bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of fermentation using different lactic acid bacteria strains on the nutrient components and mineral bioavailability of soybean yogurt alternative
Authors: Gan Jing , Kong Xiao , Wang Kuaitian , Chen Yuhang , Du Mengdi , Xu Bo , Xu Jingru , Wang Zhenhua , Cheng Yongqiang , Yu Tianying
Published: June 2023

Introduction

Analysis of the composition of yogurt alternatives (YAs) during fermentation provides critical information for evaluating its quality and nutritional attributes.

Method

We investigated the effects of homotypic (HO) and heterotypic (HE) lactic acid bacteria on the nutritional and mineral bioavailabilities of soybean YA (SYA) during fermentation.

Result

The acidic amino acid (Glu, Asp) and organic acid contents in HO-fermented YA were increased from 2.93, 1.71, and 7.43 mg/100 g to 3.23, 1.82, and 73.47 mg/100 g, respectively. Moreover, both HO and HE lactic acid bacteria fermentation enhanced mineral absorptivity. They altered the molecular speciation of minerals from a large molecular type (2,866 Da) to a small molecular type (1,500 Da), which was manifested in a time-dependent manner. Furthermore, YA substantially increased the bone mass in a zebrafish osteoporosis model, further highlighting the potential of lactic acid bacterial fermentation for mineral bioavailability.

Discussion

This study provides a foundation for understanding the effects of fermentation conditions on the composition and bioavailability of minerals in YA and can assist in its production.
The impact of nutrition on visual cognitive performance in the nutrition, vision, and cognition in sport study
Authors: Beathard Karen M. , Georghiades Nicos , Goulart Jenna B. , Riviere Aaron J. , Sullivan Caroline , Mascarro Melanie , Riechman Steven E.
Published: June 2023

Introduction

The purpose of this study was to examine the influence of nutritional intake on visual perceptual-cognitive performance (VCP) in young healthy adults.

Methods

Ninety-eight healthy men (n = 38) and women (n = 60) aged 18–33 years participated and maintained their usual dietary intake throughout the study. VCP was measured using the NeuroTracker™ CORE (NT) 3-Dimensional (3-D) software program (15 training sessions) over a 15-day period. Food logs and extensive lifestyle measures including body composition, cardiovascular health, sleep and exercise patterns, and general readiness to perform were collected. Mean intake from 10 food logs collected over the 15 days were analyzed using Nutribase software. Statistical analyses were performed in SPSS using repeated measures ANOVA including significant covariates when appropriate.

Results

Males consumed significantly more calories, macronutrients, cholesterol, choline, and zinc and performed significantly better on VCP than the females. Participants who consumed more than 40% of kcals from carbohydrates (p = 0.038), less than 24% of kcals from protein (p = 0.009), more than 2,000 μg/day lutein/zeaxanthin or more than 1.8 mg/ day vitamin B2 performed significantly better on VCP than those who consumed less than those amounts, respectively.

Discussion

VCP is an important dimension of cognitive function and in the present study is influenced by higher carbohydrate, lutein/ zeaxanthin, and vitamin B2 dietary intake while high protein consumption and the female sex negatively impacted VCP.
Sustained complete response to first-line immunochemotherapy for highly aggressive TP53/MDM2-mutated upper tract urothelial carcinoma with ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state: a case report and literature review
Authors: Xu Tianyuan , Guo Hanxu , Xie Jun , He Yanyan , Che Jianping , Peng Bo , Yang Bin , Yao Xudong
Published: June 2023

Background

Upper tract urothelial carcinoma (UTUC) is a rare malignancy. The management of metastatic or unresectable UTUC is mainly based on evidence extrapolated from histologically homologous bladder cancer, including platinum-based chemotherapy and immune checkpoint inhibitor alone, whereas UTUC exhibits more invasiveness, worse prognosis, and comparatively inferior response to treatments. First-line immunochemotherapy regimens have been attempted in clinical trials for unselected naïve-treated cases, but their efficacies relative to standard chemo- or immuno-monotherapy still remain controversial. Here, we present a case of highly aggressive UTUC for whom comprehensive genetic and phenotypic signatures predicted sustained complete response to first-line immunochemotherapy.

Case presentation

A 50-year-old man received retroperitoneoscopic nephroureterectomy and regional lymphadenectomy for high-risk locally advanced UTUC. Postoperatively, he developed rapid progression of residual unresectable metastatic lymph nodes. Pathologic analysis and next-generation sequencing classified the tumor as highly aggressive TP53/MDM2-mutated subtype with features more than expression of programmed death ligand-1, including ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state. Immunochemotherapy combining gemcitabine, carboplatin, and off-label programmed death-1 inhibitor sintilimab was initiated, and sintilimab monotherapy was maintained up to 1 year. Retroperitoneal lymphatic metastases gradually regressed to complete response. Blood-based analyses were performed longitudinally for serum tumor markers, inflammatory parameters, peripheral immune cells, and circulating tumor DNA (ctDNA) profiling. The ctDNA kinetics of tumor mutation burden and mean variant allele frequency accurately predicted postoperative progression and sustained response to the following immunochemotherapy, which were mirrored by dynamic changes in abundances of ctDNA mutations from UTUC-typical variant genes. The patient remained free of recurrence or metastasis as of this publishing, over 2 years after the initial surgical treatment.

Conclusion

Immunochemotherapy may be a promising first-line option for advanced or metastatic UTUC selected with specific genomic or phenotypic signatures, and blood-based analyses incorporating ctDNA profiling provide precise longitudinal monitoring.
Mapping knowledge landscapes and emerging trends of the biomarkers in melanoma: a bibliometric analysis from 2004 to 2022
Authors: Wan Yantong , Shen Junyi , Hong Yinghao , Liu Jinghua , Shi Tieliu , Cai Junwei
Published: June 2023

Background

Melanoma is a skin tumor with a high mortality rate, and early diagnosis and effective treatment are the key to reduce its mortality rate. Therefore, more and more attention has been paid for biomarker identification for early diagnosis, prognosis prediction and prognosis evaluation of melanoma. However, there is still a lack of a report that comprehensively and objectively evaluates the research status of melanoma biomarkers. Therefore, this study aims to intuitively analyze the research status and trend of melanoma biomarkers through the methods of bibliometrics and knowledge graph.

Objective

This study uses bibliometrics to analyze research in biomarkers in melanoma, summarize the field’s history and current status of research, and predict future research directions.

Method

Articles and Reviews related to melanoma biomarkers were retrieved by using Web of Science core collection subject search. Bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer and Bibliometrix (R-Tool of R-Studio).

Result

A total of 5584 documents from 2004 to 2022 were included in the bibliometric analysis. The results show that the number of publications and the frequency of citations in this field are increasing year by year, and the frequency of citations has increased rapidly after 2018. The United States is the most productive and influential country in this field, with the largest number of publications and institutions with high citation frequency. Caroline Robert, F. Stephen Hodi, Suzanne L. Topalian and others are authoritative authors in this field, and The New England Journal of Medicine, Journal of Clinical Oncology and Clinical Cancer Research are the most authoritative journals in this field. Biomarkers related to the diagnosis, treatment and prognosis of melanoma are hot topics and cutting-edge hotspots in this field.

Conclusion

For the first time, this study used the bibliometric method to visualize the research in the field of melanoma biomarkers, revealing the trends and frontiers of melanoma biomarkers research, which provides a useful reference for scholars to find key research issues and partners.
Case Report: Two clinical cases of Wilms tumor comorbid to gingival fibromatosis in young children with constitutionally mutated REST
Authors: Salomatina Anastasiya S. , Yasko Liudmila A. , Kurnikova Maria A. , Mareeva Yulia M. , Abasov Ruslan K. , Gegeliya Nina V. , Mitrofanova Anna M. , Usman Natalia Y. , Novichkova Galina A. , Druy Alexander E.
Published: June 2023

Introduction

Nephroblastoma (Wilms tumor (WT)) is an embryonal tumor accounting for >90% of pediatric renal cancers. About 10% of WTs harbor pathogenic germline mutations. The REST gene, classified as a putative tumor suppressor, is affected in 2% of WTs. High-throughput molecular methods facilitate advanced diagnostics of cancer. In addition to this, germline mutations in REST are also associated with familial gingival fibromatosis (GFM). Reciprocally, none of the articles on RESTmut WT mentions GFM as a comorbid condition. This report provides unique evidence on the WT-GFM comorbidity in RESTmut carriers.

Case presentation

Patient 1 (a 5-year-old boy with unilateral WT) is a proband, who has two healthy siblings. Patient 2 (a 4-year-old girl with bilateral WT) is a proband from in vitro fertilization (IVF) triplets, with a sister and brother without WT. We analyzed probands’ DNA extracted from peripheral blood leucocytes with a custom-targeted next-generation sequencing (NGS)-198 gene panel. The detected variants were checked in family members by Sanger sequencing. Patient 1 had a pathogenic germline mutation in REST: c.1035_1036insTA, p.(E346*), as did his mother and both brothers. There were two other WT cases in this family (proband’s maternal uncles). Patient 2 had a pathogenic germline variant in REST: c.2668_2671del, p.(E891Pfs*6), as well as her sister. The mutation was probably inherited from their deceased father, as he had gingival fibromatosis. Family members with REST mutations from both families had gingival fibromatosis. A somatic REST c.663C>A p.C221* mutation was identified in one patient with WT. At the moment both patients with WT are under dynamic observation without signs of the disease.

Conclusion

Here, we describe two clinical cases of WT in nonrelated young children with germline-inactivating REST variants identified by next-generation sequencing. Both patients present with familial gingival fibromatosis, regarded as clinically useful comorbidity indicative of the tumor predisposition syndrome. The two cases illustrate Wilms tumor-gingival fibromatosis comorbidity in carriers of germline-inactivated REST alleles previously identified as a predisposition factor for both conditions.
Paired-agent imaging as a rapid en face margin screening method in Mohs micrographic surgery
Authors: Torres Veronica C. , Hodge Sassan , Levy Joshua J. , Vaickus Louis J. , Chen Eunice Y. , LeBouef Matthew , Samkoe Kimberley S.
Published: June 2023

Background

Mohs micrographic surgery is a procedure used for non-melanoma skin cancers that has 97-99% cure rates largely owing to 100% margin analysis enabled by en face sectioning with real-time, iterative histologic assessment. However, the technique is limited to small and aggressive tumors in high-risk areas because the histopathological preparation and assessment is very time intensive. To address this, paired-agent imaging (PAI) can be used to rapidly screen excised specimens and identify tumor positive margins for guided and more efficient microscopic evaluation.

Methods

A mouse xenograft model of human squamous cell carcinoma (n = 8 mice, 13 tumors) underwent PAI. Targeted (ABY-029, anti-epidermal growth factor receptor (EGFR) affibody molecule) and untargeted (IRDye 680LT carboxylate) imaging agents were simultaneously injected 3-4 h prior to surgical tumor resection. Fluorescence imaging was performed on main, unprocessed excised specimens and en face margins (tissue sections tangential to the deep margin surface). Binding potential (BP) – a quantity proportional to receptor concentration – and targeted fluorescence signal were measured for each, and respective mean and maximum values were analyzed to compare diagnostic ability and contrast. The BP and targeted fluorescence of the main specimen and margin samples were also correlated with EGFR immunohistochemistry (IHC).

Results

PAI consistently outperformed targeted fluorescence alone in terms of diagnostic ability and contrast-to-variance ratio (CVR). Mean and maximum measures of BP resulted in 100% accuracy, while mean and maximum targeted fluorescence signal offered 97% and 98% accuracy, respectively. Moreover, maximum BP had the greatest average CVR for both main specimen and margin samples (average 1.7 ± 0.4 times improvement over other measures). Fresh tissue margin imaging improved similarity with EGFR IHC volume estimates compared to main specimen imaging in line profile analysis; and margin BP specifically had the strongest concordance (average 3.6 ± 2.2 times improvement over other measures).

Conclusions

PAI was able to reliably distinguish tumor from normal tissue in fresh en face margin samples using the single metric of maximum BP. This demonstrated the potential for PAI to act as a highly sensitive screening tool to eliminate the extra time wasted on real-time pathological assessment of low-risk margins.
Risk factors of LEEP margin positivity and optimal length of cervical conization in cervical intraepithelial neoplasia
Authors: Cong Qing , Yu Yi , Xie Yu , Li Yanyun , Sui Long
Published: June 2023

Background

The conization length for cervical precancerous lesions is essential for treatment but is left undetermined. This study aims to explore the reasonable and optimal conization length in patients with different types of cervical transformation zones (TZs) to reach the treatment outcome of margin negative in the surgery.

Methods

From July 2016 to September 2019, a multi-center prospective case–control study with or suspicion of cervical precancer was enrolled from five medical centers in Shanghai, China. The clinical characteristics, cytology, human papillomavirus (HPV), histopathology, and details of cervical conization were recorded.

Results

A total of 618 women were enrolled in this study; 6.8% (42/618) had positive internal (endocervical and stromal) margins and 6.8% (42/618) had positive external (ectocervical) margins of loop electrosurgical excision procedure (LEEP) specimen. Comparing the positive internal margin group with the negative group, age (p = 0.006) and cytology (p = 0.021) were significantly different. Multivariate logistic regression analysis showed that the risk factors for positive internal margin were cytology ≥ high-grade squamous intraepithelial lesion (HSIL) (odds ratio (OR) 3.82, p = 0.002) and age (OR 1.11, p < 0.001). The positive internal margin rate was 2.7%, 5.1%, and 6.9% in TZ1, TZ2, and TZ3, respectively, while the positive external margin was 6.7%, 3.4%, and 1.4%, respectively. In the TZ3 group, the HSIL positive internal margin of the 15–16-mm group (10.0%, 19/191) was significantly greater than in TZ1 (2.7%, 4/150) (p = 0.010) and TZ2 (5.0%, 9/179) (p = 0.092); when excision length increases to 17–25 mm, the positive internal margin rate dramatically decreased to 1.0% (1/98).

Conclusion

A cervical excision length of 10–15 mm is reasonable for TZ1 and TZ2 patients, while 17–25 mm is optimal for TZ3 excision with more negative internal margins.
Nurses’ knowledge and attitude towards children pain management: a multi-site survey study
Authors: Fenta Efrem , Kibret Simegnew , Hunie Metages , Tamire Tadese , Eshetie Denberu , Seid Shimelis , Fentie Yewlsew , Amaha Eleni , Desse Tiruwork , Dejen Bantayehu , Essa Keder , Teshome Diriba
Published: June 2023

Background

Adequate children’s pain management is universally considered an ethical obligation. In evaluating and treating children’s pain, nurses invest more time and take a leading role. This study aims to evaluate the knowledge and attitudes of nurses towards the treatment of pediatric pain.

Materials and Methods

A total of 292 nurses working at four South Gondar Zone hospitals of Ethiopia was surveyed. To gather information from study participants, the Pediatric Nurses’ -Knowledge and Attitudes- Survey Regarding Pain (PNKAS) was employed. Frequency, percentage, mean, and standard deviation of the data were used for descriptive analysis, while Pearson correlation, one-way between-groups analysis of variance, and independent-samples t-test were used for inferential analysis.

Results

A large percentage of nurses (74.7%) lacked adequate knowledge and attitudes (PNKAS score <50%) for pediatric pain treatment. The mean ± SD accurate response score of 43.1% ± 8.6% was achieved by nurses. An increase in pediatrics nursing experience was significantly correlated with nurses’ PNKAS score (p < 0.001). The mean PNKAS scores of nurses who had official pain management training differed in a statistically significant way as compared to its counterpart (p < 0.001).

Conclusion

Nurses who are working South Gondar Zone of Ethiopia have insufficient knowledge and attitudes towards treatment of pediatric pain. Therefore, pediatric pain treatment in-service training is urgently needed.
Validation of the children international IgA nephropathy prediction tool based on data in Southwest China
Authors: Yu Xixi , Li Jiacheng , Tao Chengrong , Jiao Jia , Wan Junli , Zhong Cheng , Yang Qin , Shi Yongqi , Zhang Gaofu , Yang Haiping , Li Qiu , Wang Mo
Published: June 2023

Background

Immunoglobulin A nephropathy (IgAN) is one of the most common kidney diseases leading to renal injury. Of pediatric cases, 25%–30% progress into end-stage kidney disease (ESKD) in 20–25 years. Therefore, predicting and intervening in IgAN at an early stage is crucial. The purpose of this study was to validate the availability of an international predictive tool for childhood IgAN in a cohort of children with IgAN treated at a regional medical centre.

Methods

An external validation cohort of children with IgAN from medical centers in Southwest China was formed to validate the predictive performance of the two full models with and without race differences by comparing four measures: area under the curve (AUC), the regression coefficient of linear prediction (PI), survival analysis curves for different risk groups, and R2D.

Results

A total of 210 Chinese children, including 129 males, with an overall mean age of 9.43 ± 2.71 years, were incorporated from this regional medical center. In total, 11.43% (24/210) of patients achieved an outcome with a GFR decrease of more than 30% or reached ESKD. The AUC of the full model with race was 0.685 (95% CI: 0.570–0.800) and the AUC of the full model without race was 0.640 (95% CI: 0.517–0.764). The PI of the full model with race and without race was 0.816 (SE = 0.006, P < 0.001) and 0.751 (SE = 0.005, P < 0.001), respectively. The results of the survival curve analysis suggested the two models could not well distinguish between the low-risk and high-risk groups (P = 0.359 and P = 0.452), respectively, no matter the race difference. The evaluation of model fit for the full model with race was 66.5% and without race was 56.2%.

Conclusions

The international IgAN prediction tool has risk factors chosen based on adult data, and the validation cohort did not fully align with the derivation cohort in terms of demographic characteristics, clinical baseline levels, and pathological presentation, so the tool may not be highly applicable to children. We need to build IgAN prediction models that are more applicable to Chinese children based on their particular data.
Laparoscopic extraction of a urethral self-inflicted needle from pelvis in a boy: a case report
Authors: Wang Xiaoqing , Wu Xiangyu , Liu Wei , Du Guoqiang , Wang Yanze , Wu Rongde , Guo Feng
Published: June 2023

Introduction

Self-insertion of foreign bodies in the urethra is an infrequent occurrence in children, and their management aims to minimize urethral morbidity. Endoscopic removal presents a significant challenge, particularly in boys. Currently, there are few reports on laparoscopic management of urethral foreign bodies that have migrated to the pelvic cavity.

Case description

An 11-year-old boy presented to the emergency department with complaints of increased frequency of micturition and dysuria. A sharp sewing needle was discovered lodged in the posterior urethra mucosa during cystoscopy. Attempts to remove the needle using an endoscopic grasping forceps were unsuccessful due to the forceps' weak biting power. During a digital rectal examination, the needle migrated into the pelvic region, wedged between the prostatic urethra and the rectal ampulla. After careful inspection of the peritoneal reflection over the fundus of the bladder, the needle was identified and successfully removed through laparoscopy without any complications. Psychiatric counseling was advised for this patient, who was in good condition during an 8-week follow-up.

Conclusions

Our case demonstrates the first recorded use of laparoscopy to remove a self-inserted urethral needle that had migrated into the pelvic region, after failed attempts at endoscopic extraction. Future cases may benefit from considering laparoscopic interventions for similar circumstances.
COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies
Authors: Li Hui-Jun , Yang Qi-Chao , Yao Yang-Yang , Huang Cheng-Yang , Yin Fu-Qiang , Xian-Yu Chen-Yang , Zhang Chao , Chen Shao-Juan
Published: June 2023

Background: Even 3 years into the COVID-19 pandemic, questions remain about how to safely and effectively vaccinate vulnerable populations. A systematic analysis of the safety and efficacy of the COVID-19 vaccine in at-risk groups has not been conducted to date.

Methods: This study involved a comprehensive search of PubMed, EMBASE, and Cochrane Central Controlled Trial Registry data through 12 July 2022. Post-vaccination outcomes included the number of humoral and cellular immune responders in vulnerable and healthy populations, antibody levels in humoral immune responders, and adverse events.

Results: A total of 23 articles assessing 32 studies, were included. The levels of IgG (SMD = −1.82, 95% CI [−2.28, −1.35]), IgA (SMD = −0.37, 95% CI [−0.70, −0.03]), IgM (SMD = −0.94, 95% CI [−1.38, −0.51]), neutralizing antibodies (SMD = −1.37, 95% CI [−2.62, −0.11]), and T cells (SMD = −1.98, 95% CI [−3.44, −0.53]) were significantly lower in vulnerable than in healthy populations. The positive detection rates of IgG (OR = 0.05, 95% CI [0.02, 0.14]) and IgA (OR = 0.03, 95% CI [0.01, 0.11]) antibodies and the cellular immune response rates (OR = 0.20, 95% CI [0.09, 0.45]) were also lower in the vulnerable populations. There were no statistically significant differences in fever (OR = 2.53, 95% CI [0.11, 60.86]), chills (OR = 2.03, 95% CI [0.08, 53.85]), myalgia (OR = 10.31, 95% CI [0.56, 191.08]), local pain at the injection site (OR = 17.83, 95% CI [0.32, 989.06]), headache (OR = 53.57, 95% CI [3.21, 892.79]), tenderness (OR = 2.68, 95% CI [0.49, 14.73]), and fatigue (OR = 22.89, 95% CI [0.45, 1164.22]) between the vulnerable and healthy populations.

Conclusion: Seroconversion rates after COVID-19 vaccination were generally worse in the vulnerable than healthy populations, but there was no difference in adverse events. Patients with hematological cancers had the lowest IgG antibody levels of all the vulnerable populations, so closer attention to these patients is recommended. Subjects who received the combined vaccine had higher antibody levels than those who received the single vaccine.
Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
Authors: Santoyo Jean Michell , Noguera José Antonio , Avilés Francisco , Hernández-Caselles Trinidad , de Paco-Matallana Catalina , Delgado Juan Luis , Cuevas Santiago , Llinás M. Teresa , Hernández Isabel
Published: June 2023

Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia.

Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers.

Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001).

Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease.
Aortic dissection induced by vascular endothelial growth factor inhibitors
Authors: Dai Shuqi , Zhong Yu , Cui Hongxia , Zhao Jin , Li Su
Published: June 2023

Vascular endothelial growth factor (VEGF) contributes to angiogenesis and vasculogenesis. The occurrence and progression of tumors are accompanied by angiogenesis. Vascular endothelial growth factor inhibitors (VEGFI) have been used in anti-tumor treatment. However, aortic dissection (AD) is one of the VEGFI-associated adverse reactions with cute onset, rapid progression, and high case fatality rate. We collected case reports of VEGFI related to aortic dissection in PubMed and CNKI (China National Knowledge Infrastructure) from inception to 28 April 2022. Seventeen case reports were selected. The medication included sunitinib, sorafenib, pazopanib, axitinib, apatinib, anlotinib, bevacizumab, and ramucirumab. This review discusses the pathology, risk factors, diagnosis, and treatment of AD. Vascular endothelial growth factor inhibitors are related to aortic dissection. Although current literature lacks clear statistical evidence on the population, we offer points to encourage further confirmation of the best methods of care for these patients.
Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53
Authors: Herrera-Calderon Oscar , Herrera-Ramírez Angie , Cardona-G Wilson , Melgar-Merino Elizabeth Julia , Chávez Haydee , Pari-Olarte Josefa Bertha , Loyola-Gonzales Eddie , Kong-Chirinos José Francisco , Almeida-Galindo José Santiago , Peña-Rojas Gilmar , Andía-Ayme Vidalina
Published: June 2023

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.
Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
Authors: Imig John D.
Published: June 2023

Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs have been developed for nuclear receptors such as peroxisome proliferator-activated receptors (PPARα and PPARγ) and farnesoid X receptor (FXR). PPARα, PPARγ, and FXR agonists are used clinically to treat lipid disorders and metabolic diseases. Evidence from clinical studies and animal hypertension models have demonstrated that PPARα, PPARγ, and FXR agonism can lower blood pressure and decrease end organ damage which could be useful for the treatment of hypertension in patients with metabolic diseases. Unfortunately, PPAR and FXR agonists have unwanted clinical side effects. There have been recent developments to limit side effects for PPAR and FXR agonists. Combining PPAR and FXR agonism with soluble epoxide hydrolase (sEH) inhibition or Takeda G protein receptor 5 (TGR5) agonism has been demonstrated in preclinical studies to have actions that would decrease clinical side effects. In addition, these dual modulating drugs have been demonstrated in preclinical studies to have blood pressure lowering, anti-fibrotic, and anti-inflammatory actions. There is now an opportunity to thoroughly test these novel dual modulators in animal models of hypertension associated with metabolic diseases. In particular, these newly developed dual modulating PPAR and FXR drugs could be beneficial for the treatment of metabolic diseases, organ fibrosis, and hypertension.
A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults
Authors: Mah Eunice , Blonquist Traci M. , Kaden Valerie N. , Beckman Dawn , Boileau Amy C. , Anthony Joshua C. , Stubbs Brianna J.
Published: June 2023

Introduction: Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB).

Methods: We undertook a randomized, parallel, open-label study in healthy adults (n = 33) to elucidate blood BHB, HEX and BDO concentrations for 8 h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50 g/day) before (Day 0) and after 7 days of daily BH-BD consumption (Day 7).

Results: Maximal concentration and area under the curve of all metabolites increased proportionally to SS and were greatest for BHB followed by BDO then HEX on both Day 0 and 7. Metabolite half-life tended to decrease with increasing SS for BHB and HEX. Time to peak concentration increased with increasing SS for BHB and BDO on both days. In vitro incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis.

Conclusion: These results demonstrate that orally ingested BH-BD is hydrolyzed into products that appear in the plasma and undergo conversion to BHB in a SS dependent manner, and that metabolism of BH-BD neither becomes saturated at serving sizes up to 50 g nor displays consistent adaptation after 7 days of daily consumption.
Construction of a genetic linkage map and QTL mapping of fruit quality traits in guava (Psidium guajava L.)
Authors: Maan Sukhjinder Singh , Brar Jaswinder Singh , Mittal Amandeep , Gill Manav Indra Singh , Arora Naresh Kumar , Sohi Harjot Singh , Chhuneja Parveen , Dhillon Guriqbal Singh , Singh Navdeep , Thakur Sujata
Published: June 2023

Guava (Psidium guajavaL.) is an important fruit crop of the Indian sub-continent, with potential for improvements in quality and yield. The goal of the present study was to construct a genetic linkage map in an intraspecific cross between the elite cultivar ‘Allahabad Safeda’ and the Purple Guava landrace to identify the genomic regions responsible for important fruit quality traits, viz., total soluble solids, titratable acidity, vitamin C, and sugars. This population was phenotyped in field trials (as a winter crop) for three consecutive years, and showed moderate-to-high values of heterogeneity coefficients along with higher heritability (60.0%–97.0%) and genetic-advance-over-mean values (13.23%–31.17%), suggesting minimal environmental influence on the expression of fruit-quality traits and indicating that these traits can be improved by phenotypic selection methods. Significant correlations and strong associations were also detected among fruit physico-chemical traits in segregating progeny. The constructed linkage map consisted of 195 markers distributed across 11 chromosomes, spanning a length of 1,604.47 cM (average inter-loci distance of 8.80 markers) and with 88.00% coverage of the guava genome. Fifty-eight quantitative trait loci (QTLs) were detected in three environments with best linear unbiased prediction (BLUP) values using the composite interval mapping algorithm of the BIP (biparental populations) module. The QTLs were distributed on seven different chromosomes, explaining 10.95%–17.77% of phenotypic variance, with the highest LOD score being 5.96 for qTSS.AS.pau-6.2. Thirteen QTLs detected across multiple environments with BLUPs indicate stability and utility in a future breeding program for guava. Furthermore, seven QTL clusters with stable or common individual QTLs affecting two or more different traits were located on six linkage groups (LGs), explaining the correlation among fruit-quality traits. Thus, the multiple environmental evaluations conducted here have increased our understanding of the molecular basis of phenotypic variation, providing the basis for future high-resolution fine-mapping and paving the way for marker-assisted breeding of fruit-quality traits.
Nitrogen reduction combined with ETc irrigation maintained summer maize yield and increased water and nitrogen use efficiency
Authors: Gu Limin , Mu Xinyuan , Qi Jianshuang , Tang Baojun , Zhen Wenchao , Xia Laikun
Published: June 2023

Introduction

High rainfall and excessive urea application are counterproductive to summer maize growth requirements and lower grain yield and water/nitrogen (N) use efficiency. The objective of this study was to determine whether ETc irrigation based on summer maize demand and reduced nitrogen rate in the Huang Huai Hai Plain increased water and nitrogen use efficiency without sacrificing yield.

Methods

To achieve this, we conducted an experiment with four irrigation levels [ambient rainfall (I0) and 50% (I1), 75% (I2), and 100% (I3) of actual crop evapotranspiration (ETc)] and four nitrogen rates [no nitrogen fertilizer (N0), recommended nitrogen rate of urea (NU), recommended nitrogen rate of blending controlled-release urea with conventional urea fertilizer (BCRF) (NC), and reduced nitrogen rate of BCRF (NR)] in 2016–2018.

Results

The results show that reduced irrigation and nitrogen rate reduced Fv/Fm, 13C-photosynthate, and nitrogen accumulation both in the kernel and plant. I3NC and I3NU accumulated higher 13C-photosynthate, nitrogen, and dry matter. However, 13C-photosynthate and nitrogen distribution to the kernel was decreased from I2 to I3 and was higher in BCRF than in urea. I2NC and I2NR promoted their distribution to the kernel, resulting in a higher harvest index. Compared with I3NU, I2NR increased root length density by 32.8% on average, maintaining considerable leaf Fv/Fm and obtaining similar kernel number and kernel weight. The higher root length density of I2NR of 40–60 cm promoted 13C-photosynthate and nitrogen distribution to the kernel and increased the harvest index. As a result, the water use efficiency (WUE) and nitrogen agronomic use efficiency (NAUE) in I2NR increased by 20.5%–31.9% and 11.0%–38.0% than that in I3NU, respectively.

Discussion

Therefore, 75%ETc deficit irrigation and BCRF fertilizer with 80% nitrogen rate improved root length density, maintained leaf Fv/Fm in the milking stage, promoted 13C-photosynthate, and distributed nitrogen to the kernel, ultimately providing a higher WUE and NAUE without significantly reducing grain yield.
Genetic diversity and genome-wide association analysis of pine wood nematode populations in different regions of China
Authors: Aixia Yang , Xiaolei Ding , Yuan Feng , Ruiwen Zhao , Jianren Ye
Published: June 2023

Introduction

Pine wilt disease (Bursaphelenchus xylophilus) was recently detected in Liaoning Province, which was previously considered an unfavourable area for B. xylophilus due to its low temperatures. This study aims to compare the reproductivity and genetic variations of B. xylophilus isolates from Liaoning Province and other parts of China to explore their phenotypic and genomic differences.

Methods

The samples from Liaoning, Anhui, Hubei, Henan, Zhejiang and Jiangsu were isolated and purified to obtain the strains. The reproductivity of the strains was determined at 15 °C. The genetic structure was analyzed by using SNP molecular markers, and the whole genome association analysis was carried out by integrating SNP information and feculence traits.

Results

A reproductivity experiment showed that Liaoning isolates have higher reproductive ability at 15 °C. Subsequent SNP profiling and population differentiation analysis revealed obvious genetic differentiation of Liaoning isolates from other isolates. A genome-wide association study showed that SNPs closely related to low-temperature tolerance were mainly located in GPCR, Acyl-CoA, and Cpn10, which are responsible for adaptation to environmental factors, such as temperature change.

Discussion

Pine wood nematodes likely adapted to the climate in Liaoning and maintained a certain reproductive capacity at low temperature via variants of adaptation-related genes. This study provides a theoretical basis for elucidating the prevalence and diffusion status of B. xylophilus in China.
Allelic expression of AhNSP2-B07 due to parent of origin affects peanut nodulation
Authors: Zhao Zifan , Wang Yichun , Peng Ze , Luo Ziliang , Zhao Meixia , Wang Jianping
Published: June 2023

Legumes are well-known for establishing a symbiotic relationship with rhizobia in root nodules to fix nitrogen from the atmosphere. The nodulation signaling pathway 2 (NSP2) gene plays a critical role in the symbiotic signaling pathway. In cultivated peanut, an allotetraploid (2n = 4x = 40, AABB) legume crop, natural polymorphisms in a pair of NSP2 homoeologs (Na and Nb) located on chromosomes A08 and B07, respectively, can cause loss of nodulation. Interestingly, some heterozygous (NBnb) progeny produced nodules, while some others do not, suggesting non-Mendelian inheritance in the segregating population at the Nb locus. In this study, we investigated the non-Mendelian inheritance at the NB locus. Selfing populations were developed to validate the genotypical and phenotypical segregating ratios. Allelic expression was detected in roots, ovaries, and pollens of heterozygous plants. Bisulfite PCR and sequencing of the Nb gene in gametic tissue were performed to detect the DNA methylation variations of this gene in different gametic tissues. The results showed that only one allele at the Nb locus expressed in peanut roots during symbiosis. In the heterozygous (Nbnb) plants, if dominant allele expressed, the plants produced nodules, if recessive allele expressed, then no nodules were produced. qRT-PCR experiments revealed that the expression of Nb gene in the ovary was extremely low, about seven times lower than that in pollen, regardless of genotypes or phenotypes of the plants at this locus. The results indicated that Nb gene expression in peanut depends on the parent of origin and is imprinted in female gametes. However, no significant differences of DNA methylation level were detected between these two gametic tissues by bisulfite PCR and sequencing. The results suggested that the remarkable low expression of Nb in female gametes may not be caused by DNA methylation. This study provided a unique genetic basis of a key gene involved in peanut symbiosis, which could facilitate understanding the regulation of gene expression in symbiosis in polyploid legumes.
Responses to water stress extremes in diverse red clover germplasm accessions
Authors: Heslop Angus D. , Jahufer Zulfi , Hofmann Rainer W.
Published: June 2023

Red clover (Trifolium pratense L.), a key perennial pastoral species used globally, can strengthen pastural mixes to withstand increasingly disruptive weather patterns from climate change. Breeding selections can be refined for this purpose by obtaining an in-depth understanding of key functional traits. A replicated randomized complete block glasshouse pot trial was used to observe trait responses critical to plant performance under control (15% VMC), water deficit (5% VMC) and waterlogged conditions (50% VMC) in seven red clover populations and compared against white clover. Twelve morphological and physiological traits were identified as key contributors to the different plant coping mechanisms displayed. Under water deficit, the levels of all aboveground morphological traits decreased, highlighted by a 41% decrease in total dry matter and 50% decreases in both leaf number and leaf thickness compared to the control treatment. An increase in root to shoot ratio indicated a shift to prioritizing root maintenance by sacrificing shoot growth, a trait attributed to plant water deficit tolerance. Under waterlogging, a reduction in photosynthetic activity among red clover populations reduced several morphological traits including a 30% decrease in root dry mass and total dry matter, and a 34% decrease in leaf number. The importance of root morphology for waterlogging was highlighted with low performance of red clover: there was an 83% decrease in root dry mass compared to white clover which was able to maintain root dry mass and therefore plant performance. This study highlights the importance of germplasm evaluation across water stress extremes to identify traits for future breeding programs.
Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus
Authors: De Bruyn Charlotte , Ruttink Tom , Lacchini Elia , Rombauts Stephane , Haegeman Annelies , De Keyser Ellen , Van Poucke Christof , Desmet Sandrien , Jacobs Thomas B. , Eeckhaut Tom , Goossens Alain , Van Laere Katrijn
Published: June 2023

Industrial chicory (Cichorium intybus var. sativum) and witloof (C. intybus var. foliosum) are crops with an important economic value, mainly cultivated for inulin production and as a leafy vegetable, respectively. Both crops are rich in nutritionally relevant specialized metabolites with beneficial effects for human health. However, their bitter taste, caused by the sesquiterpene lactones (SLs) produced in leaves and taproot, limits wider applications in the food industry. Changing the bitterness would thus create new opportunities with a great economic impact. Known genes encoding enzymes involved in the SL biosynthetic pathway are GERMACRENE A SYNTHASE (GAS), GERMACRENE A OXIDASE (GAO), COSTUNOLIDE SYNTHASE (COS) and KAUNIOLIDE SYNTHASE (KLS). In this study, we integrated genome and transcriptome mining to further unravel SL biosynthesis. We found that C. intybus SL biosynthesis is controlled by the phytohormone methyl jasmonate (MeJA). Gene family annotation and MeJA inducibility enabled the pinpointing of candidate genes related with the SL biosynthetic pathway. We specifically focused on members of subclade CYP71 of the cytochrome P450 family. We verified the biochemical activity of 14 C. intybus CYP71 enzymes transiently produced in Nicotiana benthamiana and identified several functional paralogs for each of the GAO, COS and KLS genes, pointing to redundancy in and robustness of the SL biosynthetic pathway. Gene functionality was further analyzed using CRISPR/Cas9 genome editing in C. intybus. Metabolite profiling of mutant C. intybus lines demonstrated a successful reduction in SL metabolite production. Together, this study increases our insights into the C. intybus SL biosynthetic pathway and paves the way for the engineering of C. intybus bitterness.