bluuebunny/crossref_metadata_2025 huggingface dataset:
Context-Aware Point-of-Interest Recommendation Based on Similar User Clustering and Tensor Factorization
Authors: Zhou Yan , Zhou Kaixuan , Chen Shuaixian
Published: March 2023

The rapid development of big data technology and mobile intelligent devices has led to the development of location-based social networks (LBSNs). To understand users’ behavioral patterns and improve the accuracy of location-based services, point-of-interest (POI) recommendation has become an important task. In contrast to the general task of product recommendation, POI recommendation faces the problems of the sparsity and weak semantics of user check-in data. To address these issues, an increasing number of studies have improved the accuracy of POI recommendations by introducing contextual information such as geographical, temporal, textual, and social relations. However, the rich context also brings great challenges to POI recommendation, such as the low utilization rate of context information, difficulty in balancing the richness of contextual information, and the complexity of the recommendation matrix. Considering that similar users have more interest preferences in common than users generally have, the check-in information of similar users has greater reference meaning. Thus, we propose a personalized POI recommendation method named CULT-TF, which incorporates similar users’ contextual information into the tensor factorization model. First, we present a user activity model and a user similarity model, which integrate contextual information to calculate the user activity and similarity between users. According to user activity, the most representative active users are selected as user clustering centers, and then users are clustered based on user similarity into several similar user clusters (C). Next, we construct a third-order tensor (user-location-time matrix) for each user cluster by using user activity, POI popularity, and time slot popularity as the eigenvalues in the user (U), location (L), and time (T) dimensions, and the eigenvalue of each dimension is modeled by integrating contextual information of users’ check-in behavior at the user, location, and time levels. Similar user clustering reduces the number of users in tensor modeling, reducing the U dimension. To further reduce the complexity of the recommendation matrix, the reduction of the L dimension is achieved through ROI (region of interest) clustering, and the reduction of the T dimension is achieved through time slot encoding. Then, we use tensor factorization (TF) to obtain the recommendation results. Our method decreases the complexity of the tensor matrix and integrates rich contextual information on users’ check-in behavior. Finally, we conducted a comprehensive performance evaluation of CULT-TF using real-world LBSN datasets from Brightkite. The experimental results show that our proposed method performs much better than other recommendation methods in terms of precision and recall.
PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression
Authors: Alkaabi Duaa , Arafat Kholoud , Sulaiman Shahrazad , Al-Azawi Aya Mudhafar , Attoub Samir
Published: March 2023

Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively.
The Role of SCL Isoforms in Embryonic Hematopoiesis
Authors: Chuang Chin-Kai , Chen Su-Fen , Su Yu-Hsiu , Chen Wei-Hsin , Lin Wei-Ming , Wang I-Ching , Shyue Song-Kun
Published: March 2023

Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The SCLΔ/Δ homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34+ and CD43+ cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5 SCLΔ/Δ embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.
Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview
Authors: Bianchi Laura , Damiani Isabella , Castiglioni Silvia , Carleo Alfonso , De Salvo Rossana , Rossi Clara , Corsini Alberto , Bellosta Stefano
Published: March 2023

Cigarette smoke (CS) is a risk factor for inflammatory diseases, such as atherosclerosis. CS condensate (CSC) contains lipophilic components that may represent a systemic cardiac risk factor. To better understand CSC effects, we incubated mouse and human aortic smooth muscle cells (SMCs) with CSC. We evaluated specific markers for contractile [i.e., actin, aortic smooth muscle (ACTA2), calponin-1 (CNN1), the Kruppel-like factor 4 (KLF4), and myocardin (MYOCD) genes] and inflammatory [i.e., IL-1β, and IL-6, IL-8, and galectin-3 (LGALS-3) genes] phenotypes. CSC increased the expression of inflammatory markers and reduced the contractile ones in both cell types, with KLF4 modulating the SMC phenotypic switch. Next, we performed a mass spectrometry-based differential proteomic approach on human SMCs and could show 11 proteins were significantly affected by exposition to CSC (FC ≥ 2.7, p ≤ 0.05). These proteins are active in signaling pathways related to expression of pro-inflammatory cytokines and IFN, inflammasome assembly and activation, cytoskeleton regulation and SMC contraction, mitochondrial integrity and cellular response to oxidative stress, proteostasis control via ubiquitination, and cell proliferation and epithelial-to-mesenchymal transition. Through specific bioinformatics resources, we showed their tight functional correlation in a close interaction niche mainly orchestrated by the interferon-induced double-stranded RNA-activated protein kinase (alternative name: protein kinase RNA-activated; PKR) (EIF2AK2/PKR). Finally, by combining gene expression and protein abundance data we obtained a hybrid network showing reciprocal integration of the CSC-deregulated factors and indicating KLF4 and PKR as the most relevant factors.
Mouse Spinal Cord Vascular Transcriptome Analysis Identifies CD9 and MYLIP as Injury-Induced Players
Authors: Martins Isaura , Neves-Silva Dalila , Ascensão-Ferreira Mariana , Dias Ana Filipa , Ribeiro Daniel , Isidro Ana Filipa , Quitéria Raquel , Paramos-de-Carvalho Diogo , Barbosa-Morais Nuno L. , Saúde Leonor
Published: March 2023

Traumatic spinal cord injury (SCI) initiates a cascade of cellular events, culminating in irreversible tissue loss and neuroinflammation. After the trauma, the blood vessels are destroyed. The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, is disrupted, facilitating the infiltration of immune cells, and contributing to a toxic spinal microenvironment, affecting axonal regeneration. Understanding how the vascular constituents of the BSCB respond to injury is crucial to prevent BSCB impairment and to improve spinal cord repair. Here, we focus our attention on the vascular transcriptome at 3- and 7-days post-injury (dpi), during which BSCB is abnormally leaky, to identify potential molecular players that are injury-specific. Using the mouse contusion model, we identified Cd9 and Mylip genes as differentially expressed at 3 and 7 dpi. CD9 and MYLIP expression were injury-induced on vascular cells, endothelial cells and pericytes, at the injury epicentre at 7 dpi, with a spatial expression predominantly at the caudal region of the lesion. These results establish CD9 and MYLIP as two new potential players after SCI, and future studies targeting their expression might bring promising results for spinal cord repair.
Incidence of Bloodstream Infection in Patients with Pulmonary Hypertension under Intravenous Epoprostenol or Iloprost—A Multicentre, Retrospective Study
Authors: Camara Raquel Paulinetti , Coelho Francisco das Neves , Cruz-Martins Natália , Marques-Alves Patrícia , Castro Graça , Baptista Rui , Ferreira Filipa
Published: March 2023

Intravenous synthetic prostacyclin analogs (iPCAs), such as epoprostenol, treprostinil and iloprost have been widely used for the treatment of pulmonary arterial hypertension (PAH). Despite having good outcomes, continuous infusion of iPCAs has been associated with some adverse effects. Bloodstream infection (BSI) is one of the most severe complications, although poorly recognized, especially under iloprost administration, which few studies have addressed. This study aimed to compare the BSI incidence rates between intravenous iloprost and epoprostenol administration. Patients with pulmonary hypertension (PH) functional class III or IV receiving intravenous iloprost or epoprostenol through Hickman catheter, between 2004 and 2019, were retrospectively selected from two PH treatment centers. From a total of 36 patients (13 for iloprost and 23 for epoprostenol), 75% (n = 27) fulfilled the PAH criteria, mainly belonging to the idiopathic group. Overall BSI rate was 1.5/1000 days of treatment (3.38 and 0.09/1000 days for iloprost and epoprostenol, respectively). Patients receiving iloprost were at a higher risk of developing BSI than those receiving epoprostenol (HR: 12.5; 95% CI: 1.569–99.092). A higher mortality rate from BSI was also identified in the iloprost group (p = 0.04). Twenty-seven patients developed BSI, with 92% of them requiring hospitalization. A total of 29 agents were found, 10 Gram-positive (mainly Staphylococcus aureus; n = 5) and 19 Gram-negative (mainly Pseudomonas aeruginosa; n = 6) bacteria. Iloprost administration was linked to a significantly higher incidence of BSI, worse prognosis, and more BSI-related deaths than epoprostenol. BSI due to Gram-negative, commensal, low-virulence bacteria was also higher in the iloprost group. In short, physicians should be aware when prescribing iPCA to guarantee their patients’ safety and best medical care.
Sex Difference in Cardioprotection against Acute Myocardial Infarction in MAO-B Knockout Mice In Vivo
Authors: Heger Jacqueline , Szabados Tamara , Brosinsky Paulin , Bencsik Péter , Ferdinandy Péter , Schulz Rainer
Published: March 2023

The cardiomyocyte-specific knockout (KO) of monoamine oxidase (MAO)-B, an enzyme involved in the formation of reactive oxygen species (ROS), reduced myocardial ischemia/reperfusion (I/R) injury in vitro. Because sex hormones have a strong impact on MAO metabolic pathways, we analyzed the myocardial infarct size (IS) following I/R in female and male MAO-B KO mice in vivo. Method and Results: To induce the deletion of MAO-B, MAO-B KO mice (Myh6 Cre+/MAO-Bfl/fl) and wild-type (WT, Cre-negative MAO-Bfl/fl littermates) were fed with tamoxifen for 2 weeks followed by 10 weeks of normal mice chow. Myocardial infarction (assessed by TTC staining and expressed as a percentage of the area at risk as determined by Evans blue staining)) was induced by 45 min coronary occlusion followed by 120 min of reperfusion. Results: The mortality following I/R was higher in male compared to female mice, with the lowest mortality found in MAO-B KO female mice. IS was significantly higher in male WT mice compared to female WT mice. MAO-B KO reduced IS in male mice but had no further impact on IS in female MAO-B KO mice. Interestingly, there was no difference in the plasma estradiol levels among the groups. Conclusion: The cardiomyocyte-specific knockout of MAO-B protects male mice against acute myocardial infarction but had no effect on the infarct size in female mice.
Glutamate-Evoked Ca2+ Responses in the Rat Suprachiasmatic Nucleus: Involvement of Na+/K+-ATPase and Na+/Ca2+-Exchanger
Authors: Cheng Pi-Cheng , Cheng Ruo-Ciao , Huang Rong-Chi
Published: March 2023

Glutamate mediates photic entrainment of the central clock in the suprachiasmatic nucleus (SCN) by evoking intracellular Ca2+ signaling mechanisms. However, the detailed mechanisms of glutamate-evoked Ca2+ signals are not entirely clear. Here, we used a ratiometric Ca2+ and Na+ imaging technique to investigate glutamate-evoked Ca2+ responses. The comparison of Ca2+ responses to glutamate (100 μM) and high (20 mM) K+ solution indicated slower Ca2+ clearance, along with rebound Ca2+ suppression for glutamate-evoked Ca2+ transients. Increasing the length of exposure time in glutamate, but not in 20 mM K+, slowed Ca2+ clearance and increased rebound Ca2+ suppression, a result correlated with glutamate-induced Na+ loads. The rebound Ca2+ suppression was abolished by ouabain, monensin, Na+-free solution, or nimodipine, suggesting an origin of activated Na+/K+-ATPase (NKA) by glutamate-induced Na+ loads. Ouabain or Na+-free solution also slowed Ca2+ clearance, apparently by retarding Na+/Ca2+-exchanger (NCX)-mediated Ca2+ extrusion. Together, our results indicated the involvement of glutamate-induced Na+ loads, NKA, and NCX in shaping the Ca2+ response to glutamate. Nevertheless, in the absence of external Na+ (NMDG substituted), Ca2+ clearance was still slower for the Ca2+ response to glutamate than for 20 mM K+, suggesting participation of additional Ca2+ handlers to the slower Ca2+ clearance under this condition.
Cancer Cell-Derived PDGFB Stimulates mTORC1 Activation in Renal Carcinoma
Authors: Abuhamad Asmaa Y. , Mohamad Zamberi Nurul Nadia , Vanharanta Sakari , Mohd Yusuf Siti Nur Hasanah , Mohtar M. Aiman , Syafruddin Saiful Effendi
Published: March 2023

Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC.
Editorial to the IJMS Special Issue on “ncRNAS in Therapeutics”
Authors: Hueso Miguel , Navarro Estanis
Published: March 2023

For many years, the RNA world of eukaryotic cells remained stable and predictable, organized by a few families of functionally different molecules [...]
Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick’s Law Model of Diffusion
Authors: Steyn-Ross D. Alistair , Steyn-Ross Moira L. , Sleigh Jamie W. , Voss Logan J.
Published: March 2023

To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and viable. One of the gold-standard approaches to identifying tissue viability status is to measure the rate of tissue oxygen consumption under specific controlled conditions. Here, we work with thin (400 μm) slices of mouse cortical brain tissue which are sustained by a steady flow of oxygenated artificial cerebralspinal fluid (aCSF) at room temperature. To quantify tissue oxygen consumption (Q), we measure oxygen partial pressure (pO2) as a function of probe depth. The curvature of the obtained parabolic (or parabola-like) pO2 profiles can be used to extract Q, providing one knows the Krogh coefficient Kt, for the tissue. The oxygen trends are well described by a Fick’s law diffusion–consumption model developed by Ivanova and Simeonov, and expressed in terms of ratio (Q/K), being the rate of oxygen consumption in tissue divided by the Krogh coefficient (oxygen diffusivity × oxygen solubility) for tissue. If the fluid immediately adjacent to the tissue can be assumed to be stationary (i.e., nonflowing), one may invoke conservation of oxygen flux K·(∂P/∂x) across the interface to deduce (Kt/Kf), the ratio of Krogh coefficients for tissue and fluid. Using published interpolation formulas for the effect of salt content and temperature on oxygen diffusivity and solubility for pure water, we estimate Kf, the Krogh coefficient for aCSF, and hence deduce the Kt coefficient for tissue. We distinguish experimental uncertainty from natural biological variability by using pairs of repeated profiles at the same tissue location. We report a dimensionless Krogh ratio (Kt/Kf)=0.562±0.088 (mean ± SD), corresponding to a Krogh coefficient Kt=(1.29±0.21)×10−14 mol/(m·s·Pa) for mouse cortical tissue at room temperature, but acknowledge the experimental limitation of being unable to verify that the fluid boundary layer is truly stationary. We compare our results with those reported in the literature, and comment on the challenges and ambiguities caused by the extensive use of ‘biologically convenient’ non-SI units for tissue Krogh coefficient.
Study on Properties and Degradation Behavior of Poly (Adipic Acid/Butylene Terephthalate-Co-Glycolic Acid) Copolyester Synthesized by Quaternary Copolymerization
Authors: Wang Yanning , Hou Boyou , Huang Liping , Li Bingjian , Liu Shi , He Mingyang , Chen Qun , Li Jinchun
Published: March 2023

At present, the development and usage of degradable plastics instead of traditional plastics is an effective way to solve the pollution of marine microplastics. Poly (butylene adipate-co-terephthalate) (PBAT) is known as one of the most promising biodegradable materials. Nevertheless, the degradation rate of PBAT in water environment is slow. In this work, we successfully prepared four kinds of high molecular weight polyester copolyesters (PBATGA) via quaternary copolymerization. The results showed that the intrinsic viscosity of PBATGA copolymers ranged from 0.74 to 1.01 dL/g with a glycolic acid content of 0–40%. PBATGA copolymers had excellent flexibility and thermal stability. The tensile strength was 5~40 MPa, the elongation at break was greater than 460%, especially the elongation at break of PBATGA10 at 1235%, and the thermal decomposition temperature of PBATGA copolyesters was higher than 375 °C. It was found that PBATGA copolyester had a faster hydrolysis rate than PBAT, and the weight loss of PBATGA copolymers showed a tendency of pH = 12 > Lipase ≈ pH = 7 > pH = 2. The quaternary polymerization of PBAT will have the advantage of achieving industrialization, unlike the previous polymerization process. In addition, the polymerization of PBATGA copolyesters not only utilizes the by-products of the coal chemical industry, but also it can be promising in the production of biodegradable packaging to reduce marine plastic pollution.
Hydroxy-Selenomethionine Mitigated Chronic Heat Stress-Induced Porcine Splenic Damage via Activation of Nrf2/Keap1 Signal and Suppression of NFκb and STAT Signal
Authors: Liu Yan , Yin Shenggang , He Ying , Tang Jiayong , Pu Junning , Jia Gang , Liu Guangmang , Tian Gang , Chen Xiaoling , Cai Jingyi , Kang Bo , Che Lianqiang , Zhao Hua
Published: March 2023

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.
New Strategies for Endometrial Cancer Detection and Management
Authors: Paleari Laura
Published: March 2023

With 400,000 new cases and over 80,000 deaths a year worldwide, endometrial cancer (EC) holds a rather unfortunate record, namely, that of the tumour with the highest increase in incidence, a unique trend among gynaecological cancers [...]
Oncostatin M-Enriched Small Extracellular Vesicles Derived from Mesenchymal Stem Cells Prevent Isoproterenol-Induced Fibrosis and Enhance Angiogenesis
Authors: Tejedor Sandra , Buigues Marc , González-King Hernán , Silva Andreia M. , García Nahuel Aquiles , Dekker Niek , Sepúlveda Pilar
Published: March 2023

Myocardial fibrosis is a pathological hallmark of cardiac dysfunction. Oncostatin M (OSM) is a pleiotropic cytokine that can promote fibrosis in different organs after sustained exposure. However, OSM released by macrophages during cardiac fibrosis suppresses cardiac fibroblast activation by modulating transforming growth factor beta 1 (TGF-β1) expression and extracellular matrix deposition. Small extracellular vesicles (SEVs) from mesenchymal stromal cells (MSCs) are being investigated to treat myocardial infarction, using different strategies to bolster their therapeutic ability. Here, we generated TERT-immortalized human MSC cell lines (MSC-T) engineered to overexpress two forms of cleavage-resistant OSM fused to CD81TM (OSM-SEVs), which allows the display of the cytokine at the surface of secreted SEVs. The therapeutic potential of OSM-SEVs was assessed in vitro using human cardiac ventricular fibroblasts (HCF-Vs) activated by TGF-β1. Compared with control SEVs, OSM-loaded SEVs reduced proliferation in HCF-V and blunted telo-collagen expression. When injected intraperitoneally into mice treated with isoproterenol, OSM-loaded SEVs reduced fibrosis, prevented cardiac hypertrophy, and increased angiogenesis. Overall, we demonstrate that the enrichment of functional OSM on the surface of MSC-T-SEVs increases their potency in terms of anti-fibrotic and pro-angiogenic properties, which opens new perspectives for this novel biological product in cell-free-based therapies.
Macrophage–Neuroglia Interactions in Promoting Neuronal Regeneration in Zebrafish
Authors: Zeng Chih-Wei
Published: March 2023

The human nervous system exhibits limited regenerative capabilities following damage to the central nervous system (CNS), leading to a scarcity of effective treatments for nerve function recovery. In contrast, zebrafish demonstrate remarkable regenerative abilities, making them an ideal model for studying the modulation of inflammatory processes after injury. Such research holds significant translational potential to enhance our understanding of recovery from damage and disease. Macrophages play a crucial role in tissue repair and regeneration, with their subpopulations indirectly promoting axonal regeneration through developmental signals. The AP-1 signaling pathway, mediated by TNF/Tnfrsf1a, can elevate HDAC1 expression and facilitate regeneration. Furthermore, following spinal cord injury (SCI), pMN progenitors have been observed to switch between oligodendrocyte and motor neuron fates, with macrophage-secreted TNF-α potentially regulating the differentiation of ependymal–radial glia progenitors and oligodendrocytes. Radial glial cells (RGs) are also essential for CNS regeneration in zebrafish, as they perform neurogenesis and gliogenesis, with specific RG subpopulations potentially existing for the generation of neurons and oligodendrocytes. This review article underscores the critical role of macrophages and their subpopulations in tissue repair and regeneration, focusing on their secretion of TNF-α, which promotes axonal regeneration in zebrafish. We also offer insights into the molecular mechanisms underlying TNF-α’s ability to facilitate axonal regeneration and explore the potential of pMN progenitor cells and RGs following SCI in zebrafish. The review concludes with a discussion of various unresolved questions in the field, and ideas are suggested for future research. Studying innate immune cell interactions with neuroglia following injury may lead to the development of novel strategies for treating the inflammatory processes associated with regenerative medicine, which are commonly observed in injury and disease.
The Landscape of Global Ocean Microbiome: From Bacterioplankton to Biofilms
Authors: Lu Jie , Shu Yi , Zhang Heng , Zhang Shangxian , Zhu Chengrui , Ding Wei , Zhang Weipeng
Published: March 2023

The development of metagenomics has opened up a new era in the study of marine microbiota, which play important roles in biogeochemical cycles. In recent years, the global ocean sampling expeditions have spurred this research field toward a deeper understanding of the microbial diversities and functions spanning various lifestyles, planktonic (free-living) or sessile (biofilm-associated). In this review, we deliver a comprehensive summary of marine microbiome datasets generated in global ocean expeditions conducted over the last 20 years, including the Sorcerer II GOS Expedition, the Tara Oceans project, the bioGEOTRACES project, the Micro B3 project, the Bio-GO-SHIP project, and the Marine Biofilms. These datasets have revealed unprecedented insights into the microscopic life in our oceans and led to the publication of world-leading research. We also note the progress of metatranscriptomics and metaproteomics, which are confined to local marine microbiota. Furthermore, approaches to transforming the global ocean microbiome datasets are highlighted, and the state-of-the-art techniques that can be combined with data analyses, which can present fresh perspectives on marine molecular ecology and microbiology, are proposed.
Transcriptome Dynamics Underlying Planticine®-Induced Defense Responses of Tomato (Solanum lycopersicum L.) to Biotic Stresses
Authors: Rakoczy-Lelek Roksana , Czernicka Małgorzata , Ptaszek Magdalena , Jarecka-Boncela Anna , Furmanczyk Ewa M. , Kęska-Izworska Kinga , Grzanka Marlena , Skoczylas Łukasz , Kuźnik Nikodem , Smoleń Sylwester , Macko-Podgórni Alicja , Gąska Klaudia , Chałańska Aneta , Ambroziak Krzysztof , Kardasz Hubert
Published: March 2023

The induction of natural defense mechanisms in plants is considered to be one of the most important strategies used in integrated pest management (IPM). Plant immune inducers could reduce the use of chemicals for plant protection and their harmful impacts on the environment. Planticine® is a natural plant defense biostimulant based on oligomers of α(1→4)-linked D-galacturonic acids, which are biodegradable and nontoxic. The aim of this study was to define the molecular basis of Planticine’s biological activity and the efficacy of its use as a natural plant resistance inducer in greenhouse conditions. Three independent experiments with foliar application of Planticine® were carried out. The first experiment in a climatic chamber (control environment, no pest pressure) subjected the leaves to RNA-seq analysis, and the second and third experiments in greenhouse conditions focused on efficacy after a pest infestation. The result was the RNA sequencing of six transcriptome libraries of tomatoes treated with Planticine® and untreated plants; a total of 3089 genes were found to be differentially expressed genes (DEGs); among them, 1760 and 1329 were up-regulated and down-regulated, respectively. DEG analysis indicated its involvement in such metabolic pathways and processes as plant-pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, photosynthesis, and regulation of transcription. We detected up-regulated gene-encoded elicitor and effector recognition receptors (ELRR and ERR), mitogen-activated protein kinase (MAPKs) genes, and transcription factors (TFs), i.e., WRKY, ERF, MYB, NAC, bZIP, pathogenesis-related proteins (PRPs), and resistance-related metabolite (RRMs) genes. In the greenhouse trials, foliar application of Planticine® proved to be effective in reducing the infestation of tomato leaves by the biotrophic pathogen powdery mildew and in reducing feeding by thrips, which are insect herbivores. Prophylactic and intervention use of Planticine® at low infestation levels allows the activation of plant defense mechanisms.
Pathophysiological Effects of Various Interleukins on Primary Cell Types in Common Heart Disease
Authors: Liu Yong , Zhang Donghui , Yin Dan
Published: March 2023

Myocardial infarction (MI), heart failure, cardiomyopathy, myocarditis, and myocardial ischemia-reperfusion injury (I/R) are the most common heart diseases, yet there is currently no effective therapy due to their complex pathogenesis. Cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), and immune cells are the primary cell types involved in heart disorders, and, thus, targeting a specific cell type for the treatment of heart disease may be more effective. The same interleukin may have various effects on different kinds of cell types in heart disease, yet the exact role of interleukins and their pathophysiological pathways on primary cell types remain largely unexplored. This review will focus on the pathophysiological effects of various interleukins including the IL-1 family (IL-1, IL-18, IL-33, IL-37), IL-2, IL-4, the IL-6 family (IL-6 and IL-11), IL-8, IL-10, IL-17 on primary cell types in common heart disease, which may contribute to the more precise and effective treatment of heart disease.
Real-Time Cost Optimization Approach Based on Deep Reinforcement Learning in Software-Defined Security Middle Platform
Authors: Li Yuancheng , Qin Yongtai
Published: March 2023

In today’s business environment, reducing costs is crucial due to the variety of Internet of Things (IoT) devices and security infrastructure. However, applying security measures to complex business scenarios can lead to performance degradation, making it a challenging task. To overcome this problem, we propose a novel algorithm based on deep reinforcement learning (DRL) for optimizing cost in multi-party computation software-defined security middle platforms (MPC-SDSmp) in real-time. To accomplish this, we first integrate fragmented security requirements and infrastructure into the MPC-SDSmp cloud model with privacy protection capabilities to reduce deployment costs. By leveraging the power of DRL and cloud computing technology, we enhance the real-time matching and dynamic adaptation capabilities of the security middle platform (Smp). This enables us to generate a real-time scheduling strategy for Smp resources that meet low-cost goals to reduce operating costs. Our experimental results demonstrate that the proposed method not only reduces the costs by 13.6% but also ensures load balancing, improves the quality-of-service (QoS) satisfaction by 18.7%, and reduces the average response time by 34.2%. Moreover, our solution is highly robust and better suited for real-time environments compared to the existing methods.
Older but Stronger: Development of Platinum-Based Antitumor Agents and Research Advances in Tumor Immunity
Authors: Liu Jianing , Cao Yi , Hu Bin , Li Tao , Zhang Wei , Zhang Zhongze , Gao Jinhua , Niu Hanjing , Ding Tengli , Wu Jinzhong , Chen Yutong , Zhang Pengfei , Ma Ruijuan , Su Shihao , Wang Chaojie , Wang Peng George , Ma Jing , Xie Songqiang
Published: March 2023

Platinum (Pt) drugs have developed rapidly in clinical applications because of their broad and highly effective antitumor effects. In recent years, with the rapid development of immunotherapy, Pt-based antitumor agents have gained new challenges and opportunities. Since the discovery of their pharmacological effects in immunotherapy and tumor microenvironment regulation, research into Pt drugs has progressed to multi-ligand and multi-functional Pt precursors and their own shortcomings have been further highlighted. With the development of antitumor immunotherapy and the rise of combination therapy, the development of Pt-based drugs has started to move in the direction of multi-targeting, nanocarrier modification, immunotherapy and photodynamic therapy. In this paper, we first overview the recent applications of Pt-based drugs in antitumor inorganic chemistry, with a focus on summarizing the application of Pt-based drugs and their precursors in the anticancer immune response. The paper also provides a reasonable outlook on the future development of Pt-based drugs from the chemical and immunological perspectives, relying on the existing content and problems of Pt-based drug development. On the basis of the gathered information, joint multidisciplinary programs on implementing comprehensive immune analyses for the future development of novel anticancer metal compounds should be initiated.
Scanning Electron Microscopy of Antennae and Mouthparts of Mezira yunnana Hsiao (Hemiptera: Aradidae): Specialized Microstructures Reflecting Adaptation to Mycetophagy
Authors: Zha Shiyu , Wang Zhiyao , Tian Li , Zhao Yisheng , Bai Xiaoshuan , Chen Zhaoyang , Cai Wanzhi , Li Xinyu , Li Hu
Published: March 2023

Many species of the family Aradidae (also known as flat bugs) feed on fungal mycelia and fruiting bodies. In order to better understand the morphological adaptation to this unique feeding habit, we examined the microstructure of antennae and mouthparts of an aradid species, Mezira yunnana Hsiao, using scanning electron microscope, and documented the fungal feeding process under laboratory conditions. The antennal sensilla include three subtypes of sensilla trichodea, three subtypes of sensilla basiconica, two subtypes of sensilla chaetica, sensilla campaniformia, and sensilla styloconica. The apex of the second segment of flagellum has a large number of various sensilla forming a sensilla cluster. The labial tip is distally constricted, which is rarely observed in other Pentatomomorpha species. The labial sensilla include three subtypes of sensilla trichodea, three subtypes of sensilla basiconica, and a sensilla campaniformia. The tip of the labium has only three pairs of sensilla basiconica III and small comb-shaped cuticular processes. The external surface of the mandibular apex has 8–10 ridge-like central teeth. A series of key morphological structures associated with mycetophagous feeding habit were identified, which will facilitate future studies on adaptive evolution of species in Pentatomomorpha as well as in other heteropteran lineages.
Effects of Low-Temperature Acclimation on Nutrients of Bumble Bee Bombus terrestris Queens during Prediapause and Diapause
Authors: Shi Mengnan , Dong Kun , Wu Jie , Huang Jiaxing
Published: March 2023

A queen’s diapause is a key period of the bumble bee life cycle that enables them to survive under unfavorable conditions. During diapause, queens fast, and nutritional reserves depend on the accumulation of nutrients during the prediapause period. Temperature is one of the most important factors affecting queens’ nutrient accumulation during prediapause and nutrient consumption during diapause. Here, we used a 6-day-old mated queen of the bumble bee Bombus terrestris to evaluate the effect of temperature (10, 15, and 25 °C) and time (3, 6, and 9 days) on free water, protein, lipids, and total sugars during prediapause and at the end of 3 months of diapause. Stepwise regression analysis revealed that total sugars, free water, and lipids were much more affected by temperature than protein (p < 0.05). Lower temperature acclimation significantly increased (p < 0.05) free water and lipid accumulation by queens during prediapause. In contrast, higher temperature acclimation significantly increased (p < 0.05) protein and total sugar accumulation by queens during prediapause. The effect of temperature acclimation on the queen survival rate was not significantly different (p > 0.05) after 3 months of diapause. Moreover, lower temperature acclimation reduced protein, lipid, and total sugar consumption by queens during diapause. In conclusion, low-temperature acclimation increases queens’ lipid accumulation during prediapause and reduces the nutritional consumption of queens during diapause. Low-temperature acclimation during prediapause could benefit queens by improving cold resistance and increasing reserves of major nutrient lipids during diapause.
Microplitis manilae Ashmead (Hymenoptera: Braconidae): Biology, Systematics, and Response to Climate Change through Ecological Niche Modelling
Authors: Ghafouri Moghaddam Mostafa , Butcher Buntika A.
Published: March 2023

The parasitoid wasp Microplitis manilae Ashmead (Braconidae: Microgastrinae) is an important natural enemy of caterpillars and of a range of noctuids, including pest species of armyworms (Spodoptera spp.). Here, the wasp is redescribed and, for the first time, illustrated based on the holotype. An updated list of all the Microplitis species attacking the noctuid Spodoptera spp. along with a discussion on host-parasitoid-food plant associations is offered. Based on information about the actual distribution of M. manilae and a set of bioclimatic variables, the maximum entropy (MaxEnt) niche model and the quantum geographic information system (QGIS) were explored to predict the potential distribution of this wasp in a global context. The worldwide geographical distribution of potential climatic suitability of M. manilae at present and in three different periods in the future was simulated. The relative percent contribution score of environmental factors and the Jackknife test were combined to identify dominant bioclimatic variables and their appropriate values influencing the potential distribution of M. manilae. The results showed that under current climate conditions, the prediction of the maximum entropy model highly matches the actual distribution, and that the obtained value of simulation accuracy was very high. Likewise, the distribution of M. manilae was mainly affected by five bioclimatic variables, listed in order of importance as follows: precipitation during the wettest month (BIO13), annual precipitation (BIO12), annual mean temperature (BIO1), temperature seasonality (BIO4), and mean temperature during the warmest quarter (BIO10). In a global context, the suitable habitat of M. manilae would be mainly in tropical and subtropical countries. Furthermore, under the four greenhouse gas concentration scenarios (representative concentration pathways: RCP2.6, RCP4.5, RCP6.0, and RCP8.5) in the future period of the 2070s, the areas with high, medium, and low suitability showed varying degrees of change from current conditions and are expected to expand in the future. This work provides theoretical backing for studies associated with the safeguarding of the environment and pest management.
Assisted Reproductive Technology Results Using Donor or Partner Sperm: A Danish Nationwide Register-Based Cohort Study
Authors: Catalini Laura , Fedder Jens , Nørgård Bente Mertz , Jølving Line Riis
Published: March 2023

This was a nationwide cohort study based on Danish health registers focusing on assisted reproductive technology (ART) treatments in women using donor or partner sperm from 2007 to 2017. Women using donor sperm were subdivided into groups based on relationship status: women with male partners, single women, or women with female partners. The live birth adjusted odds ratios (aORs) after the IUI treatments in women using donor sperm compared with women using partner sperm were 1.48 (95% CI: 1.38–1.59) in women with male partners using donor sperm, 1.20 (95% CI: 1.13–1.28) in single women, and 1.46 (95% CI: 1.32–1.62) in women with female partners. The live birth aORs after IVF treatments in women using donor sperm compared with women using partner sperm were 1.16 (95% CI: 1.02–1.32) in women with male partners using donor sperm, 0.88 (95% CI: 0.80–0.96) in single women, and 1.20 (95% CI: 1.00–1.44), in women with female partners. The use of donor sperm was associated with a higher chance of a live birth after the IUI treatments, but there was no difference after the IVF treatments. Our study invites healthcare professionals to increase their attention toward the different needs and fertility issues of all women attending fertility clinics.
Management of Non-Culprit Lesions in STEMI Patients with Multivessel Disease
Authors: Piccolo Raffaele , Manzi Lina , Simonetti Fiorenzo , Leone Attilio , Angellotti Domenico , Immobile Molaro Maddalena , Verde Nicola , Cirillo Plinio , Di Serafino Luigi , Franzone Anna , Spaccarotella Carmen Anna Maria , Esposito Giovanni
Published: March 2023

Multivessel disease is observed in approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Data from randomized clinical trials has shown that complete revascularization in the STEMI setting improves clinical outcomes by reducing the risk of reinfarction and urgent revascularization. However, the timing and modality of revascularization of non-culprit lesions are still debated. PCI of non-culprit lesions can be performed during the index primary PCI or as a staged procedure and can be guided by angiography, functional assessment, or intracoronary imaging. In this review, we summarize the available evidence about the management of non-culprit lesions in STEMI patients with or without cardiogenic shock.
The Impact of Nonmotor Symptoms on Health-Related Quality of Life in Parkinson’s Disease: A Network Analysis Approach
Authors: Heimrich Konstantin G. , Schönenberg Aline , Santos-García Diego , Mir Pablo ,   COPPADIS Study Group, Prell Tino
Published: March 2023

Nonmotor symptoms negatively affect health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD). However, it is unknown which nonmotor symptoms are most commonly associated with HRQoL. Considering the complex interacting network of various nonmotor symptoms and HRQoL, this study aimed to reveal the network structure, explained HRQoL variance, and identify the nonmotor symptoms that primarily affect HRQoL. We included 689 patients with PD from the Cohort of Patients with Parkinson’s Disease in Spain (COPPADIS) study who were rated on the Nonmotor Symptoms Scale in Parkinson’s disease (NMSS) and the Parkinson´s Disease Questionnaire 39 (PDQ-39) at baseline. Network analyses were performed for the 30 items of the NMSS and both the PDQ-39 summary index and eight subscales. The nodewise predictability, edge weights, strength centrality, and bridge strength were determined. In PD, nonmotor symptoms are closely associated with the mobility, emotional well-being, cognition, and bodily discomfort subscales of the PDQ-39. The most influential nonmotor symptoms were found to be fatigue, feeling sad, hyperhidrosis, impaired concentration, and daytime sleepiness. Further research is needed to confirm whether influencing these non-motor symptoms can improve HRQoL.
Does an Extraoral Suction Device Reduce Aerosol Generation and Prevent Droplet Exposure to the Examiner during Esophagogastroduodenoscopy?
Authors: Fujihara Shintaro , Kobara Hideki , Nishiyama Noriko , Tada Naoya , Goda Yasuhiro , Kozuka Kazuhiro , Matsui Takanori , Chiyo Taiga , Kobayashi Nobuya , Yachida Tatsuo , Masaki Tsutomu
Published: March 2023

Esophagogastroduodenoscopy (EGD) is an aerosol-generating procedure. A major challenge in the COVID-19 era is how to prevent the spread of aerosols and droplets in endoscopic units. We evaluated the effectiveness of an extraoral suction device in preventing indoor aerosol diffusion and droplet exposure for examiners. The study involved 61 patients who underwent EGD at our institution from 1 February to 31 March 2022. To determine whether aerosol spread increases before or after EGD examination with an extraoral suction device located in front of the patient’s mouth, aerosols of 0.3, 0.5, 1, 3, 5, and 10 μm were measured with a handheld particle counter. The degree of contamination of the plastic gowns on the examiners was assessed using the rapid adenosine triphosphate test. The extraoral suction device significantly reduced the diffusion of large particles (3, 5, and 10 μm) after finishing the EGD examination. However, the diffusion of small particles (0.3 and 0.5 μm) was significantly increased. This extraoral suction device was effective in reducing large particle diffusion during EGD examination but was limited for minimizing small particle diffusion or droplet exposure to the examiner.