bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis
Authors: Wu Shuo , Zhang Lijie , Zhang Ruidan , Yang Kang , Wei Qin , Jia Qiyu , Guo Jian , Ma Chuang 
Published: March 2023

Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential.Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p &lt; 0.05.Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p &lt; 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8 weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused.Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.
Transposon-derived transcription factors across metazoans
Authors: Mukherjee Krishanu , Moroz Leonid L. 
Published: March 2023

Transposable elements (TE) could serve as sources of new transcription factors (TFs) in plants and some other model species, but such evidence is lacking for most animal lineages. Here, we discovered multiple independent co-options of TEs to generate 788 TFs across Metazoa, including all early-branching animal lineages. Six of ten superfamilies of DNA transposon-derived conserved TF families (ZBED, CENPB, FHY3, HTH-Psq, THAP, and FLYWCH) were identified across nine phyla encompassing the entire metazoan phylogeny. The most extensive convergent domestication of potentially TE-derived TFs occurred in the hydroid polyps, polychaete worms, cephalopods, oysters, and sea slugs. Phylogenetic reconstructions showed species-specific clustering and lineage-specific expansion; none of the identified TE-derived TFs revealed homologs in their closest neighbors. Together, our study established a framework for categorizing TE-derived TFs and informing the origins of novel genes across phyla.
Fusobacterium nucleatum induces a tumor microenvironment with diminished adaptive immunity against colorectal cancers
Authors: Kim Han Sang , Kim Chang Gon , Kim Won Kyu , Kim Kyung-A , Yoo Jinseon , Min Byung Soh , Paik Soonmyung , Shin Sang Joon , Lee Hyukmin , Lee Kyungwon , Kim Hoguen , Shin Eui-Cheol , Kim Tae-Min , Ahn Joong Bae 
Published: March 2023

Background &amp; AimsFusobacterium nucleatum (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated.MethodsThe abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. Ex vivo tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes.ResultsGene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8+ and FoxP3+ regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner.ConclusionFN enhanced the suppressive immune microenvironment with high depletion of CD8+ T cells and enrichment of FoxP3+ regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.
A GHRHR founder mutation causes isolated growth hormone deficiency type IV in a consanguineous Pakistani family
Authors: Ahmad Safeer , Ali Muhammad Zeeshan , Abbasi Sumra Wajid , Abbas Safdar , Ahmed Iftikhar , Abbas Shakil , Nawaz Shoaib , Ziab Mubarak , Ahmed Ikhlak , Fakhro Khalid A. , Khan Muzammil Ahmad , Akil Ammira Al-Shabeeb 
Published: March 2023

BackgroundIsolated growth hormone deficiency (IGHD) is caused by a severe shortage or absence of growth hormone (GH), which results in aberrant growth and development. Patients with IGHD type IV (IGHD4) have a short stature, reduced serum GH levels, and delayed bone age.ObjectivesTo identify the causative mutation of IGHD in a consanguineous family comprising four affected patients with IGHD4 (MIM#618157) and explore its functional impact in silico.MethodsClinical and radiological studies were performed to determine the phenotypic spectrum and hormonal profile of the disease, while whole-exome sequencing (WES) and Sanger sequencing were performed to identify the disease-causing mutation. In-silico studies involved protein structural modeling and docking, and molecular dynamic simulation analyses using computational tools. Finally, data from the Qatar Genome Program (QGP) were screened for the presence of the founder variant in the Qatari population.ResultsAll affected individuals presented with a short stature without gross skeletal anomalies and significantly reduced serum GH levels. Genetic mapping revealed a homozygous nonsense mutation [NM_000823:c.G214T:p.(Glu72*)] in the third exon of the growth-hormone-releasing hormone receptor gene GHRHR (MIM#139191) that was segregated in all patients. The substituted amber codon (UAG) seems to truncate the protein by deleting the C-terminus GPCR domain, thus markedly disturbing the GHRHR receptor and its interaction with the growth hormone-releasing hormone.ConclusionThese data support that a p.Glu72* founder mutation in GHRHR perturbs growth hormone signaling and causes IGHD type IV. In-silico and biochemical analyses support the pathogenic effect of this nonsense mutation, while our comprehensive phenotype and hormonal profiling has established the genotype–phenotype correlation. Based on the current study, early detection of GHRHR may help in better therapeutic intervention.
Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Zhou Juyue , Du Zhonghai , Fu Jie , Yi Xiuxiu 
Published: March 2023

BackgroundCancer is concerning owing to its high mortality rate. Consequently, methods of prolonging the life of patients with cancer have become the primary focus of attention research. In recent years, immune checkpoint inhibitors (ICIs) have achieved good clinical efficacy as antitumor drugs; however, their severe adverse effects have made their use challenging. In order to clarify the predictors of adverse effects, scientists have conducted a series of studies. Blood counts can potentially monitor risk factors associated with the occurrence of immune-related adverse events (irAEs). Herein, a meta-analysis was performed to clarify further the guiding significance of blood counts in the clinical setting.MethodsStudies that satisfied the inclusion criteria were obtained by searching the database. Included studies were those in which irAEs had been observed, and evidence of an association between blood counts and irAEs was reported. The included ones were evaluated for quality. In addition to sensitivity analysis and subgroup analysis, a meta-analysis was performed using the odds ratio (OR) and 95% confidence interval (CI) for each study.ResultsA total of 18 articles were included in our study. The analyses were performed separately according to different blood cell count indicators. The blood cell count metrics associated with irAEs were: absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio.ConclusionOur review and meta-analysis of studies suggest that absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio may serve as predictors of the emergence of irAEs. Given the small number of studies focusing on the relationship between patient blood cell counts and the risk of irAEs, future studies need to further explore the mechanisms of occurrence and potential associations.
Tissue specific imprinting on innate lymphoid cells during homeostasis and disease process revealed by integrative inference of single-cell transcriptomics
Authors: Song Peng , Cao Ke , Mao Yonghuan , Ai Shichao , Sun Feng , Hu Qiongyuan , Liu Song , Wang Meng , Lu Xiaofeng , Guan Wenxian , Shen Xiaofei 
Published: March 2023

IntroductionInnate lymphoid cells (ILCs) are key components of the immune system, yet the similarity and distinction of the properties across tissues under homeostasis, inflammation and tumor process remain elusive.MethodsHere we performed integrative inference of ILCs to reveal their transcriptional profiles and heterogeneity from single-cell genomics. We collected a large number of ILCs from human six different tissues which can represent unique immune niches (circulation, lymphoid tissue, normal and inflamed mucosa, tumor microenvironment), to systematically address the transcriptional imprinting.ResultsILCs are profoundly imprinted by their organ of residence, and tissue-specific distinctions are apparent under pathological conditions. In the hepatocellular carcinoma microenvironment, we identified intermediate c-kit+ ILC2 population, and lin-CD127- NK-like cells that expressed markers of cytotoxicity including CCL5 and IFNG. Additionally, CD127+CD94+ ILC1s were preferentially enriched in inflamed ileum from patients with Crohn’s disease.DiscussionThese analyses depicted a comprehensive characterization of ILC anatomical distribution and subset heterogeneity, and provided a base line for future temporal or spatial studies focused on tissue-specific ILC-mediated immunity.
Humoral and cellular immunogenicity of homologous and heterologous booster vaccination in Ad26.COV2.S-primed individuals: Comparison by breakthrough infection
Authors: Hyun Hakjun , Jang A-Yeung , Park Heedo , Heo Jung Yeon , Seo Yu Bin , Nham Eliel , Yoon Jin Gu , Seong Hye , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Yoon Soo-Young , Seok Jong Hyeon , Kim Jineui , Park Man-Seong , Song Joon Young 
Published: March 2023

BackgroundWhether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised.MethodsA prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3–4 weeks, 3 months, and 6 months after booster vaccination.ResultsA total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections.ConclusionBooster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.
Evaluating historic and modern optical techniques for monitoring phytoplankton biomass in the Atlantic Ocean
Authors: Brewin Robert J. W. , Pitarch Jaime , Dall’Olmo Giorgio , van der Woerd Hendrik J. , Lin Junfang , Sun Xuerong , Tilstone Gavin H. 
Published: March 2023

Traditional measurements of the Secchi depth (zSD) and Forel-Ule colour were collected alongside modern radiometric measurements of ocean clarity and colour, and in-situ measurements of chlorophyll-a concentration (Chl-a), on four Atlantic Meridional Transect (AMT) cruises. These data were used to evaluate historic and modern optical techniques for monitoring Chl-a, and to evaluate remote-sensing algorithms. Historic and modern optical measurements were broadly consistent with current understanding, with Secchi depth inversely related to Forel-Ule colour and to beam and diffuse attenuation, positively related to the ratio of blue to green remote-sensing reflectance and euphotic depth. The relationship between Secchi depth and Forel-Ule on AMT was found to be in closer agreement to historical relationships when using data of the Forel-Ule colour of infinite depth, rather than the Forel-Ule colour of the water above the Secchi disk at half zSD. Over the range of 0.03-2.95 mg m-3, Chl-a was tightly correlated with these optical variables, with the ratio of blue to green remote-sensing reflectance explaining the highest amount of variance in Chl-a (89%), closely followed by the Secchi depth (85%) and Forel-Ule colour (71-81%, depending on the scale used). Existing algorithms that predict Chl-a from these variables were evaluated, and found to perform well, albeit with some systematic differences. Remote sensing algorithms of Secchi depth were in good agreement with in-situ data over the range of values collected (8.5 - 51.8 m, r2&gt;0.77, unbiased root mean square differences around 4.5 m), but with a slight positive bias (2.0 - 5.4 m). Remote sensing algorithms of Forel-Ule agreed well with Forel-Ule colour data of infinite water (r2&gt;0.68, mean differences &lt;1). We investigated the impact of environmental conditions and found wind speed to impact the estimation of zSD, and propose a path forward to include the effect of wind in current Secchi depth theory. We discuss the benefits and challenges of collecting measurements of the Secchi depth and Forel-Ule colour and propose future directions for research. Our dataset is made publicly available to support the research community working on the topic.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis
Authors: Wang Yane , Liu Zhimin , Zhang Mengli , Yu Bo , Ai Fen 
Published: March 2023

ObjectiveMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates the inflammatory immune response and organ dysfunction, which are closely implicated in sepsis pathogenesis and progression. This study aimed to explore the role of MALT1 in sepsis-induced organ injury, immune cell dysregulation, and inflammatory storms.MethodsSeptic mice were constructed by intraperitoneal injection of lipopolysaccharide, followed by overexpression or knockdown of MALT1 by tail vein injection of the corresponding lentivirus. Mouse naïve CD4+ T cells and bone marrow-derived macrophages were treated with MALT1 overexpression/knockdown lentivirus plus lipopolysaccharide.ResultsIn the lungs, livers, and kidneys of septic mice, MALT1 overexpression exaggerated their injuries, as shown by hematoxylin and eosin staining (all p &lt; 0.05), elevated cell apoptosis, as reflected by the TUNEL assay and cleaved caspase-3 expression (p &lt; 0.05 in the lungs and kidneys), and promoted macrophage infiltration, as illustrated by CD68 immunofluorescence (p &lt; 0.05 in the lungs and kidneys). Meanwhile, in the blood, MALT1 overexpression reduced T-helper (Th)1/Th2 cells, increased Th17/regulatory T-cell ratios (both p &lt; 0.05), promoted systematic inflammation, as revealed by tumor necrosis factor-α, interleukin-6, interleukin-1β, and C-reactive protein (all p &lt; 0.05), elevated oxidative stress, as shown by nitric oxide (p &lt; 0.05), superoxide dismutase, and malondialdehyde (p &lt; 0.05), and enhanced liver and kidney dysfunction, as revealed by an automatic animal biochemistry analyzer (all p &lt; 0.05 except for aspartate aminotransferase). However, MALT1 knockdown exerted the opposite effect as MALT1 overexpression. Ex vivo experiments revealed that MALT1 overexpression promoted the polarization of M1 macrophages and naïve CD4+ T cells toward Th2 and Th17 cells (all p &lt; 0.05), while MALT1 knockdown attenuated these effects (all p &lt; 0.05). Mechanistically, MALT1 positively regulated the nuclear factor-κB (NF-κB) pathway both in vivo and ex vivo (p &lt; 0.05).ConclusionMucosa-associated lymphoid tissue lymphoma translocation protein 1 amplifies multiple organ injury, inflammation, oxidative stress, and imbalance of macrophages and CD4+ T cells by activating the NF-κB pathway in sepsis.
Whole-body vibration as a passive alternative to exercise after myocardial damage in middle-aged female rats: Effects on the heart, the brain, and behavior
Authors: Tóth Kata , Oroszi Tamás , Nyakas Csaba , van der Zee Eddy A. , Schoemaker Regien G. 
Published: March 2023

BackgroundFemales with cardiovascular disease seem more vulnerable to develop concomitant mental problems, such as depression and cognitive decline. Although exercise is shown beneficial in cardiovascular disease as well as in mental functions, these patients may be incapable or unmotivated to perform exercise. Whole body vibration (WBV) could provide a passive alternative to exercise. Aim of the present study was to compare WBV to exercise after isoproterenol (ISO)-induced myocardial damage in female rats, regarding effects on heart, brain and behavior.MethodsOne week after ISO (70 mg/kg s.c., on 2 consecutive days) or saline injections, 12 months old female rats were assigned to WBV (10 minutes daily), treadmill running (30 minutes daily) or pseudo intervention for 5 weeks. During the last 10 days, behavioral tests were performed regarding depressive-like behavior, cognitive function, and motor performance. Rats were sacrificed, brains and hearts were dissected for (immuno)histochemistry.ResultsSignificant ISO-induced cardiac collagen deposition (0.67 ± 0.10 vs 0.18 ± 0.03%) was absent after running (0.45 ± 0.26 vs 0.46 ± 0.08%), but not after WBV (0.83 ± 0.12 vs 0.41 ± 0.05%). However, WBV as well as running significantly reduced hippocampal (CA3) collagen content in ISO-treated rats. Significant regional differences in hippocampal microglia activity and brain derived neurotrophic factor (BDNF) expression were observed. Significant ISO-induced CA1 microglia activation was reduced after WBV as well as running, while opposite effects were observed in the CA3; significant reduction after ISO that was restored by WBV and running. Both WBV and running reversed the ISO-induced increased BDNF expression in the CA1, Dentate gyrus and Hilus, but not in the CA3 area. Whereas running had no significant effect on behavior in the ISO-treated rats, WBV may be associated with short-term spatial memory in the novel location recognition test.ConclusionAlthough the female rats did not show the anticipated depressive-like behavior or cognitive decline after ISO, our data indicated regional effects on neuroinflammation and BDNF expression in the hippocampus, that were merely normalized by both WBV and exercise. Therefore, apart from the potential concern about the lack of cardiac collagen reduction, WBV may provide a relevant alternative for physical exercise.