bluuebunny/crossref_metadata_2025 huggingface dataset:
GLTM: A Global-Local Attention LSTM Model to Locate Dimer Motif of Single-Pass Membrane Proteins
Authors: Ma Quanchao , Zou Kai , Zhang Zhihai , Yang Fan
Published: March 2022

Single-pass membrane proteins, which constitute up to 50% of all transmembrane proteins, are typically active in significant conformational changes, such as a dimer or other oligomers, which is essential for understanding the function of transmembrane proteins. Finding the key motifs of oligomers through experimental observation is a routine method used in the field to infer the potential conformations of other members of the transmembrane protein family. However, approaches based on experimental observation need to consume a lot of time and manpower costs; moreover, they are hard to reveal the potential motifs. A proposed approach is to build an accurate and efficient transmembrane protein oligomer prediction model to screen the key motifs. In this paper, an attention-based Global-Local structure LSTM model named GLTM is proposed to predict dimers and screen potential dimer motifs. Different from traditional motifs screening based on highly conserved sequence search frame, a self-attention mechanism has been employed in GLTM to locate the highest dimerization score of subsequence fragments and has been proven to locate most known dimer motifs well. The proposed GLTM can reach 97.5% accuracy on the benchmark dataset collected from Membranome2.0. The three characteristics of GLTM can be summarized as follows: First, the original sequence fragment was converted to a set of subsequences which having the similar length of known motifs, and this additional step can greatly enhance the capability of capturing motif pattern; Second, to solve the problem of sample imbalance, a novel data enhancement approach combining improved one-hot encoding with random subsequence windows has been proposed to improve the generalization capability of GLTM; Third, position penalization has been taken into account, which makes a self-attention mechanism focused on special TM fragments. The experimental results in this paper fully demonstrated that the proposed GLTM has a broad application perspective on the location of potential oligomer motifs, and is helpful for preliminary and rapid research on the conformational change of mutants.
A Review on Measures to Rejuvenate Immune System: Natural Mode of Protection Against Coronavirus Infection
Authors: Islam Md. Aminul , Haque Md. Atiqul , Rahman Md. Arifur , Hossen Foysal , Reza Mahin , Barua Abanti , Marzan Abdullah Al , Das Tuhin , Kumar Baral Sumit , He Cheng , Ahmed Firoz , Bhattacharya Prosun , Jakariya Md.
Published: March 2022

SARS-CoV-2, a novel Corona virus strain, was first detected in Wuhan, China, in December 2019. As of December 16, 2021, almost 4,822,472 people had died and over 236,132,082 were infected with this lethal viral infection. It is believed that the human immune system is thought to play a critical role in the initial phase of infection when the viruses invade the host cells. Although some effective vaccines have already been on the market, researchers and many bio-pharmaceuticals are still working hard to develop a fully functional vaccine or more effective therapeutic agent against the COVID-19. Other efforts, in addition to functional vaccines, can help strengthen the immune system to defeat the corona virus infection. Herein, we have reviewed some of those proven measures, following which a more efficient immune system can be better prepared to fight viral infection. Among these, dietary supplements like- fresh vegetables and fruits offer a plentiful of vitamins and antioxidants, enabling to build of a healthy immune system. While the pharmacologically active components of medicinal plants directly aid in fighting against viral infection, supplementary supplements combined with a healthy diet will assist to regulate the immune system and will prevent viral infection. In addition, some personal habits, like- regular physical exercise, intermittent fasting, and adequate sleep, had also been proven to aid the immune system in becoming an efficient one. Maintaining each of these will strengthen the immune system, allowing innate immunity to become a more defensive and active antagonistic mechanism against corona-virus infection. However, because dietary treatments take longer to produce beneficial effects in adaptive maturation, personalized nutrition cannot be expected to have an immediate impact on the global outbreak.
Elective Tracheal Intubation With the VieScope—A Prospective Randomized Non-inferiority Pilot Study (VieScOP-Trial)
Authors: Petzoldt Martin , Engels Yasmin , Popal Zohal , Tariparast Pischtaz A. , Sasu Phillip B. , Brockmann Andrés , Punke Mark A. , Grensemann Jörn
Published: March 2022

Background

Tracheal intubation is commonly performed after direct laryngoscopy using Macintosh laryngoscopes (MacL), but visualization of the larynx may be inadequate. The VieScope (VSC) as a new type of laryngoscope consisting of a straight, shielded, illuminated tube used to perform intubation via a bougie was investigated in this prospective randomized trial in patients without expected difficult airways.

Methods

With ethics approval, 2 × 29 patients for elective surgery were randomized 1:1 to intubation with VSC or MacL. Endpoints were first attempt success rates (FAS), Percentage of Glottis Opening Scale (POGO), time to intubation (TTI), and difficulty ratings on visual analog scales (0–100, lower values better). Data are given as mean ± standard deviation.

Results

The FAS was 83 ± 38% for VSC and 86 ± 34% for MacL (P = 0.723). For VSC, POGO was 86 ± 17% and for MacL 68 ± 30% (P = 0.007). TTI for VSC was 93 ± 67s vs. 38 ± 17 for MacL (P < 0.001). Difficulty of intubation was rated 23 ± 22 for VSC vs. 18 ± 22 for MacL (P = 0.422), viewing conditions 12 ± 15 vs. 24 ± 25 (P = 0.031), and difficulty of tube placement was rated 27 ± 30 vs. 7 ± 8 (P = 0.001).

Conclusion

No difference in FAS was detected between VSC and MacL. Visualization of the larynx was superior using the VSC, while TTI was prolonged and tube placement via bougie was more challenging. The VSC could be an alternative to MacL in patients with difficult laryngoscopy, but this should be investigated further in patients with expected difficult airways.
Physiological Roles of Short-Chain and Long-Chain Menaquinones (Vitamin K2) in Lactococcus cremoris
Authors: Liu Yue , Charamis Nikolaos , Boeren Sjef , Blok Joost , Lewis Alisha Geraldine , Smid Eddy J. , Abee Tjakko
Published: March 2022

Lactococcus cremoris and L. lactis are well known for their occurrence and applications in dairy fermentations, but their niche extends to a range of natural and food production environments. L. cremoris and L. lactis produce MKs (vitamin K2), mainly as the long-chain forms represented by MK-9 and MK-8, and a detectable number of short-chain forms represented by MK-3. The physiological significance of the different MK forms in the lifestyle of these bacterial species has not been investigated extensively. In this study, we used L. cremoris MG1363 to construct mutants producing different MK profiles by deletion of genes encoding (i) a menaquinone-specific isochorismate synthase, (ii) a geranyltranstransferase, and (iii) a prenyl diphosphate synthase. These gene deletions resulted in (i) a non-MK producer (ΔmenF), (ii) a presumed MK-1 producer (ΔispA), and (iii) an MK-3 producer (Δllmg_0196), respectively. By examining the phenotypes of the MG1363 wildtype strain and respective mutants, including biomass accumulation, stationary phase survival, oxygen consumption, primary metabolites, azo dye/copper reduction, and proteomes, under aerobic, anaerobic, and respiration-permissive conditions, we could infer that short-chain MKs like MK-1 and MK-3 are preferred to mediate extracellular electron transfer and reaction with extracellular oxygen, while the long-chain MKs like MK-9 and MK-8 are more efficient in aerobic respiratory electron transport chain. The different electron transfer routes mediated by short-chain and long-chain MKs likely support growth and survival of L. cremoris in a range of (transiently) anaerobic and aerobic niches including food fermentations, highlighting the physiological significance of diverse MKs in L. cremoris.
Identification of Bacterial Drug-Resistant Cells by the Convolutional Neural Network in Transmission Electron Microscope Images
Authors: Hayashi-Nishino Mitsuko , Aoki Kota , Kishimoto Akihiro , Takeuchi Yuna , Fukushima Aiko , Uchida Kazushi , Echigo Tomio , Yagi Yasushi , Hirose Mika , Iwasaki Kenji , Shin’ya Eitaro , Washio Takashi , Furusawa Chikara , Nishino Kunihiko
Published: March 2022

The emergence of bacteria that are resistant to antibiotics is common in areas where antibiotics are used widely. The current standard procedure for detecting bacterial drug resistance is based on bacterial growth under antibiotic treatments. Here we describe the morphological changes in enoxacin-resistant Escherichia coli cells and the computational method used to identify these resistant cells in transmission electron microscopy (TEM) images without using antibiotics. Our approach was to create patches from TEM images of enoxacin-sensitive and enoxacin-resistant E. coli strains, use a convolutional neural network for patch classification, and identify the strains on the basis of the classification results. The proposed method was highly accurate in classifying cells, achieving an accuracy rate of 0.94. Using a gradient-weighted class activation mapping to visualize the region of interest, enoxacin-resistant and enoxacin-sensitive cells were characterized by comparing differences in the envelope. Moreover, Pearson’s correlation coefficients suggested that four genes, including lpp, the gene encoding the major outer membrane lipoprotein, were strongly associated with the image features of enoxacin-resistant cells.
Porcine Endogenous Retroviruses: Quantification of the Viral Copy Number for the Four Miniature Pig Breeds in China
Authors: Lu Tao-feng , Sun Bo , Yu Tai-yong , Wu Yan-jun , Zhou Jie , Wu Shu-guang
Published: March 2022

Domestic pigs has served not only as one of the most important economy livestock but also as ideal organ-source animals owing to similarity in anatomy, physiology, and organ size to humans. Howerer, the barrier of the cross-species transmission risk of porcine endogenous retrovirus (PERVs) blocked the pig-to-human xenotransplantation. PERVs are integrated into pigs’ genomes and cannot be eliminated by designated or specified pathogen-free breeding. PERVs are an important biosafety issue in xenotransplantation because they can be released from normal pig cells and infect human cellsin vitrounder certain conditions. Screening and analyzing the presence of PERVs in pig genome will provide essential parameters for pig breed sources. In China, four miniature pig breeds, such as Guizhou miniature pig (GZ), Bama miniature pig (BM), Wuzhishan miniature pig (WZS), and Juema miniature pig (JM), were the main experimental miniature pig breeds, which were widely used. In this study, PCR was performed to amplifyenv-A,env-B, andenv-Cfor all individuals from the four breeds. The results revealed that PERVenv-Aandenv-Bwere detected in all individuals and the lowest ratios of PERVenv-Cwas 17.6% (3/17) in the GZ breed. Then, PERVpolandGAPDHwere detected using the droplet digital PCR (ddPCR) method. As the reference ofGAPDHcopy number, the copy numbers of PERVs were at the median of 12, 16, 14, and 16 in the four miniature pig breeds (GZ, BM, WZS, and JM), respectively. Furthermore, the copy number of the PERVpolgene in many organs from the GZ breed was analyzed using ddPCR. The copy numbers of PERVpolgene were at the median of 7 copies, 8 copies, 8 copies, 11 copies, 5 copies, 6 copies, and 7 copies in heart, liver, spleen, lung, kidney, muscle, and skin, and the maximum number was 11 copies in the lung. The minimum number was 5 copies in the kidney as the reference ofGAPDH. These data suggest that GZ breed has the lower PERVs copy number in the genome, and may be an ideal organ-source miniature pig breed for the study of the pig-to-human xenotransplantation.
Development of a Rapid and Efficient RPA-CRISPR/Cas12a Assay for Mycoplasma pneumoniae Detection
Authors: Li Feina , Xiao Jing , Yang Haiming , Yao Yao , Li Jieqiong , Zheng Huiwen , Guo Qian , Wang Xiaotong , Chen Yuying , Guo Yajie , Wang Yonghong , Shen Chen
Published: March 2022

Mycoplasma pneumoniae (MP) is a one of most common pathogen in causing respiratory infection in children and adolescents. Rapid and efficient diagnostic methods are crucial for control and treatment of MP infections. Herein, we present an operationally simple, rapid and efficient molecular method for MP identification, which eliminates expensive instruments and specialized personnel. The method combines recombinase polymerase amplification (RPA) with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins (Cas) 12a-based detection, with an optimal procedure less than 1 h from sample to result including DNA extraction (25 min), RPA reaction (39°C for 15-20 min), CRISPR/Cas12a detection (37°C for 10 min) and visual detection by naked eyes (2 min). This diagnostic method shows high sensitivity (two copies per reaction) and no cross-reactivity against other common pathogenic bacteria. Preliminary evaluation using 201 clinical samples shows sensitivity of 99.1% (107/108), specificity of 100% (93/93) and consistency of 99.5% (200/201), compared with real-time PCR method. The above data demonstrate that our developed method is reliable for rapid diagnosis of MP. In conclusion, the RPA-CRISPR/Cas12a has a great potential to be as a useful tool for reliable and quick diagnosis of MP infection, especially in primary hospitals with limited conditions.
Selective Inhibition of Bromodomain-Containing Protein 4 Reduces Myofibroblast Transdifferentiation and Pulmonary Fibrosis
Authors: Bernau Ksenija , Skibba Melissa , Leet Jonathan P. , Furey Sierra , Gehl Carson , Li Yi , Zhou Jia , Sandbo Nathan , Brasier Allan R.
Published: March 2022

Idiopathic pulmonary fibrosis is a lethal disease driven by myofibroblast expansion. Currently no therapies exist that target the epigenetic mechanisms controlling myofibroblast transdifferentiation, which is responsible for unregulated extracellular matrix (ECM) production. We have recently shown that bromodomain-containing protein 4 (BRD4), an epigenetic regulator that forms a scaffold for nuclear activators and transcription factors, is essential for TGFβ-induced myofibroblast transdifferentiation. However, its role in the development and progression of pulmonary fibrosis in vivo has not been established. Here, we evaluate the hypothesis that BRD4 bromodomain interactions mediate myofibroblast expansion and fibrosing disease in vivo. C57BL/6J mice challenged with intratracheal bleomycin were systemically treated with a selective allosteric inhibitor of the BRD4 bromodomain 1 (BD1), ZL0591 (10 mg/kg), during the established fibrotic phase (14 days post-bleomycin) in a rigorous therapeutic paradigm. Eleven days after initiation of ZL0591 treatment (25 days post-bleomycin), we detected a significant improvement in blood O2 saturation compared to bleomycin/vehicle control. Twenty-eight days post-bleomycin, we observed a reduction in the volumetric Hounsfield Unit (HU) density by micro computed tomography (µCT) in the ZL0591-treated group, as well as a reduction in collagen deposition (hydroxyproline content) and severity of injury (Ashcroft scoring). Myofibroblast transdifferentiation was measured by smooth muscle α-actin (αSMA) staining, indicating a loss of this cell population in the ZL0591-treated group, and corresponded to reduced transcript levels of myofibroblast-associated extracellular matrix genes, tenascin-C and collagen 1α1. We conclude that BRD4 BD1 interactions are critical for myofibroblast transdifferentiation and fibrotic progression in a mouse model of pulmonary fibrosis.
Clinical Features and Imaging Findings of Myelin Oligodendrocyte Glycoprotein-IgG-Associated Disorder (MOGAD)
Authors: Li Yunjie , Liu Xia , Wang Jingxuan , Pan Chao , Tang Zhouping
Published: March 2022

Myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is a nervous system (NS) demyelination disease and a newly recognized distinct disease complicated with various diseases or symptoms; however, MOGAD was once considered a subset of neuromyelitis optica spectrum disorder (NMOSD). The detection of MOG-IgG has been greatly improved by the cell-based assay test method. In one study, 31% of NMOSD patients with negative aquaporin-4 (AQP-4) antibody were MOG-IgG positive. MOGAD occurs in approximately the fourth decade of a person’s life without a markedly female predominance. Usually, optic neuritis (ON), myelitis or acute disseminated encephalomyelitis (ADEM) encephalitis are the typical symptoms of MOGAD. MOG-IgG have been found in patients with peripheral neuropathy, teratoma, COVID-19 pneumonia, etc. Some studies have revealed the presence of brainstem lesions, encephalopathy or cortical encephalitis. Attention should be given to screening patients with atypical symptoms. Compared to NMOSD, MOGAD generally responds well to immunotherapy and has a good functional prognosis. Approximately 44-83% of patients undergo relapsing episodes within 8 months, which mostly involve the optic nerve, and persistently observed MOG-IgG and severe clinical performance may indicate a polyphasic course of illness. Currently, there is a lack of clinical randomized controlled trials on the treatment and prognosis of MOGAD. The purpose of this review is to discuss the clinical manifestations, imaging features, outcomes and prognosis of MOGAD.
Early Supported Discharge and Transitional Care Management After Stroke: A Systematic Review and Meta-Analysis
Authors: Jee Sungju , Jeong Minah , Paik Nam-Jong , Kim Won-Seok , Shin Yong-Il , Ko Sung-Hwa , Kwon In Sun , Choi Bo Mi , Jung Yunsun , Chang Wonkee , Sohn Min Kyun
Published: March 2022

Objective

To investigate the available evidence on early supported discharge (ESD) and transitional care (TC) delivery service in patients with cerebrovascular disease.

Methods

A systematic literature search was conducted to collect all available evidence on the use of ESD and TC services. We included cluster-randomized pragmatic trials or randomized controlled trials (RCTs) that recruited patients with stroke or transient ischemic attack to receive either conventional care or any care service intervention that included rehabilitation or support provided by professional medical personnel with the aim of accelerating and supporting home discharge. Relevant data were electronically searched through international databases (Cochrane Library, EMBASE, and PubMed) and incorporated into a summary grid to investigate research outcomes and provide a narrative synthesis. Furthermore, we compared the outcomes in terms of length of hospital stay, patient and caregiver outcomes, and mortality through meta-analysis.

Results

We identified and included a total of 20 publications of various original randomized studies. There were 18 studies conducted in western countries and 2 in eastern countries. The meta-analysis revealed a tendency that ESD or TC could decrease the length of hospital stay more than the usual care [standardized mean difference (SMD) −0.13; 95% confidence interval (CI) −0.31 to 0.04 days; P = 0.14]. Moreover, there was a tendency that ESD resulted in better activities of daily living (ADL) than usual care (SMD 0.29; 95% CI −0.04 to 0.61; P = 0.08). Patient outcome based on modified Rankin scale (mRS) score (SMD −0.11; 95% CI −0.38 to 0.17; P = 0.45] and mortality (odds ratio 0.80; 95% CI 0.56–1.17; P = 0.25) did not reveal any significant difference. The Caregiver Strain Index revealed no difference.

Conclusion

We did not find a large effect size for the use of TC and ESD. When implementing the TC and ESD model from western to Asian countries, services should be prepared and implemented in accordance with national medical rehabilitation pathways for cerebrovascular disease.
The Temporal Lobe as a Symptomatogenic Zone in Medial Parietal Lobe Epilepsy
Authors: Jaafar Nadim , Bhatt Amar , Eid Alexandra , Koubeissi Mohamad Z.
Published: March 2022

Some surgical failures after temporal lobe epilepsy surgery may be due to the presence of an extratemporal epileptogenic zone. Of particular interest is the medial parietal lobe due to its robust connectivity with mesial temporal structures. Seizures in that area may be clinically silent before propagating to the symptomatogenic temporal lobe. In this paper, we present an overview of the anatomical connectivity, semiology, radiology, electroencephalography, neuropsychology, and outcomes in medial parietal lobe epilepsy. We also present two illustrative cases of seizures originating from the precuneus and the posterior cingulate cortex. We conclude that the medial parietal lobe should be strongly considered for sampling by intracranial electrodes in individuals with nonlesional temporal lobe epilepsy, especially if scrutinizing the presurgical data produces discordant findings.
Immunopathology of Tumefactive Demyelinating Lesions-From Idiopathic to Drug-Related Cases
Authors: Vakrakou Aigli G. , Brinia Maria-Evgenia , Svolaki Ioanna , Argyrakos Theodore , Stefanis Leonidas , Kilidireas Constantinos
Published: March 2022

Tumefactive demyelinating lesions (TDL) represent a diagnostic dilemma for clinicians, and in rare atypical cases a collaboration of a neuroradiologist, a neurologist, and a neuropathologist is warranted for accurate diagnosis. Recent advances in neuropathology have shown that TDL represent an umbrella under which many different diagnostic entities can be responsible. TDL can emerge not only as part of the spectrum of classic multiple sclerosis (MS) but also can represent an idiopathic monophasic disease, a relapsing disease with recurrent TDL, or could be part of the myelin oligodendrocyte glycoprotein (MOG)- and aquaporin-4 (AQP4)-associated disease. TDL can appear during the MS disease course, and increasingly cases arise showing an association with specific drug interventions. Although TDL share common features with classic MS lesions, they display some unique features, such as extensive and widespread demyelination, massive and intense parenchymal infiltration by macrophages along with lymphocytes (mainly T but also B cells), dystrophic changes in astrocytes, and the presence of Creutzfeldt cells. This article reviews the existent literature regarding the neuropathological findings of tumefactive demyelination in various disease processes to better facilitate the identification of disease signatures. Recent developments in immunopathology of central nervous system disease suggest that specific pathological immune features (type of demyelination, infiltrating cell type distribution, specific astrocyte pathology and complement deposition) can differentiate tumefactive lesions arising as part of MS, MOG-associated disease, and AQP4 antibody-positive neuromyelitis optica spectrum disorder. Lessons from immunopathology will help us not only stratify these lesions in disease entities but also to better organize treatment strategies. Improved advances in tissue biomarkers should pave the way for prompt and accurate diagnosis of TDL leading to better outcomes for patients.
Neuroprotective Effects of a Cholecystokinin Analogue in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Parkinson’s Disease Mouse Model
Authors: Zhang Zijuan , Li Hai , Su Yunfang , Ma Jinlian , Yuan Ye , Yu Ziyang , Shi Ming , Shao Simai , Zhang Zhenqiang , Hölscher Christian
Published: March 2022

Parkinson’s disease (PD) is a chronic neurodegenerative disease. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for PD. Drugs originally developed for T2DM treatment such as liraglutide have shown neuroprotective effects in mouse models of PD. Cholecystokinin (CCK) is a peptide hormone with growth factor properties. Here, we demonstrate the neuroprotective effects of the (pGLu)-(Gln)-CCK8 analogue in an acute PD mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Administration of CCK analogue (50 nmol/kg ip.) for 14 days treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. The CCK analogue administration also restored tyrosine hydroxylase (TH) positive dopaminergic neurons number and synapse number (synaptophysin levels) in the substantia nigra pars compacta (SNpc). The CCK analogue decreased glia activation and neuroinflammation in the SNpc, and regulated autophagy dysfunction induced by MPTP. CCK analogue protected against mitochondrial damage and ER stress, and also decreased the ratio of apoptosis signaling molecules Bax/Bcl-2. Importantly, the CCK analogue improved the decrease of p-CREBS133 growth factor signaling in the SNpc. Therefore, the CCK analogue promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB pathway that also inhibits apoptosis and regulates autophagy impairment. The present results indicate that CCK analogue shows a promising potential for the treatment of PD.
Combining Regional and Connectivity Metrics of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Individualized Prediction of Pain Sensitivity
Authors: Zou Rushi , Li Linling , Zhang Li , Huang Gan , Liang Zhen , Xiao Lizu , Zhang Zhiguo
Published: March 2022

Characterization and prediction of individual difference of pain sensitivity are of great importance in clinical practice. MRI techniques, such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), have been popularly used to predict an individual’s pain sensitivity, but existing studies are limited by using one single imaging modality (fMRI or DTI) and/or using one type of metrics (regional or connectivity features). As a result, pain-relevant information in MRI has not been fully revealed and the associations among different imaging modalities and different features have not been fully explored for elucidating pain sensitivity. In this study, we investigated the predictive capability of multi-features (regional and connectivity metrics) of multimodal MRI (fMRI and DTI) in the prediction of pain sensitivity using data from 210 healthy subjects. We found that fusing fMRI-DTI and regional-connectivity features are capable of more accurately predicting an individual’s pain sensitivity than only using one type of feature or using one imaging modality. These results revealed rich information regarding individual pain sensitivity from the brain’s both structural and functional perspectives as well as from both regional and connectivity metrics. Hence, this study provided a more comprehensive characterization of the neural correlates of individual pain sensitivity, which holds a great potential for clinical pain management.
Immune Checkpoint Inhibitor-Based Systemic Therapy Shows Remarkable Curative Effect in a Hepatocellular Carcinoma Patient With Intractable Postoperative Recurrence and Metastases: A Case Report and Literature Review
Authors: He Xing , Peng Yaorong , Zhou Zhenyu , Li Wenbin
Published: March 2022

Hepatocellular carcinoma (HCC) is a systemic disease, and most patients make the diagnosis at an advanced stage. In the past, treatments for recurrence of liver cancer with multiple metastases after surgery was very palliative, The case we present is a primary massive HCC patient with inferior vena cava tumor thrombus. Radical hepatectomy was performed in July 2016. Postoperative follow-up showed that sorafenib (a tyrosine kinase inhibitor TKI, 0.8g qd) failed to stop the progression of the disease. Fourteen months later, the patient gradually developed residual liver recurrence, multiple lung metastases and suspected splenic metastasis. The monotherapy regimen was changed from sorafenib to regorafenib (a TKI,160mg qd), but the disease continued to progress. The systematic treatment regimen was changed to Lenvatinib (a TKI, 8mg qd) plus Pembrolizumab (a immune checkpoint inhibitor ICI, 200mg q3w) in April 2019. Following treatment, partial remission (PR) was achieved. According to the mRECIST standard, the PFS has reached 24 months until March 2021, and the overall postoperative survival is 60 months until July 2021. The case we provide show that immune checkpoint inhibitor (ICI)-based systemic therapy may be an effective rescue treatment choice for HCC patients with intractable postoperative recurrence and metastasis.
Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer
Authors: Li Wan-Wan , Liu Bin , Dong Shu-Qing , He Shi-Qing , Liu Yu-Ying , Wei Si-Yu , Mou Jing-Yi , Zhang Jia-Xin , Liu Zhao
Published: March 2022

Background

Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongation and a novel key molecule in the poor prognosis of many cancers. However, its role in the development and progression of breast cancer remains unclear.

Methods

The transcript expression of CHPF in the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA), Gene Expression Omnibus (GEO) database was analyzed separately using the limma package of R software, and the relationship between CHPF transcriptional expression and CHPF DNA methylation was investigated in TCGA-BRCA. Kaplan-Meier curves were plotted using the Survival package to further assess the prognostic impact of CHPF DNA methylation/expression. The association between CHPF transcript expression/DNA methylation and cancer immune infiltration and immune markers was investigated using the TIMER and TISIDB databases. We also performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the clusterProfiler package. Western blotting and RT-PCR were used to verify the protein level and mRNA level of CHPF in breast tissue and cell lines, respectively. Small interfering plasmids and lentiviral plasmids were constructed for transient and stable transfection of breast cancer cell lines MCF-7 and SUM1315, respectively, followed by proliferation-related functional assays, such as CCK8, EDU, clone formation assays; migration and invasion-related functional assays, such as wound healing assay and transwell assays. We also conducted a preliminary study of the mechanism.

Results

We observed that CHPF was significantly upregulated in breast cancer tissues and correlated with poor prognosis. CHPF gene transcriptional expression and methylation are associated with immune infiltration immune markers. CHPF promotes proliferation, migration, invasion of the breast cancer cell lines MCF-7 and SUM1315, and is significantly enriched in pathways associated with the ECM-receptor interaction and PI3K-AKT pathway.

Conclusion

CHPF transcriptional expression and DNA methylation correlate with immune infiltration and immune markers. Upregulation of CHPF in breast cancer promotes malignant behavior of cancer cells and is associated with poorer survival in breast cancer, possibly through ECM-receptor interactions and the PI3K-AKT pathway.
IL-6/JAK/STAT3 Signaling in Breast Cancer Metastasis: Biology and Treatment
Authors: Manore Sara G. , Doheny Daniel L. , Wong Grace L. , Lo Hui-Wen
Published: March 2022

Breast cancer is the most commonly diagnosed cancer in women. Metastasis is the primary cause of mortality for breast cancer patients. Multiple mechanisms underlie breast cancer metastatic dissemination, including the interleukin-6 (IL-6)-mediated signaling pathway. IL-6 is a pleiotropic cytokine that plays an important role in multiple physiological processes including cell proliferation, immune surveillance, acute inflammation, metabolism, and bone remodeling. IL-6 binds to the IL-6 receptor (IL-6Rα) which subsequently binds to the glycoprotein 130 (gp130) receptor creating a signal transducing hexameric receptor complex. Janus kinases (JAKs) are recruited and activated; activated JAKs, in turn, phosphorylate signal transducer and activator of transcription 3 (STAT3) for activation, leading to gene regulation. Constitutively active IL-6/JAK/STAT3 signaling drives cancer cell proliferation and invasiveness while suppressing apoptosis, and STAT3 enhances IL-6 signaling to promote a vicious inflammatory loop. Aberrant expression of IL-6 occurs in multiple cancer types and is associated with poor clinical prognosis and metastasis. In breast cancer, the IL-6 pathway is frequently activated, which can promote breast cancer metastasis while simultaneously suppressing the anti-tumor immune response. Given these important roles in human cancers, multiple components of the IL-6 pathway are promising targets for cancer therapeutics and are currently being evaluated preclinically and clinically for breast cancer. This review covers the current biological understanding of the IL-6 signaling pathway and its impact on breast cancer metastasis, as well as, therapeutic interventions that target components of the IL-6 pathway including: IL-6, IL-6Rα, gp130 receptor, JAKs, and STAT3.
Intraluminal Diverticular Duodenal Duplication With Recurrent Abdominal Pain: A Case Report
Authors: Chen Jie , Xiong Guo-zuo , Tan Xiong , Wu Fei , Luo Dong-yang , Zou Qing-qing , Deng Zhihe , Bi Guo-shan
Published: March 2022

Duodenal duplication is a rare congenital anomaly and may manifest as pancreatitis, gastrointestinal bleeding, abdominal pain, perforation, and obstruction. Here, we present a case of intraluminal diverticular duodenal duplication (IDDD) in a child with recurrent abdominal pain caused by a large hole-like structure in the duodenal bulb. This condition has rarely been reported. An 11-year-old boy presented with recurrent attacks of abdominal pain. Upper endoscopy examination and barium swallowing led to an initial diagnosis of IDDD; this diagnosis was confirmed by operative findings and histopathological signs. He underwent a subtotal excision and duodenal anastomosis. No serious complications occurred following treatment. The patient was followed up for 8 months, and his condition improved without symptoms.
The Modulation of Chaihu Shugan Formula on Microbiota Composition in the Simulator of the Human Intestinal Microbial Ecosystem Technology Platform and its Influence on Gut Barrier and Intestinal Immunity in Caco-2/THP1-Blue™ Cell Co-Culture Model
Authors: Liu Ling , Lu Yi , Xu Chao , Chen Haitao , Wang Xuanying , Wang Yijie , Cai Biyu , Li Bing , Verstrepen Lynn , Ghyselinck Jonas , Marzorati Massimo , Yao Qinghua
Published: March 2022

The traditional Chinese medicine (TCM)–Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, is derived from the ancient Chinese pharmacopeia. It has been used for more than thousands of years in various suboptimal health statuses and diseases induced by chronic stress based on empirical therapy. Recent studies confirm the role of CSF in the development of many diseases, including depression, stress-induced hepatic injury and tumors. However, little has been known about the mechanisms behind the health effects of CSF. Here, we investigate the influence of CSF on the modulation of the simulated colonic microbiota of five healthy donors, gut barrier integrity, and intestinal immunity by combining the simulator of the human intestinal microbial ecosystem (SHIME®) technology platform with co-culture of intestinal and immune cells. This approach revealed that CSF stimulated the production of SCFA (acetate, propionate and butyrate) across donors while significantly lowering the production of branched SCFA (bSCFA). In terms of community composition, CSF stimulated a broad spectrum of health-related Bifidobacterium species, which are potent acetate and lactate producers. At the same time, it lowered the abundance of opportunistic pathogenic Escherichia coli. Later, we explore the effect of colonic fermentation of CSF on the gut barrier and intestinal immunity in the Caco-2/THP1-blue™ cell co-culture model. Based on the study using SHIME technology platform, CSF showed protective effects on inflammation-induced intestinal epithelial barrier disruption in all donors. Also, the treatment of CSF showed pronounced anti-inflammatory properties by strongly inducing anti-inflammatory cytokines IL-6 and IL-10 and reducing pro-inflammatory cytokine TNF-α. These findings demonstrate a significant modulatory effect of CSF on intestinal gut microbiota. CSF-microbial fermentation products improved the gut barrier and controlled intestinal inflammation.
Natural Product Alantolactone Targeting AKR1C1 Suppresses Cell Proliferation and Metastasis in Non-Small-Cell Lung Cancer
Authors: Fu Zhiwen , Li Shijun , Liu Jinmei , Zhang Cong , Jian Chen , Wang Lulu , Zhang Yu , Shi Chen
Published: March 2022

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, characterized by high invasion and metastasis. Aldo-keto reductase family 1 member C1 (AKR1C1) plays an important role in cancer cell proliferation and metastasis, and has gained attention as an anticancer drug target. Here, we report that the natural sesquiterpene lactone alantolactone (ALA) was shown to bind directly to AKR1C1 through the Proteome Integral Solubility Alteration (PISA) analysis, a label-free target identification approach based on thermal proteome profiling. Acting as a specific inhibitor of AKR1C1, ALA selectively inhibits the activity of AKR1C1 and ALA treatment in human non-small-cell lung cancer (NSCLC) cell results in a reduction in cell proliferation and metastasis, inhibition of AKR1C1 expression, and deactivation of STAT3. Moreover, ALA inhibited tumor growth in vivo, and the inhibition of AKR1C1 and STAT3 activation were also found in the murine xenograft model. Collectively, our work not only gives mechanistic insights to explain the bioactivity of ALA in anticancer but also provides opportunities of developing novel sesquiterpene lactone-based AKR1C1 inhibitors for the treatment of NSCLC.
Lysosome-Targeted Biosensor for the Super-Resolution Imaging of Lysosome–Mitochondrion Interaction
Authors: Wang Han , Fang Guiqian , Chen Huimin , Hu Maomao , Cui Yajuan , Wang Boyang , Su Yudong , Liu Yu , Dong Bo , Shao Xintian
Published: March 2022

Background: The interaction between lysosomes and mitochondria includes not only mitophagy but also mitochondrion–lysosome contact (MLC) that enables the two organelles to exchange materials and information. In our study, we synthesised a biosensor with fluorescence characteristics that can image lysosomes for structured illumination microscopy and, in turn, examined morphological changes in mitochondria and the phenomenon of MLC under pathological conditions.

Methods: After designing and synthesising the biosensor, dubbed CNN, we performed an assay with a Cell Counting Kit-8 to detect CNN’s toxicity in relation to H9C2 cardiomyocytes. We next analysed the co-localisation of CNN and the commercial lysosomal probe LTG in cells, qualitatively analysed the imaging characteristics of CNN in different cells (i.e. H9C2, HeLa and HepG2 cells) via structured illumination microscopy and observed how CNN entered cells at different temperatures and levels of endocytosis. Last, we treated the H9C2 cells with mannitol or glucose to observe the morphological changes of mitochondria and their positions relative to lysosomes.

Results: After we endocytosed CNN, a lysosome-targeted biosensor with a wide, stable pH response range, into cells in an energy-dependent manner. SIM also revealed that conditions in high glucose induced stress in lysosomes and changed the morphology of mitochondria from elongated strips to round spheres.

Conclusion: CNN is a new tool for tracking lysosomes in living cells, both physiologically and pathologically, and showcases new options for the design of similar biosensors.
Beep Test Does Not Induce Phosphorylation of Ras/MAPK- or JAK/STAT-Related Proteins in Peripheral Blood T Lymphocytes
Authors: Kostrzewa-Nowak Dorota , Nowak Robert
Published: March 2022

The Th1 cell subset is involved in the immunological response induced by physical exercise. The aim of this work is to evaluate the post-effort activation of Ras/MAPK and JAK/STAT signaling pathways in T cells of young, physically active men. Seventy-six physically active, healthy men between 15 and 21 years old performed a standard physical exercise protocol (Beep test). Phosphorylation levels of Ras/MAPK-(p38 MAPK, ERK1/2) and JAK/STAT-related (STAT1, STAT3, STAT5, and STAT6) proteins were evaluated by flow cytometry in Th and Tc cells post-effort and during the lactate recovery period. The performed physical effort was not a strong enough physiological stimulant to provoke the phosphorylation of ERK1/2, p38 MAPK, STAT1, STAT3, STAT5, and STAT6 in T cells, at least for the duration of our study (the end of the lactate recovery period). We conclude that more observation time-points, including shorter and longer times after the exercise, are required to determine if the Ras/MAPK signaling pathway is involved in modulating the post-effort immunological response.
Pancreatic Stellate Cells and Metabolic Alteration: Physiology and Pathophysiology
Authors: Hamada Shin , Matsumoto Ryotaro , Masamune Atsushi
Published: March 2022

Pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis. A wide variety of external stimuli can cause PSC activation accompanied by metabolic changes, which alters the tissue microenvironment by producing extracellular matrix proteins, cytokines, growth factors, and other mediators. Several metabolites aggravate fibrosis and inflammation by acting as key activating factors for PSCs. In other words, PSCs sense systemic metabolic changes. The detrimental effects of PSC activation on normal pancreatic cells, especially islet cells, further complicate metabolic imbalance through the dysregulation of glucose metabolism. PSC activation promotes cancer by altering the metabolism in pancreatic cancer cells, which collaborate with PSCs to efficiently adapt to environmental changes, promoting their growth and survival. This collaboration also contributes to the acquisition of chemoresistance. PSCs sequester chemotherapeutic agents and produce competing molecules as additional resistance mechanisms. The application of these metabolic targets for novel therapeutic strategies is currently being explored. This mini-review summarizes the role of PSCs in metabolic regulation of normal and cancerous cells.
Appropriate and Constant Potassium Supply Promotes the Growth of M9T337 Apple Rootstocks by Regulating Endogenous Hormones and Carbon and Nitrogen Metabolism
Authors: Xu Xinxiang , Wang Fen , Xing Yue , Liu Jingquan , Lv Mengxue , Meng Hao , Du Xin , Zhu Zhanling , Ge Shunfeng , Jiang Yuanmao
Published: March 2022

Potassium (K) is an indispensable nutrient element in the development of fruit trees in terms of yield and quality. It is unclear how a stable or unstable supply of K affects plant growth. We studied the root morphology and physiological and molecular changes in the carbon and nitrogen metabolism of M9T337 apple rootstock under different K levels and supply methods using hydroponics. Five K supply treatments were implemented: continuous low K (KL), initial low and then high K (KLH), appropriate and constant K (KAC), initial high and then low K (KHL), and continuous high K (KH). The results showed that the biomass, root activity, photosynthesis, and carbon and nitrogen metabolism of the M9T337 rootstocks were inhibited under KL, KH, KLH and KHL conditions. The KAC treatment promoted root growth by optimizing endogenous hormone content, enhancing carbon and nitrogen metabolism enzyme activities, improving photosynthesis, optimizing the distribution of carbon and nitrogen, and upregulating the transcription levels of nitrogen assimilation-related genes (nitrate reductase, glutamine synthetase, glutamate synthase, MdNRT1.1, MdNRT1.2, MdNRT1.5, MdNRT2.4). These results suggest that an appropriate and constant K supply ensures the efficient assimilation and utilization of nitrogen and carbon.
Exploring Green Creativity: The Effects of Green Transformational Leadership, Green Innovation Climate, and Green Autonomy
Authors: Maitlo Qamaruddin , Wang Xiuting , Jingdong Yan , Lashari Ishfaque Ahmed , Faraz Naveed Ahmad , Hajaro Nazim Hussain
Published: March 2022

None of the studies published in the extant literature has discussed the role of green innovation climate and green autonomy concerning green creativity and this study aims to offer these two novel constructs. By introducing the componential theory of creativity, this study explores green transformational leadership (GTL), green innovation climate, and green autonomy as antecedents of green creativity. The authors employed structural equation modeling (SEM) to analyze survey-based data collected from automotive firms in China. Data were collected from employee-supervisor working in the automotive industry located in Liaoning province, China. The findings reveal that GTL directly and indirectly via green innovation climate partially mediates the green creativity of employees in China. Moreover, green autonomy moderates the relationship between green innovation climate and green creativity. This pivotal contribution suggests that automotive business enterprises should develop GTL to nurture a green innovation climate and offer green autonomy for the green creativity of employees. The above antecedents of green creativity may enable business firms to gain a competitive advantage by innovating green products and practices.
Critical Incidents for Hispanic Students on the Path to the STEM Doctorate
Authors: Horton Dawn , Torres-Catanach Irma
Published: March 2022

Hispanics are grossly underrepresented in the receipt of STEM Ph.Ds. The National Science Foundation (NSF) Science and Engineering Indicators (Trapani and Hale, 2019) suggest that only 7.8% of S and E doctoral recipients are Hispanic while their representation in the population is more than twice that, and that figure goes even higher if restricted to those within the college-age range. To address this gap, the NSF has awarded a grant (the Hispanic Alliance for Graduate Education and the Professoriate, H-AGEP) to the City College of New York and the University of Texas at El Paso to work with Hispanic STEM doctoral students to provide teaching training and preparation for academic positions so they can become role models for Hispanic community college undergraduates. In working to understand the career-decision making of our Fellows, in-depth interviews were conducted (n = 13) to understand what put them on the path to defy the odds and become a STEM doctoral recipient. Interview results suggest that isolated, critical incidents and chance events were responsible for a number of our students entering into doctoral programs. This research suggests that for some Hispanic STEM doctoral students the experience of chance events meant the path to a STEM doctorate was not assured from a young age and further, that the provision of “planned” critical incidents may support an increase in Hispanic STEM doctoral enrollment.