Showing papers by "Laboratory of Molecular Biology published in 2022"
TL;DR: In this article , the structure determination by cryogenic electron microscopy was used to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains.
Abstract: Abstract Many age-dependent neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are characterized by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β, α-synuclein and transactive response DNA-binding protein (TARDBP; also known as TDP-43) are the most common 1,2 . Here we used structure determination by cryogenic electron microscopy to show that residues 120–254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including those resulting from sporadic and inherited tauopathies, amyloid-β amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 individuals with normal neurology and no or only a few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29-kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific to the carboxy-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, individuals with normal neurology indicates that they form in an age-dependent manner.
47 citations
TL;DR: In this article , the effects of CD36 on hepatic de novo lipogenesis and elucidated the underlying mechanisms of the effect of fatty acid translocase (FAT/CD36) on DNL.
Abstract: Enhanced de novo lipogenesis (DNL) in hepatocytes is a major contributor to nonalcoholic fatty liver disease (NAFLD). Fatty acid translocase (FAT/CD36) is involved in the pathogenesis of NAFLD through facilitating free fatty acids uptake. Here, we explored the effects of CD36 on DNL and elucidated the underlying mechanisms.We generated hepatocyte-specific CD36 knockout (CD36LKO) mice to study in vivo effects of CD36 on DNL under high-fat diet (HFD). Lipid deposition and DNL were analyzed in primary hepatocytes isolated from CD36LKO mice or HepG2 cells with CD36 overexpression. RNA sequence, co-immunoprecipitation, and proximity ligation assay were carried out to determine its role in regulating DNL.Hepatic CD36 expression was upregulated in NAFLD mice and patients, and CD36LKO mice exhibited attenuated HFD-induced hepatic steatosis and insulin resistance. We identified hepatocyte CD36 as a key regulator for DNL in the liver. Sterol regulatory element-binding protein 1 (SREBP1) and its downstream lipogenic enzymes such as FASN, ACCα, and ACLY were significantly downregulated in the liver of HFD-fed CD36LKO mice, whereas overexpression CD36 stimulated insulin-mediated DNL and lipid droplet formation in vitro. Mechanistically, CD36 was activated by insulin and formed a complex with insulin-induced gene-2 (INSIG2) that disrupts the interaction between SREBP cleavage-activating protein (SCAP) and INSIG2, thereby leading to the translocation of SREBP1 from ER to Golgi for processing. Furthermore, treatment with 25-hydroxycholesterol or betulin molecules shown to enhance SCAP-INSIG interaction, reversed the effects of CD36 on SREBP1 cleavage.Our findings identify a previously unsuspected role of CD36 in the regulation of hepatic lipogenic program through mediating SREBP1 processing by INSIG2, providing additional evidence for targeting CD36 in NAFLD.
30 citations
TL;DR: In this article , a pseudovirus-based assay was used to evaluate SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.7 variants, which showed enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization.
Abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.
15 citations
TL;DR: The uptake of triadimefon from soils by wheat plants was similar to that in hydroponics and its accumulation were mainly governed by adsorption of the fungicide onto soils, and positively correlated with its concentration in in situ pore water (CIPW).
14 citations
TL;DR: Using the organometallic framework as a template and taking advantage of its high porosity, a cobalt disulfide rhombic dodecahedral nanocomposites with nitrogen coordination and graphene coating (N-CoS2@graphene) was presented in this paper.
Abstract: As a highly toxic substance that may be harmful to the environment and human beings, hydrazine has been paid growing attention in the field of electrochemical detection. Using the organometallic framework as a template and taking advantage of its high porosity, we prepared cobalt disulfide rhombic dodecahedral nanocomposites with nitrogen coordination and graphene coating (N-CoS2@graphene) in this study. Nitrogen coordination can effectively boost the intrinsic activity of the active site by modulating the electronic structure of the Co center in N-CoS2@graphene. The surface graphene layers not only work as protective layers to enhance stability but also promote electron transfer. It has been proved that this electrocatalyst has excellent hydrazine electrochemical sensing performance with a high sensitivity of 1580 μA mM−1 cm−2, a low detection limit of 30 nM at S/N = 3, a linear range from 1.0 μM to 1.0 mM, and satisfactory reproducibility and stability at 0.1 V. It can be seen that this catalyst has a very attractive application prospect in an electrochemical sensor.
14 citations
TL;DR: Using the organometallic framework as a template and taking advantage of its high porosity, a cobalt disulfide rhombic dodecahedral nanocomposites with nitrogen coordination and graphene coating (N-CoS2@graphene) was presented in this article .
Abstract: As a highly toxic substance that may be harmful to the environment and human beings, hydrazine has been paid growing attention in the field of electrochemical detection. Using the organometallic framework as a template and taking advantage of its high porosity, we prepared cobalt disulfide rhombic dodecahedral nanocomposites with nitrogen coordination and graphene coating (N-CoS2@graphene) in this study. Nitrogen coordination can effectively boost the intrinsic activity of the active site by modulating the electronic structure of the Co center in N-CoS2@graphene. The surface graphene layers not only work as protective layers to enhance stability but also promote electron transfer. It has been proved that this electrocatalyst has excellent hydrazine electrochemical sensing performance with a high sensitivity of 1580 μA mM−1 cm−2, a low detection limit of 30 nM at S/N = 3, a linear range from 1.0 μM to 1.0 mM, and satisfactory reproducibility and stability at 0.1 V. It can be seen that this catalyst has a very attractive application prospect in an electrochemical sensor.
14 citations
TL;DR: In this article, a SCNN model with attention mechanism (SCNN-ATT) was proposed for herbicide type and level classification of different stress durations and SCNN-based feature selection model was proposed to screen out the characteristic wavelengths.
12 citations
TL;DR: In this article , the role of metal ions in the formation of the Caulobacter crescentus S-layer using high-resolution structural and cell biology techniques, as well as molecular simulations was investigated.
11 citations
TL;DR: In this article , the authors investigated the role of Sterol regulatory element binding protein cleavage-activating protein (SCAP) in the development of lean NAFLD and found that SCAP was abnormally increased in the adipose and liver tissues of PD-fed mice.
Abstract: Background & AimsSterol regulatory element binding protein cleavage-activating protein (SCAP) is a cholesterol sensor that confers a broad range of functional effects in metabolic diseases. Lean nonalcoholic fatty liver disease (NAFLD) is characterized by a decrease in subcutaneous fat and ectopic fat deposition in the liver. SCAP may mediate the development of lean NAFLD, but the mechanism of action remains unclear.MethodsC57BL/6J wild-type and macrophage SCAP-specific knockout mice (SCAPΔMϕ) were subjected to Paigen diet (PD) feeding induced lean NAFLD. Inflammation and lipid metabolism of adipose and liver were evaluated. The STING–NF-κB signaling pathway was examined in vivo and in vitro to explore the underlying mechanism of macrophage SCAP on metaflammation.ResultsThe data showed heterogeneity of lipid metabolic processes in liver and epididymal white adipose tissue due to inflammation mediated by macrophage infiltration. Meanwhile, we found that the macrophage SCAP was abnormally increased in the adipose and liver tissues of PD-fed mice. Intriguingly, the SCAPΔMϕ mice attenuated PD-induced metaflammation and ectopic lipid deposition by reducing hepatic stimulator of interferon gene (STING)–nuclear factor kappa B (NF-κB) pathway activation. In-depth molecular analysis revealed that SCAP specifically recruits the STING and tank-binding kinase 1 onto the Golgi to activate the NF-κB in macrophages, thereby promoting the release of inflammatory factors. This process ultimately led to an increased lipolysis in adipocytes and lipid uptake and synthesis in hepatocytes.ConclusionsOur findings suggest that SCAP acts as a novel regulator of the macrophage inflammatory response and the pathogenesis of lean NAFLD by activating the STING–NF-κB signaling pathway. Inhibition of macrophage SCAP may represent a new therapeutic strategy for the treatment of lean NAFLD. Sterol regulatory element binding protein cleavage-activating protein (SCAP) is a cholesterol sensor that confers a broad range of functional effects in metabolic diseases. Lean nonalcoholic fatty liver disease (NAFLD) is characterized by a decrease in subcutaneous fat and ectopic fat deposition in the liver. SCAP may mediate the development of lean NAFLD, but the mechanism of action remains unclear. C57BL/6J wild-type and macrophage SCAP-specific knockout mice (SCAPΔMϕ) were subjected to Paigen diet (PD) feeding induced lean NAFLD. Inflammation and lipid metabolism of adipose and liver were evaluated. The STING–NF-κB signaling pathway was examined in vivo and in vitro to explore the underlying mechanism of macrophage SCAP on metaflammation. The data showed heterogeneity of lipid metabolic processes in liver and epididymal white adipose tissue due to inflammation mediated by macrophage infiltration. Meanwhile, we found that the macrophage SCAP was abnormally increased in the adipose and liver tissues of PD-fed mice. Intriguingly, the SCAPΔMϕ mice attenuated PD-induced metaflammation and ectopic lipid deposition by reducing hepatic stimulator of interferon gene (STING)–nuclear factor kappa B (NF-κB) pathway activation. In-depth molecular analysis revealed that SCAP specifically recruits the STING and tank-binding kinase 1 onto the Golgi to activate the NF-κB in macrophages, thereby promoting the release of inflammatory factors. This process ultimately led to an increased lipolysis in adipocytes and lipid uptake and synthesis in hepatocytes. Our findings suggest that SCAP acts as a novel regulator of the macrophage inflammatory response and the pathogenesis of lean NAFLD by activating the STING–NF-κB signaling pathway. Inhibition of macrophage SCAP may represent a new therapeutic strategy for the treatment of lean NAFLD.
11 citations
TL;DR: In this paper, a case of prolonged COVID-19 caused by the SARS-CoV-2 Gamma variant in a fully vaccinated healthcare worker, 387 days after an infection caused by lineage B.1.33.
10 citations
TL;DR: In this paper, a 3D cobalt phosphide coated nickel-cobalt layered double hydroxide heteronanosheet array on Ni foam was constructed using electrodeposition and high-temperature phosphating technology.
TL;DR: In this paper , a SARS-CoV-2 S protein construct called S-R/x3 was constructed to stabilize the lock-1 and lock-2 conformation.
Abstract: The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct “S-R/x3” to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.
TL;DR: In this article , a 3D cobalt phosphide coated nickel-cobalt layered double hydroxide heteronanosheet array on Ni foam was constructed using electrodeposition and high-temperature phosphating technology.
TL;DR: In this paper, the effects of CBD on the spermatogenesis and sperm quality of mice were investigated, and it was shown that chronic exposure to CBD decreased the frequency of stages VII-VIII and XII and an increase of stage IX were noted.
TL;DR: In this paper , a modification of initiation site sequencing (ini-seq) based on density substitution is described, which allows precise mapping of 23,905 replication origins simultaneously with an assignment of a replication initiation initiation efficiency score to each.
Abstract: Replication of the human genome initiates within broad zones of ∼150 kb. The extent to which firing of individual DNA replication origins within initiation zones is spatially stochastic or localised at defined sites remains a matter of debate. A thorough characterisation of the dynamic activation of origins within initiation zones is hampered by the lack of a high-resolution map of both their position and efficiency. To address this shortcoming, we describe a modification of initiation site sequencing (ini-seq), based on density substitution. Newly replicated DNA is rendered 'heavy-light' (HL) by incorporation of BrdUTP while unreplicated DNA remains 'light-light' (LL). Replicated HL-DNA is separated from unreplicated LL-DNA by equilibrium density gradient centrifugation, then both fractions are subjected to massive parallel sequencing. This allows precise mapping of 23,905 replication origins simultaneously with an assignment of a replication initiation efficiency score to each. We show that origin firing within early initiation zones is not randomly distributed. Rather, origins are arranged hierarchically with a set of very highly efficient origins marking zone boundaries. We propose that these origins explain much of the early firing activity arising within initiation zones, helping to unify the concept of replication initiation zones with the identification of discrete replication origin sites.
TL;DR: In this article , the expression and function of the novel inhibitory receptor immunoglobulin-like transcript-2 (ILT2) on NK cells from 131 CHB patients and 36 healthy controls were analyzed.
TL;DR: In this article, a plant microbial fuel cell (P-MFC) has been used to evaluate the improvement of power generation in the growth of four cactus pear genotypes aided by ammonium nitrate under semi-arid conditions.
TL;DR: A miniaturized/portable visual colorimetric system based on hydride generation headspace solid phase extraction (HG-HS-SPE) was proposed for arsenic detection by naked eyes as discussed by the authors .
08 Jan 2022
TL;DR: In this paper , the authors describe the structure of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-A Nuc reconstituted onto α-satellite DNA.
Abstract: Abstract Accurate chromosome segregation, controlled by kinetochore-mediated chromatid attachments to the mitotic spindle, ensures the faithful inheritance of genetic information. Kinetochores assemble onto specialized CENP-A nucleosomes (CENP-A Nuc ) of centromeric chromatin. In humans, this is mostly organized as thousands of copies of an ∼171 bp α -satellite repeat. Here, we describe the cryo-EM structure of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-A Nuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-A Nuc , while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel which tightly grips the DNA. The CENP-TWSX histone-fold module, together with CENP-HIK Head , further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the α -satellite repeat linker DNA by CCAN provides a robust mechanism by which the kinetochore withstands the pushing and pulling of centromeres associated with chromosome congression and segregation forces. One-Sentence Summary The human inner kinetochore CCAN complex tightly grips the linker DNA of the α-satellite CENP-A nucleosome.
TL;DR: This paper identified Atlas virus, an intact retrovirus-like EVE in the human hookworm Ancylostoma ceylanicum, with an envelope protein genetically related to GN-GC glycoproteins from the family Phenuiviridae.
Abstract: Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse and informative of virus evolution. We identify Atlas virus-an intact retrovirus-like EVE in the human hookworm Ancylostoma ceylanicum, with an envelope protein genetically related to GN-GC glycoproteins from the family Phenuiviridae. A cryo-EM structure of Atlas GC reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas GC has the structural hallmarks of an active fusogen. Atlas GC trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas GC has cell-cell fusion activity. With its preserved biological activities, Atlas GC has the potential to acquire a cellular function. Our work reveals structural plasticity in reverse-transcribing RNA viruses.
TL;DR: In this article , the authors presented new cryo-EM image processing methods for amyloids, including automated picking and strategies for helical structure determination in RELION, and showed examples of tau filament structures that were solved using these methods.
Abstract: This paper presents new cryo-EM image processing methods for amyloids, including automated picking and strategies for helical structure determination in RELION. The image shows examples of tau filament structures that were solved using these methods.
TL;DR: In this article , the bivariate Reitsma model and the hierarchical receiver operating characteristic curve model were used to evaluate the diagnostic performance of molecular tests at a 95% confidence interval.
Abstract: Syphilis continues to be a public health problem, and its diagnosis still has limitations. Molecular diagnosis provides an alternative for rapid and effective management. The objective is to determine the accuracy of tests in the molecular diagnosis of syphilis.We searched PubMed and Web of Sciences for articles related to molecular detection of syphilis from January 1, 2009, to December 31, 2019. The bivariate Reitsma model and the hierarchical receiver operating characteristic curve model were used to evaluate the diagnostic performance of molecular tests at a 95% confidence interval. A subgroup meta-analysis was performed to explore sources of heterogeneity.Forty-seven articles were identified for qualitative synthesis, of which 23 met the inclusion criteria for meta-analysis. The pooled sensitivities in conventional polymerase chain reaction (PCR) and real-time PCR were 77.52 (59.50-89.01) and 68.43 (54.96-79.39), respectively. The pooled specificities were 98.00 (90.73-99.59) and 98.84 (97.55-99.46), respectively. Ulcer samples had a better performance (sensitivity of 79.88 [69.00-87.62] and specificity of 98.58 [97.25-99.27]), and the major target genes were the polymerase A gene and tpp47 gene.Our work showed that conventional PCR was more widely used than real-time PCR in the diagnosis of syphilis, and ulcers were the best specimens. Sample types and target genes are factors that may influence the quality of the different tests. These results could provide evidence for further work in the direction of providing a more efficient diagnostic test.
TL;DR: In this article, a process for the manufacture of electron cryomicroscopy (cryoEM) specimen supports with an integrated foil-grid structure, using cryogenic vacuum evaporation and patterned electroplating on a silicon wafer substrate.
TL;DR: In this article , a process for the manufacture of electron cryomicroscopy (cryoEM) specimen supports with an integrated foil-grid structure, using cryogenic vacuum evaporation and patterned electroplating on a silicon wafer substrate.
01 Sep 2022
TL;DR: In this article , an approach based on discrete-event simulation is presented to predict the elective waiting list backlog along with the delay in treatment based on a predetermined prioritisation policy. But the model is limited to the case of endoscopy waiting lists.
Abstract: The COVID-19 pandemic had a major impact on healthcare systems across the world. In the United Kingdom, one of the strategies used by hospitals to cope with the surge in patients infected with SARS-Cov-2 was to cancel a vast number of elective treatments planned and limit its resources for non-critical patients. This resulted in a 30% drop in the number of people joining the waiting list in 2020–2021 versus 2019–2020. Once the pandemic subsides and resources are freed for elective treatment, the expectation is that the patients failing to receive treatment throughout the pandemic would trigger a significant backlog on the waiting list post-pandemic with major repercussions to patient health and quality of life. As the nation emerges from the worst phase of the pandemic, hospitals are focusing on strategies to prioritise patients for elective treatments. A key challenge in this context is the ability to quantify the expected backlog and predict the delays experienced by patients as an outcome of the prioritisation policies. This study presents an approach based on discrete-event simulation to predict the elective waiting list backlog along with the delay in treatment based on a predetermined prioritisation policy. The model is demonstrated using data on the endoscopy waiting list at Cambridge University Hospitals. The model shows that 21% of the patients on the waiting list will experience a delay less than 18-weeks, the acceptable threshold set by the National Health Service (NHS). A longer-term scenario analysis based on the model reveals investment in NHS resources will have a significant positive outcome for addressing the waiting lists. The model presented in this paper has the potential to be an invaluable tool for post-pandemic planning for hospitals around the world that are facing a crisis of treatment backlog.
TL;DR: In this article, the effects of Deltamethrin (DM) exposure on zebrafish locomotor activity was studied, showing that it significantly reduced the average swimming speed of the larvae.
16 May 2022
TL;DR: In this paper , the Mps1-phosphorylation dependent association of Bub1 and Mad1, together with a tripartite assembly of Bub 1 and Cdc20 onto the C- terminal domain of Mad1 (Mad1 CTD ), was shown to accelerate MCC assembly.
Abstract: Abstract In response to improper kinetochore-microtubule attachments in mitosis, the spindle assembly checkpoint (SAC) assembles the mitotic checkpoint complex (MCC) to inhibit the anaphase- promoting complex/cyclosome, thereby delaying entry into anaphase. The MCC is a complex of Mad2, Cdc20 and BubR1:Bub3. Its assembly is catalysed by unattached kinetochores on a catalytic Mad1:Mad2 platform. Mad1-bound closed-Mad2 (C-Mad2) recruits open-Mad2 (O- Mad2) through self-dimerization. This interaction, combined with Mps1 kinase-mediated phosphorylation of Bub1 and Mad1, accelerates MCC assembly, in a process that requires conversion of O-Mad2 to C-Mad2 and concomitant binding of Cdc20. How Mad1 phosphorylation catalyses MCC assembly is poorly understood. In this study we characterized Mps1 phosphorylation of Mad1 and obtained structural insights into a phosphorylation-specific Mad1:Cdc20 interaction. This interaction, together with the Mps1-phosphorylation dependent association of Bub1 and Mad1, generates a tripartite assembly of Bub1 and Cdc20 onto the C- terminal domain of Mad1 (Mad1 CTD ). We additionally identified a folded state of the Mad1:Mad2 complex that suggests how the Cdc20:Mad1 CTD interaction brings the Mad2- interacting motif (MIM) of Cdc20 (Cdc20 MIM ) into close proximity with O-Mad2. We also show that Cdc20 MIM is sufficient to catalyse Mad2 conversion and its entrapment by the Mad2 safety- belt. Thus, Mps1-dependent formation of the MCC-assembly scaffold functions to position and orient Cdc20 MIM near O-Mad2, thereby catalysing formation of C-Mad2:Cdc20.
TL;DR: In this article, the authors retrospectively analyzed the risk factors for transchemotherapy dysgeusia and found that one-fifth of the patients (19.0%) presented a significant loss of taste, with 1118 (15.0%), showing grade 1 dysgesia and 442 (6.0%).
Abstract: This study retrospectively analyzed the risk factors for transchemotherapy dysgeusia. Before each chemotherapy cycle, patients were routinely evaluated for the presence/severity of dysgeusia based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded as follows: 0, no change in taste; 1, altered taste with no impact on eating habits; or 2, altered taste with an impact on eating habits. Information from 2 years of evaluations was collected and patient medical records were reviewed to obtain data on chemotherapy cycle, sex, age, body mass index, body surface area, primary tumor, chemotherapy protocol, and history of head and neck radiotherapy. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). Among 7425 total patients, 3047, 2447, and 1931 were evaluated after the first, second, and third chemotherapy cycles, respectively. One-fifth of the patients (19.0%) presented a significant loss of taste, with 1118 (15.0%) showing grade 1 dysgeusia and 442 (6.0%) showing grade 2 dysgeusia. The chemotherapy duration (p < 0.001), female sex (p < 0.001), location of the primary tumor in the uterus (p = 0.008), head and neck (p = 0.012), and testicles (p = 0.011), and use of ifosfamide (p = 0.009), docetaxel (p = 0.001), paclitaxel (p < 0.001), pertuzumab (p = 0.005), bevacizumab (p < 0.001), and dacarbazine (p = 0.002) independently increased the risk of dysgeusia. In head and neck tumors, a previous history of radiotherapy significantly increased the prevalence of dysgeusia (p = 0.017), and the use of cisplatin (p = 0.001) increased this prevalence. Cycles of chemotherapy, sex, uterine cancer, head and neck tumors, testicular cancer, ifosfamide, docetaxel, paclitaxel, pertuzumab, bevacizumab, and dacarbazine increase the risk of dysgeusia.
TL;DR: In this article, the authors investigated the relationship between down-regulation of IKBKG gene expression and hepatocyte senescence induced by sodium fluoride (NaF) in chronic fluorosis rats and NaF-exposure human liver L02 cells.
TL;DR: In this article, the effects of taurine supplementation on adipose tissue using transcriptome analysis, 3T3-L1 adipocytes, and subcutaneous white adipose tissues (scWAT) of obese women were investigated.