bluuebunny/crossref_metadata_2025 huggingface dataset:
The antibacterial mechanism of compound preservatives combined with low voltage electric fields on the preservation of steamed mussels (Mytilus edulis) stored at ice-temperature
Authors: Wang Kunmei , Wang Han , Wu Yue , Yi Chong , Lv Yanxia , Luo Hongyu , Yang Tao
Published: March 2023

Mussels are a kind of economically valuable ocean bivalve shellfish. It has a short harvest period and is susceptible to contamination during storage and processing. Having proper preservation methods is critical to prevent quality deterioration. However, the effect of low voltage variable frequency electric field and compound preservative on the freshness of steamed mussels in ice-temperature storage are still unknown. We utilized the method of coefficient variation weighting to calculate the overall scores of steamed mussels stored under different preservation conditions. The protein physicochemical properties of samples, the growth curves of two dominant spoilage bacteria; Bacillus subtilis and Pseudomonas in the mussels as well as the Structural changes of the cell membranes were mensurated. The results show that compared with the preservative group and the low voltage variable frequency electric field group, the compound preservatives combined with the electric field group had the highest overall score and thus the best preservation effect. Compared with the blank group, the total sulfhydryl content and myogenic fibrin content of the combined group decreased at the slowest rate, 19.46%, and 44.92%, respectively. The hydrophobicity of the protein surface increased by only 5.67%, with the best water retention, indicating that the samples of the combined group had the least protein deterioration in the combined group. The inhibition mechanism of the combined group inhibited the growth of two dominant spoilage bacteria: Bacillus subtilis and Pseudomonas, in the mussels, destroying the integrity of the cell membrane structure and changing the cell morphology. Overall, we found that the combination of the composite preservatives and the low voltage variable frequency electric field can maintain the best quality of steamed mussels during ice-temperature storage and slow down the rate of protein deterioration during storage. This study proposed a new method of mussel preservation, which provides a new idea for the application of low voltage variable frequency electric field and compound preservative in the preservation of aquatic products.
Giant desmoplastic small round cell tumor of the abdomen: A case report
Authors: Wang Wuke , Chen Yunjie , Wang Chunnian , Su Hui
Published: March 2023

Background

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, mesenchymal malignancy of a separate clinicopathological entity. It has a predilection for young men, with no evidence of any ethnic predilection. The current diagnostic gold standard for DSRCT includes histopathologic, immunohistochemical, and cytogenetic studies in order to confirm the variable phenotypic expression and characteristic chromosomal translocation.

Case summary

A 65-year-old man presented with a sensation of an abdominal mass and a presentation of an incomplete bowel obstruction. Initial lab tests were in the normal range except for carbohydrate antigen. Contrast-enhanced CT showed that a large, mass-confounding density was occupied in the omentum majus area of the middle and lower abdominal wall. A 3D reconstruction of the images was performed to clarify the relationship between the tumor and the colon and was confirmed by a colonoscopy. After surgery, immunohistochemistry and fluorescence in situ hybridization (FISH) revealed EWSR1-WT1 gene rearrangement at 22q12, confirming the diagnosis of desmoplastic small round cell tumor.

Conclusion

Being different from the predilection of DSRCT for young men, the patient in our case is a 65-year-old man with a huge mass involving the transverse colon and the bladder.
BOMB trial: First results of stereotactic radiotherapy to primary breast tumor in metastatic breast cancer patients
Authors: Ippolito Edy , Silipigni Sonia , Pantano Francesco , Matteucci Paolo , Carrafiello Sofia , Marrocco Maristella , Alaimo Rita , Palumbo Vincenzo , Fiore Michele , Orsaria Paolo , D’Angelillo Rolando Maria , Altomare Vittorio , Tonini Giuseppe , Ramella Sara
Published: March 2023

Aim

A prospective dose escalation trial was developed to evaluate the maximum tolerated dose of stereotactic body radiotherapy (SABRT) to primary breast cancer in stage IV disease. The aim of the present report was to describe safety and outcome of the first dose level cohort of patients.

Material and methods

Patients with histologically confirmed diagnosis of invasive breast carcinoma (biological immuno-histochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose-limiting toxicity (DLT).

Results

To date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease, while 3 patients had an HER2 positive disease. No patient suspended ongoing systemic treatment. No protocol defined DLTs were observed. Grade 2 skin toxicity occurred in 4 patients with diseases located close to or involving the skin. Median follow-up was 13 months and all 10 patients were evaluable for response: 5 achieved a complete response, 3 achieved a partial response and 2 showed a stable disease, all with a clinical benefit (resolution of skin retraction, bleeding and pain). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%).

Conclusions

SABR to primary breast cancer seems feasible and is associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05229575.
In-vivo magnetic resonance spectroscopy of lactate as a non-invasive biomarker of dichloroacetate activity in cancer and non-cancer central nervous system disorders
Authors: Kamson David O. , Chinnasamy Viveka , Grossman Stuart A. , Bettegowda Chetan , Barker Peter B. , Stacpoole Peter W. , Oeltzschner Georg
Published: March 2023

The adverse effects of lactic acidosis in the cancer microenvironment have been increasingly recognized. Dichloroacetate (DCA) is an orally bioavailable, blood brain barrier penetrable drug that has been extensively studied in the treatment of mitochondrial neurologic conditions to reduce lactate production. Due to its effect reversing aerobic glycolysis (i.e., Warburg-effect) and thus lactic acidosis, DCA became a drug of interest in cancer as well. Magnetic resonance spectroscopy (MRS) is a well-established, non-invasive technique that allows detection of prominent metabolic changes, such as shifts in lactate or glutamate levels. Thus, MRS is a potential radiographic biomarker to allow spatial and temporal mapping of DCA treatment. In this systematic literature review, we gathered the available evidence on the use of various MRS techniques to track metabolic changes after DCA administration in neurologic and oncologic disorders. We included in vitro, animal, and human studies. Evidence confirms that DCA has substantial effects on lactate and glutamate levels in neurologic and oncologic disease, which are detectable by both experimental and routine clinical MRS approaches. Data from mitochondrial diseases show slower lactate changes in the central nervous system (CNS) that correlate better with clinical function compared to blood. This difference is most striking in focal impairments of lactate metabolism suggesting that MRS might provide data not captured by solely monitoring blood. In summary, our findings corroborate the feasibility of MRS as a pharmacokinetic/pharmacodynamic biomarker of DCA delivery in the CNS, that is ready to be integrated into currently ongoing and future human clinical trials using DCA.
Machine learning in non-small cell lung cancer radiotherapy: A bibliometric analysis
Authors: Zhang Jiaming , Zhu Huijun , Wang Jue , Chen Yulu , Li Yihe , Chen Xinyu , Chen Menghua , Cai Zhengwen , Liu Wenqi
Published: March 2023

Background

Machine learning is now well-developed in non-small cell lung cancer (NSCLC) radiotherapy. But the research trend and hotspots are still unclear. To investigate the progress in machine learning in radiotherapy NSCLC, we performed a bibliometric analysis of associated research and discuss the current research hotspots and potential hot areas in the future.

Methods

The involved researches were obtained from the Web of Science Core Collection database (WoSCC). We used R-studio software, the Bibliometrix package and VOSviewer (Version 1.6.18) software to perform bibliometric analysis.

Results

We found 197 publications about machine learning in radiotherapy for NSCLC in the WoSCC, and the journal Medical Physics contributed the most articles. The University of Texas MD Anderson Cancer Center was the most frequent publishing institution, and the United States contributed most of the publications. In our bibliometric analysis, “radiomics” was the most frequent keyword, and we found that machine learning is mainly applied to analyze medical images in the radiotherapy of NSCLC.

Conclusion

The research we identified about machine learning in NSCLC radiotherapy was mainly related to the radiotherapy planning of NSCLC and the prediction of treatment effects and adverse events in NSCLC patients who were under radiotherapy. Our research has added new insights into machine learning in NSCLC radiotherapy and could help researchers better identify hot research areas in the future.
Rare papillary renal neoplasm with reverse polarity: A case report and review of the literature
Authors: Tu Xi , Zhuang Xiyao , Chen Qiong , Wang Wei , Huang Chaoyou
Published: March 2023

Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumour and was newly named in 2019. This study reported a case of a 30-year-old female patient with a left renal tumour without any clinical symptoms and whose CT scan of her left kidney showed a mass of 2.6 cm×2.3 cm, which was considered to be renal clear cell carcinoma. Laparoscopic partial nephrectomy was performed, and histopathology and immunohistochemistry confirmed papillary renal neoplasm with reverse polarity, which had unique clinicopathological features, immunophenotype, KRAS gene mutation and relatively indolent biological behaviour. As newly diagnosed cases, rigorous and regular follow-up is necessary. In addition, a literature review was performed from 1978 to 2022, and 97 cases of papillary renal neoplasms with reverse polarity were identified and analysed.
SF3B1 mutations in myelodysplastic syndromes: A potential therapeutic target for modulating the entire disease process
Authors: Jiang Moqin , Chen Meng , Liu Qian , Jin Zhiling , Yang Xiangdong , Zhang Weifeng
Published: March 2023

Myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by ineffective hematopoiesis and dysplasia of the myeloid cell lineage and are characterized by peripheral blood cytopenia and an increased risk of transformation to acute myeloid leukemia (AML). Approximately half of the patients with MDS have somatic mutations in the spliceosome gene. Splicing Factor 3B Subunit 1A (SF3B1), the most frequently occurring splicing factor mutation in MDS is significantly associated with the MDS-RS subtype. SF3B1 mutations are intimately involved in the MDS regulation of various pathophysiological processes, including impaired erythropoiesis, dysregulated iron metabolism homeostasis, hyperinflammatory features, and R-loop accumulation. In the fifth edition of the World Health Organization (WHO) classification criteria for MDS, MDS with SF3B1 mutations has been classified as an independent subtype, which plays a crucial role in identifying the disease phenotype, promoting tumor development, determining clinical features, and influencing tumor prognosis. Given that SF3B1 has demonstrated therapeutic vulnerability both in early MDS drivers and downstream events, therapy based on spliceosome-associated mutations is considered a novel strategy worth exploring in the future.
Study on the role and pharmacology of cuproptosis in gastric cancer
Authors: Jiang Lin , Liao Junzuo , Han Yunwei
Published: March 2023

Objective

Gastric cancer has a poor prognosis and high mortality. Cuproptosis, a novel programmed cell death, is rarely studied in gastric cancer. Studying the mechanism of cuproptosis in gastric cancer is conducive to the development of new drugs, improving the prognosis of patients and reducing the burden of disease.

Methods

The TCGA database was used to obtain transcriptome data from gastric cancer tissues and adjacent tissues. GSE66229 was used for external verification. Overlapping genes were obtained by crossing the genes obtained by differential analysis with those related to copper death. Eight characteristic genes were obtained by three dimensionality reduction methods: lasso, SVM, and random forest. ROC and nomogram were used to estimate the diagnostic efficacy of characteristic genes. The CIBERSORT method was used to assess immune infiltration. ConsensusClusterPlus was used for subtype classification. Discovery Studio software conducts molecular docking between drugs and target proteins.

Results

We have established the early diagnosis model of eight characteristic genes (ENTPD3, PDZD4, CNN1, GTPBP4, FPGS, UTP25, CENPW, and FAM111A) for gastric cancer. The results are validated by internal and external data, and the predictive power is good. The subtype classification and immune type analysis of gastric cancer samples were performed based on the consensus clustering method. We identified C2 as an immune subtype and C1 as a non-immune subtype. Small molecule drug targeting based on genes associated with cuproptosis predicts potential therapeutics for gastric cancer. Molecular docking revealed multiple forces between Dasatinib and CNN1.

Conclusion

The candidate drug Dasatinib may be effective in treating gastric cancer by affecting the expression of the cuproptosis signature gene.
Epitranscriptomics in the development, functions, and disorders of cancer stem cells
Authors: Hao Linlin , Zhang Jian , Liu Zhongshan , Lin Xia , Guo Jie
Published: March 2023

Biomolecular modifications play an important role in the development of life, and previous studies have investigated the role of DNA and proteins. In the last decade, with the development of sequencing technology, the veil of epitranscriptomics has been gradually lifted. Transcriptomics focuses on RNA modifications that affect gene expression at the transcriptional level. With further research, scientists have found that changes in RNA modification proteins are closely linked to cancer tumorigenesis, progression, metastasis, and drug resistance. Cancer stem cells (CSCs) are considered powerful drivers of tumorigenesis and key factors for therapeutic resistance. In this article, we focus on describing RNA modifications associated with CSCs and summarize the associated research progress. The aim of this review is to identify new directions for cancer diagnosis and targeted therapy.
Clinical characteristics and survival of second primary breast carcinoma with extramammary malignancies
Authors: Jing Yaoyao , Wang Xiaofang , Sun Bei
Published: March 2023

Objectives

To investigate the characteristics, diagnosis, survival and prognosis of second primary breast carcinoma (SPBC).

Materials and methods

Records of 123 patients with SPBC in Tianjin Medical University Cancer Institute & Hospital between December 2002 and December 2020 were retrospectively reviewed. Clinical characteristics, imaging features and survival were analyzed and comparisons between SPBC and breast metastases (BM) were made.

Results

Of 67156 newly diagnosed breast cancer patients, 123 patients (0.18%) suffered previous extramammary primary malignancies. Of the 123 patients with SPBC, approximately 98.37%(121/123)were female. The median age was 55 years old (27-87). The average diameter of breast mass was 2.7 cm (0.5-10.7). Approximately 77.24% (95/123) of the patients presented with symptoms. The most common types of extramammary primary malignancies were thyroid, gynecological cancers, lung, and colorectal. Patients with the first primary malignant tumor of lung cancer were more likely to develop synchronous SPBC, and those with the first primary malignant tumor of ovarian cancer were more likely to develop metachronous SPBC. When comparing with BM, patients with SPBC were more often older (≥45 years old), at earlier stages (I/II), more microcalcification and less multiple breast masses in imaging. More than half (55.88%) of patients in the metachronous group developed primary breast cancer within 5 years after diagnosis of extramammary primary cancer. The median overall survival time was 71 months. Within 90 months, the prognosis of patients with synchronous SPBC was worse than that of patients with metachronous SPBC (p=0.014). Patients with BM had the worst outcome compared with patients with synchronous SPBC and metachronous SPBC (p<0.001).ER/PR-negative status, an interval of less than 6 months between the onset of two tumors, a late stage of first primary malignancy, and an age of diagnosis of first primary malignancy greater than 60 years predicted a worse prognosis for patients with SPBC.

Conclusion

The possibility of SPBC should be considered during the follow-up of patients with primary extramammary malignancy, especially within 5 years of the onset of the first tumor. The stage of first primary malignancy and the age at diagnosis of first primary malignancy have an impact on the prognosis of patients with SPBC.
Calcitonin gene relating peptide inhibitors in combination for migraine treatment: A mini-review
Authors: Shah Tulsi , Bedrin Kate , Tinsley Amanda
Published: March 2023

The discovery of calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology has led to advances in the treatment of migraine. Since 2018, the Food and Drug Administration (FDA) has approved four monoclonal antibody (mab) therapies targeting either the CGRP ligand or receptor and 3 oral small molecule CGRP receptor antagonists. These targeted therapies have been shown to be safe and effective for either preventive or acute treatment of migraine in adults. Given their efficacy and tolerability profile, CGRP inhibitors have revolutionized the approach to migraine treatment. Theoretically, combining therapies within this therapeutic class could lead to more CGRP blockade and, subsequently, improved patient outcomes. There are providers currently combining CGRP therapies in clinical practice. However, limited data are available regarding the efficacy and safety of this practice. This mini-review provides a summary of available data and poses important considerations when combining CGRP therapies for migraine treatment.
Physical activity and physical fitness in children with heritable connective tissue disorders
Authors: de Koning Lisanne , Warnink-Kavelaars Jessica , van Rossum Marion , Limmen Selina , Van der Looven Ruth , Muiño-Mosquera Laura , van der Hulst Annelies , Oosterlaan Jaap , Rombaut Lies , Engelbert Raoul ,   on behalf of the Pediatric Heritable Connective Tissue Disorders Study Group
Published: March 2023

Objectives

Health problems in patients with heritable connective tissue disorders (HCTD) are diverse and complex and might lead to lower physical activity (PA) and physical fitness (PF). This study aimed to investigate the PA and PF of children with heritable connective tissue disorders (HCTD).

Methods

PA was assessed using an accelerometer-based activity monitor (ActivPAL) and the mobility subscale of the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). PF was measured in terms of cardiovascular endurance using the Fitkids Treadmill Test (FTT); maximal hand grip strength, using hand grip dynamometry (HGD) as an indicator of muscle strength; and motor proficiency, using the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOTMP-2).

Results

A total of 56 children, with a median age of 11.6 (interquartile range [IQR], 8.8–15.8) years, diagnosed with Marfan syndrome (MFS), n = 37, Loeys-Dietz syndrome (LDS), n = 6, and genetically confirmed Ehlers-Danlos (EDS) syndromes, n = 13 (including classical EDS n = 10, vascular EDS n = 1, dermatosparaxis EDS n = 1, arthrochalasia EDS n = 1), participated. Regarding PA, children with HCTD were active for 4.5 (IQR 3.5–5.2) hours/day, spent 9.2 (IQR 7.6–10.4) hours/day sedentary, slept 11.2 (IQR 9.5–11.5) hours/day, and performed 8,351.7 (IQR 6,456.9–1,0484.6) steps/day. They scored below average (mean (standard deviation [SD]) z-score −1.4 (1.6)) on the PEDI-CAT mobility subscale. Regarding PF, children with HCTD scored well below average on the FFT (mean (SD) z-score −3.3 (3.2)) and below average on the HGD (mean (SD) z-score −1.1 (1.2)) compared to normative data. Contradictory, the BOTMP-2 score was classified as average (mean (SD) z-score.02 (.98)). Moderate positive correlations were found between PA and PF (r(39) = .378, p < .001). Moderately sized negative correlations were found between pain intensity and fatigue and time spent actively (r(35) = .408, p < .001 and r(24) = .395 p < .001, respectively).

Conclusion

This study is the first to demonstrate reduced PA and PF in children with HCTD. PF was moderately positively correlated with PA and negatively correlated with pain intensity and fatigue. Reduced cardiovascular endurance, muscle strength, and deconditioning, combined with disorder-specific cardiovascular and musculoskeletal features, are hypothesized to be causal. Identifying the limitations in PA and PF provides a starting point for tailor-made interventions.
Prenatal phenotype features and genetic etiology of the Williams-Beuren syndrome and literature review
Authors: Wang Yunan , Liu Chang , Hu Rong , Geng Juan , Lu Jian , Zhao Xianzhe , Xiong Ying , Wu Jing , Yin Aihua
Published: March 2023

Objective

To share our experience on prenatal diagnosis of Williams-Beuren syndrome(WBS) and to improve the awareness, diagnosis, and intrauterine monitoring of the fetuses of this disease.

Methods

The study retrospectively evaluated 14 cases of WBS diagnosed prenatally by single nucleotide polymorphism array (SNP-array). Clinical data from these cases were systematically reviewed, including maternal demographics, indications for invasive prenatal diagnosis, ultrasound findings, SNP-array results, trio-medical exome sequencing (Trio-MES) results, QF-PCR results, pregnancy outcomes and follow-ups.

Results

A total of 14 fetuses were diagnosed with WBS and their prenatal phenotypes were assessed retrospectively. In our case series, the most common ultrasound features were intrauterine growth retardation (IUGR), congenital cardiovascular defects, abnormal fetal placental doppler indices, thickened nuchal translucency(NT) and polyhydramnios. Other less common ultrasound features include fetal hydrops, hydroderma, bilateral pleural effusion, subependymal cysts, etc. Parental chromosome analysis was performed in seven pairs of parents, and all the deletions on chromosome 7q11.23 were de novo.

Conclusion

Prenatal ultrasound features of WBS cases are highly variable, with IUGR, cardiovascular abnormalities and abnormal fetal placental doppler indices, being the most common intrauterine phenotypes. Our case series expand the intrauterine phenotypes of WBS, including cardiovascular abnormalities right aortic arch(RAA) combined with persistent right umbilical vein(PRUV) and elevated the ratio of end-systolic peak flow velocity to end-diastonic peak flow velocity(S/D). In the meantime, with the decrease in the cost of the next-generation sequencing, the method may become widely used in prenatal diagnosis in the near future.
RAGE signaling regulates the progression of diabetic complications
Authors: Taguchi Kensei , Fukami Kei
Published: March 2023

Diabetes, the ninth leading cause of death globally, is expected to affect 642 million people by 2040. With the advancement of an aging society, the number of patients with diabetes having multiple underlying diseases, such as hypertension, obesity, and chronic inflammation, is increasing. Thus, the concept of diabetic kidney disease (DKD) has been accepted worldwide, and comprehensive treatment of patients with diabetes is required. Receptor for advanced glycation endproducts (RAGE), a multiligand receptor, belonging to the immunoglobulin superfamily is extensively expressed throughout the body. Various types of ligands, including advanced glycation endproducts (AGEs), high mobility group box 1, S100/calgranulins, and nucleic acids, bind to RAGE, and then induces signal transduction to amplify the inflammatory response and promote migration, invasion, and proliferation of cells. Furthermore, the expression level of RAGE is upregulated in patients with diabetes, hypertension, obesity, and chronic inflammation, suggesting that activation of RAGE is a common denominator in the context of DKD. Considering that ligand–and RAGE–targeting compounds have been developed, RAGE and its ligands can be potent therapeutic targets for inhibiting the progression of DKD and its complications. Here, we aimed to review recent literature on various signaling pathways mediated by RAGE in the pathogenesis of diabetic complications. Our findings highlight the possibility of using RAGE–or ligand–targeted therapy for treating DKD and its complications.
Hyaluronic acid-based hydrogels: As an exosome delivery system in bone regeneration
Authors: Deng Huiling , Wang Jiecong , An Ran
Published: March 2023

Exosomes are extracellular vesicles (EVs) containing various ingredients such as DNA, RNA, lipids and proteins, which play a significant role in intercellular communication. Numerous studies have demonstrated the important role of exosomes in bone regeneration through promoting the expression of osteogenic-related genes and proteins in mesenchymal stem cells. However, the low targeting ability and short circulating half-life of exosomes limited their clinical application. In order to solve those problems, different delivery systems and biological scaffolds have been developed. Hydrogel is a kind of absorbable biological scaffold composed of three-dimensional hydrophilic polymers. It not only has excellent biocompatibility and superior mechanical strength but can also provide a suitable nutrient environment for the growth of the endogenous cells. Thus, the combination between exosomes and hydrogels can improve the stability and maintain the biological activity of exosomes while achieving the sustained release of exosomes in the bone defect sites. As an important component of the extracellular matrix (ECM), hyaluronic acid (HA) plays a critical role in various physiological and pathological processes such as cell differentiation, proliferation, migration, inflammation, angiogenesis, tissue regeneration, wound healing and cancer. In recent years, hyaluronic acid-based hydrogels have been used as an exosome delivery system for bone regeneration and have displayed positive effects. This review mainly summarized the potential mechanism of HA and exosomes in promoting bone regeneration and the application prospects and challenges of hyaluronic acid-based hydrogels as exosome delivery devices in bone regeneration.
Anti-depressant-like effects of rannasangpei and its active ingredient crocin-1 on chronic unpredictable mild stress mice
Authors: Du Yang , Wang Yan-Li , Chen Lei , Li Qi-En , Cheng Yong
Published: March 2023

Major depressive disorder is one of the most common neuropsychiatric diseases and it is a global public health problem that leads to disabilities. Currently, there is a growing need to explore novel strategy to cure major depressive disorder due to the limitation of available treatments. Rannasangpei (RSNP) is a traditional Tibetan medicine which acts as a therapeutic agent in various acute or chronic diseases, including cardiovascular diseases and neurodegenerative diseases. Crocin-1 a coloring ingredient of saffron which exhibited anti-oxidative and anti-inflammatory properties. Here, we aimed to illustrate whether RSNP and its active ingredient crocin-1 rescue depressive-like phenotypes in chronic unpredictable mild stress (CUMS) induced mouse model of depression. Our results showed that peripheral administration of RSNP or crocin-1 ameliorated the depressive-like behaviors in CUMS-treated mice, as demonstrated by the forced swimming test and tail suspension test. Furthermore, RSNP or crocin-1 treatment reduced oxidative stress in the peripheral blood and hippocampus of the CUMS-treated mice. Additionally, the dysregulated immune system response, as demonstrated by the increased expression of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6) and the decreased expression of the anti-inflammatory factor-interleukin-10 in the prefrontal cortex and/or hippocampus of CUMS-treated mice, were at least partially restored by RSNP or crocin-1 treatment. RSNP or crocin-1 also restored apoptotic protein marker (Bcl-2 and Bax) levels in the prefrontal cortex and hippocampus of the CUMS-treated mice. Moreover, our data indicated that RSNP or crocin-1 increased astrocyte number and brain-derived neurotrophic factor levels in the hippocampus of CUMS-treated mice after RSNP or crocin-1 administration. Taken together, our study for the first time revealed an anti-depressant effect of RSNP and its active ingredient crocin-1 in a mouse model of depression, with involvement of oxidative stress, inflammatory response and apoptotic pathway.
An effective method for epidemic suppression by edge removing in complex network
Authors: Liang Guangbo , Cui Xiaodong , Zhu Peican
Published: March 2023

Since the birth of human beings, the spreading of epidemics such as COVID-19 affects our lives heavily and the related studies have become hot topics. All the countries are trying to develop effective prevention and control measures. As a discipline that can simulate the transmission process, complex networks have been applied to epidemic suppression, in which the common approaches are designed to remove the important edges and nodes for controlling the spread of infection. However, the naive removal of nodes and edges in the complex network of the epidemic would be practically infeasible or incur huge costs. With the focus on the effect of epidemic suppression, the existing methods ignore the network connectivity, leading to two serious problems. On the one hand, when we remove nodes, the edges connected to the nodes are also removed, which makes the node is isolated and the connectivity is quickly reduced. On the other hand, although removing edges is less detrimental to network connectivity than removing nodes, existing methods still cause great damage to the network performance in reality. Here, we propose a method to measure edge importance that can protect network connectivity while suppressing epidemic. In the real-world, our method can not only lower the government’s spending on epidemic suppression but also persist the economic growth and protect the livelihood of the people to some extent. The proposed method promises to be an effective tool to maintain the functionality of networks while controlling the spread of diseases, for example, diseases spread through contact networks.
Dynamics of capillary blood flow responses to acute local changes in oxygen and carbon dioxide concentrations
Authors: Russell McEvoy Gaylene M. , Wells Brenda N. , Kiley Meghan E. , Kaur Kanika K. , Fraser Graham M.
Published: March 2023

Objectives:We aimed to quantify the magnitude and time transients of capillary blood flow responses to acute changes in local oxygen concentration ([O2]), and carbon dioxide concentration ([CO2]) in skeletal muscle. Additionally, we sought to quantify the combined response to both low [O2] and high [CO2] to mimic muscle microenvironment changes at the onset of exercise.

Methods:13 Sprague Dawley rats were anaesthetized, mechanically ventilated, and instrumented with indwelling catheters for systemic monitoring. The extensor digitorum longus muscle was blunt dissected, and reflected over a microfluidic gas exchange chamber in the stage of an inverted microscope. Four O2challenges, four CO2challenges, and a combined low O2(7–2%) and high CO2(5–10%) challenges were delivered to the surface with simultaneous visualization of capillary blood flow responses. Recordings were made for each challenge over a 1-min baseline period followed by a 2-min step change. The combined challenge employed a 1-min [O2] challenge followed by a 2-min change in [CO2]. Mean data for each sequence were fit using least-squared non-linear exponential models to determine the dynamics of each response.

Results:7–2% [O2] challenges decreased capillary RBC saturation within 2 s following the step change (46.53 ± 19.56% vs. 48.51 ± 19.02%,p< 0.0001,τ= 1.44 s), increased RBC velocity within 3 s (228.53 ± 190.39 μm/s vs. 235.74 ± 193.52 μm/s,p< 0.0003,τ= 35.54 s) with a 52% peak increase by the end of the challenge, hematocrit and supply rate show similar dynamics. 5–10% [CO2] challenges increased RBC velocity within 2 s following the step change (273.40 ± 218.06 μm/s vs. 276.75 ± 215.94 μm/s,p= 0.007,τ= 79.34s), with a 58% peak increase by the end of the challenge, supply rate and hematocrit show similar dynamics. Combined [O2] and [CO2] challenges resulted in additive responses to all microvascular hemodynamic measures with a 103% peak velocity increase by the end of the collection period. Data for mean responses and exponential fitting parameters are reported for all challenges.

Conclusion:Microvascular level changes in muscle [O2] and [CO2] provoked capillary hemodynamic responses with differing time transients. Simulating exercise via combined [O2] and [CO2] challenges demonstrated the independent and additive nature of local blood flow responses to these agents.
The correlation between a Th1/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results
Authors: Tang Wenhui , Rong Yan , Zhang Hongmei , Zhan Zi’e , Yuan Long , Ning Yan , Lin Wenji
Published: March 2023

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential anti-inflammatory mechanism involved.

Methods: This study was based on the results of the “Screening and Early Diagnosis of COPD” public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined.

Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred% (r = 0.695, p < 0.001).

Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved.
ABC transporters linked to multiple herbicide resistance in blackgrass (Alopecurus myosuroides)
Authors: Goldberg-Cavalleri Alina , Onkokesung Nawaporn , Franco-Ortega Sara , Edwards Robert
Published: March 2023

Enhanced detoxification is a prominent mechanism protecting plants from toxic xenobiotics and endows resistance to diverse herbicide chemistries in grass weeds such as blackgrass (Alopecurus myosuroides). The roles of enzyme families which impart enhanced metabolic resistance (EMR) to herbicides through hydroxylation (phase 1 metabolism) and/or conjugation with glutathione or sugars (phase 2) have been well established. However, the functional importance of herbicide metabolite compartmentalisation into the vacuole as promoted by active transport (phase 3), has received little attention as an EMR mechanism. ATP-binding cassette (ABC) transporters are known to be important in drug detoxification in fungi and mammals. In this study, we identified three distinct C-class ABCCs transporters namely AmABCC1, AmABCC2 and AmABCC3 in populations of blackgrass exhibiting EMR and resistance to multiple herbicides. Uptake studies with monochlorobimane in root cells, showed that the EMR blackgrass had an enhanced capacity to compartmentalize fluorescent glutathione-bimane conjugated metabolites in an energy-dependent manner. Subcellular localisation analysis using transient expression of GFP-tagged AmABCC2 assays in Nicotiana demonstrated that the transporter was a membrane bound protein associated with the tonoplast. At the transcript level, as compared with herbicide sensitive plants, AmABCC1 and AmABCC2 were positively correlated with EMR in herbicide resistant blackgrass being co-expressed with AmGSTU2a, a glutathione transferase (GST) involved in herbicide detoxification linked to resistance. As the glutathione conjugates generated by GSTs are classic ligands for ABC proteins, this co-expression suggested AmGSTU2a and the two ABCC transporters delivered the coupled rapid phase 2/3 detoxification observed in EMR. A role for the transporters in resistance was further confirmed in transgenic yeast by demonstrating that the expression of either AmABCC1 or AmABCC2, promoted enhanced tolerance to the sulfonylurea herbicide, mesosulfuron-methyl. Our results link the expression of ABCC transporters to enhanced metabolic resistance in blackgrass through their ability to transport herbicides, and their metabolites, into the vacuole.
Natural variations of chlorophyll fluorescence and ion transporter genes influenced the differential response of japonica rice germplasm with different salt tolerances
Authors: Song Jiawei , Yang Hui , Qiao Chengbin , Zhu Chunyan , Bai Tianliang , Du Huaidong , Ma Shuaiguo , Wang Na , Luo Chengke , Zhang Yinxia , Ma Tianli , Li Peifu , Tian Lei
Published: March 2023

Soil salinity seriously restricts rice growth, development, and production globally. Chlorophyll fluorescence and ion content reflect the level of injury and resistance of rice under salt stress. To understand the differences in the response mechanisms of japonica rice with varying degrees of salt tolerance, we analyzed the chlorophyll fluorescence characteristics and ion homeostasis of 12 japonica rice germplasm accessions by comprehensive evaluation of phenotype, haplotype, and expression of salt tolerance-related genes. The results revealed that salt-sensitive accessions were rapidly affected by the damage due to salinity. Salt tolerance score (STS) and relative chlorophyll relative content (RSPAD) were extremely significantly reduced (p<0.01), and chlorophyll fluorescence and ion homeostasis were influenced by various degrees under salt stress. The STS, RSPAD, and five chlorophyll fluorescence parameters of salt-tolerant accessions (STA) were significantly higher than that of salt-sensitive accessions (SSA). Principal component analysis (PCA) with 13 indices suggested three principal components (PCs), with a cumulative contribution rate of 90.254%, which were used to screen Huangluo (typical salt-tolerant germplasm) and Shanfuliya (typical salt-sensitive germplasm) based on the comprehensive evaluation D-value (DCI). The expression characteristics of chlorophyll fluorescence genes (OsABCI7 and OsHCF222) and ion transporter protein genes (OsHKT1;5, OsHKT2;1, OsHAK21, OsAKT2, OsNHX1, and OsSOS1) were analyzed. The expressions of these genes were higher in Huangluo than in Shanfuliya under salt stress. Haplotype analysis revealed four key variations associated with salt tolerance, including an SNP (+1605 bp) within OsABCI7 exon, an SSR (−1231 bp) within OsHAK21 promoter, an indel site at OsNHX1 promoter (−822 bp), and an SNP (−1866 bp) within OsAKT2 promoter. Variation in OsABCI7 protein structure and differential expression of these three ion-transporter genes may contribute to the differential response of japonica rice to salt stress.
Co-regulatory effects of hormone and mRNA–miRNA module on flower bud formation of Camellia oleifera
Authors: Du Wei , Ding Jian , Li Jingbin , Li He , Ruan Chengjiang
Published: March 2023

Few flower buds in a high-yield year are the main factors restricting the yield of Camellia oleifera in the next year. However, there are no relevant reports on the regulation mechanism of flower bud formation. In this study, hormones, mRNAs, and miRNAs were tested during flower bud formation in MY3 (“Min Yu 3,” with stable yield in different years) and QY2 (“Qian Yu 2,” with less flower bud formation in a high-yield year) cultivars. The results showed that except for IAA, the hormone contents of GA3, ABA, tZ, JA, and SA in the buds were higher than those in the fruit, and the contents of all hormones in the buds were higher than those in the adjacent tissues. This excluded the effect of hormones produced from the fruit on flower bud formation. The difference in hormones showed that 21–30 April was the critical period for flower bud formation in C. oleifera; the JA content in MY3 was higher than that in QY2, but a lower concentration of GA3 contributed to the formation of the C. oleifera flower bud. JA and GA3 might have different effects on flower bud formation. Comprehensive analysis of the RNA-seq data showed that differentially expressed genes were notably enriched in hormone signal transduction and the circadian system. Flower bud formation in MY3 was induced through the plant hormone receptor TIR1 (transport inhibitor response 1) of the IAA signaling pathway, the miR535-GID1c module of the GA signaling pathway, and the miR395-JAZ module of the JA signaling pathway. In addition, the expression of core clock components GI (GIGANTEA) and CO (CONSTANS) in MY3 increased 2.3-fold and 1.8-fold over that in QY2, respectively, indicating that the circadian system also played a role in promoting flower bud formation in MY3. Finally, the hormone signaling pathway and circadian system transmitted flowering signals to the floral meristem characteristic genes LFY (LEAFY) and AP1 (APETALA 1) via FT (FLOWERING LOCUS T) and SOC1 (SUPPRESSOR OF OVEREXPRESSION OF CO 1) to regulate flower bud formation. These data will provide the basis for understanding the mechanism of flower bud alternate formation and formulating high yield regulation measures for C. oleifera.
Different changes of bacterial diversity and soil metabolites in tea plants-legume intercropping systems
Authors: Wang Shuangshuang , Zhang Xiaojia , Li Xiaojiang , Shen Jiazhi , Sun Litao , Zaman Shah , Wang Yu , Ding Zhaotang
Published: March 2023

As an essential agroforestry, intercropping legumes can improve the physical, chemical, and biological fertility of the soil in tea plantations. However, the effects of intercropping different legume species on soil properties, bacterial communities, and metabolites remain elusive. In this study, the 0-20 cm and 20-40 cm soils of three planting patterns (T1: tea plants/mung bean intercropping, T2: tea plants/adzuki bean intercropping, T3: tea plants/mung bean and adzuki bean intercropping) were sampled to explore the diversity of the bacterial community and soil metabolites. The findings showed that, as compared to monocropping, intercropping systems had greater concentrations of organic matter (OM) and dissolved organic carbon (DOC). Notably, pH values were significantly lower, and soil nutrients increased in intercropping systems compared with monoculture in 20-40 cm soils, especially in T3. In addition, intercropping resulted in an increased relative abundance of Proteobacteria but a decreased relative abundance of Actinobacteria. 4-methyl-Tetradecane, acetamide, and diethyl carbamic acid were key metabolites mediating the root–microbe interactions, especially in tea plants/adzuki intercropping and tea plants/mung bean, adzuki bean mixed intercropping soils. Co-occurrence network analysis showed that arabinofuranose, abundant in tea plants and adzuki bean intercropping soils, showed the most remarkable correlation with the soil bacterial taxa. Our findings demonstrate that intercropping with adzuki beans is better at enhancing the diversity of soil bacteria and soil metabolites and is more weed-suppressing than other tea plants/legume intercropping systems.