Search

Backgrounds A large proportion of patients with chronic spontaneous urticaria (CSU) are resistant to a standard dose of antihistamine. Acknowledged biomarkers for identifying these patients have not been determined. The neutrophil/lymphocyte ratio (NLR) has been considered as an important indicator of inflammation in chronic diseases. Aims To explore whether NLR could serve as a biomarker for predicting the response to H1-antihistamine in patients with CSU. Methods This hospital-based, retrospective study included 109 patients with CSU diagnosed from 2017 to 2020 in our clinic and divided them into two groups by their responses to the 2-week antihistamine therapy of standard-dose: 69 with H1-antihistamine-refractory and 40 with non-H1-antihistamine-refractory CSU. The laboratory test results were collected from the hospital information system and integrated with SPSS software. Results Patients refractory to H1-antihistamine had significantly higher median NLR (P = 0.039), age (3 P = 0.021), complement C3 (P = 0.026), presence of elevated WBC (P = 0.026) and elevated monocytes (MONO) (P = 0.045) and significantly lower IgM (P = 0.022). The binary logistic regression model revealed that NLR was significantly associated with H1-antihistamine-refractory of CSU (odds ratio (OR) 1.717, 95% confidence interval (CI) 1.065–2.766, P = 0.026), which was consistent with that after adjusted for potential confounding factors including age, complement C3, presence of elevated WBC and MONO, and IgM (OR 1.681, 95% CI 1.019–2.773, P = 0.042). Conclusion Our results showed a strong and significant association between higher NLR and H1-antihistamine resistance in CSU, suggesting that NLR may be a potential biomarker for predicting the response to H1-antihistamine therapy in patients with CSU.

Abstract Background Cutaneous infectious granulomas (CIG) are localized and chronic skin infection caused by a variety of pathogens such as protozoans, bacteria, worms, viruses and fungi. The diagnosis of CIG is difficult because microbiological examination shows low sensitivity and the histomorphological findings of CIG caused by different pathogens are commonly difficult to be distinguished. Objective The objective of this study is to explore the application of mNGS in tissue sample testing for CIG cases, and to compare mNGS with traditional microbiological methods by evaluating sensitivity and specificity. Methods We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 1st, 2020, to May 31st, 2024. Specimens from CIG patients with a clinical presentation of cutaneous infection that was supported by histological examination were retrospectively enrolled. Specimens were delivered to be tested for microbiological examinations and mNGS. Results Our data show that mNGS detected Non-tuberculosis mycobacteria, Mycobacterium tuberculosis, fungi and bacteria in CIG. Compared to culture, mNGS showed a higher positive rate (80.77% vs. 57.7%) with high sensitivity rate (100%) and negative predictive value (100%). In addition, mNGS can detect more pathogens in one sample and can be used to detect variable samples including the samples of paraffin-embedded tissue with shorter detective time. Of the 21 patients who showed clinical improvement within a 30-day follow-up, eighteen had their treatments adjusted, including fifteen who continued treatment based on the results of mNGS. Conclusions mNGS could provide a potentially rapid and effective alternative detection method for diagnosis of cutaneous infectious granulomas and mNGS results may affect the clinical prognosis resulting from enabling the patients to initiate timely treatment.

Over the past two decades, the escalating prescription of opioid medications for pain management has culminated in a widespread opioid epidemic, significantly impacting public health, social dynamics, and economic stability. The urgent need for improved treatments for opioid addiction necessitates a deeper understanding of its biological underpinnings, with genetic variations playing a crucial role in individual susceptibility to opioid use disorder (OUD) and influencing clinical practices. In this study, we leverage the genetic diversity of four rat strains (ACI/N, BN/NHsd, WKY/N, and F344/N) to examine the contribution of genetic factors to oxycodone metabolism and addiction-like behaviors. We used the extended access to intravenous oxycodone self-administration procedure (12 h/day, 0.15 mg/kg/injection) to comprehensively characterize oxycodone-related behaviors and pharmacokinetics. We measured escalation of oxycodone self-administration, motivation for drug consumption, tolerance to the analgesic effects of oxycodone, withdrawal-induced hyperalgesia, and oxycodone-induced respiratory depression. Additionally, we examined oxycodone-seeking behavior after four weeks of withdrawal by reintroducing the animals to environmental and cue stimuli previously associated with oxycodone self-administration. The findings revealed notable strain differences in several behavioral measures, including oxycodone metabolism. Intriguingly, BN/NHsd and WKY/N strains exhibited similar drug intake and escalation patterns but displayed significant disparities in oxycodone and oxymorphone metabolism. Minimal sex differences were observed within strains, primarily relating to oxycodone metabolism. In conclusion, this study identifies strain differences in the behavioral responses and pharmacokinetics associated with oxycodone self-administration in rats, providing a robust foundation for identifying genetic and molecular variants associated with various facets of the opioid addiction process.

Abstract Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.

Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor (EcR) through the 20‐hydroxyecdysone (20E) signaling pathway. EcR is a steroid nuclear receptor (SR). Several FK506‐binding proteins (FKBPs) have been identified from the mammal SR complex, and are thought to be involved in the subcellular trafficking of SR. However, their roles in insects are poorly understood. To explore whether FKBPs are involved in insect molting or metamorphosis, we injected an FKBP inhibitor (FK506) into a lepidopteran insect, Spodoptera litura, and found that molting was inhibited in 61.11% of the larvae, and that the time for larvae to pupate was significantly extended. A total of 10 FKBP genes were identified from the genome of S. litura and were clustered into 2 distinct groups, according to their subcellular localization, with FKBP13 and FKBP14 belonging to the endoplasmic reticulum (ER) group and with the other members belonging to the cytoplasmic (Cy) group. All the CyFKBPs were significantly upregulated in the prepupal or pupal stages, with the opposite being observed for the ER group members. FK506 completely blocked the transfer of EcR to the nucleus under 20E induction, and significantly downregulated the transcriptional expression of many 20E signaling genes. A similar phenomenon was observed after RNA interference of 2 CyFKBPs (FKBP45 and FKBP12b), but not for FKBP13. Taken together, our data indicate that the cytoplasmic FKBPs, especially FKBP45 and FKBP12b, mediate the nuclear localization of EcR, thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects. [ABSTRACT FROM AUTHOR]

Abstract Notopterygium incisum Ting ex H. T. Chang is a rare and endangered traditional Chinese medicinal plant. In this research, we built a comprehensive habitat suitability (CHS) model to analyze the potential suitable habitat distribution of this species in the present and future in China. First, using nine different algorithms, we built an ensemble model to explore the possible impacts of climate change on the habitat distribution of this species. Then, based on this model, we built a CHS model to further identify the distribution characteristics of N. incisum‐suitable habitats in three time periods (current, 2050s, and 2070s) while considering the effects of soil and vegetation conditions. The results indicated that the current suitable habitat for N. incisum covers approximately 83.76 × 103 km2, and these locations were concentrated in the Tibet Autonomous Region, Gansu Province, Qinghai Province, and Sichuan Province. In the future, the areas of suitable habitat for N. incisum would significantly decrease and would be 69.53 × 103 km2 and 60.21 × 103 km2 in the 2050s and 2070s, respectively. However, the area of marginally suitable habitat would remain relatively stable. This study provides a more reliable and comprehensive method for modelling the current and future distributions of N. incisum, and it provides valuable insights for highlighting priority areas for medicinal plant conservation and resource utilization.

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common type of kidney cancer. It has a poor prognosis, with approximately 20–30% of patients developing recurrent and/or metastatic diseases that is relatively high resistant to conventional therapy. Resisting cell death is a hallmark of cancer cells. Apoptosis is a form of programmed cell death mediated by the activation of caspases. Necroptosis is a form of regulated necrosis that relies on the activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL), the substrate of RIPK3. Cancer cells often display apoptosis resistance via upregulation of anti-apoptotic genes and defective necroptosis due to the epigenetic silence of Ripk3. MicroRNAs (miRNAs) are non-coding small RNAs that are involved in numerous biological processes including cell proliferation, differentiation and death. In this study, we screened a set of ∼120 miRNAs for apoptosis-regulating miRNAs and identified miR-381-3p as a suppressor of TNF-induced apoptosis in various cancer cells. Ectopic expression of miR-381-3p inhibits the activation of caspase-8 and caspase-3. The expression level of miR-381-3p inversely correlates with the sensitivity of cancer cells to TNF-induced apoptosis. Moreover, we found that overexpression of miR-381-3p blocks TNF-induced necroptosis by inhibiting the activation of RIPK3 and MLKL. Of note, Kaplan-Meier Plotter analysis demonstrates that papillary RCC patients with high miR-381-3p expression have a lower overall survival than those with low expression level of miR-381-3p. Importantly, miR-381-3p overexpression promotes colony formation in human renal cancer cells. Thus, miR-381-3p acts as an oncogenic miRNA that counteracts both apoptotic and necroptotic signaling pathways. Our findings highlight miR-381-3p as a biomarker for predicting sensitivity to apoptosis and necroptosis, and as a possible therapeutic target for RCC.

AIM: To determine whether glaucoma patients exhibit an abnormal melatonin concentration in serum and the effects of psychiatric disorders caused by glaucoma in melatonin secretion. METHODS: A sample of 80 primary angle-closure glaucoma (PACG) patients, 120 primary open angle glaucoma (POAG) patients, and 120 normal controls were enrolled in this study. All the participants were asked to complete the following questionnaires: Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Variance analysis was used to compare the subscores between the groups. After that, we chose 58 patients with primary glaucoma and 20 non-glaucoma control patients to collect their serum samples at 7-10 a.m. Serum melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). RESULTS: Of all participants, the scores of PSQI, SAS, and SDS in PACG and POAG group were 9.38±0.40, 46.08±8.99, 51.11±10.72 and 7.43±0.35, 45.42±9.87, 49.04±12.24 respectively, significantly higher than those in control group (4.16±0.28, 35.49±9.18, 40.31±13.08). The serum melatonin levels in PACG (37.29±2.99 pg/mL) and POAG (35.97±3.64 pg/mL) were significantly higher than the controls (29.96±3.94 pg/mL) (P

Mucins produced by corneal and conjunctival epithelia, conjunctival goblet cells and lacrimal apparatus are important components of preocular tear film, which play important roles as clearing molecules, lubricating agents, antimicrobial agents, dis-adhesive molecules, protective cell surface barrier, osmosensors and signal transmitter. The understanding of the functional roles of mucins and the regulatory steps governing its synthesis and secretion is necessary to develop effective treatment strategies for dry eye.

How the government scientifically forms the top management team greatly influences the performance of water conservancy project, which is a concern for practitioners and scholars. According to the investigation in many cases, the current top management team formation methods of water conservancy projects can be classified into nine categories. Through theoretical analysis and literature review, it is found that six factors influence the selection of the top management team formation methods in water conservancy projects. On this basis, a relationship matrix of top management team formation methods and influencing factors is developed, and the top management team formation method with the help of the 'entropy weight-VIKOR method' is optimized. [ABSTRACT FROM AUTHOR]