bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of PET Degradation Using Artificial Microbial Consortia
Authors: Qi Xinhua , Ma Yuan , Chang Hanchen , Li Bingzhi , Ding Mingzhu , Yuan Yingjin
Published: December 2021

Polyethylene terephthalate (PET) biodegradation is regarded as an environmentally friendly degradation method. In this study, an artificial microbial consortium composed of Rhodococcus jostii, Pseudomonas putida and two metabolically engineered Bacillus subtilis was constructed to degrade PET. First, a two-species microbial consortium was constructed with two engineered B. subtilis that could secrete PET hydrolase (PETase) and monohydroxyethyl terephthalate hydrolase (MHETase), respectively; it could degrade 13.6% (weight loss) of the PET film within 7 days. A three-species microbial consortium was further obtained by adding R. jostii to reduce the inhibition caused by terephthalic acid (TPA), a breakdown product of PET. The weight of PET film was reduced by 31.2% within 3 days, achieving about 17.6% improvement compared with the two-species microbial consortium. Finally, P. putida was introduced to reduce the inhibition caused by ethylene glycol (EG), another breakdown product of PET, obtaining a four-species microbial consortium. With the four-species consortium, the weight loss of PET film reached 23.2% under ambient temperature. This study constructed and evaluated the artificial microbial consortia in PET degradation, which demonstrated the great potential of artificial microbial consortia in the utilization of complex substrates, providing new insights for biodegradation of complex polymers.
Tapping the Role of Microbial Biosurfactants in Pesticide Remediation: An Eco-Friendly Approach for Environmental Sustainability
Authors: Raj Aman , Kumar Ashwani , Dames Joanna Felicity
Published: December 2021

Pesticides are used indiscriminately all over the world to protect crops from pests and pathogens. If they are used in excess, they contaminate the soil and water bodies and negatively affect human health and the environment. However, bioremediation is the most viable option to deal with these pollutants, but it has certain limitations. Therefore, harnessing the role of microbial biosurfactants in pesticide remediation is a promising approach. Biosurfactants are the amphiphilic compounds that can help to increase the bioavailability of pesticides, and speeds up the bioremediation process. Biosurfactants lower the surface area and interfacial tension of immiscible fluids and boost the solubility and sorption of hydrophobic pesticide contaminants. They have the property of biodegradability, low toxicity, high selectivity, and broad action spectrum under extreme pH, temperature, and salinity conditions, as well as a low critical micelle concentration (CMC). All these factors can augment the process of pesticide remediation. Application of metagenomic and in-silico tools would help by rapidly characterizing pesticide degrading microorganisms at a taxonomic and functional level. A comprehensive review of the literature shows that the role of biosurfactants in the biological remediation of pesticides has received limited attention. Therefore, this article is intended to provide a detailed overview of the role of various biosurfactants in improving pesticide remediation as well as different methods used for the detection of microbial biosurfactants. Additionally, this article covers the role of advanced metagenomics tools in characterizing the biosurfactant producing pesticide degrading microbes from different environments.
Hepatocyte Growth Factor-Dependent Antiviral Activity of Activated cdc42-Associated Kinase 1 Against Hepatitis B Virus
Authors: Lee Hye Won , Choi Yongwook , Lee Ah Ram , Yoon Cheol-Hee , Kim Kyun-Hwan , Choi Byeong-Sun , Park Yong Kwang
Published: December 2021

Activated cdc42-associated kinase 1 (ACK1) is a well-known non-receptor tyrosine kinase that regulates cell proliferation and growth through activation of cellular signaling pathways, including mitogen-activated protein kinase (MAPK). However, the anti-HBV activity of ACK1 has not been elucidated. This study aimed to investigate the role of ACK1 in the HBV life cycle and the mechanism underlying the anti-HBV activity of ACK1. To examine the antiviral activity of ACK1, we established HepG2-ACK1 cells stably overexpressing ACK1. The HBV life cycle, including HBeAg/HBsAg secretion, HBV DNA/transcription, and enhancer activity, was analyzed in HepG2 and HepG2-ACK1 cells with HBV replication-competent HBV 1.2mer (HBV 1.2). Finally, the anti-HBV activity of ACK1 was examined in an HBV infection system. ACK1 suppressed HBV gene expression and transcription in HepG2 and HepG2-ACK1 cells. Furthermore, ACK1 inhibited HBV replication by decreasing viral enhancer activity. ACK1 exhibited its anti-HBV activity via activation of Erk1/2, which consequently downregulated the expression of HNF4α binding to HBV enhancers. Furthermore, hepatocyte growth factor (HGF) induced ACK1 expression at an early stage. Finally, ACK1 mediated the antiviral effect of HGF in the HBV infection system. These results indicated that ACK1 induced by HGF inhibited HBV replication at the transcriptional level by activating the MAPK-HNF signaling pathway. Our findings suggest that ACK1 is a potentially novel upstream molecule of MAPK-mediated anti-HBV activity.
Effect of Temperature and Cell Viability on Uranium Biomineralization by the Uranium Mine Isolate Penicillium simplicissimum
Authors: Schaefer Sebastian , Steudtner Robin , Hübner René , Krawczyk-Bärsch Evelyn , Merroun Mohamed L.
Published: December 2021

The remediation of heavy-metal-contaminated sites represents a serious environmental problem worldwide. Currently, cost- and time-intensive chemical treatments are usually performed. Bioremediation by heavy-metal-tolerant microorganisms is considered a more eco-friendly and comparatively cheap alternative. The fungus Penicillium simplicissimum KS1, isolated from the flooding water of a former uranium (U) mine in Germany, shows promising U bioremediation potential mainly through biomineralization. The adaption of P. simplicissimum KS1 to heavy-metal-contaminated sites is indicated by an increased U removal capacity of up to 550 mg U per g dry biomass, compared to the non-heavy-metal-exposed P. simplicissimum reference strain DSM 62867 (200 mg U per g dry biomass). In addition, the effect of temperature and cell viability of P. simplicissimum KS1 on U biomineralization was investigated. While viable cells at 30°C removed U mainly extracellularly via metabolism-dependent biomineralization, a decrease in temperature to 4°C or use of dead-autoclaved cells at 30°C revealed increased occurrence of passive biosorption and bioaccumulation, as confirmed by scanning transmission electron microscopy. The precipitated U species were assigned to uranyl phosphates with a structure similar to that of autunite, via cryo-time-resolved laser fluorescence spectroscopy. The major involvement of phosphates in U precipitation by P. simplicissimum KS1 was additionally supported by the observation of increased phosphatase activity for viable cells at 30°C. Furthermore, viable cells actively secreted small molecules, most likely phosphorylated amino acids, which interacted with U in the supernatant and were not detected in experiments with dead-autoclaved cells. Our study provides new insights into the influence of temperature and cell viability on U phosphate biomineralization by fungi, and furthermore highlight the potential use of P. simplicissimum KS1 particularly for U bioremediation purposes.

Graphical Abstract
Dioctanoyl Ultrashort Tetrabasic β-Peptides Sensitize Multidrug-Resistant Gram-Negative Bacteria to Novobiocin and Rifampicin
Authors: Ramirez Danyel , Berry Liam , Domalaon Ronald , Li Yanqi , Arthur Gilbert , Kumar Ayush , Schweizer Frank
Published: December 2021

Recently reported peptidomimetics with increased resistance to trypsin were shown to sensitize priority multidrug-resistant (MDR) Gram-negative bacteria to novobiocin and rifampicin. To further optimize proteolytic stability, β-amino acid-containing derivatives of these compounds were prepared, resulting in three dioctanoyl ultrashort tetrabasic β-peptides (dUSTBβPs). The nonhemolytic dUSTBβP 3, comprised of three β3-homoarginine residues and two fatty acyl tails eight carbons long, enhanced the antibacterial activity of various antibiotics from different classes. Notably, compound 3 retained the ability to potentiate novobiocin and rifampicin in wild-type Gram-negative bacteria against MDR clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. dUSTBβP 3 reduced the minimum inhibitory concentration of novobiocin and rifampicin below their interpretative susceptibility breakpoints. Furthermore, compound 3 exhibited improved in vitro stability (86.8 ± 3.7% remaining) relative to its α-amino acid-based counterpart (39.5 ± 7.4% remaining) after a 2 h incubation in human plasma.
Production of Methyl-Iodide in the Environment
Authors: Duborská Eva , Balíková Katarína , Matulová Michaela , Zvěřina Ondřej , Farkas Bence , Littera Pavol , Urík Martin
Published: December 2021

Iodine is an essential micronutrient for most of the living beings, including humans. Besides its indispensable role in animals, it also plays an important role in the environment. It undergoes several chemical and biological transformations resulting in the production of volatile methylated iodides, which play a key role in the iodine’s global geochemical cycle. Since it can also mitigate the process of climate change, it is reasonable to study its biogeochemistry. Therefore, the aim of this review is to provide information on its origin, global fluxes and mechanisms of production in the environment.
Biocontrol Potential of Aspergillus Species Producing Antimicrobial Metabolites
Authors: Ngo Men Thi , Van Nguyen Minh , Han Jae Woo , Kim Bomin , Kim Yun Kyung , Park Myung Soo , Kim Hun , Choi Gyung Ja
Published: December 2021

Microbial metabolites have been recognized as an important source for the discovery of new antifungal agents because of their diverse chemical structures with novel modes of action. In the course of our screening for new antifungal agents from microbes, we found that culture filtrates of two fungal species Aspergillus candidus SFC20200425-M11 and Aspergillus montenegroi SFC20200425-M27 have the potentials to reduce the development of fungal plant diseases such as tomato late blight and wheat leaf rust. From these two Aspergillus spp., we isolated a total of seven active compounds, including two new compounds (4 and 6), and identified their chemical structures based on the NMR spectral analyses: sphaeropsidin A (1), (R)-formosusin A (2), (R)-variotin (3), candidusin (4), asperlin (5), montenegrol (6), and protulactone A (7). Based on the results of the in vitro bioassays of 11 plant pathogenic fungi and bacteria, sphaeropsidin A (1), (R)-formosusin A (2), (R)-variotin (3), and asperlin (5) exhibited a wide range of antimicrobial activity. Furthermore, when plants were treated with sphaeropsidin A (1) and (R)-formosusin A (2) at a concentration of 500 μg/ml, sphaeropsidin A (1) exhibited an efficacy disease control value of 96 and 90% compared to non-treated control against tomato late blight and wheat leaf rust, and (R)-formosusin A (2) strongly reduced the development of tomato gray mold by 82%. Asperlin (5) at a concentration of 500 μg/ml effectively controlled the development of tomato late blight and wheat leaf rust with a disease control value of 95%. Given that culture filtrates and active compounds derived from two Aspergillus spp. exhibited disease control efficacies, our results suggest that the Aspergillus-produced antifungal compounds could be useful for the development of new natural fungicides.
Energy Bilocalization Effect and the Emergence of Molecular Functions in Proteins
Authors: Chalopin Yann , Sparfel Julien
Published: December 2021

Proteins are among the most complex molecular structures, which have evolved to develop broad functions, such as energy conversion and transport, information storage and processing, communication, and regulation of chemical reactions. However, the mechanisms by which these dynamical entities coordinate themselves to perform biological tasks remain hotly debated. Here, a physical theory is presented to explain how functional dynamical behavior possibly emerge in complex/macro molecules, thanks to the effect that we term bilocalization of thermal vibrations. More specifically, our approach allows us to understand how structural irregularities lead to a partitioning of the energy of the vibrations into two distinct sets of molecular domains, corresponding to slow and fast motions. This shape-encoded spectral allocation, associated to the genetic sequence, provides a close access to a wide reservoir of dynamical patterns, and eventually allows the emergence of biological functions by natural selection. To illustrate our approach, the SPIKE protein structure of SARS-COV2 is considered.
Mitochondria-Microbiota Interaction in Neurodegeneration
Authors: Kramer Peter
Published: December 2021

Alzheimer’s and Parkinson’s are the two best-known neurodegenerative diseases. Each is associated with the excessive aggregation in the brain and elsewhere of its own characteristic amyloid proteins. Yet the two afflictions have much in common and often the same amyloids play a role in both. These amyloids need not be toxic and can help regulate bile secretion, synaptic plasticity, and immune defense. Moreover, when they do form toxic aggregates, amyloids typically harm not just patients but their pathogens too. A major port of entry for pathogens is the gut. Keeping the gut’s microbe community (microbiota) healthy and under control requires that our cells’ main energy producers (mitochondria) support the gut-blood barrier and immune system. As we age, these mitochondria eventually succumb to the corrosive byproducts they themselves release, our defenses break down, pathogens or their toxins break through, and the side effects of inflammation and amyloid aggregation become problematic. Although it gets most of the attention, local amyloid aggregation in the brain merely points to a bigger problem: the systemic breakdown of the entire human superorganism, exemplified by an interaction turning bad between mitochondria and microbiota.
High-Throughput Strategy for Profiling Sequential Section With Multiplex Staining of Mouse Brain
Authors: Chen Siqi , Liu Zhixiang , Li Anan , Gong Hui , Long Ben , Li Xiangning
Published: December 2021

The brain modulates specific functions in its various regions. Understanding the organization of different cells in the whole brain is crucial for investigating brain functions. Previous studies have focused on several regions and have had difficulty analyzing serial tissue samples. In this study, we introduced a pipeline to acquire anatomical and histological information quickly and efficiently from serial sections. First, we developed a serial brain-slice-staining method to stain serial sections and obtained more than 98.5% of slices with high integrity. Subsequently, using the self-developed analysis software, we registered and quantified the signals of imaged sections to the Allen Mouse Brain Common Coordinate Framework, which is compatible with multimodal images and slant section planes. Finally, we validated the pipeline with immunostaining by analyzing the activity variance in the whole brain during acute stress in aging and young mice. By removing the problems resulting from repeated manual operations, this pipeline is widely applicable to serial brain slices from multiple samples in a rapid and convenient manner, which benefits to facilitate research in life sciences.
Case Report: Preservation of Otolithic Function After Triple Semicircular Canal Occlusion in a Patient With Intractable Ménière Disease
Authors: Zhang Yuzhong , Cheng Ying , Chen Zichen , Chen Feiyun , Zhang Qing
Published: December 2021

Operative measures are considered when medical treatment fails to control vertigo in patients with intractable Ménière disease. The present report discusses a case in which triple semicircular canal occlusion was performed in a 30-year-old female patient who responded poorly to previously performed endolymphatic sac surgery. Her vestibular and auditory functions were evaluated both before and after surgery. Class A control of vertigo was achieved during the 76-month postoperative follow-up period. Ocular and cervical vestibular evoked myogenic potentials could be elicited before and after surgery. This case suggests that relatively long-term preservation of otolithic function can be achieved following triple semicircular canal occlusion, highlighting its potential as an alternative treatment for patients with Ménière disease.
Preliminary Application of a Quantitative Collateral Assessment Method in Acute Ischemic Stroke Patients With Endovascular Treatments: A Single-Center Study
Authors: Cao Ruoyao , Qi Peng , Jiang Yun , Hu Shen , Ye Gengfan , Zhu Yaxin , Li Ling , You Zilong , Chen Juan
Published: December 2021

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS).

Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared.

Results: tMIP CTA VCCq (r = 0.61, p < 0.01), IC volume (r = 0.66, p < 0.01), Tan score on tMIP CTA (r = 0.52, p < 0.01) and mismatch ratio (r = 0.60, p < 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p < 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079).

Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.
Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis
Authors: Giannotti Nicola , McNulty Jonathan , Foley Shane , McCabe John , Barry Marey , Crowe Morgan , Dolan Eamon , Harbison Joseph , Horgan Gillian , Kavanagh Eoin , O'Connell Martin , Marnane Michael , Murphy Sean , Donnell Ciaran Mc , O'Donohoe Martin , Williams David , Kelly Peter J.
Published: December 2021

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis.

Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (<30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax).

Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708–1,286 mm3, p = 0.03), patients who qualified with stroke (1,856–1,440 mm3, p = 0.05), and non-statin users (1,325–1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (rs = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (rs = −0.4, p = 0.02) and calcium volume (rs = −0.4, p = 0.03).

Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.
Heart Rate Variability and Recurrent Stroke and Myocardial Infarction in Patients With Acute Mild to Moderate Stroke
Authors: von Rennenberg Regina , Krause Thomas , Herm Juliane , Hellwig Simon , Scheitz Jan F. , Endres Matthias , Haeusler Karl Georg , Nolte Christian H.
Published: December 2021

Objectives: In patients with acute ischemic stroke, reduced heart rate variability (HRV) may indicate poor outcome. We tested whether HRV in the acute phase of stroke is associated with higher rates of mortality, recurrent stroke, myocardial infarction (MI) or functional outcome.

Materials and Methods: Patients with acute mild to moderate ischemic stroke without known atrial fibrillation were prospectively enrolled to the investigator-initiated Heart and Brain interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413). HRV parameters were assessed during the in-hospital stay using a 10-min section of each patient's ECG recording at day- and nighttime, calculating time and frequency domain HRV parameters. Frequency of a combined endpoint of recurrent stroke, MI or death of any cause and the respective individual events were assessed 12 months after the index stroke. Patients' functional outcome was measured by the modified Rankin Scale (mRS) at 12 months.

Results: We included 308 patients (37% female, median NIHSS = 2 on admission, median age 69 years). Complete follow-up was achieved in 286/308 (93%) patients. At 12 months, 32 (9.5%), 5 (1.7%) and 13 (3.7%) patients had suffered a recurrent stroke, MI or death, respectively. After adjustment for age, sex, stroke severity and vascular risk factors, there was no significant association between HRV and recurrent stroke, MI, death or the combined endpoint. We did not find a significant impact of HRV on a mRS ≥ 2 12 months after the index stroke.

Conclusion: HRV did not predict recurrent vascular events in patients with acute mild to moderate ischemic stroke.
Perception of Prosodic Modulations of Linguistic and Paralinguistic Origin: Evidence From Early Auditory Event-Related Potentials
Authors: Zora Hatice , Csépe Valéria
Published: December 2021

How listeners handle prosodic cues of linguistic and paralinguistic origin is a central question for spoken communication. In the present EEG study, we addressed this question by examining neural responses to variations in pitch accent (linguistic) and affective (paralinguistic) prosody in Swedish words, using a passive auditory oddball paradigm. The results indicated that changes in pitch accent and affective prosody elicited mismatch negativity (MMN) responses at around 200 ms, confirming the brain’s pre-attentive response to any prosodic modulation. The MMN amplitude was, however, statistically larger to the deviation in affective prosody in comparison to the deviation in pitch accent and affective prosody combined, which is in line with previous research indicating not only a larger MMN response to affective prosody in comparison to neutral prosody but also a smaller MMN response to multidimensional deviants than unidimensional ones. The results, further, showed a significant P3a response to the affective prosody change in comparison to the pitch accent change at around 300 ms, in accordance with previous findings showing an enhanced positive response to emotional stimuli. The present findings provide evidence for distinct neural processing of different prosodic cues, and statistically confirm the intrinsic perceptual and motivational salience of paralinguistic information in spoken communication.
Assessment of the Methodology That Is Used to Determine the Nutritional Sustainability of the Mediterranean Diet—A Scoping Review
Authors: Portugal-Nunes Carlos , Nunes Fernando M. , Fraga Irene , Saraiva Cristina , Gonçalves Carla
Published: December 2021

Mediterranean diet (MedDiet) is often used as an example of a sustainable diet that promotes a sustainable food system. MedDiet presents low environmental impacts, is characterized by high sociocultural food values, allows for positive local economic returns, and presents major health and nutrition benefits. Previous studies have not systematically examined the methodological assessment of MedDiet nutritional sustainability. In our study, we review the methodological assessment of nutritional sustainability, filling a crucial gap in the literature that can inform the state of the art regarding the cross-disciplinary assessment of MedDiet nutritional sustainability. Through a systematic search on PubMed and Scopus, we identified 28 studies, published between 2013 and 2021, that dealt with the MedDiet nutritional sustainability. Studies that assessed the sustainability of MedDiet based on dietary consumption data, studies that explored the MedDiet sustainability resorting to dietary scenarios, and studies with a mixed approach (dietary consumption and dietary scenarios) and proposals of methodological approaches to assess the MedDiet nutritional sustainability were summarized. We identified 24 studies exploring the dimensions of nutritional sustainability of the MedDiet, and 4 proposing the methodological approaches to assess the MedDiet nutritional sustainability or the sustainability of MedDiet typical agro-foods. From the 24 studies exploring the sustainability of MedDiet, none fully addressed the complexity of the four dimensions of nutritional sustainability (environmental, economic, socio-cultural, and health-nutrition). One of the methodological proposals to assess the MedDiet nutritional sustainability contemplated on the four dimensions of nutritional sustainability, as well as one of the methodological proposals to assess the sustainability of typical agro-foods of MedDiet. Environmental sustainability was the most well-studied dimension, while no study focuses on the socio-cultural dimension of sustainability. Our study reviewed for the first time the assessment of nutritional sustainability of MedDiet. To the best of our knowledge, no research has been made assessing MedDiet in all the dimensions of the complex concept, that is nutritional sustainability. Integrating health and nutrition, environmental, economic, and socio-cultural considerations across scales and contexts can offer a more complete understanding of the opportunities and barriers to achieving nutritional sustainability not only in MedDiet but also in other dietary patterns and food products.
Impacts of Betaine Addition in Sow and Piglet's Diets on Growth Performance, Plasma Hormone, and Lipid Metabolism of Bama Mini-Pigs
Authors: Cheng Yating , Song Mingtong , Zhu Qian , Azad Md. Abul Kalam , Gao Qiankun , Kong Xiangfeng
Published: December 2021

The present study evaluated the effects of betaine addition in sow and piglet's diets on growth performance, plasma hormone, and lipid metabolism of Bama mini-pigs. A total of 26 pregnant Bama mini-pigs and 104 weaned piglets were selected and divided into different dietary treatment groups (details in “Materials and Methods”). Blood and muscle samples were collected at 65-, 95-, and 125-day-old, respectively. The results showed that betaine addition in sow-offspring diets increased (P < 0.05) the body weight at 125-day-old, average daily gain from 35- to 65-day-old, and average daily feed intake at 35–65 and 35–95 days old of pigs compared with the control group. Betaine addition in sow-offspring diets increased (P < 0.05) the plasma gastrin level at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the plasma peptide YY and leptin levels at 65-day-old pigs. In the longissimus dorsi muscle of pigs, betaine addition in sow and sow-offspring diets increased (P < 0.05) the C12:0 content at 65-day-old while decreased at 95-day-old. Moreover, betaine addition in sow-offspring diets increased the C24:0 content and decreased the C18:1n9t content at 125-day-old (P < 0.05). In the biceps femoris muscle, the contents of C12:0 at 65-day-old and C20:4n6 at 125-day-old were decreased (P < 0.05) after the betaine addition in both sow and piglet's diets. In addition, betaine addition in sow diets decreased (P < 0.05) the C20:0 content at 125-day-old, while betaine addition in sow-offspring diets increased the C18:3n6 and decreased C24:0 contents at 65-day-old pigs (P < 0.05). In the psoas major muscle, betaine addition in sow and sow-offspring diets decreased (P < 0.05) the contents of C18:1n9t at 65-day-old and C20:1 at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the intramuscular fat content at 125-day-old. Moreover, betaine addition in sow-offspring diets was also associated with muscle lipid deposition and metabolisms by regulating the gene expressions related to fatty acid metabolism. These findings suggested that betaine addition in sow-offspring diets could improve the growth performance, whereas betaine addition in both sow and sow-offspring diets could enhance lipid quality by altering plasma hormone level and fatty acid composition and regulating the gene expressions related to fatty acid metabolism.
Characterization of a Novel High Internal Phase Pickering Emulsions Stabilized by Soy Protein Self-Assembled Gel Particles
Authors: Bi Chong-hao , Chi Shang-yi , Zhou Tong , Wang Xue-ying , Zhang Jia-yi , Huang Zhi-gang , Gao Fei
Published: December 2021

In this paper, a novel high-internal-phase Pickering emulsion (HIPPE) prepared by acid-induced self-assembly SPI gel (A/S-SPIG) was investigated. The steady-state shear test results showed that all HIPPEs were typical shear thinning emulsion, which could form stable emulsion (0.2–1.2% SPI concentration). The network structure of HIPPE stabilized by A/S-SPIG particles (0.2–1.2% SPI concentration) was continuously enhanced with increasing SPI concentration. The high concentration of SPI particles increased the crystallization temperature of the stabilized HIPPE. Meanwhile, at a concentration of 1.2%, HIPPE has the best cohesive property and stability against delamination due to weakened mobility. In conclusion, A/S-SPIG was proved excellent HIPPE stabilized particle.
Interdisciplinary Surgical Treatments and Long-Term Outcomes of Lumbar Spinal Tumors With Retroperitoneal Involvements: A Retrospective Case Series Study
Authors: He Shaohui , Bi Yifeng , Ye Chen , Peng Dongyu , Xiao Jianru , Wei Haifeng
Published: December 2021

Purpose

Surgical treatments are technically challenging for lumbar spinal tumor (LST) with extensive retroperitoneal involvements. Our study aimed to report the experience and outcomes concerning interdisciplinary surgical collaborations in managing such LSTs.

Patients and Methods

Nine patients underwent interdisciplinary surgical treatments which were performed by specialists, namely, spinal, vascular, and urinary surgeries. Data on clinical characteristics were collected, and the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association Score (JOAS) were used in the evaluation before and after surgery. The postoperative complications and the long-term outcomes were reported as well.

Results

The interdisciplinary work included double J catheter indwelling (n = 9), nephrostomy (n = 5), replacement of the common iliac vein (n = 2), abdominal aorta repair (n = 3), and vital vessel repair (n = 8). The early-stage complications included complaints of moderate low back pain and slight implant shift (n = 1, 11.1%) and tardive ureterodialysis (n = 1, 11.1%). The 3- and 5-year disease-free survival rates were 76.2 ± 14.8 and 50.8 ± 23.0%, respectively, during the mean follow-up of 34.6 ± 17.9 months (range, 9.5–68.7). Besides this, more blood loss was associated with recurrent and metastatic tumor status (p = 0.043) and surgery time >5 h (p = 0.023). Remarkable pain relief and favorable quality of life were achieved based on the postoperative VAS (3.3 ± 0.9, p < 0.001) and JOAS (16.6 ± 0.5, p < 0.001).

Conclusions

The treatments of LSTs with wide-range retroperitoneal involvements require interdisciplinary surgical collaborations to lower the risks and improve the long-term outcomes. High-quality prospective cohort studies with large samples are warranted to establish general surgical protocols in managing LSTs with extensive retroperitoneal involvements.
Prognostic Role of Soluble Programmed Death Ligand 1 in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Liao Guixiang , Zhao Zhihong , Qian Yuting , Ling Xiean , Chen Shanyi , Li Xianming , Kong Feng-Ming (Spring)
Published: December 2021

Objective

The objective of this study was to explore whether soluble programmed death ligand 1 (sPD-L1) is a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC).

Methods

A comprehensive search of electronic databases was carried out. Original studies with inclusion of sPD-L1, progression-free survival, and overall survival in NSCLC were eligible. The primary endpoints were overall survival and progression-free survival. Hazard ratios (HRs) and 95% confidence intervals (CIs) were applied for data analysis.

Results

Eight studies involving 710 patients with NSCLC were included in the analysis. A pooled data analysis revealed that high levels of sPD-L1 were correlated with poorer overall survival (HR = 2.34; 95% CI = 1.82–3.00; P < 0.001) and progression-free survival (HR = 2.35; 95% CI = 1.62–3.40, P < 0.001). A subgroup analysis revealed that high levels of sPD-L1 were correlated with poor overall survival in patients treated with immunotherapy (HR = 2.40; 95% CI = 1.79–3.22; P < 0.001).

Conclusion

This pooled analysis of published data suggests that sPD-L1 may serve as a readily available biomarker for survival in NSCLC patients treated with ICI based treatment. Prospective studies with well-designed standard assessment methods should be conducted to validate the prognostic role of sPD-L1 in NSCLC.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283177.
The Relationship Between Gut Microbiome Features and Chemotherapy Response in Gastrointestinal Cancer
Authors: Li Ningning , Bai Chunmei , Zhao Lin , Sun Zhao , Ge Yuping , Li Xiaoyuan
Published: December 2021

Objective

The prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of cancer therapy, especially immunotherapy. There is limited evidence to date on the influence of microbes on chemotherapeutic response.

Design

In total, 130 patients with advanced or metastatic esophageal (n=40), gastric (n=46), and colorectal cancer (n=44) were enrolled. We included 147 healthy people as controls and used 16S rRNA sequencing to analyze the fecal microbiota.

Results

Significant differences in the abundance of fecal microbiota between patients with gastrointestinal cancer and controls were identified. The abundance of Bacteroides fragilis, Escherichia coli, Akkermansia muciniphila, Clostridium hathewayi, and Alistipes finegoldii were significantly increased in the patient group. Faecalibacterium prausnitzii, Roseburia faecis, Clostridium clostridioforme, Blautia producta, Bifidobacterium adolescent, and Butyricicoccus pullicaecorum taxa were significantly more abundant in the controls. The amount of R. faecis in non-responders (NR) was more likely to decrease significantly after chemotherapy, while the amount mostly increased in responders (R) (P=0.040). The optimal abundance variation of R. faecis may be a predictor for distinguishing patients with PD from those with non-PD in all patients with gastrointestinal cancer, with a sensitivity of 75.0% and a specificity of 93.9%.

Conclusion

The gut microbiome of patients with esophageal cancer, gastric cancer, and colorectal cancer differs from those of healthy people. The abundance alteration of R. faecis in patients with GI cancer might be a predictor of chemotherapy efficacy.
β-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells
Authors: Dharmapal Dhrishya , Jyothy Athira , Mohan Amrutha , Balagopal P. G. , George Nebu Abraham , Sebastian Paul , Maliekal Tessy Thomas , Sengupta Suparna
Published: December 2021

Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.
Case Report: Sirolimus Alleviates Persistent Cytopenia After CD19 CAR-T-Cell Therapy
Authors: Xing Limin , Wang Yihao , Liu Hui , Gao Shan , Shao Qing , Yue Lanzhu , Liu Zhaoyun , Wang Huaquan , Shao Zonghong , Fu Rong
Published: December 2021

Chimeric antigen receptor T (CAR-T) cells show good efficacy in the treatment of relapsed and refractory B-cell tumors, such as acute B-cell leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The main toxicities of CAR-T include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and severe infection. It is still very difficult for CAR-T to kill tumor cells to the maximum extent and avoid damaging normal organs. Here, we report a case of DLBCL with persistent grade 4 thrombocytopenia and severe platelet transfusion dependence treated with CD19 CAR-T cells. We used sirolimus to inhibit the sustained activation of CAR-T cells and restore normal bone marrow hematopoiesis and peripheral blood cells. Moreover, sirolimus treatment did not affect the short-term efficacy of CAR-T cells, and DLBCL was in complete remission at the end of follow-up. In conclusion, sirolimus can represent a new strategy for the management of CAR-T cell therapy-related toxicity, including but not limited to hematotoxicity. However, further controlled clinical studies are required to confirm these findings.
CDKN2A Deletion Leading to Hematogenous Metastasis of Human Gastric Carcinoma
Authors: Qiao Juanli , Tian Yuan , Cheng Xiaojing , Liu Zhaojun , Zhou Jing , Gu Liankun , Zhang Baozhen , Zhang Lianhai , Ji Jiafu , Xing Rui , Deng Dajun
Published: December 2021

Introduction

Somatic copy number deletion (SCND) of CDKN2A gene is the most frequent event in cancer genomes. Whether CDKN2A SCND drives human cancer metastasis is far from clear. Hematogenous metastasis is the main reason of human gastric carcinoma (GC) death. Thus, prediction GC metastasis is eagerly awaited.

Method

GC patients (n=408) enrolled in both a cross-sectional and a prospective cohorts were analysed. CDKN2A SCND was detected with a quantitative PCR assay (P16-Light). Association of CDKN2A SCND and GC metastasis was evaluated. Effect of CDKN2A SCND by CRISPR/Cas9 on biological behaviors of cancer cells was also studied.

Results

CDKN2A SCND was detected in 38.9% of GCs from patients (n=234) enrolled in the cross-sectional cohort. Association analysis showed that more CDKN2A SCND was recognized in GCs with hematogenous metastasis than those without (66.7% vs. 35.7%, p=0.014). CDKN2A SCND was detected in 36.8% of baseline pN0M0 GCs from patients (n=174) enrolled in the prospective study, the relationship between CDKN2A SCND and hematogenous metastasis throughout the follow-up period (62.7 months in median) was also significant (66.7% vs. 34.6%, p=0.016). Using CDKN2A SCND as a biomarker for predicting hematogenous metastasis of GCs, the prediction sensitivity and specificity were 66.7% and 65.4%. The results of functional experiments indicated that CDKN2A SCND could obviously downregulate P53 expression that consequently inhibited the apoptosis of MGC803 GC and HEK293T cells. This may account for hematogenous metastasis of GCs by CDKN2A SCND.

Conclusion

CDKN2A SCND may drive GC metastasis and could be used as a predictor for hematogenous metastasis of GCs.
Anesthesia and Cancer, Friend or Foe? A Narrative Review
Authors: Montejano Julio , Jevtovic-Todorovic Vesna
Published: December 2021

Cancer remains the leading cause of death worldwide with close to 10 million deaths reported annually. Due to growth of the advanced age cohort in our population, it is predicted that the number of new cancer cases diagnosed between now until 2035 is to reach potentially 24 million individuals, a staggering increase in a relatively short time period. For many solid tumors, surgical resection along with chemotherapy is the best available approach to a potential cure which leads to almost 80% of cancer patients undergoing at least one surgical procedure during the course of their disease. During surgical intervention, the exposure to general anesthesia can be lengthy, complex and often involves various modalities resulting in an important question as to the role, if any, anesthesia may play in primary recurrence or metastatic conversion. Many components of the stress and inflammatory responses exhibited in the perioperative period can contribute to cancer growth and invasion. The agents used to induce and maintain general anesthesia have variable interactions with the immune and neuroendocrine systems and can influence the stress response during surgery. Thus, debating the best type of anesthesia that would help to attenuate sympathetic and/or pro-inflammatory responses while modulating cytokine release and transcription factors/oncogenes remains at the forefront. This may affect inducible cancer cell survival and migratory abilities not only intra-operatively, but also during the immediate post-operative phase of recovery. The ultimate question becomes how and whether the choice of anesthesia may influence the outcomes of cancer surgery with two major approaches being considered, i.e., regional and general anesthesia as well as the various hypnotics, analgesics and sympatholytics commonly used. In this review, we will address the latest information as to the role that anesthesia may play during cancer surgery with specific focus on primary recurrence and metastasis.
Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Transarterial Chemoembolization and Sorafenib vs.125Iodine Implantation
Authors: Hu Hong-Tao , Luo Jun-Peng , Cao Guang-Shao , Li Zhen , Jiang Ming , Guo Chen-Yang , Yuan Hang , Yao Quan-Jun , Geng Xiang , Park Jung-Hoon , Cheng Hong-Tao , Jiang Li , Ma Jun-Li , Zhao Yan , Li Hai-Liang
Published: December 2021

Background and Aims

This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT).

Methods

This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death.

Results

This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105–10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519–18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively.

Conclusions

This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events.

Clinical Trial Registration

Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.