bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and Physiological Effects of 17α-methyltestosterone on Sex Differentiation of Black Rockfish, Sebastes schlegelii
Authors: Huang Haijun , Liu Yuyan , Wang Qian , Dong Caichao , Dong Le , Zhang Jingjing , Yang Yu , Hao Xiancai , Li Weijing , Rosa Ivana F. , Doretto Lucas B. , Cao Xuebin , Shao Changwei
Published: May 2024

It is widely known that all-female fish production holds economic value for aquaculture. Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales of S. schlegelii for subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth of S. schlegelii, while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes (cyp19a1a and foxl2) while up-regulating male-related genes (amh) in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role in S. schlegelii sex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT in S. schlegelii and offers an initial insight into the underlying mechanism of sexual reversal in this species.
Marine Geohazards of the Bay of Naples (Southern Tyrrhenian Sea, Italy): A Review Integrating Morpho-Bathymetric and Seismo-Stratigraphic Analysis
Authors: Aiello Gemma , Caccavale Mauro
Published: May 2024

Marine geohazards in the Bay of Naples, an eruptive region during the late Quaternary, have been assessed based on both morpho-bathymetric and seismic data. Previously identified areas of high marine hazard with slide potential (northern Ischia slope, Naples canyons, and Sorrento Peninsula–Capri slope) have been confirmed and integrated through the seismo-stratigraphic analysis of selected seismic sections. We evaluated the occurrence of important fossil submarine landslides in the stratigraphic record. Several kinds of submarine landslides have been individuated through morpho-bathymetric and seismic interpretation, including creeping, debris avalanches, and debris flows, among others, often controlled by volcanic eruptions. Submarine landslides of Naples Bay are primary geohazards in the marine and coastal areas, which has been ascertained with significant volcanic and tsunami hazards involving the gulf. Despite previous studies on these topics, much work is still needed to compile a systematic database of the submarine landslides of the Bay of Naples, representing a future step of this research.
Role of IL-33/ST2 Pathway in Inflammatory Bowel Disease: An Overview and Future Perspectives
Authors: Giordano Walter , Ricciardi Gabriele , Casciaro Marco , Fiorentino Vincenzo , Pizzimenti Cristina , Viola Anna , Martini Maurizio , Tuccari Giovanni , Ieni Antonio
Published: May 2024

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions.
Anti-PF4 ELISA-Negative, SRA-Positive Heparin-Induced Thrombocytopenia
Authors: Attah Abraham , Peterson Chelsea , Jacobs Max , Bhagavatula Rama , Shah Deep , Kaplan Robert , Samhouri Yazan
Published: May 2024

Heparin products are frequently used in the inpatient setting to prevent and treat venous thromboembolism, but they simultaneously put patients at risk of developing heparin-induced thrombocytopenia (HIT). The 4Ts score determines the pretest probability of HIT. Diagnosis is made with a screening antiplatelet factor (PF4) immunoassay and the serotonin-release assay (SRA) as a confirmatory test. Anti-PF4 assays have high sensitivity (98%) but lower specificity (50%) and result in frequent false-positive tests. We present a rare case from our institution of a patient with anti-PF4–Polyanion ELISA-negative, SRA-positive HIT and describe the challenges in making a timely diagnosis in this case.
Reconstruction of a Long-Term, Reach-Scale Sediment Budget Using Lateral Channel Movement Data as a Proxy: A Case Study on the Lowland Section of the Tisza River, Hungary
Authors: Kiss Tímea , Tóth Marcell , Török Gergely T. , Sipos György
Published: May 2024

Humans have influenced the sediment transport of rivers on a centurial scale. Our goal was to use the rate of lateral channel processes as a proxy to reconstruct sediment budget (SB) changes of a lowland river (Middle Tisza, Hungary) on a historical scale (1838–2017). The gross sediment budget (GSB) refers to the total area of eroded and accumulated surfaces, and the net sediment budget (NSB) indicates the sediment sink or source characteristics. At the beginning (1838–1890), the artificial cut-offs increased the slope and channel erosion, but the eroded sediment deposited in the oxbows, so the reach acted as a sediment sink (NSB: +0.1–0.8 m2/m/y). Then (1890–1929), a quasi-equilibrium state developed (NSB: −0.2 m2/m/y to +0.4 m2/m/y). Later (1929–1976), the bank protections impeded lateral erosion, so the system became a sediment sink again (NSB: +0.1–0.7 m2/m/y). Finally (1976–2017), the erosional processes accelerated due to dam construction and revetment collapses, and now the river is a sediment source (NSB: −0.03 to −0.08 m2/m/y). This study proved that (1) the actual SB could not be projected in the long term, as it was heavily modified, and (2) lateral channel changes could be used as a proxy to estimate long-term SB.
Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes
Authors: Padron Justin Gary , Saito Reis Chelsea A. , Ng Po’okela K. , Norman Ing Nainoa D. , Baker Hannah , Davis Kamalei , Kurashima Courtney , Kendal-Wright Claire E.
Published: May 2024

Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy.
Long Non-Coding RNAs in Sjögren’s Disease
Authors: Pastva Ondřej , Klein Kerstin
Published: May 2024

Sjögren’s disease (SjD) is a heterogeneous autoimmune disease characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; and chronic pain. Chronic inflammation of the salivary and lacrimal glands, auto-antibody formation, and extra-glandular manifestations occur in subsets of patients with SjD. An aberrant expression of long, non-coding RNAs (lncRNAs) has been described in many autoimmune diseases, including SjD. Here, we review the current literature on lncRNAs in SjD and their role in regulating X chromosome inactivation, immune modulatory functions, and their potential as biomarkers.
Genome-Wide Analysis of C/S1-bZIP Subfamilies in Populus tomentosa and Unraveling the Role of PtobZIP55/21 in Response to Low Energy
Authors: Wu Jiangting , Zhou Mengyan , Cheng Yao , Chen Xin , Yan Shuaixu , Deng Shurong
Published: May 2024

C/S1 basic leucine zipper (bZIP) transcription factors are essential for plant survival under energy deficiency. However, studies on the responses of C/S1-bZIPs to low energy in woody plants have not yet been reported. In this study, members of C/S1-bZIP subfamilies in Populus tomentosa were systematically analyzed using bioinformatic approaches. Four C-bZIPs and 10 S1-bZIPs were identified, and their protein properties, phylogenetic relationships, gene structures, conserved motifs, and uORFs were systematically investigated. In yeast two-hybrid assays, direct physical interactions between C-bZIP and S1-bZIP members were observed, highlighting their potential functional synergy. Moreover, expression profile analyses revealed that low energy induced transcription levels of most C/S1-bZIP members, with bZIP55 and bZIP21 (a homolog of bZIP55) exhibiting particularly significant upregulation. When the expression of bZIP55 and bZIP21 was co-suppressed using artificial microRNA mediated gene silencing in transgenic poplars, root growth was promoted. Further analyses revealed that bZIP55/21 negatively regulated the root development of P. tomentosa in response to low energy. These findings provide insights into the molecular mechanisms by which C/S1-bZIPs regulate poplar growth and development in response to energy deprivation.
Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics
Authors: Yook Hwa Jung , Lee Ji Hyun
Published: May 2024

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review.
DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?
Authors: Tutanov Oleg , Shefer Aleksei , Shefer Evgenii , Ruzankin Pavel , Tsentalovich Yuri , Tamkovich Svetlana
Published: May 2024

Knowledge of the composition of proteins that interact with plasma DNA will provide a better understanding of the homeostasis of circulating nucleic acids and the various modes of interaction with target cells, which may be useful in the development of gene targeted therapy approaches. The goal of the present study is to shed light on the composition and architecture of histone-containing nucleoprotein complexes (NPCs) from the blood plasma of healthy females (HFs) and breast cancer patients (BCPs) and to explore the relationship of proteins with crucial steps of tumor progression: epithelial–mesenchymal transition (EMT), cell proliferation, invasion, cell migration, stimulation of angiogenesis, and immune response. MALDI-TOF mass spectrometric analysis of NPCs isolated from blood samples using affine chromatography was performed. Bioinformatics analysis showed that the shares of DNA-binding proteins in the compositions of NPCs in normal and cancer patients are comparable and amount to 40% and 33%, respectively; in total, we identified 38 types of DNA-binding motifs. Functional enrichment analysis using FunRich 3.13 showed that, in BCP blood, the share of DNA-binding proteins involved in nucleic acid metabolism increased, while the proportion of proteins involved in intercellular communication and signal transduction decreased. The representation of NPC passenger proteins in breast cancer also changes: the proportion of proteins involved in transport increases and the share of proteins involved in energy biological pathways decreases. Moreover, in the HF blood, proteins involved in the processes of apoptosis were more represented in the composition of NPCs and in the BCP blood—in the processes of active secretion. For the first time, bioinformatics approaches were used to visualize the architecture of circulating NPCs in the blood and to show that breast cancer has an increased representation of passenger proteins involved in EMT, cell proliferation, invasion, cell migration, and immune response. Using breast cancer protein data from the Human Protein Atlas (HPA) and DEPC, we found that 86% of NPC proteins in the blood of BCPs were not previously annotated in these databases. The obtained data may indirectly indicate directed protein sorting in NPCs, which, along with extracellular vesicles, can not only be diagnostically significant molecules for liquid biopsy, but can also carry out the directed transfer of genetic material from donor cells to recipient cells.
Unveiling a Microexon Switch: Novel Regulation of the Activities of Sugar Assimilation and Plant-Cell-Wall-Degrading Xylanases and Cellulases by Xlr2 in Trichoderma virens
Authors: Castañeda-Casasola Cynthia Coccet , Nieto-Jacobo María Fernanda , Soares Amanda , Padilla-Padilla Emir Alejandro , Anducho-Reyes Miguel Angel , Brown Chris , Soth Sereyboth , Esquivel-Naranjo Edgardo Ulises , Hampton John , Mendoza-Mendoza Artemio
Published: May 2024

Functional microexons have not previously been described in filamentous fungi. Here, we describe a novel mechanism of transcriptional regulation in Trichoderma requiring the inclusion of a microexon from the Xlr2 gene. In low-glucose environments, a long mRNA including the microexon encodes a protein with a GAL4-like DNA-binding domain (Xlr2-α), whereas in high-glucose environments, a short mRNA that is produced encodes a protein lacking this DNA-binding domain (Xlr2-β). Interestingly, the protein isoforms differ in their impact on cellulase and xylanase activity. Deleting the Xlr2 gene reduced both xylanase and cellulase activity and growth on different carbon sources, such as carboxymethylcellulose, xylan, glucose, and arabinose. The overexpression of either Xlr2-α or Xlr2-β in T. virens showed that the short isoform (Xlr2-β) caused higher xylanase activity than the wild types or the long isoform (Xlr2-α). Conversely, cellulase activity did not increase when overexpressing Xlr2-β but was increased with the overexpression of Xlr2-α. This is the first report of a novel transcriptional regulation mechanism of plant-cell-wall-degrading enzyme activity in T. virens. This involves the differential expression of a microexon from a gene encoding a transcriptional regulator.
Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells
Authors: Lin Ying-Chu , Ku Cha-Chien , Wuputra Kenly , Liu Chung-Jung , Wu Deng-Chyang , Satou Maki , Mitsui Yukio , Saito Shigeo , Yokoyama Kazunari K.
Published: May 2024

The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.
Syncytiotrophoblast Markers Are Downregulated in Placentas from Idiopathic Stillbirths
Authors: Vasconcelos Sara , Moustakas Ioannis , Branco Miguel R. , Guimarães Susana , Caniçais Carla , Helm Talia van der , Ramalho Carla , Marques Cristina Joana , Sousa Lopes Susana M. Chuva de , Dória Sofia
Published: May 2024

The trophoblast cells are responsible for the transfer of nutrients between the mother and the foetus and play a major role in placental endocrine function by producing and releasing large amounts of hormones and growth factors. Syncytiotrophoblast cells (STB), formed by the fusion of mononuclear cytotrophoblasts (CTB), constitute the interface between the foetus and the mother and are essential for all of these functions. We performed transcriptome analysis of human placental samples from two control groups—live births (LB), and stillbirths (SB) with a clinically recognised cause—and from our study group, idiopathic stillbirths (iSB). We identified 1172 DEGs in iSB, when comparing with the LB group; however, when we compared iSB with the SB group, only 15 and 12 genes were down- and upregulated in iSB, respectively. An assessment of these DEGs identified 15 commonly downregulated genes in iSB. Among these, several syncytiotrophoblast markers, like genes from the PSG and CSH families, as well as ALPP, KISS1, and CRH, were significantly downregulated in placental samples from iSB. The transcriptome analysis revealed underlying differences at a molecular level involving the syncytiotrophoblast. This suggests that defects in the syncytial layer may underlie unexplained stillbirths, therefore offering insights to improve clinical obstetrics practice.
BRAF Mutations in Patients with Myeloid Neoplasms: A Cancer Center Multigene Next-Generation Sequencing Analysis Experience
Authors: Fei Fei , Caporale Caitlin , Chang Lisa , Fortini Barbara K. , Ali Haris , Bell Diana , Stein Anthony , Marcucci Guido , Telatar Milhan , Afkhami Michelle
Published: May 2024

BRAF mutations are rare in myeloid neoplasms and are reported to be associated with poor treatment outcomes. The purpose of our study is to characterize BRAF mutations in myeloid neoplasms using a next-generation sequencing (NGS) panel based on the experiences of a single cancer center. We conducted a retrospective review of patients with myeloid neoplasms who underwent the HopeSeq studies between January 2018 and September 2023. A total of 14 patients with myeloid neoplasms carrying BRAF mutations were included in our cohort. The clinical, pathological, and molecular features of these patients were investigated. Our study indicates that BRAF mutations are rare in myeloid neoplasms, constituting only 0.53% (14/2632) of all myeloid neoplasm cases, with the most common BRAF mutation being BRAF V600E (4/14; 28.6%). Interestingly, we observed that six out of seven patients with acute myeloid leukemia (AML) exhibited AML with monocytic differentiation, and all the patients with AML exhibited an extremely poor prognosis compared to those without BRAF mutations. TET2 (5/14; 35.7%), ASXL1 (4/14; 28.6%), and JAK2 (4/14; 28.6%) were the three most frequently co-mutated genes in these patients. Moreover, we noted concurrent KMT2A gene rearrangement with BRAF mutations in three patients with AML (3/7; 42.9%). Our study suggests that although BRAF mutations are rare in myeloid neoplasms, they play a crucial role in the pathogenesis of specific AML subtypes. Furthermore, RAS pathway alterations, including BRAF mutations, are associated with KMT2A gene rearrangement in AML. However, these findings warrant further validation in larger studies.
Sphingosine-1-phosphate Decreases Erythrocyte Dysfunction Induced by β-Amyloid
Authors: Misiti Francesco , Diotaiuti Pierluigi , Lombardo Giovanni Enrico , Tellone Ester
Published: May 2024

Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show red blood cell (RBC) membrane-binding capacity and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Ab-treated RBCs. In RBCs following different treatments, the ATP, 2,3 DPG and cAMP levels and caspase 3 activity were determined by spectrophotometric and immunoassay. S1P rescued the inhibition of ATP release from RBCs triggered by Ab, through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.
Rapid and Sensitive Detection of Verticillium dahliae from Soil Using LAMP-CRISPR/Cas12a Technology
Authors: Fang Yuxiao , Liu Lijuan , Zhao Wenyuan , Dong Linpeng , He Lijuan , Liu Yuhan , Yin Jinyao , Zhang Yufang , Miao Weiguo , Chen Daipeng
Published: May 2024

Cotton Verticillium wilt is mainly caused by the fungus Verticillium dahliae, which threatens the production of cotton. Its pathogen can survive in the soil for several years in the form of microsclerotia, making it a destructive soil-borne disease. The accurate, sensitive, and rapid detection of V. dahliae from complex soil samples is of great significance for the early warning and management of cotton Verticillium wilt. In this study, we combined the loop-mediated isothermal amplification (LAMP) with CRISPR/Cas12a technology to develop an accurate, sensitive, and rapid detection method for V. dahliae. Initially, LAMP primers and CRISPR RNA (crRNA) were designed based on a specific DNA sequence of V. dahliae, which was validated using several closely related Verticillium spp. The lower detection limit of the LAMP-CRISPR/Cas12a combined with the fluorescent visualization detection system is approximately ~10 fg/μL genomic DNA per reaction. When combined with crude DNA-extraction methods, it is possible to detect as few as two microsclerotia per gram of soil, with the total detection process taking less than 90 min. Furthermore, to improve the method’s user and field friendliness, the field detection results were visualized using lateral flow strips (LFS). The LAMP-CRISPR/Cas12a-LFS system has a lower detection limit of ~1 fg/μL genomic DNA of the V. dahliae, and when combined with the field crude DNA-extraction method, it can detect as few as six microsclerotia per gram of soil, with the total detection process taking less than 2 h. In summary, this study expands the application of LAMP-CRISPR/Cas12a nucleic acid detection in V. dahliae and will contribute to the development of field-deployable diagnostic productions.
Exploring the Influence of Cold Plasma on Epidermal Melanogenesis In Situ and In Vitro
Authors: Hasse Sybille , Sommer Marie-Christine , Guenther Sebastian , Schulze Christian , Bekeschus Sander , von Woedtke Thomas
Published: May 2024

Epidermal melanin synthesis determines an individual’s skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.
Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects
Authors: Raphael Kalani L.
Published: May 2024

Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.
Effects of Intracerebral Aminophylline Dosing on Catalepsy and Gait in an Animal Model of Parkinson’s Disease
Authors: de Moraes Santos Corrêa Érica , Christofoletti Gustavo , de Souza Albert Schiaveto
Published: May 2024

Parkinson’s disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey’s post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient’s catalepsy and gait.
Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies
Authors: Pérez-Pérez María-Elena , Nieto-Torres Enrique , Bollain-y-Goytia Juan-José , Delgadillo-Ruíz Lucía
Published: May 2024

The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100–200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case–control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal–Wallis test and Mann–Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.
Genome-Wide Profile of Mutations Induced by Carbon Ion Beam Irradiation of Dehulled Rice Seeds
Authors: Ling Ying , Zhang Yuming , Huang Ming , Guo Tao , Yang Guili
Published: May 2024

As a physical mutagen, carbon ion beam (CIB) irradiation can induce high-frequency mutation, which is user-friendly and environment-friendly in plant breeding. In this study, we resequenced eight mutant lines which were screened out from the progeny of the CIB-irradiated dehulled rice seeds. Among these mutants, CIB induced 135,535 variations, which include single base substitutions (SBSs), and small insertion and deletion (InDels). SBSs are the most abundant mutation, and account for 88% of all variations. Single base conversion is the main type of SBS, and the average ratio of transition and transversion is 1.29, and more than half of the InDels are short-segmented mutation (1–2 bp). A total of 69.2% of the SBSs and InDels induced by CIBs occurred in intergenic regions on the genome. Surprisingly, the average mutation frequency in our study is 9.8 × 10−5/bp and much higher than that of the previous studies, which may result from the relatively high irradiation dosage and the dehulling of seeds for irradiation. By analyzing the mutation of every 1 Mb in the genome of each mutant strain, we found some unusual high-frequency (HF) mutation regions, where SBSs and InDels colocalized. This study revealed the mutation mechanism of dehulled rice seeds by CIB irradiation on the genome level, which will enrich our understanding of the mutation mechanism of CIB radiation and improve mutagenesis efficiency.
ccdC Regulates Biofilm Dispersal in Bacillus velezensis FZB42
Authors: Shao Lin , Shen Zizhu , Li Meiju , Guan Chenyun , Fan Ben , Chai Yunrong , Zhao Yinjuan
Published: May 2024

Bacillus velezensis FZB42 is a plant growth-promoting rhizobacterium (PGPR) and a model microorganism for biofilm studies. Biofilms are required for the colonization and promotion of plant growth in the rhizosphere. However, little is known about how the final stage of the biofilm life cycle is regulated, when cells regain their motility and escape the mature biofilm to spread and colonize new niches. In this study, the non-annotated gene ccdC was found to be involved in the process of biofilm dispersion. We found that the ccdC-deficient strain maintained a wrinkled state at the late stage of biofilm formation in the liquid—gas interface culture, and the bottom solution showed a clear state, indicating that no bacterial cells actively escaped, which was further evidenced by the formation of a cellular ring (biofilm pellicle) located on top of the preformed biofilm. It can be concluded that dispersal, a biofilm property that relies on motility proficiency, is also positively affected by the unannotated gene ccdC. Furthermore, we found that the level of cyclic diguanylate (c-di-GMP) in the ccdC-deficient strain was significantly greater than that in the wild-type strain, suggesting that B. velezensis exhibits a similar mechanism by regulating the level of c-di-GMP, the master regulator of biofilm formation, dispersal, and cell motility, which controls the fitness of biofilms in Pseudomonas aeruginosain. In this study, we investigated the mechanism regulating biofilm dispersion in PGPR.
Endovascular Stent-Graft Repair of True and False Aneurysms of the Splenic Artery
Authors: Borghese Ottavia , Pisani Angelo , Luparelli Antonio , Sica Simona , Minelli Fabrizio , Donati Tommaso , Tshomba Yamume
Published: May 2024

Objective: In treatment of aneurysms (SAAs) and pseudoaneurysms (SAPs) of the splenic artery, endovascular coil embolization is the approach most commonly used as it is minimally invasive and safe. However, it carries a significant rate of primary failure (up to 30%) and might be complicated by splenic infarction. The use of stent grafts might represent a valuable alternative when specific anatomical criteria are respected. We report a comprehensive review on technical and clinical outcomes achieved in this setting. Methods: We performed a comprehensive review of the literature through the MedLine and Cochrane databases (from January 2000 to December 2023) on reported cases of stenting for SAAs and SAPs. Outcomes of interest were clinical and technical success and related complications. The durability of the procedure in the long-term was also investigated. Results: Eighteen papers were included in the analysis, totalling 41 patients (n = 20 male 48.8%, mean age 55.5, range 32–82 years; n = 31, 75.6% SAAs). Mean aneurysm diameter in non-ruptured cases was 35 mm (range 20–67 mm), and most lesions were detected at the proximal third of the splenic artery. Stent grafting was performed in an emergent setting in n = 10 (24.3%) cases, achieving immediate clinical and technical success rate in 90.2% (n = 37) of patients regardless of the type of stent-graft used. There were no procedure-related deaths, but one patient died in-hospital from septic shock and n = 2 (4.9%) patients experienced splenic infarction. At the last available follow-up, the complete exclusion of the aneurysm was confirmed in 87.8% of cases (n = 36/41), while no cases of aneurysm growing nor endoleak were reported. None of the patients required re-intervention during follow-up. Conclusions: When specific anatomical criteria are respected, endovascular repair of SAAs and SAAPs using stent grafts appears to be safe and effective, and seems to display a potential advantage in respect to simple coil embolization, preserving the patient from the risk of end-organ ischemia.
Structural and Color Alterations of Teeth following Orthodontic Debonding: A Systematic Review
Authors: Inchingolo Francesco , Inchingolo Angelo Michele , Riccaldo Lilla , Morolla Roberta , Sardano Roberta , Di Venere Daniela , Palermo Andrea , Inchingolo Alessio Danilo , Dipalma Gianna , Corsalini Massimo
Published: May 2024

Aim: The objective of this study was to explore the effects of fixed orthodontic appliances on enamel structure by assessing microfractures, surface roughness, and alterations in color. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search of online databases was conducted using the keywords ‘enamel’ AND ‘orthodontic debonding’. Eligibility criteria included both in vivo and ex vivo clinical trials conducted on human teeth. Results and Discussion: A total of 14 relevant papers were analyzed. Various instruments and techniques were utilized across different studies to assess surface roughness, color change, and surface fractures. Conclusions: The findings of this study suggest that ceramic brackets may lead to an increase in enamel fractures, particularly during bracket removal. The surface roughness of enamel exhibits variability depending on the adhesive substance and polishing methods used post-removal. Fixed orthodontic appliances could induce changes in enamel color, which may be alleviated by the use of nano-hydroxyapatite or specific polishing techniques. Further research is necessary to identify effective strategies for managing these color changes and improving the overall outcomes of fixed orthodontic treatment.
Similar Recovery Rate for Patients Aged between 50 and 89 Years That Go Home on the Surgery Day and Self-Administer Their Rehabilitation after Kinematically Aligned Total Knee Arthroplasty
Authors: Akhtar Muzammil , Howell Stephen M. , Nedopil Alexander J. , Hull Maury L.
Published: May 2024

Background: for kinematic alignment (KA) total knee arthroplasty (TKA), it was unknown whether ‘the pace of recovery’ at six weeks was different for patients with ages ranging between 50–59, 60–69, 70–79, and 80–89 years who were discharged on the surgery day and self-administered their rehabilitation. Methods: a single surgeon treated 206 consecutive patients with a KA-designed femoral component and an insert with a medial ball-in-socket, lateral flat articulation, and PCL retention. Each filled out preoperative and six-week Oxford Knee Score (OKS), Knee Society Score (KSS), Knee Function Score (KFS), and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaires. The six-week minus preoperative value indicated improvement. Results: between age cohorts, the improvement was not different (p = 0.2319 to 0.9888). The mean improvement/six-week postoperative value was 6°/−2° for knee extension, 0°/119° for knee flexion, 7/31 for the OKS, 39/96 for the KSS, 7/64 for the KFS, and 13/62 for the KOOS. The 30-day hospital readmission rate was 1%. Conclusion: surgeons who perform KA TKA can counsel 50 to 89-year-old patients that they can be safely discharged home on the surgery day with a low risk of readmission and can achieve better function at six weeks than preoperatively when performing exercises without a physical therapist.
Landscape Analysis and Coastal Planning: Ría de Arosa (Pontevedra, Spain)
Authors: Nieto Carlos E. , Martínez-Graña Antonio Miguel , Merchán Leticia
Published: May 2024

Coastal areas are fundamental enclaves for economic and recreational development, attracting a large population worldwide. However, these factors have generated significant pressure on the coastal landscape, requiring territorial management strategies to protect and control its degradation. The coastal landscape, composed of abiotic and biotic elements, plays a crucial role in human wellbeing and the conservation of the natural environment. This study focuses on the southeast area of the Ría de Arosa, on the western coast of Galicia, known for its unique geomorphological features such as estuaries. The main objective is to generate high-resolution thematic maps for territorial planning and conservation of the natural and cultural landscape. Using methodologies based on geographic information systems, various factors of the natural environment will be analyzed to obtain objective results, presenting cartography of landscape units, along with quality and fragility landscape maps. In addition, active strategies are proposed such as multiple land uses or the development of geotourism to preserve, exploit, and manage the landscape better. This work contributes to better understanding the vulnerability of the coastal landscape and provides practical tools for its sustainable management in a context of accelerated global change.
Impact of Urban Expansion on Carbon Emissions in the Urban Agglomerations of Yellow River Basin, China
Authors: Wang Zhenwei , Zeng Yi , Wang Xiaochun , Gu Tianci , Chen Wanxu
Published: May 2024

Continued urban expansion (UE) has long been regarded as a huge challenge for climate change mitigation. However, much less is known about how UE affects carbon emissions (CEs), especially in the urban agglomerations of the Yellow River Basin (UAYRB), China. In this regard, this study introduced kernel density analysis, the Gini coefficient, and Markov chains to reveal the UE patterns and carbon emissions intensity (CEI) in the UAYRB at the county level, and explored the spatial heterogeneity of the impact of UE on CEI with the geographically and temporally weighted regression model. The results show that both CEI and UE in the UAYRB showed a steady growing trend during the study period. The kernel density of CEI and UE revealed that CEI in the UAYRB was weakening, while the UE rate continuously slowed down. The Gini coefficients of both CEI and UE in the UAYRB region were at high levels, indicating obvious spatial imbalance. The Markov transfer probability matrix for CEI with a time span of five years showed that CEI growth will still occur over the next five years, while that of UE was more obvious. Meanwhile, counties with a regression coefficient of UE on CEI higher than 0 covered the majority, and the distribution pattern remained quite stable. The regression coefficients of different urban landscape metrics on CEI in the UAYRB varied greatly; except for the landscape shape index, the regression coefficients of the aggregation index, interspersion and juxtaposition index, and patch density overall remained positive. These findings can advance the policy enlightenment of the high-quality development of the Yellow River Basin.
Identification of Potential Therapeutics of Mentha Essential Oil Content as Antibacterial MDR Agents against AcrAB-TolC Multidrug Efflux Pump from Escherichia coli: An In Silico Exploration
Authors: Alenazy Rawaf
Published: May 2024

Multidrug-resistant bacterial pathogens, such as E. coli, represent a major human health threat. Due to the critical need to overcome this dilemma, since the drug efflux pump has a vital function in the evolution of antimicrobial resistance in bacteria, we have investigated the potential of Mentha essential oil major constituents (1–19) as antimicrobial agents via their ability to inhibit pathogenic DNA gyrase and, in addition, their potential inhibition of the E. coli AcrB-TolC efflux pump, a potential target to inhibit MDR pathogens. The ligand docking approach was conducted to analyze the binding interactions of Mentha EO constituents with the target receptors. The obtained results proved their antimicrobial activity through the inhibition of DNA gyrase (1kzn) with binding affinity ΔG values between −4.94 and −6.49 kcal/mol. Moreover, Mentha EO constituents demonstrated their activity against MDR E. coli by their ability to inhibit AcrB-TolC (4dx7) with ΔG values ranging between −4.69 and −6.39 kcal/mol. The antimicrobial and MDR activity of Mentha EOs was supported via hydrogen bonding and hydrophobic interactions with the key amino acid residues at the binding site of the active pocket of the targeted receptors.