bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling coordination relationship of forestry industry development and ecological environment: evidence from Heilongjiang Province
Authors: Zhang Qi , Kou Chenhuan , Gao Wenbo
Published: March 2024

China’s economy has entered a new period of transformation, and the development of various industries will become the backbone of promoting economic sectors. At the same time, it will also become a booster for promoting the transformation and development of various industries. As an essential component of China’s economic construction, forestry will also enter a critical period of transformation. However, because the forestry industry mainly relies on forest resources as production factors, there is a certain contradiction between the forestry industry development and the ecological environment. Therefore, taking Heilongjiang Province as an example, this paper applies the PSR model to explain the mechanism of the relationship between forestry industry development and the ecological environment. The PSR model mainly consists of three indicators: Pressure, State, and Response, which analyze the interrelationships between elements within the system. On the other hand, the coupling coordination model is applied to analyze the coupling coordination relationship between the forestry industry development and the ecological environment in Heilongjiang Province from 2011 to 2018. The results show that the development of the forestry industry puts pressure on the ecological environment. At the same time, the environmental climate also imposes restrictions and constraints on the development of the forestry industry. The two promote, influence, and constrain each other. The development of the forestry industry was antagonistic, running in, coupled, and coordinated with the ecological environment in Heilongjiang Province from 2011 to 2018. However, there is still a particular gap in the level of coupling and coordination between the two, and they have yet to reach a state of good coordinated development. Therefore, Heilongjiang Province can promote the coordinated development of its forestry industry and the ecological environment through innovative forestry industry transformation models, policy-oriented rational development and utilization of forest resources, environmentally constrained clean production of the forestry industry, and complementary and shared development of the forestry industry and ecological environment.
Threat categories of Vatica mangachapoi should be reassessed
Authors: Yu Haoze , Pei Xuechen , Zhang Hui
Published: March 2024

Introduction

Asian tropical rainforests have the highest rates of degradation in the world. Consequently, a large decline in Chinese Vatica mangachapoi (a keystone species) had led to its listing in the category of “vulnerable” species by IUCN. However, its current status after decades of conservation efforts remains unknown.

Methods

Here, we evaluate the current status of Chinese V. mangachapoi.

Results and Discussion

We found that its population is now dispersed in 14 protected areas, the largest being a coastal forest that contains 96.84% of all the Chinese V. mangachapoi. Compared to their historic records, the age of this forest was estimated at ≤ 70 years. The mono-culturing of V. mangachapoi in this forest, since 1960, has replaced all the older trees, resulting in its extremely high (91%) relative abundance, and an extensively low (only 44) tree species richness. Further, these V. mangachapoi trees now suffer from vine strangulations and severe Amauroderma perplexum infections: 18.5% of V. mangachapoi have died and 75% are at a high risk, thereby creating a threat of its extinction. Although, the other 13 protected areas have a higher tree species richness (152–451), a lower (6.1–25%) relative abundance of V. mangachapoi, and they neither suffer from vine strangulation or disease infections, they contribute to only 3.16% of total Chinese population of this species. Therefore, an immediate revision of threat status of this species in IUCN, from vulnerable to endangered, is warranted. Further, a change in planting patterns, from monocultures to mix-plantations of native species, is needed to promote biodiversity and restrict other biotic challenges so that this species is not extinct.
Uganda chicken genetic resources: II. genetic diversity and population demographic history inferred from mitochondrial DNA D-loop sequences
Authors: Yussif Illyass , Kugonza Donald Rugira , Masembe Charles
Published: March 2024

The genetic diversity of indigenous chickens, which comprise over 80% of the chicken resources in Uganda, is largely not well-characterized for their genetic contribution. This study assessed the genetic diversity and population structure of the indigenous chicken population in Uganda to serve as an essential component for improvement and conservation strategies. A set of 344 mitochondrial DNA (mtDNA) D-loop sequences among 12 Ugandan chicken populations was evaluated. Twenty-eight polymorphic sites, accounting for 4.26% of the total analyzed loci of 658 bp, defined 32 haplotypes. The haplotype diversity (Hd) was 0.437, with a nucleotide diversity (π) of 0.0169, while the average number of nucleotide differences (k) was 0.576, indicating a population that is moderately genetically diverse. Analysis of molecular variance found 98.39% (ρ < 0.01) of the total sequence variation among the chicken haplotypes within populations, 1.08% (ρ < 0.05) among populations, and 0.75% (ρ > 0.05) among populations within regions. This revealed subtle genetic differentiation among the populations, which appeared to be influenced by population fragmentation, probably due to neutral mutation, random genetic drift, and/or balancing selection. All the haplotypes showed affinity exclusively to the haplogroup-E mtDNA phylogeny, with haplotype UGA01 signaling an ancestral haplotype in Uganda. Neutrality tests Tajima’s D (−2.320) and Fu’s Fs (−51.369), augmented with mismatch distribution to measure signatures of recent historical demographic events, supported a population expansion across the chicken populations. The results show one matrilineal ancestry of Ugandan chickens from a lineage widespread throughout the world that began in the Indian subcontinent. The lack of phylogeographic signals is consistent with recent expansion events with extensive within-country genetic intermixing among haplotypes. Thus, the findings in this study hold the potential to guide conservation strategies and breeding programs in Uganda, given that higher genetic diversity comes from within the chicken population.
Mendelian randomization study shows no causal relationship between psychiatric disorders and glaucoma in European and East Asian populations
Authors: Zhang Yan , Fu Longhui , Feng Fang , Liu Bo , Lei Ying , Kang Qianyan
Published: March 2024

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis.

Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test.

Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93–1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63–2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93–1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75–2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83–1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94–1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction (p < 0.001).

Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable.
Searching for gene-gene interactions through variance quantitative trait loci of 29 continuous Taiwan Biobank phenotypes
Authors: Lin Wan-Yu
Published: March 2024

Introduction: After the era of genome-wide association studies (GWAS), thousands of genetic variants have been identified to exhibit main effects on human phenotypes. The next critical issue would be to explore the interplay between genes, the so-called “gene-gene interactions” (GxG) or epistasis. An exhaustive search for all single-nucleotide polymorphism (SNP) pairs is not recommended because this will induce a harsh penalty of multiple testing. Limiting the search of epistasis on SNPs reported by previous GWAS may miss essential interactions between SNPs without significant marginal effects. Moreover, most methods are computationally intensive and can be challenging to implement genome-wide.

Methods: I here searched for GxG through variance quantitative trait loci (vQTLs) of 29 continuous Taiwan Biobank (TWB) phenotypes. A discovery cohort of 86,536 and a replication cohort of 25,460 TWB individuals were analyzed, respectively.

Results: A total of 18 nearly independent vQTLs with linkage disequilibrium measure r2 < 0.01 were identified and replicated from nine phenotypes. 15 significant GxG were found with p-values <1.1E-5 (in the discovery cohort) and false discovery rates <2% (in the replication cohort). Among these 15 GxG, 11 were detected for blood traits including red blood cells, hemoglobin, and hematocrit; 2 for total bilirubin; 1 for fasting glucose; and 1 for total cholesterol (TCHO). All GxG were observed for gene pairs on the same chromosome, except for the APOA5 (chromosome 11)—TOMM40 (chromosome 19) interaction for TCHO.

Discussion: This study provided a computationally feasible way to search for GxG genome-wide and applied this approach to 29 phenotypes.
In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced
Authors: Reinehr Sabrina , Wulf Julien , Theile Janine , Schulte Kim K. , Peters Marcus , Fuchshofer Rudolf , Dick H. Burkhard , Joachim Stephanie C.
Published: March 2024

Background

The neurodegenerative processes leading to glaucoma are complex. In addition to elevated intraocular pressure (IOP), an involvement of immunological mechanisms is most likely. In the new multifactorial glaucoma model, a combination of high IOP and optic nerve antigen (ONA) immunization leads to an enhanced loss of retinal ganglion cells accompanied by a higher number of microglia/macrophages in the inner retina. Here, we aimed to evaluate the immune response in this new model, especially the complement activation and the number of T-cells, for the first time. Further, the microglia/macrophage response was examined in more detail.

Methods

Six-week-old wildtype (WT+ONA) and βB1-connective tissue growth factor high-pressure mice (CTGF+ONA) were immunized with 1 mg ONA. A wildtype control (WT) and a CTGF group (CTGF) received NaCl instead. Six weeks after immunization, retinae from all four groups were processed for immunohistology, RT-qPCR, and flow cytometry, while serum was used for microarray analyses.

Results

We noticed elevated numbers of C1q+ cells (classical complement pathway) in CTGF and CTGF+ONA retinae as well as an upregulation of C1qa, C1qb, and C1qc mRNA levels in these groups. While the complement C3 was only increased in CTGF and CTGF+ONA retinae, enhanced numbers of the terminal membrane attack complex were noted in all three glaucoma groups. Flow cytometry and RT-qPCR analyses revealed an enhancement of different microglia/macrophages markers, including CD11b, especially in CTGF and CTGF+ONA retinae. Interestingly, increased retinal mRNA as well as serum levels of the tumor necrosis factor α were found throughout the different glaucoma groups. Lastly, more T-cells could be observed in the ganglion cell layer of the new CTGF+ONA model.

Conclusion

These results emphasize an involvement of the complement system, microglia/macrophages, and T-cells in glaucomatous disease. Moreover, in the new multifactorial glaucoma model, increased IOP in combination with autoimmune processes seem to enforce an additional T-cell response, leading to a more persistent pathology. Hence, this new model mimics the pathomechanisms occurring in human glaucoma more accurately and could therefore be a helpful tool to find new therapeutic approaches for patients in the future.
ROS signaling in innate immunity via oxidative protein modifications
Authors: Manoharan Renuka Ramalingam , Prasad Ankush , Pospíšil Pavel , Kzhyshkowska Julia
Published: March 2024

The innate immune response represents the first-line of defense against invading pathogens. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in various aspects of innate immune function, which involves respiratory bursts and inflammasome activation. These reactive species widely distributed within the cellular environment are short-lived intermediates that play a vital role in cellular signaling and proliferation and are likely to depend on their subcellular site of formation. NADPH oxidase complex of phagocytes is known to generate superoxide anion radical (O2•−) that functions as a precursor for antimicrobial hydrogen peroxide (H2O2) production, and H2O2 is utilized by myeloperoxidase (MPO) to generate hypochlorous acid (HOCl) that mediates pathogen killing. H2O2 modulates the expression of redox-responsive transcriptional factors, namely NF-kB, NRF2, and HIF-1, thereby mediating redox-based epigenetic modification. Survival and function of immune cells are under redox control and depend on intracellular and extracellular levels of ROS/RNS. The current review focuses on redox factors involved in the activation of immune response and the role of ROS in oxidative modification of proteins in macrophage polarization and neutrophil function.
Optimization of surface roughness in milling of EN 24 steel with WC-Coated inserts using response surface methodology: analysis using surface integrity microstructural characterizations
Authors: Patil Shashwath , Sathish Thanikodi , Rao P. S. , Prabhudev M. S. , Vijayan V. , Rajkumar S. , Sharma Shubham , Kumar Abhinav , Abbas Mohamed , Makki Emad
Published: March 2024

Introduction: Among alloys of medium-carbon and high-strength steel, EN 24 steel is characterised by its nickel-chromium-molybdenum composition. EN 24 steel is highly suitable for application in heavy-duty projects due to its notable resilience to damage, especially when exposed to low temperatures. With the objective of minimising surface irregularities, this research endeavours to enhance the milling process of EN 24 steel by employing coated tungsten carbide (WC) tool inserts.

Methods: Feed rate, cutting speed, depth of cut, and cutting fluid are all crucial process factors in the experimental investigation. Four distinct levels are applied to each factor. The research utilises the Design of Experiments (DOE)-based Central Composite Design of Response Surface Methodology. To predict output parameters, mathematical models are developed utilising analysis of variance (ANOVA) for optimisation purposes.

Results and discussions: Through the utilisation of multi-objective optimisation, the optimal combination for tungsten carbide inserts was determined, which provided surface irregularities of 0.301 µm. Cutting speed (CS) of 149.507 m/min, feed rate (FR) of 340.27 mm/min, depth of cut (DOC) of 0.599 mm, and cutting fluid (CF) of 12.50 L/min are the optimal parameters. The surface morphologies of the machined workpiece at particular parameter values can be discerned through scanning electron microscope (SEM) analysis, yielding significant insights. The optimal parameters that have been identified provide practical recommendations for improving the milling method of EN 24 steel when tungsten carbide inserts are utilised. Understanding the milling process in its entirety is facilitated by SEM analysis of surface morphologies and microstructures under particular cutting conditions. The morphology and surface irregularities of the machined workpiece are evaluated using profilometry, which provides additional insight into surface integrity. The discourse investigates the potential applications and implications of the results, as well as suggests directions for further study concerning the enhancement of milling processes for similar steel alloys.
Advantages of Chinese herbal medicine in treating rheumatoid arthritis: a focus on its anti-inflammatory and anti-oxidative effects
Authors: Wang Xiaoyu , Kong Youqian , Li Zeguang
Published: March 2024

Oxidative stress is a condition characterized by an imbalance between the oxidative and antioxidant processes within the human body. Rheumatoid arthritis (RA) is significantly influenced by the presence of oxidative stress, which acts as a pivotal factor in its pathogenesis. Elevated levels of mitochondrial reactive oxygen species (ROS) and inflammation have been found to be closely associated in the plasma of patients with RA. The clinical treatment strategies for this disease are mainly chemical drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids (GCs) and biological agents, but it is difficult for patients to accept long-term drug treatment and its side effects. In the theory of traditional Chinese medicine (TCM), RA is thought to be caused by the attack of “wind, cold, damp humor,” and herbs with the effect of removing wind and dampness are used to relieve pain. Chinese herbal medicine boasts a rich heritage in effectively attenuating the symptoms of RA, and its global recognition continues to ascend. In particular, RA-relevant anti-inflammatory/anti-oxidative effects of TCM herbs/herbal compounds. The main aim of this review is to make a valuable contribution to the expanding pool of evidence that advocates for the incorporation of Chinese herbal medicine in conventional treatment plans for RA.
Association between gut microbiota and menstrual disorders: a two-sample Mendelian randomization study
Authors: Yao Yufan , Hu Haoran , Chen Longhao , Zheng Hong
Published: March 2024

Background

Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with gynecological diseases. However, the causal relationship between gut microbiota and menstrual disorders remains to be determined.

Methods

We obtained summary data of gut microbiota from the global consortium MiBio-Gen’s genome-wide association study (GWAS) dataset and data on menstrual disorders from the IEU Open GWAS project. MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode were used to examine the causal association between gut microbiota and menstrual disorders. Thorough sensitivity studies were performed to confirm the data’s horizontal pleiotropy, heterogeneity, and robustness.

Results

Through MR analysis of 119 kinds of gut microbiota and 4 kinds of clinical phenotypes, it was discovered that 23 different kinds of gut microbiota were loosely connected to menstrual disorders. After FDR correction, the results showed that only Escherichia/Shigella (p = 0.00032, PFDR = 0.0382, OR = 1.004, 95%CI = 1.002–1.006) is related to menstrual disorders.

Conclusion

According to our MR Analysis, there are indications of a causal relationship between menstrual disorders and gut microbiota. This finding could lead to new discoveries into the mechanisms behind menstrual disorders and clinical research involving the microbiota.
Comparative metabarcoding and biodiversity of gut-associated fungal assemblages of Dendroctonus species (Curculionidae: Scolytinae)
Authors: Pineda-Mendoza Rosa María , Gutiérrez-Ávila Jorge Luis , Salazar Kevin F. , Rivera-Orduña Flor N. , Davis Thomas S. , Zúñiga Gerardo
Published: March 2024

The genus Dendroctonus is a Holarctic taxon composed of 21 nominal species; some of these species are well known in the world as disturbance agents of forest ecosystems. Under the bark of the host tree, these insects are involved in complex and dynamic associations with phoretic ectosymbiotic and endosymbiotic communities. Unlike filamentous fungi and bacteria, the ecological role of yeasts in the bark beetle holobiont is poorly understood, though yeasts were the first group to be recorded as microbial symbionts of these beetles. Our aim was characterize and compare the gut fungal assemblages associated to 14 species of Dendroctonus using the internal transcribed spacer 2 (ITS2) region. A total of 615,542 sequences were recovered yielding 248 fungal amplicon sequence variants (ASVs). The fungal diversity was represented by 4 phyla, 16 classes, 34 orders, 54 families, and 71 genera with different relative abundances among Dendroctonus species. The α-diversity consisted of 32 genera of yeasts and 39 genera of filamentous fungi. An analysis of β-diversity indicated differences in the composition of the gut fungal assemblages among bark beetle species, with differences in species and phylogenetic diversity. A common core mycobiome was recognized at the genus level, integrated mainly by Candida present in all bark beetles, Nakazawaea, Cladosporium, Ogataea, and Yamadazyma. The bipartite networks confirmed that these fungal genera showed a strong association between beetle species and dominant fungi, which are key to maintaining the structure and stability of the fungal community. The functional variation in the trophic structure was identified among libraries and species, with pathotroph-saprotroph-symbiotroph represented at the highest frequency, followed by saprotroph-symbiotroph, and saprotroph only. The overall network suggested that yeast and fungal ASVs in the gut of these beetles showed positive and negative associations among them. This study outlines a mycobiome associated with Dendroctonus nutrition and provides a starting point for future in vitro and omics approaches addressing potential ecological functions and interactions among fungal assemblages and beetle hosts.
From acidophilic to ornithogenic: microbial community dynamics in moss banks altered by gentoo penguins
Authors: Prekrasna-Kviatkovska Yevheniia , Parnikoza Ivan , Yerkhova Anna , Stelmakh Olesia , Pavlovska Mariia , Dzyndra Marta , Yarovyi Oleksandr , Dykyi Evgen
Published: March 2024

Introduction

The study explores the indirect impact of climate change driven by gentoo’s penguin colonization pressure on the microbial communities of moss banks formed by Tall moss turf subformation in central maritime Antarctica.

Methods

Microbial communities and chemical composition of the differently affected moss banks (Unaffected, Impacted and Desolated) located on Galindez Island and Сape Tuxen on the mainland of Kyiv Peninsula were analyzed.

Results

The native microbiota of the moss banks’ peat was analyzed for the first time, revealing a predominant presence of Acidobacteria (32.2 ± 14.4%), followed by Actinobacteria (15.1 ± 4.0%) and Alphaproteobacteria (9.7 ± 4.1%). Penguin colonization and subsequent desolation of moss banks resulted in an increase in peat pH (from 4.7 ± 0.05 to 7.2 ± 0.6) and elevated concentrations of soluble nitrogen (from 1.8 ± 0.4 to 46.9 ± 2.1 DIN, mg/kg) and soluble phosphorus compounds (from 3.6 ± 2.6 to 20.0 ± 1.8 DIP, mg/kg). The contrasting composition of peat and penguin feces led to the elimination of the initial peat microbiota, with an increase in Betaproteobacteria (from 1.3 ± 0.8% to 30.5 ± 23%) and Bacteroidota (from 5.5 ± 3.7% to 19.0 ± 3.7%) proportional to the intensity of penguins’ impact, accompanied by a decrease in community diversity. Microbial taxa associated with birds’ guts, such as Gottschalkia and Tissierella, emerged in Impacted and Desolated moss banks, along with bacteria likely benefiting from eutrophication. The changes in the functional capacity of the penguin-affected peat microbial communities were also detected. The nitrogen-cycling genes that regulate the conversion of urea into ammonia, nitrite oxide, and nitrate oxide (ureC, amoA, nirS, nosZ, nxrB) had elevated copy numbers in the affected peat. Desolated peat samples exhibit the highest nitrogen-cycle gene numbers, significantly differing from Unaffected peat (p < 0.05).

Discussion

The expansion of gentoo penguins induced by climate change led to the replacement of acidophilic microbiomes associated with moss banks, shaping a new microbial community influenced by penguin guano’s chemical and microbial composition.
Remote memory in a Bayesian model of context fear conditioning (BaconREM)
Authors: Krasne Franklin B. , Fanselow Michael S.
Published: March 2024

Here, we propose a model of remote memory (BaconREM), which is an extension of a previously published Bayesian model of context fear learning (BACON) that accounts for many aspects of recently learned context fear. BaconREM simulates most known phenomenology of remote context fear as studied in rodents and makes new predictions. In particular, it predicts the well-known observation that fear that was conditioned to a recently encoded context becomes hippocampus-independent and shows much-enhanced generalization (“hyper-generalization”) when systems consolidation occurs (i.e., when memory becomes remote). However, the model also predicts that there should be circumstances under which the generalizability of remote fear may not increase or even decrease. It also predicts the established finding that a “reminder” exposure to a feared context can abolish hyper-generalization while at the same time making remote fear again hippocampus-dependent. This observation has in the past been taken to suggest that reminders facilitate access to detail memory that remains permanently in the hippocampus even after systems consolidation is complete. However, the present model simulates this result even though it totally moves all the contextual memory that it retains to the neo-cortex when context fear becomes remote.
Glitches in the brain: the dangerous relationship between radiotherapy and brain fog
Authors: Marino Noemi , Bedeschi Martina , Vaccari Melania Elettra , Cambiaghi Marco , Tesei Anna
Published: March 2024

Up to approximately 70% of cancer survivors report persistent deficits in memory, attention, speed of information processing, multi-tasking, and mental health functioning, a series of symptoms known as “brain fog.” The severity and duration of such effects can vary depending on age, cancer type, and treatment regimens. In particular, every year, hundreds of thousands of patients worldwide undergo radiotherapy (RT) for primary brain tumors and brain metastases originating from extracranial tumors. Besides its potential benefits in the control of tumor progression, recent studies indicate that RT reprograms the brain tumor microenvironment inducing increased activation of microglia and astrocytes and a consequent general condition of neuroinflammation that in case it becomes chronic could lead to a cognitive decline. Furthermore, radiation can induce endothelium reticulum (ER) stress directly or indirectly by generating reactive oxygen species (ROS) activating compensatory survival signaling pathways in the RT-surviving fraction of healthy neuronal and glial cells. In particular, the anomalous accumulation of misfolding proteins in neuronal cells exposed to radiation as a consequence of excessive activation of unfolded protein response (UPR) could pave the way to neurodegenerative disorders. Moreover, exposure of cells to ionizing radiation was also shown to affect the normal proteasome activity, slowing the degradation rate of misfolded proteins, and further exacerbating ER-stress conditions. This compromises several neuronal functions, with neuronal accumulation of ubiquitinated proteins with a consequent switch from proteasome to immunoproteasome that increases neuroinflammation, a crucial risk factor for neurodegeneration. The etiology of brain fog remains elusive and can arise not only during treatment but can also persist for an extended period after the end of RT. In this review, we will focus on the molecular pathways triggered by radiation therapy affecting cognitive functions and potentially at the origin of so-called “brain fog” symptomatology, with the aim to define novel therapeutic strategies to preserve healthy brain tissue from cognitive decline.
Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy
Authors: Sun Yiyu , Chen Di , Dai Tao , Yu Ziyou , Xie Hui , Wang Xiangsheng , Zhang Wenjie
Published: March 2024

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE’s therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.
Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies—an observational proof-of-concept study
Authors: Arndt Philipp , Chahem Christian , Luchtmann Michael , Kuschel Jan-Niklas , Behme Daniel , Pfister Malte , Neumann Jens , Görtler Michael , Dörner Marc , Pawlitzki Marc , Jansen Robin , Meuth Sven G. , Vielhaber Stefan , Henneicke Solveig , Schreiber Stefanie
Published: March 2024

Background

Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology.

Methods

As a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology.

Results

In 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p < 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p < 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p < 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p > 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI.

Conclusion

Risk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual’s risk of bleeding.
Neurophysiological indices for split phenomena: correlation with age and sex and potential implications in amyotrophic lateral sclerosis
Authors: Zoccolella Stefano , Milella Giammarco , Giugno Alessia , Devitofrancesco Vito , Damato Rosaria , Tamburrino Ludovica , Misceo Salvatore , Filardi Marco , Logroscino Giancarlo
Published: March 2024

Background

Split phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.

Methods

We prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APBcmap) x first dorsal interosseous (FDI)cmap/adductor digiti minimi (ADMcmap)], SEI (BICEPScmap/TRICEPScmap), SLI (extensor digit brevis (EDB)cmap/abductor Hallucis (AH)cmap), and the neurophysiological ratios APBcmap /ADMcmap and FDIcmap/ADMcmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.

Results

The median SHI was 10.4, with a median APBcmap/ADMcmap ratio of 0.9 and a median FDIcmap/ADMcmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1–2.4) and the median SLI was 0.7 (IQR:0.5–1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.

Conclusion

Our findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.
Integrative effects of transcutaneous auricular vagus nerve stimulation on esophageal motility and pharyngeal symptoms via vagal mechanisms in patients with laryngopharyngeal reflux disease
Authors: Huang Yizhou , Liu Jie , Lv Chaolan , Sun Chenyu , Meng Muzi , Lowe Scott , Yu Yue
Published: March 2024

Background and aim

Laryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms.

Methods

A total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0 mA to 1.5 mA (n = 22), while the control group underwent sham tVNS (n = 22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. High-resolution esophageal manometry data were collected, and the patients’ autonomic function was assessed through heart rate variability analysis.

Results

There was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r = 0.619; p < 0.001), Hamilton anxiety scale (HAMA) scores (r = 0.623; p < 0.001), and Hamilton depression scale (HAMD) scores (r = 0.593; p < 0.001). Compared to the pre-tVNS phase, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p < 0.05) and lower esophageal sphincter (LESP; p < 0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p < 0.05) and high frequency (HF; p < 0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p < 0.05) and LESP (p < 0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p < 0.05) and HF (p < 0.05) in tVNS group were significantly higher than that of control group.

Conclusion

This study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nerve-dependent mechanisms.
Missense mutation of angiotensin converting enzyme gene in an Alzheimer’s disease patient: a case report
Authors: He Mingyue , Zhang Fan , Qi Jing , Zhang Wei
Published: March 2024

Alzheimer’s disease (AD) is the most common type of cognitive impairment in the elderly. In this report, we presented a case of a 52-year-old woman with rapid disease progression within 6 months. She was diagnosed with mild dementia according to the clinical symptoms and neuropsychological assessment results. Based on the results of neuropathological proteins in cerebrospinal fluid, cranial magnetic resonance imaging, and positron emission tomography/computed tomography, the patient showed the presence of β amyloid deposition, pathologic tau along with neurodegeneration [A+T+(N+)], indicative of AD. Whole exome sequencing revealed a heterozygous C-to-T missense mutation of nucleotide 3,755 (c.3755C > T) in exon 25 of the angiotensin converting enzyme (ACE) gene on chromosome 17q23 (rs762056936).
Non-canonical retinoid signaling in neural development, regeneration and synaptic function
Authors: Piazza Alicia , Carlone Robert , Spencer Gaynor E.
Published: March 2024

Canonical retinoid signaling via nuclear receptors and gene regulation is critical for the initiation of developmental processes such as cellular differentiation, patterning and neurite outgrowth, but also mediates nerve regeneration and synaptic functions in adult nervous systems. In addition to canonical transcriptional regulation, retinoids also exert rapid effects, and there are now multiple lines of evidence supporting non-canonical retinoid actions outside of the nucleus, including in dendrites and axons. Together, canonical and non-canonical retinoid signaling provide the precise temporal and spatial control necessary to achieve the fine cellular coordination required for proper nervous system function. Here, we examine and discuss the evidence supporting non-canonical actions of retinoids in neural development and regeneration as well as synaptic function, including a review of the proposed molecular mechanisms involved.
Does consumption of pearl millet cause goiter? A systematic review of existing evidence
Authors: Anitha Seetha , Upadhyay Shweta , Grando Stefania , Kane-Potaka Joanna
Published: March 2024

Millets (defined here to also include sorghum) have been consumed in Asian and African countries for centuries, and have in recent years become increasingly popular in Western countries, especially because of their proven health and environmental benefits. Nevertheless, some concerns have been raised that their consumption can interfere with thyroid function and cause goiter. This systematic review aimed to investigate the link between millet consumption and goiter. We found nine papers that were relevant to this topic and included them in this review. Among nine papers eight were on pearl millet and one was on fonio millet. The findings of the review indicate that published literature on the association of pearl millet and increased goiter prevalence are not compelling and strong enough to assert that pearl millet consumed as part of a balanced diet can lead to goiter in the general population. To ensure appropriate factual messaging about millets, we need more scientific research to conclusively state whether millet consumption mediates goitrogenic effects.
A systematic review of primary large cell neuroendocrine carcinoma of the prostate
Authors: Nguyen Ngan , Franz Ronald Dean , Mohammed Omar , Huynh Richard , Son Christine Kim , Khan Rida Nusrat , Ahmed Bilawal
Published: March 2024

Background

Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.

Materials and methods

A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.

Results

A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.

Conclusion

LCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.
Sulforaphane inhibits the growth of prostate cancer by regulating the microRNA-3919/DJ-1 axis
Authors: Zhang Fangxi , Wan Xiaofeng , Zhan Jianmin , Shen Ming , Li Runsheng
Published: March 2024

Background

Prostate cancer (PCa) is the second most common solid cancer among men worldwide and the fifth leading cause of cancer-related deaths in men. Sulforaphane (SFN), an isothiocyanate compound, has been shown to exert inhibitory effects on a variety of cancers. However, the biological function of SFN in PCa has not been fully elucidated. The objective of this study was conducted to further investigate the possible underlying mechanism of SFN in PCa using in vitro cell culture and in vivo tumor model experiments.

Methods

Cell viability, migration, invasion, and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), wound healing assay, transwell assay, or flow cytometry. Expression of microRNA (miR)-3919 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) or in situ hybridization assay. Xenograft assay was conducted to validated the antitumor effect of miR-3919. The targeting relationship between miR-3919 and DJ-1 was verified by dual-luciferase reporter assay. The level of DJ-1was measured by qRT-PCR or western blotting (WB).

Results

In the present study, SFN downregulated mRNA and protein expression of DJ-1, an oncogenic gene. Small RNA sequencing analysis and dual-luciferase reporter assay confirmed that microRNA (miR)-3919 directly targeted DJ-1 to inhibition its expression. Furthermore, miR-3919 overexpression impeded viability, migration, and invasion and promoted apoptosis of PCa cells. Tumor growth in nude mice was also inhibited by miR-3919 overexpression, and miR-3919 expression in PCa tissues was lower than that in peritumoral tissues in an in situ hybridization assay. Transfection with miR-3919 inhibitors partially reversed the effects of SFN on cell viability, migration, invasion, and apoptosis.

Conclusion

Overall, the miR-3919/DJ-1 axis may be involved in the effects of SFN on the malignant biological behavior of PCa cells, which might be a new therapeutic target in PCa.