bluuebunny/crossref_metadata_2025 huggingface dataset:
Converting the 3‐quinuclidinone reductase from Agrobacterium tumefaciens into the ethyl 4‐chloroacetoacetate reductase by site‐directed mutagenesis
Authors: Liu Di , Gou Linbo , Bai Yajun , Fan Tai‐Ping , Zheng Xiaohui , Cai Yujie
Published: June 2021

In this study, the 3‐quinuclidinone reductase from Agrobacterium tumefaciens (AtQR) was modified by site‐directed mutagenesis. And we further obtained a saturation mutant library in which the residue 197 was mutated. A single‐point mutation converted the wild enzyme that originally had no catalytic activity in reduction of ethyl 4‐chloroacetoacetate (COBE) into an enzyme with catalytic activity. The results of enzyme activity assays showed that the seven variants could asymmetrically reduce COBE to ethyl (S)‐4‐chloro‐3‐hydroxybutyrate ((S)‐CHBE) with NADH as coenzyme. In the library, the variant E197N showed higher catalytic efficiency than others. The E197N was optimally active at pH 6.0 and 40°C, and the catalytic efficiency (kcat/Km) for COBE was 51.36 s–1·mM–1. This study showed that the substrate specificity of AtQR could be changed through site‐directed mutagenesis at the residue 197.
Reshaping cell line development and CMC strategy for fast responses to pandemic outbreak
Authors: Zhang Zheng , Chen Ji , Wang Junghao , Gao Qiao , Ma Zhujun , Xu Shurong , Zhang Li , Cai Jill , Zhou Weichang
Published: June 2021

The global pandemic outbreak COVID‐19 (SARS‐COV‐2), has prompted many pharmaceutical companies to develop vaccines and therapeutic biologics for its prevention and treatment. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next‐generation sequencing (NGS) with the B cells from the convalescent patients. To fight against pandemic outbreaks like COVID‐19, biologics development strategies need to be optimized to speed up the timeline. Since the advent of therapeutic biologics, strategies of transfection and cell line selection have been continuously improved for greater productivity and efficiency. NGS has also been implemented for accelerated cell bank testing. These recent advances enable us to rethink and reshape the chemistry, manufacturing, and controls (CMC) strategy in order to start supplying Good Manufacturing Practices (GMP) materials for clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics, including using GMP‐compliant pool materials for phase I clinical trials, selecting the final clone with product quality similar to that of phase I materials for late‐stage development and commercial production.
A case of bullous pemphigoid after a long‐term administration of anti‐PD‐1 antibodies in a patient with non‐small‐cell lung cancer
Authors: Yokoyama Emi , Yamasaki Osamu , Kubo Toshio , Koga Hiroshi , Ishii Norito , Morizane Shin
Published: June 2021

We described a case of BP that developed 2.5 years after the administration of nivolumab for metastatic non‐small cell lung cancer. Our report highlights the fact that dermatologists should be aware of anti PD‐1‐related BP, which can appear very late during treatment.
Vapour–liquid–liquid and vapour–liquid equilibrium of paraffinic aromatic synthetic naphtha/water blends: Prediction of the number of phases
Authors: Lopez‐Zamora Sandra , Kong Jeonghoon , Escobedo Salvador , de Lasa Hugo
Published: June 2021

Bitumen is extracted from oil sands using warm water and additives. The resulting bitumen froth is diluted with naphtha in a froth treatment process. Residual naphtha in the aqueous tailings of the froth treatment unit is recovered in a naphtha recovery unit (NRU). It is imperative to maximize the naphtha recovery process to minimize the plant's environmental and economic impact. It is, in this respect, that NRU vapour–liquid–liquid equilibrium data is of significant value. In this work, a paraffinic‐aromatic synthetic naphtha (PASN) with a true boiling point (TBP) similar to that of froth treatment naphtha is used. Water/PASN mixtures are studied using the Soave‐Redlich‐Kwong equation of state with a Kabadi‐Danner modification. The tangent plane distance (TPD) is evaluated as a possible criterion to calculate the number of phases, with its significant shortcomings being established. As well, experimental data obtained in a CREC‐VL‐Cell is observed to display higher solubilities of PASN in water than the ones obtained by HYSYS‐Aspen Plus V9 simulation. To address these issues, a machine learning (ML)‐based phase classification methodology was considered, predicting the number of phases with a 99% recall. This anticipates that ML will be of significant value for faster convergence of the flash split calculations for the naphtha hydrocarbon‐water systems under consideration.
Computational model of silica nanoparticle penetration into tumor spheroids: Effects of methoxy and carboxy PEG surface functionalization and hyperthermia
Authors: Nagesetti Abhignyan , Dulikravich George S. , Orlande Helcio R. B. , Colaco Marcelo J. , McGoron Anthony J.
Published: June 2021

Drug delivery to tumors suffers from poor solubility, specificity, diffusion through the tumor micro‐environment and nonoptimal interactions with components of the extracellular matrix and cell surface receptors. Nanoparticles and drug–polymer complexes address many of these problems. However, large size exasperates the problem of slow diffusion through the tumor. Three‐dimensional tumor spheroids are good models to evaluate approaches to mitigate these difficulties and aid in design strategies to improve the delivery of drugs to treat cancer effectively. Diffusion of drug carriers is highly dependent on cell uptake rate parameters (association/dissociation) and temperature. Hyperthermia increases molecular transport and is known to act synergistically with chemotherapy to improve treatment. This study presents a new inverse estimation approach based on Bayesian probability for estimating nanoparticle cell uptake rates from experiments. The parameters were combined with a finite element computational model of nanoparticle transport under hyperthermia conditions to explore its effect on tumor porosity, diffusion and particle binding (association and dissociation) at cell surfaces. Carboxy‐PEG‐silane (cPEGSi) nanoparticles showed higher cell uptake compared to methoxy‐PEG‐silane (mPEGSi) nanoparticles. Simulations were consistent with experimental results from Skov‐3 ovarian cancer spheroids. Amorphous silica (cPEGSi) nanoparticles (58 nm) concentrated at the periphery of the tumor spheroids at 37°C but mild hyperthermia (43°C) increased nanoparticle penetration. Thus, hyperthermia may enhance cancer treatment by improving blood delivery to tumors, enhancing extravasation and penetration into tumors, trigger release of drug from the carrier at the tumor site and possibly lead to synergistic anti‐cancer activity with the drug.
An Open‐Label, Randomized, 2‐Way, Crossover Bioequivalence Study of Cefradine Capsules in Healthy Chinese Volunteers
Authors: Lai Xiuping , Ye Suiwen , Chen Liuhan , Chen Junyi , Zhang Nan , Zhang Yiwen , Wu Junyan , Yao Herui
Published: June 2021

The purpose of this study was to evaluate whether test cefradine capsules and reference cefradine capsules were bioequivalent in healthy Chinese volunteers. An open‐label, randomized, biperiodic, crossover design was used. In each of the 2 study periods (separated by a 1‐week washout period), 250‐mg single doses of either the test or reference cefradine capsule were administered to study participants under fasted and fed conditions. Blood samples were collected at intervals from predose to 8 hours afterward. In the fasting study, the 90% confidence intervals (90%CI) of the Cmax, AUC0‐8h, and AUC0‐∞ for the test and reference preparations were 93.7%‐112.2%, 94.6%‐100.8%, and 94.7%‐100.9%, respectively. In the fed study, the 90%CI of the Cmax, AUC0‐8h, and AUC0‐∞ for the test and reference preparations was 81.0%‐99.1%, 100.5%‐106.3%, and 100.5%‐105.9%, respectively. The results showed that the test cefradine capsules and the reference formulation are bioequivalent under both fasting and fed conditions.
Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways
Authors: Shijie Li , Zhen Pan , Kang Qin , Hua Guo , Qingcheng Yang , Dongdong Cheng
Published: June 2021

Although the treatment of osteosarcoma has improved, the overall survival rate of this common type of osseous malignancies has not changed for four decades. Thus, new targets for better therapeutic regimens are urgently needed. In this study, we found that high expression of clathrin heavy chain (CLTC) was an independent prognostic factor for tumor‐free survival (HzR, 3.049; 95% CI, 1.476–6.301) and overall survival (HzR, 2.469; 95% CI, 1.005–6.067) of patients with osteosarcoma. Down‐regulation of CLTC resulted in tumor‐suppressive effects in vitro and in vivo. Moreover, we found that CLTC was transcriptionally regulated by a transcription factor—specificity protein 1 (SP1), which binds to the CLTC promoter at the −320 to −314‐nt and +167 to +173‐nt loci. Mechanistic investigations further revealed that CLTC elicited its pro‐tumor effects by directly binding to and stabilizing trafficking from the endoplasmic reticulum to the Golgi regulator (TFG). Importantly, overexpression of TFG rescued both the tumor‐suppressive effect and inhibition of the TGF‐β and AKT/mTOR pathways caused by CLTC down‐regulation, which indicated that the activity of CLTC was TFG‐dependent. Immunohistochemistry analysis confirmed that CLTC expression was positively correlated with TFG expression. These findings collectively highlight CLTC as a new prognostic biomarker for patients with osteosarcoma, and the interruption of the SP1/CLTC/TFG axis may serve as a novel therapeutic strategy for osteosarcoma.
IRF2‐mediated upregulation of lncRNA HHAS1 facilitates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells by acting as a competing endogenous RNA
Authors: Ye Guiwen , Wang Peng , Xie Zhongyu , Li Jinteng , Zheng Guan , Liu Wenjie , Cao Qian , Li Ming , Cen Shuizhong , Li Zhaofeng , Yu Wenhui , Wu Yanfeng , Shen Huiyong
Published: June 2021

Background

Mesenchymal stem cells (MSCs) are the major source of osteoblasts. Long noncoding RNAs (lncRNAs) are abundantly expressed RNAs that lack protein‐coding potential and play an extensive regulatory role in cellular biological activities. However, the regulatory network of lncRNAs in MSC osteogenesis needs further investigation.

Methods

QRT‐PCR, western blot, immunofluorescence, and immunohistochemistry assays were used to determine the levels of relevant genes. The osteogenic differentiation capability was evaluated by using Alizarin Red S (ARS) staining, alkaline phosphatase activity assays, hematoxylin & eosin staining or micro‐CT. RNA fluorescence in situ hybridization (FISH) and RNAscope were used to detect HHAS1 expression in cells and bone tissue. A microarray assay was performed to identify differentially expressed microRNAs. RNA immunoprecipitation and RNA pull‐down were used to explore the interactions between related proteins and nucleic acids.

Results

The level of lncRNA HHAS1 increased during bone marrow‐derived MSC (BMSC) osteogenesis and was positively related to the levels of osteogenic genes and ARS intensity. HHAS1 was located in both the cytoplasm and the nucleus and was expressed in human bone tissue. HHAS1 facilitated BMSC osteogenic differentiation by downregulating miR‐204‐5p expression and enhancing the level of RUNX family transcription factor 2 (RUNX2). In addition, interferon regulatory factor 2 (IRF2) was increased during BMSC osteogenic differentiation and interacted with the promoter of HHAS1, which resulted in the transcriptional activation of HHAS1. Furthermore, IRF2 and HHAS1 helped improve bone defect repair in vivo.

Conclusions

Our study identified a novel lncRNA, HHAS1, that facilitates BMSC osteogenic differentiation and proposed a role for the IRF2/HHAS1/miR‐204‐5p/RUNX2 axis in BMSC osteogenesis regulation. These findings help elucidate the regulatory network of BMSC osteogenesis and provide potential targets for clinical application.
Integrated transcriptional‐phenotypic analysis captures systemic immunomodulation following antiangiogenic therapy in renal cell carcinoma patients
Authors: Rinchai Darawan , Verzoni Elena , Huber Veronica , Cova Agata , Squarcina Paola , De Cecco Loris , de Braud Filippo , Ratta Raffaele , Dugo Matteo , Lalli Luca , Vallacchi Viviana , Rodolfo Monica , Roelands Jessica , Castelli Chiara , Chaussabel Damien , Procopio Giuseppe , Bedognetti Davide , Rivoltini Licia
Published: June 2021

Background

The combination of immune checkpoint blockade (ICB) with standard therapies is becoming a common approach for overcoming resistance to cancer immunotherapy in most human malignancies including metastatic renal cell carcinoma (mRCC). In this regard, insights into the immunomodulatory properties of antiangiogenic agents may help designing multidrug schedules based on specific immune synergisms.

Methods

We used orthogonal transcriptomic and phenotyping platforms combined with functional analytic pipelines to elucidate the immunomodulatory effect of the antiangiogenic agent pazopanib in mRCC patients. Nine patients were studied longitudinally over a period of 6 months. We also analyzed transcriptional data from The Cancer Genome Atlas (TCGA) RCC cohort (N = 571) to assess the prognostic implications of our findings. The effect of pazopanib was assessed in vitro on NK cells and T cells. Additionally, myeloid‐derived suppressor (MDSC)‐like cells were generated from CD14+ monocytes transfected with mimics of miRNAs associated with MDSC function in the presence or absence of pazopanib.

Results

Pazopanib administration caused a rapid and dramatic reshaping in terms of frequency and transcriptional activity of multiple blood immune cell subsets, with a downsizing of MDSC and regulatory T cells in favor of a strong enhancement in PD‐1 expressing cytotoxic T and Natural Killer effectors. These changes were paired with an increase of the expression of transcripts reflecting activation of immune‐effector functions. This immunomodulation was marked but transient, peaking at the third month of treatment. Moreover, the intratumoral expression level of a MDSC signature (MDSC INT) was strongly associated with poor prognosis in RCC patients. In vitro experiments indicate that the observed immunomodulation might be due to an inhibitory effect on MDSC‐mediated suppression, rather than a direct effect on NK and T cells.

Conclusions

The marked but transient nature of this immunomodulation, peaking at the third month of treatment, provides the rationale for the use of antiangiogenics as a preconditioning strategy to improve the efficacy of ICB.
Treg deficiency‐mediated TH1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells
Authors: Jiao Xue , Zhang Xiruo , Li Nianyu , Zhang Dunfang , Zhao Shidou , Dang Yujie , Zanvit Peter , Jin Wenwen , Chen Zi‐Jiang , Chen Wanjun , Qin Yingying
Published: June 2021

Immune dysregulation has long been proposed as a component of premature ovarian insufficiency (POI), but the underlying mediators and mechanisms remain largely unknown. Here we showed that patients with POI had augmented T helper 1 (TH1) responses and regulatory T (Treg) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of TH1:Treg cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of TH1 cells in the ovary resulted in follicle atresia and ovarian insufficiency, which could be prevented and reversed by Treg cells. Importantly, interferon (IFN) ‐γ and tumor necrosis factor (TNF) ‐α cooperatively promoted the apoptosis of granulosa cells and suppressed their steroidogenesis by modulating CTGF and CYP19A1. We have thus revealed a previously unrecognized Treg cell deficiency‐mediated TH1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI.
Molecular and physical technologies for monitoring fluid and electrolyte imbalance: A focus on cancer population
Authors: Bennet Devasier , Khorsandian Yasaman , Pelusi Jody , Mirabella Amy , Pirrotte Patrick , Zenhausern Frederic
Published: June 2021

Several clinical examinations have shown the essential impact of monitoring (de)hydration (fluid and electrolyte imbalance) in cancer patients. There are multiple risk factors associated with (de)hydration, including aging, excessive or lack of fluid consumption in sports, alcohol consumption, hot weather, diabetes insipidus, vomiting, diarrhea, cancer, radiation, chemotherapy, and use of diuretics. Fluid and electrolyte imbalance mainly involves alterations in the levels of sodium, potassium, calcium, and magnesium in extracellular fluids. Hyponatremia is a common condition among individuals with cancer (62% of cases), along with hypokalemia (40%), hypophosphatemia (32%), hypomagnesemia (17%), hypocalcemia (12%), and hypernatremia (1‐5%). Lack of hydration and monitoring of hydration status can lead to severe complications, such as nausea/vomiting, diarrhea, fatigue, seizures, cell swelling or shrinking, kidney failure, shock, coma, and even death. This article aims to review the current (de)hydration (fluid and electrolyte imbalance) monitoring technologies focusing on cancer. First, we discuss the physiological and pathophysiological implications of fluid and electrolyte imbalance in cancer patients. Second, we explore the different molecular and physical monitoring methods used to measure fluid and electrolyte imbalance and the measurement challenges in diverse populations. Hydration status is assessed in various indices; plasma, sweat, tear, saliva, urine, body mass, interstitial fluid, and skin‐integration techniques have been extensively investigated. No unified (de)hydration (fluid and electrolyte imbalance) monitoring technology exists for different populations (including sports, elderly, children, and cancer). Establishing novel methods and technologies to facilitate and unify measurements of hydration status represents an excellent opportunity to develop impactful new approaches for patient care.
Reduced mTORC1‐signaling in retinal ganglion cells leads to vascular retinopathy
Authors: Jones Iwan , Hägglund Anna‐Carin , Carlsson Leif
Published: June 2021

Background

The coordinated wiring of neurons, glia and endothelial cells into neurovascular units is critical for central nervous system development. This is best exemplified in the mammalian retina where interneurons, astrocytes and retinal ganglion cells sculpt their vascular environment to meet the metabolic demands of visual function. Identifying the molecular networks that underlie neurovascular unit formation is an important step towards a deeper understanding of nervous system development and function.

Results

Here, we report that cell‐to‐cell mTORC1‐signaling is essential for neurovascular unit formation during mouse retinal development. Using a conditional knockout approach we demonstrate that reduced mTORC1 activity in asymmetrically positioned retinal ganglion cells induces a delay in postnatal vascular network formation in addition to the production of rudimentary and tortuous vessel networks in adult animals. The severity of this vascular phenotype is directly correlated to the degree of mTORC1 down regulation within the neighboring retinal ganglion cell population.

Conclusions

This study establishes a cell nonautonomous role for mTORC1‐signaling during retinal development. These findings contribute to our current understanding of neurovascular unit formation and demonstrate how ganglion cells actively sculpt their local environment to ensure that the retina is perfused with an appropriate supply of oxygen and nutrients.
Potentiality of miniaturized techniques for the analysis of drugs of abuse
Authors: Fanali Chiara , D'Orazio Giovanni , Gentili Alessandra , Fanali Salvatore
Published: June 2021

Capillary electromigration (CE) and liquid chromatographic techniques (CLC/nano‐LC) are miniaturized techniques offering distinct advantages over conventional ones in the field of separation science. Among these, high efficiency, high chromatographic resolution, and use of minute volumes of both mobile phase and sample volumes are the most important. CE and CLC/nano‐LC have been applied to the analysis of many compounds including peptides, proteins, drugs, enantiomers, ions, etc. Over the years, the methods described here have also been used for the analysis of compounds of clinical, forensic, and toxicological interest. In this review article, the main features of the mentioned techniques are summarized. Their potentiality for the analysis of drugs of abuse are discussed. Some selected applications in this field in the period of 2015–present are also reported.
Immunomodulatory Effects of Lenvatinib Plus Anti–Programmed Cell Death Protein 1 in Mice and Rationale for Patient Enrichment in Hepatocellular Carcinoma
Authors: Torrens Laura , Montironi Carla , Puigvehí Marc , Mesropian Agavni , Leslie Jack , Haber Philipp K. , Maeda Miho , Balaseviciute Ugne , Willoughby Catherine E. , Abril‐Fornaguera Jordi , Piqué‐Gili Marta , Torres‐Martín Miguel , Peix Judit , Geh Daniel , Ramon‐Gil Erik , Saberi Behnam , Friedman Scott L. , Mann Derek A. , Sia Daniela , Llovet Josep M.
Published: June 2021

Background and Aims

Lenvatinib is an effective drug in advanced HCC. Its combination with the anti‐PD1 (programmed cell death protein 1) immune checkpoint inhibitor, pembrolizumab, has generated encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed to explore the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti‐PD1.

Approach and Results

We generated three syngeneic models of HCC in C57BL/6J mice (subcutaneous and orthotopic) and randomized animals to receive placebo, lenvatinib, anti‐PD1, or combination treatment. Flow cytometry, transcriptomic, and immunohistochemistry analyses were performed in tumor and blood samples. A gene signature, capturing molecular features associated with the combination therapy, was used to identify a subset of candidates in a cohort of 228 HCC patients who might respond beyond what is expected for monotherapies. In mice, the combination treatment resulted in tumor regression and shorter time to response compared to monotherapies (P < 0.001). Single‐agent anti‐PD1 induced dendritic and T‐cell infiltrates, and lenvatinib reduced the regulatory T cell (Treg) proportion. However, only the combination treatment significantly inhibited immune suppressive signaling, which was associated with the TGFß pathway and induced an immune‐active microenvironment (P < 0.05 vs. other therapies). Based on immune‐related genomic profiles in human HCC, 22% of patients were identified as potential responders beyond single‐agent therapies, with tumors characterized by Treg cell infiltrates, low inflammatory signaling, and VEGFR pathway activation.

Conclusions

Lenvatinib plus anti‐PD1 exerted unique immunomodulatory effects through activation of immune pathways, reduction of Treg cell infiltrate, and inhibition of TGFß signaling. A gene signature enabled the identification of ~20% of human HCCs that, although nonresponding to single agents, could benefit from the proposed combination.
Streamflow response to native forest restoration in former Eucalyptus plantations in south central Chile
Authors: Lara Antonio , Jones Julia , Little Christian , Vergara Nicolás
Published: June 2021

Global increases in intensive forestry have raised concerns about forest plantation effects on water, but few studies have tested the effects of plantation forest removal and native forest restoration on catchment hydrology. We describe results of a 14‐year paired watershed experiment on ecological restoration in south central Chile which documents streamflow response to the early stages of native forest restoration, after clearcutting of plantations of exotic fast‐growing Eucalyptus, planting of native trees, and fostering natural regeneration of native temperate rainforest species. Precipitation, streamflow, and vegetation were measured starting in 2006 in four small (3 to 5 ha) catchments with Eucalyptus globulus plantations and native riparian buffers in the Valdivian Coastal Reserve. Mean annual precipitation is 2500 mm, of which 11% occurs in summer. Streamflow increased, and increases persisted, throughout the first 9 years of vigorous native forest regeneration (2011 to 2019). Annual streamflow increased by 40% to >100% in most years and >150% in fall and summer of some years. Streamflow was 50% to 100% lower than before treatment in two dry summers. Base flow increased by 28% to 87% during the restoration period compared to pre‐treatment, and remained elevated in later years despite low summer precipitation. Overall, these findings indicate that removal of Eucalyptus plantations immediately increased streamflow, and native forest restoration gradually restored deep soil moisture reservoirs that sustain base flow during dry periods, increasing water ecosystem services. To our knowledge this is the first study to assess catchment streamflow response to native forest restoration in former forest plantations. Therefore, the results of this study are relevant to global efforts to restore native forest ecosystems on land currently intensively managed with fast‐growing forest plantations and may inform policy and decision‐making in areas experiencing a drying trend associated with climate change.
Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375
Authors: Li Liheng , Xiao Chengjiang , He Ke , Xiang Guoan
Published: June 2021

Circular RNAs feature prominently in cancer development. Nonetheless, the role of circ_0072088 in hepatocellular carcinoma (HCC) remains unclear. GEO databases (GSE97332, GSE108724, GSE36915, and GSE33006) were used to screen out the differentially expressed circRNAs, miRNAs, and mRNA in HCC. The expressions of circ_0072088, miR‐375, and Janus Kinase 2 (JAK2) mRNA in HCC tissue and cell lines were determined with quantitative real‐time polymerase chain reaction. RNase R treatment assay was used to measure the stability of circ_0072088, and subcellular fraction assay was used to detect the localization of circ_0072088. Cell counting kit‐8 assay, flow cytometry, and Transwell assay were used to measure proliferation, apoptosis, migration, and invasion of HCC cells. RNA immunoprecipitation and dual‐luciferase reporter gene assay were employed for investigating the binding sequence between circ_0072088 and miR‐375, as well as miR‐375 and JAK2 3′UTR. Western blot assay was used to detect the expression of JAK2 and p‐STAT3 after circ_0072088 and miR‐375 were selectively regulated. Circ_0072088 and JAK2 mRNA expressions were highly expressed in HCC tissues and cell lines while miR‐375 expression was remarkably downregulated. Circ_0072088 was resistant to RNase R treatment and mainly located in the cytoplasm of HCC cells. The transfection of circ_0072088 overexpression plasmid or miR‐375 inhibitors promoted the proliferation, migration, and invasion, and inhibited the apoptosis of HCC cells, whereas transfection of circ_0072088 siRNA or miR‐375 mimics exerted opposite effects. Besides, miR‐375 was confirmed as a target of circ_0072088 and miR‐375 could further downregulate the expression of JAK2. MiR‐375 mimics could reverse the upregulation of JAK2 and p‐STAT3 protein induced by circ_0072088 overexpression. Circ_0072088 can enhance the proliferation, migration, and invasion, and impede apoptosis of HCC cells. Mechanistically, circ_0072088 activates JAK2/STAT3 signaling pathway by serving as a molecular sponge of miR‐375.
High‐flux strategy for electrospun nanofibers in membrane distillation to treat aquaculture wastewater: a review
Authors: Zhou Lei , Tan Soon Huat , Ahmad Abdul Latif , Low Siew Chun
Published: June 2021

Aquaculture wastewater contains a large amount of nitrogen and phosphorus compounds, which has a serious impact on the environment and is also harmful to aquatic life. Such wastewater also contains high salinity, especially for mariculture activities. This review summarizes the recent progress and potential of electrospun nanofiber membranes (ENMs) in membrane distillation (MD) to treat high‐salinity aquaculture wastewater. Superhydrophobic membranes, which display a prominent wetting resistance, have been widely used to improve the efficiency of the MD process. The intuitive hypothesis is that a membrane with a low surface energy and a low sliding angle has a higher slip effect, thereby improving the wetting resistance of the membrane. Based on this perspective, this review focuses on the wetting tendency of parahydrophobic ENMs with high water adhesion and membrane design for MD wettability. Various strategies are reviewed, including the techniques to induce surface roughness during membrane fabrication and the post‐membrane modification to improve the wetting resistance of MD for long‐term operation. This review provides an in‐depth analysis and a fundamental interpretation of novel perspectives of ENMs for more advanced MD applications. © 2021 Society of Chemical Industry (SCI).
An autochthonous aerobic bacterial community and its cultivable isolates capable of degrading fluoxetine
Authors: Luz Palma Tânia , Shylova Anastasiia , Dias Carlier Jorge , Costa Maria Clara
Published: June 2021

BACKGROUND

Fluoxetine is an antidepressant and recalcitrant fluorine pharmaceutical that is poorly biodegraded, so it enters the hydric resources and causes hazardous effects to aquatic environments. According to these fluoxetine features, the main aim of the present research was to find resistant bacteria in environmental samples with a high degradation efficiency.

RESULTS

The results obtained from raw municipal wastewater spiked with fluoxetine and inoculated with aerobic sludge from a Portuguese wastewater treatment plant under highly aerobic conditions showed that more than half and ≈89% of the drug was degraded after 48 and 144 h, respectively. During the assay, the initial population (mainly composed of Arcobacter, Bacteroides, and Macellibacteroides) shifted with an increase of members of the Acinetobacter, Rheinheimera, Shewanella, Pseudomonas, Methylobacillus, Piscinobacter genera and Aeromonadales order and the Pseudomonadaceae family, all of which were likely responsible for fluoxetine biodegradation. From the same sludge, six bacterial isolates were selected and identified as follows: Pseudomonas putida, Enterobacter ludwigii, Pseudomonas nitritireducens, Alcaligenes faecalis, Pseudomonas aeruginosa, and Pseudomonas nitroreducens; all of them grew with fluoxetine as sole carbon source. Pseudomonas nitroreducens showed the highest removal of 55 ± 1% at 20 mg L–1 fluoxetine after 24 h.

CONCLUSION

An autochthonous aerobic bacterial community and its cultivable isolates showed the capacity to biodegrade fluoxetine. Biodegradation, rather than adsorption, appears to play the main role in the fluoxetine removal in aerobic conditions using bacteria simply obtained from an environmental sample. As far as is known, those bacteria are reported for the first time as fluoxetine biodegraders; thus, these bacteria are a promising option to integrate into new bioremediation processes aiming at the removal of fluoxetine. © 2021 Society of Chemical Industry (SCI).
ABCMETAapp: R shiny application for simulation‐based estimation of mean and standard deviation for meta‐analysis via approximate Bayesian computation
Authors: Kwon Deukwoo , Reddy Roopesh Reddy Sadashiva , Reis Isildinha M.
Published: June 2021

In meta‐analysis based on continuous outcome, estimated means and corresponding standard deviations from the selected studies are key inputs to obtain a pooled estimate of the mean and its confidence interval. We often encounter the situation that these quantities are not directly reported in the literatures. Instead, other summary statistics are reported such as median, minimum, maximum, quartiles, and study sample size. Based on available summary statistics, we need to estimate estimates of mean and standard deviation for meta‐analysis. We developed an R Shiny code based on approximate Bayesian computation (ABC), ABCMETA, to deal with this situation. In this article, we present an interactive and user‐friendly R Shiny application for implementing the proposed method (named ABCMETAapp). In ABCMETAapp, users can choose an underlying outcome distribution other than the normal distribution when the distribution of the outcome variable is skewed or heavy tailed. We show how to run ABCMETAapp with examples. ABCMETAapp provides an R Shiny implementation. This method is more flexible than the existing analytical methods since estimation can be based on five different distributions (Normal, Lognormal, Exponential, Weibull, and Beta) for the outcome variable.
Chemometric evaluation of functional components and anti‐quorum sensing activity of mulberry leaves from Indian cultivars: a potential contribution to the food industry
Authors: Shreelakshmi Saligrama Viswanath , Nazareth Maria Sheeba , Matam Pradeep , Dorairaj Darshan , Shetty Nandini P
Published: June 2021

BACKGROUND

Potential use of many native, easily available vegetal materials for human consumption and value addition is not well recognized. Mulberry, being a traditional industrial crop rich in nutrients and nutraceuticals can be of great importance for the food industry. However, mulberry leaves are mainly being utilized in sericulture and are not exploited for their functional components. Thus, the selection of promising mulberry cultivars, rich in bioactive compounds, like resveratrol and 1‐deoxynojirimycin, increase their potential use in functional foods.

RESULTS

Chlorogenic acid, myricetin and kaempferol were the major polyphenols present in the nine selected cultivars, in the range 0.001–0.086, 0.003–0.079 and 0.003–0.163 g kg−1fresh weight (FW), respectively. Protocatechuic acid, epicatechin and rutin were predominantly present in cultivars V‐1, G‐2 and ML (0.103, 0.080 and 0.121 g kg−1FW, respectively). Similarly, resveratrol and 1‐deoxynojirimycin were highest in cultivars ML and K‐2 (0.078 and 0.079 g kg−1FW, respectively). Leaf extracts of cultivars G‐2 and ML were able to effectively inhibit the violacein production with 64.08% and 70.04%, respectively at the concentration of 6 mg mL−1presumably due to a higher content of polyphenols. Chemometric evaluation of chromatographic data showed the intraspecific variability and secondary metabolite co‐existence in different cultivars.

CONCLUSIONS

Considering phytoconstituents, cultivars G‐2, ML, K‐2 and V‐1 could contribute efficiently to the rational utilization of mulberry in agro‐food industries. Furthermore, cultivars G‐2 and ML leaves can be a new source of quorum sensing inhibitory agents. © 2021 Society of Chemical Industry.
Effects of yeast hydrolysate on growth performance, serum parameters, carcass traits, meat quality and antioxidant status of broiler chickens
Authors: Wang Ting , Cheng Kang , Yu CaiYun , Tong YiChun , Yang ZaiBin , Wang Tian
Published: June 2021

BACKGROUND

Yeast hydrolysate (YH) has multiple salutary biological activities. Nevertheless, the application of YH in broiler production is limited. This study was conducted to evaluate the protective effects of YH derived from Saccharomyces cerevisiae by exploring growth performance, serum parameters, organs relative weight, carcass traits, meat quality and antioxidant status of broilers.

RESULTS

Supplementing YH linearly and quadratically improved (P < 0.05) body weight gain and gain‐to‐feed ratio compared to that in the control group. Triglycerides, low‐density lipoprotein cholesterol and total cholesterol in serum, the decline in pH and cooking loss of breast muscle, and malonaldehyde concentration in serum and liver were decreased linearly and/or quadratically by YH (P < 0.05), whereas high‐density lipoprotein cholesterol in serum, superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activities in serum, GSH‐Px activity in liver, glutathione content in serum and liver, eviscerated yield rate and chest muscle yield, and the relative weight of spleen and liver were linearly and/or quadratically increased (P < 0.05). Moreover, YH enhanced the mRNA levels of nuclear factor erythroid 2‐related factor 2, heme oxygennase‐1 (HO‐1), GSH‐Px1 and SOD1 (linear and/or quadratic, P < 0.05).

CONCLUSION

Dietary YH beneficially affected growth performance, serum parameters, organ relative weight, carcass traits, meat quality and antioxidant status in broilers, indicating its potential application as a promising feed additive in broiler production. © 2021 Society of Chemical Industry.
Effects of 25‐hydroxyvitamin D3 on growth performance, serum parameters, fecal microbiota, and metabolites in weaned piglets fed diets with low calcium and phosphorus
Authors: Zhang Lianhua , Yang Ming , Piao Xiangshu
Published: June 2021

BACKGROUND

With the development of intensive farming, long‐term exposure of pigs to poor light conditions is not conducive to the production of vitamin D3, and vitamin D3 deficiency could affect absorption and metabolism of calcium (Ca) and phosphorus (P). 25‐Hydroxyvitamin D3 (25OHD3) has higher bioactivity than regular vitamin D3. This study investigated the effects of 25OHD3 on performance, serum parameters, fecal microbiota, and metabolites in weaned piglets fed with low Ca‐P diet.

RESULTS

It was found that a low Ca‐P diet supplemented with 50 μg/kg 25OHD3 (NC + 25‐D) improved (P < 0.05) average daily gain (ADG) in phase 2 and in the overall period of the experiment, and increased (P < 0.05) the immunoglobulin G (IgG), immunoglobulin A (IgA), catalase (CAT), bone‐specific alkaline phosphatase (BALP), and osteocalcin (OC) serum content on day 28 compared with a low Ca‐P diet (NC), but no differences were observed between a normal Ca‐P diet (PC) and the NC + 25‐D diet. Compared with NC, the abundance of Firmicutes was higher (P < 0.05) in PC and NC + 25‐D. NC + 25‐D decreased (P < 0.05) the abundance of Streptococcaceae compared with PC and NC, and increased (P < 0.05) the abundance of Lachnospiraceae compared with NC. Serum 25OHD3 was negatively correlated with the abundance of fecal Streptococcaceae (P < 0.05), and positively correlated with the abundance of fecal Lachnospiraceae (P < 0.05).

CONCLUSION

Supplementation of 25OHD3 in a low Ca‐P diet improved serum immunity, bone biochemical parameters, and fecal microbiota such as decreased Streptococcaceae abundance and increased Lachnospiraceae abundance, which could subsequently promote growth of piglets. The effects were similar to that of a normal Ca‐P diet. © 2021 Society of Chemical Industry.
Research advancement and commercialization of microalgae edible oil: a review
Authors: Xue Zhaohui , Li Shihao , Yu Wancong , Gao Xin , Zheng Xu , Yu Yue , Kou Xiaohong
Published: June 2021

The global food crisis has led to a great deal of attention being given to microalgal oil as a sustainable natural food source. This article provides an overview of the progress and future directions in promoting the commercialization of microalgal edible oils, including microalgal triglyceride accumulation, suitable edible oil culture strategies for high nutritional value, metabolic engineering, production, and downstream technologies. The integration of the production process, biosafety, and the economic sustainability of microalgal oil production are analyzed for their critical roles in the commercialization of microalgal edible oil to provide a theoretical and scientific basis for the comprehensive development and utilization of microalgal edible oil. © 2021 Society of Chemical Industry.
Determination of heterocyclic amines in braised sauce beef and the effects of different cooking conditions on the formation of heterocyclic amines
Authors: Zhou Ya Jun , Zhang Yu Xia , Dong Xue Wen
Published: June 2021

BACKGROUND

Cooked meat is a good source of high‐quality protein. However, during long‐term cooking of meat, radical‐induced lipid and protein oxidation may lead to the formation of poisonous compounds, such as heterocyclic amines (HAs). This work investigated a testing method for HAs and it describes that cooking temperature, cooking time and repeated cooking times have influences on the overall quality of braised sauce beef and the effect of HAs formation.

RESULTS

The improved method has a good separation effect on nine kinds of HAs. The average recovery of HAs at two spiked levels is between 51.70% and 88.25% (n = 6). The detection limit is 0.025–0.060 ng g–1, and the limit of quantitation is 0.070–0.160 ng g–1. Only harman and norharman were detected in samples. Cooking time and cooking temperature will affect the quality and HA content of samples. When the braised sauce beef soup was cooked 20 times, the HA content was the highest – as high as 21.43 ng g–1. The more times the beef was cooked repeatedly, the higher was the HA content. Under different cooking conditions, glucose has a significant effect on the formation of β‐carboline.

CONCLUSION

We have established a detection method for HAs with good repeatability and accuracy. HAs were more easily formed in braised sauce beef by high temperature, long heating and repeated brine cooking. © 2021 Society of Chemical Industry.
Shift in archaeal community along a soil profile in coastal wheat‐maize rotation fields of different reclamation ages
Authors: Wan Shaoyu , Liao Xiaolin , Zhou Tong Tong , Wu Yan , Hu Anyong , Yan Dezhi , Zhang Jiao , Long Xi‐En
Published: June 2021

Coastal mudflats reclamation activities show a strong influence on soil properties and microbial community activity, which drive soil carbon and nitrogen cycling. Studies have found there is a shift of bacterial community with reclamation time. However, effects of reclamation time on the soil archaeal community are still largely unknown. Here, we determined soil properties and archaeal community in the soil profiles (0–15, 15–30, 30–45 cm) of different reclaimed sites with different reclamation ages (R12: 12‐year; R38: 38‐year; R68: 68‐year; R100: 100‐year) in Rudong County, Jiangsu, China. Soil archaeal communities were identified via Illumina high‐throughput sequencing. Soil archaeal communities were dominated by two phyla, the Crenarchaeota (82.1–93.3%) and Thermoplasmatota (4.2–17.9%), which are associated with nitrogen cycle (Nitrosopumilaceae, Nitrososphaeraceae, and Nitrosotaleaceae) and organic carbon metabolism (Marine_Group_II), respectively. Ammonia oxidizing archaea showed a divergent response to the reclamation, i.e. Nitrosotaleaceae increased with reclamation time whereas Nitrosopumilaceae showed a decreasing trend. Soil total carbon, total nitrogen, pH, EC, C:N ratio, NO3−‐N content, soil moisture, depth, and reclamation age determined archaeal community distribution in our reclaimed sites. Our findings suggest that both reclamation time and soil depth significantly shaped the archaeal community composition, and then in turn modulated soil carbon and nitrogen cycling in the reclaimed mudflats.
Recent pharmacological advances in the repurposing of artemisinin drugs
Authors: Meng Yuqing , Ma Nan , Lyu Haining , Wong Yin Kwan , Zhang Xing , Zhu Yongping , Gao Peng , Sun Peng , Song Yali , Lin Lizhu , Wang Jigang
Published: June 2021

Artemisinins are a family of sesquiterpene lactones originally derived from the sweet wormwood (Artemisia annua). Beyond their well‐characterized role as frontline antimalarial drugs, artemisinins have also received increased attention for other potential pharmaceutical effects, which include antiviral, antiparsitic, antifungal, anti‐inflammatory, and anticancer activities. With concerted efforts in further preclinical and clinical studies, artemisinin‐based drugs have the potential to be viable treatments for a great variety of human diseases. Here, we provide a comprehensive update on recent reports of pharmacological actions and applications of artemisinins outside of their better‐known antimalarial role and highlight their potential therapeutic viability for various diseases.
Proteomics support the threespine stickleback egg coat as a protective oocyte envelope
Authors: Killingbeck Emily E. , Wilburn Damien B. , Merrihew Gennifer E. , MacCoss Michael J. , Swanson Willie J.
Published: June 2021

Ancestrally marine threespine stickleback fish (Gasterosteus aculeatus) have undergone an adaptive radiation into freshwater environments throughout the Northern Hemisphere, creating an excellent model system for studying molecular adaptation and speciation. Ecological and behavioral factors have been suggested to underlie stickleback reproductive isolation and incipient speciation, but reproductive proteins mediating gamete recognition during fertilization have so far remained unexplored. To begin to investigate the contribution of reproductive proteins to stickleback reproductive isolation, we have characterized the stickleback egg coat proteome. We find that stickleback egg coats are comprised of homologs to the zona pellucida (ZP) proteins ZP1 and ZP3, as in other teleost fish. Our molecular evolutionary analyses indicate that across teleosts,ZP3but notZP1has experienced positive Darwinian selection. MammalianZP3is also rapidly evolving, and surprisingly some residues under selection in stickleback and mammalian ZP3 directly align. Despite broad homology, however, we find differences between mammalian and stickleback ZP proteins with respect to glycosylation, disulfide bonding, and sites of synthesis. Taken together, the changes we observe in stickleback ZP protein architecture suggest that the egg coats of stickleback fish, and perhaps fish more generally, have evolved to fulfill a more protective functional role than their mammalian counterparts.
Exertional rhabdomyolysis in newly enrolled cadets of a military academy
Authors: Mao Han‐ding , Li Xin , Liu Shu‐yuan , Xing Ling , Zhao Jin‐bao , Tan Zhi‐jun , Sun Hai‐long , Song Qing
Published: June 2021

Introduction/Aims

Exertional rhabdomyolysis (ER) often occurs during prolonged intense exercise in hot environments, posing a threat to the health of military personnel. In this study we aimed to investigate possible risk factors for ER and provide further empirical data for prevention and clinical treatment strategies.

Methods

A retrospective investigation of 116 concurrent ER cases was conducted. Conditional logistic regression analyses were performed to assess the association between each potential risk (or protective) factor and ER. The clinical characteristics of the 71 hospitalized patients were analyzed descriptively.

Results

After screening, the following variables significantly increased the risk of ER: shorter length of service (recruits; odds ratios [OR], 7.49; 95% confidence interval [CI], 2.58‐21.75); higher body mass index (BMI; OR, 1.14, 95% CI, 1.03‐1.26); lack of physical exercise in the last half year (less than once per month; OR, 3.20; 95% CI, 1.08‐9.44); and previous heat injury (OR, 2.94; 95% CI, 1.26‐6.89). Frequent fruit consumption (OR, 0.57; 95% CI, 0.33‐0.99), active hydration habit (OR, 0.37; 95% CI, 0.20‐0.67), water replenishment of more than 2 L on the training day (OR, 0.15; 95% CI, 0.05‐0.45), and water replenishment of at least 500 mL within 1 hour before training (OR, 0.33; 95% CI, 0.12‐0.88) significantly decreased the risk of ER. Of the 71 hospitalized patients, 41 (57.7%) were diagnosed with hypokalemia on admission.

Discussion

In military training, emphasis should be placed on incremental adaptation training before more intense training, and close attention should be given to overweight and previously sedentary recruits. Fluid replenishment before exercise, increased fruit intake, and proper potassium supplementation may help prevent ER.