bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization and antimicrobial susceptibility of human Brucella in Northeast China
Authors: Ma Han-rui , Xu Hui-jiao , Wang Xin , Bu Zhao-yang , Yao Teng , Zheng Zun-rong , Sun Yang , Ji Xue , Liu Jun
Published: April 2023

Introduction

Northeast China has always been an area with severe brucellosis prevalence. This study will identify Brucella in Northeast China and test its resistance to antibiotics, in order to clarify its resistance mechanism. Brucella is a widespread and highly pathogenic bacteria that poses serious threats to public health and animal husbandry.

Methods

In this study, 61 Brucella isolates were identified by abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR) for biotypes and epidemic potential was clarified by multi-locus sequence analysis. Whole-genome sequencing (WGS) was performed and the antibiotic susceptibility of the Brucella strains against 13 antibiotics was detected with the use of E-test strips.

Results

The results showed that all of the isolates were Brucella melitensis ST8, group CC4 with little genetic variation and obvious geographical characteristics. All 61 Brucella isolates were sensitive to doxycycline, tetracycline, minocycline, levofloxacin, ciprofloxacin, gentamicin, and streptomycin, while 24.6%, 86.9%, 65.6%, 27.9%, 3.3%, and 1.6% were resistant to rifampin, azithromycin, cefepime, cefoperazone/sulbactam, cefotaxime, and meperidine/sulfamethoxazole, respectively. This is the first report of cephalosporin-resistant B. melitensis in China. The WGS results indicated that about 60% of the antibiotic resistance genes were associated with efflux pumps (mainly the resistance nodulation division family).

Discussion

Brucellosis is usually treated with antibiotics for several months, which can easily lead to the emergence of antibiotic resistance. To ensure the effectiveness and safety of antibiotics for treatment of brucellosis, continuous surveillance of antibiotic susceptibility is especially important.
Removal of Pseudomonas fluorescens biofilms from pilot-scale food processing equipment using ozone-assisted cleaning-in-place
Authors: Tirpanci Sivri Goksel , Abdelhamid Ahmed G. , Kasler David R. , Yousef Ahmed E.
Published: April 2023

Biofilm formation in food processing environment and within equipment increases the risk of product spoilage and contamination with pathogens. Cleaning-in-place (CIP) operations are useful in removing soils and in sanitizing processing equipment, including eliminating biofilms. However, CIP is a resource-intensive process, particularly in the usage of chemical detergents, heat, and sanitizers. The current study was initiated to investigate the feasibility of integrating ozone into CIP operations to facilitate the elimination of Pseudomonas biofilm, with the long-term goal of decreasing the dependance on conventional cleaning and sanitizing reagents. To investigate integrating ozone into CIP, a robust biofilm of Pseudomonas fluorescens was developed on a pilot-scale food processing equipment after 2 days of incubation in 10% skim milk (skim milk-water mixture, 1:9 v/v) under stagnant conditions, followed by additional 5 days of circulation while feeding 10% fresh skim milk. CIP was applied using water prerinse at 22–25°C, alkaline cleaning with 0.2% potassium hydroxide at 50°C, and a final water rinse. These CIP operations reduced planktonic cell populations below the detection method’s limit but did not fully remove P. fluorescens biofilm from either smooth or rough surfaces of the processing equipment. When the CIP process was followed by application of an aqueous ozone step (10 ppm for 10 min), the treatment reduced biofilm cell population, on smooth and rough surfaces, below the recovery method’s detection limit (0.9 and 1.4 log CFU/ 100 cm2, respectively). These findings demonstrate the utility of ozone-assisted CIP in eliminating microbial biofilms on processing equipment, but further research is needed to optimize the use of cleaning agents and the application of ozone.
Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
Authors: Su Kuan-Jui , Chen Xing-Ying , Gong Rui , Zhao Qi , Hu Shi-Di , Feng Mei-Chen , Li Ye , Lin Xu , Zhang Yin-Hua , Greenbaum Jonathan , Tian Qing , Shen Hui , Xiao Hong-Mei , Shen Jie , Deng Hong-Wen
Published: April 2023

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.
Cryptococcal infection causing longitudinal extensive transverse myelitis in an immunocompetent individual: Case report and literature review
Authors: Panda Ashwin Kumar , Hazra Sourav , Anthony Aldrin , Kushwaha Suman
Published: April 2023

Cryptococcal CNS infections in immunocompetent individuals are occasionally reported in literature. The spinal manifestations of cryptococcal CNS infections are epidural abscess, chronic arachnoiditis, intramedullary granuloma, myelitis and vasculitis. We report a rare case of CNS cryptococcal infection presenting as a longitudinal extensive transverse myelitis (LETM) in an immunocompetent male. This report highlights cryptococcus as an important etiology among infectious causes in acute LETM patients in-spite of the immunocompetent status of the patient and the utility of CRAG (cryptococcal antigen) for diagnosis in such patients. We also present a literature review of all reported cases of cryptococcal myelitis.
Case Report: Zolpidem’s paradoxical restorative action: A case report of functional brain imaging
Authors: Boisgontier Jennifer , Beccaria Kévin , Saitovitch Ana , Blauwblomme Thomas , Guida Lelio , Fillon Ludovic , Dufour Christelle , Grill Jacques , Lemaitre Hervé , Puget Stéphanie , Vinçon-Leite Alice , Dangouloff-Ros Volodia , Charpy Sarah , Benichi Sandro , Levy Raphaël , Roux Charles-Joris , Grévent David , Bourgeois Marie , Saidoun Lila , Gaillard Raphaël , Zilbovicius Monica , Boddaert Nathalie
Published: April 2023

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca’s area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.
The effect of orthokeratology lenses on optical quality and visual function in children
Authors: Lu Weiwei , Song Guanxin , Zhang Yuhan , Lian Yan , Ma Ke , Lu Qingqing , Jin Yiyu , Zhao Yang , Zhang Shuyu , Lv Fan , Jin Wanqing
Published: April 2023

Purpose

To assess changes in optical quality and visual function in children after 3 months of wearing orthokeratology (OK) lenses.

Methods

A total of 25 myopic children aged 8–12 years were recruited and completed the follow-up study. Optical quality, visual function and corneal morphology were assessed at baseline and at follow-ups 1 and 3 months after wearing OK lenses. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, objective scattering index (OSI), Strehl ratio (SR) and the predicted visual acuities (PVAs). Visual function was assessed by visual acuity, monocular contrast sensitivity function (CSF) across five spatial frequencies and the area under the log contrast sensitivity function (AULCSF) that was also computed as an index for overall CSF.

Results

The MTF cutoff and SR values both increased after 1 month of wearing the OK lenses (baseline vs. 1 month: PMTF = 0.008 and PSR = 0.049); this improvement plateaued after 3 months of lens wear (1 month vs. 3 months: PMTF = 0.626, PSR = 0.428). The corneal morphology also showed the similar change trend. The OSI showed the opposite change trend (baseline vs. 1 month: POSI < 0.001; 1 month vs. 3 months: POSI = 0.720). The mean CSF at 1.5 cpd decreased significantly after 1 month of wearing the lenses (baseline vs. 1 month: p = 0.001) and recovered after 3 months of lens wear (baseline vs. 3 months: p = 0.076). CSF at spatial frequencies of 3, 6, 12 and 18 cpd as well as the AULCSF did not significantly differ between any two timepoints (all Ps > 0.05).

Conclusion

After 3 months of wearing OK lenses, the subjects exhibited a decrease in optical quality, similar to corneal morphology, whereas their visual function remained largely unchanged. Thus, the optical quality was more susceptible to OK lenses than visual function in children. The initial month of OK treatment of children is a key period to be paid close attention to deterioration of optical quality and visual function.
Neurobiological mechanisms involved in maternal deprivation-induced behaviours relevant to psychiatric disorders
Authors: Zanta Natália Cristina , Assad Nadyme , Suchecki Deborah
Published: April 2023

Parental care is essential for proper development of stress response and emotion-related behaviours. Epidemiological studies show that parental loss in childhood represents a major risk factor for the development of mental disorders throughout the lifespan, including schizophrenia, depression, and anxiety. In most mammalian species, the mother is the main source of care and maternal behaviours regulate several physiological systems. Maternal deprivation (DEP) for 24 h is a paradigm widely used to disinhibit the hypothalamic–pituitary–adrenal axis response to stress during the stress hyporesponsive period. In this mini-review we will highlight the main DEP-induced neurobiological and behavioural outcomes, including alterations on stress-related hormones, neurogenesis, neurotransmitter/neuromodulatory systems and neuroinflammation. These neurobiological changes may be reflected by aberrant behaviours, which are relevant to the study of mental disorders. The evidence indicates that DEP consequences depend on the sex, the age when the DEP takes place and the age when the animals are evaluated, reflecting dynamic plasticity and individual variability. Individual variability and sex differences have a great relevance for the study of biological factors of stress resilience and vulnerability and the DEP paradigm is a suitable model for evaluation of phenotypes of stress- and emotion-related psychopathologies.
Regional and age-dependent changes in ubiquitination in cellular and mouse models of spinocerebellar ataxia type 3
Authors: Luo Haiyang , Todi Sokol V. , Paulson Henry L. , Costa Maria do Carmo
Published: April 2023

Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, is the most common dominantly inherited ataxia. SCA3 is caused by a CAG repeat expansion in the ATXN3 gene that encodes an expanded tract of polyglutamine in the disease protein ataxin-3 (ATXN3). As a deubiquitinating enzyme, ATXN3 regulates numerous cellular processes including proteasome- and autophagy-mediated protein degradation. In SCA3 disease brain, polyQ-expanded ATXN3 accumulates with other cellular constituents, including ubiquitin (Ub)-modified proteins, in select areas like the cerebellum and the brainstem, but whether pathogenic ATXN3 affects the abundance of ubiquitinated species is unknown. Here, in mouse and cellular models of SCA3, we investigated whether elimination of murine Atxn3 or expression of wild-type or polyQ-expanded human ATXN3 alters soluble levels of overall ubiquitination, as well as K48-linked (K48-Ub) and K63-linked (K63-Ub) chains. Levels of ubiquitination were assessed in the cerebellum and brainstem of 7- and 47-week-old Atxn3 knockout and SCA3 transgenic mice, and also in relevant mouse and human cell lines. In older mice, we observed that wild-type ATXN3 impacts the cerebellar levels of K48-Ub proteins. In contrast, pathogenic ATXN3 leads to decreased brainstem abundance of K48-Ub species in younger mice and changes in both cerebellar and brainstem K63-Ub levels in an age-dependent manner: younger SCA3 mice have higher levels of K63-Ub while older mice have lower levels of K63-Ub compared to controls. Human SCA3 neuronal progenitor cells also show a relative increase in K63-Ub proteins upon autophagy inhibition. We conclude that wild-type and mutant ATXN3 differentially impact K48-Ub- and K63-Ub-modified proteins in the brain in a region- and age-dependent manner.
Observation of the application effect of low-volume polyethylene glycol electrolyte lavage solution (PEG-ELS) combined with ascorbic acid tablets in bowel preparation for colonoscopy in hospitalized patients
Authors: Wu Le-Can , Zheng En-Dian , Sun Hao-Yue , Lin Xi-Zhou , Pan Ju-Yi , Lin Xiao-Xiao
Published: April 2023

Background

This study explored the effectiveness and safety of low-volume polyethylene glycol electrolyte lavage solution (PEG-ELS) combined with ascorbic acid tablets (PEG-ELS/Asc) in bowel preparation for a colonoscopy.

Methods

A total of 240 hospitalized patients who underwent a colonoscopy in Wenzhou People’s Hospital, Wenzhou Third Clinical College of Wenzhou Medical University from July 2020 to June 2022 were randomly divided into two groups, with 120 patients each. All of the participants were given a low-residue or residue-free diet one day before the examination and fasted after dinner (completed before 18:00) the day before the examination. The 2-L PEG-ELS/Asc group took 2-L PEG-ELS plus 10 g ascorbic acid tablets once orally, while the 3-L PEG-ELS group took 3-L PEG orally on several occasions. The primary endpoint was the achievement of preparation adequacy and an overall colon cleansing score of ≥6, both assessed by blinded investigators using the Boston Bowel Preparation Scale (BBPS). The bowel cleansing effect, polyp detection rate, adverse reaction rate, oral drug tolerance rate, renal function, and electrolyte level changes were also compared between the two patient groups.

Results

There were no significant differences in the success rate of bowel preparation, the detection rate of polyps, or the adverse reaction rate between the two groups (P > 0.05). The tolerance rate of bowel preparation in the 2-L PEG-ELS/Asc group was significantly higher than that in the 3-L PEG-ELS group (93.3% vs. 80.23%) (P < 0.05). The levels of creatinine, serum potassium, serum sodium, and serum chlorine of the two groups before and after bowel preparation were within the normal range. In addition, the intestinal cleaning effect of the two preparation schemes for the hospitalized patients with diabetes and constipation is worse than that of those without these conditions (P < 0.05).

Conclusion

The effectiveness and safety of using 2-L PEG-ELS/Asc in bowel preparation for a colonoscopy in hospitalized patients were not inferior to using 3-L PEG-ELS. For patients with diabetes and constipation, the cleansing effect of the two bowel preparation options was not very satisfactory, and further clinical research is needed in this regard.
Medical image segmentation based on self-supervised hybrid fusion network
Authors: Zhao Liang , Jia Chaoran , Ma Jiajun , Shao Yu , Liu Zhuo , Yuan Hong
Published: April 2023

Automatic segmentation of medical images has been a hot research topic in the field of deep learning in recent years, and achieving accurate segmentation of medical images is conducive to breakthroughs in disease diagnosis, monitoring, and treatment. In medicine, MRI imaging technology is often used to image brain tumors, and further judgment of the tumor area needs to be combined with expert analysis. If the diagnosis can be carried out by computer-aided methods, the efficiency and accuracy will be effectively improved. Therefore, this paper completes the task of brain tumor segmentation by building a self-supervised deep learning network. Specifically, it designs a multi-modal encoder-decoder network based on the extension of the residual network. Aiming at the problem of multi-modal feature extraction, the network introduces a multi-modal hybrid fusion module to fully extract the unique features of each modality and reduce the complexity of the whole framework. In addition, to better learn multi-modal complementary features and improve the robustness of the model, a pretext task to complete the masked area is set, to realize the self-supervised learning of the network. Thus, it can effectively improve the encoder’s ability to extract multi-modal features and enhance the noise immunity. Experimental results present that our method is superior to the compared methods on the tested datasets.
Chemotherapy-free treatment for acute promyelocytic leukemia: the pediatric view of a revolutionary tale
Authors: Masetti Riccardo , Muratore Edoardo , Leardini Davide , Baccelli Francesco , Pession Andrea , Prete Arcangelo , Locatelli Franco
Published: April 2023

The addition of all-trans retinoic acid (ATRA) to the standard anthracycline-base chemotherapy has revolutionized the treatment of acute promyelocytic leukemia (APL) over the last decades, becoming a model for precision medicine. The protocols based on the combination of ATRA and chemotherapy allowed obtaining excellent response rates both for children and adults. However, the persistence of anthracycline chemotherapy as a backbone was a matter of concern for both acute and long-term complications. Efforts in reducing anthracycline cumulative dose or even eliminating anthracycline have been pursued in more recent pediatric protocols thanks to the introduction of arsenic trioxide (ATO). The impressive results of the ATRA/ATO combinations led to the introduction of protocols completely chemotherapy-free for standard-risk adult patients as the standard of care, whereas pediatric chemo-free protocols are still currently under evaluation. In this Review, we will critically retrace the history of this unique revolution in precision medicine, discussing the peculiar advantages for pediatric patients with APL.
The mortality risk in patients with early onset colorectal cancer: the role of comorbidities
Authors: Yu Shou-Chun , Shiue Yow-Ling , Wu Yu-Cih , Wang Jhi-Joung , Liao Kuang-Ming , Ho Chung-Han
Published: April 2023

The global incidence of early-onset colorectal cancer (EO-CRC) is increasing. Although the mortality rate is relatively stable, some comorbidities have been associated with a higher mortality rate. This study estimated the mortality risk in patients with EO-CRC with various comorbidities using real-world data to identify the high-risk group using Cox proportional regression for overall and cancer-specific mortality. The incidence rate of EO-CRC significantly increased from 6.04 per 100,000 population in 2007 to 12.97 per 100,000 population in 2017. The five-year overall mortality rate was 101.50 per 1000 person year and the cancer-specific mortality rate was 94.12 per 1000 person year. Patients with cerebrovascular disease (CVD) had a higher mortality risk (hazard ratio (HR): 1.68; 95% confidence interval (CI): 1.25-2.28; p=0.0007). After subgroup analyses based on age, sex, clinical stage, and treatment type, patients with CVD had a higher overall mortality risk compared to non-CVD patients, except for patients undergoing surgery and chemotherapy. Patients with chronic kidney disease had a higher mortality risk in the early clinical stages (HR: 2.31; 95% CI: 1.08-4.96; p=0.0138). Patients who underwent radiotherapy had a higher overall mortality risk (HR: 1.38; 95% CI: 1.04-1.85; p=0.0285) than those without liver disease. Identifying specific comorbidity mortality risks in patients with EO-CRC allows for risk stratification when screening target groups and may lower disease mortality.
Combined CT and serum CA19-9 for stratifying risk for progression in patients with locally advanced pancreatic cancer receiving intraoperative radiotherapy
Authors: Cai Wei , Zhu Yongjian , Teng Ze , Li Dengfeng , Feng Qinfu , Jiang Zhichao , Cong Rong , Chen Zhaowei , Liu Siyun , Zhao Xinming , Ma Xiaohong
Published: April 2023

Background and purpose

The aim of this study was to evaluate the significance of baseline computed tomography (CT) imaging features and carbohydrate antigen 19-9 (CA19-9) in predicting prognosis of locally advanced pancreatic cancer (LAPC) receiving intraoperative radiotherapy (IORT) and to establish a progression risk nomogram that helps to identify the potential beneficiary of IORT.

Methods

A total of 88 LAPC patients with IORT as their initial treatment were enrolled retrospectively. Clinical data and CT imaging features were analyzed. Cox regression analyses were performed to identify the independent risk factors for progression-free survival (PFS) and to establish a nomogram. A risk-score was calculated by the coefficients of the regression model to stratify the risk of progression.

Results

Multivariate analyses revealed that relative enhanced value in portal-venous phase (REV-PVP), peripancreatic fat infiltration, necrosis, and CA19-9 were significantly associated with PFS (all p < 0.05). The nomogram was constructed according to the above variables and showed a good performance in predicting the risk of progression with a concordance index (C-index) of 0.779. Our nomogram stratified patients with LAPC into low- and high-risk groups with distinct differences in progression after IORT (p < 0.001).

Conclusion

The integrated nomogram would help clinicians to identify appropriate patients who might benefit from IORT before treatment and to adapt an individualized treatment strategy.
Metabonomic analysis of tumor microenvironments: a mini-review
Authors: Zeng Zeng , Chen Cong-Xian
Published: April 2023

Metabolomic analysis is a vital part of studying cancer progression. Metabonomic crosstalk, such as nutrient availability, physicochemical transformation, and intercellular interactions can affect tumor metabolism. Many original studies have demonstrated that metabolomics is important in some aspects of tumor metabolism. In this mini-review, we summarize the definition of metabolomics and how it can help change a tumor microenvironment, especially in pathways of three metabonomic tumors. Just as non-invasive biofluids have been identified as early biomarkers of tumor development, metabolomics can also predict differences in tumor drug response, drug resistance, and efficacy. Therefore, metabolomics is important for tumor metabolism and how it can affect oncology drugs in cancer therapy.
MicroRNA-494 augments fibrotic transformation of human retinal pigment epithelial cells and targets p27 with cell-type specificity
Authors: Leng Theodore , Kamboj Georgia , Sun Xiaoyun , Chang Heather , Davda Prisha , Greer Majesty , Stary Creed M.
Published: April 2023

Epiretinal membranes (ERMs) are the result of fibro-cellular proliferation that cause distortion and impairment of central vision. We hypothesized that select microRNAs (miRs) regulate retinal fibro-proliferation and ERM formation. Following IRB approval, a pilot study was performed in patients presenting for retina surgery with and without clinical ERMs. Total RNA was isolated from ERM tissue and controls from non-ERM vitreous and subjected to miR profiling via microarray analysis. MiR-494 was identified as the only miR selectively expressed at significantly greater levels, and in silico analysis identified p27 as a putative fibroproliferative gene target of miR-494. In vitro testing of miR-494 and p27 in fibrotic transformation was assessed in spontaneously immortalized human retinal pigment epithelial (RPE) and human Müller cell lines, stimulated to transform into a fibroproliferative state via transforming growth factor beta (TGFβ). Fibroproliferative transformation was characterized by de novo cellular expression of alpha smooth muscle actin (αSMA). In both RPE and Müller cells, both TGFβ and miR-494 mimic decreased p27 expression. In parallel experiments, transfection with p27 siRNA augmented TGFβ-induced αSMA expression, while only in RPE cells did co-transfection with miR-494 inhibitor decrease αSMA levels. These results demonstrate that miR-494 augments fibrotic transformation in both Müller cells and RPEs, however only in RPEs does miR-494 mediate fibrotic transformation via p27. As p27 is known to regulate cellular proliferation and differentiation, future studies should extend clinical testing of miR-494 and/or p27 as a potential novel non-surgical therapy for ERMs, as well as identify relevant miR-494 targets in Müller cells.
Drug-induced tooth discoloration: An analysis of the US food and drug administration adverse event reporting system
Authors: Wang Jun , Zou Dongna , Li Yuchao , Liu Pingping , Guo Chenyu
Published: April 2023

Background: Certain drugs can cause intrinsic or extrinsic tooth discoloration, which is not only a clinical issue but also an esthetic problem. However, limited investigations have focused on drug-induced tooth discoloration. The present work aimed to determine the drugs causing tooth discoloration and to estimate their risks of causing tooth discoloration.

Methods: An observational, retrospective, and pharmacovigilance analysis was conducted, in which we extracted adverse event (AE) reports involving tooth discoloration by using the data of the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021. Disproportionality analyses were performed to examine risk signals for tooth discoloration and determine the drugs inducing tooth discoloration.

Results: Based on predefined inclusion criteria, 1188 AE reports involving 302 suspected drugs were identified. After data mining, 25 drugs generated positive risk signals for tooth discoloration, of which 10 were anti-infectives for systemic use. The top reported drug was tetracycline (n = 106), followed by salmeterol and fluticasone (n = 68), amoxicillin (n = 60), chlorhexidine (n = 54), and nicotine (n = 52). Cetylpyridinium (PRR = 472.2, ROR = 502.5), tetracycline (PRR = 220.4, ROR = 277), stannous fluoride (PRR = 254.3, ROR = 262.8), hydrogen peroxide (PRR = 240.0, ROR = 247.6), and chlorhexidine (PRR = 107.0, ROR = 108.4) showed stronger associations with tooth discoloration than the remaining drugs. Of 625 AE reports involving 25 drugs with positive risk signals, tooth discoloration was mostly reported in patients aged 45–64 (n = 110) and ≤18 (n = 95), and 29.4% (192/652) of the reports recorded serious outcomes.

Conclusion: This study revealed that certain drugs are significantly associated with tooth discoloration. Caution should be exercised when using these drugs, especially during pregnancy and early childhood.
Hydrogen sulfide plays an important role by regulating endoplasmic reticulum stress in myocardial diseases
Authors: Zhao Huijie , Fu Xiaodi , Zhang Yanting , Yang Yihan , Wang Honggang
Published: April 2023

Endoplasmic reticulum (ER) is an important organelle for protein translation, folding and translocation, as well as the post-translational modification and assembly of newly synthesized secreted proteins. When the excessive accumulation of misfolded and/or unfolded proteins exceeds the processing capacity of ER, ER stress is triggered. The integrated intracellular signal cascade, namely the unfolded protein response, is induced to avoid ER stress. ER stress is involved in many pathological and physiological processes including myocardial diseases. For a long time, hydrogen sulfide (H2S) has been considered as a toxic gas with the smell of rotten eggs. However, more and more evidences indicate that H2S is an important gas signal molecule after nitric oxide and carbon monoxide, and regulates a variety of physiological and pathological processes in mammals. In recent years, increasing studies have focused on the regulatory effects of H2S on ER stress in myocardial diseases, however, the mechanism is not very clear. Therefore, this review focuses on the role of H2S regulation of ER stress in myocardial diseases, and deeply analyzes the relevant mechanisms so as to lay the foundation for the future researches.
Highly accurate and reliable ultrasonic focusing capability in heterogeneous media using a spherical cavity transducer
Authors: Song Dan , Xiong Jiupeng , Luo Man , Gong Xiaobo , Huang Wenjun , Zeng Chen , Zhou Yufeng , Li Faqi , Wang Zhibiao
Published: April 2023

Introduction: Focused ultrasound ablation surgery (FUAS) has been emerging to treat a wide range of conditions non-invasively and effectively with promising therapeutic outcomes. The focusing capability of an ultrasound transducer (i.e., focus shift, beam distortion, and acoustic pressure at the focus) determines the ablation effects. However, the focus shift and focal beam distortion after ultrasound propagating through multi-layered heterogeneous viscoelastic biological tissues become significant and are found to deteriorate the performance of FUAS in clinics.

Methods: To achieve an accurate and reliable focal field among patients with large variations in the anatomical structures and properties, a spherical cavity transducer with open ends and sub-wavelength focal size (Li et al., APL, 2013,102:204102) was applied here. Both experimental measurements and numerical simulations were performed to characterize the acoustic fields of the spherical cavity transducer in water, the multi-layered concentric cylindrical phantom, and the heterogeneous tissue model (an adult male pelvis enclosed by porcine skin, fat, and muscle) and then compared with those of a conventional concave transducer at the same electrical power output.

Results: It is found that standing-wave focusing using the spherical cavity transducer results in much less focus shift (0.25λ vs. 1.67λ) along the transducer axis and focal beam distortion (−6 dB beam area of 0.71 mm2vs. 4.72 mm2 in water and 2.55 mm2vs. 17.30 mm2 in tissue) in the focal plane but higher pressure focusing gain (40.05 dB vs. 33.61 dB in tissue).

Discussion: Such a highly accurate and reliable focal field is due to the excitation at an appropriate eigen-frequency of the spherical cavity with the varied media inside rather than the reverberation from the concave surface. Together with its sub-wavelength focal size, the spherical cavity transducer is technically advantageous in comparison to the concave one. The improved focusing capability would benefit ultrasound exposure for not only safer and more effective FUAS in clinics, but also broad acoustic applications.
Automatic acoustic recognition of pollinating bee species can be highly improved by Deep Learning models accompanied by pre-training and strong data augmentation
Authors: Ferreira Alef Iury Siqueira , da Silva Nádia Felix Felipe , Mesquita Fernanda Neiva , Rosa Thierson Couto , Monzón Victor Hugo , Mesquita-Neto José Neiva
Published: April 2023

Introduction

Bees capable of performing floral sonication (or buzz-pollination) are among the most effective pollinators of blueberries. However, the quality of pollination provided varies greatly among species visiting the flowers. Consequently, the correct identification of flower visitors becomes indispensable to distinguishing the most efficient pollinators of blueberry. However, taxonomic identification normally depends on microscopic characteristics and the active participation of experts in the decision-making process. Moreover, the many species of bees (20,507 worldwide) and other insects are a challenge for a decreasing number of insect taxonomists. To overcome the limitations of traditional taxonomy, automatic classification systems of insects based on Machine-Learning (ML) have been raised for detecting and distinguishing a wide variety of bioacoustic signals, including bee buzzing sounds. Despite that, classical ML algorithms fed by spectrogram-type data only reached marginal performance for bee ID recognition. On the other hand, emerging systems from Deep Learning (DL), especially Convolutional Neural Networks (CNNs), have provided a substantial boost to classification performance in other audio domains, but have yet to be tested for acoustic bee species recognition tasks. Therefore, we aimed to automatically identify blueberry pollinating bee species based on characteristics of their buzzing sounds using DL algorithms.

Methods

We designed CNN models combined with Log Mel-Spectrogram representations and strong data augmentation and compared their performance at recognizing blueberry pollinating bee species with the current state-of-the-art models for automatic recognition of bee species.

Results and Discussion

We found that CNN models performed better at assigning bee buzzing sounds to their respective taxa than expected by chance. However, CNN models were highly dependent on acoustic data pre-training and data augmentation to outperform classical ML classifiers in recognizing bee buzzing sounds. Under these conditions, the CNN models could lead to automating the taxonomic recognition of flower-visiting bees of blueberry crops. However, there is still room to improve the performance of CNN models by focusing on recording samples for poorly represented bee species. Automatic acoustic recognition associated with the degree of efficiency of a bee species to pollinate a particular crop would result in a comprehensive and powerful tool for recognizing those that best pollinate and increase fruit yields.
Contributions of leaf distribution and leaf functions to photosynthesis and water-use efficiency from leaf to canopy in apple: A comparison of interstocks and cultivars
Authors: Zhang Xiaoyun , Yang Weiwei , Tahir Muhammad Mobeen , Chen Xilong , Saudreau Marc , Zhang Dong , Costes Evelyne
Published: April 2023

Grafting has been widely used in horticulture to induce dwarfing and avoid stress-derived limitations on plant growth and yield by affecting plant architecture and leaf functions. However, the respective effects on plant photosynthesis and water use efficiency (WUE) of leaf distribution and functions that depend on both rootstock and scion have not been fully elucidated. This study aimed to (i) clarify the scion × interstock impacts on the variability of leaf photosynthetic traits and WUE, and (ii) decipher the respective effects of leaf distribution and functions on canopy photosynthesis and WUE (WUEc). Leaf gas exchange over light gradients and responses to light, CO2, temperature, and vapor pressure deficit were measured in two apple cultivars, ‘Liquan Fuji’ (‘Fuji’) and ‘Regal Gala’ (‘Gala’), grafted onto rootstocks combined with interstocks: a vigorous (VV, ‘Qinguan’), or a dwarf one (VD, M26). The 3D architecture-based RATP model was parameterized to estimate the canopy photosynthesis rate (Ac), transpiration rate (Ec), and WUEc. Then, virtual scenarios were used to compare the relative contributions of cultivar and interstock to canopy Ac, Ec, and WUEc. These scenarios changed the leaf distribution and functions of either cultivar or interstock. At the leaf scale, VD trees had significantly higher leaf nitrogen per area but a lower maximum carboxylation rate and dark respiration in both cultivars. In parallel with higher leaf stomatal conductance (gs) and transpiration in VD ‘Fuji’ and similar gs in VD ‘Gala’, VD trees showed significantly lower leaf photosynthesis rate and WUE than VV trees. However, lower leaf photosynthetic capacities in VD trees were compensated at the canopy scale, with Ac and WUEc for ‘Fuji’ significantly improved in VD trees under both sunny and cloudy conditions, and for ‘Gala’ significantly improved in VD trees under cloudy conditions compared with VV trees. Switching scenarios highlighted that ‘Gala’ leaf functions and distribution and VD leaf distributions enhanced Ac and WUEc simultaneously, irrespective of weather conditions. Up-scaling leaf gas exchange to the canopy scale by utilizing 3D architecture-based modeling and reliable measurements of tree architecture and leaf functional traits provides insights to explore the influence of genetic materials and tree management practices.
Heterologous expression of MirMAN enhances root development and salt tolerance in Arabidopsis
Authors: Xu Juanjuan , Yang Caiyu , Ji Shangyao , Ma Hui , Lin Jingwei , Li Hui , Chen Shuisen , Xu Hai , Zhong Ming
Published: April 2023

Introduction

β-Mannanase is a plant cell wall remodeling enzyme involved in the breakdown of hemicellulose and plays an important role in growth by hydrolyzing the mannan-like polysaccharide, but its function in adaptation to salt stress has been less studied.

Methods

Based on cloned the mannanase (MAN) gene from Mirabilis jalapa L., the study was carried out by heterologously expressing the gene in Arabidopsis thaliana, and then observing the plant phenotypes and measuring relevant physiological and biochemical indicators under 150 mM salt treatment.

Results and discussion

The results indicate that MirMAN is a protein with a glycohydrolase-specific structural domain located in the cell wall. We first found that MirMAN reduced the susceptibility of transgenic Arabidopsis thaliana to high salt stress and increased the survival rate of plants by 38%. This was corroborated by the following significant changes, including the reduction in reactive oxygen species (ROS) levels, increase in antioxidant enzyme activity, accumulation of soluble sugars and increase of the expression level of RD29 in transgenic plants. We also found thatthe heterologous expression of MirMAN promoted root growth mainly by elongating the primary roots and increasing the density of lateral roots. Meanwhile, the expression of ARF7, ARF19, LBD16 and LBD29 was up-regulated in the transgenic plants, and the concentration of IAA in the roots was increased. Those results indicate that MirMAN is involved in the initiation of lateral root primordia in transgenic plants through the IAA-ARF signalling pathway. In conclusion, MirMAN improves plant salt tolerance not only by regulating ROS homeostasis, but also by promoting the development of lateral roots. Reflecting the potential of the MirMAN to promote root plastic development in adaptation to salt stress adversity.
Biochemical basis for the formation of organ-specific volatile blends in mint
Authors: Lange B. Markus , Srividya Narayanan , Lange Iris , Parrish Amber N. , Benzenberg Lukas R. , Pandelova Iovanna , Vining Kelly J. , Wüst Matthias
Published: April 2023

Above-ground material of members of the mint family is commercially distilled to extract essential oils, which are then formulated into a myriad of consumer products. Most of the research aimed at characterizing the processes involved in the formation of terpenoid oil constituents has focused on leaves. We now demonstrate, by investigating three mint species, peppermint (Mentha ˣ piperita L.), spearmint (Mentha spicata L.) and horsemint (Mentha longifolia (L.) Huds.; accessions CMEN 585 and CMEN 584), that other organs – namely stems, rhizomes and roots – also emit volatiles and that the terpenoid volatile composition of these organs can vary substantially from that of leaves, supporting the notion that substantial, currently underappreciated, chemical diversity exists. Differences in volatile quantities released by plants whose roots had been dipped in a Verticillium dahliae-spore suspension (experimental) or dipped in water (controls) were evident: increases of some volatiles in the root headspace of mint species that are susceptible to Verticillium wilt disease (peppermint and M. longifolia CMEN 584) were detected, while the quantities of certain volatiles decreased in rhizomes of species that show resistance to the disease (spearmint and M. longifolia CMEN 585). To address the genetic and biochemical basis underlying chemical diversity, we took advantage of the newly sequenced M. longifolia CMEN 585 genome to identify candidate genes putatively coding for monoterpene synthases (MTSs), the enzymes that catalyze the first committed step in the biosynthesis of monoterpenoid volatiles. The functions of these genes were established by heterologous expression in Escherichia coli, purification of the corresponding recombinant proteins, and enzyme assays, thereby establishing the existence of MTSs with activities to convert a common substrate, geranyl diphosphate, to (+)-α-terpineol, 1,8-cineole, γ-terpinene, and (–)-bornyl diphosphate, but were not active with other potential substrates. In conjunction with previously described MTSs that catalyze the formation of (–)-β-pinene and (–)-limonene, the product profiles of the MTSs identified here can explain the generation of all major monoterpene skeletons represented in the volatiles released by different mint organs.
Medicago truncatula quantitative resistance to a new strain of Verticillium alfalfae from Iran revealed by a genome-wide association study
Authors: Fartash Amir Hossein , Ben Cécile , Mazurier Mélanie , Ebrahimi Asa , Ghalandar Mojtaba , Gentzbittel Laurent , Rickauer Martina
Published: April 2023

Verticillium wilt is a major threat to many crops, among them alfalfa (Medicago sativa). The model plant Medicago truncatula, a close relative of alfalfa was used to study the genetic control of resistance towards a new Verticillium alfalfae isolate. The accidental introduction of pathogen strains through global trade is a threat to crop production and such new strains might also be better adapted to global warming. Isolates of V. alfalfae were obtained from alfalfa fields in Iran and characterized. The Iranian isolate AF1 was used in a genome-wide association study (GWAS) involving 242 accessions from the Mediterranean region. Root inoculations were performed with conidia at 25°C and symptoms were scored regularly. Maximum Symptom Score and Area under Disease Progess Curve were computed as phenotypic traits to be used in GWAS and for comparison to a previous study with French isolate V31.2 at 20°C. This comparison showed high correlation with a shift to higher susceptibility, and similar geographical distribution of resistant and susceptible accessions to AF1 at 25°C, with resistant accessions mainly in the western part. GWAS revealed 30 significant SNPs linked to resistance towards isolate AF1. None of them were common to the previous study with isolate V31.2 at 20°C. To confirm these loci, the expression of nine underlying genes was studied. All genes were induced in roots following inoculation, in susceptible and resistant plants. However, in resistant plants induction was higher and lasted longer. Taken together, the use of a new pathogen strain and a shift in temperature revealed a completely different genetic control compared to a previous study that demonstrated the existence of two major QTLs. These results can be useful for Medicago breeding programs to obtain varieties better adapted to future conditions.
Responses of differential metabolites and pathways to high temperature in cucumber anther
Authors: Chen Lin , Liang Zhaojun , Xie Shuyan , Liu Wenrui , Wang Min , Yan Jinqiang , Yang Songguang , Jiang Biao , Peng Qingwu , Lin Yu’e
Published: April 2023

Cucumber is one of the most important vegetable crops, which is widely planted all over the world. Cucumber always suffers from high-temperature stress in South China in summer. In this study, liquid chromatography–mass spectrometry (LC-MS) analysis was used to study the differential metabolites of cucumber anther between high-temperature (HT) stress and normal condition (CK). After HT, the pollen fertility was significantly reduced, and abnormal anther structures were observed by the paraffin section. In addition, the metabolomics analysis results showed that a total of 125 differential metabolites were identified after HT, consisting of 99 significantly upregulated and 26 significantly downregulated metabolites. Among these differential metabolites, a total of 26 related metabolic pathways were found, and four pathways showed significant differences, namely, porphyrin and chlorophyll metabolism; plant hormone signal transduction; amino sugar and nucleotide sugar metabolism; and glycine, serine, and threonine metabolism. In addition, pollen fertility was decreased by altering the metabolites of plant hormone signal transduction and amino acid and sugar metabolism pathway under HT. These results provide a comprehensive understanding of the metabolic changes in cucumber anther under HT.