bluuebunny/crossref_metadata_2025 huggingface dataset:
One‐step purification and regulation of fructose 1,6‐bisphosphatase from the liver of the freeze‐tolerant wood frog, Rana sylvatica
Authors: Varma Anchal , Storey Kenneth B.
Published: May 2022

The wood frog (Rana sylvatica) undergoes numerous changes to its physiology and metabolic processes to survive the winter months, including adaptations that let them endure whole‐body freezing. The regulation of key enzymes of central carbohydrate metabolism in the liver plays a crucial role in mediating the synthesis and maintenance of high concentrations of glucose as a cryoprotectant during freezing as well as glucose reconversion to glycogen after thawing. The present study characterized the regulation of fructose‐1,6‐bisphosphatase (FBPase; EC 3.1.3.11) from wood frog liver during freezing, FBPase being a crucial enzyme regulating gluconeogenesis. Liver FBPase was purified to homogeneity from control and frozen wood frogs by a one‐step chromatographic process. Kinetic and regulatory parameters of the enzyme were investigated and demonstrated a significant decrease in sensitivity to its substrate fructose‐1,6‐bisphosphate in the liver of frozen frogs, as compared with controls. Immunoblotting also revealed freeze‐responsive changes in posttranslational modifications with a significant decrease in serine phosphorylation (by 53%) for FBPase from frozen frogs. Taken together, these results suggest that FBPase is suppressed, and gluconeogenesis is inhibited during freezing. This response acts as an important component of the metabolic survival strategy of the wood frog.
A General Strategy for the Design and Evaluation of Heterobifunctional Tools: Applications to Protein Localization and Phase Separation
Authors: Lackner Rachel M. , O'Connell Will , Zhang Huaiying , Chenoweth David M.
Published: May 2022

To mimic the levels of spatiotemporal control that exist in nature, tools for chemically induced dimerization (CID) are employed to manipulate protein‐protein interactions. Although linker composition is known to influence speed and efficiency of heterobifunctional compounds, modeling or in vitro experiments are often insufficient to predict optimal linker structure. This can be attributed to the complexity of ternary complex formation and the overlapping factors that impact the effective concentration of probe within the cell, such as efflux and passive permeability. Herein, we synthesize a library of modular chemical tools with varying linker structures and perform quantitative microscopy in live cells to visualize dimerization in real‐time. We use our optimized probe to demonstrate our ability to recruit a protein of interest (POI) to the mitochondria, cell membrane, and nucleus. Finally, we induce and monitor local and global phase separation. We highlight the importance of quantitative approaches to linker optimization for dynamic systems and introduce new, synthetically accessible tools for the rapid control of protein localization.
Development of metastatic Merkel cell carcinoma following the excision of same‐sided recurrent auricular melanoma
Authors: Cartwright Jake K. , Snyder Daniel H. , Moreno Francisco G.
Published: May 2022

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin that is highly aggressive and often metastasizes early. MCC is diagnosed based on histopathological findings and is most commonly treated with surgical resection, which may be accompanied by chemotherapy and/or radiation. This report describes a 55‐year‐old male patient with the history of recurrent malignant melanoma of the right pinna and subsequent excision. Three years following the excision of melanoma, he presented with a lesion to the right forehead as well as a right‐sided neck mass that were found to be metastatic Merkel cell carcinoma.
Advances towards Cell‐Specific Gene Transfection: A Small‐Molecule Approach Allows Order‐of‐Magnitude Selectivity
Authors: Dirksmeyer Thies , Stahl Paul , Vallet Cecilia , Knauer Shirley , Giese Michael , Schmuck Carsten , Hirschhäuser Christoph
Published: May 2022

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small‐molecule approach paved the way for precise structure‐activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA‐binding motif tetralysine‐guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR‐based optimization. The new vector mediated biotin receptor (BR)‐selective transfection of cell lines with different BR expression levels. Computer‐based analyses of microscopy images revealed a preference of one order of magnitude for the BR‐positive cell lines over the BR‐negative controls.
Carboxylate Catalyzed Isomerization of β,γ‐Unsaturated N‐Acetylcysteamine Thioesters**
Authors: Riuttamäki Saara , Laczkó Gergely , Madarász Ádám , Földes Tamás , Pápai Imre , Bannykh Anton , Pihko Petri M.
Published: May 2022

We demonstrate herein the capacity of simple carboxylate salts – tetrametylammonium and tetramethylguanidinium pivalate – to act as catalysts in the isomerization of β,γ‐unsaturated thioesters to α,β‐unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k1H/k1D=1.065±0.026) with a β,γ‐deuterated substrate. Computational analysis of the mechanism provides a similar value (k1H/k1D=1.05) with a mechanism where γ‐reprotonation of the enolate intermediate is rate determining.
Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells
Authors: Maki Yuta , Kawata Kazuki , Liu Yanbo , Goo Kang‐Ying , Okamoto Ryo , Kajihara Yasuhiro , Satoh Ayano
Published: May 2022

Glycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine‐linked (N‐) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B‐subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex‐type N‐glycans, was introduced to the CTB. The synthesized monomeric glycosyl‐CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N‐glycans in specific organelles of living cells.
Isosteroidal Alkaloids from Fritillaria verticillata Willd. and Their NMR Spectroscopic Characteristics
Authors: Ma Nan , Wang Ya‐Jing , Chen Gang , Meng Chu‐Ren , Guo Chun‐Lin , Lu Yong‐Fu , Dai Si‐Yang , Liu Si‐Xuan , Li Yong‐Fu , Li Chang , Pei Yue‐Hu
Published: May 2022

Comprehensive Summary

Chemical investigation of Fritillaria verticillata Willd. led to the isolation of eight novel isosteroidal alkaloids (1—4, 6, 9—11) and four known alkaloids (5, 7—8, 12), including three unprecedented cis‐fused D/E (13α, 17α) cevanine alkaloids (1—3), one rarely cis‐fused E/F (22α) cevanine alkaloid (6), and one uncommon 5β‐jervine‐type isosteroidal alkaloid featuring a cis‐fused A/B ring moiety (11). In order to establish the structures of 1, the calculated NMR with DP4+ evaluation was applied from the plausible structure candidates. The characteristic proton signals for distinguishing D/E conjunction of cevanine alkaloids were summarized. In addition, some proton and carbon signals α to nitrogen in 6 and 7 are unobservable due to the 14N nuclear quadrupolar relaxation, based on the NMR experiments in different solvents, calculated NMR method and X‐ray technology, their structures were determined. The NMR characteristics of cevanine alkaloids to distinguish orientation of long‐pair on nitrogen atom with β‐hydroxyl at C‐20 were also concluded. The anti‐inflammatory effects of compounds 1 and 4 were evaluated in LPS‐activated RAW 264.7 macrophages. Compound 4 decreased LPS‐induced releases of IL‐1β and IL‐17α in RAW264.7 cells in a dose‐dependent manner. Further mechanistic study revealed that 4 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF‐κB signaling pathway.
The neural distribution of the avian homologue of oxytocin, mesotocin, in two songbird species, the zebra finch and the canary: A potential role in song perception and production
Authors: Haakenson Chelsea M. , Balthazart Jacques , Madison Farrah N. , Ball Gregory F.
Published: May 2022

The avian homologue of oxytocin (OT), formerly called mesotocin, influences social behaviors in songbirds and potentially song production. We sought to characterize the distribution of OT peptide in the brain of two songbird species: canaries (Serinus canaria) and zebra finches (Taeniopygia guttata). To visualize OT, we performed immunocytochemistry using an antibody previously shown to identify OT in avian species. In both canaries and zebra finches, dense OT‐ir perikarya were located in the paraventricular nucleus (PVN), preoptic area (POA), supraoptic nucleus (SON), and medial bed nucleus of the stria terminalis (BNSTm). We also observed morphologically distinct OT‐ir cells scattered throughout the mesopallium. OT‐ir fibers were observed in the PVN, ventral medial hypothalamus (VMH), periaqueductal gray (PAG), intercollicular nucleus (ICo), and ventral tegmental area (VTA). We also observed punctate OT‐ir fibers in the song control nucleus HVC. In both male and female canaries, OT‐ir fibers were present in the lateral septum (LS), but innervation was greater in males. We did not observe this sex difference in zebra finches. Much of the OT staining observed is consistent with general distributions within the vertebrate hypothalamus, indicating a possible conserved function. However, some extra‐hypothalamic distributions, such as perikarya in the mesopallium, may be specific to songbirds and play a role in song perception and production. The presence of OT‐ir fibers in HVC and song control nuclei projecting dopaminergic regions provides anatomical evidence in support of the idea that OT can influence singing behavior—either directly via HVC or indirectly via the PAG, VTA, or POA.
MSSA‐Net: A novel multi‐scale feature fusion and global self‐attention network for lesion segmentation
Authors: Huang Zhaohong , Zhang Xiangchen , Zhang Guowei , Cai Guorong
Published: May 2022

In medical image segmentation tasks, it is typical to adopt convolutional neural networks with a serial encoder‐decoder structure. However, mainstream networks cannot simultaneously achieve sufficient extraction of global features and the fusion of multi‐scale information, which may lead to unpromising results for the segmentation of pathological images. Therefore, this article proposed a novel multi‐scale feature fusion and global self‐attention network (MSSA‐Net) for medical image segmentation. Specifically, we designed a parallel double‐encoder network with a multi‐scale feature fusion encoder (MS‐Encoder) and a self‐attention encoder (SA‐Encoder). The SA‐Encoder introduces the transformer's global self‐attention mechanism to extract global features, and the MS‐Encoder adopts atrous spatial pyramid pooling (ASPP) to realize multi‐scale fusion. We have evaluated the proposed MSSA‐Net using three medical segmentation datasets, covering various imaging modalities such as colonoscopy and magnetic resonance imaging. Experiments on the CVC‐ClinicDC, the 2015 MICCAI subchallenge on automatic polyp detection dataset, and anatomical tracings of lesions after stroke (ATLAS) show that our MSSA‐Net outperforms mainstream methods such as DoubleU‐Net and TransUNet. Moreover, MSSA‐Net can predict more accurate segmentation masks, especially in the case of ATLAS, which has challenging images such as multiple shadow areas and discrete lesions.
Promoting autophagy to mitigate coronavirus disease pathology in the elderly
Authors: Lund Da Costa Abby , Mehta Het , Mathur Ramkumar
Published: May 2022

In this commentary, we highlight autophagy's important function, while identifying potential therapeutic targets for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the elderly. Autophagy's decline in the elderly causes increased cell senescence and a dysregulated immune system. As this demographic often faces decreased vaccine‐provided immunity, coronavirus disease 2019 treatments must be developed. We discuss a recent study by Acharya et al. (2022) that found that SF2523 induced autophagy, reducing SARS‐CoV‐2 replication. Furthermore, across varying dosages, SF2523 was shown to have a synergistic effect with remdesivir or MU‐UNMC. Consequently, we believe that SF2523, alone or with other anti‐virals, is a promising potential therapeutic for preventing SARS‐CoV‐2‐related mortalities.
Genome‐wide gain‐of‐function screening identifies EZH2 mediating resistance to PI3Kα inhibitors in oesophageal squamous cell carcinoma
Authors: Xing Hui , Gao Mengshi , Wang Yuxiang , Zhang Xu , Shi Jiajie , Wang Xiang , Liu Xueling , Ma Qingyang , Kong Xiangyin , Yang Chunhao , Ding Jian , Meng Linghua
Published: May 2022

Phosphoinositide‐3 kinase alpha (PI3Kα) has been confirmed to be a potential therapeutic target for esophageal squamous cell carcinoma (ESCC), while the potency of PI3Kα inhibitors is often attenuated by concurrent oncogenic signalling pathways. We performed genome‐wide gain‐of‐function screening with a CRISPR‐SAM library and identified enhancer of zeste homolog 2 (EZH2) rendering ESCC cells resistant to the PI3Kα inhibitor CYH33. Enhanced expression of EZH2 frequently occurs in ESCC and is related to poor prognosis. Overexpression of full‐length EZH2 but not methyltransferase‐deficient EZH2 conferred resistance to CYH33, while downregulating EZH2 expression restored sensitivity. EZH2 expression was negatively related to the activity of CYH33 against the proliferation of ESCC cell lines and patient‐derived cells. Transcriptomic analysis revealed that EZH2 abrogated CYH33‐mediated cell cycle regulation. EZH2 epigenetically suppressed the transcription of CDKN1A, promoting RB phosphorylation and cell cycle progression. Concurrently targeting EZH2 significantly potentiated CYH33 to inhibit the growth of ESCC cells and patient‐derived xenografts accompanied by enhanced cell cycle arrest. Taken together, our study demonstrated that an EZH2‐p21‐RB axis remodeled cell cycle regulation and rendered resistance to PI3Kα inhibitors in ESCC. Simultaneously targeting PI3Kα and EZH2 may provide an effective strategy for ESCC therapy with high expression of EZH2.
Increased risk of biliary infection after biliary stent placement in users of proton pump inhibitors
Authors: Hakuta Ryunosuke , Nakai Yousuke , Oyama Hiroki , Noguchi Kensaku , Kanai Sachiko , Nomura Yusuke , Suzuki Tatsunori , Ishigaki Kazunaga , Saito Kei , Saito Tomotaka , Hamada Tsuyoshi , Takahara Naminatsu , Mizuno Suguru , Kogure Hirofumi , Moriya Kyoji , Fujishiro Mitsuhiro
Published: May 2022

Objectives

Proton pump inhibitors (PPIs) are widely prescribed medications for gastric acid‐induced diseases. Despite the effectiveness of PPIs, recent evidence suggested an increased risk of various bacterial infections in PPI users. The current study was conducted to evaluate the risk of biliary infection after endoscopic biliary stent placement in regular users of PPIs.

Methods

Consecutive patients with a native papilla who underwent endoscopic retrograde cholangiopancreatography and stent placement for biliary stricture between January 2010 and August 2019 were included in this retrospective study. The cumulative incidences of biliary infection were compared between regular and non‐regular PPI users.

Results

During the study period, 270 regular PPI users and 146 non‐regular PPI users were included in the analyses. Age, gender, and indication of endoscopic retrograde cholangiopancreatography were not different between the two groups. The incidences of biliary infection were 43% in regular PPI users and 36% in non‐regular PPI users but the time to biliary infection was significantly shorter in regular PPI users than in non‐regular users (28 vs. 87 days, p = 0.01). The cumulative incidence of biliary infection was significantly higher in regular PPI users compared with non‐regular users (p = 0.008). The multivariable Cox regression analysis also showed a significantly higher hazard ratio of biliary infection in regular PPI users (1.62 [95% confidence interval 1.16–2.26; p = 0.005]).

Conclusions

Regular PPI use was associated with a higher risk of biliary infection after endoscopic biliary drainage. Inappropriate PPI use should be avoided.
Detection of de‐N‐glycosylated EPO with SDS‐PAGE: A complementary confirmation procedure for recombinant EPO in blood samples
Authors: He Sen , Liu Xinchao , Wu Die , Zhou Xinmiao
Published: May 2022

Frameshift variant c.577del in the EPO gene can result in the extension of the amino acid sequence of EPO by invalidating the termination codon. As the molecular weight of its encoded protein EPO (VAR‐EPO) is similar to that of rEPO, the World Anti‐Doping Agency has published Annex B to the TD2022EPO in order to protect athletes with variant c.577del from the suspicion of rEPO administrations. However, it is still necessary to develop a confirmation method for rEPO that can discriminate rEPO from VAR‐EPO.

Based on the glycosylated characteristic of EPO, we selected the detection of de‐N‐glycosylated EPO as a complementary confirmation method for rEPO in blood samples. All samples were analyzed for both intact EPO and de‐N‐glycosylated EPO with SDS‐PAGE, including rEPO spiked samples and blank samples.

The results showed that, after de‐N‐glycosylation, a single‐band was detected in samples collected from non‐variant carriers, no matter whether the sample was spiked with rEPO. In samples collected from variant carriers, a double‐band was detected. The ratio of lower band to upper band increased significantly corresponding to the concentration of rEPO. We calculated a series of cut‐off values by normality distribution function to identify the presence of rEPO. Neither false positive results in blank samples nor false negative results in spiked samples at the applicable Minimum Required Performance Levels were found. This indicates that this method could be adopted as a complementary confirmation method for rEPO in blood samples. A revised testing strategy was also proposed, which would discriminate rEPO directly without further investigation.
Determination of cocaine on banknotes using innovative sample preparation coupled with multiple calibration techniques
Authors: Bilko Jonathan , Deng Yiwei
Published: May 2022

A method using innovative sample preparation was developed for determination of cocaine on banknotes. Aqueous extraction of cocaine from banknotes was performed using a sonication‐enhanced technique. Quantitation of cocaine was achieved using high performance liquid chromatography (HPLC) with UV detection at 230 nm, whereas identification was accomplished utilizing gas chromatography with mass spectrometry (GC‐MS). Multiple calibration techniques, including the external calibration method (ECM), internal standard method (ISM), and standard addition method (SAM) were incorporated into the experimental design to simultaneously determine cocaine contents and assess matrix effects. Statistical paired t tests confirmed that matrix effects were not significant with the sample preparation employed. No damage to the features of the banknotes was observed from the extraction procedure. Extraction efficiency, spike recovery, and detection limit were also determined. The unique experimental design allowed for ECM, ISM, and SAM to concurrently determine the contents of cocaine on banknotes collected around Metro‐Detroit. The concentration range of cocaine was from 1.58 to 14.7 μg per note, with an average of 6.96 μg per note. The method is simple and suitable for drug analysis and forensic science applications.
Long‐term effectiveness of epidural steroid injections after new episodes of low back pain in older adults
Authors: Curatolo Michele , Rundell Sean D. , Gold Laura. S. , Suri P. , Friedly Janna L. , Nedeljkovic Sdrj S. , Deyo Richard A. , Turner Judith A. , Bresnahan Brian W. , Avins Andrew L. , Kessler Larry , Heagerty Patrick J. , Jarvik Jeffrey G.
Published: May 2022

Background

There is limited research on the long‐term effectiveness of epidural steroid injections (ESI) in older adults despite the high prevalence of back and leg pain in this age group. We tested the hypotheses that older adults undergoing ESI, compared to patients not receiving ESI: (1) have worse pain, disability and quality of life (‘outcomes’) pre‐ESI, (2) have improved outcomes after ESI and (3) have improved outcomes due to a specific ESI effect.

Methods

We prospectively studied patients ≥65 years old presenting to primary care with new episodes of back pain in three US healthcare systems (BOLD registry). Outcomes were leg and back pain intensity, disability and quality of life, assessed at baseline and 3‐, 6‐, 12‐ and 24‐month follow‐ups. We categorized participants as: (1) ESI within 6 months from the index visit (n = 295); (2) no ESI within 6 months (n = 4809); (3) no ESI within 6 months, propensity‐score matched to group 1 (n = 483). We analysed the data using linear regression and Generalized Estimating Equations.

Results

Pain intensity, disability and quality of life at baseline were significantly worse at baseline in ESI patients (group 1) than in group 2. The improvement from baseline to 24 months in all outcomes was statistically significant for group 1. However, no statistically significant differences were observed between outcome trajectories for the propensity‐score matched groups 1 and 3.

Conclusions

Older adults treated with ESI have long‐term improvement. However, the improvement is unlikely the result of a specific ESI effect.

Significance

In this large, two‐year, prospective study in older adults with a new episode of low back pain, back pain, leg pain, disability and quality of life improved after epidural steroid injections; however, propensity‐score matching revealed that the improvement was unlikely the result of a specific effect of the injections, indicating that epidural steroids are unlikely to provide long‐term benefits in older adults with new episodes of back and leg pain.
Role of bioaerosol in virus transmission and material‐based countermeasures
Authors: Joseph John , Baby Helna Mary , Zhao Spencer , Li Xiang‐Ling , Cheung Krisco‐Cheuk , Swain Kabir , Agus Eli , Ranganathan Sruthi , Gao Jingjing , Luo James N , Joshi Nitin
Published: May 2022

Respiratory pathogens transmit primarily through particles such as droplets and aerosols. Although often overlooked, the resuspension of settled droplets is also a key facilitator of disease transmission. In this review, we discuss the three main mechanisms of aerosol generation: direct generation such as coughing and sneezing, indirect generation such as medical procedures, and resuspension of settled droplets and aerosols. The size of particles and environmental factors influence their airborne lifetime and ability to cause infection. Specifically, humidity and temperature are key factors controlling the evaporation of suspended droplets, consequently affecting the duration in which particles remain airborne. We also suggest material‐based approaches for effective prevention of disease transmission. These approaches include electrostatically charged virucidal agents and surface coatings, which have been shown to be highly effective in deactivating and reducing resuspension of pathogen‐laden aerosols.
Metamorphism of the Yilan amphibolites from the Heilongjiang Complex and deformation of the granodioritic mylonites from the Jiamusi Massif, Northeastern China
Authors: Jia Shiju , Zheng Changqing , Liang Chenyue , Zhou Jianbo , Xu Xuechun , Zhao Yingli , Wen Quanbo
Published: May 2022

The Heilongjiang Complex records the evolution history of the Mudanjiang Ocean, which is of great significance to constrain the amalgamation process of the Jiamusi and Songnen‐Zhangguangcai Range massifs. We carried out petrological, chronological, geochemical, mineral chemical and electron backscatter diffraction (EBSD) fabric analyses on the Heilongjiang Complex in the Yilan area. The latest zircon U–Pb dating results show that the protolith ages of the amphibolite are 261.3 ± 3.0 Ma and 261.8 ± 3.3 Ma, while that of the granodioritic mylonite is 207.8 ± 2.2 Ma. The amphibolites and granodioritic mylonite are enriched in large‐ion lithophile elements (e.g., Rb, Ba, and Sr) and light rare earth elements, with depletion in high‐field‐ strength elements (e.g., Nb, Ta, Zr, and Hf), indicating that the formation of the protoliths of the amphibolites and granodioritic mylonite is related to the subduction of the Mudanjiang oceanic plate under the Songnen‐Zhangguangcai Range Massif. The amphibolites and granodioritic mylonite both experienced two periods of metamorphic and deformation events. The metamorphic degree of the early period of metamorphism is low amphibolite facies, which records a clockwise P–T path from early increased temperature and pressure to a late isothermal depressurization. The P–T path reveals that this period of metamorphism is associated with the collision between two massifs. The later period of metamorphism reaches low greenschist facies, accompanied by deformation, which may be related to the rapid exhumation of the Heilongjiang Complex. This study provides a new perspective for exploring the collision and collage process of the Jiamusi and Songnen‐Zhangguangcai Range massifs.
Physical simulation experiments of structural deformation and hydrocarbon accumulation in piggyback thrust wedges
Authors: Zhao Li , Fang Chengming , Xu Xuhui , Deng Peng
Published: May 2022

The piggyback thrust wedge is a common structural style in thrust belts, which controls the lateral arrangement of hydrocarbon distribution. This study conducted physical simulation experiments of structural deformation and hydrocarbon accumulation by using the piggyback thrust wedge as the geological model. According to the experimental results, hydrocarbon accumulation patterns were obtained by investigating the evolutionary history of the fault‐sealing performance while inverting the coupling relationship between the fault evolution and hydrocarbon accumulation. The structural deformation experiment showed that the evolution of the fault displacement and dip angle was characterized by gradual and staged progress. The kaolin smear continuity deteriorated with fault evolution. The soybean oil accumulation experiment demonstrated that the fault‐sealing performance in the rear of the thrust wedge was inferior to that in the front. Hydrocarbon migration was mostly lateral in the front of the thrust wedge and mainly vertical in the rear. Quantitative analysis showed that the fault‐sealing performance had three closed, partially closed, and open stages, which gradually deteriorated with the structural evolution. Three hydrocarbon accumulation patterns were identified in the piggyback thrust wedge: synchronized, adjustment, and non‐adjustment patterns. The evolution of the structural deformation and faults‐sealing performance resulted in spatio‐temporal differences in hydrocarbon accumulation in the thrust belts of central‐western China. The front of the thrust wedge had a higher exploration potential than the rear.
The information‐seeking behavior of medical sciences students toward COVID‐19 in mass and social media: A cross‐sectional study
Authors: Amiri Parasto , Moulaei Khadijeh , Bahaadinbeigy Kambiz , Ghaemi Mohammad Mehdi , Sheikhtaheri Abbas
Published: May 2022

Background and Aims

During the COVID‐19 pandemic, college students can access health‐related information on the Internet to improve preventative behaviors, but they often judge the merits of such information and create challenges in the community. The aim of this study was to investigate information‐seeking behaviors in regard to COVID‐19 among students at Kerman University of Medical Sciences (KUMS) with the help of mass and social media.

Methods

The present study is a cross‐sectional study, which was conducted using an online researcher‐made questionnaire. An invitation to participate in the study was sent to 500 students at KUMS, of which 203 were selected according to the inclusion criteria and completed the questionnaire. Descriptive statistics were used to analyze the data.

Results

COVID‐19 news was mostly obtained through social media platforms such as WhatsApp, Telegram, Instagram, radio, and television, as well as online publications and news agencies. Social media platforms such as WhatsApp, Telegram, Instagram, and satellite networks such as BBC contained the most rumors about COVID‐19. Some of the most common misconceptions regarding COVID‐19 were as follows: “COVID‐19 is the deadliest disease in the world,” “COVID‐19 is a biological attack,” and “COVID‐19 disappears as the air temperature rises.” In addition, most of the virtual training provided through mass media focused on “refraining from visiting holy places and crowded locations such as markets,” “observing personal hygiene and refraining from touching the eyes, nose, and mouth with infected hands,” and “the role of quarantine in reducing the incidence of COVID‐19.”

Conclusion

Our findings demonstrated that during the pandemic, students used social media platforms the most to obtain health‐related information and these media have a significant impact on their willingness to engage in preventative behaviors and take the COVID‐19 risk seriously.
Propagation of age‐related diseases due to the changes of lipid peroxide and antioxidant levels in elderly people: A narrative review
Authors: Ali Julfikar , Aziz Md. Abdul , Rashid Md. Mamun Or , Basher Mohammad Anwarul , Islam Mohammad Safiqul
Published: May 2022

Background and Aims

Lipid peroxidation end products are the major culprit for inducing chronic diseases in elderly people. Along with the elevated level of lipid peroxide biomarkers, there is a significant disruption of antioxidants balance, which combinedly propagate the diseases of elderly people. The aim of the present review is to bridge the connection of changes in lipid peroxides biomarkers and antioxidants level with age‐associated diseases in elderly people.

Methods

This narrative review was performed following a comprehensive search for suitable articles in multiple online databases, including PubMed, Google Scholar, EMBASE, Web of Science, Cochrane Library, and ScienceDirect using selected search terms. The most appropriate literature was included based on the selection criteria.

Results

From the review, it is found that many age‐related diseases propagated with an increased level of the end products of lipid peroxide and reduced levels of antioxidants in elderly people. When the end products of lipid peroxidation increase in the body, it creates oxidative stress, which ultimately leads to many complicated diseases, including cancers, cardiovascular and neurogenic diseases, and many other chronic inflammatory diseases. The oxidative stress induced by peroxidation can be assessed by different lipid peroxide end products such as malondialdehyde, oxidized low‐density lipoprotein, isoprostanes, neuroprostanes, lipoperoxides, oxysterols (7‐ketocholesterol, 7β‐hydroxycholesterol), and many more.

Conclusions

This study definitively answers the correlation between the changes in lipid peroxides and antioxidants level and age‐related diseases. Our narrative article recommends future investigations for elucidating the mechanisms rigorously to establish a compact correlation.
Analysis of third‐grade liquid under the influence of wall slip and variable fluid properties in an inclined peristaltic channel
Authors: Choudhari Rajashekhar , Makinde Oluwole D. , Mebarek‐Oudina Fateh , Vaidya Hanumesh , Prasad Kerehalli V. , Devaki Palluru
Published: May 2022

The current model investigates the effect of wall slip on third‐grade liquid flow through an inclined peristaltic channel. The variation in viscosity and thermal conductivity are taken into account, along with wall properties. The governing equations are simplified using long wavelength and small Reynolds number approximations. The transformed equations are solved by using the perturbation technique. Physiological quantities such as velocity, streamlines, temperature, and concentration are obtained for different parameters of interest. The findings show that increasing the variable viscosity and slip term value improves the velocity profile. Furthermore, elasticity factors help flow, but damping causes fluid particles to slow down. Similarly, when the slip, variable viscosity, and inclination parameter values rise, the size of the trapped bolus grows, resulting in more bolus forms. Furthermore, the inclusion of variable properties helps understand the complex rheological properties of blood flowing through narrow or micro arteries.
Cancer‐associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications
Authors: Wong Kit Yee , Cheung Alvin Ho‐Kwan , Chen Bonan , Chan Wai Nok , Yu Jun , Lo Kwok Wai , Kang Wei , To Ka Fai
Published: May 2022

Lung cancer is the common and leading cause of cancer death worldwide. The tumor microenvironment has been recognized to be instrumental in tumorigenesis. To have a deep understanding of the molecular mechanism of nonsmall cell lung carcinoma (NSCLC), cancer‐associated fibroblasts (CAFs) have gained increasing research interests. CAFs belong to the crucial and dominant cell population in the tumor microenvironment to support the cancer cells. The interplay and partnership between cancer cells and CAFs contribute to each stage of tumorigenesis. CAFs exhibit prominent heterogeneity and secrete different kinds of cytokines and chemokines, growth factors and extracellular matrix proteins involved in cancer cell proliferation, invasion, metastasis and chemoresistance. Many studies focused on the protumorigenic functions of CAFs, yet many challenges about the heterogeneity of CAFS remain unresolved. This review comprehensively summarized the tumor‐promoting role and molecular mechanisms of CAFs in NSCLC, including their origin, phenotypic changes and heterogeneity and their functional roles in carcinogenesis. Meanwhile, we also highlighted the updated molecular classifications based on the molecular features and functional roles of CAFs. With the development of cutting‐edge platforms and further investigations of CAFs, novel therapeutic strategies for accurately targeting CAFs in NSCLC may be developed based on the increased understanding of the relevant molecular mechanisms.
Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration
Authors: Huang Tingben , Yu Zhou , Yu Qiong , Chen Yitong , Jiang Zhiwei , Wang Ying , Yang Guoli
Published: May 2022

Recently, a large number of studies have reported that lithium (Li) displayed a positive effect on osteogenesis. However, only a few studies have investigated the Li‐incorporated surfaces through electrochemical deposition. In this study, electrochemical deposition was conducted on a CHI600E electrochemical workstation. The characterization of electrochemical deposition (ECD) and ECD‐Li surfaces were detected by field‐emission scanning electron microscopy with energy‐dispersive spectrometer. rBMSCs were cultured on two surfaces for subsequent adhesion, proliferation and live/dead assay. To evaluate the effects of Li‐incorporated implants by electrochemical deposition on osseointegration in vivo, teeth extraction of two premolars and one first molar in bilateral mandible were performed on six male beagle dogs. After 3 months, ZDI and ZDI‐Li implants were inserted into the bilateral mandible of each beagle dog. Micro Computed Tomography (Micro‐CT) and hard tissue sectioning analysis were carried out to evaluate the osseointegration at 4‐ and 8‐weeks post‐implantation. Results showed that ECD‐Li surface promoted adhesion and proliferation of BMSCs in the early stage. More importantly, through micro‐CT analysis, the values of bone volume/total volume (BV/TV) (0.374 ± 0.015), bone‐implant contact (BIC) (0.831 ± 0.025), and Tb.Th (0.412 ± 0.007) in ZDI‐Li group was significantly higher than those of ZDI group (0.302 ± 0.009, 0.700 ± 0.023, 0.353 ± 0.001, p < .01) at 4 weeks. Similarly, ZDI‐Li group manifested more bone contact with the implant surfaces at 4 weeks based on hard tissue sectioning analysis, whereas no significant difference was detected between two groups at 8 weeks. Therefore, incorporating Li into implant surface through ECD could enhance early osseointegration in vivo.
NF‐κB‐upregulated miR‐155‐5p promotes hepatocyte mitochondrial dysfunction to accelerate the development of nonalcoholic fatty liver disease through downregulation of STC1
Authors: Shen Miao , Pan Hanghai , Ke Jinjing , Zhao Fei
Published: May 2022

Previous studies have highlighted the involvement of nuclear factor kappa B (NF‐κB) in the development of nonalcoholic fatty liver disease (NAFLD). The purpose of our investigation is to explore the interaction among NF‐κB, microRNA‐155‐5p (miR‐155‐5p), and Stanniocalcin 1 (STC1), and its effects on NAFLD by establishing a NAFLD model in Sprague Dawley rats. A highly‐expressed miR‐155‐5p and NF‐κB was revealed in the liver tissues of NAFLD rats, and a positive correlation was identified between miR‐155‐5p and NF‐κB. Next, the expression of NF‐κB and STC1 was altered in the modeled rats through lentivirus injection, followed by determination on the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglycerides, and low‐density lipoprotein cholesterol. Furthermore, the hepatocyte mitochondria were separated to measure the activities of adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex, and to observe the number, length and ultrastructural length of mitochondrial cristae. The results demonstrated that NF‐κB overexpression induced mitochondrial dysfunction, increased ROS level, decreased ATP and MMP contents, as well as inhibited the number and length of mitochondrial cristae in the hepatocyte mitochondria of NAFLD rats. Besides, miR‐155‐5p was found to negatively regulate STC1 expression based on dual luciferase reporter gene assay, which exert inhibition on mitochondrial activity of hepatocytes in NAFLD rats. These results uncover the possible involvement of NF‐κB/miR‐155‐5p/STC1 axis in NAFLD progression, that NF‐κB could increase miR‐155‐5p expression to inhibit STC1 expression, thus inducing hepatic mitochondrial dysfunction and promoting the occurrence and development of NAFLD.
Synthesis and characterization of boehmite/metal – Organic framework of type AlO(OH)/MOF‐74(Zn) for photocatalytic degradation of Congo red dye
Authors: Sohrabnezhad Shabnam , Kazemi Zahra , Pourahmad Nodehi Arad
Published: May 2022

In the present work, boehmite metal‐organic framework nanocomposite, AlO(OH)/MOF‐74(Zn), was synthesized by a simple, fast, and low‐cost process. The post‐synthetic method was used for preparing new hybrid material. The photocatalytic efficiency of AlO(OH)/MOF‐74(Zn) was investigated by photocatalytic degradation of Congo Red anionic dye. The nanocomposite was characterized by various techniques. The electron microscopy images showed that the spherical MOF‐74 with about 30 nm was located over boehmite. The optical properties indicated the boehmite/MOF‐74 can be used as a visible‐light‐driven photocatalyst. Optimization of significant variables such as adsorbent dosage and initial Congo Red concentration and photodegradation time affecting removal was investigated and the optimized values were found to be 1 g/L, 10 mg/L, and 60 min, respectively. The AlO(OH)/MOF‐74(Zn) photocatalyst exhibited the highest catalytic performance for photodegradation of dye contaminants. Results indicated about 94% of tested dye were removed by a new hybrid photocatalyst under visible light irradiation. The results confirmed that due to some considerable features of AlO(OH)/MOF‐74(Zn) such as high surface area and chemical and thermal resistance, the introduced photocatalyst acts as a high‐performance photocatalyst for degradation of Congo Red dye in aqueous solutions.
Work‐related stress and coping methods of internists and primary care physicians during the COVID‐19 pandemic in Japan: A mixed‐method study
Authors: Shikino Kiyoshi , Kuriyama Akira , Sadohara Michito , Matsuo Takahiro , Nagasaki Kazuya , Nishimura Yoshito , Nonaka Saori , Izumiya Masashi , Moriya Mitsuru , Ohtake Yoichi , Makiishi Tetsuya
Published: May 2022

Background

The COVID‐19 pandemic has affected the mental health of health care workers. This study aimed to investigate the stress factors that cause burnout in Japanese physicians and their coping methods during the COVID‐19 pandemic.

Methods

We conducted a sequential explanatory mixed‐method study to investigate the psychological responses of physicians in the early stages of the pandemic. A cross‐sectional, web‐based, anonymous survey was conducted among members of the American College of Physicians Japan Chapter to quantitatively investigate the stress factors and prevalence of burnout. An open‐ended questionnaire with questions about stress factors and coping methods was additionally administered. The qualitative data were analyzed using qualitative content analysis.

Results

Among the 1173 physicians surveyed, 214 (18.2%) responded. Among the participants, 107 (50.0%) responded “yes” to the question “I feel or have felt very stressed at work during the COVID‐19 pandemic,” and 68 (31.8%) reported burnout symptoms. Those who reported feeling stress (117 respondents) were asked to select 12 items of the stress factors related to COVID‐19. The most significant stress factor related to COVID‐19 was “Perceived risk of spreading COVID‐19 to family members” (n = 47). Content analysis identified 12 categories for the stress factors and 7 for stress‐coping methods corresponding to COVID‐19 (Cohen's kappa = 0.84 and 0.95, respectively).

Conclusion

Several distinct stressors existed during the COVID‐19 pandemic, which might be related to burnout among physicians. Practicing stress‐coping strategies, as identified in the present study, may help reduce work‐related stress and prevent burnout.
Synthesis, antioxidant, and antimicrobial activity of some novel N‐substituted derivatives of 3‐(benzo[b]thiophen‐2‐yl)‐5‐(3‐[trifluoromethyl]styryl)‐4,5‐dihydro‐1H‐pyrazole
Authors: Pandy Karthik Manikandan , Krishnan Radhakrishnan , Paratharaj Senthilkumar
Published: May 2022

The new series of various N‐substituted pyrazoline derivatives containing benzo[b]thiophene and styryl with trifluoromethyl substitution at meta‐ position were synthesized. Compound 1‐(3‐(benzo[b]thiophen‐2‐yl)‐5‐(3‐[trifluoromethyl]styryl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐2‐chloroethan‐1‐one (3b) was further substituted with various thiols. The structures of newly synthesized compounds were characterized by UV, IR, NMR, and Mass and had been screened for antioxidant and antimicrobial activity. The in vitro antioxidant screening revealed that hydroxyl radical scavenging (HRS) activities of compounds 3a, 3b, 3c, 3f, 3i, 3j, 4a, and 4c are stronger than the other compounds and the in vitro antimicrobial activities of the compounds were tested against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacillus subtilis, Staphylococcus aureus, Enterococcus faecalis, Aspergillus flavus, and Aspergillus Niger. The compounds 3d and 3e exhibit good activity against P. mirabilis. Compounds 3a, 3b, 3c, 3 h, 3i, 3j, and 4a showed significant activity against S. aureus. Compounds 3e and 3f showed very good activity against A. flavus. Compounds 3e, 3f, and 4c showed good activity against A. Niger.
IL-7 induces type 2 cytokine response in lung ILC2s and regulates GATA3 and CD25 expression
Authors: Sheikh Abdalla , Lu Julia , Melese Etienne , Seo Jung Hee , Abraham Ninan
Published: May 2022

Interleukin-7 is a cytokine with well-established roles in lymphocyte development and more recently, an expanded role in immune function. IL-7Rα is highly expressed by innate lymphoid cells (ILCs), but how IL-7 directs the development or function of ILCs is not well studied. Using mice with inducible deletion of IL-7Rα, we showed that loss of IL-7 signaling led to impaired production of IL-5, IL-13 and amphiregulin in lung ST2+ group 2 innate lymphoid cells (ILC2s) following influenza/A infection. Conversely, mice treated with IL-7 increased production of IL-5 and IL-13 by lung ILC2s. Moreover, we showed that IL-7 enhanced GATA3 and CD25 expression in ILC2s and loss of IL-7 signaling led to their reduced expression. Altogether, this study demonstrates that IL-7 regulates the function of ILC2s during airway viral infection and induces GATA3 and CD25 expression.
Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatment
Authors: Tallis Eran , Karsenty Cecile L. , Grimes Amanda B. , Karam Lina B. , Elsea Sarah H. , Sutton Vernon Reed , Rawls‐Castillo Brandy L. , Liu Ning , Soler‐Alfonso Claudia
Published: May 2022

Glycogen storage disease type Ib (GSD‐Ib) is a rare inborn error of glycogen metabolism uniquely associated with neutropenia and neutrophil dysfunction, causing severe infections, inflammatory bowel disease (IBD), and impaired wound healing. Recently, kidney sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors such as empagliflozin known to reduce plasma levels of 1,5‐anhydroglucitol (1,5‐AG) and its toxic derivatives in neutrophils, have been described as a new treatment option in case reports of patients with GSD‐Ib from Europe and Asia. We report our experience with an 11‐year‐old girl with GSD‐Ib presenting with short fasting hypoglycemia, neutropenia with neutrophil dysfunction, recurrent infections, suboptimal growth, iron‐deficiency anemia, and IBD. Treatment with daily empagliflozin improved neutrophil counts and function with a significant reduction in G‐CSF needs. Significant improvement in IBD has led to weight gain with improved nutritional markers and improved fasting tolerance. Reduction of maximum empagliflozin dose was needed due to arthralgia. No other significant side effects of empagliflozin were observed. This report uniquely highlights the novel use of untargeted metabolomics profiling for monitoring plasma levels of 1,5‐AG to assess empagliflozin dose responsiveness and guide dietary management and G‐CSF therapy. Clinical improvement correlated to rapid normalization of 1,5‐AG levels in plasma sustained after dose reduction. In conclusion, empagliflozin appeared to be a safe treatment option for GSD‐Ib‐associated neutropenia and neutrophil dysfunction. Global untargeted metabolomics is an efficient method to assess biochemical responsiveness to treatment.