bluuebunny/crossref_metadata_2025 huggingface dataset:
VertU: universal multilocus primer sets for eDNA metabarcoding of vertebrate diversity, evaluated by both artificial and natural cases
Authors: Wang Zichen , Liu Xilin , Liang Dan , Wang Qiaoyun , Zhang Lu , Zhang Peng
Published: June 2023

Environmental DNA (eDNA) metabarcoding is a powerful tool for monitoring biodiversity in natural ecosystems. The accuracy of eDNA metabarcoding relies heavily on the PCR primers that amplify target sequences. For vertebrates, most available primers are designed for particular groups. There have been inadequate attempts to design “universal” primers applicable to all vertebrates. Here, we developed three new universal primer sets (V12S-U, V16S-U, and VCOI-U) targeting mitochondrial 12S, 16S, and COI genes, respectively. They work for all vertebrate groups, with amplification length of 200-250 bp, facilitating the use of short-read sequencing platforms. We evaluated and compared the species detection ability of our primer sets and seven previously published ones through bothin-silicoPCR and experiment tests with mock DNA and zoo eDNA. The species detection success of the new primer sets is over 90%, showing better performance than previously published primer sets. We also tested our new primers with water eDNA samples of natural environments, and detected a total of 895 vertebrate OTUs (BLAST identity ≥ 0.95), comprising 182 species, 195 genera, and 94 families. Our results indicated that utilizing multiple markers can achieve better species detection than using only a single marker, which is especially important for monitoring large biological communities like vertebrates. The new primer sets enable researchers to detect the presence of species of different vertebrate groups in one eDNA metabarcoding survey, which simplifies the workflow and reduces the cost. It has the potential to serve as an alternative/complementary tool for future eDNA metabarcoding studies targeting vertebrates.
Analysis on the effects of ecological conservation redline policies in the Pearl River Delta area, China
Authors: Wang Xin , Zhang Zhe , Hao Haiguang , Zhang Chao , Wang Ding
Published: June 2023

Introduction

The ecological conservation redline (ECR) policies conducted in China are an important innovation to protect biodiversity, safeguard ecological security, and achieve sustainable development. The Pearl River Delta (PRD) area implemented the ECR policies in 2005.

Methods

This study examines the contrast between the 15 years before and after 2005. It also reveals the ECR policies' effects by comparing land use change, landscape pattern index, and habitat quality inside (IECR) and outside (OECR) the ECR area.

Results and discussion

The results suggest that: (1) The ECR area has served as an ecological barrier in maintaining the stability of natural ecosystems. Over the past 30 years, the PRD area significantly changed land use types and ecosystems, mainly concentrated in the central plains and estuaries. Specifically, in the IECR, land use change was relatively stable, with a decrease of 0.05% and 0.57% in ecological land and an increase of 0.28% and 0.68% in construction land before and after 2005. In contrast, the OECR area land use changed dramatically, with a decrease of 0.37% and 1.36% in ecological land and an increase of 7.06% and 5.02% in construction land before and after 2005. (2) A general trend of landscape fragmentation exists in the study area. The contagion (CONTAG) in the IECR area is higher than in the OECR. The Shannon's diversity index (SHDI) in the IECR is lower than in the OECR area, which indicates a high degree and rapid landscape fragmentation in the OECR area. (3) Over 85% of the IECR scale had a habitat quality of 0.8–1, while the OECR area had an almost half scale with a habitat quality of 0–0.2. On the whole, the ecological stability and landscape connectivity of in the IECR area was higher than that of the OECR area. This indicates that the prohibitions on human disturbance, industrial construction, and logging activities in the IECR area allow green vegetation to succumb under natural conditions. Habitat quality in the IECR area was also higher than that of the OECR area in the PRD area, revealing that the quality of green development in the IECR area was higher. Finally, the ECR policies’ implementation has protected the environment in the PRD area and will provide experience for ecological conservation in other areas.
Determining representative pseudo-absences for invasive plant distribution modeling based on geographic similarity
Authors: Wang Xiao , Xu Quanli , Liu Jing
Published: June 2023

Introduction

The use of pseudo-absence data constrained by environmental conditions can facilitate potential distribution predictions of invasive species. However, pseudo-absence data generated by existing methods are usually not representative because the relationship between the presence and pseudo-absence points is either simplistic or neglected. This could under or overestimate the potential distribution of invasive species.

Methods

To address this deficiency, this study proposes a new method for obtaining pseudo-absence data based on geographic similarities. First, the reliability of pseudo-absences was quantified based on the geographic similarity to the occurrence of species. Subsequently, a representative pseudo-absence reliability threshold interval was determined. Finally, different pseudo-absence acquisition methods were assessed by combining virtual species with a real invasive species.

Results

The analysis demonstrated that the geographic similarity method can improve model accuracy and achieve a more realistic distribution compared with the traditional method of sampling for pseudo-absence data.

Discussion

This result indicates that the pseudo-absence data obtained using the geographic similarity approach were more representative. Our study provides valuable insights into improving invasive plant distribution predictions by considering the geographical relationships between species occurrences and the surrounding environments.
Postharvest strategies for preventing flower wilting and leaf yellowing in cut Ranunculus flowers
Authors: Cavallaro Viviana , Bulgari Roberta , Florio Francesco Elia , Restuccia Pasquale , Vinci Gianluca , Guffanti Davide , Vignati Sara , Ferrante Antonio
Published: June 2023

Introduction

Appropriate postharvest treatment, as well as adequate conditions of storage, can be adopted to elongate the lifespan of cut flowers. Thidiazuron (TDZ), a substituted phenylurea, and 1-methylcycloproene (1-MCP), a non-toxic inhibitor of ethylene perception, are nowadays substances commonly used to prevent early damage caused by senescence and to delay chlorophyll degradation. Ranunculus asiaticus L. is cultivated for cut flower production and is highly sensitive to ethylene and leaf yellowing. In this study, the effect of different pulse-tratment in prolonging cut ranunculus vase life was analyzed.

Methods

TDZ 10 µM, 1-MCP 500 ppb, and a combination of both were applied for 24 hours after harvest. The effect of the treatments was evaluated by performing non-destructive (% loss of fresh weight, chlorophyll a fluorescence, in vivo chlorophyll content, and Nitrogen Flavonol Index – NFI) and destructive (chlorophyll, carotenoids, anthocyanins concentration, and phenolic index) analyses at 0, 1, 12, and 14 days from treatments.

Results and Discussion

Flower wilting was delayed by 4 days in 1-MCP + TDZ 10 µM treatments, which also reduced weight loss and chlorophyll degradation compared to controls. The effectiveness of these compounds in preventing senescence has been confirmed by the decreased biosynthesis of phenolic compounds.
Insights into the mechanism of growth and fat deposition by feeding different levels of lipid provided by transcriptome analysis of swamp eel (Monopterus albus, Zuiew 1793) liver
Authors: Zhang Yazhou , Guo Feng , Yang Xin , Liu Yu , Bao Yihong , Wang Zirui , Hu Zhonghua , Zhou Qiubai
Published: June 2023

Lipid is an important source of energy in fish feeds, and the appropriate fat content can improve the efficiency of protein utilization. However, excessive lipid content in the feed can lead to abnormal fat deposition in fish, which has a negative effect on the growth of fish. Therefore, the effects of feed lipid levels on swamp eel were studied. Essential functional genes were screened using transcriptomics. We divided 840 fish into seven groups (four replicates). A mixture of fish and soybean oils (1:4), 0%, 2%, 4%, 6%, 8%, 10%, and 12% was added to the basic feed were named groups one to seven (L1-L7), respectively. Isonitrogenous diets were fed swamp eel for 10 weeks. Growth performance, visceral index, nutritional components, and biochemical indexes were measured and analyzed. Livers of the 0%, 6%, and 12% groups were subjected to transcriptome sequencing analysis. The results of our study showed that: the suitable lipid level for the growth of swamp eel was 7.03%; the crude fat content of whole fish, liver, intestine, muscle, and skin increased with the increase of lipid level, with some significant difference, and excess fat was deposited in skin tissue; triglyceride, total cholesterol, and free fatty acid contents increased with the increase of feed lipid level. High-density lipoprotein levels in the L3 and L4 groups were higher than in the other groups. Blood glucose concentrations in the L5, L6, and L7 groups increased; the liver tissue structure was damaged when the lipid level was too high. two-hundred-and-twenty-eight differentially expressed genes were found. Several critical pathways regulating glucose metabolism and energy balance (e.g., glycerolipid metabolism, glycolysis synthesis, degradation of ketone bodies, and Janus Kinase/Signal Transducer and Activator of Transcription signaling pathway) were enriched in swamp eel compared with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Suitable lipid levels (7.03%) can promote the growth of swamp eel, and excessive lipid levels can cause elevated blood lipids and lead to liver cell damage. Regulatory mechanisms may involve multiple metabolic pathways for glucose and lipid metabolism in eels. This study provides new insights to explain the mechanism of fat deposition due to high levels of lipid and provides a basis for the production of efficient and environmentally friendly feed for swamp eel.
Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate
Authors: Perdiguero Beatriz , Marcos-Villar Laura , López-Bravo María , Sánchez-Cordón Pedro J. , Zamora Carmen , Valverde José Ramón , Sorzano Carlos Óscar S. , Sin Laura , Álvarez Enrique , Ramos Manuel , Del Val Margarita , Esteban Mariano , Gómez Carmen Elena
Published: June 2023

Introduction

While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential.

Methods

In an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA).

Results

In cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8+ T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8+ T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm.

Discussion

These findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.
Case report: Induction and maintenance of steroid-free remission with vedolizumab in a case of steroid-dependent autoimmune pancreatitis
Authors: Griebel Paul , Tran Florian , Luehring Janina , Schreiber Stefan
Published: June 2023

Autoimmune pancreatitis responds well to corticosteroids in most instances. Additional immunosuppression or low-dose maintenance steroids may be necessary upon relapse. There is limited data on alternative strategies when these regiments fail or cause adverse reactions. We report a case of a middle-aged woman with autoimmune pancreatitis in whom tapering of prednisolone below the dose of 25mg per day resulted in relapse of symptoms and long-term steroid use led to development of steroid induced hyperglycaemia. Induction and maintenance of steroid-free remission was ultimately successful under vedolizumab therapy. Remission has been stable for over one year with reduced need for antidiabetic intervention. This is the first reported case of treatment of refractory autoimmune pancreatitis with vedolizumab. It highlights the overlap of immunological mechanisms within inflammatory diseases of the digestive tract and how knowledge of biological data can inform treatment decisions for individual cases. The demonstrated efficacy of vedolizumab and low risk of severe side effects warrant further investigation into its use in autoimmune pancreatitis.
Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts
Authors: Sviercz Franco A. , Jarmoluk Patricio , Cevallos Cintia G. , López Cynthia A. M. , Freiberger Rosa N. , Guano Alex , Adamczyk Alan , Ostrowski Matías , Delpino M. Victoria , Quarleri Jorge
Published: June 2023

Introduction

Osteoclasts play a crucial role in bone resorption, and impairment of their differentiation can have significant implications for bone density, especially in individuals with HIV who may be at risk of altered bone health. The present study aimed to investigate the effects of HIV infection on osteoclast differentiation using primary human monocyte-derived macrophages as precursors. The study focused on assessing the impact of HIV infection on cellular adhesion, cathepsin K expression, resorptive activity, cytokine production, expression of co-receptors, and transcriptional regulation of key factors involved in osteoclastogenesis.

Methods

Primary human monocyte-derived macrophages were utilized as precursors for osteoclast differentiation. These precursors were infected with HIV, and the effects of different inoculum sizes and kinetics of viral replication were analyzed. Subsequently, osteoclastogenesis was evaluated by measuring cellular adhesion, cathepsin K expression, and resorptive activity. Furthermore, cytokine production was assessed by monitoring the production of IL-1β, RANK-L, and osteoclasts. The expression levels of co-receptors CCR5, CD9, and CD81 were measured before and after infection with HIV. The transcriptional levels of key factors for osteoclastogenesis (RANK, NFATc1, and DC-STAMP) were examined following HIV infection.

Results

Rapid, massive, and productive HIV infection severely impaired osteoclast differentiation, leading to compromised cellular adhesion, cathepsin K expression, and resorptive activity. HIV infection resulted in an earlier production of IL-1β concurrent with RANK-L, thereby suppressing osteoclast production. Infection with a high inoculum of HIV increased the expression of the co-receptor CCR5, as well as the tetraspanins CD9 and CD81, which correlated with deficient osteoclastogenesis. Massive HIV infection of osteoclast precursors affected the transcriptional levels of key factors involved in osteoclastogenesis, including RANK, NFATc1, and DC-STAMP.

Conclusions

The effects of HIV infection on osteoclast precursors were found to be dependent on the size of the inoculum and the kinetics of viral replication. These findings underscore the importance of understanding the underlying mechanisms to develop novel strategies for the prevention and treatment of bone disorders in individuals with HIV.
Using dune restoration on an urban beach as a coastal resilience approach
Authors: Johnston Karina K. , Dugan Jenifer E. , Hubbard David M. , Emery Kyle A. , Grubbs Melodie W.
Published: June 2023

Coastal dunes are globally recognized as natural features that can be important adaptation approaches for climate change along urban and natural shores. We evaluated the recovery of coastal dunes on an intensively groomed urban beach in southern California over a six-year period after grooming was discontinued. Restoration actions were minimal and included installation of three sides of perimeter sand fencing, cessation of mechanical grooming and driving, and the addition of seeds of native dune plants. To track recovery, we conducted physical and biological surveys of the restoration site and an adjacent control site (groomed beach) using metrics including sand accretion, elevation, foredune and hummock formation, vegetation recovery, and wildlife use. Sediment accretion, elevation, and geomorphic complexity increased over time in the restoration site, largely in association with sand fencing and dune vegetation. A foredune ridge (maximum elevation increase of 0.9 m) and vegetated hummocks developed, along with a general increase in elevation across the restoration site (0.3 m). After six years, an estimated total volume of approximately 1,730 m3 of sand had accreted in the restoration site and 540 m3 of sand had accreted in the foredune ridge. Over the same period, more than a meter of sediment (vertical elevation change) accumulated along the perimeter sand fencing. Groomed control areas remained flat and uniform. The total cover of vegetation in the restoration site increased over time to a maximum of approximately 7% cover by the sixth year. No vegetation was observed on the groomed control site. Native plant species formed distinct zones across the restoration site beginning by the second year and increasing over time, with dune forming species aggregating closest to the ocean in association with the incipient foredune ridge. Ecological functions observed in the restoration area included presence of dune invertebrates, shorebird roosting, and use by a breeding federally threatened shorebird, the western snowy plover (Charadrius nivosus nivosus). Our findings on geomorphic and ecological responses of a pilot dune restoration on a heavily groomed urban beach provide new insights on the opportunities and expectations for restoring dunes as nature-based solutions for climate adaptation on urban shorelines.
Influence of parameters on the ultimate penetration depth of a double-plate vertically loaded anchor in soft clay
Authors: Xing Guoqi , Cao Yupeng , Zhang Baoliang , Li Jian , Zhang Xiaotong
Published: June 2023

To make a new type of double-plate vertically loaded anchor (DPVLA) penetrate into clay deeper, the influence of parameters on the ultimate penetration depth of DPVLAs in soft clay should be investigated. The expression of the ultimate penetration depth applicable to DPVLAs in clay was determined in terms of the formula of the ultimate penetration depth of anchors with a wedge-shaped section. Based on the drag penetration tests, the movement direction of the bottom fluke of DPVLAs with different lengths of the bottom fluke and different included angles was obtained. By the finite-element method, the upper bound solutions of bearing capacity factors of DPVLAs with different included angles and different lengths of the bottom flukes were also obtained, which correspond to the maximum penetration depth induced by the initial orientation of the anchor. According to the determined expression of the ultimate penetration depth of DPVLAs, the ultimate penetration depth of DPVLAs with different included angles and different lengths of the bottom fluke in clay can be calculated. The results showed that increasing the length of the bottom fluke can increase the ultimate penetration depth when the included angles were the same for DPVLAs not only in the clay with zero strength at the seabed but also in the clay with uniform strength. However, when the length of the bottom fluke is the same, increasing the included angle of DPVLAs in clay can significantly reduce the ultimate penetration depth.
Distinct gut bacterial composition in Anoplophora glabripennis reared on two host plants
Authors: Wang Xuefei , Wang Hualing , Zeng Jianyong , Cui Zezhao , Geng Shilong , Song Xiaofei , Zhang Fengjuan , Su Xiaoyu , Li Huiping
Published: June 2023

Anoplophora glabripennis (Coleoptera: Cerambycidae: Lamiinae) is an invasive wood borer pest that has caused considerable damage to forests. Gut bacteria are of great importance in the biology and ecology of herbivores, especially in growth and adaptation; however, change in the gut bacterial community of this pest feeding on different hosts is largely unknown. In this study, we investigated the gut bacterial communities of A. glabripennis larvae fed on different preferred hosts, Salix matsudana and Ulmus pumila, using 16S rDNA high-throughput sequencing technology. A total of 15 phyla, 25 classes, 65 orders, 114 families, 188 genera, and 170 species were annotated in the gut of A. glabripennis larvae fed on S. matsudana or U. pumila using a 97% similarity cutoff level. The dominant phyla were Firmicutes and Proteobacteria and the core dominant genera were Enterococcus, Gibbsiella, Citrobacter, Enterobacter, and Klebsiella. There was significantly higher alpha diversity in the U. pumila group than in the S. matsudana group, and principal co-ordinate analysis showed significant differences in gut bacterial communities between the two groups. The genera with significant abundance differences between the two groups were Gibbsiella, Enterobacter, Leuconostoc, Rhodobacter, TM7a, norank, Rhodobacter, and Aurantisolimonas, indicating that the abundance of larval gut bacteria was affected by feeding on different hosts. Further network diagrams showed that the complexity of the network structure and the modularity were higher in the U. pumila group than in the S. matsudana group, suggesting more diverse gut bacteria in the U. pumila group. The dominant role of most gut microbiota was related to fermentation and chemoheterotrophy, and specific OTUs positively correlated with different functions were reported. Our study provides an essential resource for the gut bacteria functional study of A. glabripennis associated with host diet.
Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions
Authors: Chen Ti , Xu Huan , Yao Xiaoyan , Luo Zhen
Published: June 2023

Glucose is a crucial carbon source for the growth of Staphylococcus aureus, but an excess of glucose is detrimental and even leads to cell death. Pyruvate, the central metabolite of glycolysis, has been shown to have anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of pyruvate on S. aureus under high glucose conditions. Sodium pyruvate greatly increased the cytotoxicity of S. aureus strain BAA-1717 to human erythrocytes and neutrophils in vitro. However, the cytotoxicity and survival of S. aureus were significantly reduced by high glucose, which was restored to normal levels by the addition of sodium pyruvate. The expression of hlg and lukS in S. aureus was higher in the LB-GP cultures than that in LB-G cultures, but there was no significant difference in cytotoxicity between LB-GP and LB-G cultures. Furthermore, the hemolytic activity of S. aureus supernatants could be inhibited by the cell-free culture medium (CFCM) of LB-G cultures, suggesting that high levels of extracellular proteases were presence in the CFCM of LB-G cultures, resulting in degradation of the hemolytic factors. The expression of sarA, which negatively regulates extracellular protease secretion, was higher in LB-GP cultures than that in LB-G cultures. Additionally, sodium pyruvate increased acetate production in S. aureus, which helps maintain cell viability under acidic environment. In conclusion, pyruvate plays an important role in the survival and cytotoxicity of S. aureus under high glucose conditions. This finding may aid in the development of effective treatments for diabetic foot infections.
Transcriptomic response of Sinorhizobium meliloti to the predatory attack of Myxococcus xanthus
Authors: Soto María José , Pérez Juana , Muñoz-Dorado José , Contreras-Moreno Francisco Javier , Moraleda-Muñoz Aurelio
Published: June 2023

Bacterial predation impacts microbial community structures, which can have both positive and negative effects on plant and animal health and on environmental sustainability. Myxococcus xanthus is an epibiotic soil predator with a broad range of prey, including Sinorhizobium meliloti, which establishes nitrogen-fixing symbiosis with legumes. During the M. xanthus-S. meliloti interaction, the predator must adapt its transcriptome to kill and lyse the target (predatosome), and the prey must orchestrate a transcriptional response (defensome) to protect itself against the biotic stress caused by the predatory attack. Here, we describe the transcriptional changes taking place in S. meliloti in response to myxobacterial predation. The results indicate that the predator induces massive changes in the prey transcriptome with up-regulation of protein synthesis and secretion, energy generation, and fatty acid (FA) synthesis, while down-regulating genes required for FA degradation and carbohydrate transport and metabolism. The reconstruction of up-regulated pathways suggests that S. meliloti modifies the cell envelop by increasing the production of different surface polysaccharides (SPSs) and membrane lipids. Besides the barrier role of SPSs, additional mechanisms involving the activity of efflux pumps and the peptide uptake transporter BacA, together with the production of H2O2 and formaldehyde have been unveiled. Also, the induction of the iron-uptake machinery in both predator and prey reflects a strong competition for this metal. With this research we complete the characterization of the complex transcriptional changes that occur during the M. xanthus-S. meliloti interaction, which can impact the establishment of beneficial symbiosis with legumes.
Bioinformatic and systems biology approach revealing the shared genes and molecular mechanisms between COVID-19 and non-alcoholic hepatitis
Authors: Lu Huishuang , Ma Jiaxiu , Li Yalan , Zhang Jin , An Yaxin , Du Wei , Cai Xuefei
Published: June 2023

Introduction: Coronavirus disease 2019 (COVID-19) has become a global pandemic and poses a serious threat to human health. Many studies have shown that pre-existing nonalcoholic steatohepatitis (NASH) can worsen the clinical symptoms in patients suffering from COVID-19. However, the potential molecular mechanisms between NASH and COVID-19 remain unclear. To this end, key molecules and pathways between COVID-19 and NASH were herein explored by bioinformatic analysis.

Methods: The common differentially expressed genes (DEGs) between NASH and COVID-19 were obtained by differential gene analysis. Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out using the obtained common DEGs. The key modules and hub genes in PPI network were obtained by using the plug-in of Cytoscape software. Subsequently, the hub genes were verified using datasets of NASH (GSE180882) and COVID-19 (GSE150316), and further evaluated by principal component analysis (PCA) and receiver operating characteristic (ROC). Finally, the verified hub genes were analyzed by single-sample gene set enrichment analysis (ssGSEA) and NetworkAnalyst was used for the analysis of transcription factor (TF)-gene interactions, TF-microRNAs (miRNA) coregulatory network, and Protein-chemical Interactions.

Results: A total of 120 DEGs between NASH and COVID-19 datasets were obtained, and the PPI network was constructed. Two key modules were obtained via the PPI network, and enrichment analysis of the key modules revealed the common association between NASH and COVID-19. In total, 16 hub genes were obtained by five algorithms, and six of them, namely, Kruppel-like factor 6 (KLF6), early growth response 1 (EGR1), growth arrest and DNA-damage-inducible 45 beta (GADD45B), JUNB, FOS, and FOS-like antigen 1 (FOSL1) were confirmed to be closely related to NASH and COVID-19. Finally, the relationship between hub genes and related pathways was analyzed, and the interaction network of six hub genes was constructed with TFs, miRNAs, and compounds.

Conclusion: This study identified six hub genes related to COVID-19 and NASH, providing a new perspective for disease diagnosis and drug development.
Small extracellular vesicles: a novel drug delivery system for neurodegenerative disorders
Authors: Pan Renjie , Chen Dongdong , Hou Lanlan , Hu Rong , Jiao Zhigang
Published: June 2023

Neurodegenerative diseases (NDs) have a slow onset and are usually detected late during disease. NDs are often difficult to cure due to the presence of the blood–brain barrier (BBB), which makes it difficult to find effective treatments and drugs, causing great stress and financial burden to families and society. Currently, small extracellular vesicles (sEVs) are the most promising drug delivery systems (DDSs) for targeted delivery of molecules to specific sites in the brain as a therapeutic vehicle due to their low toxicity, low immunogenicity, high stability, high delivery efficiency, high biocompatibility and trans-BBB functionality. Here, we review the therapeutic application of sEVs in several NDs, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, discuss the current barriers associated with sEVs and brain-targeted DDS, and suggest future research directions.
Single-cell transcriptomic profiling of dorsal root ganglion: an overview
Authors: Xie Keyu , Cheng Xu , Zhu Tao , Zhang Donghang
Published: June 2023

The somatosensory neurons in the dorsal root ganglion (DRG) are responsible to detect peripheral physical and noxious stimuli, and then transmit these inputs into the central nervous system. DRG neurons are composed of various subpopulations, which are suggested to respond to different stimuli, such as mechanical, thermal, and cold perception. For a long time, DRG neurons were classified based on anatomical criteria. Recently, single-cell (scRNA-seq) and single-nucleus RNA-sequencing (snRNA-seq) has advanced our understanding of the composition and functional heterogeneity of both human and rodent DRG neurons at single-cell resolution. In this review, we summarized the current literature regarding single-cell transcriptomic profiling of DRG to provide an integral understanding in the molecular transcriptomes, cell types, and functional annotations of DRG neurons in humans and rodents.
Chronic traumatic encephalopathy neuropathologic change is uncommon in men who played amateur American football
Authors: Iverson Grant L. , Jamshidi Pouya , Fisher-Hubbard Amanda O. , Deep-Soboslay Amy , Hyde Thomas M. , Kleinman Joel E. , deJong Joyce L. , Shepherd Claire E. , Hazrati Lili-Naz , Castellani Rudolph J.
Published: June 2023

Introduction

We examined postmortem brain tissue from men, over the age of 50, for chronic traumatic encephalopathy neuropathologic change (CTE-NC). We hypothesized that (i) a small percentage would have CTE-NC, (ii) those who played American football during their youth would be more likely to have CTE-NC than those who did not play contact or collision sports, and (iii) there would be no association between CTE-NC and suicide as a manner of death.

Methods

Brain tissue from 186 men and accompanying clinical information were obtained from the Lieber Institute for Brain Development. Manner of death was determined by a board-certified forensic pathologist. Information was obtained from next of kin telephone interviews, including medical, social, demographic, family, and psychiatric history. The 2016 and 2021 consensus definitions were used for CTE-NC. Two authors screened all cases, using liberal criteria for identifying “possible” CTE-NC, and five authors examined the 15 selected cases.

Results

The median age at the time of death was 65 years (interquartile range = 57–75; range = 50–96). There were 25.8% with a history of playing American football and 36.0% who had suicide as their manner of death. No case was rated as definitively having “features” of CTE-NC by all five authors. Ten cases were rated as having features of CTE-NC by three or more authors (5.4% of the sample), including 8.3% of those with a personal history of playing American football and 3.9% of those who did not play contact or collision sports. Of those with mood disorders during life, 5.5% had features of CTE-NC compared to 6.0% of those who did not have a reported mood disorder. Of those with suicide as a manner of death, 6.0% had features of CTE-NC compared to 5.0% of those who did not have suicide as a manner of death.

Discussion

We did not identify a single definitive case of CTE-NC, from the perspective of all raters, and only 5.4% of cases were identified as having possible features of CTE-NC by some raters. CTE-NC was very uncommon in men who played amateur American football, those with mood disorders during life, and those with suicide as a manner of death.
Using histogram analysis of the intrinsic brain activity mapping to identify essential tremor
Authors: Xiao Pan , Tao Li , Zhang Xiaoyu , Li Qin , Gui Honge , Xu Bintao , Zhang Xueyan , He Wanlin , Chen Huiyue , Wang Hansheng , Lv Fajin , Luo Tianyou , Cheng Oumei , Luo Jin , Man Yun , Xiao Zheng , Fang Weidong
Published: June 2023

Background

Essential tremor (ET) is one of the most common movement disorders. Histogram analysis based on brain intrinsic activity imaging is a promising way to identify ET patients from healthy controls (HCs) and further explore the spontaneous brain activity change mechanisms and build the potential diagnostic biomarker in ET patients.

Methods

The histogram features based on the Resting-state functional magnetic resonance imaging (Rs-fMRI) data were extracted from 133 ET patients and 135 well-matched HCs as the input features. Then, a two-sample t-test, the mutual information, and the least absolute shrinkage and selection operator methods were applied to reduce the feature dimensionality. Support vector machine (SVM), logistic regression (LR), random forest (RF), and k-nearest neighbor (KNN) were used to differentiate ET and HCs, and classification performance of the established models was evaluated by the mean area under the curve (AUC). Moreover, correlation analysis was carried out between the selected histogram features and clinical tremor characteristics.

Results

Each classifier achieved a good classification performance in training and testing sets. The mean accuracy and area under the curve (AUC) of SVM, LR, RF, and KNN in the testing set were 92.62%, 0.948; 92.01%, 0.942; 93.88%, 0.941; and 92.27%, 0.939, respectively. The most power-discriminative features were mainly located in the cerebello-thalamo-motor and non-motor cortical pathways. Correlation analysis showed that there were two histogram features negatively and one positively correlated with tremor severity.

Conclusion

Our findings demonstrated that the histogram analysis of the amplitude of low-frequency fluctuation (ALFF) images with multiple machine learning algorithms could identify ET patients from HCs and help to understand the spontaneous brain activity pathogenesis mechanisms in ET patients.
The advanced characterization, post-irradiation examination, and materials informatics for the development of ultra high-burnup annular U-10Zr metallic fuel
Authors: Yao Tiankai , Bachhav Mukesh , Di Lemma Fidelma G. , Xu Fei , Teng Fei , Murray Daniel J. , Benson Michael T. , Capriotti Luca
Published: June 2023

U-Zr metallic fuel is a promising fuel candidate for Gen Ⅳ fast spectrum reactors. Previous experimental irradiation campaigns showed that the sodium thermal bonded U-10Zr fuel design can achieve a burnup of 10% fissions per initial heavy metal atom (FIMA). Advanced metallic fuel designs are pushing the burnup limit to 20% or even 30% FIMA. To achieve the higher burnup and eliminate the pyrophoric sodium, a prototypical annular fuel has been designed, fabricated, clad with HT-9 in the Materials and Fuels Complex, and irradiated in the Advanced Test Reactors of Idaho National Laboratory (INL) to a peak burnup of 3.3% FIMA. During irradiation, the mechanical contact between fuel and cladding acts as a thermal bond. The irradiation lasted for 132 days in the reactor. Recently, the archived fresh and irradiated fuel samples were characterized using advanced characterization capabilities in the Irradiated Materials Characterization Laboratory (IMCL) of INL. This article summarizes the results of advanced characterization and computer vision-based materials informatics to reveal the irradiation effects on U-Zr metallic fuel. Future work will focus on further implementation of advanced characterization and statistical data mining to improve the fidelity of fuel performance modeling and support U-Zr metallic fuel qualification for fast spectrum reactors.
Clinical significance of the advanced lung cancer inflammation index in gastrointestinal cancer patients: a systematic review and meta-analysis
Authors: Pang Hua-Yang , Chen Xiu-Feng , Yan Meng-Hua , Chen Li-Hui , Chen Zhi-Xiong , Zhang Shou-Ru , Sun Hao
Published: June 2023

Background

The advanced lung cancer inflammation index (ALI) has been identified as a scientific and clinical priority in multiple malignancies. The aim of this study is to investigate the value of the ALI before treatment in evaluating postoperative complications (POCs) and survival outcomes in patients with gastrointestinal (GI) cancer.

Methods

Electronic databases including PubMed, Embase and Web of Science were comprehensively reviewed up to June 2022. The endpoints were POCs and survival outcomes. Subgroup analyses and sensitivity analyses were also performed.

Results

Eleven studies including 4417 participants were included. A significant heterogeneity in the ALI cut-off value among studies was observed. Patients in the low ALI group showed increased incidence of POCs (OR=2.02; 95%CI:1.60-2.57; P<0.001; I2 = 0%). In addition, a low ALI was also significantly associated with worse overall survival (HR=1.96; 95%CI: 1.58-2.43; P<0.001; I2 = 64%), which remained consistent in all subgroups based on country, sample size, tumor site, tumor stage, selection method and Newcastle Ottawa Scale score. Moreover, patients in the low ALI group had an obviously decreased disease-free survival compared to these in the high ALI group (HR=1.47; 95%CI: 1.28-1.68; P<0.001; I2 = 0%).

Conclusion

Based on existing evidence, the ALI could act as a valuable predictor of POCs and long-term outcomes in patients with GI cancer. However, the heterogeneity in the ALI cut-off value among studies should be considered when interpreting these findings.
Cancer-associated fibroblasts refine the classifications of gastric cancer with distinct prognosis and tumor microenvironment characteristics
Authors: Gu Lei , Ding Dan , Wei Cuicui , Zhou Donglei
Published: June 2023

Background

Cancer-associated fibroblasts (CAFs) are essential tumoral components of gastric cancer (GC), contributing to the development, therapeutic resistance and immune-suppressive tumor microenvironment (TME) of GC. This study aimed to explore the factors related to matrix CAFs and establish a CAF model to evaluate the prognosis and therapeutic effect of GC.

Methods

Sample information from the multiply public databases were retrieved. Weighted gene co-expression network analysis was used to identify CAF-related genes. EPIC algorithm was used to construct and verify the model. Machine-learning methods characterized CAF risk. Gene set enrichment analysis was employed to elucidate the underlying mechanism of CAF in the development of GC.

Results

A three-gene (GLT8D2, SPARC and VCAN) prognostic CAF model was established, and patients were markedly divided according to the riskscore of CAF model. The high-risk CAF clusters had significantly worse prognoses and less significant responses to immunotherapy than the low-risk group. Additionally, the CAF risk score was positively associated with CAF infiltration in GC. Moreover, the expression of the three model biomarkers were significantly associated with the CAF infiltration. GSEA revealed significant enrichment of cell adhesion molecules, extracellular matrix receptors and focal adhesions in patients at a high risk of CAF.

Conclusion

The CAF signature refines the classifications of GC with distinct prognosis and clinicopathological indicators. The three-gene model could effectively aid in determining the prognosis, drug resistance and immunotherapy efficacy of GC. Thus, this model has promising clinical significance for guiding precise GC anti-CAF therapy combined with immunotherapy.
Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing
Authors: Gómez de Cedrón Marta , Moreno Palomares Rocío , Ramírez de Molina Ana
Published: June 2023

Epigenetic modifications are chemical modifications that affect gene expression without altering DNA sequences. In particular, epigenetic chemical modifications can occur on histone proteins -mainly acetylation, methylation-, and on DNA and RNA molecules -mainly methylation-. Additional mechanisms, such as RNA-mediated regulation of gene expression and determinants of the genomic architecture can also affect gene expression. Importantly, depending on the cellular context and environment, epigenetic processes can drive developmental programs as well as functional plasticity. However, misbalanced epigenetic regulation can result in disease, particularly in the context of metabolic diseases, cancer, and ageing. Non-communicable chronic diseases (NCCD) and ageing share common features including altered metabolism, systemic meta-inflammation, dysfunctional immune system responses, and oxidative stress, among others. In this scenario, unbalanced diets, such as high sugar and high saturated fatty acids consumption, together with sedentary habits, are risk factors implicated in the development of NCCD and premature ageing. The nutritional and metabolic status of individuals interact with epigenetics at different levels. Thus, it is crucial to understand how we can modulate epigenetic marks through both lifestyle habits and targeted clinical interventions -including fasting mimicking diets, nutraceuticals, and bioactive compounds- which will contribute to restore the metabolic homeostasis in NCCD. Here, we first describe key metabolites from cellular metabolic pathways used as substrates to “write” the epigenetic marks; and cofactors that modulate the activity of the epigenetic enzymes; then, we briefly show how metabolic and epigenetic imbalances may result in disease; and, finally, we show several examples of nutritional interventions - diet based interventions, bioactive compounds, and nutraceuticals- and exercise to counteract epigenetic alterations.
Potential biomarkers for the early detection of bone metastases
Authors: Hao Yang , Zhang Feifan , Ma Yan , Luo Yage , Zhang Yongyong , Yang Ning , Liu Man , Liu Hongjian , Li Jitian
Published: June 2023

The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient’s quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases.
Liquid chromatography-tandem mass spectrometry analysis of a ratio-optimized drug pair of Sophora flavescens Aiton and Coptis chinensis Franch and study on the mechanism of anti-colorectal cancer effect of two alkaloids thereof
Authors: Chen Zihan , Dong Yingying , Yan Qiuying , Li Qin , Yu Chengtao , Lai Yueyang , Tan Jiani , Fan Minmin , Xu Changliang , Li Liu , Shen Weixing , Gu Junfei , Cheng Haibo , Sun Dongdong
Published: June 2023

The drug pair consisting of Sophora flavescens Aiton (Sophorae flavescentis radix, Kushen) and Coptis chinensis Franch. (Coptidis rhizoma, Huanglian), as described in Prescriptions for Universal Relief (Pujifang), is widely used to treat laxation. Matrine and berberine are the major active components of Kushen and Huanglian, respectively. These agents have shown remarkable anti-cancer and anti-inflammatory effects. A mouse model of colorectal cancer was used to determine the most effective combination of Kushen and Huanglian against anti-colorectal cancer. The results showed that the combination of Kushen and Huanglian at a 1:1 ratio exerted the best anti-colorectal cancer effect versus other ratios. Moreover, the anti-colorectal cancer effect and potential mechanism underlying the effects of matrine and berberine were evaluated by the analysis of combination treatment or monotherapy. In addition, the chemical constituents of Kushen and Huanglian were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 67 chemical components were identified from the Kushen–Huanglian drug pair (water extraction), and the levels of matrine and berberine were 129 and 232 µg/g, respectively. Matrine and berberine reduced the growth of colorectal cancer and relieved the pathological conditions in mice. In addition, the combination of matrine and berberine displayed better anti-colorectal cancer efficacy than monotherapy. Moreover, matrine and berberine reduced the relative abundance of Bacteroidota and Campilobacterota at phylum level and that of Helicobacter, Lachnospiraceae_NK4A136_group, Candidatus_Arthromitus, norank_f_Lachnospiraceae, Rikenella, Odoribacter, Streptococcus, norank_f_Ruminococcaceae, and Anaerotruncus at the genus level. Western blotting results demonstrated that treatment with matrine and berberine decreased the protein expressions of c-MYC and RAS, whereas it increased that of sirtuin 3 (Sirt3). The findings indicated that the combination of matrine and berberine was more effective in inhibiting colorectal cancer than monotherapy. This beneficial effect might depend on the improvement of intestinal microbiota structure and regulation of the RAS/MEK/ERK-c-MYC-Sirt3 signaling axis.