bluuebunny/crossref_metadata_2025 huggingface dataset:
SQSTM1/p62 in intrahepatic cholangiocarcinoma promotes tumor progression via epithelial–mesenchymal transition and mitochondrial function maintenance
Authors: Chen Jiafeng , Gao Zheng , Li Xiaogang , Shi Yinghong , Tang Zheng , Liu Weiren , Zhang Xin , Huang Ao , Luo Xuanming , Gao Qiang , Ding Guangyu , Song Kang , Zhou Jian , Fan Jia , Fu Xiutao , Ding Zhenbin
Published: June 2022

Background

SQSTM1/p62 is a selective autophagy receptor that regulates multiple signaling pathways participating in the initiation and progression of tumors. Metastasis is still the main cause for intrahepatic cholangiocarcinoma (ICC)‐associated mortality. Hence, this study aimed to explore the mechanism of p62 promoting the progression of ICC.

Methods

Western blotting and immunohistochemical analyses were conducted to detect the expression level of protein p62 in ICC tissues and its correlation with prognosis. Subsequently, the loss‐of‐function experiments in vitro and in vivo were performed to define the role of p62 in ICC cell proliferation, invasion, and metastasis. Then, the effect of p62 knockdown on mitochondrial function and mitophagy was evaluated by measuring the oxygen consumption rate, and using immunofluorescence and western blotting analyses.

Results

The expression of p62 was significantly upregulated in ICC specimens compared with normal tissues. We further illustrated that p62 expression positively correlated with lymph node metastasis and poor prognosis. The loss‐of‐function assays revealed that p62 not only promoted ICC cell proliferation, migration, and invasive capacities in vitro, but also induced lung metastasis in the xenograft mouse model. Mechanistically, high expression of p62‐induced epithelial–mesenchymal transition (EMT) with the upregulation of Snail, vimentin, N‐cadherin, and downregulation of E‐cadherin. Moreover, the autophagy‐dependent function of p62 might play a vital role in maintaining the mitochondrial function of ICC by mitophagy which might further promote EMT.

Conclusion

These data provided new evidence for the mechanism by which abundant p62 expression promoted ICC progression, suggesting a promising therapeutic target for antimetastatic strategies in patients with ICC.
Integrative metabolomics and transcriptomics analysis reveals novel therapeutic vulnerabilities in lung cancer
Authors: Thaiparambil Jose , Dong Jianrong , Grimm Sandra L. , Perera Dimuthu , Ambati Chandra Shekar R. , Putluri Vasanta , Robertson Matthew J. , Patel Tajhal D. , Mistretta Brandon , Gunaratne Preethi H. , Kim Min P. , Yustein Jason T. , Putluri Nagireddy , Coarfa Cristian , El‐Zein Randa
Published: June 2022

Background

Non‐small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi‐modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite‐related gene signature and altered metabolic pathways associated with LUAD and LUSC.

Methods

We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co‐expression was used to identify modules of metabolites that were altered between normal and tumor.

Results

We identified unique metabolite‐related gene signatures specific for LUAD and LUSC and key pathways aberrantly regulated at both transcriptional and metabolic levels. Differential co‐expression analysis revealed that loss of coherence between metabolites in tumors is a major characteristic in both LUAD and LUSC. We identified one metabolic onco‐module gained in LUAD, characterized by nine metabolites and 57 metabolic genes. Multi‐omics integrative analysis revealed a 28 metabolic gene signature associated with poor survival in LUAD, with six metabolite‐related genes as individual prognostic markers.

Conclusions

We demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD‐6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28‐gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment.
Single Entity Electrochemical Detection of As‐prepared Metallic and Dielectric Nanoparticle Stochastic Impacts in a Phosphonium Ionic Liquid
Authors: Ahmadinasab Nazanin , Stockmann Talia Jane
Published: June 2022

Invited for this issue's Front Cover is the group of Dr. Talia Jane Stockmann from Memorial University of Newfoundland (Canada). The cover picture shows a platinum nanoparticle stochastic impact at a carbon fiber ultramicroelectrode along with the associated, recorded signal in an ionic liquid medium. Read the full text of the Research Article at 10.1002/celc.202200162.
H2, B−H, and Si−H Bond Activation and Facile Protonolysis Driven by Pt‐Base Metal Cooperation
Authors: Govindarajan Ramadoss , Deolka Shubham , Khaskin Eugene , Fayzullin Robert R. , Pal Shrinwantu , Vasylevskyi Serhii , Khusnutdinova Julia R.
Published: June 2022

We report a series of heterobimetallic Pt/Zn and Pt/Ca complexes to study the effect of proximity of a dicationic base metal on the organometallic Pt species. Varying degrees of Pt⋅⋅⋅Zn and Zn interaction with the bridging Me group are achieved, showcasing snapshots of a hypothetical process of retrotransmetalation from Pt to Zn. In contrast, only weak interactions were observed for Ca with a Pt‐bound Me group. Activation of H2, B−H and Si−H bonds leads to the formation of hydride‐bridged Pt−H−Zn complexes, which is not observed in the absence of Zn, pointing out the importance of metal‐metal cooperation. Reactivity of PtMe2/M2+ with terminal acetylene, water and methanol is also studied, leading to facile protonation of one of the Me groups at the Pt center only when Zn is present. This study sheds light on various ways in which the presence of a 2+ metal cation significantly affects the reactivity of a common organoplatinum complex.
Carboxymethyl‐β‐cyclodextrin and histidine‐zeolitic imidazolate framework‐8 used for enantioseparation of three basic drugs in open‐tubular capillary electrochromatography
Authors: Miao Pandeng , Gan Jie , Zhang Jian , Ma Mingxuan , Li Xiaoqi , Du Yingxiang , Feng Zijie , Zhang Liu
Published: June 2022

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine‐zeolitic imidazolate framework‐8 (His‐ZIF‐8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl‐β‐cyclodextrin (CM‐β‐CD) as the chiral selector was chemically bonded to the His‐ZIF‐8@capillary column. The prepared CM‐β‐CD@His‐ZIF‐8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM‐β‐CD@capillary column without His‐ZIF‐8, the CM‐β‐CD@His‐ZIF‐8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs: 0 → 2.29), propranolol (Rs: 0 → 1.69), and atenolol (Rs: 0 → 0.79). His‐ZIF‐8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day‐to‐day, and column‐to‐column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.
Obsidian – das Glas der Natur
Authors: Sicker Dieter
Published: June 2022

Reisen Sie gern? Oft hat man dabei unerwartete Erlebnisse, die irgendwie mit Chemie zu tun haben und chemisches Lehrbuchwissen wird ungeahnt erweitert. Es verknüpft sich mit Geschichte und Geschichten, unbekannten Anwendungen, praktischen Handgriffen und dem realen Leben anderer Menschen. Über solche kleinen Wunder soll diese Serie berichten. Diesmal führt uns die Suche zu Obsidian, vulkanischem Glas, nach Guatemala.
A correlation for average droplet diameter in rotating packed beds
Authors: Golshan Shahab , Shams Alireza , Rabiee Roshanak , Jafari Rouzbeh , Chaouki Jamal , Blais Bruno
Published: June 2022

A rotating packed bed (RPB) is a novel process intensification technology that increases mass transfer rate using a strong centrifugal acceleration. Inside an RPB, the inlet jet of the liquid absorbent is broken into tiny droplets. It is reported that RPBs provide 11 times larger mass transfer area compared to equal‐sized packed beds and two to three orders of magnitude higher mass transfer compared to equal‐sized stirred tanks. The novelty of the technology and lack of research, however, undermines the adoption of RPBs where a low mass transfer rate is the main bottleneck. In this work, we study the effect of bed size on the average droplet diameter in RPBs and investigate scale‐up criteria to preserve the average droplet diameter at a large scale. Furthermore, we develop a correlation for the average droplet diameter using the experimental data and simulation results obtained using a volume of fluid (VOF) method. This correlation is obtained from dimensional analysis. The effects of rotating speed, absorbent flow rate, wire mesh packing diameter, bed diameter, absorbent viscosity, density, and surface tension are included in the dataset. Among these parameters, rotating speed, centrifugal force, and surface tension have the highest correlation coefficients (R2 = 0.88, 0.83, and 0.42, respectively) with the average droplet diameter.
Length‐Dependent Collective Vibrational Dynamics in Alpha‐Helices
Authors: Zhang Zhenyu , Chen Mu , Zhan Lijian , Zheng Fei , Si Wei , Sha Jingjie , Chen Yunfei
Published: June 2022

The front cover artwork is provided by Prof. Yunfei Chen's group at the Southeast University. The image shows collective vibrational motions of alpha‐helices inside a protein. Studying the vibrations allows connecting protein structure and function, and therefore benefits de novo protein design. Read the full text of the Research Article at 10.1002/cphc.202200082.
Exposure of Fexofenadine, but Not Pseudoephedrine, Is Markedly Decreased by Green Tea Extract in Healthy Volunteers
Authors: Misaka Shingen , Ono Yuko , Taudte R. Verena , Hoier Eva , Ogata Hiroshi , Ono Tomoyuki , König Jörg , Watanabe Hiroshi , Fromm Martin F. , Shimomura Kenju
Published: June 2022

Green tea (GT) alters the disposition of a number of drugs, such as nadolol and lisinopril. However, it is unknown whether GT affects disposition of hydrophilic anti‐allergic drugs. The purpose of this study was to investigate whether pharmacokinetics of fexofenadine and pseudoephedrine are affected by catechins, major GT components. A randomized, open, 2‐phase crossover study was conducted in 10 healthy Japanese volunteers. After overnight fasting, subjects were simultaneously administered fexofenadine (60 mg) and pseudoephedrine (120 mg) with an aqueous solution of green tea extract (GTE) containing (−)‐epigallocatechin gallate (EGCG) of ~ 300 mg or water (control). In vitro transport assays were performed using HEK293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2‐mediated fexofenadine transport. In the GTE phase, the area under the plasma concentration‐time curve and the amount excreted unchanged into urine for 24 hours of fexofenadine were significantly decreased by 70% (P < 0.001) and 67% (P < 0.001), respectively, compared with control. There were no differences in time to maximum plasma concentration and the elimination half‐life of fexofenadine between phases. Fexofenadine was confirmed to be a substrate of OATP1A2, and EGCG (100 and 1,000 μM) and GTE (0.1 and 1 mg/mL) inhibited OATP1A2‐mediated uptake of fexofenadine. On the contrary, the concomitant administration of GTE did not influence the pharmacokinetics of pseudoephedrine. These results suggest that intake of GT may result in a markedly reduced exposure of fexofenadine, but not of pseudoephedrine, putatively by inhibiting OATP1A2‐mediated intestinal absorption.
Metabolism and Excretion of Nirmatrelvir in Humans Using Quantitative Fluorine Nuclear Magnetic Resonance Spectroscopy: A Novel Approach for Accelerating Drug Development
Authors: Singh Ravi Shankar P. , Walker Gregory S. , Kadar Eugene P. , Cox Loretta M. , Eng Heather , Sharma Raman , Bergman Arthur J. , Van Eyck Lien , Hackman Frances , Toussi Sima S. , Kalgutkar Amit S. , Obach R. Scott
Published: June 2022

Typically human absorption, distribution, metabolism, and excretion (ADME) studies are executed using radiolabeled (e.g., carbon‐14) material, the synthesis of which is a time‐consuming activity. In this study, we were able to assess the metabolism and excretion of unlabeled nirmatrelvir (PF‐07321332) within the first‐in‐human study via a novel application of quantitative fluorine (19F) nuclear magnetic resonance (NMR) spectroscopy in place of a standard radiolabel ADME study. Six healthy participants received a single 300‐mg oral dose of nirmatrelvir (in combination with ritonavir), and excreta were collected up to 10 days. Virtually all drug‐related material was recovered within 5 days, and mass balance was achieved with 84.9 ± 8.9% (range = 70.7–95.5%) of the administered dose recovered in urine and feces. The excretion of fluorine‐containing material in urine and feces was 47.0% and 33.7%, respectively. Unchanged nirmatrelvir represented 82.5% of the normalized drug‐related material with a carboxylic acid metabolite M5, derived from hydrolysis of the P2 amide bond, present at 12.1% of dose. Nirmatrelvir was the only drug‐related entity observed in plasma. Approximately 4.2% of the dose was excreted as metabolite M8 (measured by liquid chromatography–mass spectrometry), which was 19F NMR silent due to hydrolysis of the trifluoroacetamide moiety. Hydrolysis of nirmatrelvir to M5 and M8 was shown to occur in cultures of human gut microflora. This successful demonstration of quantitative 19F NMR spectroscopy to establish the mass‐balance, excretion, and metabolic profile of nirmatrelvir offers an advantageous means to execute human ADME studies for fluorine‐containing compounds early in drug development.
Implementing of aMMP‐8 point‐of‐care test with a modified new disease classification in Finnish adolescent cohorts
Authors: Heikkinen Anna M. , Raivisto Teija , Räisänen Ismo , Tervahartiala Taina , Bostanci Nagihan , Sorsa Timo
Published: June 2022

Objectives

Periodontitis is a multifactorial biofilm‐induced inflammatory disease; however, clinical and radiographic information reflects events that have already occurred. aMMP‐8 lateral‐flow chairside or point‐of‐care‐test (POC‐test) results have also come to complement the overall status of the patient's current situation. The current study aimed to clarify the usefulness of aMMP‐8 chairside‐test (aMMP‐8 POCT) results to alert the initial or early periodontitis in adolescents, a potential periodontitis risk group with cut off 20 ng/ml in Stage I periodontitis, according to the current periodontitis classification system.

Material and Methods

A total of 117 adolescents were aMMP‐8 POC tested for aMMP‐8 levels and examined for the full mouth and were interviewed for questions concerning health behavior.

Results

Of all 117 participants, N = 38 (32.5%) was aMMP‐8 POCT positive, and N = 34 (29.1%) had at least one 4 mm periodontal deepened pocket; however, only N = 16 (13.7%) had both characteristics. The subclinical stage (N = 47) could not be classified either as gingivitis or Stage I. Of the participants, who did not have any deepened periodontal pockets, 18  tested negative.

Conclusions

Stage I is preceded by antecedent stages that should be tackled by oral healthcare prevention and personalized treatment modalities by professionals. Elevated (>20 ng/ml), positive aMMP‐8 POCT results can be regarded as initial alarmer such as emerging risk. This should be utilized in the preventive personalized interventions by oral health professionals.
60°phase difference current control‐based open‐phase fault‐tolerant operation strategy for open‐end winding permanent synchronous motor
Authors: Zhong Liping , Hu Song
Published: June 2022

As the most favorable candidate of electric vehicle drive system, the fault tolerance of open‐end winding permanent synchronous motor (OEW‐PMSM) fed by dual inverter with common DC bus is of great significance because it is related to the reliability and safety of the system. Aiming at the most common fault of open‐phase, a fault‐tolerant operation strategy based on 60° phase difference current control is proposed by making full use of the characteristics that each phase of OEW‐PMSM can be controlled independently. Through this method, the same stator rotating magnetic field can be generated before and after the open‐phase fault without reconfiguring the controller, so as to reduce the torque ripple after the fault and ensure the continuous and stable fault‐tolerant operation of the motor. In addition, this method can reduce the switching times by 50%. The proposed method can reduce the switching loss by 50% compared with the ordinary modulation method, reduce the switching loss, and will not produce large zero sequence current. Experimental results show that the fault‐tolerant performance of this strategy is significantly improved compared with the traditional methods.
Singular solitons interaction of dust ion acoustic waves in the framework of Korteweg de Vries and Modified Korteweg‐de Vries equations with (r,q) distributed electrons
Authors: Ghosh Uday Narayan
Published: June 2022

Two nonlinear evolution equations (NLEEs), namely, Korteweg‐de Vries (KdV) and modified Korteweg‐de Vries (MKdV) are derived from the dust hydrodynamic model of collisionless, unmagnetized dusty plasma with electrons following double spectral velocity distribution, that is, (r,q) distribution. Regular as well as singular analytic solutions of derived KdV equations and MKdV equations are obtained separately with the aid of the Hirota Bilinear method. Two singular soliton solutions of both KdV and MKdV equations are obtained separately. The efficiency and interactive approach of the heuristic Hirota Bilinear method leads to multiple singular soliton solutions for its beautiful algebraic technique which generates solitons solutions as well as singular solitons explicitly. Then the significance of multi singular soliton interaction has been studied for KdV singular solitons and for MKdV singular solitons in the critical parameter set.
Methoxido‐Bridged Lacunary Heterocubane Oxidovanadium(IV) Cluster with Azo Ligands: Synthesis, X‐ray Structure, Magnetic Properties, and Antiproliferative Activity
Authors: Roy Satabdi , Böhme Michael , Lima Sudhir , Mohanty Monalisa , Banerjee Atanu , Buchholz Axel , Plass Winfried , Rathnam Sharan , Banerjee Indranil , Kaminsky Werner , Dinda Rupam
Published: June 2022

The new μ3‐methoxido bridged trinuclear vanadium(IV) complexes [VIV3O3(μ3‐OMe)(μ2‐OMe)3(L1,2)2] (1 and 2) have been synthesized using the azo ligands 1‐(2‐(thiazol‐2‐yl)diazenyl)naphthalene‐2‐ol (HL1) and 2‐(2‐(thiazol‐2‐yl)diazenyl)‐4‐methylphenol (HL2). X‐ray crystallography revealed a trinuclear structure with a lacunary heterocubane {(VO)3(μ3‐OMe)(μ2‐OMe)3}2+ core unit for complex 1, which contains a central μ3‐methoxido bridge. All three vanadium centers are in a slightly distorted octahedral coordination environment. Magnetic and theoretical studies reveal an antiferromagnetic coupling between the three vanadium(IV) centers within the triangular arrangement in 1. The complexes were also screened for in vitro cytotoxicity study against HeLa and HT‐29 cancer cell lines. The results indicated that both the complexes are cytotoxic but possess varying specificity towards different cell types.
Paper‐based Wearable Electrochemical Sensors: A New Generation of Analytical Devices
Authors: Deroco Patricia Batista , Wachholz Junior Dagwin , Kubota Lauro Tatsuo
Published: June 2022

Over the past few years, the emergence of electrochemical wearable sensors has attracted considerable attention because of their promising application in point‐of‐care testing due to some features such as high sensitivity, simplicity, miniaturization, and low fabrication cost. Recent developments in new fabrication approaches and innovative substrates have resulted in sensors able to real‐time and on‐body measurements. Wearable electrochemical sensors have also been combined with paper‐based substrates and directly used on human skin for different applications for non‐invasive analyses. Furthermore, wearable electrochemical sensors enable monitoring analytes in different biofluids without complex procedures, such as pre‐treatment or sample manipulation. The coupling of IoT to various wearable sensors has also attracted attention due to real‐time data collection and handling in remote and resource‐limited conditions. This mini‐review presents the significant advances in developing wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discusses some critical challenges for higher performance in this field. We also present an overview of the application of paper as an intelligent substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, conclude by highlighting the future advances in wearable sensors and diagnostics by coupling real‐time and on‐body measurements to multiplexed detection of different biomarkers simultaneously, reducing the cost and time of classical analysis to provide fast and complete overall physiological conditions to the wearer.
An energy‐aware and lightweight routing algorithm using clustering and mobile sinks in wireless sensor networks
Authors: Adabi Sepideh , Mohammadifar Ali , Ebrahimi Nezhad Mohammad Mahdi
Published: June 2022

A wireless sensor network (WSN) consists of a number of small sensors which are powered by low‐cost irreplaceable batteries. Therefore, one of the main issues inWSNdesign is to prolong the battery life of the individual sensors. Clustering and utilization of mobile sinks in collaboration with base station (BS) are two common solutions to address energy consumption challenge. Based on these solutions, a new algorithm in name “Energy‐aware Routing algorithm using Clustering and Mobile Sinks (ERCMS)” is proposed in this article. The distinguishing features ofERCMSare as follows: (1) a geometric pattern is applied to divide entire network area into some parts and make cluster in each part. This pattern adjusts the cluster size based on the distance from the sink. Thus, hotspot problem is expected to be reduced, (2) computational load is distributed over sensors, (3) length of messages are controlled and each message is defined in the format with minimum required information, (4) simple mathematics approaches those impose lightweight computations are adopted, and (5) accuracy of mobile sink dispatching procedure is improved in critical conditions of the network. The simulation results show thatERCMSoutperformsDFCR,MDFCR,andTEO‐MCRPin terms of consumed energy, delivery ratio, delay, routing overhead, and throughput.
Cellular mechanisms mediating activity‐dependent extracellular space shrinkage in the retina
Authors: Chiang Pei‐Pei , Kuo Sidney P. , Newman Eric A.
Published: June 2022

Volume transmission plays an essential role in CNS function, with neurotransmitters released from synapses diffusing through the extracellular space (ECS) to distant sites. Changes in the ECS volume fraction (α) will influence the diffusion and the concentration of transmitters within the ECS. We have recently shown that neuronal activity evoked by physiological photic stimuli results in rapid decreases in ECSαas large as 10% in the retina. We now characterize the cellular mechanisms responsible for this ECS shrinkage. We find that block of inwardly rectifying K+channels with Ba2+, inhibition of the Na+/K+/2Cl−cotransporter with bumetanide, or block of AQP4 water channels with TGN‐020 do not diminish the light‐evoked ECS decrease. Inhibition of the Na+/HCO3−cotransporter by removing HCO3−from the superfusate, in contrast, reduces the light‐evoked ECS decrease by 95.6%. Inhibition of the monocarboxylate transporter with alpha‐cyano‐4‐hydroxycinnamate (4‐CIN) also reduces the ECS shrinkage, but only by 32.5%. We tested whether the swelling of Müller cells, the principal glial cells of the retina, is responsible for the light‐evoked ECS shrinkage. Light stimulation evoked a 6.3% increase in the volume of the fine processes of Müller cells. This volume increase was reduced by 97.1% when HCO3−was removed from the superfusate. We conclude that a large fraction of the activity‐dependent decrease in ECSαis generated by the activation of the Na+/HCO3−cotransporter in Müller cells. The monocarboxylate transporter may also contribute to the response.
A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary tract cancer
Authors: Farhat Zeinab , Freedman Neal D. , Sampson Joshua N. , Falk Roni T. , Koshiol Jill , Weinstein Stephanie J. , Albanes Demetrius , Sinha Rashmi , Loftfield Erikka
Published: June 2022

Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case–control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography–tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74–11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26–10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41–11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41–21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70–14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32–14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.
Hydrological monitoring of a slope covered by stratified pyroclastic deposits and analysis of infiltration processes
Authors: Capparelli Giovanna , Spolverino Gennaro
Published: June 2022

In addition to the duration and intensity of rainfall, infiltration processes are strongly affected by the hydraulic properties of the soil. In the case of heterogeneous and stratified soil profiles, the analysis of the infiltration process becomes more complex, since conflicting hydraulic properties of adjacent layers can induce locally diverted flow. Soils of volcanic origin present these characteristics, because during the various eruptive phases, layers with very different textures are deposited. In this article, data are analysed which have been recorded by a monitoring station installed on a slope made up of volcanic deposits. The station consists of a rain gauge to measure rainfall and seven tensiometers and eight TDR probes installed at different depths to measure suction and volumetric water content, respectively. The slope is made up of alternating volcanic ash (silt‐sandy‐clay paleosoils) interspersed with pumice (sandy‐gravel), due to the different eruptive phases of the volcanic complexes in the area. The analysis of the data established that the layers of coarser material (pumices), depending on the initial moisture conditions, may hinder or even favour the infiltration of water into the deeper layers. In particular, when water content is low, the pumices presented a low unsaturated conductivity which hindered infiltration. By contrast, in wetter conditions, they favoured the flow of water. Therefore, the initial moisture conditions of the soil layers must be taken into account for a correct prediction of the infiltration phenomena. Dry conditions of the pumice layers can hinder drainage into the lower layers, thus favouring the rapid accumulation of soil water during rainfall events, which could eventually lead to slope failure.
Global and national trends in the age‐specific sex ratio of esophageal cancer and gastric cancer by subtype
Authors: Wang Shaoming , Zheng Rongshou , Arnold Melina , Abnet Christian , Zeng Hongmei , Zhang Siwei , Chen Ru , Sun Kexin , Li Li , An Lan , Bray Freddie , Wei Wenqiang , He Jie
Published: June 2022

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age‐specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003‐2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age‐standardized incidence rates (ASIRs) and male‐to‐female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male‐to‐female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male‐to‐female incidence rate ratios increased from young ages, approaching a peak at ages 60‐64, but sharply declined thereafter. Similar “low‐high‐low” trends of age‐specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age‐dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.
miRNAs are now starring in “No Time to Die: Overcoming the chemoresistance in cancer”
Authors: Bhatia Anmol , Upadhyay Atul Kumar , Sharma Siddharth
Published: June 2022

Cancer is a leading cause of death globally, with about 19.3 million new cases reported each year. Current therapies for cancer management include—chemotherapy, radiotherapy, and surgery. However, they are loaded with side effects and tend to cause toxicity in the patient's body posttreatment, ultimately hindering the response towards the treatment building up resistance. This is where noncoding RNAs such as miRNAs help provide us with a helping hand for taming the chemoresistance and providing potential holistic cancer management. MicroRNAs are promising targets for anticancer therapy as they perform critical regulatory roles in various signaling cascades related to cell proliferation, apoptosis, migration, and invasion. Combining miRNAs and anticancer drugs and devising a combination therapy has managed cancer well in various independent studies. This review aims to provide insights into how miRNAs play a mechanistic role in cancer development and progression and regulate drug resistance in various types of cancers. Furthermore, next‐generation novel therapies using miRNAs in combination with anticancer treatments in multiple cancers have been put forth and how they improve the efficacy of the treatments. Exemplary studies currently in the preclinical and clinical models have been summarized. Ultimately, we briefly talk through the challenges that come forward with it and minimize them.
Dual response of fibroblasts viability and Porphyromonas gingivalis adhesion on nanostructured zirconia abutment surfaces
Authors: Wen Cheng , Muhetaer Huo Jia , Gao Zhengyang , Wu Jincheng
Published: June 2022

Soft tissue integration surrounding dental implant is considered as a biological barrier against the oral microorganisms and external stimuli. At present, successful soft tissues integration around implants remains a challenge. The aim of this study was to evaluate the effects of nanostructured zirconia abutment surfaces on fibroblasts viability and Porphyromonas gingivalis adhesion, which are the two main factors influencing the quality of peri‐implant soft‐tissue seal. Zirconia samples were made from three‐dimensional gel deposition approach and divided into three groups: zirconia surfaces, zirconia film coated surfaces (CZr) and polished surfaces (PZr). The Surface properties were characterized by scanning electron microscopy, atomic force microscopy and water contact angle. The behavior of human gingival fibroblasts (HGFs) on samples, including of proliferation, morphology, gene expression and protein expression as well as collagen synthesis were assessed. Additionally, the adhesion of P. gingivalis on samples was analyzed by scanning electron microscopy and live/dead staining. CZr and PZr group significantly enhanced fibroblasts viability such as cell proliferation, cell spreading and extracellular matrix secretion, and impaired P. gingivalis adhesion. Therefore, our findings demonstrated that CZr and PZr surfaces with nano‐grains or grinding grooves might be considered as the feasible zirconia abutments substrate for reinforcing HGFs response and minimizing P. gingivalis adhesion, and thereby enhance peri‐implant soft‐tissue integration.
Effect of a mixture of pyrethroids at doses similar to human exposure through food in the Indian context
Authors: Ravula Anandha R. , Yenugu Suresh
Published: June 2022

Residual amounts of pyrethroids were detected in rice and vegetables of the Indian market. Thus, consumers are exposed to a mixture of pyrethroids on a daily basis through food. Though a large number of studies reported the toxic effects of pyrethroids, there are no reports that used doses equivalent to human consumption. In this study, male Wistar rats were exposed daily to a mixture of pyrethroids for 1–15 months which is equivalent to the amount present in rice and vegetables consumed by an average Indian each day. The oxidant‐antioxidant status (lipid peroxidation, nitric oxide; activities of catalase, glutathione peroxidase, glutathione S transferase, and superoxide dismutase) and anatomical changes in the general organs (liver, lung, and kidney) and male reproductive tract tissues (caput, cauda, testis, and prostate) were evaluated. Further, liver and kidney function tests, lipid profile, and complete blood picture were analyzed. Increased oxidative stress, perturbations in the antioxidant enzyme activities, and damage to the anatomical architecture were observed. Disturbances in the liver function and lipid profile were significant. Results of our study demonstrate that exposure to a mixture of pyrethroids at a dose that is equivalent to human consumption can cause systemic and reproductive toxicity, which may ultimately result in the development of lifestyle diseases. This first line of evidence will fuel further studies to determine the impact of food‐based pyrethroid exposure on the long‐term health of humans and to envisage policies to reduce pesticide content in food products.
Vitamin B6 rescues insulin resistance and glucose‐induced DNA damage caused by reduced activity of Drosophila PI3K
Authors: Mascolo Elisa , Liguori Francesco , Merigliano Chiara , Schiano Ludovica , Gnocchini Eleonora , Pilesi Eleonora , Volonté Cinzia , Di Salvo Martino L. , Contestabile Roberto , Tramonti Angela , Vernì Fiammetta
Published: June 2022

The insulin signaling pathway controls cell growth and metabolism, thus its deregulation is associated with both cancer and diabetes. Phosphatidylinositol 3‐kinase (PI3K) contributes to the cascade of phosphorylation events occurring in the insulin pathway by activating the protein kinase B (PKB/AKT), which phosphorylates several substrates, including those involved in glucose uptake and storage. PI3K inactivating mutations are associated with insulin resistance while activating mutations are identified in human cancers. Here we show that RNAi‐induced depletion of the Drosophila PI3K catalytic subunit (Dp110) results in diabetic phenotypes such as hyperglycemia, body size reduction, and decreased glycogen content. Interestingly, we found that hyperglycemia produces chromosome aberrations (CABs) triggered by the accumulation of advanced glycation end‐products and reactive oxygen species. Rearing PI3KRNAi flies in a medium supplemented with pyridoxal 5′‐phosphate (PLP; the catalytically active form of vitamin B6) rescues DNA damage while, in contrast, treating PI3KRNAi larvae with the PLP inhibitor 4‐deoxypyridoxine strongly enhances CAB frequency. Interestingly, PLP supplementation rescues also diabetic phenotypes. Taken together, our results provide a strong link between impaired PI3K activity and genomic instability, a crucial relationship that needs to be monitored not only in diabetes due to impaired insulin signaling but also in cancer therapies based on PI3K inhibitors. In addition, our findings confirm the notion that vitamin B6 is a good natural remedy to counteract insulin resistance and its complications.
Advances in exopolysaccharide production from marine bacteria
Authors: García Andrés , Fernández‐Sandoval Marco T. , Morales‐Guzmán Daniel , Martínez‐Morales Fernando , Trejo‐Hernández María R.
Published: June 2022

Over the last two decades, a wealth of novel marine exopolysaccharides (EPS) from bacteria have been found to possess many potential applications in industrial, medical, and environmental applications due to their chemical structure, which determines their functional properties. Marine bacteria communities rely on EPS to endure the extremes of temperature, salinity, and nutrient availability found in this ecosystem. Bacterial EPS are biodegradable, generally not toxic, and renewable with potential applications in many fields. However, the major challenge faced by marine bacteria EPS for commercial application is the high production cost that limits downstream processes. Therefore, the optimization of the fermentation parameters has been researched to achieve large‐scale production. This review summarize the characteristics and properties of marine bacterial EPS and evaluate some of the most important findings in the development of fermentation strategies that have shown promising results in terms of productivity improvement. © 2022 Society of Chemical Industry (SCI).
Efficient adsorption of aflatoxin B1 from water with a reusable magnetic covalent organic framework
Authors: Wu Jinhai , Qiu Yu , Liu Mingzhu , Wu Jin , Zhao Zunquan , Zhao Jiamei , Li Hanle , Shen Huijing , Peng Yuan , Bai Jialei
Published: June 2022

BACKGROUND

Aflatoxin B1 (AFB1) is the most toxic and harmful aflatoxin, and has good thermal stability. Research reveals that AFB1 also exists in water, which is potentially harmful to human health. Therefore, it is urgent to remove AFB1 from water. In this work, a novel magnetic covalent organic framework composite (Fe3O4@COFs) is synthesized.

RESULTS

The specific surface area is as high as 1293.32 m2 g−1. The adsorption capacity for AFB1 is 420 μg mg−1, which is six times or more that of other adsorbents. Fe3O4@COFs is employed for the adsorption and elimination of AFB1 from water. The removal efficiency is above 90% and it can be reused at least eight times. In addition, Fe3O4@COFs has been successfully used to remove trace AFB1 in actual water samples.

CONCLUSIONS

The synthesized Fe3O4@COFs has good thermal stability, fast adsorption and large adsorption capacity, and can be recycled many times. Fe3O4@COFs exhibits excellent performance for the removal of AFB1, and has exceptional promise for application in water purification.

© 2022 Society of Chemical Industry (SCI).
Study on the morpho‐anatomy of Lepisorus species through light microscopy and scanning electron microscopy and its systematic implications
Authors: Mondal Sinjini , Moktan Saurav
Published: June 2022

The genus Lepisorus is often associated with complex lineages in Polypodiaceae, which leads to difficulty in understanding taxonomic relationships among the species. The taxa is mostly epiphytic with some distinct features like rhizomes covered with clathrate scales, simple fronds, sori in a single row, intermixed with peltate paraphyses. In this study, we precisely focus on the Lepisorus species and seek a broader understanding of the taxonomic relationships that prevail in this genus. The morpho‐anatomical traits of rhizomes, stipe, lamina, and sporangia were explored in nine species with the aid of light microscopy and scanning electron microscopy techniques for gathering the qualitative and quantitative data sets. These character traits were resolved into groups based on degree of similarity and principal component analysis to comprehend the covariance among the variables. The data were then employed to prepare an artificial dichotomous key and hierarchical cluster analysis was established that revealed five related clades with eight members whereas one member emerged as outgroup. The results correspond with other recent phylogenetic studies of the concerned genus hence confirming immense reliability and thrust of light microscopy, scanning electron microscopy, and morphology‐based studies that are being less utilized in fern taxonomy.
Synthesis and characterization of single‐walled carbon nanotube: Cyto‐genotoxicity in Allium cepa root tips and molecular docking studies
Authors: Ince Yardimci Atike , Istifli Erman Salih , Acikbas Yaser , Liman Recep , Yagmurcukardes Nesli , Yilmaz Selahattin , Ciğerci İbrahim Hakkı
Published: June 2022

Herein, single‐walled carbon nanotubes (SWCNTs) were synthesized by the thermal chemical vapor deposition (CVD) method, and characterized by scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX), transmission electron microscopy (TEM), Raman spectroscopy, dynamic light scattering (DLS), and thermo‐gravimetric analysis (TGA). The results indicated that obtained nanotubes were SWCNTs with high crystallinity and their average diameter was 10.15 ± 3 nm. Allium cepa ana–telophase and comet assays on the root meristem were employed to evaluate the cytotoxic and genotoxic effects of SWCNTs by examining mitotic phases, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage. A. cepa root tip cells were exposed to SWCNTs at concentrations of 12.5, 25, 50, and 100 μg/ml for 4 h. Distilled water and methyl methanesulfonate (MMS, 10 μg/ml) were used as the negative and positive control groups, respectively. It was observed that MIs decreased statistically significantly for all applied doses. Besides, CAs such as chromosome laggards, disturbed anaphase–telophase, stickiness and bridges and also DNA damage increased in the presence of SWCNTs in a concentration‐dependent manner. In the molecular docking study, the SWCNT were found to be a strong DNA major groove binder showing an energetically very favorable binding free energy of −21.27 kcal/mol. Furthermore, the SWCNT interacted effectively with the nucleotides on both strands of DNA primarily via hydrophobic π and electrostatic interactions. As a result, cytotoxic and genotoxic effects of SWCNTs in A. cepa root meristematic cells which is a reliable system for assessment of nanoparticle toxicology were demonstrated in this study.

Research Highlights

SWCNT synthesis with high crystallinity was achieved by the CVD method.

Cytotoxic and genotoxic influences of SWCNTs were investigated.

Allium and Comet tests were utilized.

For all of the applied concentrations of SWCNTs, the MIs significantly decreased.

SWCNTs were found genotoxic.
COVID‐19 and platelet traits: A bidirectional Mendelian randomization study
Authors: Cheung Ching‐Lung , Ho Shun‐Cheong , Krishnamoorthy Suhas , Li Gloria H.‐Y.
Published: June 2022

This study aimed to evaluate the host genetic liability of coronavirus disease 2019 (covid‐19) with platelet traits using the Mendelian randomization (MR) approach. We conducted a bidirectional two‐sample MR using summary statistics from the largest genome‐wide association study of three variables, covid‐19 severity (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] infection, covid‐19 hospitalization, and severe covid‐19, N = ~1 059 456–1 557 411) and four platelet traits (mean platelet volume [MPV], plateletcrit, platelet distribution width, and platelet count; N = 408 112). Inverse‐variance weighted (IVW), median weighted, MR‐Egger, and contamination mixture methods were used to estimate the causal association. Null and inconsistent associations in the IVW and sensitivity analyses were observed for SARS‐CoV‐2 infection and covid‐19 hospitalization with platelet traits. For severe covid‐19, significant associations with MPV and platelet count were observed in the IVW and sensitivity analyses, with the betaIVW of 0.01 (95% confidence interval [CI]: 0.005–0.016, p = 3.51 × 10−4) and −0.009 (95% CI: −0.015 to −0.002, p = 0.008) per doubling in odds of severe covid‐19, respectively. Conversely, null associations were observed for platelet traits with covid‐19 traits. In conclusion, host genetic liability to severe covid‐19 was causally associated with increased MPV and reduced platelet count, which may provide insights into evaluating hypercoagulability and thromboembolic events in covid‐19 patients.
The prevalence and distribution of human papillomavirus in 4267 Turkish women with or without cervical lesions: A hospital‐based study
Authors: Altay‐Kocak Aylin , Kazanci Ferah , Dogu‐Tok Canan , Onan Anil , Erdem Ozlem , Ozkan Secil , Bozdayi Gulendam
Published: June 2022

In the present study, it was aimed to screen the genotypes of human papillomavirus (HPV) retrospectively in women with gynecological symptoms who were admitted to a tertiary care university hospital in Ankara, Turkey. A total of 4267 cervical swab samples of women aged 18–79 years were sent to Medical Virology Laboratory from January 2017 to November 2020. Nucleic acid extraction and amplification of samples were done by an automated system. The test can detect 14 high‐risk HPV (HR‐HPV) types in a single analysis that performs a real‐time polymerase chain reaction, by providing individual results on the highest‐risk genotypes HPV 16 and HPV 18 and pooled results on other high‐risk genotypes (OHR‐HPV) (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). HPV DNA positivity was detected in 14.2% (605/4267) of the samples. HPV type 16 and type 18 were detected in 2.4% and 0.7% of the samples, respectively. OHR‐HPV types were found in 8.8% of the samples. Of the 1.9% and 0.4% samples had mixed types with type 16+ OHR‐HPV and type 18+ OHR‐HPV, respectively. The results of this study presented the rates of HR‐HPV genotypes of a university hospital in Ankara, over a 4‐year period. It was observed that the positivity rate of type 18 is decreasing and some OHR‐HPV types are increasing. HPV vaccination is not in the national immunization program in Turkey yet, however, HPV vaccines are available and the vaccination rates for women are increasing.