bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioredoxin-interacting protein (TXNIP) inhibition promotes retinal ganglion cell survival and facilitates M1-like microglial transformation via the PI3K/Akt pathway in glaucoma
Authors: Chen Junjue , Zhong Huimin , Shen Bingqiao , Yu Huan , Zhang Yang , Han Ruiqi , Huang Ping , Huang Shouyue , Zhong Yisheng 
Published: December 2024

Abstract
Background
Glaucoma is a group of heterogeneous neurodegenerative diseases with abnormal energy metabolism and imbalanced neuroinflammation in the retina. Thioredoxin-interacting protein (TXNIP) is involved in glucose and lipid metabolism, and associated with oxidative stress and inflammation, however, not known whether to be involved in glaucoma neuropathy and its underlying mechanisms.

Methods
To establish the chronic ocular hypertension (COH) mice model. Western blot, RT-PCR, immunofluorescence and F-VEP were used to detect neuroinflammation level, glial activation and RGCs survival in retina of wild type, TXNIP knockout and MCC950 treatment COH mice. Microglia high-pressure cultured model was constructed. Western blot, RT-PCR and immunofluorescence were used to investigate the proinflammatory cytokines secretion, glucose uptake and phenotype transformation in wild type, TXNIP knockout and overexpressed microglia combined with IL-17A treatment. Finally, we explored the possible underlying mechanisms using relevant pathway inhibitor interventions.

Results
In this study, for the first time we reported that TXNIP expression was remarkably increased in experimental glaucomatous retina of chronic ocular hypertension (COH) mice, and it was mainly expressed in the ganglion cells layer (GCL). In addition, we found that ablation of TXNIP promoted retinal ganglion cells (RGCs) survival and alleviated visual function impairment in experimental glaucoma. Then, we explored the spatiotemporal consistency between glial activation and retinal inflammation levels in COH mice respectively with TXNIP-deficiency and under treatment of a thermo-containing protein domain 3 (NLRP3) inhibitor MCC950, and the results indicated that TXNIP probably mediated neuroinflammation in glaucomatous retina by activating microglia. Furthermore, upregulation of TXNIP was found in pressure-stimulated microglia, whereas silencing TXNIP facilitated microglial polarization trending towards M1 type and reduced glucose transporter-1 (Glut-1) expression on microglia under high pressure in vitro. Moreover, IL-17A was found to play a role in acting synergistically with TXNIP upon the regulation of microglia polarity transformation. Finally, knockout of TXNIP was revealed to promote PI3K phosphorylation, whereas inhibition of PI3K by LY294002 effectively suppressed Glut-1 expression, glucose uptake, and M1-like transformation tendency in microglia obtained from TXNIP-deficiency mice under high pressure stimulation.

Conclusions
TXNIP is significantly involved in the inflammation-related neuropathy of experimental glaucoma and probably facilitates M1-like microglial transformation via PI3K/Akt pathway.
Development of an optimized protocol for protoplast-to-plant regeneration of selected varieties of Brassica oleracea L.
Authors: Stelmach-Wityk Katarzyna , Szymonik Kamil , Grzebelus Ewa , Kiełkowska Agnieszka 
Published: December 2024

Abstract
Background
Brassica oleracea L. is a key plant in the Brassicaceae family, known for popular vegetables like cabbage, broccoli, kale and collard. Collard (B. oleracea var. viridis) is a non-heading leafy vegetable grown in urban farms and community gardens in the United States and Europe. Improving collard and other Brassica germplasm can benefit from both traditional and new plant breeding technologies (NPBTs), such as CRISPR-Cas mediated transformation. An efficient transformation or protoplast fusion can only be achieved with a robust and reproducible protocol for protoplast-to-plant regeneration. This research focuses on optimizing in vitro culture conditions to enhance cell divisions, microcallus formation, and the regeneration of shoots and roots in four Brassica oleracea varieties, including collard.

Results
The protocol of protoplast release, purification and immobilization was optimized to obtain a suitable number and quality of protoplasts from seven cultivars of B. oleracea. The protoplast isolation efficiency after digestion of young leaves in optimized enzyme solution reached on average 2.5 × 106 of cells per gram of fresh weight. Protoplasts were embedded in thin alginate layers and subjected to culture in three different media. Protoplasts of all studied cultivars were viable (88.2%), underwent cell wall resynthesis and re-entered mitotic divisions in the 5th day of culture. After 30 days of culture, protoplast-derived cells of all the tested cultivars formed microcallus. Six cultivars regenerated shoots, although the shoot formation efficiency strongly depended on the genotype and composition of the regeneration medium. The regeneration medium supplemented with 1 mg l−1 of NAA, 1 mg l−1 of 2iP, 0.02 mg l−1 GA3 and with 2% of mannitol showed the highest shoot formation efficiency for five cultivars of B. oleracea.

Conclusions
The results of this research have led to the development of a robust protoplast-to-plant regeneration protocol for four varieties of B. oleracea that could be exploited as a tool for production of transformants and somatic hybrids. Furthermore, we present the first successful regeneration of protoplast-derived plants of collard, an overlooked but valuable variety of Brassica oleracea.
Human blood metabolites and gastric cancer: a Mendelian randomization analysis
Authors: Zhang Chao , Huang Dao Lai , Zhou Kun , Cai Jin Tao , Liu Dang , Tan Ming Hao , Zhu Guan Yu , Wu Xiang Hua 
Published: December 2024

Abstract
Background
Gastric cancer (GC) remains one of the predominant malignant tumors within the digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective of this study is to delineate the causal relationship between circulating metabolites and GC.

Method
The primary Mendelian randomization (MR) analysis was based on three large GWAS datasets. While the inverse variance weighted served as the primary analysis technique for investigating causal relationships, additional sensitivity analyses were facilitated through methods such as MR-PRESSO, the weighted median, and MR-Egger. Subsequently, replication, meta-analysis, and multivariable MR were executed using another GC GWAS.

Results
The results of this study indicated significant associations between three metabolites 3-methyl-2-oxovalerate (OR 5.8, 95%CI: 1.53–22.05, p = 0.0099), piperine (OR 2.05, 95%CI: 1.13–3.7, p = 0.0175), Phe-Phe dipeptide (OR 0.16, 95%CI: 0.03–0.93, p = 0.0409) and GC.

Conclusion
The present study provides evidence supporting a causal relationship between these three circulating metabolites and GC risk. Elevated levels of 3-methyl-2-oxovalerate and piperine may increase the risk of GC, while Phe-Phe dipeptide may have a protective effect. By integrating genomics and metabolomics, we offer a novel perspective on the biological mechanisms underlying GC. Such insights have the potential to enhance strategies for the screening, prevention, and treatment of GC.
Early therapeutic efficacy of condoliase chemonucleolysis for lumbar disc herniation
Authors: Kobayashi Kazuyoshi , Sato Koji , Morita Yoshinori 
Published: December 2024

Abstract
Background
Low back pain is often caused by lumbar disc herniation (LDH). Treatment of LDH is possible using chemonucleolysis of the nucleus pulposus with condoliase injection. However, onset of the therapeutic effect varies among patients, with improvement from an early stage to 3 months post-injection. This study was performed to identify the characteristics of early responders to condoliase therapy.

Methods
A retrospective cohort study was performed in 371 consecutive patients (259 males, 112 females; age, 49.9 ± 18.7 years; follow-up period, 13.1 ± 7.4 months) treated with condoliase injection for LDH between August 2018 and January 2024. Chemonucleolysis was performed with 1 mL of condoliase (1.25 U/mL) injected into the intervertebral nucleus pulposus. Clinical assessments were made before injection and 1 day, and 1, 4 and 12 weeks post-injection. Pain was measured on a visual analogue scale. Herniation parameters were evaluated on axial MRI. The herniated disc volume was measured on plain lumbar radiography. Demographic and clinical data were taken from medical charts. Multivariate logistic regression analysis was used to identify factors with independent relationships with treatment efficacy.

Results
Improvement of leg pain from baseline by ≥ 50% occurred in 21% of cases within one day after condoliase treatment. Patients with this improvement at 1 week post-injection were defined as early responders (n = 142, 38.3%). In multivariate analysis, age < 40 years (p = 0.022, odds ratio (OR): 1.71, 95% confidence interval (CI): 1.12–4.35), Pfirrmann Grade II or III at baseline (p = 0.032, OR: 1.86, 95% CI: 1.17–5.41), and a high intensity MRI signal in the herniation (p = 0.041, OR: 1.87, 95% CI: 1.06–5.27) were significantly associated with early improvement. No patients had anaphylactic shock or neurologic sequelae.

Conclusions
This study confirms the safety and efficacy of chemonucleolysis with condoliase for treating patients with painful LDH. Age, high-intensity MRI signals, and baseline Pfirrmann grade were significant factors associated with early improvement.
Safety and efficacy of omaveloxolone v/s placebo for the treatment of Friedreich's ataxia in patients aged more than 16 years: a systematic review
Authors: Umrao Ankita , Pahuja Monika , Chatterjee Nabendu Sekhar 
Published: December 2024

Abstract
Background
Friedreich’s ataxia (FA) is a rare genetic disorder caused by silencing of the frataxin gene (FXN), which leads to multiorgan damage. Nrf2 is a regulator of FXN, which is a modulator of oxidative stress in animals and humans. Omaveloxolone (Omav) is an Nrf2 activator and has been reported to have antioxidative potential in various disease conditions. The present review was conducted to determine the use of Omav, the only FDA-approved treatment for FA.

Methods
Three electronic databases, Cochrane, PubMed and Google Scholar, were searched with terms such as ‘Omaveloxolone’, ‘Friedreich ataxia’, ‘genetic diseases’, ‘autosomal recessive’, and ‘rare disorders’ using various advanced search filters. Articles were screened, extracted, and assessed for quality, and a qualitative synthesis of the data was performed. The study protocol was registered in PROSPERO (CRD42024531449).

Results
A total of 201 records were found, with very few published research articles on the topic. Only two randomized clinical trials published in a series of three research articles were included in the current systematic review. Peak load exercise and modified Friedreich’s Ataxia Rating Scale (mFARS) values were considered the major outcome measures for determining the efficacy of 150 mg Omav capsules/day in FA. Exploratory outcome measures, such as low-contrast letter visual acuity test, exercise test, T25-FW, 9-HPT, health-related quality of life, and biochemical tests, were also assessed along with adverse events in all the studies.

Conclusion
Although, the quality of the articles demonstrated low bias. However, the short duration, small sample size, and missing data, including the values of different measures of mFARS scores in patients, limit the generalizability of the results. Further studies with longer durations and in severe patients with foot deformities are needed to clearly define the efficacy of Omav in FA and to determine the optimal drug for FA patients in India.
VIPAS39 related arthrogryposis-renal dysfunction-cholestasis syndrome—case report and systematic review
Authors: Kafol Jan , Gnidovec Strazisar Barbara , Drole Torkar Ana , Homan Matjaz , Bertok Sara , Mlinaric Matej , Sikonja Jaka , Kovač Jernej , Perkovic Benedik Mirjana , Kersnik Levart Tanja , Zerjav Tansek Mojca , Praprotnik Marina , Battelino Tadej , Debeljak Maruša , Groselj Urh 
Published: December 2024

Abstract
Background
Arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome, a rare autosomal recessive disorder, exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor.

Results
We present two related patients from Kosovo, describing the clinical, genetic, and therapeutic aspects of the syndrome. The identified novel VIPAS39 pathological variants (c.762G > A; c.1064_1082delinsAGTG) emphasize the complex phenotypic expression of ARC syndrome. A systematic literature review identified 8 VIPAS39-related ARC cases with notable variability in clinical features. Prognostically, patients fell into severe and milder groups, with some reaching adolescence. Our report aligns with others noting milder ARC courses and emphasizes the value of genetic testing, especially in atypical presentations. Challenges included incomplete literature data, early mortality affecting diagnostic workup, and limited VIPAS39-related ARC cases. Comparisons with the more prevalent VPS33B pathological variants revealed no distinct clinical differences.

Conclusion
Our study expands understanding of ARC syndrome, highlighting its genetic diversity and clinical variability. Milder presentations underscore diagnostic challenges and the potential prevalence of undiagnosed cases. Increased awareness and comprehensive genetic testing are crucial for early and accurate diagnosis.
Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation
Authors: Sirera Jessy , Sarlak Saharnaz , Teisseire Manon , Carminati Alexandrine , Nicolini Victoria J. , Savy Coline , Brest Patrick , Juel Thierry , Bontoux Christophe , Deckert Marcel , Ohanna Mickael , Giuliano Sandy , Dufies Maeva , Pages Gilles , Luciano Frederic 
Published: December 2024

Abstract
Background
Multiple Myeloma (MM) is the second most common hematological malignancy, characterized by the accumulation of monoclonal plasmocytes in the bone marrow. Despite advancements with proteasome inhibitors, immunomodulatory agents, and CD38-targeting antibodies, MM remains largely incurable due to resistant clones and frequent relapses. The success of the proteasome inhibitor bortezomib (BTZ) in MM treatment highlights the critical role of the ubiquitin–proteasome system (UPS) in this disease. Deubiquitinases (DUBs), which regulate protein stability, interactions, and localization by removing ubiquitin modifications, have emerged as promising therapeutic targets in various cancers, including MM.

Methods
Through a comprehensive loss-of-function screen, we identified USP39 as a critical survival factor for MM cells. Gene Set Enrichment Analysis (GSEA) was employed to correlate USP39 mRNA levels with clinical outcomes in MM patients. USP39 protein expression was evaluated via immunohistochemistry (IHC) on bone marrow samples from MM patients and healthy controls. The impact of USP39 knockdown via SiRNA was assessed through in vitro assays measuring cellular metabolism, clonogenic capacity, cell cycle progression, apoptosis, and sensitivity to BTZ. Co-immunoprecipitation and deubiquitination assays were conducted to elucidate the interaction and regulation of ZEB1 by USP39. Finally, in vitro and in vivo zebrafish experiments were used to characterize the biological consequences of ZEB1 regulation by USP39.

Results
Our study found that elevated USP39 mRNA levels are directly associated with shorter survival in MM patients. USP39 protein expression is significantly higher in MM patient plasmocytes compared to healthy individuals. USP39 knockdown inhibits clonogenic capacity, induces cell cycle arrest, triggers apoptosis, and overcomes BTZ resistance. Gain-of-function assays revealed that USP39 stabilizes the transcription factor ZEB1, enhancing the proliferation and the trans-migratory potential of MM cells.

Conclusions
Our findings highlight the critical role of the deubiquitinase USP39, suggesting that the USP39/ZEB1 axis could serve as a potential diagnostic marker and therapeutic target in MM.
Transcriptional induction of the IMD signaling pathway and associated antibacterial activity in the digestive tract of cat fleas (Ctenocephalides felis)
Authors: Weber Katie , Karnik Dhruva , Brown Lisa D. 
Published: December 2024

Abstract
Background
Fleas are insect vectors that transmit several Gram-negative bacterial pathogens acquired by ingesting infected vertebrate blood. To combat foodborne illness, insect midgut epithelial cells are armed with efficient microbial recognition and control systems, such as the immune deficiency (IMD) pathway that regulates the expression of antimicrobial peptides (AMPs). However, despite their medical and veterinary importance, relatively little is known about the IMD signaling pathway and production of AMPs in the digestive tract of cat fleas (Ctenocephalides felis).

Methods
In the present study, we measured the expression of target genes comprising the IMD pathway, as well as corresponding AMP transcripts, in the digestive tract of C. felis following exposure to three different species of bacteria: Gram-negative Bartonella henselae (a flea-borne pathogen), Gram-negative Serratia marcescens (a model laboratory species), and Gram-positive Micrococcus luteus (a model laboratory species). Additionally, we examined the antibacterial activity of proteins isolated from the flea digestive tract in vitro following bacterial challenge and at different days post adult emergence to determine if feeding-induced antibacterial activity varies with age.

Results
In our analysis of C. felis, we observed an increase in the expression of representative IMD pathway genes and associated AMP transcripts, indicating the activation of the IMD pathway. Furthermore, our results revealed that different bacterial species elicit distinct transcriptional profiles of IMD pathway genes, suggesting a species-specific response to bacterial invasion. We found that the gut of C. felis produces antibacterial molecules as a localized defense mechanism. Additionally, we observed that proteins with antimicrobial properties are synthesized as part of local defense mechanisms in the gut, with differential patterns of antibacterial activity related to infection status and age.

Conclusions
Our findings provide essential insights into the potential mechanisms by which cat fleas regulate immune responses in their digestive tract against different bacterial species.

Graphical Abstract
Reducing DNA extraction costs through factorial design for the DNAdvance Kit
Authors: Neal Carson J. , Zbinden Zachery D. , Douglas Michael E. , Douglas Marlis R. 
Published: December 2024

Abstract
Objective
Extracting DNA is essential in wildlife genetic studies, and numerous methods are available. However, the process is costly and time-consuming for non-model organisms, including most wildlife species. Therefore, we optimized a cost-efficient protocol to extract DNA from the muscle tissue of White-tailed Deer using the DNAdvance kit (Beckman Coulter), a magnetic-bead-based approach. We devised a 3 × 3 factorial design using combinations of tissue mass (10 mg, 50 mg, or 100 mg) and reaction volume (25%, 33%, and 50% of the manufacturer's recommended volumes). DNA was extracted for N = 81 tissue sub-samples (9 replicates/treatment).

Results
Our target yield was 500 ng of genomic DNA per sample, sufficient for population genetic assessments. A combination of 50 mg tissue and 25% reaction volume yielded enough DNA at the lowest cost. The factorial design revealed that varying tissue mass and reagent volume significantly affected extracted DNA yield. Our study demonstrates that sufficient DNA can be extracted at 75% lower costs than the manufacturer's standard protocol. Other researchers can directly use our modified DNAdvance protocol to perform cost-effective DNA extractions.
Dynamically triggered seismicity in Japan following the 2024 Mw7.5 Noto earthquake
Authors: An Like , Enescu Bogdan , Peng Zhigang , Miyazawa Masatoshi , Gonzalez-Huizar Hector , Ito Yoshihiro 
Published: December 2024

AbstractOn January 1st, 2024, a moment magnitude (Mw) 7.5 earthquake occurred on an active reverse fault in the northern part of Noto Peninsula, being one of the largest intraplate events recorded in Japan. In previous studies, the dynamic triggering of seismicity in Japan following some large remote earthquakes has been well documented, such as in the case of the 2011 Mw9.0 Tohoku–Oki earthquake, the 2016 Mw 7.1 Kumamoto earthquake, and other large teleseismic events. In this study, we investigate the remote triggering of microearthquakes by the 2024 Noto earthquake and their characteristics. We analyze waveform data recorded at high-sensitivity seismic stations in Japan, before and after the occurrence of the Noto mainshock. Local earthquakes are detected on high-pass filtered three-component seismograms. Low-pass filtered waveforms are used for visualizing the mainshock surface waves and estimating dynamic stresses. Our results show a relatively widespread activation of small earthquakes—none of them listed in the Japan Meteorological Agency (JMA) earthquake catalog—that were triggered by the passage of the mainshock surface waves in many regions of Japan. These include Hokkaido and Tohoku in northeastern Japan, Kanto in central Japan, and Kyushu in southern Japan. The triggering is mostly observed in volcanic regions, supporting the hypothesis that such places are relatively easy to be activated dynamically, likely due to the excitation of fluids by the passage of mainshock surface waves. The calculated dynamic stress changes estimated from peak ground velocities, which triggered the earthquakes after the Noto mainshock, are in the range 12.8–102.6 kPa. We also report potential, less well-constrained dynamic triggering by the Mw 5.3 Noto foreshock, which occurred ~ 4 min before the mainshock, at levels of stress about 100 times smaller. The analysis of a longer-term (1 month) seismicity pattern, based on the JMA catalog, revealed a statistically significant increase of seismicity in the remote Akita–Yakeyama (Tohoku region) volcanic area, following the Noto earthquake.
Graphical Abstract