bluuebunny/crossref_metadata_2025 huggingface dataset:
First report on metagenomics and their predictive functional analysis of fermented bamboo shoot food of Tripura, North East India
Authors: Das Rohit , Tamang Buddhiman , Najar Ishfaq Nabi , Thakur Nagendra , Mondal Krishnendu
Published: April 2023

Moiya pansung, mileye amileye, moiya koshak, and midukeye are naturally fermented bamboo shoot foods of Tripura. The present study aimed to reveal the whole microbial community structure of naturally fermented moiya pangsung, mileye amileye, moiya koshak, and midukeye along with the prediction of microbial functional profiles by shotgun metagenomic sequence analysis. The metataxonomic profile of moiya pangsung, mileye amileye, moiya koshak, and midukeye samples showed different domains, viz., bacteria (97.70%) followed by the virus (0.76%), unclassified (0.09%), eukaryotes (1.46%) and archaea (0.05%). Overall, 49 phyla, 409 families, 841 genera, and 1,799 species were found in all the fermented bamboo shoot samples collected from different places of Tripura. Firmicutes was the most abundant phylum (89.28%) followed by Proteobacteria (5.13%), Bacteroidetes (4.38%), Actinobacteria (1.02%), and Fusobacteria (0.17%). Lactiplantibacillus plantarum was the most abundant species in moiya pangsung, mileye amileye, moiya koshak, and midukeye followed by Lactococcus lactis, Levilactobacillus brevis, Leuconostoc mesenteroides, Weissella paramesenteroides, Leuconostoc kimchii, Pediococcus pentosaceus, Leuconostoc gasicomitatum, and Lacticaseibacillus casei. A few phyla of fungus were found, viz., Ascomycota, Basidiomycota, and Glomeromycota, where Ascomycota was present in high abundance. Functional analysis of moiya pangsung, mileye amileye, moiya koshak, and midukeye metagenome revealed the genes for the synthesis and metabolism of a wide range of bioactive compounds including, various essential amino acids, and conjugated amino acids. The abundance profile and predictive analysis of fermented bamboo shoots revealed a huge plethora of essential microorganisms and KEGG analysis revealed genes for amino acid metabolism, pectin degradation, lipid metabolism, and many other essential pathways that can be essential for the improvement of nutritional and sensory qualities of the fermented bamboo shoot products.
A halophilic Chromohalobacter species from estuarine coastal waters as a detoxifier of manganese, as well as a novel bio-catalyst for synthesis of n-butyl acetate
Authors: Pereira Flory , Kerkar Savita , Dias Dominic Savio , Gobre Vivekanand V.
Published: April 2023

Anthropogenic pollution due to ferro-manganese ore transport by barges through the Mandovi estuary in Goa, India is a major environmental concern. In this study a manganese (Mn) tolerant, moderately halophilic Chromohalobacter sp. belonging to the family Halomonadaceae was isolated from the sediments of a solar saltern adjacent to this Mandovi estuary. Using techniques of Atomic absorption spectroscopy, Scanning electron microscopy-Energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy and Atomic Force Microscopy, the Chromohalobacter sp. was explored for its ability to tolerate and immobilize Mn in amended and unamended media with 20% natural salt concentration (w/v). In aqueous media supplemented with 0.1 mM Mn, the Chromohalobacter sp. was capable of sequestering up to 76% Mn with an average immobilization rate of 8 mg Mn /g /day. Growth rate kinetic analysis using Gompertz mathematical functions was found to model the experimental data well. The model inferred that the maximum growth rate of Chromohalobacter sp. was at 10% natural salt concentration (w/v). The Chromohalobacter sp. was further found to be multimetal tolerant showing high tolerance to Iron (Fe), Nickel (Ni) and Cobalt (Co), (each at 4 mM), and tolerated Manganese (Mn) up to 6 mM. Morphologically, the Chromohalobacter sp. was a non-spore forming, Gram negative motile rod (0.726 μ× 1.33 μ). The adaptative mechanism of Chromohalobacter sp. to elevated Mn concentrations (1 mM) resulted in the reduction of its cell size to 0.339 μ× 0.997 μ and the synthesis of an extracellular slime, immobilizing Mn from the liquid phase forming Manganese oxide, as confirmed by Scanning Electron Microscopy. The expression of Mnx genes for manganese oxidation further substantiated the finding. This bacterial synthesized manganese oxide also displayed catalytic activity (∼50% conversion) for the esterification of butan-1-ol with CH3COOH to yield n-butyl acetate. This Chromohalobacter sp. being indigenous to marine salterns, has adapted to high concentrations of heavy metals and high salinities and can withstand this extremely stressed environment, and thus holds a tremendous potential as an environmentally friendly “green bioremediator” of Mn from euryhaline environments. The study also adds to the limited knowledge about metal-microbe interactions in extreme environments. Further, since Chromohalobacter sp. exhibits commendable catalytic activity for the synthesis of n-butyl acetate, it would have several potential industrial applications.
Polycladia myrica-based delivery of selenium nanoparticles in combination with radiotherapy induces potent in vitro antiviral and in vivo anticancer activities against Ehrlich ascites tumor
Authors: Abo-Neima Sahar E. , Ahmed Abdelhamid A. , El-Sheekh Mostafa , Makhlof Mofida E. M.
Published: April 2023

Background: Over the last few decades, nanotechnology has entered daily life through various applications, therefore, there has been a trend toward developing new approaches to green-mediated nanotechnology that encourage nanomaterial formation through biological methods such as plants or microorganisms. Algae have gained increasing attention from nanotechnology scientists and have paved the way for the emergence of “algae nanotechnology” as a promising field.

Methods: Via using the aqueous extract of the brown alga Polycladia myrica, selenium nanoparticles were synthesized and characterized by using seven instruments: SEM, TEM, UV spectra, Zeta potential, EDX, X-ray diffraction, and FTIR. P. myrica selenium nanoparticles (PoSeNPs) were then examined for their antiviral activity against HSV-1 (Herpes simplex I) and anticancer against human colon cancer cell line (HCT-116) in vitro and in vivo alone and in combination with laser therapy of power 2 mW against Ehrlich carcinoma (EAC).

Results: PoSeNPs ranging between 17.48 nm and 23.01 nm in size, and EDX revealed the selenium mass and its atoms as 0.46% ± 0.07% and 0.08% ± 0.01% respectively. Their anticancer potentiality in vitro was with maximum inhibitions of 80.57% and 73% and IC50 = 14.86 μg/mL and 50 mg/mL against HCT-116 and EAC cell lines respectively, while their in vivo alone and in combination with laser therapy of power 2 mW showed a potent therapy effect against Ehrlich ascites carcinoma (EAC).

Conclusion: This study concluded that PoSeNPs do not have a toxic effect; they exhibit high effectiveness as a photothermal agent for cancer therapy, with promising applications in future biomedical fields. The combined therapy showed a significant decrease in tumor volume, massive tumor cell necrosis, shrinking, and disappearance. It also showed improvement in liver TEM, histology, kidney function: urea and creatinine, and liver enzymes: ALT, and AST.
Ginseng intake and Alzheimer disease-specific cognition in older adults according to apolipoprotein ε4 allele status
Authors: Lee Boung Chul , Choe Young Min , Suh Guk-Hee , Choi Ihn-Geun , Kim Hyun Soo , Hwang Jaeuk , Yi Dahyun , Jhoo Jin Hyeong , Kim Jee Wook
Published: April 2023

Background

The probable association among ginseng intake, Alzheimer’s disease (AD)-specific cognition, and apolipoprotein ε4 (APOE4) remains poorly investigated. Hence, we examined the association between ginseng intake and AD-specific cognition in older adults under the moderating effect of APOE4 status.

Methods

This study enrolled 160 adults aged 65–90 years without dementia. All participants underwent comprehensive dietary and clinical assessments including ginseng intake, AD-related cognition (i.e., delayed episodic memory, as the earliest cognitive change in AD), and non-memory cognition for comparative purposes.

Results

Ginseng intake was associated with higher delayed episodic memory, but not non-memory cognition, compared to no ginseng intake. The interaction between ginseng intake and APOE4 status had a significant effect on delayed episodic memory. Subgroup analyses showed that ginseng intake was associated with higher delayed episodic memory in the APOE4-negative but not the APOE4-positive subgroup. The benefits of ginseng intake on delayed episodic memory were prominent in the high duration (≥5 years) and midlife onset (<65 years) groups.

Conclusion

Our study of older adults with no dementia suggests that ginseng intake (with high duration and midlife onset) had a beneficial effect on AD-specific cognitive decline, i.e., the delayed episodic memory. In addition, APOE4 status moderates the association between ginseng intake status and AD-specific cognitive decline.
The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study
Authors: Stewart Charlotte B. , Ledingham David , Foster Victoria K. , Anderson Kirstie N. , Sathyanarayana Sahana , Galley Debra , Pavese Nicola , Pasquini Jacopo
Published: April 2023

Background

Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated.

Objectives

We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment.

Methods

Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively.

Results

Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = −0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004).

Conclusions

Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.
Self-processing in coma, unresponsive wakefulness syndrome and minimally conscious state
Authors: Ferré Fabrice , Heine Lizette , Naboulsi Edouard , Gobert Florent , Beaudoin-Gobert Maude , Dailler Frédéric , Buffières William , Corneyllie Alexandra , Sarton Benjamine , Riu Béatrice , Luauté Jacques , Silva Stein , Perrin Fabien
Published: April 2023

Introduction

Behavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness.

Methods

Hence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject’s own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN (‘SON effect’, primary endpoint assessed by temporal clustering permutation tests).

Results

Patients were either coma (n = 38), unresponsive wakefulness syndrome (UWS, n = 30) or minimally conscious state (MCS, n = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a ‘SON effect’. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients (p = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients (p = 0.013 for comparison between groups). Among the 72 survivors’ patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome.

Discussion

About 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome.
Association of heartbeat complexity with survival in advanced non-small cell lung cancer patients
Authors: Wu Shuang , Li Guangqiao , Chen Man , Zhang Sai , Zhou Yufu , Shi Bo , Zhang Xiaochun
Published: April 2023

Background

Previous studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.

Methods

This study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).

Results

Univariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p < 0.05). After adjusting for confounders in the multivariate analysis, HF, REC, and DET were found to be independent prognostic factors for the survival of patients with advanced NSCLC (all p < 0.05).

Conclusion

There was an independent association between heartbeat complexity and survival in advanced NSCLC patients. The nonlinear analysis method based on RQA may provide valuable additional information for the prognostic stratification of patients with advanced NSCLC and may supplement the traditional time domain and frequency domain analysis methods.
EEG microstate changes during hyperbaric oxygen therapy in patients with chronic disorders of consciousness
Authors: Wang Jiameng , Xu Long , Ge Qianqian , Xue Lianbi , Liu Yaling , Wang Cong , Wu Yue , Liu Yun , Chen Lichao , Zhuang Yutong , Geng Xiaoli , Chen Xueling , Wang Bo , Yu Qiuhong , He Jianghong , Zhao Xudong
Published: April 2023

Hyperbaric oxygen (HBO) therapy is an effective treatment for patients with disorders of consciousness (DOC). In this study, real-time electroencephalogram (EEG) recordings were obtained from patients with DOC during HBO therapy. EEG microstate indicators including mean microstate duration (MMD), ratio of total time covered (RTT), global explained variance (GEV), transition probability, mean occurrence, and mean global field power (GFP) were compared before and during HBO therapy. The results showed that the duration of microstate C in all patients with DOC increased after 20 min of HBO therapy (p < 0.05). Further statistical analysis found that the duration of microstate C was longer in the higher CRS-R group (≥8, 17 cases) than in the lower group (<8, 24 cases) during HBO treatment. In the higher CRS-R group, the transition probabilities from microstate A to microstate C and from microstate C to microstate A also increased significantly compared with the probability before treatment (p < 0.05). Microstate C is generally considered to be related to a salience network; an increase in the transition probability between microstate A and microstate C indicates increased information exchange between the auditory network and the salience network. The results of this study show that HBO therapy has a specific activating effect on attention and cognitive control in patients and causes increased activity in the primary sensory cortex (temporal lobe and occipital lobe). This study demonstrates that real-time EEG detection and analysis during HBO is a clinically feasible method for assessing brain function in patients with DOC. During HBO therapy, some EEG microstate indicators show significant changes related to the state of consciousness in patients with chronic DOC. This will be complementary to important electrophysiological indicators for assessing consciousness and may also provide an objective foundation for the precise treatment of patients with DOC.
Role of integrating cannabinoids and the endocannabinoid system in neonatal hypoxic-ischaemic encephalopathy
Authors: Xiao Jie , Zhou Yue , Sun Luqiang , Wang Haichuan
Published: April 2023

Neonatal hypoxic-ischaemic events, which can result in long-term neurological impairments or even cell death, are among the most significant causes of brain injury during neurodevelopment. The complexity of neonatal hypoxic-ischaemic pathophysiology and cellular pathways make it difficult to treat brain damage; hence, the development of new neuroprotective medicines is of great interest. Recently, numerous neuroprotective medicines have been developed to treat brain injuries and improve long-term outcomes based on comprehensive knowledge of the mechanisms that underlie neuronal plasticity following hypoxic-ischaemic brain injury. In this context, understanding of the medicinal potential of cannabinoids and the endocannabinoid system has recently increased. The endocannabinoid system plays a vital neuromodulatory role in numerous brain regions, ensuring appropriate control of neuronal activity. Its natural neuroprotection against adult brain injury or acute brain injury also clearly demonstrate the role of endocannabinoid signalling in modulating neuronal activity in the adult brain. The goal of this review is to examine how cannabinoid-derived compounds can be used to treat neonatal hypoxic-ischaemic brain injury and to assess the critical function of the endocannabinoid system and its potential for use as a new neuroprotective treatment for neonatal hypoxic-ischaemic brain injury.
The Role of Lymph Node Dissection for Non-Metastatic Renal Cell Carcinoma: An Updated Systematic Review and Meta-Analysis
Authors: Shi Xu , Feng Dechao , Li Dengxiong , Zhang Facai , Wei Wuran
Published: April 2023

Introduction

To compare the survival benefit of nephrectomy with or without lymph node dissection (LND) for non-metastatic, especially for high-risk renal cell carcinoma (RCC) patients by investigating different survival evaluation indicators.

Evidence Acquisition

Eligible studies were identified until September 2021, through common databases including PubMed, the Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) on RCC and LND without language restriction. Data analysis was performed through Stata software, version 16.0 (Stata Corp., College Station, TX, USA).

Evidence Synthesis

22 articles were included in this meta-analysis. For non-metastatic RCC, performing LND comitantly with nephrectomy did not change the overall survival (OS) of patients of all T stages [hazard ratio (HR)=1.10, 95%CI: 0.95-1.27] and also for T2+NxM0 patients (HR=0.88, 95%CI: 0.68-1.14) as well as for T3+NxM0 patients (HR=0.95, 95%CI: 0.61-1.50). At the same time, cumulative meta-analysis has shown that the survival benefit of LND has a significant declining trend since 1979. However, it is worth noting that the operation of LND presented as a risk factor for cancer specific survival (CSS) (HR=1.22, 95%CI: 1.05-1.43).

Conclusions

Latest evidence indicated that LND might not be suitable for all non-metastatic RCC patients, especially in the current situation of various non-invasive examinations for judging lymph node metastasis and adjuvant treatments. On the contrary, excess LND could damage the survival of patients.

Systematic Review Registration

This study is registered as PROSPERO CRD42021271124.
Correlation between gene mutation status and clinicopathologic features in early multiple primary lung cancer
Authors: Teng Fei , Xu Jian , Wang Jian , Yang Bo , Wu Yong-Zhong , Jiang Yue-Quan , Wang Zhi-Qiang
Published: April 2023

Objective

To understand the characteristics of genetic mutation in multiple primary lung cancer so as to guide clinical decisions in targeted therapy.

Methods

We analyzed a total of 265 tumors from 111 patients who underwent surgery for multiple lung cancers. Individual tumors were subjected to histological evaluation and gene mutation analysis using ABI 7500 Fluorescence quantitative PCR.

Results

In this study, we analyzed demographic and clinical parameters such as age, gender, smoking, alcohol consumption, pathological type, number of nodules, and other details of 111 patients with early multiple primary lung cancer. We also compared the clinicopathologic characteristics of different populations based on the gene mutation status of pulmonary nodules. Subsequently, we performed a clinicopathological analysis of all 265 pulmonary nodules from these patients. Results showed significant differences in clinicopathological features of pulmonary nodules in different genetic mutations.

Conclusion

This study revealed the gene mutation characteristics and clinicopathological features in early multiple primary lung cancer. We found that the gene mutation status between different nodules in patients with early multiple primary lung cancer was inconsistent in most cases. Therefore, the use of targeted therapy based on the genetic sequencing of only one nodule, is unreliable. We hope this study can be helpful in guiding clinical treatment decisions.
Intraoperative and postoperative short-term outcomes of intracorporeal anastomosis versus extracorporeal anastomosis in laparoscopic right hemicolectomy
Authors: Zhou Yuhang , Zhou Yuchen , Wang Chuandong , Ye Rong , Lin Xiaojun , Tan Song , Chen Weijie , Mi Yulong , Yang Changshun , Lin Shengtao , Li Weihua
Published: April 2023

Background

Intracorporeal anastomosis (IA) is a difficult but popular anastomotic approach for reconstruction of digestive tract after laparoscopic right hemicolectomy, which may reduce some limitations faced during extracorporeal anastomosis (EA).

Methods

A retrospective review of 78 patients who underwent laparoscopic right hemicolectomy by a veteran surgeon in a high-volume public tertiary hospital, including 50 patients with IA and 28 patients with EA. The intraoperative-related factors and short-term results of the two anastomotic approaches were compared.

Results

There was no significant difference in demographics and clinical characteristics between the two groups (P>0.05). The intraoperative blood loss was less (P=0.010) and the incision length was shorter (P<0.001) in the intracorporeal group. Postoperative farting time was faster (P=0.005) and postoperative pain score (VAS) was lower (P<0.001) in IA group. Although the anastomotic time of IA was shorter (P<0.001), the operative time of the two groups were similar. And number of lymph nodes harvested, NLR from POD1 to POD3, postoperative hospital stay and overall hospital stay between the two groups were comparable. Except for significant difference in abdominal infection rate, the Clavien-Dindo classification and the incidence of other postoperative complications were not statistically different. Moreover, the morbidity of abdominal infection decreased with time in the IA group (P=0.040).

Conclusion

IA is a reliable and feasible procedure, which has faster anastomotic time, earlier return of bowel function and superior postoperative comfort of patient, compared to EA. The postoperative complication rate of IA is similar to that of EA, and may be improved with the IA technical maturity of surgeons, which potentially contributes to the development of ERAS.
A comparison of machine learning models for predicting urinary incontinence in men with localized prostate cancer
Authors: Hasannejadasl Hajar , Osong Biche , Bermejo Inigo , van der Poel Henk , Vanneste Ben , van Roermund Joep , Aben Katja , Zhang Zhen , Kiemeney Lambertus , Van Oort Inge , Verwey Renee , Hochstenbach Laura , Bloemen Esther , Dekker Andre , Fijten Rianne R. R.
Published: April 2023

Introduction

Urinary incontinence (UI) is a common side effect of prostate cancer treatment, but in clinical practice, it is difficult to predict. Machine learning (ML) models have shown promising results in predicting outcomes, yet the lack of transparency in complex models known as “black-box” has made clinicians wary of relying on them in sensitive decisions. Therefore, finding a balance between accuracy and explainability is crucial for the implementation of ML models. The aim of this study was to employ three different ML classifiers to predict the probability of experiencing UI in men with localized prostate cancer 1-year and 2-year after treatment and compare their accuracy and explainability.

Methods

We used the ProZIB dataset from the Netherlands Comprehensive Cancer Organization (Integraal Kankercentrum Nederland; IKNL) which contained clinical, demographic, and PROM data of 964 patients from 65 Dutch hospitals. Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM) algorithms were applied to predict (in)continence after prostate cancer treatment.

Results

All models have been externally validated according to the TRIPOD Type 3 guidelines and their performance was assessed by accuracy, sensitivity, specificity, and AUC. While all three models demonstrated similar performance, LR showed slightly better accuracy than RF and SVM in predicting the risk of UI one year after prostate cancer treatment, achieving an accuracy of 0.75, a sensitivity of 0.82, and an AUC of 0.79. All models for the 2-year outcome performed poorly in the validation set, with an accuracy of 0.6 for LR, 0.65 for RF, and 0.54 for SVM.

Conclusion

The outcomes of our study demonstrate the promise of using non-black box models, such as LR, to assist clinicians in recognizing high-risk patients and making informed treatment choices. The coefficients of the LR model show the importance of each feature in predicting results, and the generated nomogram provides an accessible illustration of how each feature impacts the predicted outcome. Additionally, the model’s simplicity and interpretability make it a more appropriate option in scenarios where comprehending the model’s predictions is essential.
miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction
Authors: Morimoto Masahiro , Maishi Nako , Tsumita Takuya , Alam Mohammad Towfik , Kikuchi Hiroshi , Hida Yasuhiro , Yoshioka Yusuke , Ochiya Takahiro , Annan Dorcas A. , Takeda Ryo , Kitagawa Yoshimasa , Hida Kyoko
Published: April 2023

Background

Tumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis.

Methods

We analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined.

Results

Intravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3′ UTR assay.

Conclusion

miR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier.
Sinapis Semen: A review on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics
Authors: Dang Rui , Guan Huida , Wang Changhong
Published: April 2023

Sinapis Semen (SS), the dried mature seed of Sinapis alba L. and Brassica juncea (L.) Czern. et Coss., is one of the traditional Chinese medicinal materials with a wide range of pharmacological effects being used for asthma, cough and many other ailments. SS is also widely used in food agriculture, medicine and other industries in North America and South Asia. More recently, the research on SS has gradually intensified and increased. However, there is no systematic review of SS. In this review, through literature exploration and analysis, the research advance on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics of SS was aggregated initially. Total 144 compounds have been isolated and identified from SS. Among them, glucosinolates and their hydrolysates and volatile oils are the main active ingredients and important chemical classification markers. SS has a wide range of pharmacological effects, especially in cough suppressing, asthma calming, anti-inflammatory, neuroprotective, cardiovascular protective, inhibiting androgenic effects, anti-tumor, and skin permeation promoting effects. Sinapine and sinapic acid are the main active ingredients of SS for its medicinal effects. However, SS has a strong skin irritation, presumably related to the time of application, the method of processing, and original medicinal plants. This review will provide useful data for the follow-up research and safe and reasonable clinical application of SS.
Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy
Authors: Zhou Ji-Chao , Jin Cai-Cai , Wei Xiao-Li , Xu Rui-Bing , Wang Ruo-Yu , Zhang Zhi-Meng , Tang Bo , Yu Jin-Mei , Yu Jiao-Jiao , Shang Shuang , Lv Xiao-Xi , Hua Fang , Li Ping-Ping , Hu Zhuo-Wei , Shen Yong-Mei , Wang Feng-Peng , Ma Xiu-Ying , Cui Bing , Geng Fu-Neng , Zhang Xiao-Wei
Published: April 2023

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.
A decline in avian cytokine expression with age revealed by commercially available cytokine array
Authors: Levkovich Guy , Almagor Dana , Saibaba Ganesan , Bendikov-Bar Inna , Rusal Mark , Lokshtanov Dmitri , Shinder Dmitri , Sagi Dror
Published: April 2023

Cytokines are secreted immunomodulators that are key regulators of the avian immune response. Currently, the most commonly used method to follow cytokine expression is qPCR, which measures cellular levels of mRNA, rather their extracellular circulating levels. Here we present a commercially available cytokine array designed to assay circulating expression levels of multiple cytokines and immunomodulators simultaneously. Upon minor modifications to the manufacturer protocol, background noise was reduced, leading to a significant increase in the sensitivity of the device. Our data indicate that the array is reliable and produce consistent data between biological repeats. We tested the reproducibility of the array in a biologically relevant context by assessing age-related changes in circulating cytokines. While individual features did not show a consistent pattern, our data revealed a consistent decline in the median of all cytokine values, supporting the validity of the array in studying biological processes.
The Role of Heterotrimeric G-Protein Beta Subunits During Nodulation in Medicago truncatula Gaertn and Pisum sativum L.
Authors: Bovin Andrey D. , Pavlova Olga A. , Dolgikh Aleksandra V. , Leppyanen Irina V. , Dolgikh Elena A.
Published: April 2023

Heterotrimeric G-proteins regulate plant growth and development as master regulators of signaling pathways. In legumes with indeterminate nodules (e.g., Medicago truncatula and Pisum sativum), the role of heterotrimeric G-proteins in symbiosis development has not been investigated extensively. Here, the involvement of heterotrimeric G-proteins in M. truncatula and P. sativum nodulation was evaluated. A genome-based search for G-protein subunit-coding genes revealed that M. truncatula and P. sativum harbored only one gene each for encoding the canonical heterotrimeric G-protein beta subunits, MtG beta 1 and PsG beta 1, respectively. RNAi-based suppression of MtGbeta1 and PsGbeta1 significantly decreased the number of nodules formed, suggesting the involvement of G-protein beta subunits in symbiosis in both legumes. Analysis of composite M. truncatula plants carrying the pMtGbeta1:GUS construct showed β-glucuronidase (GUS) staining in developing nodule primordia and young nodules, consistent with data on the role of G-proteins in controlling organ development and cell proliferation. In mature nodules, GUS staining was the most intense in the meristem and invasion zone (II), while it was less prominent in the apical part of the nitrogen-fixing zone (III). Thus, MtG beta 1 may be involved in the maintenance of meristem development and regulation of the infection process during symbiosis. Protein–protein interaction studies using co-immunoprecipitation revealed the possible composition of G-protein complexes and interaction of G-protein subunits with phospholipase C (PLC), suggesting a cross-talk between G-protein- and PLC-mediated signaling pathways in these legumes. Our findings provide direct evidence regarding the role of MtG beta 1 and PsG beta 1 in symbiosis development regulation.
Minimalizing Non-point Source Pollution Using a Cooperative Ion-Selective Electrode System for Estimating Nitrate Nitrogen in Soil
Authors: Su Rui , Wu Junfeng , Hu Jiandong , Ma Liuzheng , Ahmed Shakeel , Zhang Yanyan , Abdulraheem Mukhtar Iderawumi , Birech Zephania , Li Linze , Li Can , Wei Wentao
Published: April 2023

Nitrate nitrogen (NO3- -N) in the soil is one of the important nutrients for growing crops. During the period of precipitation or irrigation, an excessive NO3- -N readily causes its leaching or runoff from the soil surface to rivers due to inaccurate fertilization and water management, leading to non-point source pollution. In general, the measurement of the NO3--N relies upon the laboratory-based absorbance, which is often time-consuming, therefore not suitable for the rapid measurements in the field directly. Ion-selective electrodes (ISEs) support the possibility of NO3--N measurement by measuring the nitrate (NO3-) ions in soil quickly and accurately due to the high water solubility and mobility of NO3- ions. However, such a method suffers from a complicated calibration to remove the influences caused by both temperature and other ions in the measured solution, thus limiting field use. In this study, a kind of all-solid ISE system combined with a temperature sensor and a pH electrode is proposed to automatically measure the concentrations of the NO3--N. In this study, a soil water content calibration function was established, which significantly reduces a relative error (RE) by 13.09%. The experimental results showed that the stabilization time of this electrode system was less than 15 s with a slope of −51.63 mV/decade in the linear range of 10–5–10–2.2 mol/L. Both the limit of detection of 0.5 ppm of the NO3--N and a relative SD of less than 3% were obtained together with the recovery rate of 90–110%. Compared with the UV-Vis spectroscopy method, a correlation coefficient (R2) of 0.9952 was obtained. The performances of this all-solid ISE system are satisfied for measuring the NO3--N in the field.
Multi-model genome-wide association studies of leaf anatomical traits and vein architecture in rice
Authors: Narawatthana Supatthra , Phansenee Yotwarit , Thammasamisorn Bang-On , Vejchasarn Phanchita
Published: April 2023

Introduction

The anatomy of rice leaves is closely related to photosynthesis and grain yield. Therefore, exploring insight into the quantitative trait loci (QTLs) and alleles related to rice flag leaf anatomical and vein traits is vital for rice improvement.

Methods

Here, we aimed to explore the genetic architecture of eight flag leaf traits using one single-locus model; mixed-linear model (MLM), and two multi-locus models; fixed and random model circulating probability unification (FarmCPU) and Bayesian information and linkage disequilibrium iteratively nested keyway (BLINK). We performed multi-model GWAS using 329 rice accessions of RDP1 with 700K single-nucleotide polymorphisms (SNPs) markers.

Results

The phenotypic correlation results indicated that rice flag leaf thickness was strongly correlated with leaf mesophyll cells layer (ML) and thickness of both major and minor veins. All three models were able to identify several significant loci associated with the traits. MLM identified three non-synonymous SNPs near NARROW LEAF 1 (NAL1) in association with ML and the distance between minor veins (IVD) traits.

Discussion

Several numbers of significant SNPs associated with known gene function in leaf development and yield traits were detected by multi-model GWAS performed in this study. Our findings indicate that flag leaf traits could be improved via molecular breeding and can be one of the targets in high-yield rice development.
A comparison of three different delivery methods for achieving CRISPR/Cas9 mediated genome editing in Cichorium intybus L.
Authors: Salvagnin Umberto , Unkel Katharina , Sprink Thorben , Bundock Paul , Sevenier Robert , Bogdanović Milica , Todorović Slađana , Cankar Katarina , Hakkert Johanna Christina , Schijlen Elio , Nieuwenhuis Ronald , Hingsamer Maria , Kulmer Veronika , Kernitzkyi Michael , Bosch Dirk , Martens Stefan , Malnoy Mickael
Published: April 2023

Root chicory (Cichorium intybus L. var. sativum) is used to extract inulin, a fructose polymer used as a natural sweetener and prebiotic. However, bitter tasting sesquiterpene lactones, giving chicory its known flavour, need to be removed during inulin extraction. To avoid this extraction and associated costs, recently chicory variants with a lower sesquiterpene lactone content were created by inactivating the four copies of the germacrene A synthase gene (CiGAS-S1, -S2, -S3, -L) which encode the enzyme initiating bitter sesquiterpene lactone biosynthesis in chicory. In this study, different delivery methods for CRISPR/Cas9 reagents have been compared regarding their efficiency to induce mutations in the CiGAS genes, the frequency of off-target mutations as well as their environmental and economic impacts. CRISPR/Cas9 reagents were delivered by Agrobacterium-mediated stable transformation or transient delivery by plasmid or preassembled ribonucleic complexes (RNPs) using the same sgRNA. All methods used lead to a high number of INDEL mutations within the CiGAS-S1 and CiGAS-S2 genes, which match the used sgRNA perfectly; additionally, the CiGAS-S3 and CiGAS-L genes, which have a single mismatch with the sgRNA, were mutated but with a lower mutation efficiency. While using both RNPs and plasmids delivery resulted in biallelic, heterozygous or homozygous mutations, plasmid delivery resulted in 30% of unwanted integration of plasmid fragments in the genome. Plants transformed via Agrobacteria often showed chimerism and a mixture of CiGAS genotypes. This genetic mosaic becomes more diverse when plants were grown over a prolonged period. While the genotype of the on-targets varied between the transient and stable delivery methods, no off-target activity in six identified potential off-targets with two to four mismatches was found. The environmental impacts (greenhouse gas (GHG) emissions and primary energy demand) of the methods are highly dependent on their individual electricity demand. From an economic view - like for most research and development activities - employment and value-added multiplier effects are high; particularly when compared to industrial or manufacturing processes. Considering all aspects, we conclude that using RNPs is the most suitable method for genome editing in chicory since it led to a high efficiency of editing, no off-target mutations, non-transgenic plants with no risk of unwanted integration of plasmid DNA and without needed segregation of transgenes.
The combined formulation of brassinolide and pyraclostrobin increases biomass and seed yield by improving photosynthetic capacity in Arabidopsis thaliana
Authors: An Ya-Qi , Qin Zi-Ting , Li Dan-Dan , Zhao Rui-Qi , Bi Bo-Shi , Wang Da-Wei , Ma De-Jun , Xi Zhen
Published: April 2023

In the context of global food crisis, applying the phytohormone-brassinosteroids (BRs) in combination with the fungicide-pyraclostrobin (Pyr) was beneficial for plant quality and productivity in several field trials. However, in addition to the benefits of disease control due to the innate fungicidal activity of Pyr, it remains to be understood whether the coapplication of BL+ Pyr exerts additional growth-promoting effects. For this purpose, the effects of BL treatment, Pyr treatment, and BL+ Pyr treatment in Arabidopsis thaliana were compared. The results showed that the yield increased at a rate of 25.6% in the BL+Pyr group and 9.7% in the BL group, but no significant change was observed in the Pyr group. Furthermore, the BL+Pyr treatment increased the fresh weight of both the leaves and the inflorescences. In contrast, the Pyr and BL treatments only increased the fresh weight of leaves and inflorescences, respectively. Additionally, the BL + Pyr treatment increased the Pn, Gs, Tr, Vc, max, Jmax, VTPU, ETR, Fv’/Fm’, ΦPSII, Rd, AYE and Rubisco enzyme activity by 26%, 38%, 40%, 16%, 19%, 15%, 9%, 10%, 17%, 179%, 18% and 32%, respectively. While, these paraments did not change significantly by the BL or Pyr treatments. Treatment with BL + Pyr and Pyr, rather than BL, improved the chlorophyll a and chlorophyll b contents by upregulating genes related to chlorophyll biosynthesis and downregulating genes related to chlorophyll degradation. Additionally, according to transcriptomic and metabolomic analysis, the BL+ Pyr treatment outperformed the individual BL or Pyr treatments in activating the transcription of genes involved in photosynthesis and increasing sugar accumulation. Our results first validated that the combined usage of BL and Pyr exerted striking synergistic effects on enhancing plant biomass and yield by increasing photosynthetic efficiency. These results might provide new understanding for the agricultural effects by the co-application of BL and Pyr, and it might stimulate the efforts to develop new environment-friendly replacement for Pyr to minimize the ecotoxicology of Pyr.