bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulsive choice in two different rat models of ADHD—Spontaneously hypertensive and Lphn3 knockout rats
Authors: Carbajal Monica S. , Bounmy Asiah J. C. , Harrison Olivia B. , Nolen Hunter G. , Regan Samantha L. , Williams Michael T. , Vorhees Charles V. , Sable Helen J. K.
Published: January 2023

Introduction

Impulsivity is a symptom of attention-deficit/hyperactivity disorder (ADHD) and variants in the Lphn3 (Adgrl3) gene (OMIM 616417) have been linked to ADHD. This project utilized a delay-discounting (DD) task to examine the impact of Lphn3 deletion in rats on impulsive choice. “Positive control” measures were also collected in spontaneously hypertensive rats (SHRs), another animal model of ADHD.

Methods

For Experiment I, rats were given the option to press one lever for a delayed reward of 3 food pellets or the other lever for an immediate reward of 1 pellet. Impulsive choice was measured as the tendency to discount the larger, delayed reward. We hypothesized that impulsive choice would be greater in the SHR and Lphn3 knockout (KO) rats relative to their control strains - Wistar-Kyoto (WKY) and Lphn3 wildtype (WT) rats, respectively.

Results

The results did not completely support the hypothesis, as only the SHRs (but not the Lphn3 KO rats) demonstrated a decrease in the percent choice for the larger reward. Because subsequent trials did not begin until the end of the delay period regardless of which lever was selected, rats were required to wait for the next trial to start even if they picked the immediate lever. Experiment II examined whether the rate of reinforcement influenced impulsive choice by using a DD task that incorporated a 1 s inter-trial interval (ITI) immediately after delivery of either the immediate (1 pellet) or delayed (3 pellet) reinforcer. The results of Experiment II found no difference in the percent choice for the larger reward between Lphn3 KO and WT rats, demonstrating reinforcement rate did not influence impulsive choice in Lphn3 KO rats.

Discussion

Overall, there were impulsivity differences among the ADHD models, as SHRs exhibited deficits in impulsive choice, while the Lphn3 KO rats did not.
A new FRDA mouse model [Fxnnull:YG8s(GAA) > 800] with more than 800 GAA repeats
Authors: Kalef-Ezra Ester , Edzeamey Fred Jonathan , Valle Adamo , Khonsari Hassan , Kleine Paula , Oggianu Carlo , Al-Mahdawi Sahar , Pook Mark A. , Anjomani Virmouni Sara
Published: January 2023

Introduction

Friedreich’s ataxia (FRDA) is an inherited recessive neurodegenerative disorder caused by a homozygous guanine-adenine-adenine (GAA) repeat expansion within intron 1 of the FXN gene, which encodes the essential mitochondrial protein frataxin. There is still no effective therapy for FRDA, therefore the development of optimal cell and animal models of the disease is one of the priorities for preclinical therapeutic testing.

Methods

We obtained the latest FRDA humanized mouse model that was generated on the basis of our previous YG8sR, by Jackson laboratory [YG8JR, Fxnnull:YG8s(GAA) > 800]. We characterized the behavioral, cellular, molecular and epigenetics properties of the YG8JR model, which has the largest GAA repeat sizes compared to all the current FRDA mouse models.

Results

We found statistically significant behavioral deficits, together with reduced levels of frataxin mRNA and protein, and aconitase activity in YG8JR mice compared with control Y47JR mice. YG8JR mice exhibit intergenerational GAA repeat instability by the analysis of parent and offspring tissue samples. Somatic GAA repeat instability was also detected in individual brain and cerebellum tissue samples. In addition, increased DNA methylation of CpG U13 was identified in FXN GAA repeat region in the brain, cerebellum, and heart tissues. Furthermore, we show decreased histone H3K9 acetylation and increased H3K9 methylation of YG8JR cerebellum tissues within the FXN gene, upstream and downstream of the GAA repeat region compared to Y47JR controls.

Discussion

These studies provide a detailed characterization of the GAA repeat expansion-based YG8JR transgenic mouse models that will help investigations of FRDA disease mechanisms and therapy.
Epigallocatechin-3-gallate alleviates gestational stress-induced postpartum anxiety and depression-like behaviors in mice by downregulating semaphorin3A and promoting GSK3β phosphorylation in the hippocampus
Authors: Xu Fang , Wu Hui , Xie Linghua , Chen Qing , Xu Qi , Sun Lihong , Li Hua , Xie Jiaqian , Chen Xinzhong
Published: January 2023

Introduction

Postpartum depression (PPD) is a common neuropsychiatric disorder characterized by depression and comorbid anxiety during the postpartum period. PPD is difficult to treat because of its elusive mechanisms. Epigallocatechin-3-gallate (EGCG), a component of tea polyphenols, is reported to exert neuroprotective effects in emotional disorders by reducing inflammation and apoptosis. However, the effect of EGCG on PPD and the underlying mechanism are unknown.

Methods

We used a mouse model of PPD established by exposing pregnant mice to gestational stress. Open field, forced swimming and tail suspension tests were performed to investigate the anxiety and depression-like behaviors. Immunohistochemical staining was used to measure the c-fos positive cells. The transcriptional levels of hippocampal semaphorin3A(sema3A), (glycogen synthase kinase 3-beta)GSK3β and collapsin response mediator protein 2(CRMP2) were assessed by RT-PCR. Alterations in protein expression of Sema3A, GSK3β, p-GSK3β, CRMP2 and p-CRMP2 were quantified by western blotting. EGCG was administrated to analyze its effect on PPD mice.

Results

Gestational stress induced anxiety and depression-like behaviors during the postpartum period, increasing Sema3A expression while decreasing that of phosphorylated GSK3β as well as c-Fos in the hippocampus. These effects were reversed by systemic administration of EGCG.

Conclusions

Thus, EGCG may alleviate anxiety and depression-like behaviors in mice by downregulating Sema3A and increasing GSK3β phosphorylation in the hippocampus, and has potential application in the treatment of PPD.
Revising human-systems engineering principles for embedded AI applications
Authors: Cummings M. L.
Published: January 2023

The recent shift from predominantly hardware-based systems in complex settings to systems that heavily leverage non-deterministic artificial intelligence (AI) reasoning means that typical systems engineering processes must also adapt, especially when humans are direct or indirect users. Systems with embedded AI rely on probabilistic reasoning, which can fail in unexpected ways, and any overestimation of AI capabilities can result in systems with latent functionality gaps. This is especially true when humans oversee such systems, and such oversight has the potential to be deadly, but there is little-to-no consensus on how such system should be tested to ensure they can gracefully fail. To this end, this work outlines a roadmap for emerging research areas for complex human-centric systems with embedded AI. Fourteen new functional and tasks requirement considerations are proposed that highlight the interconnectedness between uncertainty and AI, as well as the role humans might need to play in the supervision and secure operation of such systems. In addition, 11 new and modified non-functional requirements, i.e., “ilities,” are provided and two new “ilities,” auditability and passive vulnerability, are also introduced. Ten problem areas with AI test, evaluation, verification and validation are noted, along with the need to determine reasonable risk estimates and acceptable thresholds for system performance. Lastly, multidisciplinary teams are needed for the design of effective and safe systems with embedded AI, and a new AI maintenance workforce should be developed for quality assurance of both underlying data and models.
Effects of dietary nutmeg (Myristica fragrans) seed meals on growth, non-specific immune indices, antioxidant status, gene expression analysis, and cold stress tolerance in zebrafish (Danio rerio)
Authors: Vakili Farzaneh , Roosta Zahra , Safari Roghieh , Raeisi Mojtaba , Hossain Md. Sakhawat , Guerreiro Inês , Akbarzadeh Arash , Hoseinifar Seyed Hossein
Published: January 2023

Introduction

A medicinal plant, Myristica fragrans seed meal (nutmeg), was utilized to evaluate its impact on the growth, immunity, and antioxidant defense of zebrafish (Danio rerio).

Methods

In this regard, zebrafish (0.47 ± 0.04 g) (mean ± S.D.) were fed with 0% (control), 1% (T1-nutmeg), 2% (T2-nutmeg), and 3% (T3-nutmeg) of powdered nutmeg for 70 days. At the end of the feeding trial, growth performance, survival rate of fish, and temperature-challenge effects were recorded. Immune and antioxidant parameters were also assessed through the collection of serum and skin mucus samples.

Results

The results indicated that nutmeg supplementation did not significantly influence the growth of zebrafish (P > 0.05); however, the survival rate of fish fed with 2 and 3% of nutmeg supplementation significantly decreased (P < 0.05). The skin mucus and serum total protein, total immunoglobulin (Ig), and lysozyme activity were significantly increased in T3-nutmeg treatment in comparison to the control (P < 0.05). Superoxide dismutase (SOD) and catalase (CAT) activities were also enhanced in the T3-nutmeg group (P < 0.05). Nutmeg supplementation significantly upregulated the mRNA expression of growth hormone (gh) and insulin growth factor-1 (igf-1). Moreover, the nutmeg inclusion upregulated the expression of interleukin-1β (IL-1β), lysozyme, sod, and cat. The dietary supplementation of nutmeg significantly increased the resistance of zebrafish against cold-water shock and survivability afterward (P < 0.05).

Discussion

In conclusion, the supplementation of 3% powdered nutmeg in zebrafish diets could be suggested as an effective immune stimulator that improves antioxidant defense and stress tolerance.
Selenium intake help prevent age-related cataract formation: Evidence from NHANES 2001–2008
Authors: Xu Baiwei , Liu Zhongwei , Zhao Jiangyue , Yu Ziyan
Published: January 2023

Introduction

Cataract is one of the leading causes of blindness and visual impairment, about 16 million people around the world. Trace elements play an important role in a variety of the processes in human body. This study aimed to investigate the association between daily dietary intake of trace elements and age-related cataract incidence based on data from the National Health and Nutrition Examination Survey (NHANES) 2001–2008.

Methods

Iron, zinc, copper, and selenium were conducted in this study among subjects aged 50 years and older for African Americans and 55 and older in US adults. Multivariate logistic regression analysis was used in different models to investigate the association of trace elements intake and cataract.

Results

After screening, 7,525 subjects were ultimately included in this study. A significant negative association was found between selenium intake and cataract incidence in adjusted models using multivariate logistic regression analysis (model 1: OR = 0.998, 95% CI = 0.997–1.000; model 2: OR = 0.997, 95% CI = 0.995–1.000; and model 3: OR = 0.998, 95% CI = 0.995–1.000). After dividing selenium intake into quintiles, significant negative associations between selenium intake and cataract were observed in the first quintile of model 3, the fourth and fifth quintiles of all models. In subgroup analyses adjusted for age and sex, a significant negative association was observed only in women aged 65–74 years.

Discussion

Our study points out that maintaining daily dietary selenium intake at higher levels is helpful for cataract prevention, and that increasing daily dietary selenium intake in American women aged 65–74 years may contribute to the prevention of age-related cataract. The intakes of iron, zinc, copper may not be associated with age-related cataract.
Changes of polyphenols and antioxidants of arabica coffee varieties during roasting
Authors: Mestanza Marilu , Mori-Culqui Pati Llanina , Chavez Segundo G.
Published: January 2023

Coffee is the most consumed beverage in the world after water. Multiple benefits are attributed to it in human health due to the presence of antioxidant compounds, whose content depends, among other factors, on the processing conditions of the coffee bean. The objective of this study was to determine the kinetics of polyphenols and antioxidants during the roasting of three varieties of arabica coffee. For this, we worked with varieties of coffee, Catimor, Caturra, and Bourbon, from the province of La Convencion, Cuzco, Peru. The samples were roasted in an automatic induction roaster, and 12 samples were taken during roasting (at 0, 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 min of roasting) in triplicate. For green coffee beans, titratable acidity, total soluble solids, moisture and apparent density were determined. The change in polyphenol content was determined using the Folin-Ciocalteu method, and antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis- (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS+) free radical capture technique during roasting. Polyphenol and antioxidant contents increased until minute 5 of roasting and then decreased until minute 20, and in some cases, there were slight increases in the last minute. The model that best described the changes in these bioactive compounds was the cubic model (R2 0.634 and 0.921), and the best fits were found for the Bourbon variety, whose green grain had more homogeneous characteristics. The changes in the relative abundances of nine phenolic compounds were determined using high-performance liquid chromatography (HPLC). In conclusion, roasting modifies phenolic compounds and antioxidants differently in the coffee varieties studied. The content of some phenols increases, and in other cases, it decreases as the roasting time increases. The roasting process negatively affects the bioactive compounds and increases the fracturability of Arabica coffee beans, elements that should be taken into account at the moment of developing roasting models in the industry.
Insights into the metabolic profiling of Polygonati Rhizoma fermented by Lactiplantibacillus plantarum under aerobic and anaerobic conditions using a UHPLC-QE-MS/MS system
Authors: Wang ZiLing , Lao Jia , Kang XingYi , Xie ZhenNi , He Wei , Liu XiaoLiu , Zhong Can , Zhang ShuiHan , Jin Jian
Published: January 2023

Introduction

Polygonati Rhizoma is a multi-purpose food with medicinal uses. Fermentation of Polygonati Rhizoma by lactic acid bacteria could provide new insights into the development of Polygonati Rhizoma products.

Methods

In this study, Lactiplantibacillus plantarum was fermented with Polygonati Rhizoma extracts in a bioreactor under aerobic and anaerobic conditions with pH and DO real-time detection. Metabolic profiling was determined by UHPLC-QE-MS/MS system. Principal component analysis and orthogonal partial least-squares discriminant analysis were used to perform multivariate analysis.

Results

A total of 98 differential metabolites were identified in broth after fermentation, and 36 were identified between fermentation under aerobic and anaerobic conditions. The main metabolic pathways in the fermentation process are ABC transport and amino acid biosynthesis. Most of the compounds such as L-arginine, L-aspartic acid, leucine, L-lysine, citrate, inosine, carnitine, betaine, and thiamine were significantly increased during fermentation, playing a role in enhancing food flavor. Compared with anaerobic fermentation, aerobic conditions led to a significant rise in the levels of some compounds such as valine, isoleucine, and glutamate; this increase was mainly related to branched-chain amino acid transaminase, isocitrate dehydrogenase, and glutamate dehydrogenase.

Discussion

Aerobic fermentation is more beneficial for the fermentation of Polygonati Rhizoma by L. plantarum to produce flavor and functional substances. This study is the first report on the fermentation of Polygonati Rhizoma by L. plantarum and provides insights that would be applicable in the development of Polygonati Rhizoma fermented products.
Initial experience with triple port laparoscopic distal gastrectomy
Authors: Wei Jiangpeng , Yang Xisheng , Gao Ruiqi , Wang Weidong , Li Xiaohua , Ji Gang
Published: January 2023

Objective

This study aimed to compare the feasibility and short-term clinical efficacy of triple-port laparoscopic distal gastrectomy (TPLDG) with five-port laparoscopic distal gastrectomy (FPLDG).

Methods

From April 2020 to December 2021, this retrospective study included all consecutive patients (n = 21) who underwent TPLDG + D2 lymph node dissection, and randomly screened patients who underwent FPLDG + D2 lymph node dissection during this period (n = 30).

Results

There were no significant differences in intraoperative (P > 0.05) and postoperative complication rate (P = 0.635) between the two groups. The changes in the first ambulation, flatus, water intake after surgery and postoperative hospitalization were also similar between the two groups (P > 0.05). However, time to abdominal drainage tube removal (1.62 ± 0.15 days vs. 2.00 ± 0.12 days, P = 0.046), NRS pain score on the first postoperative day (1.91 ± 0.15 days vs. 2.47 ± 0.12 days, P = 0.004) and hemameba level on the third postoperative day (7.89 ± 0.51 days vs. 10.52 ± 0.58 days, P = 0.002) were significantly lower in the TPLDG group compared to the FPLDG group.

Conclusion

TPLDG is a safer, feasible, and short-term alternative to conventional LDG for distal gastric cancer.
What is the appropriate “first lymph node” in the era of segmentectomy for non-small cell lung cancer?
Authors: Seitlinger Joseph , Stasiak Florent , Piccoli Juliette , Maffeis Gabriele , Streit Arthur , Wollbrett Christophe , Siat Joelle , Gauchotte Guillaume , Renaud Stéphane
Published: January 2023

Introduction

The place of segmentectomy in the management of lung cancer is shifting following the inspiring results of the Japanese JCOG0802 trial. I n this study, authors suggested that performing segmentectomy would require in an optimal way an intraoperative confirmation of pN0 tumor with a frozen section. Our objective was to determine whether the proposed technique, i.e. adjacent lymph node analysis, is consistent with the results of our study on sentinel lymph node (SLN) detection using fluorescence.

Methods

This is a retrospective, observational, single center study. Eighty-one patients with suspected localized stage NSCLC (IA to IIA) were included between December 2020 and March 2022. All patients received an intra-operative injection of indocyanine green (ICG) directly in the peritumoral area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed by using an infrared fluorescence camera.

Results

In our cohort, SLN was identified in 60/81 patients (74.1%). In 15/60 patients with identified SLN (25%), NIR-guided SLN was concordant with the suggestions of JCOG0802 study. A retrospective SLN pathological analysis was performed in 43 patients/60 cases with identified SLN (71.2%), including 37 cases of malignant disease. Occult micro-metastases were found in 4 patients out of 37 SLN analyzed, leading to a 10.8% upstaging with NIR-guided SLN analysis.

Dicussion

At the time of segmentectomies, ICG technique allowed the identification of the SLN in a high percent of cases and in some areas usually out of the recommended stations for lymph node dissection.
Phytoradiotherapy to enhance cancer treatment outcomes with cannabidiol, bitter melon juice, and plant hemoglobin
Authors: Alfonzetti Tyler , Moreau Michele , Yasmin-Karim Sayeda , Ngwa Wilfred , Avery Stephen , Goia Denisa
Published: January 2023

Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, much of the world lacks access to expensive, modern treatment options. The need for innovative, cost-effective solutions that can improve patient treatment outcomes is essential. Phytomedicines have been shown to induce apoptotic tumor cell death, diminish tumor progression, reduce cancer incidence, alleviate harmful hypoxic conditions, and more. While an ample amount of research is available that characterizes many phytomedicines as having anti-cancer properties that increase tumor cell killing/control and mitigate the harmful side effects of radiation damage, little work has been done to investigate the synergistic effect of phytoradiotherapy: combining radiation treatment with phytomedicines. In this study, a protocol for testing the radiosensitizing effects of phytomedicines was validated and used to investigate the well-known plant based medicine cannabidiol (CBD) and the lesser-known medicinal fruit Bitter Melon. Additionally, based on its high concentration of plant hemoglobin which has been shown to abate hypoxia, the African-indigenous Justicia plant was tested in pancreatic adenocarcinoma mouse models. The studies reveal that these phytomedicines can effectively enhance tumor cell killing, minimize tumor growth, and prolong mice survival. There is certainly the need for additional research in this regard, however, phytoradiotherapy: the use of phytomedicines to enhance radiation therapy treatment outcomes, continues to show potential as a promising, innovative way to improve cancer care.
Extraskeletal Ewing’s sarcoma of the mediastinum: Case report
Authors: Caltavituro Aldo , Buonaiuto Roberto , Salomone Fabio , Morra Rocco , Pietroluongo Erica , De Placido Pietro , Tortora Marianna , Peddio Annarita , Picozzi Fernanda , Ottaviano Margaret , Marino Mirella , De Placido Sabino , Palmieri Giovannella , Giuliano Mario
Published: January 2023

Background

Ewing sarcoma (ES) represents the second most common malignant bone tumor in children and young adults. ES is not a frequent finding in sites different from the skeletal. Common sites of appearance of ES are lower extremities, the pelvis, paravertebral spaces and head and neck. Primary extraskeletal ES located in the anterior mediastinum are very rare. These neoplasms should be discussed in specialized contests with a high volume of patients treated. Here, we present an uncommon mediastinal mass challenging in its characterization and management.

Case description

A thirty-year-old woman performed a thoracic CT scan for dyspnea and persistent cough. Imaging showed a solid mass of 14 x 11 cm involving the left thorax with mediastinal deviation to the right side. Patient underwent an en bloc resection of the mass. Initial histological examination was suggestive for B3 thymoma/thymic carcinoma. Patient was then referred to our rare tumor reference center where a histological review excluded the diagnosis of thymic/thymoma neoplasms meanwhile a third revision assessed a diagnosis of ES. Patient refused adjuvant chemotherapy due to her desire of maternity and radiation therapy was not indicated because surgery was performed too many months earlier. A close follow-up was considered. After a few months the patient relapsed and first line chemotherapy was proposed. She reached a complete response at the first evaluation maintained also at the end of the protocol. In order to consolidate the obtained response, high dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) was suggested and the patient agreed.

Conclusions

This case underlined that, potentially, ES can arise from any soft tissue site in the body, even in rare sites such as mediastinum. The evaluation of expert centers was critical to establish a correct diagnosis and therapeutic approach in this complex case. Taking into account the time lasting from the diagnosis and the aggressiveness of this kind of neoplasm, frequently relapsing, the patient after a multidisciplinary discussion was a candidate for a multimodal treatment.
Clinical value of 18F-FDG PET/CT in the management of HIV-associated lymphoma
Authors: Liu Qi , Yang Tao , Chen Xiaoliang , Liu Yao
Published: January 2023

HIV is still a major public health problem. At present, HIV-associated lymphoma remains the leading cause of deaths among people living with HIV, which should be paid more attention to. 18F-fluorodeoxglucose (FDG) PET/CT has been recommended in the initial staging, restaging, response assessment and prognostic prediction of lymphomas in general population. HIV-associated lymphoma is, however, a different entity from lymphoma in HIV-negative with a poorer prognosis. The ability to accurately risk-stratify HIV-infected patients with lymphoma will help guide treatment strategy and improve the prognosis. In the review, the current clinical applications of 18F-FDG PET/CT in HIV-associated lymphoma will be discussed, such as diagnosis, initial staging, response evaluation, prognostic prediction, PET-guided radiotherapy decision, and surveillance for recurrence. Moreover, future perspectives will also be presented.
Lactate dehydrogenase and the severity of adenoviral pneumonia in children: A meta-analysis
Authors: Zou Min , Zhai Yang , Mei Xiaoping , Wei Xing
Published: January 2023

Background

Children with severe adenoviral pneumonia (ADVP) have poor prognosis and high risk of mortality. We performed a meta-analysis to evaluate the association between pretreatment lactate dehydrogenase (LDH) and severity, postinfectious bronchiolitis obliterans (PIBO), and mortality in children with ADVP.

Methods

Relevant observational studies were identified by search of PubMed, Embase, Web of Science, Wanfang, and CNKI databases from inception to August 3, 2022. A random effect model was used to pool the results by incorporating the potential between-study heterogeneity.

Results

Overall, 23 studies with 4,481 children with ADVP were included in this meta-analysis. Results of meta-analysis showed that children with severe ADVP had a significantly higher level of pretreatment LDH as compared to those with non-severe ADVP (standard mean difference [SMD]: 0.51, 95% confidence interval [CI]: 0.36 to 0.66, p < 0.001; I2 = 69%). Besides, pooled results also suggested that the pretreatment LDH was significantly higher in children who developed PIBO as compared to those who did not (SMD: 0.47, 95% CI: 0.09 to 0.84, p = 0.02, I2 = 80%). Finally, results of the meta-analysis also confirmed that a higher pretreatment LDH (>500 IU/L) was a risk factor of increased mortality during hospitalization (odds ratio: 3.10, 95% CI: 1.62 to 5.92, p < 0.001, I2 = 0%). Sensitivity analyses by excluding one dataset at a time showed consistent results.

Conclusion

High pretreatment LDH may be associated with disease severity, development of PIBO, and increased risk of mortality in children with ADVP.
Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism
Authors: Li Bohai , Kwok Lai-Yu , Wang Dandan , Li Lu , Guo Shuai , Chen Yongfu
Published: January 2023

Many drugs have been shown to be metabolized by the human gut microbiome, but probiotic-driven drug-metabolizing capacity is rarely explored. Here, we developed an integrated metabolomics, culturomics, and bionics framework for systematically studying probiotics-driven drug metabolism. We discovered that 75% (27/36 of the assayed drugs) were metabolized by five selected probiotics, and drugs containing nitro or azo groups were more readily metabolized. As proof-of-principle experiments, we showed that Lacticaseibacillus casei Zhang (LCZ) could metabolize racecadotril to its active products, S-acetylthiorphan and thiorphan, in monoculture, in a near-real simulated human digestion system, and in an ex vivo fecal co-culture system. However, a personalized effect was observed in the racecadotril-metabolizing activity of L. casei Zhang, depending on the individual’s host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among L. casei Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics.
Current use of complementary and conventional medicine for treatment of pediatric patients with gastrointestinal disorders
Authors: Sayre Casey L. , Yellepeddi Venkata Kashyap , Job Kathleen M. , Krepkova Lubov V. , Sherwin Catherine M. T. , Enioutina Elena Y.
Published: January 2023

Infants, children, and adolescents are at risk of experiencing a multitude of gastrointestinal disorders (GID). These disorders can adversely affect the quality of life or be life-threatening. Various interventions that span the conventional and complementary therapeutic categories have been developed. Nowadays, parents increasingly seek complementary options for their children to use concurrently with conventional therapies. Due to the high prevalence and morbidity of diarrhea, constipation, and irritable bowel syndrome (IBS) in children, in this review, we decided to focus on the current state of the evidence for conventional and complementary therapies used for the treatment of these diseases in children. Diarrhea treatment focuses on the identification of the cause and fluid management. Oral rehydration with supplementation of deficient micronutrients, especially zinc, is well established and recommended. Some probiotic strains have shown promise in reducing the duration of diarrhea. For the management of constipation, available clinical trials are insufficient for conclusive recommendations of dietary modifications, including increased use of fruit juice, fiber, and fluid. However, the role of laxatives as conventional treatment is becoming more established. Polyethylene glycol is the most studied, with lactulose, milk of magnesia, mineral oil, bisacodyl, and senna presenting as viable alternatives. Conventional treatments of the abdominal pain associated with IBS are poorly studied in children. Available studies investigating the effectiveness of antidepressants on abdominal pain in children with IBS were inconclusive. At the same time, probiotics and peppermint oil have a fair record of benefits and safety. The overall body of evidence indicates that a careful balance of conventional and complementary treatment strategies may be required to manage gastrointestinal conditions in children.
Sodium aescinate inhibits microglia activation through NF-κB pathway and exerts neuroprotective effect
Authors: Xu Fei , Jiang Yiguo , Wang Xiaoyu , Shen Li , Yan Yan , Guo Dongkai , Wang Cheng
Published: January 2023

Background: Microglia are resident immune cells of the central nervous system that sense environmental changes and maintain central nervous system homeostasis. Dysfunctional microglia produce toxic mediators that lead to neuronal death. Recent studies suggest that Sodium Aescinate has a neuroprotective effect. However, it is unclear whether Sodium Aescinate exerts neuroprotective effects by inhibiting activation of microglia.

Method: Traumatic brain injury and lipopolysaccharide neuroinflammation model were used to evaluate the microglia activation in vivo. BV2 and primary microglia cells were used to assess the microglia activation in vitro. Molecular docking technique was used to predict the binding energy of Sodium Aescinate to NF-κB signaling pathway proteins.

Result: Sodium Aescinate inhibited microglial activation in-vivo and in-vitro. Sodium Aescinate inhibited the activation of microglia in Traumatic brain injury and lipopolysaccharide mouse models. Sodium Aescinate also inhibited the expression of inflammatory proteins in BV2 and primary microglia cells. Western blot experiment showed that SA inhibited the activation of NF-κB pathway in BV2 and primary microglia cells. Molecular docking results also showed that Sodium Aescinate had a better affinity with the core protein of the NF-κB pathway. Western blot identified that SA inhibited activation of NF-κB pathway. In Traumatic brain injury model and conditioned medium experiment, Sodium Aescinate pretreatment inhibited inflammation and protected neuron.

Conclusion: Our study confirmed that the protection effects of Sodium Aescinate on neurons by inhibiting microglia activation through NF-κB pathway.
Emerging role of non-coding RNAs in resistance to platinum-based anti-cancer agents in lung cancer
Authors: Mondal Priya , Meeran Syed Musthapa
Published: January 2023

Platinum-based drugs are the first line of therapeutics against many cancers, including lung cancer. Lung cancer is one of the leading causes of cancer-related death worldwide. Platinum-based agents target DNA and prevent replication, and transcription, leading to the inhibition of cell proliferation followed by cellular apoptosis. About twenty-three platinum-based drugs are under different stages of clinical trials, among cisplatin, carboplatin, and oxaliplatin are widely used for the treatment of various cancers. Among them, cisplatin is the most commonly used drug for cancer therapy, which binds with RNA, and hinders the cellular RNA process. However, long-term use of platinum-based drugs can cause different side effects and has been shown to develop chemoresistance, leading to poor clinical outcomes. Chemoresistance became an important challenge for cancer treatment. Platinum-based chemoresistance occurs due to the influence of intrinsic factors such as overexpression of multidrug resistance proteins, advancement of DNA repair mechanism, degradation, and deactivation of intracellular thiols. Recently, epigenetic modifications, especially non-coding RNAs (ncRNAs) mediated gene regulation, grasp the attention for reversing the sensitivity of platinum-based drugs due to their reversible nature without altering genome sequence. ncRNAs can also modulate the intrinsic and non-intrinsic mechanisms of resistance in lung cancer cells. Therefore, targeting ncRNAs could be an effective approach for developing novel therapeutics to overcome lung cancer chemoresistance. The current review article has discussed the role of ncRNA in chemoresistance and its underlying molecular mechanisms in human lung cancer.
Fenchone, a monoterpene: Toxicity and diuretic profiling in rats
Authors: Bashir Asifa , Mushtaq Muhammad Naveed , Younis Waqas , Anjum Irfan
Published: January 2023

Fenchone is a monoterpene present in the essential oils of various plants, includingFoeniculum vulgareandPeumus boldus. Previous studies confirmed the anti-inflammatory, antioxidant, wound-healing, antidiarrheal, antifungal, antinociceptive, and bronchodilator activities of fenchone. Owing to various pharmacological activities of Fenchone, the current research was designed to evaluate its diuretic activity along with toxicity profiling. For evaluating acute toxicity, OECD guideline 425 was followed in which a single dose of 2000 mg/kg was orally administered to rats. For evaluating the diuretic potential in rats, three doses of Fenchone (100, 200, and 400 mg/kg) were assayed in comparison to furosemide (15 mg/kg) as the standard drug, followed by measurements of urinary volume, urinary electrolytes, uric acid, and urinary creatinine in saline-loaded rats for 8 h. The acute toxicity study showed a significant increase in hemoglobin (Hb), red blood cells (RBCs), alkaline phosphatase (ALP), and alkaline transaminase (ALT) along with a significant decrease in serum triglycerides, cholesterol, and uric acid levels when compared with the control group. The oxidative stress parameter, superoxide dismutase (SOD), was increased in the heart and spleen. Nitrite (NO) and glutathione were significantly increased in the kidney. The acute diuretic effect of Fenchone (400 mg/kg) significantly increased the urinary output, electrolytes (Na+, K+, and Ca++), urinary creatinine, and urinary uric acid in a dose-dependent manner. The Na+/K+ratio was remarkably higher in the treatment group than that of the control group. The diuretic index, saluretic index, and Lipschitz value were also calculated from electrolyte concentration and urinary volume measurements, and the values were significantly increased in rats administered with fenchone at 400 mg/kg dose. The current study concluded that fenchone is safe and has remarkable diuretic action.
Dilated convolution network with edge fusion block and directional feature maps for cardiac MRI segmentation
Authors: Chen Zhensen , Bai Jieyun , Lu Yaosheng
Published: January 2023

Cardiac magnetic resonance imaging (MRI) segmentation task refers to the accurate segmentation of ventricle and myocardium, which is a prerequisite for evaluating the soundness of cardiac function. With the development of deep learning in medical imaging, more and more heart segmentation methods based on deep learning have been proposed. Due to the fuzzy boundary and uneven intensity distribution of cardiac MRI, some existing methods do not make full use of multi-scale characteristic information and have the problem of ambiguity between classes. In this paper, we propose a dilated convolution network with edge fusion block and directional feature maps for cardiac MRI segmentation. The network uses feature fusion module to preserve boundary information, and adopts the direction field module to obtain the feature maps to improve the original segmentation features. Firstly, multi-scale feature information is obtained and fused through dilated convolutional layers of different scales while downsampling. Secondly, in the decoding stage, the edge fusion block integrates the edge features into the side output of the encoder and concatenates them with the upsampled features. Finally, the concatenated features utilize the direction field to improve the original segmentation features and generate the final result. Our propose method conducts comprehensive comparative experiments on the automated cardiac diagnosis challenge (ACDC) and myocardial pathological segmentation (MyoPS) datasets. The results show that the proposed cardiac MRI segmentation method has better performance compared to other existing methods.
Analysis of the role of BrRPP1 gene in Chinese cabbage infected by Plasmodiophora brassicae
Authors: Ge Wenjie , Lv Mingcan , Feng Hui , Wang Xinlei , Zhang Bo , Li Ken , Zhang Jing , Zou Jiawei , Ji Ruiqin
Published: January 2023

Introduction

The clubroot disease caused by Plasmodiophora brassicae (P. brassicae) poses a serious threat to the economic value of cruciferous crops, which is a serious problem to be solved worldwide. Some resistance genes to clubroot disease in Brassica rapa L. ssp pekinensis cause by P. brassicae have been located on different chromosomes. Among them, Rcr1 and Rcr2 were mapped to the common candidate gene Bra019410, but its resistance mechanism is not clear yet.

Methods

In this experiment, the differences of BrRPP1 between the resistant and susceptible material of Chinese cabbage were analyzed by gene cloning and qRT-PCR. The gene function was verified by Arabidopsis homologous mutants. The expression site of BrRPP1 gene in cells was analyzed by subcellular localization. Finally, the candidate interaction protein of BrRPP1 was screened by yeast two-hybrid library.

Results

The results showed that the cDNA sequence, upstream promoter sequence and expression level of BrRPP1 were quite different between the resistant and susceptible material. The resistance investigation found that the Arabidopsis mutant rpp1 was more susceptible to clubroot disease than the wild type, which suggested that the deletion of rpp1 reduces resistance of plant to clubroot disease. Subcellular location analysis confirmed that BrRPP1 was located in the nucleus. The interaction proteins of BrRPP1 screened from cDNA Yeast Library by yeast two-hybrid are mainly related to photosynthesis, cell wall modification, jasmonic acid signal transduction and programmed cell death.

Discussion

BrRPP1 gene contains TIR-NBS-LRR domain and belongs to R gene. The cDNA and promoter sequence of BrRPP1 in resistant varieties was different from that in susceptible varieties led to the significant difference of the gene expression of BrRPP1 between the resistant varieties and the susceptible varieties. The high expression of BrRPP1 gene in resistant varieties enhanced the resistance of Chinese cabbage to P. brassicae, and the interaction proteins of BrRPP1 are mainly related to photosynthesis, cell wall modification, jasmonic acid signal transduction and programmed cell death. These results provide important clues for understanding the mechanism of BrRPP1 in the resistance of B. rapa to P. brassicae.
Non-growing/growing season non-uniform-warming increases precipitation use efficiency but reduces its temporal stability in an alpine meadow
Authors: Han Fusong , Yu Chengqun , Fu Gang
Published: January 2023

There are still uncertainties on the impacts of season-non-uniform-warming on plant precipitation use efficiency (PUE) and its temporal stability (PUEstability) in alpine areas. Here, we examined the changes of PUE and PUEstability under two scenes of non-growing/growing season non-uniform-warming (i.e., GLNG: growing-season-warming lower than non-growing-season-warming; GHNG: growing-season-warming higher than non-growing-season-warming) based on a five-year non-uniform-warming of non-growing/growing season experiment. The GLNG treatment increased PUE by 38.70% and reduced PUEstability by 50.47%, but the GHNG treatment did not change PUE and PUEstability. This finding was mainly due to the fact that the GLNG treatment had stronger influences on aboveground biomass (AGB), non-growing-season soil moisture (SMNG), temporal stability of AGB (AGBstability), temporal stability of non-growing-season air temperature (Ta_NG_stability), temporal stability of growing-season vapor pressure deficit (VPDG_stability) and temporal stability of start of growing-season (SGSstability). Therefore, the warming scene with a higher non-growing-season-warming can have greater influences on PUE and PUEstability than the warming scene with a higher growing-season-warming, and there were possibly trade-offs between plant PUE and PUEstability under season-non-uniform-warming scenes in the alpine meadow.
Characterization of the soybean KRP gene family reveals a key role for GmKRP2a in root development
Authors: Guo Binhui , Chen Lin , Dong Lu , Yang Chunhong , Zhang Jianhua , Geng Xiaoyan , Zhou Lijuan , Song Li
Published: January 2023

Kip-related proteins (KRPs), as inhibitory proteins of cyclin-dependent kinases, are involved in the growth and development of plants by regulating the activity of the CYC-CDK complex to control cell cycle progression. The KRP gene family has been identified in several plants, and several KRP proteins from Arabidopsis thaliana have been functionally characterized. However, there is little research on KRP genes in soybean, which is an economically important crop. In this study, we identified nine GmKRP genes in the Glycine max genome using HMM modeling and BLASTP searches. Protein subcellular localization and conserved motif analysis showed soybean KRP proteins located in the nucleus, and the C-terminal protein sequence was highly conserved. By investigating the expression patterns in various tissues, we found that all GmKRPs exhibited transcript abundance, while several showed tissue-specific expression patterns. By analyzing the promoter region, we found that light, low temperature, an anaerobic environment, and hormones-related cis-elements were abundant. In addition, we performed a co-expression analysis of the GmKRP gene family, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) set enrichment analysis. The co-expressing genes were mainly involved in RNA synthesis and modification and energy metabolism. Furthermore, the GmKRP2a gene, a member of the soybean KRP family, was cloned for further functional analysis. GmKRP2a is located in the nucleus and participates in root development by regulating cell cycle progression. RNA-seq results indicated that GmKRP2a is involved in cell cycle regulation through ribosome regulation, cell expansion, hormone response, stress response, and plant pathogen response pathways. To our knowledge, this is the first study to identify and characterize the KRP gene family in soybean.
UAV imagery data and machine learning: A driving merger for predictive analysis of qualitative yield in sugarcane
Authors: Barbosa Júnior Marcelo Rodrigues , Moreira Bruno Rafael de Almeida , de Oliveira Romário Porto , Shiratsuchi Luciano Shozo , da Silva Rouverson Pereira
Published: January 2023

Predicting sugarcane yield by quality allows stakeholders from research centers to industries to decide on the precise time and place to harvest a product on the field; hence, it can streamline workflow while leveling up the cost-effectiveness of full-scale production. °Brix and Purity can offer significant and reliable indicators of high-quality raw material for industrial processing for food and fuel. However, their analysis in a relevant laboratory can be costly, time-consuming, and not scalable. We, therefore, analyzed whether merging multispectral images and machine learning (ML) algorithms can develop a non-invasive, predictive framework to map canopy reflectance to °Brix and Purity. We acquired multispectral images data of a sugarcane-producing area via unmanned aerial vehicle (UAV) while determining °Brix and analytical Purity from juice in a routine laboratory. We then tested a suite of ML algorithms, namely multiple linear regression (MLR), random forest (RF), decision tree (DT), and support vector machine (SVM) for adequacy and complexity in predicting °Brix and Purity upon single spectral bands, vegetation indices (VIs), and growing degree days (GDD). We obtained evidence for biophysical functions accurately predicting °Brix and Purity. Those can bring at least 80% of adequacy to the modeling. Therefore, our study represents progress in assessing and monitoring sugarcane on an industrial scale. Our insights can offer stakeholders possibilities to develop prescriptive harvesting and resource-effective, high-performance manufacturing lines for by-products.
Removal of the endoplasma membrane upon sperm cell activation after pollen tube discharge
Authors: Sugi Naoya , Izumi Rie , Tomomi Shun , Susaki Daichi , Kinoshita Tetsu , Maruyama Daisuke
Published: January 2023

In pollen and pollen tubes, immotile sperm cells are enclosed by an inner vegetative plasma membrane (IVPM), a single endomembrane originating from the vegetative-cell plasma membrane. It is widely believed that sperm cells must be removed from the IVPM prior to gamete associations and fusions; however, details of the timing and morphological changes upon IVPM dissociation remain elusive. Here, we report a rapid IVPM breakdown immediately before double fertilization in Arabidopsis thaliana. The IVPM was stably observed in coiling pollen tubes when pollen tube discharge was prevented using lorelei mutant ovules. In contrast, a semi-in vivo fertilization assay in wild-type ovules demonstrated fragmented IVPM around sperm nuclei 1 min after pollen tube discharge. These observations revealed the dynamic alteration of released sperm cells and provided new insights into double fertilization in flowering plants. With a summary of recent findings on IVPM lipid composition, we discussed the possible physiological signals controlling IVPM breakdown.