bluuebunny/crossref_metadata_2025 huggingface dataset:
TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver
Authors: Lücke Jöran , Nawrocki Mikolaj , Schnell Josa , Meins Nicholas , Heinrich Fabian , Zhang Tao , Bertram Franziska , Sabihi Morsal , Böttcher Marius , Blankenburg Tom , Pfaff Marie , Notz Sara , Kempski Jan , Reeh Matthias , Wolter Stefan , Mann Oliver , Izbicki Jakob R. , Lütgehetmann Marc , Duprée Anna , Giannou Anastasios D. , Ondruschka Benjamin , Huber Samuel
Published: March 2023

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.
Changes in risk factors for food sensitization in early life: Analysis over a period of 10 years
Authors: Ma Zhuoying , Chen Lin , Xian Ruoling , Fang Heping , Chen Jing , Li Haiqi , Wang Juan , Hu Yan
Published: March 2023

Background

Although epidemiological trends of childhood food sensitization (FS) in IgE-mediated food allergy were reported in China, few studies have examined at changes in its risk factors.

Objective

To investigate the change in early-life risk factors associated with childhood food sensitization during 2009–2019 in China.

Methods

Data from two cross-sectional surveys conducted in 2009 and 2019 (401 and 513 children, respectively) were analyzed. The results of skin prick tests and information on food sensitization-related risk factors in children were summarized, including family history of atopic disease (FHA), demographic characteristics, method of delivery, feeding patterns, sibship size, pet ownership, and vitamin D supplementation. Binary logistic regression was used to calculate the odds ratio and the regression coefficient β-value of risk factors in the 2009 and 2019 surveys separately. Then, coefficient β-value differences between the two surveys were analyzed by the bdiff command in STATA to describe the change in risk factors over 10 years.

Results

The 2009 survey revealed that FHA, age, only child, and feeding patterns were associated with food sensitization. The 2019 survey showed that food sensitization was affected by age, sex, and feeding patterns. However, from 2009 to 2019, the probability of food sensitization in the only-child group significantly increased by 226.0% (β-value difference = 0.81, P = 0.024) and decreased by 65.0% in female children (β-value difference = −1.06, P = 0.008). The effect of age on food sensitization decreased by 50.0% (β-value difference = −0.69, P < 0.001) over 10 years.

Conclusion

The effect of FHA and common lifestyle factors on food sensitization did not significantly change during 2009−2019. However, the influence of demographic characteristics on food sensitization has changed since 2009; that is, older age, male gender, and only child are more likely to develop food sensitization, which needs to be considered in future epidemiological surveys.

Clinical Trial Registration

http://www.chictr.org.cn/, identifier ChiCTR1900024338.
Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome
Authors: Tan Yuan , Liu Qi , Li Zhongxin , Yang Shuo , Cui Liyan
Published: March 2023

APS (antiphospholipid syndrome) is a systematic autoimmune disease presenting with the high levels of aPLs (antiphospholipid antibodies). These autoantibodies are involved in various clinical manifestations, mainly including arterial or venous thrombosis formation, proinflammatory response, and recurrent pregnant loss. Pyroptosis is a form of lytic programmed cell death, and it aggravates autoimmune diseases progression via activating NOD-like receptors, especially the NLRP3 inflammasome and its downstream inflammatory factors IL (interleukin)-1β and IL-18. However, the underlying mechanisms of pyroptosis-induced APS progression remain to be elucidated. ECs (endothelial cells), monocytes, platelets, trophoblasts, and neutrophils are prominent participants in APS development. Of significance, pyroptosis of APS-related cells leads to the excessive release of proinflammatory and prothrombotic factors, which are the primary contributors to APOs (adverse pregnancy outcomes), thrombosis formation, and autoimmune dysfunction in APS. Furthermore, pyroptosis-associated medicines have made encouraging advancements in attenuating inflammation and thrombosis. Given the potential of pyroptosis in regulating APS development, this review would systematically expound the molecular mechanisms of pyroptosis, and elaborate the role of pyroptosis-mediated cellular effects in APS progression. Lastly, the prospective therapeutic approaches for APS would be proposed based on the regulation of pyroptosis.
Preoperative inflammatory markers predict postoperative clinical outcomes in patients undergoing heart valve surgery: A large-sample retrospective study
Authors: Tian Hongni , Jiang Xuetao , Duan Guangyou , Chen Jie , Liu Qi , Zhang Yamei , Li Shiqi , Bao Xiaohang , Huang He
Published: March 2023

Introduction

Preoperative inflammation affects the postoperative outcomes of patients undergoing heart valve surgery. This study aimed to explore the role and predictive effects of preoperative inflammation on the primary outcomes after valvular cardiac surgery.

Methods

This retrospective study utilized a medical recording system to screen 5075 patients who underwent heart valve surgery. Data on the C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) before heart valve surgery were collected from the hospital’s medical system. Postoperative hepatic insufficiency, acute kidney injury, heart failure, and myocardial damage were assessed using blood indicators. Patients with and without prolonged mechanical ventilation, extended intensive care unit stays, prolonged hospital stays, and death within 30 days after surgery (considered the primary outcome in this study) were compared. Group comparisons, receiver operating characteristic (ROC) curve analyses, and logistic analyses were performed to determine the associations between preoperative inflammation and outcomes after heart valve surgery.

Results

A total of 3249 patients were included in the analysis. Significant differences in CRP level, ESR, and NLR were found between patients with and without postoperative adverse outcomes. ROC analysis showed that CRP levels >5 mg/L effectively predicted postoperative heart failure, and NLR >3.5 had a good predictive effect on all-cause mortality within 30 days after surgery. Patients with CRP levels >5 mg/L had a higher incidence of postoperative heart failure than other patients (20.7% vs. 12.6%, P<0.001), with a relative risk of 1.447 (95% confidence interval: 1.155–1.814). Patients with NLR >3.5 had a higher incidence of death within 30 days after surgery (5.3% vs. 1.2%, P<0.001), with a relative risk of 3.236 (95% confidence interval: 1.773–5.906).

Conclusion

Preoperative inflammation can affect postoperative outcomes in patients undergoing heart valve surgery. CRP level >5 mg/L and NLR >3.5 can effectively predict postoperative heart failure and death within 30 days after surgery, respectively.
A review of cytokine-based pathophysiology of Long COVID symptoms
Authors: Low Russell N. , Low Ryan J. , Akrami Athena
Published: March 2023

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.
Comparative genomics of 40 Weissella paramesenteroides strains
Authors: Wan Xing , Takala Timo M. , Huynh Vy A. , Ahonen Susanna L. , Paulin Lars , Björkroth Johanna , Sironen Tarja , Kant Ravi , Saris Per
Published: March 2023

Weissella strains are often detected in spontaneously fermented foods. Because of their abilities to produce lactic acid and functional exopolysaccharides as well as their probiotic traits, Weissella spp. improve not only the sensorial properties but also nutritional values of the fermented food products. However, some Weissella species have been associated with human and animal diseases. In the era of vast genomic sequencing, new genomic/genome data are becoming available to the public on daily pace. Detailed genomic analyses are due to provide a full understanding of individual Weissella species. In this study, the genomes of six Weissella paramesenteroides strains were de novo sequenced. The genomes of 42 W. paramesenteroides strains were compared to discover their metabolic and functional potentials in food fermentation. Comparative genomics and metabolic pathway reconstructions revealed that W. paramesenteroides is a compact group of heterofermentative bacteria with good capacity of producing secondary metabolites and vitamin Bs. Since the strains rarely harbored plasmid DNA, they did not commonly possess the genes associated with bacteriocin production. All 42 strains were shown to bear vanT gene from the glycopeptide resistance gene cluster vanG. Yet none of the strains carried virulence genes.
Proteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis
Authors: Paunkov Ana , Hummel Karin , Strasser Doris , Sóki József , Leitsch David
Published: March 2023

The anaerobic gut bacteria and opportunistic pathogen Bacteroides fragilis can cause life-threatening infections when leaving its niche and reaching body sites outside of the gut. The antimicrobial metronidazole is a mainstay in the treatment of anaerobic infections and also highly effective against Bacteroides spp. Although resistance rates have remained low in general, metronidazole resistance does occur in B. fragilis and can favor fatal disease outcomes. Most metronidazole-resistant Bacteroides isolates harbor nim genes, commonly believed to encode for nitroreductases which deactivate metronidazole. Recent research, however, suggests that the mode of resistance mediated by Nim proteins might be more complex than anticipated because they affect the cellular metabolism, e.g., by increasing the activity of pyruvate:ferredoxin oxidoreductase (PFOR). Moreover, although nim genes confer only low-level metronidazole resistance to Bacteroides, high-level resistance can be much easier induced in the laboratory in the presence of a nim gene than without. Due to these observations, we hypothesized that nim genes might induce changes in the B. fragilis proteome and performed comparative mass-spectrometric analyses with B. fragilis 638R, either with or without the nimA gene. Further, we compared protein expression profiles in both strains after induction of high-level metronidazole resistance. Interestingly, only few proteins were repeatedly found to be differentially expressed in strain 638R with the nimA gene, one of them being the flavodiiron protein FprA, an enzyme involved in oxygen scavenging. After induction of metronidazole resistance, a far higher number of proteins were found to be differentially expressed in 638R without nimA than in 638R with nimA. In the former, factors for the import of hemin were strongly downregulated, indicating impaired iron import, whereas in the latter, the observed changes were not only less numerous but also less specific. Both resistant strains, however, displayed a reduced capability of scavenging oxygen. Susceptibility to metronidazole could be widely restored in resistant 638R without nimA by supplementing growth media with ferrous iron sulfate, but not so in resistant 638R with the nimA gene. Finally, based on the results of this study, we present a novel hypothetic model of metronidazole resistance and NimA function.
Advances and challenges in CRISPR-based real-time imaging of dynamic genome organization
Authors: Thuma Jenna , Chung Yu-Chieh , Tu Li-Chun
Published: March 2023

Nuclear chromosome compaction is non-random and dynamic. The spatial distance among genomic elements instantly modulates transcription. Visualization of the genome organization in the cell nucleus is essential to understand nuclear function. In addition to cell type-dependent organization, high-resolution 3D imaging shows heterogeneous compaction of chromatin organization among the same cell type. Questions remain to be answered if these structural variations were the snapshots of dynamic organization at different time points and if they are functionally different. Live-cell imaging has provided unique insights into dynamic genome organization at short (milliseconds) and long (hours) time scales. The recent development of CRISPR-based imaging opened windows for studying dynamic chromatin organization in single cells in real time. Here we highlight these CRISPR-based imaging techniques and discuss their advances and challenges as a powerful live-cell imaging method that poses high potential to generate paradigm-shifting discoveries and reveal functional implications of dynamic chromatin organization.
Value of white matter hyperintensity volume and total white matter volume for evaluating cognitive impairment in patients with cerebral small-vessel disease
Authors: Zhang Sen , Hu Yaya , Yang Huilin , Li Qianqian , Chen Jing , Bai Hongying
Published: March 2023

Background

White matter hyperintensities (WMH) are a key imaging feature of cerebral small-vessel disease (CSVD). However, there is a lack of standardized methods for determining WMH volume, and the value of total white matter (WM) volume in the assessment of cognitive impairment in patients with CSVD remains unknown.

Objective

We aimed to explore the correlations of WMH volume and WM volume with cognitive dysfunction and its components in patients with CSVD. We also aimed to compare the value of the Fazekas score, WMH volume, and ratio of WMH volume to total WM volume in the assessment of cognitive dysfunction.

Methods

The study included 99 patients with CSVD. Patients were categorized into following groups based on MoCA scores: patients with mild cognitive impairment and those without. Brain magnetic resonance images were processed to investigate differences in WMH and WM volumes between the groups. Logistic regression analysis was used to determine whether these two factors were independent risk factors for cognitive dysfunction. Correlation analysis was used to examine the relationships of WMH and WM volume with different types of cognitive impairment. Receiver operating characteristic curves were used to compare the effectiveness of the WMH score, WMH volume, and WMH to WM ratio for evaluating cognitive dysfunction.

Results

There were significant differences in age, education level, WMH volume, and WM volume between the groups (P < 0.05). After adjusting for age and education, the multivariate logistic analysis indicated that both WMH volume and WM volume were independent risk factors for cognitive dysfunction. Correlation analysis indicated that WMH volume was mainly related to cognition involving the visual space and delayed recall. WM volume was not strongly associated with different types of cognitive dysfunction. The WMH to WM ratio was the strongest predictor, with an area under the curve value of 0.800 and a 95% confidence interval of 0.710–0.891.

Conclusion

Increases in WMH volume may aggravate cognitive dysfunction in patients with CSVD, and a higher WM volume may reduce the effect of WMH volume on cognitive function to a certain extent. The ratio of WMH to total WM volume may reduce the impact of brain atrophy, allowing for more accurate evaluation of cognitive dysfunction in older adults with CSVD.
Extracranial-intracranial bypass surgery for intracranial aneurysm of the anterior cerebral circulation: A systematic review and meta-analysis
Authors: Chen Yang , Chen Pengyu , Duan Guosheng , Li Ren , Li Ziao , Guo Geng
Published: March 2023

Background

The safety of extracranial–intracranial (EC–IC) bypass in the management of anterior circulation intracranial aneurysms (IAs) remains to be determined. This systematic review aims to summarize the existing evidence and provide guidance for the precise management of IAs.

Data source

We constructed search strategies and comprehensively searched Pubmed, Medline, Embase, Web of science, and Cochrane library.

Methods

This systematic review was actualized according to the PRISMA statement. We evaluated study quality using the methodological index for non-randomized study (MINORS). Effect sizes were pooled using a random-effects model. Heterogeneity between studies was assessed using the I2 test. Publication bias was assessed using the Egger's test. The registration number for this systematic review is CRD42023396730.

Result

This systematic review included a total of 21 articles, involving 915 patients. Postoperative bypass patency rate was 99% (95% CI 0.98–1.00); short-term follow-up was 98% (95% CI 0.94–1.00); long-term follow-up was 95% (95% CI 0.93–0.97). The long-term follow-up occlusion rate of saphenous vein was higher than that of radial artery (OR 6.10 95% CI 1.04–35.59). Short-term surgery-related mortality was 0.3% (95% CI 0.000–0.012); long-term follow-up was 0.4% (95% CI 0.000–0.013); The proportion of patients with a score of 0–2 on the modified Rankin Scale (mRS) during long-term follow-up was 92% (95% CI 0.86–0.98). The incidence rates of long-term follow-up complications were: ischemic 3% (95% CI 0.01–0.06); hemorrhagic 1% (95% CI 0.00–0.03); neurological deficit 1% (95% CI 0.00–0.03); other 3% (95% CI 0.01–0.06).

Limitation

Most of the included studies were retrospective studies. Studies reporting preoperative status were not sufficient to demonstrate postoperative improvement. Lack of sufficient subgroup information such as aneurysm rupture status.

Conclusion

EC–IC therapy for anterior circulation IAs has a high safety profile. Higher level of evidence is still needed to support clinical decision.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396730, identifier: CRD42023396730.
Simultaneous real-time EEG-fMRI neurofeedback: A systematic review
Authors: Ciccarelli Giuseppina , Federico Giovanni , Mele Giulia , Di Cecca Angelica , Migliaccio Miriana , Ilardi Ciro Rosario , Alfano Vincenzo , Salvatore Marco , Cavaliere Carlo
Published: March 2023

Neurofeedback (NF) is a biofeedback technique that teaches individuals self-control of brain functions by measuring brain activations and providing an online feedback signal to modify emotional, cognitive, and behavioral functions. NF approaches typically rely on a single modality, such as electroencephalography (EEG-NF) or a brain imaging technique, such as functional magnetic resonance imaging (fMRI-NF). The introduction of simultaneous EEG-fMRI tools has opened up the possibility of combining the high temporal resolution of EEG with the high spatial resolution of fMRI, thereby increasing the accuracy of NF. However, only a few studies have actively combined both techniques. In this study, we conducted a systematic review of EEG-fMRI-NF studies (N = 17) to identify the potential and effectiveness of this non-invasive treatment for neurological conditions. The systematic review revealed a lack of homogeneity among the studies, including sample sizes, acquisition methods in terms of simultaneity of the two procedures (unimodal EEG-NF and fMRI-NF), therapeutic targets field, and the number of sessions. Indeed, because most studies are based on a single session of NF, it is difficult to draw any conclusions regarding the therapeutic efficacy of NF. Therefore, further research is needed to fully understand non-clinical and clinical potential of EEG-fMRI-NF.
Ultra-rapid Idylla™ EGFR mutation screening followed by next-generation sequencing: An integrated solution to molecular diagnosis of non-small cell lung cancer
Authors: Qiu Tian , Zhang Fanshuang , Zheng Bo , Feng Zitong , Li Weihua , Zeng Hua , Chu Lixia , Ying Jianming
Published: March 2023

Background

Rapid profiling of the EGFR mutations is crucial to help clinicians choose the optimal treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer (NSCLC). Unfortunately, current diagnostic techniques, including ARMS-PCR and NGS, generally require several days to deliver final results. This diagnostic delay may lead to treatment delays for patients who are worsening rapidly.

Methods

This study introduced the ultra-rapid Idylla™ system for rapid, sensitive and specific identification of the EGFR mutations among Chinese NSCLC patients. Idylla™ EGFR Assay, an integrated cartridge running on the Idylla™ system, which can detect 51 EGFR mutations directly from Formalin-Fixed, Paraffin-Embedded (FFPE) samples within 2.5 hours, was used in this study. The sensitivity and specificity of the Idylla™ system were evaluated in comparison with ARMS-PCR or NGS using 95 clinical samples.

Results

The Idylla™ system achieved a sensitivity of 97.6%, a specificity of 100%, and an overall concordance of 97.9% for 95 retrospective samples. When compared to ARMS-PCR, the Idylla™ system demonstrated high accuracy with an overall agreement of 97.1% (34/35), a sensitivity of 95.2% (20/21) (95% CI, 76.2% - 99.9%), and an estimated specificity of 100% (12/12) (95% CI, 76.8% - 100%) for 35 prospective samples.

Conclusions

This Idylla system provides a rapid, accurate and simple approach for screening EGFR mutations, which can guide Tyrosine Kinase Inhibitors (TKI) treatment for NSCLC patients in a timely manner.
Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study
Authors: Kjellstadli Camilla , Forster Rachel  B. , Myklebust Tor  Å. , Bjørge Tone , Bønaa Kaare  H. , Helle Svein  I. , Kvåle Rune
Published: March 2023

Objective

To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT).

Materials and methods

We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups.

Results

After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism.

Conclusions

During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.
RETRACTED: The value, diagnostic efficacy and clinical significance of functional magnetic resonance imaging in evaluating the efficacy of neoadjuvant chemotherapy in patients with triple negative breast cancer
Authors: He Xiaoping , Wang Zongsheng , Zhou Ying , Feng Yongli
Published: March 2023

Background

Breast cancer (BC) is a common malignant tumor in female. In recent years, with the change of fertility pattern and lifestyle, the incidence of breast cancer is increasing year by year, seriously endangering the health and life of women. MRI is suitable for follow-up evaluation of the course of neoadjuvant chemotherapy in LABC, but there are few related studies and reports. Based on the above background, it is necessary to further evaluate the value of functional magnetic resonance imaging in neoadjuvant chemotherapy in patients with triple negative breast cancer, so as to lay a theoretical foundation for the popularization and application of this detection method. Based on this, this study was to explore the value, diagnostic efficacy and clinical importance of functional magnetic resonance imaging in evaluating the efficacy of neoadjuvant chemotherapy in patients with triple negative breast cancer.

Methods

A total of 62 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in our hospital from September 2017 to September 2022 were selected. To compare the differences of functional magnetic resonance imaging (fMRI) between effective and ineffective patients with neoadjuvant chemotherapy, the related data were statistically analyzed.

Results

There was no significant difference between the mode of tumor withdrawal and the pathological complete remission of tumor tissue (P>0.05). There was no significant difference in anti-Trop-2 antibody-drug conjugates (ADC) data before and after chemotherapy between over-expressed patients with human epidermal growth factor receptor-2 (HER-2) and non-over-expressed patients with HER-2 (P>0.05). The levels of ADC and Δ ADC in pathological complete remission patients after chemotherapy were significantly higher than those in non-pathological complete remission patients (P<0.05). Using the ΔADC value as the evaluation parameter, the pathological response of tumor tissue was classified as the “gold standard” to draw the ROC curve, the area under curve (AUC) was 0.673, the cut-off of ΔADC to evaluate the significant response of tumor tissue after chemotherapy was 1.418, the sensitivity of evaluating the efficacy was 71.9%, and the specificity was 55.0%.

Conclusion

Functional magnetic resonance imaging (fMRI) has diagnostic value for neoadjuvant chemotherapy in patients with triple negative breast cancer. According to the change of ADC value, the curative effect can be predicted early and the treatment strategy can be adjusted in time.
Case report: Primary pleural giant extraskeletal Ewing sarcoma in a child
Authors: Wu Yang , Xie Chao-Bang , Huang Qiong , Zhao Kai-Fei
Published: March 2023

Primary extraskeletal Ewing sarcoma (EES) is a rare small round cell malignancy that accounts for less than 1% of all sarcomas. It is found most commonly in the trunk and lower limbs and very rarely in the pleura and can be easily misdiagnosed in clinical practice. This study presents the case of an 11-year-old boy who presented to our hospital with no apparent cause of left shoulder pain for 6 months. On physical examination, tenderness was noted in the left chest wall and shoulder joint, which had a limited range of motion. Computed tomography (CT) and magnetic resonance imaging (MRI) of the chest revealed an irregular soft tissue mass in the upper left thorax, with a wide base attached to the adjacent pleura and bone destruction of the adjacent left first rib. The patient’s bone scan showed a dense focus of increased radiotracer accumulation in the left first rib. A subsequent CT-guided aspiration biopsy of the left pleural mass with histomorphology and immunohistochemical phenotyping led to a diagnosis of extraskeletal Ewing sarcoma. To inhibit tumor growth, alternating systemic chemotherapy cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) and isocyclophosphamide and etoposide (IE) were administered at 3-week intervals. After completing three VDC and two IE cycles, the child’s condition was well and the pain in the left shoulder joint was relieved. However, a repeat MRI of the chest showed that the mass did not shrink.
Construction and validation of a metabolic-associated lncRNA risk index for predicting colorectal cancer prognosis
Authors: Lin Quanjun , Wang Zhiqiang , Wang Jue , Xu Ming , Yuan Yihang
Published: March 2023

Background

Metabolic reprogramming is one of the most important events in the development of tumors. Similarly, long non-coding RNAs are closely related to the occurrence and development of colorectal cancer (CRC). However, there is still a lack of systematic research on metabolism-related lncRNA in CRC.

Methods

Expression data of metabolism-related genes and lncRNA were obtained from The Cancer Genome Atlas (TCGA). Hub metabolism-related genes (HMRG) were screened out by differential analysis and univariate Cox analysis; a metabolism-related lncRNA risk index (MRLncRI) was constructed by co-expression analysis, univariate Cox regression analysis, LASSO, and multivariate Cox regression analysis. Survival curves were drawn by the Kaplan-Meier method. The ssGSEA method assessed the tumor microenvironment of the sample, and the IPS assessed the patient’s response to immunotherapy. “Oncopredict” assessed patient sensitivity to six common drugs.

Results

MRLncRI has excellent predictive ability for CRC prognosis. Based on this, we also constructed a nomogram that is more suitable for clinical applications. Most immune cells and immune-related terms were higher in the high-risk group. IPS scores were higher in the high-risk group. In addition, the high-risk and low-risk groups were sensitive to different drugs.

Conclusion

MRLncRI can accurately predict the prognosis of CRC patients, is a promising biomarker, and has guiding significance for the clinical treatment of CRC.
A mass balance study of [14C]SHR6390 (dalpiciclib), a selective and potent CDK4/6 inhibitor in humans
Authors: Zhang Hua , Yan Shu , Zhan Yan , Ma Sheng , Bian Yicong , Li Shaorong , Tian Junjun , Li Guangze , Zhong Dafang , Diao Xingxing , Miao Liyan
Published: March 2023

SHR6390 (dalpiciclib) is a selective and effective cyclin-dependent kinase (CDK) 4/6 inhibitor and an effective cancer therapeutic agent. On 31 December 2021, the new drug application was approved by National Medical Product Administration (NMPA). The metabolism, mass balance, and pharmacokinetics of SHR6390 in 6 healthy Chinese male subjects after a single oral dose of 150 mg [14C]SHR6390 (150 µCi) in this research. The Tmax of SHR6390 was 3.00 h. In plasma, the t1/2 of SHR6390 and its relative components was approximately 17.50 h. The radioactivity B/P (blood-to-plasma) AUC0-t ratio was 1.81, indicating the preferential distribution of drug-related substances in blood cells. At 312 h after administration, the average cumulative excretion of radioactivity was 94.63% of the dose, including 22.69% in urine and 71.93% in stool. Thirteen metabolites were identified. In plasma, because of the low level of radioactivity, only SHR6390 was detected in pooled AUC0-24 h plasma. Stool SHR6390 was the main component in urine and stool. Five metabolites were identified in urine, and 12 metabolites were identified in stool. Overall, faecal clearance is the main method of excretion.
Endothelial KCa channels: Novel targets to reduce atherosclerosis-driven vascular dysfunction
Authors: Vera O. Daniel , Wulff Heike , Braun Andrew P.
Published: March 2023

Elevated levels of cholesterol in the blood can induce endothelial dysfunction, a condition characterized by impaired nitric oxide production and decreased vasodilatory capacity. Endothelial dysfunction can promote vascular disease, such as atherosclerosis, where macrophages accumulate in the vascular intima and fatty plaques form that impair normal blood flow in conduit arteries. Current pharmacological strategies to treat atherosclerosis mostly focus on lipid lowering to prevent high levels of plasma cholesterol that induce endothelial dysfunction and atherosclerosis. While this approach is effective for most patients with atherosclerosis, for some, lipid lowering is not enough to reduce their cardiovascular risk factors associated with atherosclerosis (e.g., hypertension, cardiac dysfunction, stroke, etc.). For such patients, additional strategies targeted at reducing endothelial dysfunction may be beneficial. One novel strategy to restore endothelial function and mitigate atherosclerosis risk is to enhance the activity of Ca2+-activated K+ (KCa) channels in the endothelium with positive gating modulator drugs. Here, we review the mechanism of action of these small molecules and discuss their ability to improve endothelial function. We then explore how this strategy could mitigate endothelial dysfunction in the context of atherosclerosis by examining how KCa modulators can improve cardiovascular function in other settings, such as aging and type 2 diabetes. Finally, we consider questions that will need to be addressed to determine whether KCa channel activation could be used as a long-term add-on to lipid lowering to augment atherosclerosis treatment, particularly in patients where lipid-lowering is not adequate to improve their cardiovascular health.
Inhibition of the calcium-sensing receptor by extracellular phosphate ions and by intracellular phosphorylation
Authors: Centeno Patricia P. , Binmahfouz Lenah S. , Alghamdi Khaleda , Ward Donald T.
Published: March 2023

As both a sensor of extracellular calcium (Ca2+o) concentration and a key controller of Ca2+o homeostasis, one of the most interesting properties of the calcium-sensing receptor (CaR) is its sensitivity to, and modulation by, ions and small ligands other than Ca2+. There is emerging evidence that extracellular phosphate can act as a partial, non-competitive CaR antagonist to modulate parathyroid hormone (PTH) secretion, thus permitting the CaR to integrate mineral homeostasis more broadly. Interestingly, phosphorylation of certain intracellular CaR residues can also inhibit CaR responsiveness. Thus, negatively charged phosphate can decrease CaR activity both extracellularly (via association with arginine) and intracellularly (via covalent phosphorylation).
Exploring the metabolic and physiological roles of HQT in S. lycopersicum by gene editing
Authors: D’Orso Fabio , Hill Lionel , Appelhagen Ingo , Lawrenson Tom , Possenti Marco , Li Jie , Harwood Wendy , Morelli Giorgio , Martin Cathie
Published: March 2023

The most abundant phenolic compound in Solanaceous plants is chlorogenic acid (CGA), which possesses protective properties such as antimicrobial and antioxidant activities. These properties are particularly relevant when plants are under adverse conditions, such as pathogen attack, excess light, or extreme temperatures that cause oxidative stress. Additionally, CGA has been shown to absorb UV-B light. In tomato and potato, CGA is mainly produced through the HQT pathway mediated by the enzyme hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase. However, the absence of natural or induced mutants of this gene has made it unclear whether other pathways contribute to CGA production and accumulation. To address this question, we used CRISPR technology to generate multiple knock-out mutant lines in the tomato HQT gene. The resulting slhqt plants did not accumulate CGA or other caffeoylquinic acids (CQAs) in various parts of the plant, indicating that CQA biosynthesis depends almost entirely on the HQT pathway in tomato and, likely, other Solanaceous crops. We also found that the lack of CGA in slhqt plants led to higher levels of hydroxycinnamoyl-glucose and flavonoids compared to wild-type plants. Gene expression analysis revealed that this metabolic reorganization was partly due to flux redirection, but also involved modulation of important transcription factor genes that regulate secondary metabolism and sense environmental conditions. Finally, we investigated the physiological role of CGA in tomato and found that it accumulates in the upper epidermis where it acts as a protector against UV-B irradiation.
Transcriptome and functional analysis revealed the intervention of brassinosteroid in regulation of cold induced early flowering in tobacco
Authors: Dai Xiumei , Zhang Yan , Xu Xiaohong , Ran Mao , Zhang Jiankui , Deng Kexuan , Ji Guangxin , Xiao Lizeng , Zhou Xue
Published: March 2023

Cold environmental conditions may often lead to the early flowering of plants, and the mechanism by cold-induced flowering remains poorly understood. Microscopy analysis in this study demonstrated that cold conditioning led to early flower bud differentiation in two tobacco strains and an Agilent Tobacco Gene Expression microarray was adapted for transcriptomic analysis on the stem tips of cold treated tobacco to gain insight into the molecular process underlying flowering in tobacco. The transcriptomic analysis showed that cold treatment of two flue-cured tobacco varieties (Xingyan 1 and YunYan 85) yielded 4176 and 5773 genes that were differentially expressed, respectively, with 2623 being commonly detected. Functional distribution revealed that the differentially expressed genes (DEGs) were mainly enriched in protein metabolism, RNA, stress, transport, and secondary metabolism. Genes involved in secondary metabolism, cell wall, and redox were nearly all up-regulated in response to the cold conditioning. Further analysis demonstrated that the central genes related to brassinosteroid biosynthetic pathway, circadian system, and flowering pathway were significantly enhanced in the cold treated tobacco. Phytochemical measurement and qRT-PCR revealed an increased accumulation of brassinolide and a decreased expression of the flowering locus c gene. Furthermore, we found that overexpression of NtBRI1 could induce early flowering in tobacco under normal condition. And low-temperature-induced early flowering in NtBRI1 overexpression plants were similar to that of normal condition. Consistently, low-temperature-induced early flowering is partially suppressed in NtBRI1 mutant. Together, the results suggest that cold could induce early flowering of tobacco by activating brassinosteroid signaling.
Integrated transcriptome and metabolome analysis revealed that flavonoids enhanced the resistance of Oryza sativa against Meloidogyne graminicola
Authors: Zhang Lianhu , Li Songyan , Shan Chonglei , Liu Yankun , Zhang Yifan , Ye Lifang , Lin Yachun , Xiong Guihong , Ma Jian , Adnan Muhammad , Shi Xugen , Sun Xiaotang , Kuang Weigang , Cui Ruqiang
Published: March 2023

Rice is a crucial food crop worldwide, but its yield and quality are significantly affected by Meloidogyne graminicola is a root knot nematode. No rice variety is entirely immune to this nematode disease in agricultural production. Thus, the fundamental strategy to combat this disease is to utilize rice resistance genes. In this study, we conducted transcriptome and metabolome analyses on two rice varieties, ZH11 and IR64. The results indicated that ZH11 showed stronger resistance than IR64. Transcriptome analysis revealed that the change in gene expression in ZH11 was more substantial than that in IR64 after M. graminicola infection. Moreover, GO and KEGG enrichment analysis of the upregulated genes in ZH11 showed that they were primarily associated with rice cell wall construction, carbohydrate metabolism, and secondary metabolism relating to disease resistance, which effectively enhanced the resistance of ZH11. However, in rice IR64, the number of genes enriched in disease resistance pathways was significantly lower than that in ZH11, which further explained susceptibility to IR64. Metabolome analysis revealed that the metabolites detected in ZH11 were enriched in flavonoid metabolism and the pentose phosphate pathway, compared to IR64, after M. graminicola infection. The comprehensive analysis of transcriptome and metabolome data indicated that flavonoid metabolism plays a crucial role in rice resistance to M. graminicola infection. The content of kaempferin, apigenin, and quercetin in ZH11 significantly increased after M. graminicola infection, and the expression of genes involved in the synthetic pathway of flavonoids also significantly increased in ZH11. Our study provides theoretical guidance for the precise analysis of rice resistance and disease resistance breeding in further research.
Omics-assisted characterization of two-component system genes from Gossypium Raimondii in response to salinity and molecular interaction with abscisic acid
Authors: Rasool Asima , Azeem Farrukh , Ur-Rahman Mahmood , Rizwan Muhammad , Hussnain Siddique Muhammad , Bay Daniyah Habiballah , Binothman Najat , Al Kashgry Najla Amin T. , Qari Sameer H.
Published: March 2023

The two-component system (TCS) genes are involved in a wide range of physiological processes in prokaryotes and eukaryotes. In plants, the TCS elements help in a variety of functions, including cell proliferation, response to abiotic and biotic stresses, leaf senescence, nutritional signaling, and division of chloroplasts. Three different kinds of proteins make up the TCS system in plants. These are known as HKs (histidine kinases), HPs (histidine phosphotransfer), and RRs (response regulators). We investigated the genome of Gossypium raimondii and discovered a total of 59 GrTCS candidates, which include 23 members of the HK family, 8 members of the HP family, and 28 members of the RR family. RR candidates are further classified as type-A (6 members), type-B (11 members), type-C (2 members), and pseudo-RRs (9 members). The GrTCS genes were analyzed in comparison with the TCS components of other plant species such as Arabidopsis thaliana, Cicer arietinum, Sorghum bicolor, Glycine max, and Oryza sativa. This analysis revealed both conservation and changes in their structures. We identified 5 pairs of GrTCS syntenic homologs in the G. raimondii genome. All 59 TCS genes in G. raimondii are located on all thirteen chromosomes. The GrTCS promoter regions have several cis-regulatory elements, which function as switches and respond to a wide variety of abiotic stresses. RNA-seq and real-time qPCR analysis showed that the majority of GrTCS genes are differentially regulated in response to salt and cold stress. 3D structures of GrTCS proteins were predicted to reveal the specific function. GrTCSs were docked with abscisic acid to assess their binding interactions. This research establishes the groundwork for future functional studies of TCS elements in G. raimondii, which will further focus on stress resistance and overall development.
Plastome evolution in the East Asian lobelias (Lobelioideae) using phylogenomic and comparative analyses
Authors: Li Chun-Jiao , Xie Xin-Tong , Liu Hong-Xin , Wang Ruo-Nan , Li De-Zhu
Published: March 2023

Lobelia species, as rich source of the alkaloid lobeline which has been shown to have important biological activity, have been used in folk medicine throughout East Asia to treat various diseases. However, Lobelia is a complex and varied genus in East Asia and is thus difficult to identify. Genomic resources would aid identification, however the availability of such information is poor, preventing a clear understanding of their evolutionary history from being established. To close this gap in the available genomic data, in this study, 17 plastomes of East Asian lobelias were newly sequenced and assembled. Although the plastomes of Lobelia sect. Hypsela, L. sect. Speirema, and L. sect. Rhynchopetalum shared the gene structure, the inverted repeat (IR)/large single copy (LSC) boundaries, genome size, and the number of repeats were variable, indicating the non-conservative nature of plastome evolution within these sections. However, the genomes of the Lobelia sect. Delostemon and L. sect. Stenotium showed rearrangements, revealing that these two sections might have undergone different evolutionary histories. We assessed nine hotspot genes and 27-51 simple sequence repeat motifs, which will also serve as valuable DNA barcode regions in future population genetics studies and for the delineation of plant species. Our phylogenetic analysis resolved the evolutionary positions of the five sections in agreement with previous evolutionary trees based on morphological features. Although phylogenetic reconstruction of Lobelioideae based on the rpoC2 gene has rarely been performed, our results indicated that it contains a considerable amount of phylogenetic information and offers great promise for further phylogenetic analysis of Lobelioideae. Our site-specific model identified 173 sites under highly positive selections. The branch-site model exhibited 11 positive selection sites involving four genes in the East Asian branches. These four genes may play critical roles in the adaptation of East Asian taxa to diverse environments. Our study is the first to detect plastome organization, phylogenetic utility, and signatures of positive selection in the plastomes of East Asian lobelias, which will help to further advance taxonomic and evolutionary studies and the utilization of medicinal plant resources.