A Neural Circuit For Bergamot Essential Oil-Induced Anxiolytic Effects.

Aromatic essential oils have been shown to relieve anxiety and enhance relaxation, although the neural circuits underlying these effects have remained unknown. Here, it is found that treatment with 1.0% bergamot essential oil (BEO) exerts anxiolytic-like effects through a neural circuit projecting from the anterior olfactory nucleus (AON) to the anterior cingulate cortex (ACC) in acute restraint stress model mice. Collectively, in vivo two-photon calcium imaging, viral tracing, and whole-cell patch clamp recordings show that inhalation exposure to 1.0% BEO can activate glutamatergic projections from the AON to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (AONGlu→ACCGABA→Glu). Optogenetic or chemogenetic manipulation of this pathway can recapitulate or abolish the BEO-induced anxiolytic-like behavioral effects in mice with ARS. Beyond depicting a previously unrecognized pathway involved in stress response, this study provides a circuit mechanism for the effects of BEO and suggests a potential target for anxiety treatment.

Enhancing palliative care for advanced cancer patients: evaluating implementation and impact of a virtual nurse-led symptom monitoring and telehealth initiative.

BACKGROUND: As a result of the COVID-19 pandemic, we implemented a novel nurse-led symptom monitoring and virtual telehealth program for patients with advanced cancer on palliative care. AIMS: To evaluate the reach, effectiveness, adoption, implementation, maintenance and acceptability of our program. METHODS: This was a prospective study carried out in a cohort of patients with advanced cancer over the period of 3rd June 2020 to 22nd October 2021. Demographic characteristics, cancer diagnosis, and functional status of patients were collected upon recruitment. Patients were asked to complete a patient-reported outcome measure (the Integrated Palliative Care Outcome Scale, IPOS) prior to the first palliative care consult and subsequently every week for the duration of their participation in the program (12 weeks). The IPOS measures the severity of physical symptoms, emotional concerns, information, and financial needs. Participants' utilization of healthcare services by participants 3 months before, during and 3 months after the telemedicine program was reviewed. At the end of the program, a client satisfaction questionnaire (CSQ-4) to survey participants' experience with the telehealth program and their willingness to pay for this program was administered. RESULTS: Reach: The recruitment to adoption ratio of the program was 0.71. Acceptability:: Participants expressed satisfactory experience. EFFECTIVENESS: We noted that the severity of patients' symptoms and number of emergency department visits decreased over time with nurse support. Adoption: we received referrals from 23 oncologists, yielding an adoption rate of 70%. IMPLEMENTATION: Of the 99 patients recruited for the program, 88.9% of them managed to complete their initial video consults as planned. 16% of them failed to complete the program due to factors such as patient demising. Maintenance: The declining rate of IPOS completion throughout the study period (98.9% at week 1 to 60.8% at week 12) demonstrated the difficulties in sustaining regular administration of self-reported patient outcome measures. CONCLUSION: The telemedicine program was effective and acceptable. We noted challenges in sustaining the administration of patient reported outcome measures over time. Further studies on how we can improve the sustainability of symptom monitoring in a telehealth program for patients with advanced illnesses, under palliative care, should be conducted.

CONTRIBUTIONS TO THE LITERATURE: • A virtual, nurse-led telehealth symptom monitoring service for patients with advanced cancer under palliative care, has acceptable reach, adoption from oncologists, is effective and could be implemented satisfactorily in the Asian population. • However, there are challenges in sustaining the regular reporting of patient reported outcome measures over time. • The use of the REAIM framework in this study has helped guide the evaluation of programs and helped generate areas for future studies.

The effects of fresh embryo transfer and frozen-thawed embryo transfer on the perinatal outcomes of single fetuses from mothers with PCOS.

PURPOSE: To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS. METHOD: Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed. RESULTS: The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice. CONCLUSION: Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice.

Exploring the anti-NSCLC mechanism of phillyrin targeting inhibition of the HSP90-AKT pathway.

Phillyrin (PHN), derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a kind of Chinese herbal medicine with the effect of clearing heat, and has been used in China for thousands of years in treating various tumors. However, the mechanism of its main components on non-small cell lung cancer (NSCLC) remains unclear. PHN is a distinct component extracted from Forsythia suspensa with promising anti-cancer activity against various tumor types. This study sought to elucidate the promising effects of PHN on NSCLC. Based on network pharmacology results, we identified potential PHN targets and pathways for NSCLC treatment. CCK-8 assay, wound healing assay, apoptosis assay, western blot, and in vivo experiments verified the inhibitory effect of PHN on NSCLC. Network pharmacology identified 160 potential PHN targets, 955 NSCLC-related targets, and 54 common targets, along with 132 pathways and 2 core genes. Biological experiments demonstrated that PHN significantly inhibited the growth and migration of A549 and LLC cells while promoting their apoptosis. Western blot analysis revealed down-regulation of AKT, HSP90AA1, and CDC37 expression, suggesting that PHN inhibits A549 and LLC cell proliferation by down-regulating the HSP90-AKT pathway. In vivo experiments confirmed that PHN significantly inhibited NSCLC growth with low toxicity. This study, using network pharmacology and biological experiments, verified the effectiveness of PHN against NSCLC through the HSP90-AKT pathway. These findings provide a foundation for further research and analysis.

Sirt1-mediated deacetylation of PGC-1α alleviated hepatic steatosis in type 2 diabetes mellitus via improving mitochondrial fatty acid oxidation.

Being activated by deacetylation, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has become an important regulator of metabolic-related diseases. The activation of Sirtuin 1 (Sirt1) by resveratrol was likely to deacetylate PGC-1α. However, the role of deacetylated PGC-1α in the alleviation of activated Sirt1 on type 2 diabetes mellitus (T2DM)-related fatty liver disease (FLD) remained unexplored. The aim of this study was to investigate the potential impact of Sirt1-mediated deacetylation of PGC-1α on T2DM-associated FLD and its underlying mechanisms. Our findings revealed that, along with the decreased Sirt1, the levels of acetylated PGC-1α were up-regulated in hepatocytes co-stimulated with high glucose (HG) and free fatty acids (FFA). Down-regulated Sirt1 inactivated PGC-1α by inhibiting its deacetylation, while activating Sirt1 improved hepatic injury by reducing lipid droplet accumulation through the deacetylation of PGC-1α. However, the beneficial effects of Sirt1 activation on hepatic steatosis were inhibited by PGC-1α antagonist in vitro. Mechanistically, activating Sirt1 enhanced mitochondrial function by promoting PGC-1α activity, thereby facilitating hepatic fatty acid oxidation (FAO). In conclusion, Sirt1-mediated deacetylation of PGC-1α mitigated hepatic lipotoxicity by enhancing mitochondrial FAO, which contributed to the restoration of mitochondrial function in T2DM. The activation of Sirt1-mediated PGC-1α deacetylation might represent a promising therapeutic approach for T2DM-associated FLD.

Bone assessment of the sacroiliac joint in ankylosing spondylitis: Comparison between computed tomography and zero echo time MRI.

PURPOSE: To demonstrate the clinical applicability of zero echo time magnetic resonance imaging (ZTE MRI) in bone assessment of the sacroiliac joint in ankylosing spondylitis. METHOD: Between January 2021 and November 2021, twenty-one ankylosing spondylitis patients underwent clinically indicated MRI including ZTE sequence, in addition, all patients underwent a CT scan covering the sacroiliac joints within 6 months of the MRI examination. The sensitivity, specificity, and accuracy of ZTE MRI were calculated using CT as the reference standard. Cohen's κappa tests were applied to assess the agreement of positive imaging findings (including erosions, osteosclerosis, bony cystic changes, and joint space changes) between MRI and CT as well as the inter-reader agreement for the grading of sacroiliitis in AS patients. RESULTS: There was no statistical significance between ZTE MRI and CT in detecting of ankylosing spondylitis(p＞0.05). The consistency of the diagnosis of positive imaging findings between ZTE MRI and CT was moderate to excellent (ranging from 0.611 to 0.889), and the consistency of the scores of positive imaging was good to excellent (ranging from 0.857 to 0.979). CONCLUSIONS: ZTE MRI provides "CT-like" contrast for bony changes of the sacroiliac joint in ankylosing spondylitis and could simplify and reduce costs for some AS patients when both MRI and CT are typically required.

Short-term respiratory cadmium exposure partially activates pulmonary NLRP3 inflammasome by inducing ferroptosis in mice.

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1ß and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1ß and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs.

Mortality associated with osteoporosis and pathological fractures in the United States (1999-2020): a multiple-cause-of-death study.

BACKGROUND: Osteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach. METHODS: Annual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test. RESULTS: From 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8-6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P < 0.05). White individuals had the highest number of deaths. The leading causes of death were heart diseases, chronic lower respiratory diseases, and alzheimer's disease. In addition, the number of deaths of patients with prostate cancer and breast cancer showed a significant downward trend, and the change of trend ratio between the two groups in different years was statistically significant (P < 0.05). CONCLUSIONS: Although mortality from osteoporosis with pathological fractures is decreasing, anti-osteoporosis therapy remains essential for elderly patients. Healthcare providers should remain vigilant for potential complications, including malignant neoplasms, and ensure timely diagnosis and treatment to further reduce mortality in this population.

Family history and genetic risk score combined to guide cancer risk stratification: A prospective cohort study.

Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (Ptrend < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies.

Based on UPLC-Q-TOF/MS and Network Pharmacology to Explore the Mechanism of Qingre Lishi Decoction in the Treatment of Psoriasis.

Background: Psoriasis is an immune-mediated chronic inflammatory disease. Qingre Lishi Decoction (QRLSD) has achieved great clinical effect in the treatment of psoriasis. However, the potential bioactive components and the mechanisms are yet unclear. Aim: To analyze the serum parameters of rats fed with QRLSD, screen out the active components of QRLSD, and explore the potential targets and pathway of QRLSD in the treatment of psoriasis. Materials and Methods: The active components of serum containing QRLSD were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The targets of QRLSD in the treatment of psoriasis were predicted by network pharmacology and molecular docking. In vitro experiments verified the underlying mechanism. Results: By UPLC-Q-TOF/MS, 15 prototype components and 22 metabolites were identified in serum containing QRLSD. Subsequently, 260 chemical composition targets and 218 psoriasis targets were overlapped to obtain 23 intersection targets, including LGALS3, TNF, F10, DPP4, EGFR, MAPK14, STAT3 and others. TNF, IL-10, GAPDH, STAT3, EGFR, ITGB1, LGALS3 genes were identified as potential drug targets in the PPI network analyzed by CytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that QRLSD may improve psoriasis by regulating immune and inflammatory pathways, the cytokine mediated signal transduction pathways and other signaling pathways. Molecular docking results showed that the main active components of the serum containing QRLSD had higher affinities for TNF and LGALS3. In vitro experiments confirmed that QRLSD may decrease levels of inflammatory cytokines by suppressing the NF-κB signaling pathway activated by TNF-α in human keratinocytes. Conclusion: This study explores the potential compounds, targets and signaling pathways of QRLSD in the treatment of psoriasis, which will help clarify the efficacy and mechanism of QRLSD.

MGDA-assisted plant washing agent for improving the removal of Cd and Cu from farmland soils.

Utilizing plant extracts for soil washing is a promising and cost-efficient strategy to permanently remove toxic metals from farmland soils. However, the efficiency of current plant extracts in heavy metals removal is constrained by the need of excessively high liquid-solid ratios (>10:1), which limits their practical application in the farmland soils. To address this challenge, we developed a novel binary washing agent consisting of Fructus mume residue extract (RPM) and methylglycinediacetate acid (MGDA). Through optimization experiments, we determined an optimal composition of 50 g L-1 RPM and 0.34 g L-1 MGDA (RPMG3), which exhibited a remarkable synergistic effect on the removal of Cd and Cu from two polluted farmland soils. Compared to the single use of RPM or MGDA, RPMG3 increased metal removal efficiency by 44.6%-303.8% in the alkaline dryland soil and 55.8%-141.9% in the slightly acidic paddy soil, at an optimum liquid-solid ratio of 2:1. The contents of soil Cd and Cu can be reduced to below the risk screening values via acid activation, metal ion exchange, and complexation of functional groups. Moreover, the potential ecological risks associated with Cd in the soils were significantly mitigated due to the decrease in exchangeable and reducible Cd fractions following RPMG3 washing. Additionally, RPM and RPMG3 washing led to enhancements in soil organic carbon and nutrient concentrations, as well as increased activities of soil enzymes including catalase, urease, and ß-glucosidase. Notably, RPMG3 washing exhibited the most pronounced promotion effect on wheat seed germination and growth. Taken together, the binary complex of RPMG3 demonstrates potential as an environmentally friendly green washing agent capable of in reducing heavy metals from farmland soil with great efficiency, even at low liquid-solid ratios.

A robust near-field body area network based on coaxially-shielded textile metamaterial.

A body area network involving wearable sensors distributed around the human body can continuously monitor physiological signals, finding applications in personal healthcare and athletic evaluation. Existing solutions for near-field body area networks, while facilitating reliable and secure interconnection among battery-free sensors, face challenges including limited spectral stability against external interference. Here we demonstrate a textile metamaterial featuring a coaxially-shielded internal structure designed to mitigate interference from extraneous loadings. The metamaterial can be patterned onto clothing to form a scalable, customizable network, enabling communication between near-field reading devices and battery-free sensing nodes placed within the network. Proof of concept demonstration shows the metamaterial's robustness against mechanical deformation and exposure to lossy, conductive saline solutions, underscoring its potential applications in wet environments, particularly in athletic activities involving water or significant perspiration, offering insights for the future development of radio frequency components for a robust body area network at a system level.

Interleukin-26 in channel catfish (Ictalurus punctatus): Molecular characterization and immune functional activity.

IL-26 is a crucial inflammatory cytokine that participates in defending host cells against infections. We initially cloned and identified the cDNA sequences of interleukin (IL)-26 in channel catfish (Ictalurus punctatus). The open reading frame (ORF) of IpIL-26 was 537 bp in length, encoding 178 amino acids (aa). Constitutive expression of IpIL-26 was observed in tested tissues, with the highest level found in the gill and spleen. To explore the function of IpIL-26 in channel catfish, different stimuli were used to act on both channel catfish and channel catfish kidney cells (CCK). The expression of IpIL-26 could be up-regulated by bacteria and viruses in multiple tissues. In vitro, recombinant IpIL-26 (rIpIL-26) could induce the expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, IL-20, and IL-22 playing vital roles in defending the host against infections. Our results demonstrated that IpIL-26 might be an essential cytokine, significantly affecting the immune defense of channel catfish against pathogen infections.

Potential of resveratrol in the treatment of systemic lupus erythematosus (Review).

Systemic lupus erythematosus (SLE) is a multi­system chronic autoimmune disease with a complex occurrence and development process, associated with immune disorders, uncertain prognosis, and treatment modalities which vary by patient and disease activity. At present, the clinical treatment of SLE mainly focuses on hormones and immunosuppressants. In recent years, the research on new treatment strategies for SLE has been booming, and strong preclinical results and clinical research have promoted the development of numerous drugs (such as rituximab and orencia), but numerous of these drugs have failed to achieve effectiveness in clinical trials, and there are some adverse reactions. Recent evidence suggests that resveratrol (RSV) has the effect of ameliorating immune disorders by inhibiting overactivation of immune cells. In the present review, advances in research on the protective effects and potential mechanisms of RSV against SLE are summarized and the potential potency of RSV and its use as a promising therapeutic option for the treatment of SLE are highlighted.

An interpretable artificial intelligence model based on CT for prognosis of intracerebral hemorrhage: a multicenter study.

OBJECTIVES: To develop and validate a novel interpretable artificial intelligence (AI) model that integrates radiomic features, deep learning features, and imaging features at multiple semantic levels to predict the prognosis of intracerebral hemorrhage (ICH) patients at 6 months post-onset. MATERIALS AND METHODS: Retrospectively enrolled 222 patients with ICH for Non-contrast Computed Tomography (NCCT) images and clinical data, who were divided into a training cohort (n = 186, medical center 1) and an external testing cohort (n = 36, medical center 2). Following image preprocessing, the entire hematoma region was segmented by two radiologists as the volume of interest (VOI). Pyradiomics algorithm library was utilized to extract 1762 radiomics features, while a deep convolutional neural network (EfficientnetV2-L) was employed to extract 1000 deep learning features. Additionally, radiologists evaluated imaging features. Based on the three different modalities of features mentioned above, the Random Forest (RF) model was trained, resulting in three models (Radiomics Model, Radiomics-Clinical Model, and DL-Radiomics-Clinical Model). The performance and clinical utility of the models were assessed using the Area Under the Receiver Operating Characteristic Curve (AUC), calibration curve, and Decision Curve Analysis (DCA), with AUC compared using the DeLong test. Furthermore, this study employs three methods, Shapley Additive Explanations (SHAP), Grad-CAM, and Guided Grad-CAM, to conduct a multidimensional interpretability analysis of model decisions. RESULTS: The Radiomics-Clinical Model and DL-Radiomics-Clinical Model exhibited relatively good predictive performance, with an AUC of 0.86 [95% Confidence Intervals (CI): 0.71, 0.95; P < 0.01] and 0.89 (95% CI: 0.74, 0.97; P < 0.01), respectively, in the external testing cohort. CONCLUSION: The multimodal explainable AI model proposed in this study can accurately predict the prognosis of ICH. Interpretability methods such as SHAP, Grad-CAM, and Guided Grad-Cam partially address the interpretability limitations of AI models. Integrating multimodal imaging features can effectively improve the performance of the model. CLINICAL RELEVANCE STATEMENT: Predicting the prognosis of patients with ICH is a key objective in emergency care. Accurate and efficient prognostic tools can effectively prevent, manage, and monitor adverse events in ICH patients, maximizing treatment outcomes.

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

A modified withdrawal time estimation and risk assessment of enrofloxacin in grass carp (Ctenopharyngodon idella) after ad libitum medicated feed based on statistical approaches in natural cultured environments.

Enrofloxacin (EF) is a broad-spectrum and highly efficient antibiotic commonly used for treating diseases in aquatic animals. However, its abuse in aquaculture applications often leads to excess residue in tissues of grass carp (Ctenopharyngodon idella). Hence, this study aimed to estimate the withdrawal time (WT) of EF and its metabolite of ciprofloxacin (CF) administered medicated feed in natural culture environments and conduct a risk assessment. Plasma and tissue samples were gathered at appropriate time points and detected by high-performance liquid chromatography. The data homogeneity was evaluated by Bartlett's test and Cochran's test. The linearity of the regressed line was evaluated by visual inspection and F test. Outliers were estimated on a normal probability scale by plotting the standardized residual versus their cumulative frequency distribution. Finally, the WT was calculated to be 51 days in muscle + skin based on the maximum residue limit of 100 µg/kg. After 51 days, the concentration of EF and CF fell below 10 µg/kg. The estimated daily intake was calculated to be 0.009 µg/kg/d. Hazard quotient was computed to be 0.002, which was far below one. These results suggested that calculated WT of EF could ensure the safety of products from grass carp for humans.

Development and evaluation of a risk prediction tool for risk-adapted screening of colorectal cancer in China.

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.

Wireless, customizable coaxially shielded coils for magnetic resonance imaging.

Anatomy-specific radio frequency receive coil arrays routinely adopted in magnetic resonance imaging (MRI) for signal acquisition are commonly burdened by their bulky, fixed, and rigid configurations, which may impose patient discomfort, bothersome positioning, and suboptimal sensitivity in certain situations. Herein, leveraging coaxial cables' inherent flexibility and electric field confining property, we present wireless, ultralightweight, coaxially shielded, passive detuning MRI coils achieving a signal-to-noise ratio comparable to or surpassing that of commercially available cutting-edge receive coil arrays with the potential for improved patient comfort, ease of implementation, and substantially reduced costs. The proposed coils demonstrate versatility by functioning both independently in form-fitting configurations, closely adapting to relatively small anatomical sites, and collectively by inductively coupling together as metamaterials, allowing for extension of the field of view of their coverage to encompass larger anatomical regions without compromising coil sensitivity. The wireless, coaxially shielded MRI coils reported herein pave the way toward next-generation MRI coils.