Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood.Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach.Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy.Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies

Genome-Wide Identification, Evolution, and Female-Biased Expression Analysis of Odorant Receptors in <i>Tuta absoluta</i> (Lepidoptera: Gelechiidae)

The tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae), is a highly destructive invasive pest targeting Solanaceae crops. Its olfactory system plays a crucial role in host location, mate finding, and other behavioral activities. However, there is a notable gap in the literature regarding the characterization of its chemosensory genes. In this study, we conducted a genome-wide identification of 58 odorant receptors (ORs) of T. absoluta. The identified ORs exhibit coding sequence (CDS) lengths ranging from 1062 bp to 1419 bp, encoding proteins of 354 to 473 amino acids. Gene structure analysis showed that the majority of these ORs consist of five, seven, eight, or nine exons, collectively representing 67% of the total ORs identified. Through chromosomal mapping, we identified several tandemly duplicate genes, including TabsOR12a, TabsOR12b, TabsOR12c, TabsOR21a, TabsOR21b, TabsOR34a, TabsOR34b, TabsOR34c, TabsOR62a, and TabsOR62b. The phylogenetic analysis indicated that six TabsORs were clustered within the lepidopteran sex pheromone receptor clade, while an expansion clade containing ten TabsORs resulted from tandem duplication events. Additionally, five TabsORs were classified into a specific OR clade in T. absoluta. Furthermore, through RNA-Seq and RT-qPCR analyses, we identified five TabsORs (TabsOR21a, TabsOR26a, TabsOR34a, TabsOR34c, and TabsOR36) exhibiting female-antennae-biased expression. Our study provides a valuable foundation to further investigations into the molecular and ecological functions of TabsORs, particularly in relation to oviposition behavior. These findings provide foundational data for the future exploration of the functions of female-biased expression OR genes in T. absoluta, thereby facilitating the further development of eco-friendly attract-and-kill techniques for the prevention and control of T. absoluta

Activity of 9-cis-retinoic acid and receptor-selective retinoids in small cell lung cancer cell lines

Dysregulation of retinoid signaling pathways appears to be an early event in the pathogenesis of small cell lung cancer (SCLC). We evaluated the activity of 9-cis-retinoic acid (9cRA), a pan-receptor agonist, and two synthetic retinoids, TTNPB and LG100153, which are RAR- and RXR-selective, respectively, against a panel of SCLC cell lines. LG100153 was the most potent agent with an IC50 \u3c 1.0 μM in three cell lines. TTNPB had an IC50 \u3c 1.0 μM in two lines, and 9cRA an IC50 \u3c 1.0 μM in only one. By fluorescent microscopy, LG100153, TTNPB and 9cRA also induced morphologic evidence of apoptosis in three, two and one cell lines, respectively. Although the expression of RARs and RXRs varied widely between cell lines, there was no clear correlation between the level or pattern of receptor expression and retinoid activity. These data suggest that novel retinoids, especially RXR-selective agents, deserve further evaluation in the treatment of SCLC

Late Cretaceous Neo-Tethyan slab roll-back: Evidence from zircon U-Pb-O and whole-rock geochemical and Sr-Nd-Fe isotopic data of adakitic plutons in the Himalaya-Tibetan Plateau

Late Cretaceous (ca. 100-80 Ma) magmatism in southern Lhasa subterrane records critical geological events, which can provide important insights into the regional tectonic evolution and geodynamic process of South Tibet. This study presents new zircon U-Pb ages, whole-rock geochemistry and Sr-Nd-Fe and zircon U-Pb-O isotopic data for two dioritic plutons in the southern Lhasa subterrane. Secondary ion mass spectrometry U-Pb dating on magmatic zircons from these rocks yielded a consistent age at ca. 90 Ma. The rocks exhibit variable SiO2 contents (52-59 wt%), high Fe2O3T contents (7.1-10.0 wt%), and low K2O/Na2O ratios (0.18-0.48). Most samples have high Al2O3 (17.0-19.5 wt%) and Sr (493-678 ppm), but low Yb (0.9-2.4 ppm) and Y (9-25.2 ppm) concentrations, and thus high Sr/Y (23-74) ratios, typical of adakite-like geochemical features. The adakitic rocks have relatively uniform initial Sr-87/Sr-86 isotopic ratios (0.7043-0.7046) and epsilon(Nd)(t) values (+3.67 to +4.16), indicating derivation from similar parental magmas. The delta Fe-56 values of whole-rock samples vary from 0.011 to 0.091 parts per thousand with an average of 0.045 +/- 0.046 parts per thousand (two standard deviations), reflecting a homogeneous Fe isotopic composition, which is associated with melt-mantle interaction. In addition, the rocks are characterized by relatively high zircon delta O-18 values of 5.72-7.19 parts per thousand, indicating the involvement of an O-18-enriched component during magma formation. The calculation of Al-in-hornblende barometer indicates that the adakitic rocks were emplaced at pressures of 6.4-9.8 kbar. Therefore, it is proposed that the adakitic rocks were most likely generated by partial melting of mantle wedge that had been previously modified by slab-melts at a relatively shallow depth, followed by minor fractional crystallization of hornblende. Taking into account previously published data in the southern Lhasa subterrane, we suggest that the ca. 90 Ma magmatism could be related to a period of Neo-Tethyan oceanic slab rollback, which can provide new insights into the revolution process of the Neo-Tethyan ocean realm and the accretion of the Himalaya-Tibetan Plateau

Micro-expression recognition with small sample size by transferring long-term convolutional neural network

Abstract Micro-expression is one of important clues for detecting lies. Its most outstanding characteristics include short duration and low intensity of movement. Therefore, video clips of high spatial-temporal resolution are much more desired than still images to provide sufficient details. On the other hand, owing to the difficulties to collect and encode micro-expression data, it is small sample size. In this paper, we use only 560 micro-expression video clips to evaluate the proposed network model: Transferring Long-term Convolutional Neural Network (TLCNN). TLCNN uses Deep CNN to extract features from each frame of micro-expression video clips, then feeds them to Long Short Term Memory (LSTM) which learn the temporal sequence information of micro-expression. Due to the small sample size of micro-expression data, TLCNN uses two steps of transfer learning: (1) transferring from expression data and (2) transferring from single frame of micro-expression video clips, which can be regarded as “big data”. Evaluation on 560 micro-expression video clips collected from three spontaneous databases is performed. The results show that the proposed TLCNN is better than some state-of-the-art algorithms

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation comprising Citrus bergamia, in subjects with moderate cardiometabolic risk factors

We examined the clinical safety and efficacy of F105 in 11 subjects with moderate dyslipidemia. F105 is a combination of bergamot fruit extract (Citrus bergamia, BFE) and nine phytoextracts selected for their ability to improve the antioxidant and anti-inflammatory activity of BFE. In vitro F105 exhibited a synergistic inhibition of oxygen radical absorbing capacity, peroxynitrite formation and myeloperoxidase activity. Following 12 weeks of F105 daily, no treatment-related adverse events or changes in body weight were seen. Statistically significant changes were noted in total cholesterol (-7.3%), LDL-cholesterol (-10%), non-HDL cholesterol (-7.1%), cholesterol/HDL (-26%) and Apolipoprotein B (-2.8%). A post hoc analysis of eight subjects with HbA1c >5.4 and HOMA-IR score >2 or elevated triglycerides revealed additional statistically significant changes in addition to those previously observed in all subjects including triglycerides (-27%), oxLDL (-19%), LDL/HDL (-25%), triglycerides/HDL (-27%), oxLDL/HDL (-25%), and PAI-1(-37%). A follow-up case report of a 70-year old female patient, nonresponsive to statin therapy and placed on F105 daily, demonstrated improved cardiometabolic variables over 12 weeks similar to the subgroup. In summary, F105 was clinically well-tolerated and effective for ameliorating dyslipidemia in subjects with moderate cardiometabolic risk factors, particularly in the individuals with HbA1c >5.4%.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author