggests that radiomic features are capable of distinguishing between radioactive distribution patterns that demonstrate different levels of heterogeneity. Therefore, radiomic features could serve as an adjuvant diagnostic tool along with traditional imaging. However, the choice of the radiomic features needs to account for variability introduced when different reconstruction settings are used. Standardization of PET image reconstruction settings across sites performing radiomic analysis in multi-centre trials should be considered.
Review of novel functions and implications of circular RNAs in hepatocellular carcinoma
Authors: Liu Zheng , Yang Fangming , Xiao Zhun , Liu Yuexuan
Published: February 2023

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies, with high incidence and mortality. As the majority of HCC patients are diagnosed at an advanced stage and die of recurrence and metastasis, its pathology and new biomarkers are needed. Circular RNAs (circRNAs) are a large subclass of long non-coding RNAs (lncRNAs) with covalently closed loop structures and abundant, conserved, stable, tissue-specific expression in mammalian cells. CircRNAs exert multiple functions in HCC initiation, growth and progression, serving as promising biomarkers for diagnosis, prognosis and therapeutic targets for this disease. This review briefly describes the biogenesis and biological functions of circRNAs and elucidates the roles of circRNAs in the development and progression of HCC, especially regarding epithelial-mesenchymal transition (EMT), drug resistance and interactions with epigenetic modifications. In addition, this review highlights the implications of circRNAs as potential biomarkers and therapeutic targets for HCC. We hope to provide novel insight into the roles of circRNAs in HCC.
Association between small nucleolar RNA host gene expression and survival outcome of colorectal cancer patients: A meta-analysis based on PRISMA and bioinformatics analysis
Authors: Luo Pei , Du Jie , Li Yinan , Ma Jilong , Shi Wenjun
Published: February 2023

Introduction

Growing evidence shows that long non-coding RNA small nucleolar RNA host genes (lncRNA SNHGs) enact an pivotal regulatory roles in the shorter survival outcome of colorectal cancer (CRC). However, no research has systematically evaluated the correlation among lncRNA SNHGs expression and survival outcome of CRC. This research indented to screen whether exist potential prognostic effect of lncRNA SNHGs in CRC patientss using comprehensive review and meta-analysis.

Methods

Systematic searches were performed from the six relevant databases from inception to October 20, 2022. The quality of published papers was evaluated in details. We pooled the hazard ratios (HR) with 95% confidence interval (CI) through direct or indirect collection of effect sizes, and odds ratios (OR) with 95% CI by collecting effect sizes within articles. Detailed downstream signaling pathways of lncRNA SNHGs were summarized in detail

Results

25 eligible publications including 2,342 patients were finally included to appraise the association of lncRNA SNHGs with prognosis of CRC. Elevated lncRNA SNHGs expression was revealed in colorectal tumor tissues. High lncSNHG expression means bad survival prognosis in CRC patients (HR=1.635, 95% CI: 1.405–1.864, P<0.001). Additionally, high lncRNA SNHGs expression was inclined to later TNM stage (OR=1.635, 95% CI: 1.405–1.864, P<0.001), distant lymph node invasion, distant organ metastasis, larger tumor diameter and poor pathological grade. Begg's funnel plot test using the Stata 12.0 software suggested that no significant heterogeneity was found.

Conclusion

Elevated lncRNA SNHGs expression was revealed to be positively correlated to discontented CRC clinical outcome and lncRNA SNHG may act as a potential clinical prognostic index for CRC patients.
Emerging roles of endoplasmic reticulum stress in the cellular plasticity of cancer cells
Authors: Wang Hao , Mi Kun
Published: February 2023

Cellular plasticity is a well-known dynamic feature of tumor cells that endows tumors with heterogeneity and therapeutic resistance and alters their invasion–metastasis progression, stemness, and drug sensitivity, thereby posing a major challenge to cancer therapy. It is becoming increasingly clear that endoplasmic reticulum (ER) stress is a hallmark of cancer. The dysregulated expression of ER stress sensors and the activation of downstream signaling pathways play a role in the regulation of tumor progression and cellular response to various challenges. Moreover, mounting evidence implicates ER stress in the regulation of cancer cell plasticity, including epithelial–mesenchymal plasticity, drug resistance phenotype, cancer stem cell phenotype, and vasculogenic mimicry phenotype plasticity. ER stress influences several malignant characteristics of tumor cells, including epithelial-to-mesenchymal transition (EMT), stem cell maintenance, angiogenic function, and tumor cell sensitivity to targeted therapy. The emerging links between ER stress and cancer cell plasticity that are implicated in tumor progression and chemoresistance are discussed in this review, which may aid in formulating strategies to target ER stress and cancer cell plasticity in anticancer treatments.
Intrathymic growing bronchogenic cyst mimicking thymoma: A case report
Authors: Grigoroiu Madalina , Paisley Sarah , Brian Emmanuel , Natali Delphine
Published: February 2023

Intrathymic bronchogenic cysts are extremely rare lesions, and the differential diagnosis with a banal thymic cyst or a solid tumor can be problematic. Thymic carcinomas arising within thymic cysts have also been reported. We report a case of radical thymectomy for a slowly growing small thymic cyst. The pathological finding revealed a bronchogenic cyst rather than a thymic neoplasm.
ARID1A in cancer: Friend or foe?
Authors: Fontana Beatrice , Gallerani Giulia , Salamon Irene , Pace Ilaria , Roncarati Roberta , Ferracin Manuela
Published: February 2023

ARID1A belongs to a class of chromatin regulatory proteins that function by maintaining accessibility at most promoters and enhancers, thereby regulating gene expression. The high frequency of ARID1A alterations in human cancers has highlighted its significance in tumorigenesis. The precise role of ARID1A in cancer is highly variable since ARID1A alterations can have a tumor suppressive or oncogenic role, depending on the tumor type and context. ARID1A is mutated in about 10% of all tumor types including endometrial, bladder, gastric, liver, biliopancreatic cancer, some ovarian cancer subtypes, and the extremely aggressive cancers of unknown primary. Its loss is generally associated with disease progression more often than onset. In some cancers, ARID1A loss is associated with worse prognostic features, thus supporting a major tumor suppressive role. However, some exceptions have been reported. Thus, the association of ARID1A genetic alterations with patient prognosis is controversial. However, ARID1A loss of function is considered conducive for the use of inhibitory drugs which are based on synthetic lethality mechanisms. In this review we summarize the current knowledge on the role of ARID1A as tumor suppressor or oncogene in different tumor types and discuss the strategies for treating ARID1A mutated cancers.
Chronic pain and local pain in usually painless conditions including neuroma may be due to compressive proximal neural lesion
Authors: Macionis Valdas
Published: February 2023

It has been unexplained why chronic pain does not invariably accompany chronic pain-prone disorders. This question-driven, hypothesis-based article suggests that the reason may be varying occurrence of concomitant peripheral compressive proximal neural lesion (cPNL), e.g., radiculopathy and entrapment plexopathies. Transition of acute to chronic pain may involve development or aggravation of cPNL. Nociceptive hypersensitivity induced and/or maintained by cPNL may be responsible for all types of general chronic pain as well as for pain in isolated tissue conditions that are usually painless, e.g., neuroma, scar, and Dupuytren's fibromatosis. Compressive PNL induces focal neuroinflammation, which can maintain dorsal root ganglion neuron (DRGn) hyperexcitability (i.e., peripheral sensitization) and thus fuel central sensitization (i.e., hyperexcitability of central nociceptive pathways) and a vicious cycle of chronic pain. DRGn hyperexcitability and cPNL may reciprocally maintain each other, because cPNL can result from reflexive myospasm-induced myofascial tension, muscle weakness, and consequent muscle imbalance- and/or pain-provoked compensatory overuse. Because of pain and motor fiber damage, cPNL can worsen the causative musculoskeletal dysfunction, which further accounts for the reciprocity between the latter two factors. Sensitization increases nerve vulnerability and thus catalyzes this cycle. Because of these mechanisms and relatively greater number of neurons involved, cPNL is more likely to maintain DRGn hyperexcitability in comparison to distal neural and non-neural lesions. Compressive PNL is associated with restricted neural mobility. Intermittent (dynamic) nature of cPNL may be essential in chronic pain, because healed (i.e., fibrotic) lesions are physiologically silent and, consequently, cannot provide nociceptive input. Not all patients may be equally susceptible to develop cPNL, because occurrence of cPNL may vary as vary patients' predisposition to musculoskeletal impairment. Sensitization is accompanied by pressure pain threshold decrease and consequent mechanical allodynia and hyperalgesia, which can cause unusual local pain via natural pressure exerted by space occupying lesions or by their examination. Worsening of local pain is similarly explainable. Neuroma pain may be due to cPNL-induced axonal mechanical sensitivity and hypersensitivity of the nociceptive nervi nervorum of the nerve trunk and its stump. Intermittence and symptomatic complexity of cPNL may be the cause of frequent misdiagnosis of chronic pain.
Impact of extracellular vesicles on the pathogenesis, diagnosis, and potential therapy in cardiopulmonary disease
Authors: Soto-Vázquez Yixel M. , Genschmer Kristopher R.
Published: February 2023

Cardiopulmonary diseases span a wide breadth of conditions affecting both heart and lung, the burden of which is globally significant. Chronic pulmonary disease and cardiovascular disease are two of the leading causes of morbidity and mortality worldwide. This makes it critical to understand disease pathogenesis, thereby providing new diagnostic and therapeutic avenues to improve clinical outcomes. Extracellular vesicles provide insight into all three of these features of the disease. Extracellular vesicles are membrane-bound vesicles released by a multitude, if not all, cell types and are involved in multiple physiological and pathological processes that play an important role in intercellular communication. They can be isolated from bodily fluids, such as blood, urine, and saliva, and their contents include a variety of proteins, proteases, and microRNA. These vesicles have shown to act as effective transmitters of biological signals within the heart and lung and have roles in the pathogenesis and diagnosis of multiple cardiopulmonary diseases as well as demonstrate potential as therapeutic agents to treat said conditions. In this review article, we will discuss the role these extracellular vesicles play in the diagnosis, pathogenesis, and therapeutic possibilities of cardiovascular, pulmonary, and infection-related cardiopulmonary diseases.
NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment
Authors: Rastogi Shubham , Aldosary Sara , Saeedan Abdulaziz S. , Ansari Mohd. Nazam , Singh Manjari , Kaithwas Gaurav
Published: February 2023

Hypoxia is caused by a cancer-promoting milieu characterized by persistent inflammation. NF-κB and HIF-1α are critical participants in this transition. Tumor development and maintenance are aided by NF-κB, while cellular proliferation and adaptability to angiogenic signals are aided by HIF-1α. Prolyl hydroxylase-2 (PHD-2) has been hypothesized to be the key oxygen-dependent regulator of HIF-1α and NF-transcriptional B’s activity. Without low oxygen levels, HIF-1α is degraded by the proteasome in a process dependent on oxygen and 2-oxoglutarate. As opposed to the normal NF-κB activation route, where NF-κB is deactivated by PHD-2-mediated hydroxylation of IKK, this method actually activates NF-κB. HIF-1α is protected from degradation by proteasomes in hypoxic cells, where it then activates transcription factors involved in cellular metastasis and angiogenesis. The Pasteur phenomenon causes lactate to build up inside the hypoxic cells. As part of a process known as lactate shuttle, MCT-1 and MCT-4 cells help deliver lactate from the blood to neighboring, non-hypoxic tumour cells. Non-hypoxic tumour cells use lactate, which is converted to pyruvate, as fuel for oxidative phosphorylation. OXOPHOS cancer cells are characterized by a metabolic switch from glucose-facilitated oxidative phosphorylation to lactate-facilitated oxidative phosphorylation. Although PHD-2 was found in OXOPHOS cells. There is no clear explanation for the presence of NF-kappa B activity. The accumulation of the competitive inhibitor of 2-oxo-glutarate, pyruvate, in non-hypoxic tumour cells is well established. So, we conclude that PHD-2 is inactive in non-hypoxic tumour cells due to pyruvate-mediated competitive suppression of 2-oxo-glutarate. This results in canonical activation of NF-κB. In non-hypoxic tumour cells, 2-oxoglutarate serves as a limiting factor, rendering PHD-2 inactive. However, FIH prevents HIF-1α from engaging in its transcriptional actions. Using the existing scientific literature, we conclude in this study that NF-κB is the major regulator of tumour cell growth and proliferation via pyruvate-mediated competitive inhibition of PHD-2.
Protective effect of bioactive iridium nanozymes on high altitude-related hypoxia-induced kidney injury in mice
Authors: Wang Yujing , Shi Meijun , Chu Zongtang , Yan Xinlin , You Guoxing , Chen Gan , Zhou Hong
Published: February 2023

Introduction: High altitude-related hypoxia-induced organ damage significantly impacts people who are exposed to acute high-altitude environment. At present, kidney injury still lacks effective treatment strategies. Iridium nanozymes (Ir-NPs) are a nanomaterial with various enzymatic activities and are expected to be used in kidney injury treatment.

Methods: In this study, we simulated a high-altitude environment (6000 m) to induce a kidney injury model, and explored the therapeutic effect of Ir-NPs in mice with kidney injury in this environment. Changes in the microbial community and metabolites were analyzed to explore the possible mechanism underlying the improvement of kidney injury during acute altitude hypoxia in mice treated with Ir-NPs.

Results: It was discovered that plasma lactate dehydrogenase and urea nitrogen levels were considerably increased in mice exposed to acute altitude hypoxia compared to mice in a normal oxygen environment. Furthermore, there was a substantial increase in IL-6 expression levels in hypoxic mice; contrastingly, Ir-NPs decreased IL-6 expression levels, reduced the levels of succinic acid and indoxyl sulfate in the plasma and kidney pathological changes caused by acute altitude hypoxia. Microbiome analysis showed that bacteria, such as Lachnospiraceae_UCG_006 predominated in mice treated with Ir-NPs.

Conclusion: Correlation analysis of the physiological, biochemical, metabolic, and microbiome-related parameters showed that Ir-NPs could reduce the inflammatory response and protect kidney function under acute altitude hypoxia, which may be related to intestinal flora distribution regulation and plasma metabolism in mice. Therefore, this study provides a novel therapeutic strategy for hypoxia-related kidney injury, which could be applied to other hypoxia-related diseases.
The effects and safety of anticoagulation or antiplatelet therapy following TIPS in cirrhotic patients with portal hypertension: A meta-analysis
Authors: Xu Xiaotong , Fu Yunlai , Jiang Minjie , Wu Muchen , Wu Jing , Meng Qinghua
Published: February 2023

Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective way to improve portal hypertension, however, the role of anticoagulation or antiplatelet therapy following TIPS remains controversial. We conducted this study to evaluate the efficacy and safety of anticoagulation or antiplatelet therapy following TIPS.

Methods: A literature search was conducted on anticoagulation or antiplatelet therapy after TIPS using Pubmed, Web of Science, EMBASE, and Cochrane. The retrieval period was from the earliest accessible date in the database to 31 October 2022. We collected information on the incidence of stent dysfunction, bleeding, hepatic encephalopathy, the new occurrence of portal vein thrombosis, and the survival rate. Stata was analyzed in RevMan.

Results: 1. Four studies received anticoagulation or antiplatelet therapy after TIPS without control groups. According to the single-group rate meta-analysis, stent dysfunction occurred at 27% [95% CI (0.19, 0.38)], bleeding occurred at 21% [95% CI (0.14, 0.29)], new portal vein thrombosis occurred at 17% [(95%CI(0.04.0.71)], hepatic encephalopathy occurred at 47% [95%CI (0.34, 0.63)], and death occurred at 31% [95% CI (0.22, 0.42)]. 2. Eight studies, including 1025 patients, compared anticoagulation and antiplatelet therapy after TIPS to TIPS alone. In terms of stent dysfunction, bleeding, and hepatic encephalopathy, there were no significant differences between the two groups. The use of anticoagulation or antiplatelet therapy may result in a significant decrease in the incidence of new portal vein thrombosis and mortality over 1 year.

Discussion: Anticoagulant or antiplatelet therapy may not improve the patency rate of TIPS, but may effectively prevent new portal vein thrombosis after TIPS. Following TIPS, the use of anticoagulants or antiplatelet drugs does not lead to an increase in bleeding or death.
Development, testing, parameterisation, and calibration of a human PBPK model for the plasticiser, di-(2-ethylhexyl) terephthalate (DEHTP) using in silico, in vitro and human biomonitoring data
Authors: McNally Kevin , Sams Craig , Hogg Alex , Loizou George
Published: February 2023

A physiologically based pharmacokinetic model for di-(2-ethylhexyl) terephthalate (DEHTP) based on a refined model for di-(2-propylheptyl) phthalate (DPHP) was developed to interpret the metabolism and biokinetics of DEHTP following a single oral dose of 50 mg to three male volunteers. In vitro and in silico methods were used to generate parameters for the model. For example, measured intrinsic hepatic clearance scaled from in vitro to in vivo and plasma unbound fraction and tissue:blood partition coefficients (PCs) were predicted algorithmically. Whereas the development and calibration of the DPHP model was based upon two data streams, blood concentrations of parent chemical and first metabolite and the urinary excretion of metabolites, the model for DEHTP was calibrated against a single data stream, the urinary excretion of metabolites. Despite the model form and structure being identical significant quantitative differences in lymphatic uptake between the models were observed. In contrast to DPHP the fraction of ingested DEHTP entering lymphatic circulation was much greater and of a similar magnitude to that entering the liver with evidence for the dual uptake mechanisms discernible in the urinary excretion data. Further, the absolute amounts absorbed by the study participants, were much higher for DEHTP relative to DPHP. The in silico algorithm for predicting protein binding performed poorly with an error of more than two orders of magnitude. The extent of plasma protein binding has important implications for the persistence of parent chemical in venous blood—inferences on the behaviour of this class of highly lipophilic chemicals, based on calculations of chemical properties, should be made with extreme caution. Attempting read across for this class of highly lipophilic chemicals should be undertaken with caution since basic adjustments to PCs and metabolism parameters would be insufficient, even when the structure of the model itself is appropriate. Therefore, validation of a model parameterized entirely with in vitro and in silico derived parameters would need to be calibrated against several human biomonitoring data streams to constitute a data rich source chemical to afford confidence for future evaluations of other similar chemicals using the read-across approach.
Topological rainbow trapping based on gradual valley photonic crystals
Authors: Wang Xinyue , Zhao Wen , Elshahat Sayed , Lu Cuicui
Published: February 2023

Valley photonic crystals (PCs) play a crucial role in controlling light flow and realizing robust nanophotonic devices. In this study, rotated gradient valley PCs are proposed to realize topological rainbow trapping. A topological rainbow is observed despite the presence of pillars of different shapes, which indicates the remarkable universality of the design. Then, the loss is introduced to explore the topological rainbow trapping of the non-Hermitian valley PC. For the step-angle structure, the same or different losses can be applied, which does not affect the formed topological rainbow trapping. For a single-angle structure, the applied progressive loss can also achieve rainbow trapping. The rainbow is robust and topologically protected in both Hermitian and non-Hermitian cases, which is confirmed by the introduction of perturbations and defects. The proposed method in the current study presents an intriguing step for light control and potential applications in optical buffering and frequency routing.
Blood pressure stratification using photoplethysmography and light gradient boosting machine
Authors: Hu Xudong , Yin Shimin , Zhang Xizhuang , Menon Carlo , Fang Cheng , Chen Zhencheng , Elgendi Mohamed , Liang Yongbo
Published: February 2023

Introduction: Globally, hypertension (HT) is a substantial risk factor for cardiovascular disease and mortality; hence, rapid identification and treatment of HT is crucial. In this study, we tested the light gradient boosting machine (LightGBM) machine learning method for blood pressure stratification based on photoplethysmography (PPG), which is used in most wearable devices.

Methods: We used 121 records of PPG and arterial blood pressure (ABP) signals from the Medical Information Mart for Intensive Care III public database. PPG, velocity plethysmography, and acceleration plethysmography were used to estimate blood pressure; the ABP signals were used to determine the blood pressure stratification categories. Seven feature sets were established and used to train the Optuna-tuned LightGBM model. Three trials compared normotension (NT) vs. prehypertension (PHT), NT vs. HT, and NT + PHT vs. HT.

Results: The F1 scores for these three classification trials were 90.18%, 97.51%, and 92.77%, respectively. The results showed that combining multiple features from PPG and its derivative led to a more accurate classification of HT classes than using features from only the PPG signal.

Discussion: The proposed method showed high accuracy in stratifying HT risks, providing a noninvasive, rapid, and robust method for the early detection of HT, with promising applications in the field of wearable cuffless blood pressure measurement.
Imputation models and error analysis for phase contrast MR cerebral blood flow measurements
Authors: Shah Payal , Doyle Eamon , Wood John C. , Borzage Matthew T.
Published: February 2023

Cerebral blood flow (CBF) supports brain metabolism. Diseases impair CBF, and pharmacological agents modulate CBF. Many techniques measure CBF, but phase contrast (PC) MR imaging through the four arteries supplying the brain is rapid and robust. However, technician error, patient motion, or tortuous vessels degrade quality of the measurements of the internal carotid (ICA) or vertebral (VA) arteries. We hypothesized that total CBF could be imputed from measurements in subsets of these 4 feeding vessels without excessive penalties in accuracy. We analyzed PC MR imaging from 129 patients, artificially excluded 1 or more vessels to simulate degraded imaging quality, and developed models of imputation for the missing data. Our models performed well when at least one ICA was measured, and resulted in R2 values of 0.998–0.990, normalized root mean squared error values of 0.044–0.105, and intra-class correlation coefficient of 0.982–0.935. Thus, these models were comparable or superior to the test-retest variability in CBF measured by PC MR imaging. Our imputation models allow retrospective correction for corrupted blood vessel measurements when measuring CBF and guide prospective CBF acquisitions.
Pathogen-triggered metabolic adjustments to potato virus Y infection in potato
Authors: Manasseh Richard , Berim Anna , Kappagantu Madhu , Moyo Lindani , Gang David R. , Pappu Hanu R.
Published: February 2023

Potato (Solanum tuberosum L) is affected by several viral pathogens with the most economically damaging being potato virus Y (PVY). At least nine biologically distinct variants of PVY are known to attack potato, with necrotic types named PVYNTN and PVYN-Wi being the most recent additions to the list. So far, the molecular plant-virus interactions underlying this pathogenicity are not fully understood. In this study, gas chromatography coupled with mass spectroscopy (GC–MS) was used for an untargeted investigation of the changes in leaf metabolomes of PVY-resistant cultivar Premier Russet, and a susceptible cultivar, Russet Burbank, following inoculation with three PVY strains, PVYNTN, PVYN-Wi, and PVYO. Analysis of the resulting GC–MS spectra with the online software Metaboanalyst (version 5.0) uncovered several common and strain-specific metabolites that are induced by PVY inoculation. In Premier Russet, the major overlap in differential accumulation was found between PVYN-Wi and PVYO. However, the 14 significant pathways occurred solely due to PVYN-Wi. In contrast, the main overlap in differential metabolite profiles and pathways in Russet Burbank was between PVYNTN and PVYO. Overall, limited overlap was observed between PVYNTN and PVYN-Wi. As a result, PVYN-Wi-induced necrosis may be mechanistically distinguishable from that of PVYNTN. Furthermore, 10 common and seven cultivar-specific metabolites as potential indicators of PVY infection and susceptibility/resistance were identified by using PLS-DA and ANOVA. In Russet Burbank, glucose-6-phosphate and fructose-6-phosphate were particularly affected by strain–time interaction. This highlights the relevance of the regulation of carbohydrate metabolism for defense against PVY. Some strain- and cultivar-dependent metabolite changes were also observed, reflecting the known genetic resistance–susceptibility dichotomy between the two cultivars. Consequently, engineering broad-spectrum resistance may be the most effective breeding strategy for managing these necrotic strains of PVY.
Transcriptomic and epigenomic analyses revealed that polycomb repressive complex 2 regulates not only developmental but also stress responsive metabolism in Brassica rapa
Authors: Nugroho Adji Baskoro Dwi , Kim Sujeong , Lee Sang Woo , Kim Dong-Hwan
Published: February 2023

Polycomb group proteins (PcG) play a crucial role in developmental programs in eukaryotic organisms, including plants. PcG-mediated gene repression is achieved by epigenetic histone modification on target chromatins. Loss of PcG components leads to severe developmental defects. CURLY LEAF (CLF), a PcG component in Arabidopsis, catalyzes the trimethylation of histone H3 on lysine 27 (H3K27me3), a repressive histone mark in numerous genes in Arabidopsis. In this study, we isolated a single homolog of Arabidopsis CLF, namely, BrCLF, in Brassica rapa ssp. trilocularis. Transcriptomic analysis revealed that BrCLF participated in B. rapa developmental processes, such as seed dormancy, leaf and flower organ development, and floral transition. BrCLF was also involved in stress signaling and stress-responsive metabolism, such as aliphatic and indolic glucosinolate metabolism in B. rapa. Epigenome analysis showed that H3K27me3 was substantially enriched in genes related to these developmental and stress-responsive processes. Thus, this study provided a basis for elucidating the molecular mechanism of the PcG-mediated regulation of development and stress responses in B. rapa.
Application of ionizing radiation as an elicitor to enhance the growth and metabolic activities in Chlamydomonas reinhardtii
Authors: Kim Jin-Hong , Dubey Shubham Kumar , Hwangbo Kwon , Chung Byung Yeoup , Lee Seung Sik , Lee Sungbeom
Published: February 2023

Chlamydomonas reinhardtii is a eukaryotic, unicellular photosynthetic organism and a potential algal platform for producing biomass and recombinant proteins for industrial use. Ionizing radiation is a potent genotoxic and mutagenic agent used for algal mutation breeding that induces various DNA damage and repair responses. In this study, however, we explored the counterintuitive bioeffects of ionizing radiation, such as X- and γ-rays, and its potential as an elicitor to facilitate batch or fed-batch cultivation of Chlamydomonas cells. A certain dose range of X- and γ-rays was shown to stimulate the growth and metabolite production of Chlamydomonas cells. X- or γ-irradiation with relatively low doses below 10 Gy substantially increased chlorophyll, protein, starch, and lipid content as well as growth and photosynthetic activity in Chlamydomonas cells without inducing apoptotic cell death. Transcriptome analysis demonstrated the radiation-induced changes in DNA damage response (DDR) and various metabolic pathways with the dose-dependent expression of some DDR genes, such as CrRPA30, CrFEN1, CrKU, CrRAD51, CrOASTL2, CrGST2, and CrRPA70A. However, the overall transcriptomic changes were not causally associated with growth stimulation and/or enhanced metabolic activities. Nevertheless, the radiation-induced growth stimulation was strongly enhanced by repetitive X-irradiation and/or subsequent cultivation with an inorganic carbon source, i.e., NaHCO3, but was significantly inhibited by treatment of ascorbic acid, a scavenger of reactive oxygen species (ROS). The optimal dose range of X-irradiation for growth stimulation differed by genotype and radiation sensitivity. Here, we suggest that ionizing radiation within a certain dose range determined by genotype-dependent radiation sensitivity could induce growth stimulation and enhance metabolic activities, including photosynthesis, chlorophyll, protein, starch, and lipid synthesis in Chlamydomonas cells via ROS signaling. The counterintuitive benefits of a genotoxic and abiotic stress factor, i.e., ionizing radiation, in a unicellular algal organism, i.e., Chlamydomonas, may be explained by epigenetic stress memory or priming effects associated with ROS-mediated metabolic remodeling.
Changes in the morphology traits, anatomical structure of the leaves and transcriptome in Lycium barbarum L. under salt stress
Authors: Yao Xiao-Cui , Meng Li-Fang , Zhao Wang-Li , Mao Gui-Lian
Published: February 2023

Salt stress directly affects the growth of plants. The limitation of leaf grow is among the earliest visible effects of salt stress. However, the regulation mechanism of salt treatments on leaf shape has not been fully elucidated. We measured the morphological traits and anatomical structure. In combination with transcriptome analysis, we analyzed differentially expressed genes (DEGs) and verified the RNA-seq data by qRT-PCR. Finally, we analyzed correlation between leaf microstructure parameters and expansin genes. We show that the leaf thickness, the width, and the leaf length significantly increased at elevated salt concentrations after salt stress for 7 days. Low salt mainly promoted the increase in leaves length and width, but high salt concentration accelerated the leaf thickness. The anatomical structure results indicated that palisade mesophyll tissues contribute more to leaf thickness than spongy mesophyll tissues, which possibly contributed to the increase in leaf expansion and thickness. Moreover, a total of 3,572 DEGs were identified by RNA-seq. Notably, six of the DEGs among 92 identified genes concentrated on cell wall synthesis or modification were involved in cell wall loosening proteins. More importantly, we demonstrated that there was a strong positive correlation between the upregulated EXLA2 gene and the thickness of the palisade tissue in L. barbarum leaves. These results suggested that salt stress possibly induced the expression of EXLA2 gene, which in turn increased the thickness of L. barbarum leaves by promoting the longitudinal expansion of cells of the palisade tissue. This study lays a solid knowledge for revealing the underlying molecular mechanisms of leaf thickening in L. barbarum in response to salt stresses.
Bacillus vallismortis TU-Orga21 blocks rice blast through both direct effect and stimulation of plant defense
Authors: Thepbandit Wannaporn , Srisuwan Anake , Siriwong Supatcharee , Nawong Siriwan , Athinuwat Dusit
Published: February 2023

Beneficial microorganisms are an important strategy for sustainable plant production processes such as stimulate root exudation, stress tolerance, and yield improvement. This study investigated various microorganisms isolated from the rhizosphere of Oryza sativa L. in order to inhibit Magnaporthe oryzae cause of rice blast, by direct and indirect mode of action. The results indicated that Bacillus vallismortis strain TU–Orga21 significantly reduced M. oryzae mycelium growth and deformed the hyphal structures. The effects of biosurfactant TU–Orga21 was studied against M. oryzae spore development. The dose of ≥5% v/v biosurfactant significantly inhibited the germ tubes and appressoria formation. The biosurfactants were evaluated as surfactin and iturin A by Matrix-assisted laser desorption ionization dual time-of-flight tandem mass spectrometry. Under greenhouse conditions, priming the biosurfactant three times before M. oryzae infection significantly accumulated endogenous salicylic acid, phenolic compounds, and hydrogen peroxide (H2O2) during the infection process of M. oryzae. The SR-FT-IR spectral changes from the mesophyll revealed higher integral area groups of lipids, pectins, and proteins amide I and amide II in the elicitation sample. Furthermore, scanning electron microscope revealed appressorium and hyphal enlargement in un-elicitation leaves whereas appressorium formation and hyphal invasion were not found in biosurfactant-elicitation at 24 h post inoculation. The biosurfactant treatment significantly mitigated rice blast disease severity. Therefore, B. vallismortis can be a promising novel biocontrol agent which contains the preformed active metabolites for a rapid control of rice blast by a direct action against pathogen and by boosting plant immunity.
A novel high-affinity potassium transporter SeHKT1;2 from halophyte Salicornia europaea shows strong selectivity for Na+ rather than K+
Authors: Haxim Yakupjan , Wang Lei , Pan Zhendong , Fan Xiaorong , Ma Jinbiao
Published: February 2023

High-affinity K+ transporters (HKTs) are known as transmembrane cation transporters and are involved in Na+ or Na+-K+ transport in plants. In this study, a novel HKT gene SeHKT1;2 was isolated and characterized from the halophyte, Salicornia europaea. It belongs to subfamily I of HKT and shows high homology with other halophyte HKT proteins. Functional characterization of SeHKT1;2 indicated that it contributes to facilitating Na+ uptake in Na+-sensitive yeast strains G19, however, cannot rescue the K+ uptake-defective phenotype of yeast strain CY162, demonstrating SeHKT1;2 selectively transports Na+ rather than K+. The addition of K+ along with NaCl relieved the Na+ sensitivity. Furthermore, heterologous expression of SeHKT1;2 in sos1 mutant of Arabidopsis thaliana increased salt sensitivity and could not rescued the transgenic plants. This study will provide valuable gene resources for improving the salt tolerance in other crops by genetic engineering.
Evaluate the guide RNA effectiveness via Agrobacterium-mediated transient assays in Nicotiana benthamiana
Authors: Wang Zhibo , Shea Zachary , Li Qi , Wang Kunru , Mills Kerri , Zhang Bo , Zhao Bingyu
Published: February 2023

CRISPR/Cas9-based genome editing system is a powerful tool for plant genetic improvement. However, the variable efficiency of guide RNA(s) (gRNA) represents a key limiting factor that hampers the broad application of the CRISPR/Cas9 system in crop improvement. Here, we employed the Agrobacterium-mediated transient assays to evaluate the effectiveness of gRNAs for editing genes in Nicotiana benthamiana and soybean. We designed a facile screening system based on indels that can be introduced by CRISPR/Cas9-mediated gene editing. A gRNA binding sequence (23 nucleotides) was inserted into the open reading frame of yellow fluorescent protein (YFP) gene (gRNA-YFP), which disrupted the YFP reading frame and results in no fluorescent signal when it was expressed in plant cells. Transiently co-expression of Cas9 and a gRNA targeting the gRNA-YFP gene in plant cells could restore the YFP reading frame and recover the YFP signals. We evaluated five gRNAs targeting Nicotiana benthamiana and soybean genes and confirmed the reliability of the gRNA screening system. The effective gRNAs targeting NbEDS1, NbWRKY70, GmKTI1, and GmKTI3 had been used to generate transgenic plants and resulted in expected mutations on each gene. While a gRNA targeting NbNDR1 was confirmed to be ineffective in transient assays. This gRNA indeed failed to trigger target gene mutations in stable transgenic plants. Thus, this new transient assay system can be used to validate the effectiveness of gRNAs before generating stable transgenic plants.
Inoculum production of Phytophthora medicaginis can be used to screen for partial resistance in chickpea genotypes
Authors: Bithell Sean L. , Drenth Andre , Backhouse David , Harden Steve , Hobson Kristy
Published: February 2023

Phytophthora root rot caused by Phytophthora medicaginis is an important disease of chickpeas (Cicer arietinum) in Australia with limited management options, increasing reliance on breeding for improved levels of genetic resistance. Resistance based on chickpea–Cicer echinospermum crosses is partial with a quantitative genetic basis provided by C. echinospermum and some disease tolerance traits originating from C. arietinum germplasm. Partial resistance is hypothesised to reduce pathogen proliferation, while tolerant germplasm may contribute some fitness traits, such as an ability to maintain yield despite pathogen proliferation. To test these hypotheses, we used P. medicaginis DNA concentrations in the soil as a parameter for pathogen proliferation and disease assessments on lines of two recombinant inbred populations of chickpea–C. echinospermum crosses to compare the reactions of selected recombinant inbred lines and parents. Our results showed reduced inoculum production in a C. echinospermum backcross parent relative to the C. arietinum variety Yorker. Recombinant inbred lines with consistently low levels of foliage symptoms had significantly lower levels of soil inoculum compared to lines with high levels of visible foliage symptoms. In a separate experiment, a set of superior recombinant inbred lines with consistently low levels of foliage symptoms was tested for soil inoculum reactions relative to control normalised yield loss. The in-crop P. medicaginis soil inoculum concentrations across genotypes were significantly and positively related to yield loss, indicating a partial resistance-tolerance spectrum. Disease incidence and the rankings for in-crop soil inoculum were correlated strongly to yield loss. These results indicate that soil inoculum reactions may be useful to identify genotypes with high levels of partial resistance.
Transcriptomic and metabolomic insights on the molecular mechanisms of flower buds in responses to cold stress in two Camellia oleifera cultivars
Authors: Wang Ya-Jun , Wu Ling-Li , Sun Min-hong , Li Ze , Tan Xiao-Feng , Li Jian-An
Published: February 2023

Introduction

The Camellia oleifera (C. oleifera) cultivars 'Huashuo' (HS) and 'Huaxin' (HX) are new high-yielding and economically valuable cultivars that frequently encounter prolonged cold weather during the flowering period, resulting in decreased yields and quality. The flower buds of HS sometimes fail to open or open incompletely under cold stress, whereas the flower buds of HX exhibit delayed opening but the flowers and fruits rarely drop.

Methods

In this study, flower buds at the same development stage of two C. oleifera cultivars were used as test materials for a combination of physiological, transcriptomic and metabolomic analyses, to unravel the different cold regulatory mechanisms between two cultivars of C. oleifera.

Results and discussion

Key differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) involved in sugar metabolism, phenylpropanoid biosynthesis, and hormone signal transduction were significantly higher in HX than in HS, which is consistent with phenotypic observations from a previous study. The results indicate that the flower buds of HX are less affected by long-term cold stress than those of HS, and that cold resistance in C. oleifera cultivars varies among tissues or organs.This study will provide a basis for molecular markers and molecular breeding of C. oleifera.