bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparisons of Chloroplast Genome Mutations among 13 Samples of Oil-Tea Camellia from South China
Authors: Chen Jing , Zhou Kaibing , Hu Xinwen
Published: May 2023

The differences in cpDNA SNPs and InDels of 13 samples from single trees of different species or populations of oil-tea camellia in South China were examined in this study, and phylogenetic trees were reconstructed based on CDSs and non-CDSs of cpDNAs to research the evolutionary relationships among all samples. The SNPs of all samples included all kinds of substitutions, and the frequency of the transition from AT to GC was highest; meanwhile, the frequencies of all kinds of transversions differed among the samples, and the SNPs exhibited polymorphism. The SNPs were distributed in all the different functional regions of cpDNAs, and approximately half of all SNPs in exons led to missense mutations and the gain or loss of termination codons. There were no InDels in the exons of any cpDNA samples, except those retrieved from Camellia gigantocarpa, although this InDel did not lead to a frame shift. The InDels of all cpDNA samples were unevenly distributed in the intergenic region and upstream and downstream of genes. The genes, regions of the same gene, sites and mutation types in the same region related to the distributions of SNPs, and InDels were inconsistent among samples. The 13 samples were divided into 2 clades and 7 or 6 subclades, and the samples of species from the same sections of the Camellia genus did not belong to the same subclades. Meanwhile, the genetic relationship between the samples of Camellia vietnamensis and the undetermined species from Hainan Province or the population of C. gauchowensis in Xuwen was closer than that between C. vietnamensis and the population of C. gauchowensis in Luchuan, and the genetic relationship among C. osmantha, C. vietnamensis and C. gauchowensis was very close. In sum, SNPs and InDels in the different cpDNAs resulted in variable phenotypes among the different species or populations, and they could be developed into molecular markers for studies on species and population identification and phylogenetic relationships. The conclusion from the identification of undetermined species from Hainan Province and the phylogenetic relationships among 13 oil-tea camellia samples based on cpCDS and cpnon-CDS sequences were the same as those from the former report.
The Genome of a Pigeonpea Compatible Rhizobial Strain ‘10ap3’ Appears to Lack Common Nodulation Genes
Authors: Bopape Francina , Hassen Ahmed , Chiulele Rogerio , Shonhai Addmore , Gwata Eastonce
Published: May 2023

The symbiotic fixation of atmospheric nitrogen (N) in root nodules of tropical legumes such as pigeonpea (Cajanus cajan) is a complex process, which is regulated by multiple genetic factors at the host plant genotype microsymbiont interface. The process involves multiple genes with various modes of action and is accomplished only when both organisms are compatible. Therefore, it is necessary to develop tools for the genetic manipulation of the host or bacterium towards improving N fixation. In this study, we sequenced the genome of a robust rhizobial strain, Rhizobium tropici ‘10ap3’ that was compatible with pigeonpea, and we determined its genome size. The genome consisted of a large circular chromosome (6,297,373 bp) and contained 6013 genes of which 99.13% were coding sequences. However only 5833 of the genes were associated with proteins that could be assigned to specific functions. The genes for nitrogen, phosphorus and iron metabolism, stress response and the adenosine monophosphate nucleoside for purine conversion were present in the genome. However, the genome contained no common nod genes, suggesting that an alternative pathway involving a purine derivative was involved in the symbiotic association with pigeonpea.
Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins
Authors: Nasyrova Regina F. , Shnayder Natalia A. , Osipova Sofia M. , Khasanova Aiperi K. , Efremov Ilya S. , Al-Zamil Mustafa , Petrova Marina M. , Narodova Ekaterina A. , Garganeeva Natalia P. , Shipulin German A.
Published: May 2023

Antipsychotic (AP)—induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel “Transporter protein (PT)—Antipsychotic (AP) Pharmacogenetic test (PGx)” (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.
Modeling the Trajectories of Ballistics in the Summit Area of Mt. Etna (Italy) during the 2020–2022 Sequence of Lava Fountains
Authors: Costa Giorgio , Mereu Luigi , Prestifilippo Michele , Scollo Simona , Viccaro Marco
Published: May 2023

Between 2020 and 2022, more than sixty lava fountains occurred at Mt. Etna (Italy), which formed high eruption columns rising up to 15 km above sea level (a.s.l.). During those events, several ballistics fell around the summit craters, sometimes reaching touristic areas. The rather frequent activity poses questions on how the impact associated with the fallout of those particles, can be estimated. In this work, we present field data collected soon after the lava fountain on 21 February 2022. This event produced a volcanic plume of about 10 km a.s.l. which was directed toward the southeast. Several ballistics fell in the area of the Barbagallo Craters (just southeast of the summit area at around 2900 m a.s.l.), which is one of the most popular touristic areas on Etna. Hence, we collected several samples and performed laboratory analyses in order to retrieve their size, shape and density. Those values together with a quantitative analysis of the lava fountain were compared with results obtained by a free-available calculator of ballistic trajectories named the ‘Eject!’. A similar approach was hence applied to other lava fountains of the 2020–2022 sequence for which the fallout of large clasts was reported. This work is a first step to identifying in near real-time the area affected by the fallout of ballistics during Etna lava fountains and quantifying their hazard.
Implementation and Optimization of Algal Biomass in Value-Added Products Recovery: A Step towards Algae-Based Green Economy
Authors: Dutta Nalok , Kundu Pritha , Lee Jonathan Tian En , Bhattacharya Sayan
Published: May 2023

Algal biomass is a prospective feedstock for the eco-sustainable production of many different products with added value, such as meals, feeds, and fuels. The remaining biomass from the algae can be used as raw material and can be transformed into useful secondary products after the important macromolecules have been removed. By optimizing algal biomass hydrolysate utilizing microbial fermentation, several studies demonstrated the generation of bioenergy (bioalcohol, biogas, and biohydrogen) and biochemicals (organic acids and biopolymers). Since the harvest and maintenance of sustainable algal cultivation incur considerable energy and economical prowess, developing products from algae remains a challenge to be countered in commercial applications. This is a typical bottleneck issue when processing algae for fuels or chemicals at the pilot scale. Implementation of integrated algae biorefinery methods can substantially reduce the cost of production and energy consumption. An algae-based green economy can be financially more viable and utilizable, especially for countries with weaker economies. This review’s goal is to examine the implementation of integrated biorefineries for the recovery of bioproducts generated from algae and potential applications. In this context, the life cycle analysis and business elements of a unified algal biorefinery are also addressed.
Growth Monitoring and Promotion Service Utilisation and Associated Factors among Children in Afar Region, Northeast Ethiopia
Authors: Kiros Semhal , Ibrahim Ibrahim Mohammed , Ahmed Kedir Y.
Published: May 2023

The use of growth monitoring and promotion (GMP) services in the first two years of life can facilitate the early identification of common childhood health issues such as malnutrition and infections. It also creates an opportunity to promote education and nutritional counselling. This study is the first to investigate the use of GMP and its influencing factors among mothers in Ethiopia’s pastoralist regions, including the Afar National and Regional State, where childhood malnutrition is a significant cause of morbidity and mortality. Between May and June 2021, a cross-sectional study was conducted within the Semera-Logia city administration. The study used a random sampling technique to select 396 children under two, and data were gathered using an interviewer-administered questionnaire. Multivariable logistic regression was used to analyse the influence of explanatory variables, which included socio-demographic, health service, and health literacy factors, on the utilisation of GMP services. The overall utilisation of GMP services was 15.9% (95% confidence intervals [CI]: 12.0%, 19.5%). Children whose fathers had college or higher education were more likely to utilise GMP services (adjusted odd ratios [AOR] = 7.75; 95% CI: 3.01, 19.99), whereas children living in households with more children were less likely to utilise GMP services (AOR = 0.11; 95% CI: 0.04, 0.28 for households with 3–4 children and AOR = 0.23; 95% CI: 0.08, 0.67 for households with 4+ children). Children who received postnatal care had higher odds of GMP service use (AOR = 8.09; 95% CI: 3.19, 20.50). GMP services are not being fully utilised to decrease infant and child morbidity and mortality caused by malnutrition in Ethiopia. We recommend strengthening GMP services in Ethiopia and taking targeted action to address the low attainment of parental education and poor postnatal care utilisation. Public health initiatives such as the implementation of mobile health (mHealth) approaches and education of mothers by female community healthcare workers on the significance of GMP services could be effective in increasing GMP service utilisation.
Teamwork Management and Benefit of Telemedicine in COVID-19 Outbreak Control on an Offshore Vessel in the Gulf of Thailand, Songkhla Province, Thailand: A Case Report
Authors: Pongpattarapokin Rujjirat , Chusri Sarunyou , Ingviya Thammasin , Chaichulee Sitthichok , Kwanyuang Atichart , Horsiritham Kanakorn , Varopichetsan Suebsai , Surasombatpattana Smonrapat , Sathirapanya Chutarat , Sathirapanya Pornchai , Kongkamol Chanon
Published: May 2023

In May 2021, there was a COVID-19 outbreak on board a construction support ship traveling from India to Thailand. Controlling the outbreak on this offshore vessel from 11 May to 2 June 2021 was applied. This case report describes the teamwork management of COVID-19 control on the vessel in the Gulf of Thailand. We summarized the COVID-19 outbreak control process on board, including active COVID-19-infected cases (CoIC) and close contacts (CoCC) identification, isolation, quarantine, treatment, and clinical monitoring using telemedicine to report their health measurements twice daily, including emergency conditions if they occurred. Active COVID-19 cases were identified by two rounds of reverse transcription polymerase chain reaction (RT-PCR) tests in all crew members, in which 7 of 29 (24.1%) showed positive results. Both the CoIC and CoCC were strictly and absolutely isolated and quarantined on the vessel. No serious medical conditions were reported during the monitoring. The third-round RT-PCR tests were conducted, and all tested negative one week later. Teamwork management in proactive COVID-19 case identification, isolation, comprehensive treatment, and close monitoring of health conditions using telemedicine devices is beneficial for controlling the COVID-19 outbreak on board.
Evaluating Landslide Susceptibility Using Sampling Methodology and Multiple Machine Learning Models
Authors: Song Yingze , Yang Degang , Wu Weicheng , Zhang Xin , Zhou Jie , Tian Zhaoxu , Wang Chencan , Song Yingxu
Published: May 2023

Landslide susceptibility assessment (LSA) based on machine learning methods has been widely used in landslide geological hazard management and research. However, the problem of sample imbalance in landslide susceptibility assessment, where landslide samples tend to be much smaller than non-landslide samples, is often overlooked. This problem is often one of the important factors affecting the performance of landslide susceptibility models. In this paper, we take the Wanzhou district of Chongqing city as an example, where the total number of data sets is more than 580,000 and the ratio of positive to negative samples is 1:19. We oversample or undersample the unbalanced landslide samples to make them balanced, and then compare the performance of machine learning models with different sampling strategies. Three classic machine learning algorithms, logistic regression, random forest and LightGBM, are used for LSA modeling. The results show that the model trained directly using the unbalanced sample dataset performs the worst, showing an extremely low recall rate, indicating that its predictive ability for landslide samples is extremely low and cannot be applied in practice. Compared with the original dataset, the sample set optimized through certain methods has demonstrated improved predictive performance across various classifiers, manifested in the improvement of AUC value and recall rate. The best model was the random forest model using over-sampling (O_RF) (AUC = 0.932).
A Dynamic Management and Integration Framework for Models in Landslide Early Warning System
Authors: Liu Liang , Deng Jiqiu , Tang Yu
Published: May 2023

The landslide early warning system (LEWS) relies on various models for data processing, prediction, forecasting, and warning level discrimination. The potential different programming implementations and dependencies of these models complicate the deployment and integration of LEWS. Moreover, the coupling between LEWS and models makes it hard to modify or replace models rapidly and dynamically according to changes in business requirements (such as updating the early warning business process, adjusting the model parameters, etc.). This paper proposes a framework for dynamic management and integration of models in LEWS by using WebAPIs and Docker to standardize model interfaces and facilitate model deployment, using Kubernetes and Istio to enable microservice architecture, dynamic scaling, and high availability of models, and using a model repository management system to manage and orchestrate model-related information and application processes. The results of applying this framework to a real LEWS demonstrate that our approach can support efficient deployment, management, and integration of models within the system. Furthermore, it provides a rapid and feasible implementation method for upgrading, expanding, and maintaining LEWS in response to changes in business requirements.
The Tango between Cancer-Associated Fibroblasts (CAFs) and Immune Cells in Affecting Immunotherapy Efficacy in Pancreatic Cancer
Authors: Stouten Imke , van Montfoort Nadine , Hawinkels Lukas J. A. C.
Published: May 2023

The lack of response to therapy in pancreatic ductal adenocarcinoma (PDAC) patients has contributed to PDAC having one of the lowest survival rates of all cancer types. The poor survival of PDAC patients urges the exploration of novel treatment strategies. Immunotherapy has shown promising results in several other cancer types, but it is still ineffective in PDAC. What sets PDAC apart from other cancer types is its tumour microenvironment (TME) with desmoplasia and low immune infiltration and activity. The most abundant cell type in the TME, cancer-associated fibroblasts (CAFs), could be instrumental in why low immunotherapy responses are observed. CAF heterogeneity and interactions with components of the TME is an emerging field of research, where many paths are to be explored. Understanding CAF–immune cell interactions in the TME might pave the way to optimize immunotherapy efficacy for PDAC and related cancers with stromal abundance. In this review, we discuss recent discoveries on the functions and interactions of CAFs and how targeting CAFs might improve immunotherapy.
Temperature-Dependent Effects of Eicosapentaenoic Acid (EPA) on Browning of Subcutaneous Adipose Tissue in UCP1 Knockout Male Mice
Authors: Zu Yujiao , Pahlavani Mandana , Ramalingam Latha , Jayarathne Shasika , Andrade Jose , Scoggin Shane , Festuccia William T. , Kalupahana Nishan S. , Moustaid-Moussa Naima
Published: May 2023

Uncoupling protein 1 (UCP1) plays a central role in thermogenic tissues by uncoupling cellular respiration to dissipate energy. Beige adipocytes, an inducible form of thermogenic cells in subcutaneous adipose tissue (SAT), have become a major focus in obesity research. We have previously shown that eicosapentaenoic acid (EPA) ameliorated high-fat diet (HFD)-induced obesity by activating brown fat in C57BL/6J (B6) mice at thermoneutrality (30 °C), independently of UCP1. Here, we investigated whether ambient temperature (22 °C) impacts EPA effects on SAT browning in wild-type (WT) and UCP1 knockout (KO) male mice and dissected underlying mechanisms using a cell model. We observed resistance to diet-induced obesity in UCP1 KO mice fed HFD at ambient temperature, with significantly higher expression of UCP1-independent thermogenic markers, compared to WT mice. These markers included the fibroblast growth factor 21 (FGF21) and sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b), suggesting the indispensable role of temperature in beige fat reprogramming. Surprisingly, although EPA induced thermogenic effects in SAT-derived adipocytes harvested from both KO and WT mice, EPA only increased thermogenic gene and protein expression in the SAT of UCP1 KO mice housed at ambient temperature. Collectively, our findings indicate that the thermogenic effects of EPA, which are independent of UCP1, occur in a temperature-dependent manner.
Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities
Authors: Adimulam Theolan , Arumugam Thilona , Gokul Anmol , Ramsuran Veron
Published: May 2023

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.
Characterization of the Flash-Induced Fluorescence Wave Phenomenon in the Coral Endosymbiont Algae, Symbiodiniaceae
Authors: Mohammad Aslam Sabit , Vass Imre , Szabó Milán
Published: May 2023

The dinoflagellate algae, Symbiodiniaceae, are significant symbiotic partners of corals due to their photosynthetic capacity. The photosynthetic processes of the microalgae consist of linear electron transport, which provides the energetic balance of ATP and NADPH production for CO2 fixation, and alternative electron transport pathways, including cyclic electron flow, which ensures the elevated ATP requirements under stress conditions. Flash-induced chlorophyll fluorescence relaxation is a non-invasive tool to assess the various electron transport pathways. A special case of fluorescence relaxation, the so-called wave phenomenon, was found to be associated with the activity of NAD(P)H dehydrogenase (NDH) in microalgae. We showed previously that the wave phenomenon existed in Symbiodiniaceae under acute heat stress and microaerobic conditions, however, the electron transport processes related to the wave phenomenon remained unknown. In this work, using various inhibitors, we show that (i) the linear electron transport has a crucial role in the formation of the wave, (ii) the inhibition of the donor side of Photosystem II did not induce the wave, whereas inhibition of the Calvin–Benson cycle accelerated it, (iii) the wave phenomenon was related to the operation of type II NDH (NDH-2). We therefore propose that the wave phenomenon is an important marker of the regulation of electron transport in Symbiodiniaceae.
Synthesis and Characterization of Tetraphenylethene AIEgen-Based Push–Pull Chromophores for Photothermal Applications: Could the Cycloaddition–Retroelectrocyclization Click Reaction Make Any Molecule Photothermally Active?
Authors: Roger Maxime , Bretonnière Yann , Trolez Yann , Vacher Antoine , Arbouch Imane , Cornil Jérôme , Félix Gautier , De Winter Julien , Richeter Sébastien , Clément Sébastien , Gerbier Philippe
Published: May 2023

Three new tetraphenylethene (TPE) push–pull chromophores exhibiting strong intramolecular charge transfer (ICT) are described. They were obtained via [2 + 2] cycloaddition–retroelectrocyclization (CA-RE) click reactions on an electron-rich alkyne-tetrafunctionalized TPE (TPE-alkyne) using both 1,1,2,2-tetracyanoethene (TCNE), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) as electron-deficient alkenes. Only the starting TPE-alkyne displayed significant AIE behavior, whereas for TPE-TCNE, a faint effect was observed, and for TPE-TCNQ and TPE-F4-TCNQ, no fluorescence was observed in any conditions. The main ICT bands that dominate the UV–Visible absorption spectra underwent a pronounced red-shift beyond the near-infrared (NIR) region for TPE-F4-TCNQ. Based on TD-DFT calculations, it was shown that the ICT character shown by the compounds exclusively originated from the clicked moieties independently of the nature of the central molecular platform. Photothermal (PT) studies conducted on both TPE-TCNQ and TPE-F4-TCNQ in the solid state revealed excellent properties, especially for TPE-F4-TCNQ. These results indicated that CA-RE reaction of TCNQ or F4-TCNQ with donor-substituted are promising candidates for PT applications.
Evolution of Resistance to Irinotecan in Cancer Cells Involves Generation of Topoisomerase-Guided Mutations in Non-Coding Genome That Reduce the Chances of DNA Breaks
Authors: Kumar Santosh , Gahramanov Valid , Patel Shivani , Yaglom Julia , Kaczmarczyk Lukasz , Alexandrov Ivan A. , Gerlitz Gabi , Salmon-Divon Mali , Sherman Michael Y.
Published: May 2023

Resistance to chemotherapy is a leading cause of treatment failure. Drug resistance mechanisms involve mutations in specific proteins or changes in their expression levels. It is commonly understood that resistance mutations happen randomly prior to treatment and are selected during the treatment. However, the selection of drug-resistant mutants in culture could be achieved by multiple drug exposures of cloned genetically identical cells and thus cannot result from the selection of pre-existent mutations. Accordingly, adaptation must involve the generation of mutations de novo upon drug treatment. Here we explored the origin of resistance mutations to a widely used Top1 inhibitor, irinotecan, which triggers DNA breaks, causing cytotoxicity. The resistance mechanism involved the gradual accumulation of recurrent mutations in non-coding regions of DNA at Top1-cleavage sites. Surprisingly, cancer cells had a higher number of such sites than the reference genome, which may define their increased sensitivity to irinotecan. Homologous recombination repairs of DNA double-strand breaks at these sites following initial drug exposures gradually reverted cleavage-sensitive “cancer” sequences back to cleavage-resistant “normal” sequences. These mutations reduced the generation of DNA breaks upon subsequent exposures, thus gradually increasing drug resistance. Together, large target sizes for mutations and their Top1-guided generation lead to their gradual and rapid accumulation, synergistically accelerating the development of resistance.
Dopamine-Dependent Ketamine Modulation of Glutamatergic Synaptic Plasticity in the Prelimbic Cortex of Adult Rats Exposed to Acute Stress
Authors: Forti Lia , Ndoj Elona , Mingardi Jessica , Secchi Emanuele , Bonifacino Tiziana , Schiavon Emanuele , Carini Giulia , La Via Luca , Russo Isabella , Milanese Marco , Gennarelli Massimo , Bonanno Giambattista , Popoli Maurizio , Barbon Alessandro , Musazzi Laura
Published: May 2023

Traumatic stress is the main environmental risk factor for the development of psychiatric disorders. We have previously shown that acute footshock (FS) stress in male rats induces rapid and long-lasting functional and structural changes in the prefrontal cortex (PFC), which are partly reversed by acute subanesthetic ketamine. Here, we asked if acute FS may also induce any changes in glutamatergic synaptic plasticity in the PFC 24 h after stress exposure and whether ketamine administration 6 h after stress may have any effect. We found that the induction of long-term potentiation (LTP) in PFC slices of both control and FS animals is dependent on dopamine and that dopamine-dependent LTP is reduced by ketamine. We also found selective changes in ionotropic glutamate receptor subunit expression, phosphorylation, and localization at synaptic membranes induced by both acute stress and ketamine. Although more studies are needed to understand the effects of acute stress and ketamine on PFC glutamatergic plasticity, this first report suggests a restoring effect of acute ketamine, supporting the potential benefit of ketamine in limiting the impact of acute traumatic stress.
The Males Absent on the First (MOF) Mediated Acetylation Alters the Protein Stability and Transcriptional Activity of YY1 in HCT116 Cells
Authors: Wu Tingting , Zhao Bingxin , Cai Chengyu , Chen Yuyang , Miao Yujuan , Chu Jinmeng , Sui Yi , Li Fuqiang , Chen Wenqi , Cai Yong , Wang Fei , Jin Jingji
Published: May 2023

Yin Yang 1 (YY1) is a well-known transcription factor that controls the expression of many genes and plays an important role in the occurrence and development of various cancers. We previously found that the human males absent on the first (MOF)-containing histone acetyltransferase (HAT) complex may be involved in regulating YY1 transcriptional activity; however, the precise interaction between MOF-HAT and YY1, as well as whether the acetylation activity of MOF impacts the function of YY1, has not been reported. Here, we present evidence that the MOF-containing male-specific lethal (MSL) HAT complex regulates YY1 stability and transcriptional activity in an acetylation-dependent manner. First, the MOF/MSL HAT complex was bound to and acetylated YY1, and this acetylation further promoted the ubiquitin–proteasome degradation pathway of YY1. The MOF-mediated degradation of YY1 was mainly related to the 146–270 amino acid residues of YY1. Further research clarified that acetylation-mediated ubiquitin degradation of YY1 mainly occurred through lysine 183. A mutation at the YY1K183 site was sufficient to alter the expression level of p53-mediated downstream target genes, such as CDKN1A (encoding p21), and it also suppressed the transactivation of YY1 on CDC6. Furthermore, a YY1K183R mutant and MOF remarkably antagonized the clone-forming ability of HCT116 and SW480 cells facilitated by YY1, suggesting that the acetylation–ubiquitin mode of YY1 plays an important role in tumor cell proliferation. These data may provide new strategies for the development of therapeutic drugs for tumors with high expression of YY1.
The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis
Authors: Kotlyarov Stanislav
Published: May 2023

Tobacco smoking is a major cause of chronic obstructive pulmonary disease (COPD) and atherosclerotic cardiovascular disease (ASCVD). These diseases share common pathogenesis and significantly influence each other’s clinical presentation and prognosis. There is increasing evidence that the mechanisms underlying the comorbidity of COPD and ASCVD are complex and multifactorial. Smoking-induced systemic inflammation, impaired endothelial function and oxidative stress may contribute to the development and progression of both diseases. The components present in tobacco smoke can have adverse effects on various cellular functions, including macrophages and endothelial cells. Smoking may also affect the innate immune system, impair apoptosis, and promote oxidative stress in the respiratory and vascular systems. The purpose of this review is to discuss the importance of smoking in the mechanisms underlying the comorbid course of COPD and ASCVD.
Mycobacterium leprae’s Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a Schwann Cells Infection Model
Authors: Chavarro-Portillo Bibiana , Soto Carlos Y. , Guerrero Martha Inírida
Published: May 2023

Peripheral nerves and Schwann cells (SCs) are privileged and protected sites for initial colonization, survival, and spread of leprosy bacillus. Mycobacterium leprae strains that survive multidrug therapy show a metabolic inactivation that subsequently induces the recurrence of typical clinical manifestations of leprosy. Furthermore, the role of the cell wall phenolic glycolipid I (PGL-I) in the M. leprae internalization in SCs and the pathogenicity of M. leprae have been extensively known. This study assessed the infectivity in SCs of recurrent and non-recurrent M. leprae and their possible correlation with the genes involved in the PGL-I biosynthesis. The initial infectivity of non-recurrent strains in SCs was greater (27%) than a recurrent strain (6.5%). In addition, as the trials progressed, the infectivity of the recurrent and non-recurrent strains increased 2.5- and 2.0-fold, respectively; however, the maximum infectivity was displayed by non-recurrent strains at 12 days post-infection. On the other hand, qRT-PCR experiments showed that the transcription of key genes involved in PGL-I biosynthesis in non-recurrent strains was higher and faster (Day 3) than observed in the recurrent strain (Day 7). Thus, the results indicate that the capacity of PGL-I production is diminished in the recurrent strain, possibly affecting the infective capacity of these strains previously subjected to multidrug therapy. The present work opens the need to address more extensive and in-depth studies of the analysis of markers in the clinical isolates that indicate a possible future recurrence.
Structural Basis of the Transcriptional Elongation Factor Paf1 Core Complex from Saccharomyces eubayanus
Authors: Qin Yan , Zhou Yuqiao , Cao Yinghua , Ren Yanpeng , Deng Pujuan , Jiang Junyi , Wang Zhanxin
Published: May 2023

The multicomponent polymerase associated factor 1 (Paf1) complex (PAF1C) is an important transcription elongation factor that upregulates RNA polymerase II-mediated genome-wide transcription. PAF1C can regulate transcription through direct association with the polymerase or by impacting the chromatin structure epigenetically. In recent years, significant progress has been made in understanding the molecular mechanisms of PAF1C. However, high-resolution structures that can clarify the interaction details among the components of the complex are still needed. In this study, we evaluated the structural core of the yeast PAF1C containing the four components Ctr9, Paf1, Cdc73 and Rtf1 at high resolution. We observed the interaction details among these components. In particular, we identified a new binding surface of Rtf1 on PAF1C and found that the C-terminal sequence of Rtf1 dramatically changed during evolution, which may account for its different binding affinities to PAF1C among species. Our work presents a precise model of PAF1C, which will facilitate our understanding of the molecular mechanism and the in vivo function of the yeast PAF1C.
CD30 Expression and Its Functions during the Disease Progression of Adult T-Cell Leukemia/Lymphoma
Authors: Nakashima Makoto , Uchimaru Kaoru
Published: May 2023

CD30, a member of the tumor necrosis factor receptor superfamily, plays roles in pro-survival signal induction and cell proliferation in peripheral T-cell lymphoma (PTCL) and adult T-cell leukemia/lymphoma (ATL). Previous studies have identified the functional roles of CD30 in CD30-expressing malignant lymphomas, not only PTCL and ATL, but also Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL), and a portion of diffuse large B-cell lymphoma (DLBCL). CD30 expression is often observed in virus-infected cells such as human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is capable of immortalizing lymphocytes and producing malignancy. Some ATL cases caused by HTLV-1 infection overexpress CD30. However, the molecular mechanism-based relationship between CD30 expression and HTLV-1 infection or ATL progression is unclear. Recent findings have revealed super-enhancer-mediated overexpression at the CD30 locus, CD30 signaling via trogocytosis, and CD30 signaling-induced lymphomagenesis in vivo. Successful anti-CD30 antibody-drug conjugate (ADC) therapy for HL, ALCL, and PTCL supports the biological significance of CD30 in these lymphomas. In this review, we discuss the roles of CD30 overexpression and its functions during ATL progression.
SGLT2 Inhibitors: A New Therapeutical Strategy to Improve Clinical Outcomes in Patients with Chronic Kidney Diseases
Authors: Di Costanzo Assunta , Esposito Giovanni , Indolfi Ciro , Spaccarotella Carmen Anna Maria
Published: May 2023

The purpose of this manuscript is to review the effects of sodium-glucose cotransport protein 2 inhibitors (SGLT2is) in patients with chronic kidney disease according to basic mechanisms, current recommendations, and future perspectives. Based on growing evidence from randomized, controlled trials, SGLT2is have proven their benefit on cardiac and renal adverse complications, and their indications expanded into the following five categories: glycemic control, reduction in atherosclerotic cardiovascular disease (ASCVD), heart failure, diabetic kidney disease, and nondiabetic kidney disease. Although kidney disease accelerates the progression of atherosclerosis, myocardial disease, and heart failure, so far, no specific drugs were available to protect renal function. Recently, two randomized trials, the DAPA-CKD and EMPA-Kidney, demonstrated the clinical benefit of the SGLT2is dapagliflozin and empagliflozin in improving the outcome in patients with chronic kidney disease. For the consistently positive results in cardiorenal protection, the SGLT2i represents an effective treatment to reduce the progression of kidney disease or death from cardiovascular causes in patients with and without diabetes mellitus.
ZmDRR206 Regulates Nutrient Accumulation in Endosperm through Its Role in Cell Wall Biogenesis during Maize Kernel Development
Authors: Li Yanmei , Li Dongdong , E Lizhu , Yang Jiayi , Liu Wenjing , Xu Mingliang , Ye Jianrong
Published: May 2023

Dirigent proteins (DIRs) contribute to plant fitness by dynamically reorganizing the cell wall and/or by generating defense compounds during plant growth, development, and interactions with environmental stresses. ZmDRR206 is a maize DIR, it plays a role in maintaining cell wall integrity during seedling growth and defense response in maize, but its role in regulating maize kernel development is unclear. Association analysis of candidate genes indicated that the natural variations of ZmDRR206 were significantly associated with maize hundred-kernel weight (HKW). ZmDRR206 plays a dominant role in storage nutrient accumulation in endosperm during maize kernel development, ZmDRR206 overexpression resulted in small and shrunken maize kernel with significantly reduced starch content and significantly decreased HKW. Cytological characterization of the developing maize kernels revealed that ZmDRR206 overexpression induced dysfunctional basal endosperm transfer layer (BETL) cells, which were shorter with less wall ingrowth, and defense response was constitutively activated in developing maize kernel at 15 and 18 DAP by ZmDRR206 overexpression. The BETL-development-related genes and auxin signal-related genes were down-regulated, while cell wall biogenesis-related genes were up-regulated in developing BETL of the ZmDRR206-overexpressing kernel. Moreover, the developing ZmDRR206-overexpressing kernel had significantly reduced contents of the cell wall components such as cellulose and acid soluble lignin. These results suggest that ZmDRR206 may play a regulatory role in coordinating cell development, storage nutrient metabolism, and stress responses during maize kernel development through its role in cell wall biogenesis and defense response, and provides new insights into understanding the mechanisms of kernel development in maize.
QTL Mapping of Agronomic and Physiological Traits at the Seedling and Maturity Stages under Different Nitrogen Treatments in Barley
Authors: Zeng Zhaoyong , Song Shiyun , Ma Jian , Hu Deyi , Xu Yinggang , Hou Yao , He Chengjun , Tang Xiaoyan , Lan Ting , Zeng Jian , Gao Xuesong , Chen Guangdeng
Published: May 2023

Nitrogen (N) stress seriously constrains barley (Hordeum vulgare L.) production globally by influencing its growth and development. In this study, we used a recombinant inbred line (RIL) population of 121 crosses between the variety Baudin and the wild barley accession CN4027 to detect QTL for 27 traits at the seedling stage in hydroponic culture trials and 12 traits at the maturity stage in field trials both under two N treatments, aiming to uncover favorable alleles for N tolerance in wild barley. In total, eight stable QTL and seven QTL clusters were detected. Among them, the stable QTL Qtgw.sau-2H located in a 0.46 cM interval on the chromosome arm 2HL was a novel QTL specific for low N. Notably, Clusters C4 and C7 contained QTL for traits at both the seedling and maturity stages. In addition, four stable QTLs in Cluster C4 were identified. Furthermore, a gene (HORVU2Hr1G080990.1) related to grain protein in the interval of Qtgw.sau-2H was predicted. Correlation analysis and QTL mapping showed that different N treatments significantly affected agronomic and physiological traits at the seedling and maturity stages. These results provide valuable information for understanding N tolerance as well as breeding and utilizing the loci of interest in barley.
Exploring the Potential of Royal-Jelly-Incorporated Hydrogel Dressings as Innovative Wound Care Materials
Authors: Kudłacik-Kramarczyk Sonia , Krzan Marcel , Jamroży Mateusz , Przybyłowicz Alicja , Drabczyk Anna
Published: May 2023

The development of multifunctional dressing materials with beneficial properties for wound healing has become a recent focus of research. Many studies are being conducted to incorporate active substances into dressings to positively impact wound healing processes. Researchers have investigated various natural additives, including plant extracts and apiproducts such as royal jelly, to enhance the properties of dressings. In this study, polyvinylpyrrolidone (PVP)-based hydrogel dressings modified with royal jelly were developed and analyzed for their sorption ability, wettability, surface morphology, degradation, and mechanical properties. The results showed that the royal jelly and crosslinking agent content had an impact on the physicochemical properties of the hydrogels and their potential for use as innovative dressing materials. This study investigated the swelling behavior, surface morphology, and mechanical properties of hydrogel materials containing royal jelly. The majority of the tested materials showed a gradual increase in swelling ratio with time. The pH of the incubated fluids varied depending on the type of fluid used, with distilled water having the greatest decrease in pH due to the release of organic acids from the royal jelly. The hydrogel samples had a relatively homogeneous surface, and no dependence between composition and surface morphology was observed. Natural additives like royal jelly can modify the mechanical properties of hydrogels, increasing their elongation percentage while decreasing their tensile strength. These findings suggest possible future applications in various fields requiring high flexibility and elasticity.
Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis
Authors: Liang Haifeng , Yan Yiran , Sun Wei , Ma Xiaogang , Su Zhiwen , Liu Zhongxun , Chen Yan , Yu Bo
Published: May 2023

(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA.
Ru(II) Oxygen Sensors for Co(III) Complexes and Amphotericin B Antifungal Activity Detection by Phosphorescence Optical Respirometry
Authors: Turecka Katarzyna , Chylewska Agnieszka , Dąbrowska Aleksandra M. , Hałasa Rafał , Orlewska Czesława , Waleron Krzysztof
Published: May 2023

The measurement of oxygen consumption is an important element in the understanding of an organism’s metabolic state. Oxygen is also a phosphorescence quencher, which allows the evaluation of phosphorescence emitted by oxygen sensors. Two Ru(II)-based oxygen-sensitive sensors were used to study the effect of chemical compounds [(1) = [CoCl2(dap)2]Cl, and (2) = [CoCl2(en)2]Cl (AmB = amphotericin B) against reference and clinical strains of Candida albicans. The tris-[(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)] chloride ([Ru(DPP)3]Cl2) (Box) adsorbed onto the DavisilTM silica gel was embedded in the silicone rubber Lactite NuvaSil® 5091 and the coating on the bottom of 96-well plates. The water-soluble oxygen sensor (BsOx = tris-[(4,7-diphenyl-1,10-phenanthrolinedisulphonic acid disodium)ruthenium(II)] chloride ‘x’ hydrate = {Ru[DPP(SO3Na)2]3}Cl2 = water molecules were omitted in the BsOx formula) was synthesized and characterized by RP-UHPLC, LCMS, MALDI, elemental analysis, ATR, UV-Vis, 1H NMR, and TG/IR techniques. The microbiological studies were performed in the environment of RPMI broth and blood serum. Both Ru(II)-based sensors turned out to be useful in the study of the activity of Co(III) complexes and the commercial antifungal drug amphotericin B. In addition, a new activity of the oxygen sensor, the soluble Ru(II) complex BsOx, was demonstrated, which is a mixture with amphotericin B that caused a significant increase in its antifungal activity. Thus, it is also possible to demonstrate the synergistic effect of compounds active against the microorganisms under study.
Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN
Authors: Wang Ying-Hsuan , Chen Ying-Ju , Lai Yi-Hua , Wang Ming-Chung , Chen Yi-Yang , Wu Yu-Ying , Yang Yao-Ren , Tsou Hsing-Yi , Li Chian-Pei , Hsu Chia-Chen , Huang Cih-En , Chen Chih-Cheng
Published: May 2023

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.