bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell RNA sequencing reveals the immune microenvironment and signaling networks in cystitis glandularis
Authors: Zhou Tai Lai , Chen Heng Xin , Wang Yin Zhao , Wen Si Jie , Dao Ping Hong , Wang Yu Hang , Chen Min Feng
Published: February 2023

Introduction

Cystitis glandularis (CG) is a rare chronic bladder hyperplastic disease that mainly manifests by recurrent frequent urination, dysuria and gross hematuria. The current lack of unified diagnosis and treatment criteria makes it essential to comprehensively describe the inflammatory immune environment in CG research.

Methods

Here, we performed scRNA-sequencing in CG patients for the first time, in which four inflamed tissues as well as three surrounding normal bladder mucosa tissues were included. Specifically, we isolated 18,869 cells to conduct bioinformatic analysis and performed immunofluorescence experiments.

Results

Our genetic results demonstrate that CG does not have the classic chromosomal variation observed in bladder tumors, reveal the specific effects of TNF in KRT15 epithelial cells, and identify a new population of PIGR epithelial cells with high immunogenicity. In addition, we confirmed the activation difference of various kinds of T cells during chronic bladder inflammation and discovered a new group of CD27-Switch memory B cells expressing a variety of immunoglobulins.

Discussion

CG was regarded as a rare disease and its basic study is still weak.Our study reveals, for the first time, the different kinds of cell subgroups in CG and provides the necessary basis for the clinical treatment of cystitis glandularis. Besides, our study significantly advances the research on cystitis glandularis at the cellular level and provides a theoretical basis for the future treatment of cystitis glandularis.
The effects of traditional Chinese medicine and dietary compounds on digestive cancer immunotherapy and gut microbiota modulation: A review
Authors: Feng Xiaoli , Li Zhenhao , Guo Weihong , Hu Yanfeng
Published: February 2023

Digestive tract-related cancers account for four of the top ten high-risk cancers worldwide. In recent years, cancer immunotherapy, which exploits the innate immune system to attack tumors, has led to a paradigm shifts in cancer treatment. Gut microbiota modification has been widely used to regulate cancer immunotherapy. Dietary compounds and traditional Chinese medicine (TCM) can alter the gut microbiota and its influence on toxic metabolite production, such as the effect of iprindole on lipopolysaccharide (LPS), and involvement in various metabolic pathways that are closely associated with immune reactions. Therefore, it is an effective strategy to explore new immunotherapies for gastrointestinal cancer to clarify the immunoregulatory effects of different dietary compounds/TCMs on intestinal microbiota. In this review, we have summarized recent progress regarding the effects of dietary compounds/TCMs on gut microbiota and their metabolites, as well as the relationship between digestive cancer immunotherapy and gut microbiota. We hope that this review will act as reference, providing a theoretical basis for the clinical immunotherapy of digestive cancer via gut microbiota modulation.
A semi high-throughput whole blood-based flow cytometry assay to detect and monitor Bordetella pertussis-specific Th1, Th2 and Th17 responses
Authors: Corbière Véronique , Lambert Eleonora E. , Rodesch Marine , van Gaans-van den Brink Jacqueline A. M. , Misiak Alicja , Simonetti Elles , Van Praet Anne , Godefroid Audrey , Diavatopoulos Dimitri A. , van Els Cécile A. C. M. , Mascart Françoise ,   PERISCOPE WP5 Task 7 working group
Published: February 2023

Introduction

The characterization of B. pertussis (Bp) antigen-specific CD4+ T cell cytokine responses should be included in the evaluation of immunogenicity of pertussis vaccines but is often hindered by the lack of standardized robust assays.

Methods

To overcome this limitation, we developed a two-step assay comprising a short-term stimulation of fresh whole blood with Bp antigens and cryopreservation of the stimulated cells, followed later on by batch-wise intracellular cytokine analysis by flow cytometry. Blood samples collected from recently acellular (aP) vaccine boosted subjects with a whole-cell- or aP-primed background was incubated for 24 hrs with Pertussis toxin, Filamentous hemagglutinin or a Bp lysate (400µl per stimulation). Antigen-specific IFN-γ-, IL-4/IL-5/IL-13-, IL-17A/IL-17F- and/or IL-22-producing CD4+ T cells were quantified by flow cytometry to reveal Th1, Th2, and Th17-type responses, respectively. The frequencies of IFN-γ-producing CD8+ T cells were also analyzed.

Results

We demonstrate high reproducibility of the Bp-specific whole blood intracellular staining assay. The results obtained after cryopreservation of the stimulated and fixed cells were very well correlated to those obtained without cryopreservation, an approach used in our previously published assay. Optimization resulted in high sensitivity thanks to very low non-specific backgrounds, with reliable detection of Bp antigen-specific Th1, Th2 and Th17-type CD4+ T cells, in the lowest range frequency of 0.01-0.03%. Bp antigen-specific IFN-γ+ CD8+ T lymphocytes were also detected. This test is easy to perform, analyse and interpret with the establishment of strict criteria defining Bp antigen responses.

Discussion

Thus, this assay appears as a promising test for evaluation of Bp antigen-specific CD4+ T cells induced by current and next generation pertussis vaccines.
TRAF3: Guardian of T lymphocyte functions
Authors: Hornick Emma L. , Bishop Gail A.
Published: February 2023

Tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is an adapter protein with many context-specific functions. Early studies of lymphocyte TRAF3 hinted at TRAF3’s importance for T cell function, but elucidation of specific mechanisms was delayed by early lethality of globally TRAF3-/- mice. Development of a conditional TRAF3-deficient mouse enabled important descriptive and mechanistic insights into how TRAF3 promotes optimal T cell function. Signaling through the T cell antigen receptor (TCR) fails to induce normal proliferation and survival in TRAF3-/- T cells, and TCR-activated cells in vitro and in vivo have deficient cytokine production. These defects can be traced to incorrect localization and function of negative regulatory phosphatases acting at different parts of the signaling cascade, as can dysregulated effector responses and memory T cell homeostasis in vivo and an enlarged regulatory T cell (Treg) compartment. The important regulatory activity of TRAF3 is also evident at members of the TNFR superfamily and cytokine receptors. Here, we review significant advances in mechanistic understanding of how TRAF3 regulates T cell differentiation and function, through modulation of signaling through the TCR, costimulatory receptors, and cytokine receptors. Finally, we briefly discuss the recent identification of families carrying single allele loss-of-function mutations in TRAF3, and compare the findings in their T cells with the T cell defects identified in mice whose T cells completely lack T cell TRAF3. Together, the body of work describing TRAF3-mediated regulation of T cell effector function and differentiation frame TRAF3 as an important modulator of T cell signal integration.
Spotted! Computer-aided individual photo-identification allows for mark-recapture of invasive spotted lanternfly (Lycorma delicatula)
Authors: Belouard Nadège , Behm Jocelyn E.
Published: February 2023

The spotted lanternfly is an invasive pest for which we lack individual movement data due in part to the difficulty posed by individual identification. We developed a computer‐aided method to identify individual adult spotted lanternfly using wing spot patterns from photos processed in the software I3S and demonstrated the method’s accuracy with lab and field validations. Based on 176 individuals in the lab, we showed that digitizing the spots of one wing allowed a 100% reliable individual identification. The errors due to user input and the variation in the angle of the image were largely negligible compared to inter-individual variations. We applied this method in the context of a mark-recapture experiment to assess the feasibility of this method in the field. We initially identified a total of 84 unique spotted lanternflies, 31 of which were recaptured after four hours along with 49 new individuals. We established that the analysis of recaptures can possibly be automated based on scores and may not require systematic visual pairwise comparison. The demonstration of the effectiveness of this method on relatively small sample sizes makes it a promising tool for field experimentation as well as lab manipulations. Once validated on larger datasets and in different contexts, it will provide ample opportunity to collect useful data on spotted lanternfly ecology that can greatly inform management.
Mitochondrial DNA diversity and genetic structure of striped dolphin Stenella coeruleoalba in the Northern Ionian Sea
Authors: Antonacci Rachele , Linguiti Giovanna , Paradiso Federica , Scalone Chiara , Fanizza Carmelo , Ciani Elena , Cipriano Giulia , Ciccarese Salvatrice , Carlucci Roberto
Published: February 2023

In the framework of global and EU policies focused on stopping the loss of biodiversity process, deepening the genetic variability, especially of populations species identified as threatened, is crucial for defining conservation units and developing appropriate conservation strategies. This is more urgent for cetacean species in the Mediterranean because they assume a key ecological role in the marine food web and are severely affected by numerous and different anthropogenic pressures. This study aims to increase information on the genetic variability of striped dolphin in the Northern Ionian Sea by investigating the population structure, phylogenetic relationships and phylogeographic patterns using two mtDNA markers. From October 2020 to August 2021, a total of 88 skin tissue samples were collected from free-ranging dolphins in the Gulf of Taranto by applying the non-invasive technique of skin swabbing. An acceptable amount of DNA was extracted from 86 samples and used for subsequent genetic analysis conducted on the partial sequences of 421 and 704 bp in length of the cytb gene and D-loop control region, respectively. In addition, the sequences of the two mtDNA markers were joined together to compose a mtDNA concatenated sequence of 1125 bp for each sampled dolphin in order to investigate the genetic variability of the species population in the study area. Genetic analysis highlighted a low nucleotide diversity and high haplotypic diversity of the striped dolphin of the Gulf of Taranto, suggesting a population in rapid expansion after a period of reduction in size and diversity of the initial population. The phylogenetic analyses revealed the presence of at least two different lineages ofStenella coeruleoalbain the Mediterranean Sea, one specific to the Northern Ionian Sea and one shared with the Mediterranean population, confirming results already obtained for the local unit in the Gulf of Taranto. The results point out a potential problem of hybridization between striped and common dolphins which needs to be further investigated. Therefore, increasing the analysis of several markers may increase understanding of the genetic diversity of the population in the Ionian Sea and represent a useful tool to support the implementation of future effective conservation measures.
Teleost TRAF7, a protein functions in the host antiviral responses via NF-κB and IRF3/7 mediated signaling
Authors: Li Peng Tian , Li Ying , Chen Ying , Zhang Jia Xi , Luo Zi Hao , Zhang Yi Fan , Jiang Jing , Wang Yi Lei , Zhang Zi Ping , Jiang Yong Hua , Zou Peng Fei
Published: February 2023

Tumor necrosis factor receptor-associated factors (TRAFs) play vital roles in tumor necrosis factor receptor (TNF-R) and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) mediated signaling pathway. However, the role that TRAF7 plays in the host immune responses is largely unknown in comparison to the extensive and in-depth research that has been conducted on other members of the TRAF family. Notably, Lc-TRAF7, a cloned TRAF7 ortholog, was discovered in the large yellow croaker (Larimichthys crocea) in the current study, which has an open reading frame (ORF) of 1,962 base pairs and encodes a protein of 653 amino acids (aa). Lc-TRAF7 is consisted of a RING finger domain, a coiled-coil domain, and seven WD40 domains, with the genomic organization consisted of 20 exons and 19 introns. According to the expression analysis, Lc-TRAF7 was presented in a wide range of detected organs and tissues of the healthy fish, and was able to significantly induced by stimulations of poly I:C, LPS, PGN, and Pseudomonas plecoglossicida infection. Subcellular distribution analysis revealed that Lc-TRAF7 was a cytoplasmic protein, with the RING finger and coiled-coil domain function importantly in its subcellular localization. Luciferase assays demonstrated that Lc-TRAF7 overexpression significantly induced the activation of NF-κB, IRF3, IRF7, and IFN1 promoters. In addition, the WD40 domains play a pivotal role in the NF-κB promoter activation, whereas the RING finger and coiled-coil domain were essential in the IRF3, IRF7, and IFN1 promoter activation. Notably, Lc-TRAF7 overexpression could suppress SVCV proliferation in EPC cells, and the expression levels of IRF3, IRF7, ISG15, ISG56, RSAD2, and TNF-α were up-regulated under Lc-TRAF7 overexpression in LYCMS cells. These findings collectively implied that Lc-TRAF7 may function as an important regulator in the host antiviral responses via the NF-κB as well as IRF3/7 involved signaling pathways.
Upscaling cultivation of Saccharina latissima on net or line systems; comparing biomass yields and nutrient extraction potentials
Authors: Boderskov Teis , Rasmussen Michael Bo , Bruhn Annette
Published: February 2023

Production of sugar kelp, Saccharina latissima, has the potential of extracting nutrients and carbon from the seawater and returning it to land as a bioresource. The production thereby acts as an emission capture and utilization instrument contributing to mitigation of eutrophication and climate change. To achieve higher biomass yields improving the effects on climate and environment, and the economic feasibility of the production, cultivation techniques need to be optimized. In Denmark so far, S. latissima production yields have been lower than yields documented from Norway and the Faroe Islands. Use of alternative cultivation infrastructure designs with a higher line density per area, and better understanding the effects of annual and seasonal variations in abiotic parameters on growth, could lead the way towards a future higher yield of the S. latissima production. In this study, S. latissima was cultivated in a Danish commercial scale cultivation site for two consecutive seasons comparing the yields of different cultivation techniques: cultivation on nets and a multi-layer single line system, while also testing the possibility of coppicing the blades instead of applying a full harvest. Biomass yields of 5.0 - 6.8 kg FW m-1 cultivation line year-1, and 10.9 – 30.4 kg FW m-2 net structure were achieved. Biomass production, nutrient and carbon extraction potentials up to 91.3 t FW, 110 kg N, 13.1 kg P and 5.1 t C ha-1 were obtained using net cultivation systems and a 1.5 years growth period. Depth of cultivation had a significant effect on yield, but no effect on dry matter, C, N or P contents of S. latissima in a multi-layered line system. Biomass yields from the same system and site varied with a factor of four between years. The use of coppicing enabled multiple harvests of S. latissima, providing however biomass of reduced quality in the second year. This study demonstrates that the production yield of S. latissima can be increased by optimizing cultivation infrastructure, and indicates that net systems, or other cultivation systems with a high line density in the upper water column, can be a means to increase the areal yield of S. latissima.
Biomass-derived fiber materials for biomedical applications
Authors: Li Daixiu , Wang Yilin , Huang Wenhua , Gong Haihuan
Published: February 2023

Graphical Abstract

Schema of biomass-derived fiber materials (cellulose, chitin, alginate, silk fibroin, collagen, hyaluronic acid, etc.,) for biomedical applications, such as antibacterial skin-wound dressings, tissue engineering, and drug delivery.
Effects of laser energy density on morphology features and microstructures of the single molten track in selective laser melting
Authors: Wang Sen , Wang Linzhi , Liu Jiquan , Yang Runqi , Li Jing , Wang Guoyu
Published: February 2023

Single molten track (SMT) is the basic unit of the selective laser melting (SLM) process, of which the morphology features and microstructures have great significance on the molding quality. In this study, the effects of laser energy density (LED) on characteristics of SMT were studied with 316 L stainless steel processing by SLM. The results indicate that an optimized range of LED was between 200 and 500 J/mm3, which was the best for SLM process of 316 L leading to beautiful SMT appearance such as continuous uniform water-ridge-like surface, good contour straightness, smooth edges, little adhesive powder, and high densification. The microstructures of the SMT molten pool are mainly composed of equiaxed cellular and columnar dendrites. As the LED decreased, the cellular became smaller and disappeared, while the length and width of columnar crystals even gradually increased. The size of the cellular varies between 0.43 and 1.70 μm with the LEDs increase. The relationship between SMT characteristics and LED found in this work can be readily used to optimize SMT and control the microstructures in situ, and the laser energy density range that the work has identified will simplify most of the guess work in additive manufacturing.
Numerical and experimental investigation of gas flow field variations in three-dimensional printed gas-dynamic virtual nozzles
Authors: Nazari Reza , Ansari Adil , Herrmann Marcus , Adrian Ronald J. , Kirian Richard A.
Published: February 2023

Gas-dynamic virtual nozzles (GDVNs) play a vital role in delivering biomolecular samples during diffraction measurements at X-ray free-electron laser facilities. Recently, submicrometer resolution capabilities of two-photon polymerization 3D printing techniques opened the possibility to quickly fabricate gas-dynamic virtual nozzles with practically any geometry. In our previous work, we exploited this capability to print asymmetric gas-dynamic virtual nozzles that outperformed conventional symmetric designs, which naturally leads to the question of how to identify the optimal gas-dynamic virtual nozzle geometry. In this work, we develop a 3D computational fluid dynamics pipeline to investigate how the characteristics of microjets are affected by gas-dynamic virtual nozzle geometry, which will allow for further geometry optimizations and explorations. We used open-source software (OpenFOAM) and an efficient geometric volume-of-fluid method (isoAdvector) to affordably and accurately predict jet properties for different nozzle geometries. Computational resources were minimized by utilizing adaptive mesh refinement. The numerical simulation results showed acceptable agreement with the experimental data, with a relative error of about 10% for our test cases that compared bell- and cone-shaped sheath-gas cavities. In these test cases, we used a relatively low sheath gas flow rate (6 mg/min), but future work including the implementation of compressible flows will enable the investigation of higher flow rates and the study of asymmetric drip-to-jet transitions.
Minimally invasive 1,444-nm Nd:YAG laser treatment for axillary bromhidrosis
Authors: Piccolo Domenico , Mutlag Mohammed Hussein , Pieri Laura , Fusco Irene , Conforti Claudio , Crisman Giuliana , Bonan Paolo
Published: February 2023

Background

Axillary bromhidrosis is an apocrine glands hyperactivity disease.

Methods

A total of 24 patients (15 men and 9 women) with axillary bromhidrosis underwent a laser procedure with a 1,444-nm Nd:YAG laser. Parameters evaluated in this study were as follows: the degree of malodor (T0, baseline; T30, after 1 month; and T180, after 6 months), postoperative pain, short-term decreased mobility (T1, after 1 day; T7, after 7 days; and T30, after 1 month), and overall satisfaction (T30, after 1 month and T180, after 6 months). A visual analog scale (VAS), from 0 to 10, was used to assess pain and decreased mobility, with lower values denoting less severity.

Results

A total of 24 patients were followed up for 6 months after laser treatment. At baseline, all patients (100%) complained of a strong axillary malodor (mean degree of malodor at T0 = 2.0 ± 0.00). It decreased to 0.50 ± 0.64 at T30. At T180, the degree of malodor was 0.54 ± 0.57. Both T30 and T180 degrees of malodor significantly decreased from the baseline value (p < 0.01). The mean degree of patient satisfaction at T30 was 1.75 ± 0.52, and at T180, it was 1.67 ± 0.21. Among the 24 patients, eight complained of moderated pain 1 day after treatment. The pain subsided on day 7, except for two patients, with VAS = 1. Pain and mobility restrictions were in any case resolved within T30.

Conclusion

Treatment with a 1,444-nm Nd:YAG laser for subdermal interstitial coagulation could be a less invasive and more effective option treatment for axillary bromhidrosis.
Replacement of water yam (Dioscorea alata L.) indigenous root endophytes and rhizosphere bacterial communities via inoculation with a synthetic bacterial community of dominant nitrogen-fixing bacteria
Authors: Liswadiratanakul Sumetee , Yamamoto Kosuke , Matsutani Minenosuke , Wattanadatsaree Vatanee , Kihara Shunta , Shiwa Yuh , Shiwachi Hironobu
Published: February 2023

Biofertilizers containing high-density plant growth-promoting bacteria are gaining interest as a sustainable solution to environmental problems caused by eutrophication. However, owing to the limitations of current investigative techniques, the selected microorganisms are not always preferred by the host plant, preventing recruitment into the native microbiota or failing to induce plant growth-promoting effects. To address this, five nitrogen-fixing bacteria previously isolated from water yam (Dioscorea alata L.) plants and showing dominant abundance of 1% or more in the water yam microbiota were selected for analysis of their plant growth-promoting activities when used as a synthetic bacterial inoculant. Water yam cv. A-19 plants were inoculated twice at 10 and 12 weeks after planting under greenhouse conditions. Bacterial communities in root, rhizosphere, and bulk soil samples were characterized using high-throughput 16S rRNA amplicon sequencing. Compared with non-inoculated plants, all bacterial communities were significantly altered by inoculation, mainly at the genus level. The inoculation effects were apparently found in the root communities at 16 weeks after planting, with all inoculated genera showing dominance (in the top 35 genera) compared with the control samples. However, no significant differences in any of the growth parameters or nitrogen contents were observed between treatments. At 20 weeks after planting, the dominance of Stenotrophomonas in the inoculated roots decreased, indicating a decline in the inoculation effects. Interestingly, only the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade was dominant (>1% relative abundance) across all samples, suggesting that bacteria related to this clade are essential core bacteria for water yam growth. This is the first report on addition of a synthetic nitrogen-fixing bacterial community in water yam plants showing that native bacterial communities can be replaced by a synthetic bacterial community, with declining in the effects of Stenotrophomonas on the modified communities several weeks after inoculation.
Effect of dietary biochanin A on lactation performance, antioxidant capacity, rumen fermentation and rumen microbiome of dairy goat
Authors: Xu Qingbiao , Li Yanjun , Du Wenjuan , Zheng Nan , Wang Jiaqi , Zhao Shengguo
Published: February 2023

Biochanin A (BCA), an isoflavone phytoestrogen, is a secondary metabolite produced mainly in leguminous plants. The objective of this study was to evaluate the effect of BCA on lactation performance, nitrogen metabolism, and the health of dairy goat. Thirty mid-lactation Saanen dairy goats were divided into three groups randomly: control, 2 g/d BCA group, and 6 g/d BCA group. After 36 days of feeding, 30 dairy goats were transferred to individual metabolic cages. Subsequently, milk yield, feed intake, total feces, and urine excretion were recorded and samples were collected continuously for 3 days. Blood and ruminal fluid samples were collected over the subsequent 4 days. Milk yield, milk protein, fat content, and the feed conversion ratio of dairy goat were significantly increased by the BCA treatment. The levels of serum 17β-estradiol, growth hormone, insulin-like growth factor 1, glutathione peroxidase activity, and total antioxidant capacity were also increased significantly by BCA, indicating that BCA enhanced the antioxidant capacity of dairy goat. Amino acid degradation was significantly inhibited, while the ammonia nitrogen content was reduced significantly by BCA. Total volatile fatty acids was significantly increased by BCA supplementation. In addition, the relative abundance of Verrucomicrobiota was decreased significantly. However, the growth of nitrogen metabolism and cellulolytic bacteria was significantly increased under BCA treatment, including Prevotella sp., Treponema sp., Ruminococcus flavefaciens, and Ruminobacter amylophilus. In conclusion, supplementation with BCA improved the milk production performance, nitrogen metabolism, rumen fermentation and antioxidant capacity, and regulated the rumen microbiome of dairy goat.
Quantitative comparison of protein-protein interaction interface using physicochemical feature-based descriptors of surface patches
Authors: Shin Woong-Hee , Kumazawa Keiko , Imai Kenichiro , Hirokawa Takatsugu , Kihara Daisuke
Published: February 2023

Driving mechanisms of many biological functions in a cell include physical interactions of proteins. As protein-protein interactions (PPIs) are also important in disease development, protein-protein interactions are highlighted in the pharmaceutical industry as possible therapeutic targets in recent years. To understand the variety of protein-protein interactions in a proteome, it is essential to establish a method that can identify similarity and dissimilarity between protein-protein interactions for inferring the binding of similar molecules, including drugs and other proteins. In this study, we developed a novel method, protein-protein interaction-Surfer, which compares and quantifies similarity of local surface regions of protein-protein interactions. protein-protein interaction-Surfer represents a protein-protein interaction surface with overlapping surface patches, each of which is described with a three-dimensional Zernike descriptor (3DZD), a compact mathematical representation of 3D function. 3DZD captures both the 3D shape and physicochemical properties of the protein surface. The performance of protein-protein interaction-Surfer was benchmarked on datasets of protein-protein interactions, where we were able to show that protein-protein interaction-Surfer finds similar potential drug binding regions that do not share sequence and structure similarity. protein-protein interaction-Surfer is available at https://kiharalab.org/ppi-surfer.
Mobility and associations with levels of cerebrospinal fluid amyloid β and tau in a memory clinic cohort
Authors: Tangen Gro Gujord , Sverdrup Karen , Taraldsen Kristin , Persson Karin , Engedal Knut , Bekkhus-Wetterberg Peter , Knapskog Anne-Brita
Published: February 2023

Background

Mobility impairments, in terms of gait and balance, are common in persons with dementia. To explore this relationship further, we examined the associations between mobility and cerebrospinal fluid (CSF) core biomarkers for Alzheimer’s disease (AD).

Methods

In this cross-sectional study, we included 64 participants [two with subjective cognitive decline (SCD), 13 with mild cognitive impairment (MCI) and 49 with dementia] from a memory clinic. Mobility was examined using gait speed, Mini-Balance Evaluation Systems test (Mini-BESTest), Timed Up and Go (TUG), and TUG dual-task cost (TUG DTC). The CSF biomarkers included were amyloid-β 42 (Aβ42), total-tau (t-tau), and phospho tau (p-tau181). Associations between mobility and biomarkers were analyzed through correlations and multiple linear regression analyses adjusted for (1) age, sex, and comorbidity, and (2) SCD/MCI vs. dementia.

Results

Aβ42 was significantly correlated with each of the mobility outcomes. In the adjusted multiple regression analyses, Aβ42 was significantly associated with Mini-BESTest and TUG in the fully adjusted model and with TUG DTC in step 1 of the adjusted model (adjusting for age, sex, and comorbidity). T-tau was only associated with TUG DTC in step 1 of the adjusted model. P-tau181 was not associated with any of the mobility outcomes in any of the analyses.

Conclusion

Better performance on mobility outcomes were associated with higher levels of CSF Aβ42. The association was strongest between Aβ42 and Mini-BESTest, suggesting that dynamic balance might be closely related with AD-specific pathology.
Alcohol and cannabinoid binges and daily exposure to nicotine in adolescent/young adult rats induce sex-dependent long-term appetitive instrumental learning impairment
Authors: Abela Norbert , Haywood Katie , Di Giovanni Giuseppe
Published: February 2023

Adolescence is a critical developmental period, concerning anatomical, neurochemical and behavioral changes. Moreover, adolescents are more sensitive to the long-term deleterious effects of drug abuse. Binge-like consumption of alcohol and marijuana, along with tobacco smoking, is a dangerous pattern often observed in adolescents during weekends. Nevertheless, the long-term effect of their adolescent co-exposure has not been yet experimentally investigated. Long-Evans adolescent male (n = 20) and female (n = 20) rats from postnatal day 30 (P30) until P60 were daily treated with nicotine (0.3 mg/kg, i.p.), and, on two consecutive ‘binging days’ per week (for a total of eight times), received an intragastric ethanol solution (3 g/kg) and an intraperitoneal (i.p.) dose of cannabinoid 1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). These rats were tested after treatment discontinuation at > P90 for associative food-rewarded operant learning in the two-lever conditioning chambers for six consecutive days on a fixed ratio 1 (FR1) schedule followed by another six days of daily FR2 schedule testing, after 42 days rest. We found the main effects of sex x treatment interactions in FR1 but not in FR2 experiments. Treated females show attenuated operant responses for food pellets during all FR1 and the FR2 schedule, whilst the treated males show an impairment in FR2 but not in the FR1 schedule. Moreover, the treated females’ percentage of learners was significantly lower than female controls in FR1 while treated males were lower than controls in FR2. Our findings suggest that intermittent adolescent abuse of common drugs, such as alcohol and marijuana, and chronic tobacco exposure can cause significant long-term effects on motivation for natural reinforcers later in adulthood in both sexes. Females appear to be sensitive earlier to the deleterious effects of adolescent polydrug abuse, with both sexes having an increased likelihood of developing lifelong brain alterations.
Mechanisms of robustness in gene regulatory networks involved in neural development
Authors: Arcuschin Camila D. , Pinkasz Marina , Schor Ignacio E.
Published: February 2023

The functions of living organisms are affected by different kinds of perturbation, both internal and external, which in many cases have functional effects and phenotypic impact. The effects of these perturbations become particularly relevant for multicellular organisms with complex body patterns and cell type heterogeneity, where transcriptional programs controlled by gene regulatory networks determine, for example, the cell fate during embryonic development. Therefore, an essential aspect of development in these organisms is the ability to maintain the functionality of their genetic developmental programs even in the presence of genetic variation, changing environmental conditions and biochemical noise, a property commonly termed robustness. We discuss the implication of different molecular mechanisms of robustness involved in neurodevelopment, which is characterized by the interplay of many developmental programs at a molecular, cellular and systemic level. We specifically focus on processes affecting the function of gene regulatory networks, encompassing transcriptional regulatory elements and post-transcriptional processes such as miRNA-based regulation, but also higher order regulatory organization, such as gene network topology. We also present cases where impairment of robustness mechanisms can be associated with neurodevelopmental disorders, as well as reasons why understanding these mechanisms should represent an important part of the study of gene regulatory networks driving neural development.
Temperature controlled microcapsule loaded with Perilla essential oil and its application in preservation of peaches
Authors: Tai Zhigang , Zheng Minjie , Yang Ye , Xie Cheng , Li Zhenjie , Xu Chunping
Published: February 2023

In this study, Perilla frutescens essential oil (PEO) loaded microcapsules (PEOM) were successfully prepared and their thermal stability, temperature-responsive releasing effect, antioxidant activity, antibacterial activity, and preservation of peach were systematically investigated. PEOM showed excellent encapsulation efficiency (91.5%) with a core-shell ratio of 1.4:1 and exhibited high thermal stability, indicating that PEOM could effectively maintain PEO release rate. In vitro assays indicated that the optimal kinetic model for PEO release fitted well with first order with a diffusion mechanism. A high level of antioxidant and antibacterial activity of PEOM was maintained. In addition, owing to its sustained release, PEOM could prolong the shelf life of peaches significantly. Therefore, PEOM has potential application and development prospects in the field of food preservation.
Heterogeneous disease and intermittent treatment in metastatic colorectal cancer: A case report
Authors: De Stefano Alfonso , Zanaletti Nicoletta , Cassata Antonino , Silvestro Lucrezia , Nappi Anna , Casaretti Rossana , Romano Carmela , Foschini Francesca , Cardone Claudia , Borrelli Marco , Petrillo Antonella , Budillon Alfredo , Delrio Paolo , Avallone Antonio
Published: February 2023

Background

Metastatic colorectal cancer is one of the most common causes of cancer death worldwide. RAS and BRAF mutational analyses are strongly recommended before beginning chemotherapy in the metastatic setting for their predictive role for the efficacy of anti-EGFR monoclonal antibodies. In most of cases, mutational status coincides between primary tumor and metastases. In RAS and BRAF wild-type patients treated with anti-EGFRs, after an induction treatment period, recent evidence supports the role of a maintenance treatment with fluoropyrimidines and anti-EGFRs. However, skin toxicity is the most described and limiting side-effect of maintenance. Moreover, it is described that the continuous administration of these monoclonal antibodies leads to an acquired resistance to anti-EGFRs, with subsequent treatment failure. Intermittent strategy with chemotherapy plus anti-EGFR may help maintain treatment efficacy, delaying resistance.

Case presentation

In this case report, we describe the case of a RAS-BRAF wild-type elderly patient undergoing first-line chemotherapy with FOLFOX + panitumumab, reporting response of disease on all metastatic sites except for a node. This node, surgically removed, revealed host BRAF V600 mutant clones. After surgery, patient continued chemotherapy with a stop-and-go strategy continuing to benefit from the same drugs after 4 years since diagnosis, and continuing to achieve response when on treatment, avoiding unacceptable anti-EGFR toxicity. This patient, still alive after 6 years since the diagnosis, represents the case of a good synergy between molecular profiling of disease, surgery, and intermittent treatment.
Myeloid leukemia factor 1: A “double-edged sword” in health and disease
Authors: Li Zixuan , Yang Yuanyuan , Wu Kun , Li Yuntao , Shi Mingxia
Published: February 2023

The occurrence and development of malignancies are closely related to abnormal cell cycle regulation. Myeloid leukemia factor 1 (MLF1) is a small nucleocytoplasmic shuttling protein associated with cell cycle exit, apoptosis, and certain immune functions. Therefore, it is pertinent to explore the role of MLF1 in health and diseases. Studies to date have suggested that MLF1 could act as a double-edged sword, regulating biochemical activities directly or indirectly. In hematopoietic cells, it serves as a protective factor for the development of lineages, and in malignancies, it serves as an oncogenesis factor. The diversity of its functions depends on the binding partners, including tumor inhibitors, scaffolding molecules, mitochondrial membrane proteins, and transcription factors. Emerging evidence indicates that MLF1 influences immune responses as well. This paper reviews the structure, biological function, and research progress on MLF1 in health and diseases to provide new insights for future research.
Efficacy and survival analysis of nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma
Authors: Wang Lili , Zhuang Hengzhao , Xu Xiaoyan , Zhou Juying , Jiao Yang
Published: February 2023

Objective

This study investigated the curative effect of adding nimotuzumab (NTZ) in patients with locally advanced nasopharyngeal carcinoma (NPC) who were treated with concurrent chemoradiotherapy (CCRT) and explored significant prognostic factors of NPC.

Materials and methods

The clinical data of 307 patients with NPC treated in the First Affiliated Hospital of Soochow University from January 2013 to December 2018 were retrospectively analyzed. The patients were divided into the NTZ-CCRT group and the CCRT group according to whether they were associated with NTZ. We applied propensity score matching to reduce the interference of biases and compared the short-term efficacy and long-term survival rate of the two groups. Moreover, univariate and multivariate analyses were performed for all patients, and subgroup analysis was used to compare the efficacy of therapy combined with NTZ in different subgroups.

Results

In primary nasopharyngeal tumors, the objective response rates in the NTZ-CCRT group and CCRT group were 95.8% and 85.7%, respectively (P =0.007). In cervical positive lymph nodes, the objective response rates in the NTZ-CCRT group and CCRT group were 98.3% and 87.4%, respectively (P =0.001). Compared with CCRT alone, the addition of NTZ significantly improved the 5-year OS (94.1% vs. 81.8%, P=0.014) and the 5-year DFS (84.2% vs. 75.5%, P=0.031) of NPC patients; however, the addition of NTZ was accompanied by more severe hematologic toxicity and acute oral mucositis. Multivariate analysis demonstrated that the addition of NTZ was an important prognostic factor for OS and DFS (HR 0.367, 95% CI 0.167-0.808, P=0.013 for OS and HR 0.536, 95% CI 0.312-0.919, P=0.023 for DFS) and the level of pretreatment LDH (HR 5.170, 95% CI 2.125-12.580, P<0.001 for OS and HR 2.421, 95% CI 1.027-5.707, P=0.043 for DFS). Moreover, patients with high levels of hsCRP before treatment (HR 0.389, 95% CI 0.177-0.853, P=0.018) may gain more benefits from combined treatment with NTZ.

Conclusions

For locally advanced NPC patients treated with concurrent chemoradiotherapy, the addition of NTZ can significantly improve their survival outcome. However, it is necessary to guard against the associated increase in hematological toxicity and acute oral mucositis.
Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice
Authors: Chen Qiong , Zhou Ting , Yuan Jun-jie , Xiong Xiao-yi , Liu Xue-hui , Qiu Zong-ming , Hu Lin-lin , Lu Hui , He Qian , Liu Chang , Yang Qing-wu
Published: February 2023

Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.
Posterior reversible encephalopathy syndrome after anlotinib treatment for small cell lung cancer: A case report and literature review
Authors: Zou Xiaomeng , Zhou Peng , Lv Wei , Liu Chuanyong , Liu Jie
Published: February 2023

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC) in China. The neurotoxicity is less reported. Posterior reversible encephalopathy syndrome (PRES) is characterized by headaches, seizures, encephalopathy, and visual disturbances, as well as focal reversible vasogenic edema seen on neuroimages. Here, we presented a case of PRES in a small cell lung cancer (SCLC) patient associated with anlotinib. A 37-year-old female patient, who had a history of diabetes, with extensive-stage SCLC received anlotinib after third-line chemotherapy. Ten cycles of anlotinib later, the patient experienced visual disturbance and was diagnosed with PRES based on the typical demyelination of white matter obtained in the brain magnetic resonance. During anlotinib therapy, the patient did not develop anti-VEGF therapy-induced hypertension. Subsequently, the patient stopped anlotinib, but she did not recover from symptoms. We also summarized the characteristics of fifty-four cases of PRES caused by antiangiogenic drugs in the literature. Based on our experience and the literature review, the incidence of PRES induced by antiangiogenic drugs is low, and the symptom can resolve upon stopping the medications. However, some cases still have a poor prognosis and the underlying mechanism requires further investigation. In addition, early detection and treatment of PRES are essential for physicians.
Highly charged ion (HCI) clocks: Frontier candidates for testing variation of fine-structure constant
Authors: Yu Yan-Mei , Sahoo B. K. , Suo Bing-Bing
Published: February 2023

Attempts are made to unify gravity with the other three fundamental forces of nature. As suggested by higher dimensional models, this unification may require space and time variation of some of the dimensionless fundamental constants. In this scenario, probing temporal variation of the electromagnetic fine structure constant (α=e2ℏc) in a low energy regime at the cosmological time scale is of immense interest. Atomic clocks are ideal candidates for probing α variation because their transition frequencies are measured with ultra-high precision. Since atomic transition frequency is a function of α, measurement of a clock frequency at different temporal and spatial locations can yield signatures to ascertain variation of α. Highly charged ions (HCIs) are very sensitive to variation of α and are least affected by external perturbations, making them excellent platforms for searching for temporal variation of α. In this work, we overview HCIs suitable for building atomic clocks because of their spectroscopic features and sensitivity to variation of α. The selection of HCI clock candidates is outlined based on two general rules—by analyzing trends in fine structure splitting and level-crossing patterns along a series of isoelectronic atomic systems of the periodic table. Two variants of relativistic many-body methods in the configuration interaction and coupled-cluster theory frameworks are employed to determine the properties of HCIs proposed for atomic clocks. These methods treat electronic correlation and relativistic effects under the frame of the Dirac-Coulomb Hamiltonian rigorously, while other higher-order relativistic effects are included approximately. Typical systematic effects of the HCI clock frequency measurements are discussed using the calculated atomic properties. This review will help understand limits and potentials of the proposed HCIs as the prospective atomic clock candidates and guide future HCI clock experiments.