bluuebunny/crossref_metadata_2025 huggingface dataset:
SMO mutation predicts the effect of immune checkpoint inhibitor: From NSCLC to multiple cancers
Authors: Ji Wenxiang , Niu Xiaomin , Yu Yongfeng , Li Ziming , Gu LinPing , Lu Shun
Published: November 2022

Background

The emergence of immune checkpoint inhibitors (ICIs) is one of the most promising breakthroughs for the treatment of multiple cancer types, but responses vary. Growing evidence points to a link between developmental signaling pathway-related genes and antitumor immunity, but the association between the genomic alterations in these genes and the response to ICIs still needs to be elucidated.

Methods

Clinical data and sequencing data from published studies and our cohort were collected to analyze the association of the mutation status of SMO with the efficacy of ICI therapy in the non-small cell lung cancer (NSCLC) cohort and the pan-cancer cohort. Furthermore, the correlation between SMO mutation and immunotherapeutic biomarkers such as immune cell infiltration, immune-related genes, and underlying signaling pathways was analyzed. Three SMO mutant plasmids were transfected into cells to explore the SMO mutation status in the context of its expression and cell growth.

Result

In the NSCLC discovery cohort, the median progression-free survival in the SMO mutant (SMO_MUT) was longer than that in the wild type (SMO_WT) (23.0 vs. 3.8 months, adjusted p = 0.041). This finding was further confirmed in the NSCLC validation cohort (8.7 vs. 5.1 months, adjusted p = 0.013). In the pan-cancer cohort (n = 1,347), a significant overall survival advantage was observed in patients with SMO mutations [not reached (NR) vs. 18 months, adjusted p = 0.024]. In the subgroup analysis, the survival advantage of SMO_MUT against SMO_WT was prominent and consistent across genders, ages, treatment types, cancer types, and the tumor mutation burden (TMB) status (all pinteraction > 0.05). In an in vitro experiment, we found that both the mutant and wild-type plasmids can promote the expression of SMO, but the mutant plasmid had lower SMO mRNA and protein levels than the wild type. In CCK-8 experiments, we found that SMO_MUT plasmids can improve the growth of Calu-1 and PC-9 cells, but this capability varied between different mutations and cells. Upon further exploration, the SMO mutation status was found to be related to a higher TMB, more neoantigen load, more DNA damage repair (DDR) mutations, higher microsatellite instability (MSI) score, and higher CD8+ T-cell infiltration.

Conclusions

The SMO mutation status is an independent prognostic factor that can be used to predict better clinical outcomes of ICI treatment across multiple cancer types.
Single cell analysis of docosahexaenoic acid suppression of sequential LPS-induced proinflammatory and interferon-regulated gene expression in the macrophage
Authors: Wierenga Kathryn A. , Riemers Frank M. , Westendorp Bart , Harkema Jack R. , Pestka James J.
Published: November 2022

Preclinical and clinical studies suggest that consumption of long chain omega-3 polyunsaturated fatty acids (PUFAs) reduces severity of chronic inflammatory and autoimmune diseases. While these ameliorative effects are conventionally associated with downregulated expression of proinflammatory cytokine and chemokine genes, our laboratory has recently identified Type 1 interferon (IFN1)-regulated gene expression to be another key target of omega-3 PUFAs. Here we used single cell RNA sequencing (scRNAseq) to gain new mechanistic perspectives on how the omega-3 PUFA docosahexaenoic acid (DHA) influences TLR4-driven proinflammatory and IFN1-regulated gene expression in a novel self-renewing murine fetal liver-derived macrophage (FLM) model. FLMs were cultured with 25 µM DHA or vehicle for 24 h, treated with modest concentration of LPS (20 ng/ml) for 1 and 4 h, and then subjected to scRNAseq using the 10X Chromium System. At 0 h (i.e., in the absence of LPS), DHA increased expression of genes associated with the NRF2 antioxidant response (e.g. Sqstm1, Hmox1, Chchd10) and metal homeostasis (e.g.Mt1, Mt2, Ftl1, Fth1), both of which are consistent with DHA-induced polarization of FLMs to a more anti-inflammatory phenotype. At 1 h post-LPS treatment, DHA inhibited LPS-induced cholesterol synthesis genes (e.g. Scd1, Scd2, Pmvk, Cyp51, Hmgcs1, and Fdps) which potentially could contribute to interference with TLR4-mediated inflammatory signaling. At 4 h post-LPS treatment, LPS-treated FLMs reflected a more robust inflammatory response including upregulation of proinflammatory cytokine (e.g. Il1a, Il1b, Tnf) and chemokine (e.g.Ccl2, Ccl3, Ccl4, Ccl7) genes as well as IFN1-regulated genes (e.g. Irf7, Mx1, Oasl1, Ifit1), many of which were suppressed by DHA. Using single-cell regulatory network inference and clustering (SCENIC) to identify gene expression networks, we found DHA modestly downregulated LPS-induced expression of NF-κB-target genes. Importantly, LPS induced a subset of FLMs simultaneously expressing NF-κB- and IRF7/STAT1/STAT2-target genes that were conspicuously absent in DHA-pretreated FLMs. Thus, DHA potently targeted both the NF-κB and the IFN1 responses. Altogether, scRNAseq generated a valuable dataset that provides new insights into multiple overlapping mechanisms by which DHA may transcriptionally or post-transcriptionally regulate LPS-induced proinflammatory and IFN1-driven responses in macrophages.
Temperature denpendent microwave absorption properties of SrFe12O19 in X-band
Authors: Li Xiling , Qiao Liang , Shi Huigang , Chai Guozhi , Wang Tao , Wang Jianbo
Published: November 2022

Researchers are currently focusing on the electromagnetic and microwave absorption properties of SrFe12O19 hexaferrites. The high-temperature absorption (more than 573 K) is highly demanded in various including the military, national defense, aviation, and other fields. SrFe12O19 has good thermal stability at high temperature, and it has large coercivity, which also determines that it has good stability in magnetic properties and is not easy to be affected by the environment. Thus, it is necessary to explore the magnetic characteristics of SrFe12O19 hexaferrites at high temperatures. SrFe12O19 hexaferrites were fabricated by the molten salt method and their microstructure, high-temperature electromagnetic properties, and microwave properties were investigated in detail. The complex permeability and permittivity of SrFe12O19 were measured at varying temperatures (293–673 K) in the X band. While the real parts of permittivity and permeability increased with the increasing temperature, the imaginary parts of permittivity and permeability did not change significantly with increasing temperature. The calculated absorption properties displayed that as temperature increased from 293K to 623K, the frequency of the RL peaks moved to a low-frequency direction, and the sample’s minimum value of RL could be smaller than -10dB across the whole X band. The results indicate that SrFe12O19 particles have better absorption properties and can be used in high-temperature environments. These particles can be possibly used in many particular fields.
Therapeutic targeting of microglia mediated oxidative stress after neurotrauma
Authors: Smith Austin N. , Shaughness Michael , Collier Sean , Hopkins Deanna , Byrnes Kimberly R.
Published: November 2022

Inflammation is a primary component of the central nervous system injury response. Traumatic brain and spinal cord injury are characterized by a pronounced microglial response to damage, including alterations in microglial morphology and increased production of reactive oxygen species (ROS). The acute activity of microglia may be beneficial to recovery, but continued inflammation and ROS production is deleterious to the health and function of other cells. Microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), mitochondria, and changes in iron levels are three of the most common sources of ROS. All three play a significant role in post-traumatic brain and spinal cord injury ROS production and the resultant oxidative stress. This review will evaluate the current state of therapeutics used to target these avenues of microglia-mediated oxidative stress after injury and suggest avenues for future research.
Predictive markers for efficiency of the amino-acid deprivation therapies in cancer
Authors: Pokrovsky Vadim S. , Abo Qoura Louay , Morozova Elena , Bunik Victoria I.
Published: November 2022

Amino acid deprivation therapy (AADT) is a promising strategy for developing novel anticancer treatments, based on variations in metabolism of healthy and malignant cells. L-asparaginase was the first amino acid-degrading enzyme that received FDA approval for the treatment of acute lymphoblastic leukemia (ALL). Arginase and arginine deiminase were effective in clinical trials for the treatment of metastatic melanomas and hepatocellular carcinomas. Essential dependence of certain cancer cells on methionine explains the anticancer efficacy of methionine-g-lyase. Along with significant progress in identification of metabolic vulnerabilities of cancer cells, new amino acid-cleaving enzymes appear as promising agents for cancer treatment: lysine oxidase, tyrosine phenol-lyase, cysteinase, and phenylalanine ammonia-lyase. However, sensitivity of specific cancer cell types to these enzymes differs. Hence, search for prognostic and predictive markers for AADT and introduction of the markers into clinical practice are of great importance for translational medicine. As specific metabolic pathways in cancer cells are determined by the enzyme expression, some of these enzymes may define the sensitivity to AADT. This review considers the known predictors for efficiency of AADT, emphasizing the importance of knowledge on cancer-specific amino acid significance for such predictions.
A deep learning-based approach toward differentiating scalp psoriasis and seborrheic dermatitis from dermoscopic images
Authors: Yu Zhang , Kaizhi Shen , Jianwen Han , Guanyu Yu , Yonggang Wang
Published: November 2022

Objectives

This study aims to develop a new diagnostic method for discriminating scalp psoriasis and seborrheic dermatitis based on a deep learning (DL) model, which uses the dermatoscopic image as input and achieved higher accuracy than dermatologists trained with dermoscopy.

Methods

A total of 1,358 pictures (obtained from 617 patients) with pathological and diagnostic confirmed skin diseases (508 psoriases, 850 seborrheic dermatitides) were randomly allocated into the training, validation, and testing datasets (1,088/134/136) in this study. A DL model concerning dermatoscopic images was established using the transfer learning technique and trained for diagnosing two diseases.

Results

The developed DL model exhibits good sensitivity, specificity, and Area Under Curve (AUC) (96.1, 88.2, and 0.922%, respectively), it outperformed all dermatologists in the diagnosis of scalp psoriasis and seborrheic dermatitis when compared to five dermatologists with various levels of experience. Furthermore, non-proficient doctors with the assistance of the DL model can achieve comparable diagnostic performance to dermatologists proficient in dermoscopy. One dermatology graduate student and two general practitioners significantly improved their diagnostic performance, where their AUC values increased from 0.600, 0.537, and 0.575 to 0.849, 0.778, and 0.788, respectively, and their diagnosis consistency was also improved as the kappa values went from 0.191, 0.071, and 0.143 to 0.679, 0.550, and 0.568, respectively. DL enjoys favorable computational efficiency and requires few computational resources, making it easy to deploy in hospitals.

Conclusions

The developed DL model has favorable performance in discriminating two skin diseases and can improve the diagnosis, clinical decision-making, and treatment of dermatologists in primary hospitals.
Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis
Authors: Liu Jingjing , Liu Zheng Ai , Liu Yichun , Cheng Lei , Yan Lei
Published: November 2022

Objective

The aim of this study was to investigate the effect of antibiotic treatment for chronic endometritis (CE) on reproductive outcomes.

Design

Systematic review and meta-analysis.

Patients

Women with reproductive failures, including recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL).

Interventions

Literature searches were performed using three electronic databases (PubMed, Embase, and Web of Science) until 1 December 2021 (without date restriction). The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with normal endometrial histology (negative for CE); and women with cured CE vs. women with persistent CE (PCE). The summary measures were indicated as odds ratio (OR) with a 95% confidence interval (CI).

Main outcome measures

These include on-going pregnancy rate/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), and miscarriage rate/pregnancy loss rate (MR/PLR).

Results

A total of 2,154 women (from twelve studies) were enrolled. Compared with the control group, women with CE receiving antibiotics did not show a statistically significant difference in OPR/LBR (P = 0.09) and CPR (P = 0.36), although there was a lower MR (P = 0.03). Women with cured CE have higher OPR/LBR (OR 1.57) and CPR (OR 1.56) in comparison with those with non-CE. There was a statistically significantly higher OPR/LBR (OR 6.82, P < 0.00001) and CPR (OR 9.75, P < 0.00001) in women with cured CE vs. those with persistent CE.

Conclusion

While antibiotic treatment is a sensible option to cure CE, more well-designed prospective studies are needed to evaluate the reproductive impact of antibiotic treatment. Cured CE provides high-quality maternal conditions for subsequent embryo transfer and successful pregnancy.
No evidence for a causal link between Helicobacter pylori infection and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study
Authors: Liu Yuwei , Xu Hongqin , Zhao ZiHan , Dong Yutong , Wang Xiaomei , Niu Junqi
Published: November 2022

Although clinical studies have shown the possible relationship between Helicobacter pylori (H. pylori) infection and the development of nonalcoholic fatty liver disease (NAFLD), their causal relationship is still unknown. This bidirectional Mendelian randomization (MR) study aimed to investigate the causal link between H. pylori infection and NAFLD. Two previously reported genetic variants SNPs rs10004195 and rs368433 were used as the instrumental variables (IVs) of H. pylori infection. The genetic variants of NAFLD were extracted from the largest genome-wide association study (GWAS) summary data with 1,483 cases and 17,781 controls. The exposure and outcome data were obtained from the publicly available GWAS dataset. Then, a bidirectional MR was carried out to evaluate the causal relationship between H. pylori infection and NAFLD. In addition, the GWAS data were also collected to explore the causal relationship between H. pylori infection and relevant clinical traits of NAFLD, including triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and body mass index (BMI). Genetically predicted H. pylori infection showed no association with NAFLD both in FinnGen GWAS (OR, 1.048; 95% CI, 0.778–1.411; value of p = 0.759) and the GWAS conducted by Anstee (OR, 0.775; 95% CI, 0.475–1.265; value of p = 0.308). An inverse MR showed no causal effect of NAFLD on H. pylori infection (OR,0.978;95% CI, 0.909–1.052; value of p = 0.543). No significant associations were observed between H. pylori infection and the levels of triglycerides, LDL-C, HDL-C, or FBG, while H. pylori infection was associated with an increase in BMI. These results indicated that there was no genetic evidence for a causal link between H. pylori and NAFLD, suggesting that the eradication or prevention of H. pylori infection might not benefit NAFLD and vice versa.
Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran
Authors: Saki Morteza , Amin Mansour , Savari Mohammad , Hashemzadeh Mohammad , Seyedian Seyed Saeid
Published: November 2022

This study investigated the molecular epidemiology of carbapenem-resistant classic Klebsiella pneumoniae (CR-cKp) and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolates in southwestern Iran. From 2019 to 2021, 136 (88.9%) cKp and 17 (11.1%) hvKp isolates were identified using biochemical tests and polymerase chain reaction (PCR). Antibiotic resistance, beta-lactamases, and clonal relatedness of carbapenem-resistant isolates were investigated using disk diffusion, PCR, and enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), respectively. The different markers of hvKp isolates were as follows: string test (35.3%, n = 6/17), magA (11.8%, n = 2/17), rmpA (11.8%, n = 2/17), rmpA2 (52.9%, n = 9/17), iucA (52.9%, n = 9/17), and peg344 (35.3%, n = 6/17). Also, 55.1% (n = 75/136) of cKp and 47.1% (n = 8/17) of hvKp isolates were CR-cKp and CR-hvKp, respectively. All CR-hvKp (100.0%, n = 8) isolates were MDR. Colistin, tetracycline, and tigecycline were the most effective antibiotics. The occurrence of beta-lactamase genes in 75 CR-cKp and 8 CR-hvKp isolates was as follows: blaNDM (41.3, 25.0%), blaIMP (4.0, 0.0%), blaVIM (8.0, 0.0%), blaGES (14.7, 25.0%), blaOXA–48–like (20.0, 0.0%), blaCTX–M (26.7, 12.5%), blaSHV (24.0, 12.5%), blaTEM (10.7, 0.0%), blaFOX (6.7, 0.0%), blaDHA (6.7, 0.0%), blaCMY (5.3, 0.0%), blaLAT (12.0, 0.0%), and blaACT (8.0, 0.0%). ERIC-PCR showed a high diversity among isolates. In this study, the occurrence of MDR CR-hvKp isolates harboring blaNDM and blaGES was detected for the first time in southwestern Iran. To prevent the spread of CR-hvKp and reduce selection pressure, long-term surveillance and more effective treatment strategies should be implemented.
Risk factors of severe fever with thrombocytopenia syndrome combined with central neurological complications: A five-year retrospective case–control study
Authors: Wang Min , Huang Peng , Liu Wei , Tan Weilong , Chen Tianyan , Zeng Tian , Zhu Chuanlong , Shao Jianguo , Xue Hong , Li Jun , Yue Ming
Published: November 2022

Objective

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality rate, especially SFTS combined with central neurological complications. The purpose of this study was to explore risk factors of central neurological complications in SFTS patients.

Methods

In this retrospective study, SFTS patients admitted to the First Affiliated Hospital of Nanjing Medical University between January 2017 and December 2021 were enrolled. Based on the presence or absence of central neurological complications, SFTS patients were divided into case group and control group. The patients’ laboratory parameters and clinical data were collected for statistical analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of independent risk factors in identifying SFTS patients with central neurological complications.

Results

In total, 198 hospitalized SFTS patients with complete medical records, clear etiological diagnosis and clinical outcomes were enrolled in this study. Of these, 74 (37.4%) cases were diagnosed with SFTS with central neurological complications, 29 (39.2%) cases died, and no death occurred in the control group. Multivariate logistic regression analysis revealed pulmonary rales, atrial fibrillation, and high serum SFTSV RNA, lactate dehydrogenase level during the fever stage as independent risk factors for the development of central neurological complications in SFTS patients. ROC curve analysis showed that the area under the ROC curve (AUC) of serum SFTSV RNA and lactate dehydrogenase levels were 0.748 (95%CI: 0.673–0.823, p < 0.001) and 0.864 (95%CI: 0.815–0.914, p < 0.001), respectively, in central neurological complications predicted in SFTS patients.

Conclusion

Severe fever with thrombocytopenia syndrome (SFTS) combined with central neurological complications has high morbidity and mortality and diverse clinical manifestations. Early monitoring of lung signs, electrocardiogram, blood SFTSV RNA, and lactate dehydrogenase levels in SFTS patients may be useful in predicting the occurrence of central neurological complications.
An old confusion: Entomophthoromycosis versus mucormycosis and their main differences
Authors: Acosta-España Jaime David , Voigt Kerstin
Published: November 2022

Fungal diseases were underestimated for many years. And the global burden of fungal infections is substantial and has increased in recent years. Invasive fungal infections have been linked to several risk factors in humans which basically depend on the individual homeostasis of the patients. However, many fungi can infect even apparently healthy people. Knowledge of these pathogens is critical in reducing or stopping morbidity and/or mortality statistics due to fungal pathogens. Successful therapeutic strategies rely on rapid diagnosis of the causative fungal agent and the underlying disease. However, the terminology of the diseases was updated to existing phylogenetic classifications and led to confusion in the definition of mucormycosis, conidiobolomycosis, and basidiobolomycosis, which were previously grouped under the now-uncommon term zygomycosis. Therefore, the ecological, taxonomic, clinical, and diagnostic differences are addressed to optimize the understanding and definition of these diseases. The term “coenocytic hyphomycosis” is proposed to summarize all fungal infections caused by Mucorales and species of Basidiobolus and Conidiobolus.
Complete genome analysis reveals evolutionary history and temporal dynamics of Marek’s disease virus
Authors: Li Kai , Yu Zhenghao , Lan Xingge , Wang Yanan , Qi Xiaole , Cui Hongyu , Gao Li , Wang Xiaomei , Zhang Yanping , Gao Yulong , Liu Changjun
Published: November 2022

Marek’s disease has caused enormous losses in poultry production worldwide. However, the evolutionary process and molecular mechanisms underlying Marek’s disease virus (MDV) remain largely unknown. Using complete genomic sequences spanning an unprecedented diversity of MDVs, we explored the evolutionary history and major patterns in viruses sampled from 1964 to 2018. We found that the evolution of MDV strains had obvious geographical features, with the Eurasian and North American strains having independent evolutionary paths, especially for Asian strains. The evolution of MDVs generally followed a clock-like structure with a relatively high evolutionary rate. Asian strains had evolved at a faster rate than European strains, with most genetic mutations occurring in Asian strains. Our results showed that all recombination events occurred in the UL and US subregions. We found direct evidence of a closer correlation between Eurasian strains, related to a series of reorganization events represented by the European strain ATE2539. We also discovered that the vaccine strains had recombined with the wild virulent strains. Base substitution and recombination were found to be the two main mechanisms of MDV evolution. Our study offers novel insights into the evolution of MDVs that could facilitate predicting the spread of infections, and hence their control.
Geographic patterns and determinants of antibiotic resistomes in coastal sediments across complex ecological gradients
Authors: Xiong Shangling , Wang Kai , Yan Huizhen , Hou Dandi , Wang Yanting , Li Meng , Zhang Demin
Published: November 2022

Coastal areas are highly influenced by terrestrial runoffs and anthropogenic disturbances, commonly leading to ecological gradients from bay, nearshore, to offshore areas. Although the occurrence and distribution of sediment antibiotic resistome are explored in various coastal environments, little information is available regarding geographic patterns and determinants of coastal sediment antibiotic resistomes across ecological gradients at the regional scale. Here, using high-throughput quantitative PCR, we investigated the geographic patterns of 285 antibiotic resistance genes (ARGs) in coastal sediments across a  ~  200  km scale in the East China Sea. Sediment bacterial communities and physicochemical properties were characterized to identify the determinants of sediments antibiotic resistome. Higher richness and abundance of ARGs were detected in the bay samples compared with those in nearshore and offshore samples, and significant negative correlations between the richness and/or abundance of ARGs and the distance to coastline (DTC) were identified, whereas different types of ARGs showed inconsistency in their relationships with DTC. The composition of antibiotic resistome showed significant correlations with nutrition-related variables (including NH4+-N, NO3−-N, and total phosphorus) and metals/metalloid (including As, Cu, Ni, and Zn), suggesting that terrestrial disturbances largely shape the antibiotic resistome. The Bipartite network showed strong associations between ARGs and mobile genetic elements (MGEs), and Partial Least Squares Path Modeling further revealed that terrestrial disturbance strength (as indicated by DTC) directly affected abiotic environmental conditions and bacterial community composition, and indirectly affected antibiotic resistome via MGEs. These findings provide insights into regional variability of sediment antibiotic resistome and its shaping path across complex ecological gradients, highlighting terrestrial disturbances as determinative forces in shaping coastal sediment antibiotic resistomes.
Application of ecosystem-specific reference databases for increased taxonomic resolution in soil microbial profiling
Authors: Overgaard Christina Karmisholt , Tao Ke , Zhang Sha , Christensen Bent Tolstrup , Blahovska Zuzana , Radutoiu Simona , Kelly Simon , Dueholm Morten Kam Dahl
Published: November 2022

Intensive agriculture systems have paved the way for a growing human population. However, the abundant use of mineral fertilizers and pesticides may negatively impact nutrient cycles and biodiversity. One potential alternative is to harness beneficial relationships between plants and plant-associated rhizobacteria to increase nutrient-use efficiency and provide pathogen resistance. Plant-associated microbiota profiling can be achieved using high-throughput 16S rRNA gene amplicon sequencing. However, interrogation of these data is limited by confident taxonomic classifications at high taxonomic resolution (genus- or species level) with the commonly applied universal reference databases. High-throughput full-length 16S rRNA gene sequencing combined with automated taxonomy assignment (AutoTax) can be used to create amplicon sequence variant resolved ecosystems-specific reference databases that are superior to the traditional universal reference databases. This approach was used here to create a custom reference database for bacteria and archaea based on 987,353 full-length 16S rRNA genes from Askov and Cologne soils. We evaluated the performance of the database using short-read amplicon data and found that it resulted in the increased genus- and species-level classification compared to commonly use universal reference databases. The custom database was utilized to evaluate the ecosystem-specific primer bias and taxonomic resolution of amplicon primers targeting the V5–V7 region of the 16S rRNA gene commonly used within the plant microbiome field. Finally, we demonstrate the benefits of custom ecosystem-specific databases through the analysis of V5–V7 amplicon data to identify new plant-associated microbes for two legumes and two cereal species.
Dual-gene detection in a single-tube system based on CRISPR-Cas12a/Cas13a for severe fever thrombocytopenia syndrome virus
Authors: Zhu Yating , Xing Chen , Yang Li , Li Qian , Wang Xiaofeng , Zhou Jing , Zhang Cong , Ren Cuiping , Liu Fahu , He Jun , Shen Bing , Du Yinan , Liu Yan
Published: November 2022

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV). The disease results in high mortality and increased morbidity and threatens global public health. Rapid detection of SFTSV is crucial for epidemic prevention in low-resource settings. Here we developed deployable, sensitive and rapid detection methods based on CRISPR/Cas12a or Cas13a technologies. The CRISPR/Cas12a-based detection assay could stably detect the SFTSV L or M genes at 10 cp/μl. The Cas13a-based method could detect the L gene as low as 0.75 cp/μl. For point-of-care testing, we combined fluorescence visualization and lateral flow detection with CRISPR/Cas-based assays. Furthermore, using the orthogonal DNA/RNA collateral activity of the Cas12a/Cas13a system, we present the dual-gene detection platform for SFTSV, which can simultaneously detect the L and M genes in a single tube. Based on the dual-gene detection, we designed multiplexed test strips to detect SFTSV. All our methods were initially validated using 52 clinical samples, showing 100% sensitivity and specificity. These new CRISPR/Cas-based detection methods are promising candidates for on-site detection of SFTSV.
In silico genomic analysis of the potential probiotic Lactiplantibacillus pentosus CF2-10N reveals promising beneficial effects with health promoting properties
Authors: Abriouel Hikmate , Manetsberger Julia , Caballero Gómez Natacha , Benomar Nabil
Published: November 2022

Lactiplantibacillus pentosus CF2-10 N, isolated from brines of naturally fermented Aloreña green table olives, exhibited high probiotic potential. High throughput sequencing and annotation of genome sequences underline the potential of L. pentosus CF2-10 N as excellent probiotic candidate of vegetable origin. In a previous study we could show the probiotic potential of CF2-10 N in vitro, while in this study in silico analysis of its genome revealed new insights into its safety and functionality. Our findings highlight the microorganism’s ecological flexibility and adaptability to a broad range of environmental niches, food matrices and the gastrointestinal tract. These features are shared by both phylogenetically very close L. pentosus strains (CF2-10 N and MP-10) isolated from the same ecological niche with respect to their genome size (≅ 3.6 Mbp), the presence of plasmids (4–5) and several other properties. Nonetheless, additional and unique features are reported in the present study for L. pentosus CF2-10 N. Notably, the safety of L. pentosus CF2-10 N was shown by the absence of virulence determinants and the determination of acquired antibiotic resistance genes, i.e., resistome, which is mostly represented by efflux-pump resistance genes responsible for the intrinsic resistance. On the other hand, defense mechanisms of L. pentosus CF2-10 N include eight prophage regions and a CRISPR/cas system (CRISPR-I and CRISPR-II) as acquired immune system against mobile elements. Finally, the probiotic potential of this strain was further demonstrated by the presence of genes coding for proteins involved in adhesion, exopolysaccharide biosynthesis, tolerance to low pH and bile salts, immunomodulation, and vitamin and enzyme production. Taken together these results, we propose the use of L. pentosus CF2-10 N as a potential and promising probiotic candidate able to colonize several niches and adapt to different lifestyles. The strain can provide attractive functional and probiotic features necessary for its application as starter culture and probiotic.
Taxonomic dependency of beta diversity for bacteria, archaea, and fungi in a semi-arid lake
Authors: Yuan Haijun , Zhang Weizhen , Yin Huaqun , Zhang Runyu , Wang Jianjun
Published: November 2022

Microbial beta diversity has been recently studied along the water depth in aquatic ecosystems, however its turnover and nestedness components remain elusive especially for multiple taxonomic groups. Based on the beta diversity partitioning developed by Baselga and Local Contributions to Beta Diversity (LCBD) partitioning by Legendre, we examined the water-depth variations in beta diversity components of bacteria, archaea and fungi in surface sediments of Hulun Lake, a semi-arid lake in northern China, and further explored the relative importance of environmental drivers underlying their patterns. We found that the relative abundances of Proteobacteria, Chloroflexi, Euryarchaeota, and Rozellomycota increased toward deep water, while Acidobacteria, Parvarchaeota, and Chytridiomycota decreased. For bacteria and archaea, there were significant (p < 0.05) decreasing water-depth patterns for LCBD and LCBDRepl (i.e., species replacement), while increasing patterns for total beta diversity and turnover, implying that total beta diversity and LCBD were dominated by species turnover or LCBDRepl. Further, bacteria showed a strong correlation with archaea regarding LCBD, total beta diversity and turnover. Such parallel patterns among bacteria and archaea were underpinned by similar ecological processes like environmental selection. Total beta diversity and turnover were largely affected by sediment total nitrogen, while LCBD and LCBDRepl were mainly constrained by water NO2−-N and NO3−-N. For fungal community variation, no significant patterns were observed, which may be due to different drivers like water nitrogen or phosphorus. Taken together, our findings provide compelling evidences for disentangling the underlying mechanisms of community variation in multiple aquatic microbial taxonomic groups.
Single-molecule dynamics suggest that ribosomes assemble at sites of translation in Bacillus subtilis
Authors: Stoll Joshua , Zegarra Victor , Bange Gert , Graumann Peter L.
Published: November 2022

Eukaryotic cells transcribe ribosomal RNA and largely assemble ribosomes in a structure called the nucleolus, where chromosomal regions containing rRNA operons are clustered. In bacteria, many rRNA operons cluster close to the origin regions that are positioned on the outer borders of nucleoids, close to polar areas, where translating 70S ribosomes are located. Because outer regions of the nucleoids contain the highest accumulation of RNA polymerase, it has been hypothesized that bacteria contain “nucleolus-like” structures. However, ribosome subunits freely diffuse through the entire cells, and could thus be assembled and matured throughout the non-compartmentalized cell. By tracking single molecules of two GTPases that play an essential role in ribosomal folding and processing in Bacillus subtilis, we show that this process takes place at sites of translation, i.e., predominantly at the cell poles. Induction of the stringent response led to a change in the population of GTPases assumed to be active in maturation, but did not abolish nucleoid occlusion of ribosomes or of GTPases. Our findings strongly support the idea of the conceptualization of nucleolus-like structures in bacteria, i.e., rRNA synthesis, ribosomal protein synthesis and subunit assembly occurring in close proximity at the cell poles, facilitating the efficiency of ribosome maturation even under conditions of transient nutrient deprivation.
Association of cognitive function with Neurofilament light chain in the aqueous humor of human eye
Authors: Bai Jianhao , Wan Zhongqi , Wang Minli , Wu Xue , Wang Tianyu , Zhang Yuanyuan , Xue Yawen , Xu Hong , Peng Qing
Published: November 2022

Objectives

To evaluate the predictive clinical role of neurofilament light chain (NfL), amyloid-β (Aβ), glial fibrillary acidic protein (GFAP), and phosphorylated tau at threonine 181 (p-tau181) proteins in human aqueous humor (AH) and quantify the retinal macular microvascular parameters by optical coherence tomography angiography (OCTA) as early diagnostic markers of Alzheimer’s disease (AD).

Methods

This prospective, single-site, cross-sectional, cohort study enrolled 55 participants, including 38 patients with neovascular age-related macular degeneration (nAMD) and 17 individuals with senile cataracts. The single-molecule array platform was used to quantitatively measure the levels of AH NfL, Aβ40, Aβ42, GFAP, and p-tau181 proteins in AH. The mini-mental state examination (MMSE) score was used to assess the global cognitive function. OCTA scan with 6 × 6 mm macular area was used to quantify the retinal thickness and microvascular densities of superficial retinal capillary plexuses and deep retinal capillary plexuses.

Results

NfL, Aβ40, Aβ42, GFAP, and p-tau181 were detected in all AH samples by Simoa platform. Individuals with cataract had higher concentrations of NfL and p-tau181 but lower Aβ40 and Aβ42 and similar GFAP compared to those with nAMD. Lower MMSE scores showed a negative correlation with NfL concentration of AH not only in the nAMD group (p = 0.043), but also in the cataract group (p = 0.032). However, the MMSE scores were not associated with the levels of Aβ40, Aβ42, GFAP, or p-Tau181. Further analysis found that the Aβ40 and Aβ42 concentrations showed a strong positive correlation (p < 0.0001). In addition, the NfL concentration showed a mild positive correlation with that of GFAP in the cataract group (p = 0.021). Although it has not reached statistical significance, there was a correlation between the levels of NfL and Aβ42 in the nAMD group (p = 0.051). Moreover, the macular superficial vessel density values had a negative correlation with the concentration of NfL (p = 0.004) but a positive correlation with MMSE scores (p = 0.045). The macular deep vessel density values were negatively correlated with the concentration of p-tau181 (p = 0.031) and positively correlated with MMSE scores (p = 0.020).

Conclusion

The examination of AD-related biomarkers in human AH and OCTA may improve the ocular-based AD detection methods and contribute to forestalling the progression of preclinical AD.
Multi-omics analysis reveals neuroinflammation, activated glial signaling, and dysregulated synaptic signaling and metabolism in the hippocampus of aged mice
Authors: Lu Yinzhong , Xu Kejia , Lin Dongyang , Wang Shuyan , Fu Rao , Deng Xiaobei , Croppi Giorgia , Zhang Junjie
Published: November 2022

Aging is an intricate biological event that occurs in both vertebrates and invertebrates. During the aging process, the brain, a vulnerable organ, undergoes structural and functional alterations, resulting in behavioral changes. The hippocampus has long been known to be critically associated with cognitive impairment, dementia, and Alzheimer’s disease during aging; however, the underlying mechanisms remain largely unknown. In this study, we hypothesized that altered metabolic and gene expression profiles promote the aging process in the hippocampus. Behavioral tests showed that exploration, locomotion, learning, and memory activities were reduced in aged mice. Metabolomics analysis identified 69 differentially abundant metabolites and showed that the abundance of amino acids, lipids, and microbiota-derived metabolites (MDMs) was significantly altered in hippocampal tissue of aged animals. Furthermore, transcriptomic analysis identified 376 differentially expressed genes in the aged hippocampus. A total of 35 differentially abundant metabolites and 119 differentially expressed genes, constituting the top 200 correlations, were employed for the co-expression network. The multi-omics analysis showed that pathways related to inflammation, microglial activation, synapse, cell death, cellular/tissue homeostasis, and metabolism were dysregulated in the aging hippocampus. Our data revealed that metabolic perturbations and gene expression alterations in the aged hippocampus were possibly linked to their behavioral changes in aged mice; we also provide evidence that altered MDMs might mediate the interaction between gut and brain during the aging process.
Exploring decision-making strategies in the Iowa gambling task and rat gambling task
Authors: Hultman Cathrine , Tjernström Nikita , Vadlin Sofia , Rehn Mattias , Nilsson Kent W. , Roman Erika , Åslund Cecilia
Published: November 2022

Decision-making requires that individuals perceive the probabilities and risks associated with different options. Experimental human and animal laboratory testing provide complimentary insights on the psychobiological underpinnings of decision-making. The Iowa gambling task (IGT) is a widely used instrument that assesses decision-making under uncertainty and risk. In the task participants are faced with a choice conflict between cards with varying monetary reinforcer/loss contingencies. The rat gambling task (rGT) is a pre-clinical version using palatable reinforcers as wins and timeouts mimicking losses. However, interspecies studies elaborating on human and rat behavior in these tasks are lacking. This study explores decision-making strategies among young adults (N = 270) performing a computerized version of the IGT, and adult outbred male Lister Hooded rats (N = 72) performing the rGT. Both group and individual data were explored by normative scoring approaches and subgroup formations based on individual choices were investigated. Overall results showed that most humans and rats learned to favor the advantageous choices, but to a widely different extent. Human performance was characterized by both exploration and learning as the task progressed, while rats showed relatively consistent pronounced preferences for the advantageous choices throughout the task. Nevertheless, humans and rats showed similar variability in individual choice preferences during end performance. Procedural differences impacting on the performance in both tasks and their potential to study different aspects of decision-making are discussed. This is a first attempt to increase the understanding of similarities and differences regarding decision-making processes in the IGT and rGT from an explorative perspective.
The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia
Authors: Visini Gabriela , Brown Samara , Weston-Green Katrina , Shannon Weickert Cynthia , Chesworth Rose , Karl Tim
Published: November 2022

Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it’s potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.
Brivaracetam exhibits mild pro-inflammatory features in an in vitro astrocyte-microglia co-culture model of inflammation
Authors: Ismail Fatme Seval , Faustmann Pedro M. , Kümmel Marie-Luise , Förster Eckart , Faustmann Timo Jendrik , Corvace Franco
Published: November 2022

Implications of glia in the pathophysiology of epilepsy raise the question of how these cells besides neurons are responsive to antiseizure medications (ASMs). Understanding ASM effects on glia and glia-mediated inflammation may help to explore astrocytes and microglia as potential targets for alternative anti-epileptogenic therapies. The aim of this study was to investigate the effects of the new generation ASM brivaracetam (BRV) in an astrocyte-microglia co-culture model of inflammation. Primary rat astrocytes co-cultures containing 5%–10% (M5, “physiological” conditions) or 30%–40% (M30, “pathological inflammatory” conditions) of microglia were treated with different concentrations of BRV (0.5, 2, 10, and 20 μg/ml) for 24 h. Glial cell viability was measured by MTT assay. Microglial activation states were analyzed by immunocytochemistry and astroglial connexin 43 (Cx43) expression by Western blot analysis and immunocytochemistry. Gap-junctional coupling was studied via Scrape Loading. Incubation with high, overdose concentration (20 μg/ml) of BRV significantly reduced the glial cell viability under physiological conditions (p < 0.01: **). Treatment with BRV in therapeutic concentrations (0.5 and 2 μg/ml) reduced the resting microglia (p < 0.05: *) and increased the microglial activation under inflammatory conditions (p < 0.01: **). Astroglial Cx43 expression was not affected. The gap-junctional coupling significantly increased only by 0.5 μg/ml BRV under physiological conditions (p < 0.05: *). Our findings suggest mild pro-inflammatory, in vitro features of BRV with regard to microglia morphology. BRV showed no effects on Cx43 expression and only limited effects on gap-junctional coupling. Reduction of glial viability by overdose BRV indicates possible toxic effects.