Interpersonal Sensitivity and Subjective Well-Being of Migrant Workers' Accompanying Children: Role of Perception of Exclusion and Peer Support.

Introduction: To investigate the impact of interpersonal sensitivity on the subjective well-being of accompanying children of migrant workers and the role of perception of exclusion and peer support in the process. Methods: A questionnaire survey was conducted among 304 migrant workers' accompanying children and 501 urban children in grades 4-9 in seven schools in Jiangxi Province, China. Hierarchical regression and bootstrap analysis were used. Results: Interpersonal sensitivity not only had a significant direct negative effect on the subjective well-being of migrant workers' accompanying children (ß= -0.27, 95% CI = [-0.37, -0.17]), but also had an indirect effect through perception of exclusion (ß= -0.06, 95% CI = [-0.11, -0.03]). Peer support negatively moderated the relationship between interpersonal sensitivity and perception of exclusion (ß= -0.18, 95% CI = [-0.28, -0.08]) and the mediating effect of perceptions of exclusion between interpersonal sensitivity and subjective well-being (ß = 0.06, CI = [0.02, 0.11]). Conclusion: The subjective well-being of migrant children is indeed lower than that of urban children, and one of the most important reasons is their higher interpersonal sensitivity. Interpersonal sensitivity not only directly reduces their subjective well-being, but also reduces it by triggering their perception of exclusion, while peer support can effectively mitigate this negative effect. Therefore, one way to improve the subjective well-being of these children is to reduce their excessive interpersonal sensitivity. Their parents should help them to adapt to urban life, to develop correct professional values and to deal correctly with "occupational stigma", to overcome feelings of inferiority, while communities can create specialized activity centers to provide more social opportunities and psychological counseling services for these children.

Association between the blood urea nitrogen-to-creatinine ratio and 3-month outcomes in patients with acute ischemic stroke: a secondary analysis based on a prospective cohort study.

Introduction: This study aimed to assess the correlation between the blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio and adverse outcomes (AOs) at 3 months in patients with acute ischemic stroke (AIS) in the Korean population. Methods: This cohort study encompassed 1906 cases of AIS at a South Korean hospital from January 2010 to December 2016. To determine the linear correlation between the BUN/Cr ratio and AOs in AIS, a binary logistic regression model (BLRM) was employed. Additionally, generalized additive models and techniques for smooth curve fitting were utilized to reveal the nonlinear dynamics between the BUN/Cr ratio and AOs in patients with AIS. Results: The prevalence of AOs was 28.65%, with a median BUN/Cr ratio of 18.96. Following adjustments for covariates, the BLRM disclosed that the association between the BUN/Cr ratio and the risk of AOs in patients with AIS did not attain statistical significance. Nevertheless, a nonlinear relationship surfaced, pinpointing an inflection point at 21.591. To the left of this inflection point, a 31.42% reduction in the risk of AOs was noted for every 1-unit surge in the Z score of the BUN/Cr ratio [odds ratio (OR) = 0.686, 95% confidence interval (CI): 0.519, 0.906, p = 0.008]. On the right side of the inflection point, the effect size (OR = 1.405, 95% CI: 1.018, 1.902, p = 0.039) was determined. Conclusion: The findings of this study underscore the intricate nature of the relationship between the BUN/Cr ratio and 3-month outcomes in patients with AIS, establishing a robust groundwork for future investigations.

Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia.

BACKGROUND: Cancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia's National Strategic Plan for Cancer Control Programme 2021-2025, emphasizing primary prevention and early detection to address cancer's impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer. METHODS: This cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests. RESULTS: The study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care. CONCLUSION: This study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice.

Bacteria such as the oral microbiome member Peptostreptococcus anaerobius can exacerbate colorectal cancer (CRC) development. Little is known regarding whether these immunomodulatory bacteria also affect antitumour immune checkpoint blockade therapy. Here we show that administration of P. anaerobius abolished the efficacy of anti-PD1 therapy in mouse models of CRC. P. anaerobius both induced intratumoral myeloid-derived suppressor cells (MDSCs) and stimulated their immunosuppressive activities to impair effective T cell responses. Mechanistically, P. anaerobius administration activated integrin α2ß1-NF-κB signalling in CRC cells to induce secretion of CXCL1 and recruit CXCR2+ MDSCs into tumours. The bacterium also directly activated immunosuppressive activity of intratumoral MDSCs by secreting lytC_22, a protein that bound to the Slamf4 receptor on MDSCs and promoted ARG1 and iNOS expression. Finally, therapeutic targeting of either integrin α2ß1 or the Slamf4 receptor were revealed as promising strategies to overcome P. anaerobius-mediated resistance to anti-PD1 therapy in CRC.

Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov., isolated from desert soil, and reclassification of Pedobacter xinjiangensis as Desertivirga xinjiangensis comb. nov. and Pedobacter mongoliensis as Paradesertivirga mongoliensis gen.nov., comb. nov.

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.

A case report to understand the use of an evidence-based approach of prolonged grief therapy in Chinese culture.

Prolonged grief disorder (PGD) is a new diagnosis that may cause significant functional impairment. Prolonged grief therapy (PGT) is a manualized 16-session intervention, whose efficacy has been demonstrated in studies primarily from Western cultures. The current report aimed to present a case to illustrate the use of PGT in Chinese culture. The client was a bereaved adult suffering from PGD after the death of her mother ten years ago. Additionally, she lost her father three months ago. Questionnaires were completed before and after treatment. In-depth interview was conducted at a 3-month follow-up. The client's scores for grief, functional impairment, grief-related beliefs and avoidance, depression and insomnia all decreased substantially after treatment. The follow-up feedbacks indicated that the beneficial effects of PGT persisted in the client's life. This case report provides preliminary evidence that bereaved people in China could benefit greatly from PGT, with minimal cultural adaptation.

Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma.

OBJECTIVE: Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear. DESIGN: We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry. RESULTS: Hepatocyte-specific Sqle tg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-γ+ and Granzyme B+ CD8+ T cells while enriching Arg-1+ myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqle knockout suppressed tumour growth with increased cytotoxic CD8+ T cells and reduced Arg-1+ MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+ T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+ T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+ T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+ T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models. CONCLUSION: SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+ T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

A novel LVPA-UNet network for target volume automatic delineation: An MRI case study of nasopharyngeal carcinoma.

Accurate delineation of Gross Tumor Volume (GTV) is crucial for radiotherapy. Deep learning-driven GTV segmentation technologies excel in rapidly and accurately delineating GTV, providing a basis for radiologists in formulating radiation plans. The existing 2D and 3D segmentation models of GTV based on deep learning are limited by the loss of spatial features and anisotropy respectively, and are both affected by the variability of tumor characteristics, blurred boundaries, and background interference. All these factors seriously affect the segmentation performance. To address the above issues, a Layer-Volume Parallel Attention (LVPA)-UNet model based on 2D-3D architecture has been proposed in this study, in which three strategies are introduced. Firstly, 2D and 3D workflows are introduced in the LVPA-UNet. They work in parallel and can guide each other. Both the fine features of each slice of 2D MRI and the 3D anatomical structure and spatial features of the tumor can be extracted by them. Secondly, parallel multi-branch depth-wise strip convolutions adapt the model to tumors of varying shapes and sizes within slices and volumetric spaces, and achieve refined processing of blurred boundaries. Lastly, a Layer-Channel Attention mechanism is proposed to adaptively adjust the weights of slices and channels according to their different tumor information, and then to highlight slices and channels with tumor. The experiments by LVPA-UNet on 1010 nasopharyngeal carcinoma (NPC) MRI datasets from three centers show a DSC of 0.7907, precision of 0.7929, recall of 0.8025, and HD95 of 1.8702 mm, outperforming eight typical models. Compared to the baseline model, it improves DSC by 2.14 %, precision by 2.96 %, and recall by 1.01 %, while reducing HD95 by 0.5434 mm. Consequently, while ensuring the efficiency of segmentation through deep learning, LVPA-UNet is able to provide superior GTV delineation results for radiotherapy and offer technical support for precision medicine.

A Spectroscopic Method for Distinguishing Two Novel Sandwich-Type Tungsten Oxide Cluster Compounds.

This study introduces two novel sandwich-type tungsten-oxygen cluster compounds synthesized by hydrothermal methods, H4(C6H12N2H2)3{Na(H2O)2[Mn2(H2O)(GeW9O34)]}2 (Compound 1) and H2(C6H12N2H2)3.5{Na3(H2O)4[Co2(H2O)(GeW9O34)]2}·17H2O (Compound 2). The two compounds comprise cluster anions [GeW9O34]10- coordinated with transition metal atoms, either Mn or Co, and are stabilized by organic ligands. These compounds are crystallized in the hexagonal crystal system and P63/m space group. The two compounds were characterized through various techniques. Fourier transform infrared (IR) spectroscopy showed absorption peaks of anionic backbone vibrations of the Keggin cluster at 500-1000 cm-1, IR spectral peaks of δ(N-H) and νas(C-N) of the ligand triethylenediamine at 1000-2000 cm-1, and IR spectral peaks of the ligand νas(N-H) and νas(O-H) of water at 3000-3500 cm-1. Despite similar one-dimensional (1D) IR spectra due to the same cluster anions and similar molecular structures, the two compounds exhibited distinct responses in two-dimensional correlation spectroscopy with IR under magnetic and thermal perturbations. Under magnetic perturbation, Compound 1 showed a strong response peak for νas(W-Ob-W), while Compound 2 exhibited a strong response peak for νas(W=Od), possibly linked to differing magnetic particles. Similarly, Compound 1 displayed a strong response peak under thermal perturbation for νas(W-Oc-W). In contrast, Compound 2 showed a strong response peak for νas(W=Od); these results may be attributed to the different hydrogen bonding connections between the two compounds, which affect the groups in distinct ways through vibration and transmit these vibrations to the W-O bonds. The research presented in this paper expands the theoretical and experimental data of 2D correlation IR spectroscopy.

Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response.

The infection caused by porcine epidemic diarrhea virus (PEDV) is associated with high mortality in piglets worldwide. Host factors involved in the efficient replication of PEDV, however, remain largely unknown. Our recent proteomic study in the virus-host interaction network revealed a significant increase in the accumulation of CALML5 (EF-hand protein calmodulin-like 5) following PEDV infection. A further study unveiled a biphasic increase of CALML5 in 2 and 12 hours after viral infection. Similar trends were observed in the intestines of piglets in the early and late stages of the PEDV challenge. Moreover, CALML5 depletion reduced PEDV mRNA and protein levels, leading to a one-order-of-magnitude decrease in virus titer. At the early stage of PEDV infection, CALML5 affected the endosomal trafficking pathway by regulating the expression of endosomal sorting complex related cellular proteins. CALML5 depletion also suppressed IFN-ß and IL-6 production in the PEDV-infected cells, thereby indicating its involvement in negatively regulating the innate immune response. Our study reveals the biological function of CALML5 in the virology field and offers new insights into the PEDV-host cell interaction.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion. / ç”µå¤´é’ˆè°ƒæŽ§å¤§è„‘ä¸­åŠ¨è„‰æ “å¡žå¤§é¼ ç¼ºè¡€å¤§è„‘çš®å±‚åŒºCYP27a1/b1、CYP24aåŠç›¸å ³ç‚Žæ€§ç»†èƒžå› å­è¡¨è¾¾çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.

Relationship between triglyceride-glucose index and blood eosinophils among asthmatic individuals in the USA.

BACKGROUND: Presently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma. METHODS: This study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups. RESULTS: Four linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI. CONCLUSIONS: In patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

Exploring the Light-Emitting Agents in Renilla Luciferases by an Effective QM/MM Approach.

Bioluminescence is a fascinating natural phenomenon, wherein organisms produce light through specific biochemical reactions. Among these organisms, Renilla luciferase (RLuc) derived from the sea pansy Renilla reniformis is notable for its blue light emission and has potential applications in bioluminescent tagging. Our study focuses on RLuc8, a variant of RLuc with eight amino acid substitutions. Recent studies have shown that the luminescent emitter coelenteramide can adopt multiple protonation states, which may be influenced by nearby residues at the enzyme's active site, demonstrating a complex interplay between protein structure and bioluminescence. Herein, using the quantum mechanical consistent force field method and the semimacroscopic protein dipole-Langevin dipole method with linear response approximation, we show that the phenolate state of coelenteramide in RLuc8 is the primary light-emitting species in agreement with experimental results. Our calculations also suggest that the proton transfer (PT) from neutral coelenteramide to Asp162 plays a crucial role in the bioluminescence process. Additionally, we reproduced the observed emission maximum for the amide anion in RLuc8-D120A and the pyrazine anion in the presence of a Na+ counterion in RLuc8-D162A, suggesting that these are the primary emitters. Furthermore, our calculations on the neutral emitter in the engineered AncFT-D160A enzyme, structurally akin to RLuc8-D162A but with a considerably blue-shifted emission peak, aligned with the observed data, possibly explaining the variance in emission peaks. Overall, this study demonstrates an effective approach to investigate chromophores' bimolecular states while incorporating the PT process in emission spectra calculations, contributing valuable insights for future studies of PT in photoproteins.

Deciphering the pathogenic risks of microplastics as emerging particulate organic matter in aquatic ecosystem.

Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities. We found that both microplastics and leaves have comparable impacts on microbial community structures and functions, enriching opportunistic pathogens and ARGs, which may pose potential environmental risks. These effects are likely driven by their influences on water properties, including dissolved organic carbon, nitrate, DO, and pH. However, microplastics uniquely promoted pathogens as keystone species and further amplified their capacity as hosts for ARGs, potentially posing a higher pathogenic risk than natural POM. Our research also emphasized the importance of considering both PA and FL bacteria when assessing microplastic impacts, as they exhibited different responses. Overall, our study elucidates the role and underlying mechanism of microplastics as an emerging POM in intensifying pathogenic risks of aquatic ecosystems in comparison with conventional natural POM.