bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of the proto-type basin and tectono-paleogeography of Tarim Block in the Mesozoic
Authors: Li Xiang , Chang Haining , Huang Shaoying , Luo Caiming , Duan Yunjiang , Zhang Hao , Xia Jinkai , Zhong Ziqi , Wei Lunyan
Published: July 2023

The reconstruction of the proto-type basin and tectono-paleogeography of the Tarim Basin during the Mesozoic is crucial for hydrocarbon exploration, particularly for identifying hydrocarbon source rocks. This study reconstructs the position, thickness, and distribution of the original stratigraphy, the shortening amount by structural deformation, and the distribution of sedimentary facies in each Mesozoic period using paleomagnetic data, residual stratigraphy data, seismic profiles, and lithofacies distribution. During the Triassic period, a syn-collision thrust fault structure formed in the southern Tarim Block due to the successive collision of the Tianshuihai-Bayankara terrane, North Qiangtang terrane, and South Qiangtang terrane with the Tarim Block. The sedimentary strata mainly distributed in the Northern Depression and Kuqa Depression, and their sedimentary centers continuously moved northward. In the Early-Middle Jurassic, faulted basins representing post-collision extensional structures developed on the margins of the Tarim Block. In the Late Jurassic, the Tarim Block was compressed, and the faulted basin transformed into a depressional downwarped basin with red coarse clastic sediments due to the collision of the Amdo-Dongkacuo microcontinent with the Tarim Block. In the late Early Cretaceous, the collision between the Lhasa Block and the Tarim Block caused the entire uplift of the Tarim Block, which stopped accepting deposition except for the deposition of marine facies in the southwestern Tarim Basin influenced by a large-scale transgression event. The complex evolution of the Paleo-Tethys and Neo-Tethys Oceans during the Mesozoic significantly influenced the sediment distribution and structural features of the Tarim Basin.
The number of production wells affects the heat extraction performance of an enhanced geothermal system: insights from engineering-scale 3D THM coupling numerical simulations
Authors: Wang Ziwei , Zhang Bo , Yin Likun , Yang Liming , Fan Yifan , Yin Hongmei , Zhao Peng , Liu Jun
Published: July 2023

Enhanced geothermal systems (EGSs) are expected to be one of the most promising methods of supplying energy to meet the world’s increasing energy demand. However, little attention has been paid to the influence of the number of production wells on the heat extraction performance of an EGS. A series of numerical simulations is organized in this work with three cases: Case 1 (one production well), Case 2 (two production wells), and Case 3 (three production wells). The results indicate that a slight temperature difference exists among the three simulation cases at the planes X-Y (Z = 0) and Y-Z (X = 0), while Case 1 ensures a greater cooling area, and the more production wells, the smaller the cooling area during the heat extraction in plane X-Z (Y = 0). In addition, the continuous injection of cooling water from the injection well and its arrival at different reference points enable the temperature at each point to declining with a variable amplitude of variation. This work also sets an efficiency (ef) to investigate the temperature variation in the EGS, where Case 1 exhibits a similar variation as Case 2, which is also similar to Case 3. It is hoped that this work will play a guiding role in EGS-related exploration and exploitation.
Korean immigrants’ perceptions of library services and library multicultural programs for Asian communities before and during COVID-19
Authors: Kim Yanghee , Kim Hyun Chu Leah , Kim Jihye
Published: July 2023

This study explored 141 Korean immigrant parents’ use of local libraries to enhance their families’ social and cultural capital and adjust to the host country. We searched resources in Korean, and multicultural programs planned for the public and immigrants, Asian immigrants in particular, at three libraries before COVID-19 and at two libraries during COVID-19. Parents reported dissatisfaction with library services because of language barriers (38%) and the lack of Korean resources (38%) and cultural programs (25%). Except for 18 books and 24 e-resources, no library resources in Korean were published after 2008. At Branches B and C, before COVID-19, only one multicultural program was offered for children. During COVID-19, hate crimes against Asians increased by 77%. However, at Branches B and C, the number of adult programs related to Asian culture decreased to 0% from 6% and increased to 3% from 0%, respectively, during COVID-19. The respondents’ concerns about the lack of programs supporting their adjustment and fostering multicultural dialog were validated.
A systematic review and meta-analysis of cohort studies on the potential association between NAFLD/MAFLD and risk of incident atrial fibrillation
Authors: Zhou Ben‐Gang , Ju Sheng-Yong , Mei Yu-Zhou , Jiang Xin , Wang Meng , Zheng Ai-Jing , Ding Yan-Bing
Published: July 2023

Background and objective

The association between atrial fibrillation (AF) and non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD) has been explored in recent cohort studies, however, the results have been controversial and inconclusive. This meta-analysis aimed to explore this potential association.

Methods

We systematically searched PubMed, Embase, and Web of Science databases to identify all relevant cohort studies investigating the association between NAFLD/MAFLD and AF published from database inception to October 30, 2022. Random-effects models were utilized to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for summary purposes. Additionally, subgroup and sensitivity analyses were performed.

Results

A total of 13 cohort studies with 14 272 735 participants were included. Among these, 12 cohort studies with 14 213 289 participants (median follow-up of 7.8 years) showed a significant association between NAFLD and an increased risk of incident AF (HR = 1.18, 95% CI: 1.12-1.23, P < 0.00001). Our subgroup analyses mostly yielded similar results, and the results of sensitivity analyses remained unchanged. However, meta-analysis of data from 2 cohort studies with 59 896 participants (median follow-up of 2.15 years) showed that MAFLD was not linked to incident AF (HR = 1.36, 95% CI: 0.63-2.92, P = 0.44).

Conclusion

Current evidence shows that NAFLD may be linked to a slightly higher risk of developing AF, particularly among Asian populations and those diagnosed with NAFLD using FLI criteria. Nevertheless, there is not enough evidence to support the proposed association between MAFLD and an increased risk of AF. To better understand this relationship, future studies should consider factors such as specific population, the severity of NAFLD/MAFLD, diagnostic methods of NAFLD and AF, and cardiometabolic risk factors.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022371503.
The intricate mechanism of PLS3 in bone homeostasis and disease
Authors: Zhong Wenchao , Pathak Janak L. , Liang Yueting , Zhytnik Lidiia , Pals Gerard , Eekhoff Elisabeth M. W. , Bravenboer Nathalie , Micha Dimitra
Published: July 2023

Since our discovery in 2013 that genetic defects in PLS3 lead to bone fragility, the mechanistic details of this process have remained obscure. It has been established that PLS3 variants cause syndromic and nonsyndromic osteoporosis as well as osteoarthritis. PLS3 codes for an actin-bundling protein with a broad pattern of expression. As such, it is puzzling how PLS3 specifically leads to bone-related disease presentation. Our review aims to summarize the current state of knowledge regarding the function of PLS3 in the predominant cell types in the bone tissue, the osteocytes, osteoblasts and osteoclasts. This is related to the role of PLS3 in regulating mechanotransduction, calcium regulation, vesicle trafficking, cell differentiation and mineralization as part of the complex bone pathology presented by PLS3 defects. Considering the consequences of PLS3 defects on multiple aspects of bone tissue metabolism, our review motivates the study of its mechanism in bone diseases which can potentially help in the design of suitable therapy.
Case Report: Prenatal neurological injury in a neonate with pyruvate carboxylase deficiency type B
Authors: Xue Mei
Published: July 2023

Background

Pyruvate carboxylase (PC) is a key enzyme for gluconeogenesis. PC deficiency (PCD) is an extremely rare autosomal recessive metabolic disease and is divided into three types. Type B PCD is clinically featured by lactic acidosis, hyperammonemia, hypercitrullinemia, hypotonia, abnormal movement, and seizures.

Case presentation

Here, we report the first case of type B PCD in China, presenting with intractable lactic acidosis shortly after birth. A compound heterozygous mutation in the PC gene was identified by whole-exome sequencing, NM_001040716.2: c.1154_1155del and c.152G>A, which were inherited from her asymptomatic parents, respectively. Furthermore, prenatal neuroradiological presentations including widened posterior horns of lateral ventricles, huge subependymal cysts, and increased biparietal diameter and head circumference were concerned. Symptomatic treatment was taken and the infant died at 26 days.

Conclusion

To our knowledge, this is the minimum gestational age (22w5d) that’s when the prenatal onset of the neuroradiologic phenotype of PCD was observed. PCD has a poor prognosis and lacks an effective treatment, so this paper is shared to highlight the importance of PCD prenatal diagnosis in the absence of family history.
GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis
Authors: Oteng Antwi-Boasiako , Liu Liu
Published: July 2023

Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.
Pleiotrophin and metabolic disorders: insights into its role in metabolism
Authors: Ballesteros-Pla Cristina , Sánchez-Alonso María Gracia , Pizarro-Delgado Javier , Zuccaro Agata , Sevillano Julio , Ramos-Álvarez María Pilar
Published: July 2023

Pleiotrophin (PTN) is a cytokine which has been for long studied at the level of the central nervous system, however few studies focus on its role in the peripheral organs. The main aim of this review is to summarize the state of the art of what is known up to date about pleiotrophin and its implications in the main metabolic organs. In summary, pleiotrophin promotes the proliferation of preadipocytes, pancreatic β cells, as well as cells during the mammary gland development. Moreover, this cytokine is important for the structural integrity of the liver and the neuromuscular junction in the skeletal muscle. From a metabolic point of view, pleiotrophin plays a key role in the maintenance of glucose and lipid as well as whole-body insulin homeostasis and favors oxidative metabolism in the skeletal muscle. All in all, this review proposes pleiotrophin as a druggable target to prevent from the development of insulin-resistance-related pathologies.
The value of functional magnetic resonance imaging in the evaluation of diabetic kidney disease: a systematic review and meta-analysis
Authors: Zhang Ziqi , Chen Yu , Zhou Xiqiao , Liu Su , Yu Jiangyi
Published: July 2023

Background

The diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold standard, is almost impossible in the assessment of diabetic kidney disease, and the value of functional magnetic resonance imaging in the evaluation of diabetic pathological alterations is increasingly recognized.

Methods

The literature on functional magnetic resonance imaging (fMRI) for the assessment of renal alterations in diabetic kidney disease was searched in PubMed, Web of Science, Cochrane Library, and Embase databases. The search time limit is from database creation to March 10, 2023. RevMan was used to perform a meta-analysis of the main parameters of fMRIs extracted from DKD patients and healthy volunteers (HV).

Results

24 publications (1550 subjects) were included in this study, using five functional MRIs with seven different parameters. The renal blood flow (RBF) values on Arterial spin labeling magnetic resonance imaging (ASL-MRI) was significantly lower in the DKD group than in the HV group. The [WMD=-99.03, 95% CI (-135.8,-62.27), P<0.00001]; Diffusion tensor imaging magnetic resonance imaging (DTI-MRI) showed that the fractional anisotropy (FA) values in the DKD group were significantly lower than that in HV group [WMD=-0.02, 95%CI (-0.03,-0.01), P<0.0001]. And there were no statistically significant differences in the relevant parameters in Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) or Intro-voxel incoherent movement magnetic resonance imaging (IVIM-DWI).

Discussion

ASL and DWI can identify the differences between DKD and HV. DTI has a significant advantage in assessing renal cortical changes; IVIM has some value in determining early diabetic kidney disease from the cortex or medulla. We recommend combining multiple fMRI parameters to assess structural or functional changes in the kidney to make the assessment more comprehensive. We did not observe a significant risk of bias in the present study.

Systematic review registration

https://www.crd.york.ac.uk, identifier CRD42023409249.
Circular RNAs in hepatocellular carcinoma: biogenesis, function, and pathology
Authors: Rao Guocheng , Peng Xi , Tian Yan , Fu Xianghui , Zhang Yuwei
Published: July 2023

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Both genetic and environmental factors through a multitude of underlying molecular mechanisms participate in the pathogenesis of HCC. Recently, numerous studies have shown that circular RNAs (circRNAs), an emerging class of non-coding RNAs characterized by the presence of covalent bonds linking 3’ and 5’ ends, play an important role in the initiation and progression of cancers, including HCC. In this review, we outline the current status of the field of circRNAs, with an emphasis on the functions and mechanisms of circRNAs in HCC and its microenvironment. We also summarize and discuss recent advances of circRNAs as biomarkers and therapeutic targets. These efforts are anticipated to throw new insights into future perspectives about circRNAs in basic, translational and clinical research, eventually advancing the diagnosis, prevention and treatment of HCC.
Structure and function analyses of the Mmd2 gene in pacific white shrimp Litopenaeus vannamei
Authors: Si Shuqing , Zhang Xiaojun , Yu Yang , Zhang Xiaoxi , Zhong Xiaoyun , Yuan Jianbo , Yang Song , Li Fuhua
Published: July 2023

Monocyte to macrophage differentiation factor 2 gene (Mmd2) encodes a member of the progestin and adipoQ receptor (PAQR) family, and plays a key role in growth and development. Our previous studies had found Mmd2 (Monocyte to macrophage differentiation factor 2) is a new candidate gene for growth traits in Pacific white shrimp (Litopenaeus vannamei). For the purpose of understanding the underlying mechanism of LvMmd2 affecting the growth of shrimp, we analyzed the gene structure, phylogeny, expression profiles and RNA interference of this gene in L. vannamei. We found the LvMmd2 gene sequence was highly conserved in transmembrane regions, it was widely expressed in different tissues, with the highest expression level in the eye stalk. Knockdown LvMmd2 could significantly promote body length and body weight gain, suggesting it is a growth suppressor. Through transcriptome analysis we identified 422 differentially expressed genes (DEGs) between the dsMmd2 group and control group, among which 337 genes were upregulated in the dsMmd2 group, including numerous muscle-related genes and protein synthesis genes. Further bioinformatics analysis showed that growth, metabolism, and immune-related signal pathway had changed significantly. The above results greatly increase our understanding on the conservative structure and function of LvMmd2 gene, and provide potential application prospects in genetics and breeding.
Induction of humoral and cell-mediated immunity to the NS1 protein of TBEV with recombinant Influenza virus and MVA affords partial protection against lethal TBEV infection in mice
Authors: Beicht Jana , Kubinski Mareike , Zdora Isabel , Puff Christina , Biermann Jeannine , Gerlach Thomas , Baumgärtner Wolfgang , Sutter Gerd , Osterhaus Albert D. M. E. , Prajeeth Chittappen Kandiyil , Rimmelzwaan Guus F.
Published: July 2023

Introduction

Tick-borne encephalitis virus (TBEV) is one of the most relevant tick-transmitted neurotropic arboviruses in Europe and Asia and the causative agent of tick-borne encephalitis (TBE). Annually more than 10,000 TBE cases are reported despite having vaccines available. In Europe, the vaccines FSME-IMMUN® and Encepur® based on formaldehyde-inactivated whole viruses are licensed. However, demanding vaccination schedules contribute to sub-optimal vaccination uptake and breakthrough infections have been reported repeatedly. Due to its immunogenic properties as well as its role in viral replication and disease pathogenesis, the non-structural protein 1 (NS1) of flaviviruses has become of interest for non-virion based flavivirus vaccine candidates in recent years.

Methods

Therefore, immunogenicity and protective efficacy of TBEV NS1 expressed by neuraminidase (NA)-deficient Influenza A virus (IAV) or Modified Vaccinia virus Ankara (MVA) vectors were investigated in this study.

Results

With these recombinant viral vectors TBEV NS1-specific antibody and T cell responses were induced. Upon heterologous prime/boost regimens partial protection against lethal TBEV challenge infection was afforded in mice.

Discussion

This supports the inclusion of NS1 as a vaccine component in next generation TBEV vaccines.
Are the integrin binding motifs within SARS CoV-2 spike protein and MHC class II alleles playing the key role in COVID-19?
Authors: Gerencer Marijan , McGuffin Liam J.
Published: July 2023

The previous studies on the RGD motif (aa403-405) within the SARS CoV-2 spike (S) protein receptor binding domain (RBD) suggest that the RGD motif binding integrin(s) may play an important role in infection of the host cells. We also discussed the possible role of two other integrin binding motifs that are present in S protein: LDI (aa585-587) and ECD (661-663), the motifs used by some other viruses in the course of infection. The MultiFOLD models for protein structure analysis have shown that the ECD motif is clearly accessible in the S protein, whereas the RGD and LDI motifs are partially accessible. Furthermore, the amino acids that are present in Epstein-Barr virus protein (EBV) gp42 playing very important role in binding to the HLA-DRB1 molecule and in the subsequent immune response evasion, are also present in the S protein heptad repeat-2. Our MultiFOLD model analyses have shown that these amino acids are clearly accessible on the surface in each S protein chain as monomers and in the homotrimer complex and bind to HLA-DRB1 β chain. Therefore, they may have the identical role in SARS CoV-2 immune evasion as in EBV infection. The prediction analyses of the MHC class II binding peptides within the S protein have shown that the RGD motif is present in the core 9-mer peptide IRGDEVRQI within the two HLA-DRB1*03:01 and HLA-DRB3*01.01 strong binding 15-mer peptides suggesting that RGD motif may be the potential immune epitope. Accordingly, infected HLA-DRB1*03:01 or HLA-DRB3*01.01 positive individuals may develop high affinity anti-RGD motif antibodies that react with the RGD motif in the host proteins, like fibrinogen, thrombin or von Willebrand factor, affecting haemostasis or participating in autoimmune disorders.
Muscle fiber necroptosis in pathophysiology of idiopathic inflammatory myopathies and its potential as target of novel treatment strategy
Authors: Kamiya Mari , Kimura Naoki , Umezawa Natsuka , Hasegawa Hisanori , Yasuda Shinsuke
Published: July 2023

Idiopathic inflammatory myopathies (IIMs), which are a group of chronic and diverse inflammatory diseases, are primarily characterized by weakness in the proximal muscles that progressively leads to persistent disability. Current treatments of IIMs depend on nonspecific immunosuppressive agents (including glucocorticoids and immunosuppressants). However, these therapies sometimes fail to regulate muscle inflammation, and some patients suffer from infectious diseases and other adverse effects related to the treatment. Furthermore, even after inflammation has subsided, muscle weakness persists in a significant proportion of the patients. Therefore, the elucidation of pathophysiology of IIMs and development of a better therapeutic strategy that not only alleviates muscle inflammation but also improves muscle weakness without increment of opportunistic infection is awaited. Muscle fiber death, which has been formerly postulated as “necrosis”, is a key histological feature of all subtypes of IIMs, however, its detailed mechanisms and contribution to the pathophysiology remained to be elucidated. Recent studies have revealed that muscle fibers of IIMs undergo necroptosis, a newly recognized form of regulated cell death, and promote muscle inflammation and dysfunction through releasing inflammatory mediators such as damage-associated molecular patterns (DAMPs). The research on murine model of polymyositis, a subtype of IIM, revealed that the inhibition of necroptosis or HMGB1, one of major DAMPs released from muscle fibers undergoing necroptosis, ameliorated muscle inflammation and recovered muscle weakness. Furthermore, not only the necroptosis-associated molecules but also PGAM5, a mitochondrial protein, and reactive oxygen species have been shown to be involved in muscle fiber necroptosis, indicating the multiple target candidates for the treatment of IIMs acting through necroptosis regulation. This article overviews the research on muscle injury mechanisms in IIMs focusing on the contribution of necroptosis in their pathophysiology and discusses the potential treatment strategy targeting muscle fiber necroptosis.
Therapeutically targeting essential metabolites to improve immunometabolism manipulation after liver transplantation for hepatocellular carcinoma
Authors: Zhang Wenhui , Zhao Yu , He Qiang , Lang Ren
Published: July 2023

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy worldwide and is associated with a poor prognosis. Sophisticated molecular mechanisms and biological characteristics need to be explored to gain a better understanding of HCC. The role of metabolites in cancer immunometabolism has been widely recognized as a hallmark of cancer in the tumor microenvironment (TME). Recent studies have focused on metabolites that are derived from carbohydrate, lipid, and protein metabolism, because alterations in these may contribute to HCC progression, ischemia-reperfusion (IR) injury during liver transplantation (LT), and post-LT rejection. Immune cells play a central role in the HCC microenvironment and the duration of IR or rejection. They shape immune responses through metabolite modifications and by engaging in complex crosstalk with tumor cells. A growing number of publications suggest that immune cell functions in the TME are closely linked to metabolic changes. In this review, we summarize recent findings on the primary metabolites in the TME and post-LT metabolism and relate these studies to HCC development, IR injury, and post-LT rejection. Our understanding of aberrant metabolism and metabolite targeting based on regulatory metabolic pathways may provide a novel strategy to enhance immunometabolism manipulation by reprogramming cell metabolism.
Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders
Authors: Gonzalez Caldito Natalia
Published: July 2023

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The cytokine exists as either a transmembrane or a soluble molecule, and targets two distinct receptors, TNF-α receptor 1 (TNFR1) and TNF-α receptor 2 (TNFR2), which activate different signaling cascades and downstream genes. TNF-α cellular responses depend on its molecular form, targeted receptor, and concentration levels. TNF-α plays a multifaceted role in normal physiology that is highly relevant to human health and disease. In the central nervous system (CNS), this cytokine regulates homeostatic functions, such as neurogenesis, myelination, blood-brain barrier permeability and synaptic plasticity. However, it can also potentiate neuronal excitotoxicity and CNS inflammation. The pleiotropism of TNF-α and its various roles in the CNS, whether homeostatic or deleterious, only emphasizes the functional complexity of this cytokine. Anti-TNF-α therapy has demonstrated effectiveness in treating various autoimmune inflammatory diseases and has emerged as a significant treatment option for CNS autoimmune diseases. Nevertheless, it is crucial to recognize that the effects of this therapeutic target are diverse and complex. Contrary to initial expectations, anti-TNF-α therapy has been found to have detrimental effects in multiple sclerosis. This article focuses on describing the various roles, both physiological and pathological, of TNF-α in the CNS. Additionally, it discusses the specific disease processes that are dependent or regulated by TNF-α and the rationale of its use as a therapeutic target.
Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential
Authors: Bao Lei , Zhu Ping , Mou Yuan , Song Yinhong , Qin Ye
Published: July 2023

Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns “cold tumors” into “hot tumors” and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.
HBV-associated DLBCL of poor prognosis: advance in pathogenesis, immunity and therapy
Authors: Wan Xin , Young Ken H. , Bai Ou
Published: July 2023

Advanced studies have shown a biological correlation between hepatitis B virus (HBV) and B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL). Patients with DLBCL infected with HBV (HBV-associated DLBCL) are clinically characterized by an advanced clinical stage, poor response to front-line immunochemotherapy regimens, and worse clinical prognosis. HBV-associated DLBCL often exhibits abnormal activation of the nuclear factor kappa B pathway as well as mutations in oncogenes, including Myc and BCL-6. Currently, there is no consensus on any specific and effective treatment for HBV-associated DLBCL. Therefore, in this review, we comprehensively and mechanistically analyzed the natural history of HBV infection and immunity, including HBV-mediated oncogenes, immune escape, epigenetic alterations, dysregulated signaling pathways, and potential therapeutic approaches for HBV-associated DLBCL. We hope that an improved understanding of the biology of HBV-associated DLBCL would lead to the development of novel therapeutic approaches, enhance the number of effective clinical trials, and improve the prognosis of this disease.
A review of genomics methods and bioinformatics tools for the analysis of close-kin mark-recapture
Authors: Casas Laura , Saborido-Rey Fran
Published: July 2023

Stock assessments serve to monitor the condition of fish stocks and exploit them sustainably but require accurate data such as growth and mortality rates as input parameters. Most species fished worldwide lack the data needed to assess their status and even those closely assessed are often based on parameters that are known to contain uncertainty. This has resulted in an increased share of overfished stocks over the last half century, demanding urgently innovative methodologies that can provide novel means to reduce uncertainty of fish stocks assessments and expand the range of assessed species. CKMR has emerged recently attracting a great interest due to its potential to provide accurate demographic parameters of interest in stock assessments. The method is at the crossroads between fisheries science and genomics, requiring specialized knowledge that is usually outside of the experience of fisheries scientist and modellers, complicating the application of the method and its uptake in regular fisheries assessments. In this review, we provide useful information to perform the genomics and bioinformatics steps required to complete successfully a CKMR study. We discuss the most suitable genomics assays, considering the amount of information they provide, their easiness of use and cost of genotyping accurately the large number of individuals needed to assess most fish stocks. We provide an overview of methods of analysis and statistical methodologies that can be used to infer kinship with the accuracy required in a large population setting with sparse sampling, where most individuals are unrelated, determining a low probability of finding closely related individuals. We analyse potential sources of biases and errors and provide recommendations to facilitate the application of CKMR to a wider range of fish stocks.
Deoxygenation of the Baltic Sea during the last millennium
Authors: Börgel Florian , Neumann Thomas , Rooze Jurjen , Radtke Hagen , Barghorn Leonie , Meier H. E. Markus
Published: July 2023

Over the last 1,000 years, changing climate strongly influenced the ecosystem of coastal oceans such as the Baltic Sea. Sedimentary records revealed that changing temperatures could be linked to changing oxygen levels, spreading anoxic, oxygen-free areas in the Baltic Sea. However, the attribution of changing oxygen levels remains to be challenging. This work simulates a preindustrial period of 850 years, covering the Medieval Climate Anomaly (MCA) and the Little Ice Age using a coupled physical-biogeochemical model. We conduct a set of sensitivity studies that allow us to disentangle the contributions of different biogeochemical processes to increasing hypoxia during the last millennium. We find that the temperature-dependent mineralization rate is a key process contributing to hypoxia formation during the MCA. Faster mineralization enhances the vertical phosphorus flux leading to higher primary production. Our results question the hypothesis that increased cyanobacteria blooms are the reason for increased hypoxia in the Baltic Sea during the MCA. Moreover, the strong contribution of the mineralization rate suggests that the role of temperature-dependent mineralization in current projections should be revisited.
Hidradenitis suppurativa and psoriasis: the odd couple
Authors: Macca Laura , Li Pomi Federica , Ingrasciotta Ylenia , Morrone Pietro , Trifirò Gianluca , Guarneri Claudio
Published: July 2023

Psoriasis and hidradenitis suppurativa are chronic inflammatory skin diseases that can develop together, negatively impacting on the patient’s quality of life. We aimed to review the most up-to-date information regarding the epidemiology, pathogenesis, clinical presentation and possible therapeutical choices in patients with both psoriasis and hidradenitis suppurativa, thus linking these two autoimmune and autoinflammatory conditions. A narrative review of articles dating from 2017 to 2022 has been performed using the PubMed database. We analyzed the case reports and case series found in the literature regarding patients who suffered from both psoriasis and HS. Psoriasis arose before hidradenitis suppurativa in the majority of cases, while only a minority of them had hidradenitis suppurativa before psoriasis. Interestingly, some patients suffered from paradoxical hidradenitis suppurativa following biological therapy administered to treat the already present psoriasis. Lastly, new biological drugs have been marketed with great success for the outcome of psoriasis, but similar progress did not happen for hidradenitis. Novel therapeutic approaches and lines of research are needed for the treatment of these pathologies, even if concomitant, in order to improve patient’s quality of life.
Gut bacteria of adult and larval Cotinis nitida Linnaeus (Coleoptera: Scarabaeidae) demonstrate community differences according to respective life stage and gut region
Authors: Kucuk Roy A. , Campbell Barbara J. , Lyon Nicholas J. , Shelby Emily A. , Caterino Michael S.
Published: July 2023

The close association between bacteria and insect hosts has played an indispensable role in insect diversity and ecology. Thus, continued characterization of such insect-associated-microbial communities is imperative, especially those of saprophagous scarab beetles. The bacterial community of the digestive tract of adults and larvae of the cetoniine scarab species Cotinis nitida is characterized according to life stage, gut structure, and sex via high-throughput 16S rRNA gene amplicon sequencing. Through permutational ANOVAs of the resulting sequences, bacterial communities of the digestive system are shown to differ significantly between adults and larvae in taxon richness, evenness and relatedness. Significant bacterial community-level differences are also observed between the midgut and hindgut in adult beetles, while no significant host-sex differences are observed. The partitioning between bacterial communities in the larval digestive system is shown through significant differences in two distinct hindgut regions, the ileum and the expanded paunch, but not between the midgut and ileum portion of the hindgut region. These data further corroborate the hypothesis of strong community partitioning in the gut of members of the Scarabaeoidea, suggest hypotheses of physiological-digestive association, and also demonstrate the presence of a seemingly unusual non-scarab-associated taxon. These findings contribute to a general portrait of scarabaeoid digestive tract bacterial communities while illuminating the microbiome of a common new world cetoniine of the Gymnetini—a tribe largely neglected in scarab and beetle microbiome and symbiosis literature.
The Helicobacter pylori single nucleotide polymorphisms SNPs associated with multiple therapy resistance in Colombia
Authors: Guzman Kevin , Montenegro Lidia , Pazos Alvaro
Published: July 2023

The eradication of Helicobacter pylori (H. pylori) using multiple therapies is used as a prevention strategy. However, its efficacy has been compromised by the emergence of single nucleotide polymorphisms in genes associated with H. pylori's resistance to multiple antibiotics. To estimate antibiotic resistance rates associated with mutations in H. pylori genes in the high-cancer-risk population in Colombia, we included 166 H. pylori whole genome sequences from a cohort of individuals with a high risk of gastric cancer. By using the reference strain ATCC 26695, we identified mutations in specific genes to evaluate resistance rates for different antibiotics: 23S rRNA for clarithromycin, 16S rRNA for tetracycline, pbp1A for amoxicillin, gyrA for levofloxacin, and rdxA for metronidazole. The phylogenomic analysis was conducted using the core genome consisting of 1,594 genes of H. pylori-ATCC 26695. Our findings revealed that the resistance rate of H. pylori to clarithromycin was 3.62%, primarily associated with mutations A2143G and A2142G in the 23S rRNA gene. For tetracycline, the resistance rate was 7.23%, with mutations A926G, A926T, and A928C observed in the 16S rRNA gene. Amoxicillin resistance was found in 25.9% of cases, with observed mutations in the pbp1A gene, including T556S, T593, R649K, R656P, and R656H. In the gyrA gene, mutations N87K, N87I, D91G, D91N, and D91Y were identified, resulting in a resistance rate of 12.04% to levofloxacin. The most common mutations in the rdxA gene associated with metronidazole resistance were a stop codon, and mutations at D59N and D59S, resulting in a resistance rate of 99.3%. The high resistance rate of H. pylori to metronidazole indicated that this drug should be excluded from the eradication therapy. However, the resistance rates for tetracycline and clarithromycin did not exceed the established resistance threshold in Colombia. The increased resistance rate of H. pylori to levofloxacin and amoxicillin may partially explain the observed therapeutic failures in Colombia. The phylogenomic tree showed that the H. pylori isolate belongs to its own lineage (hspColombia). These findings offer valuable insights to enhance the characterization of treatment protocols for the specific H. pylori lineage (hspColombia) at the local level.
A straightforward approach utilizing an exponential model to compensate for turbidity in chemical oxygen demand measurements using UV-vis spectrometry
Authors: Wang Hongliang , Xiang Houkui , Xiong Tongqiang , Feng Jinping , Zhang Jianquan , Li Xuemei
Published: July 2023

Recently, ultraviolet-visible (UV-vis) absorption spectrometry has garnered considerable attention because it enables real-time and unpolluted detection of chemical oxygen demand (COD) and plays a crucial role in the early warning of emerging organic contaminants. However, the accuracy of detection is inevitably constrained by the co-absorption of organic pollutants and turbidity at UV wavelengths. To ensure accurate detection of COD, it is necessary to directly subtract the absorbance caused by turbidity from the overlaid spectrum using the principle of superposition. The absorbance of COD is confined to the UV range, whereas that of turbidity extends across the entire UV-vis spectrum. Therefore, based on its visible absorbance, the UV absorbance of turbidity can be predicted. In this way, the compensation for turbidity is achieved by subtracting the predicted absorbance from the overlaid spectrum. Herein, a straightforward yet robust exponential model was employed based on this principle to predict the corresponding absorbance of turbidity at UV wavelengths. The model was used to analyze the overlaid absorption spectra of synthetic water samples containing COD and turbidity. The partial least squares (PLS) method was employed to predict the COD concentrations in synthetic water samples based on the compensated spectra, and the corresponding root mean square error (RMSE) values were recorded. The results indicated that the processed spectra yielded a considerably lower RMSE value (9.51) than the unprocessed spectra (29.9). Furthermore, the exponential model outperformed existing turbidity compensation models, including the Lambert-Beer law-based model (RMSE = 12.53) and multiple-scattering cluster method (RMSE = 79.34). Several wastewater samples were also analyzed to evaluate the applicability of the exponential model to natural water. UV analysis yielded undesirable results owing to filtration procedures. However, the consistency between the compensated spectra and filtered wastewater samples in the visible range demonstrated that the model is applicable to natural water. Therefore, this proposed method is advantageous for improving the accuracy of COD measurement in turbid water.
Effects of human probiotics on memory and psychological and physical measures in community-dwelling older adults with normal and mildly impaired cognition: results of a bi-center, double-blind, randomized, and placebo-controlled clinical trial (CleverAge biota)
Authors: Bartos Ales , Weinerova Josefina , Diondet Sofia
Published: July 2023

Objectives

This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at clinicaltrials.gov NCT05051501 and described in detail in our previous paper.

Methods

Community dwelling participants aged between 55 and 80  years were randomly assigned to receive a single dose of 106 colony-forming units of human Streptococcus thermophilus GH, Streptococcus salivarius GH NEXARS, Lactobacilus plantarum GH, and Pediococcus pentosaceus GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3  months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6  months a small number of volunteers were additionally assessed after 2  months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance.

Results

At baseline, the probiotic-placebo group A (n = 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (n = 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8  months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3  months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months.

Conclusion

The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions.

Clinical trial registration

clinicaltrials.gov, identifier NCT05051501.
Enriched environment-induced neuroplasticity in ischemic stroke and its underlying mechanisms
Authors: Han Ping-Ping , Han Yu , Shen Xin-Ya , Gao Zhen-Kun , Bi Xia
Published: July 2023

Stroke is a common cerebrovascular disease that can interrupt local blood flow in the brain, causing neuronal damage or even death, resulting in varying degrees of neurological dysfunction. Neuroplasticity is an important neurological function that helps neurons reorganize and regain function after injury. After cerebral ischemia, neuroplasticity changes are critical factors for restoring brain function. An enriched environment promotes increased neuroplasticity, thereby aiding stroke recovery. In this review, we discuss the positive effects of the enriched environment on neuroplasticity after cerebral ischemia, including synaptic plasticity, neurogenesis, and angiogenesis. In addition, we also introduce some studies on the clinical application of enriched environments in the rehabilitation of post-stroke patients, hoping that they can provide some inspiration for doctors and therapists looking for new approaches to stroke rehabilitation.
RNA atlas and competing endogenous RNA regulation in tissue-derived exosomes from luminal B and triple-negative breast cancer patients
Authors: Wang Ji , Zhang Xianyu , You Zilong , Meng Yuhuan , Fan Xijie , Qiao Guangdong , Pang Da
Published: July 2023

Background

Luminal B and triple-negative breast cancer (TNBC) are malignant subtypes of breast cancer (BC), which can be attributed to the multifaceted roles of tissue-derived exosomes (T-exos). Competing endogenous RNA (ceRNA) networks can regulate gene expression post-transcriptionally.

Methods

RNAs in T-exos from luminal B BC (n=8) and TNBC (n=8) patients were compared with those from persons with benign breast disease (n=8). The differentially expressed (DE) mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) target genes were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the relevant biological processes.The ceRNA networks were constructed to show distinct regulation, and the mRNAs involved were annotated. The miRNAs involved in the ceRNA networks were screened with the Kaplan–Meier Plotter database to identify dysregulated ceRNAs with prognostic power.

Results

In total, 802 DE mRNAs, 441 DE lncRNAs, and 104 DE miRNAs were identified in luminal B BC T-exos, while 1699 DE mRNAs, 590 DE lncRNAs, and 277 DE miRNAs were identified in TNBC T-exos. Gene annotation revealed that the RAS–MAPK pathway was the primary biological process in luminal B BC T-exos, while endocrine system development and growth were the main processes in TNBC T-exos. Survival analysis established seven survival-related lncRNA/miRNA/mRNA regulations in luminal B BC T-exos, and nineteen survival-related lncRNA/miRNA/mRNA regulations in TNBC T-exos.

Conclusion

In addition to survival-related ceRNA regulations, ceRNA regulation of RAS–MAPK in luminal B and endocrine system development and growth regulation in TNBC might contribute to the tumorigenesis of BC.