Proteomic change in the upper lobe of the left lung of Beagle dogs at the lung migration stage of Toxocara canis infection.

BACKGROUND: Toxocara canis is considered one of the most neglected parasitic zoonoses and threatens the health of millions of people worldwide with a predilection for pediatric and adolescent populations in impoverished communities. Exploring the invasion and developmental mechanisms associated with T. canis infection in its definitive canine hosts will help to better control zoonotic toxocariasis. METHODS: Proteomic changes in samples from the upper lobe of the left lung of Beagle puppies were systematically analyzed by quantitative proteomic technology of data-independent acquisition (DIA) at 96 h post-infection (hpi) with T. canis. Proteins with P-values < 0.05 and fold change > 1.5 or < 0.67 were considered proteins with differential abundance (PDAs). RESULTS: A total of 28 downregulated PDAs and 407 upregulated PDAs were identified at 96 hpi, including RhoC, TM4SFs and LPCAT1, which could be associated with the maintenance and repair of lung homeostasis. GO annotation and KEGG pathway enrichment analyses of all identified proteins and PDAs revealed that many lung proteins have correlation to signal transduction, lipid metabolism and immune system. CONCLUSIONS: The present study revealed lung proteomic alterations in Beagle dogs at the lung migration stage of T. canis infection and identified many PDAs of Beagle dog lung, which may play important roles in the pathogenesis of toxocariasis, warranting further experimental validation.

Effect of propofol and ciprofol on the euphoric reaction in patients with painless gastroscopy: A prospective randomized controlled trial.

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

BmNPV p35 regulates apoptosis in Bombyx mori via a novel target of interaction with the BmVDAC2-BmRACK1 complex.

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2-dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway.

The mediating roles of depressive symptoms and social participation in the relationship between the effects of pain and cognitive function among Chinese older adults: A longitudinal study.

Decline in cognitive function poses a substantial burden on individuals, families, and society. However, the longitudinal potential mechanism underlying the link of pain and cognitive function remains unclear. Using data of 4247 participants aged 60 years and over from the China Health and Retirement Longitudinal Study in 2011, 2013, 2018, and 2020, we discussed the longitudinal predictive effect of pain on cognitive function and the mediating effects of depressive symptoms and social participation. The longitudinal mediation model analysis revealed that pain could not directly influence cognitive function, but it could indirectly predict cognitive function through the independent mediation effects of depressive symptoms and social participation. Moreover, the association between pain and cognitive function was serially mediated by depressive symptoms and social participation. Diversified interventions aimed at relieving pain and depressive symptoms, and increasing social participation in older adults would be beneficial for their cognitive function.

Foramen Facet Spinal Classification for Ossification of the Posterior Longitudinal Ligament on Computed Tomography: Closely Related to Clinical Efficacy.

STUDY DESIGN: Retrospective study. OBJECTIVE: To develop and validate computed tomography (CT)-based classification schemes to eliminate ambiguity as much as possible and evaluate the adequacy and clinical value of its classification. BACKGROUND: There is no objective criteria for laminoplasty of more than one million Chinese patients with ossification of the posterior longitudinal ligament (OPLL) every year. CT imaging can accurately show the location, size, and shape of ossification, it is very important to propose a recognized simple classification of ossifications. PATIENTS AND METHODS: From 2016 to 2018, 100 patients with "moderate to severe" OPLL on CT were performed according to the following criteria. This study simply classifies the grade of the ossification as 1-2-3, the zone is A-B by the foramen facet spinal canal classification, and the interexaminer reliability is 96%. A prospective series of 60 patients for laminoplasty was performed between 2018 and 2019, and this classification scheme was verified according to the new standard. All patients with size 1 were selectively excluded from consideration for surgery. The Japanese Orthopedic Association scores from both series are superior to most published results for patients with OPLL. RESULTS: The first and second series reported good to excellent results of 89% and 93.3%, respectively, and 80% and 85% for 24 months. The difference in the incidence of C5 paralysis and axial pain was statistically significant among the different zones, and most of them recovered within 6 months. The most common size and location types are 2-AB, 3-AB, and 2A. The most severe type is 3-AB. CONCLUSIONS: The foramen facet spinal classification of OPLL is a simple and reliable method for objectively evaluating the ossification of patients with OPLL based on CT research. LEVEL OF EVIDENCE: Level III.

A Preliminary Study on the Application of Contrast-Enhanced Ultrasonography in Children With Peripheral Neuroblastic Tumors.

The purpose of this study was to retrospectively analyze the characteristics of contrast-enhanced ultrasound (CEUS) images and quantitative parameters of time-intensity curves (TICs) in children's peripheral neuroblastic tumors (pNTs). By comparing the imaging features and quantitative parameters of the TICs of neuroblastoma (NB) and ganglioneuroblastoma (GNB) patients, we attempted to identify the distinguishing points between NB and GNB. A total of 35 patients confirmed to have pNTs by pathologic examination were included in this study. Each child underwent CEUS with complete imaging data (including still images and at least 3 min of video files). Twenty-four patients were confirmed to have NB, and 11 were considered to have GNB according to differentiation. The CEUS image features and quantitative parameters of the TICs of all lesions were analyzed to determine whether there were CEUS-related differences between the two types of pNT. There was a significant difference in the enhancement patterns of the CEUS features (χ2 = 5.303, p < 0.05), with more "peripheral-central" enhancement in the NB group and more "central-peripheral" enhancement in the GNB group. In the TIC, the rise time and time to peak were significantly different (p < 0.05). The receiver operating characteristic curve showed that the probability of ganglion cell NB increased significantly after RT > 15.29, with a sensitivity of 0.636 and a specificity of 0.958. When the peak time was greater than 16.155, the probability of NB increased significantly, with a sensitivity of 0.636 and a specificity of 0.958. The CEUS features of NB and GNB patients are very similar, and it is difficult to distinguish them. Rise time and time to peak may be useful in identifying GNB and NB, but the sample size of this study was small, and the investigation was only preliminary; a larger sample size is needed to support these conclusions.

Sybil Attacks Detection and Traceability Mechanism Based on Beacon Packets in Connected Automobile Vehicles.

Connected Automobile Vehicles (CAVs) enable cooperative driving and traffic management by sharing traffic information between them and other vehicles and infrastructures. However, malicious vehicles create Sybil vehicles by forging multiple identities and sharing false location information with CAVs, misleading their decisions and behaviors. The existing work on defending against Sybil attacks has almost exclusively focused on detecting Sybil vehicles, ignoring the traceability of malicious vehicles. As a result, they cannot fundamentally alleviate Sybil attacks. In this work, we focus on tracking the attack source of malicious vehicles by using a novel detection mechanism that relies on vehicle broadcast beacon packets. Firstly, the roadside units (RSUs) randomly instruct vehicles to perform customized key broadcasting and listening within communication range. This allows the vehicle to prove its physical presence by broadcasting. Then, RSU analyzes the beacon packets listened to by the vehicle and constructs a neighbor graph between the vehicles based on the customized particular fields in the beacon packets. Finally, the vehicle's credibility is determined by calculating the edge success probability of vehicles in the neighbor graph, ultimately achieving the detection of Sybil vehicles and tracing malicious vehicles. The experimental results demonstrate that our scheme achieves the real-time detection and tracking of Sybil vehicles, with precision and recall rates of 98.53% and 95.93%, respectively, solving the challenge of existing detection schemes failing to combat Sybil attacks from the root.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

Molybdenum inhibited the growth of Phytophthora nicotiana and improved the resistance of Nicotiana tabacum L. against tobacco black shank.

Tobacco black shank (TBS) is a soil-borne fungal disease caused by Phytophthora nicotiana (P. nicotianae), significantly impeding the production of high-quality tobacco. Molybdenum (Mo), a crucial trace element for both plants and animals, plays a vital role in promoting plant growth, enhancing photosynthesis, bolstering antioxidant capacity, and maintaining ultrastructural integrity. However, the positive effect of Mo on plant biotic stress is little understood. This study delves into the inhibitory effects of Mo on P. nicotianae and seeks to unravel the underlying mechanisms. The results showed that 16.32 mg/L of Mo significantly inhibited mycelial growth, altered mycelial morphological structure, damaged mycelial cell membrane, and ultimately led to the leakage of cell inclusions. In addition, 0.6 mg/kg Mo applied in soil significantly reduced the severity of TBS. Mo increased photosynthetic parameters and photosynthetic pigment contents of tobacco leaves, upregulated expression of NtPAL and NtPPO resistance genes, as well as improved activities of SOD, POD, CAT, PPO, and PAL in tobacco plants. Furthermore, Mo could regulate nitrogen metabolism and amino acids metabolism to protect tobacco plants against P. nicotianae infection. These findings not only present an ecologically sound approach to control TBS but also contribute valuable insights to the broader exploration of the role of microelements in plant disease management.

Cyclic Peptide Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Design, Synthesis, and In Vivo Treatment of Acute Lung Injury.

Directly blocking the Keap1-Nrf2 pathway is a promising strategy for the mitigation of acute lung injury (ALI). Peptide Keap1-Nrf2 inhibitors have been reported to have a high Keap1 binding affinity. However, these inhibitors showed weak activity in cells and/or animals. In this study, we designed a series of linear peptides from an Nrf2-based 9-mer Ac-LDEETGEFL-NH2. To improve the cellular activity, we further designed cyclic peptides based on the crystal complex of Keap1 with a linear peptide. Among them, cyclic 9-mer ZC9 targeting Keap1 showed a better affinity (KD2 = 51 nM). Specifically, it exhibited an acceptable water solubility (>38 mg/mL), better cell permeability, cell activity, and metabolic stability (serum t1/2 > 24 h). In the in vitro LPS-induced oxidative damages and ALI model, ZC9 showed significant dose-response reversal activity without apparent toxicity. In conclusion, our results suggested ZC9 as a lead cyclic peptide targeting the Keap1-Nrf2 pathway for ALI clinical treatment.

Yi-Qi-Huo-Xue decoction alleviates intracerebral hemorrhage injury through inhibiting neuronal autophagy of ipsilateral cortex via BDNF/TrkB pathway.

BACKGROUND: Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over a decade. Nevertheless, the precise pharmacotherapeutic compounds of YQHXD capable of penetrating into cerebral tissue and the pharmacological underpinnings of YQHXD remain ambiguous. METHODS: The active components of YQHXD in rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential targets, pathways and biological progresses of YQHXD ameliorating ICH induced injury was predicted by network pharmacology. Moreover, collagenase-induced ICH rat model, primary cortex neurons exposed to hemin and molecular docking were applied to validate the molecular mechanisms of YQHXD. RESULTS: Eleven active components of YQHXD were identified within the brains. Employing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, our investigation concentrated on the roles of autophagy and the BDNF/TrkB signaling pathway in the pharmacological context. The pharmacological results revealed that YQHXD alleviated neurological dysfunction, brain water content, brain swelling, and pathological injury caused by ICH. Meanwhile, YQHXD inhibited autophagy influx and autophagosome in vivo, and regulated cortex neuronal autophagy and TrkB/BDNF pathway both in vivo and in vitro. Subsequently, N-acetyl serotonin (NAS), a selective TrkB agonist, was employed to corroborate the significance of the BDNF/TrkB pathway in this process. The combination of NAS and YQHXD did not further enhance the protective efficacy of YQHXD in ICH rats. Additionally, outcomes of molecular docking analysis revealed that nine compounds of YQHXD exhibited potential regulatory effects on TrkB. CONCLUSIONS: Ipsilateral neuronal autophagy and BDNF/TrkB pathway were activated 72 h after ICH. YQHXD effectively resisted injury induced by ICH, which was related with suppression of ipsilateral neuronal autophagy via BDNF/TrkB pathway. This study provides novel insights into the therapeutic mechanisms of traditional Chinese medicine in the context of ICH treatment.

FOSL1 regulates hyperproliferation and NLRP3-mediated inflammation of psoriatic keratinocytes through the NF-kB signaling via transcriptionally activating TRAF3.

Psoriasis is a common and immune-mediated skin disease related to keratinocytes hyperproliferation and inflammation. Fos-like antigen-1 (FOSL1) is an important transcription factor involved in various diseases. FOSL1 has been reported to be differentially expressed in psoriasis. However, the roles and mechanism of FOSL1 in psoriasis progression remain largely unknown. FOSL1 is an upregulated transcription factor in psoriasis and increased in M5-treated HaCaT cells. FOSL1 had a diagnostic value in psoriasis, and positively associated with PASI score, TNF-α and IL-6 levels in psoriasis patients. FOSL1 silencing attenuated M5-induced HaCaT cell hyperproliferation through decreasing cell viability and proliferative ability and increasing cell apoptosis. FOSL1 knockdown mitigated M5-induced NLRP3 inflammasome activation and it-mediated inflammatory cytokine (IL-6, IL-8 and CCL17) expression. TRAF3 expression was increased in psoriasis patients and M5-treated HaCaT cells. FOSL1 transcriptionally activating TRAF3 in HaCaT cells. TRAF3 overexpression reversed the suppressive effects of FOSL1 silencing on M5-induced hyperproliferation and NLRP3-mediated inflammation. FOSL1 knockdown attenuated M5-induced NF-κB signaling activation by reducing TRAF3. Activation of NF-κB signaling reversed the effects of FOSL1 knockdown on hyperproliferation and inflammation in M5-treated cells. FOSL1 silencing prevented M5-induced hyperproliferation and NLRP3-mediated inflammation of keratinocytes by inhibiting TRAF3-mediated NF-κB activity, indicating FOSL1 might act as a therapeutic target of psoriasis.

Selenium Improves the Control Efficacy of Phytophthora nicotianae by Damaging the Cell Membrane System and Promoting Plant Energy Metabolism.

Tobacco black shank (TBS), caused by Phytophthora nicotianae, poses a significant threat to tobacco plants. Selenium (Se), recognized as a beneficial trace element for plant growth, exhibited inhibitory effects on P. nicotianae proliferation, disrupting the cell membrane integrity. This action reduced the energy supply and hindered hyphal transport through membrane proteins, ultimately inducing hyphal apoptosis. Application of 8 mg/L Se through leaf spraying resulted in a notable decrease in TBS incidence. Moreover, Se treatment preserved chloroplast structure, elevated chitinase activities, ß-1,3-GA, polyphenol oxidase, phenylalanine ammonia-lyase, and increased hormonal content. Furthermore, Se enhanced flavonoid and sugar alcohol metabolite levels while diminishing amino acid and organic acid content. This shift promoted amino acid degradation and flavonoid synthesis. These findings underscore the potential efficacy of Se in safeguarding tobacco and potentially other plants against P. nicotianae.

Deep medullary vein damage correlates with small vessel disease in small vessel occlusion acute ischemic stroke.

OBJECTIVES: We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. METHODS: The DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. RESULTS: We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. CONCLUSION: The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. CLINICAL RELEVANCE STATEMENT: The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. KEY POINTS: • The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

Role of TGF-ß3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-ß3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-ß3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-ß3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-ß3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-ß3 in order to evaluate its therapeutic effects. The expression pattern of TGF-ß3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-ß3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-ß3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-ß3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-ß3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

The Role of Nicotinamide Mononucleotide Supplementation in Psoriasis Treatment.

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients' lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Exenatide and Metformin Improve Serum Indices and Intestinal Flora in patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

The aim of the study was to investigate th e in flue nce of Exenatide comb ined with Met formin on fasti ng blood glucose, postpr andial glucose, triglycerides, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and inte s tinal flora in typ e 2 diab etes mellitus cases with non-alcoholic fatty liver disease. A total of 128 type 2 diabetes mellitus patients with non-alcoholic fatty liver disease, diagnosed from Januar y 2019 to January 2022, were included and randomly assigned to either G roup A (n=64) or Gro up B (n =64). Group A received Metformin, while Group B received Exenatide injection and Metfor min. After 24 weeks of treat ment, blood glucose indices (fasting blood glucose and postprandial glucose), blood lipid indices (triglycerides and total cholesterol), liver func tion indices (alanine aminotransferase and aspar tate aminotransferase) were all lower in Group B than in Group A (p<0.001 for all). Counts o f Escherichia coli and Enterococcus faecalis were lower in Group B than in Group A (both p<0.05), counts of Bifidobacteria and Lactobacillus were highe r i n Group B than in Grou p A (both p<0.05). Combin ation of Exenati de and Metformi n may have synergistic effects in improving metabo lic an d hepatic pa rameters, a s well as re gulat ing intestinal flora, which cou ld provide a pro misin g therapeutic option for the management of these patients.

The association between dual sensory loss and healthcare expenditure: Mediating effect of depression.

BACKGROUND: Previous studies have suggested the dual sensory loss (DSL) is linked to depression, and that they are associated with higher healthcare expenditures, respectively. However, the association between DSL, depression and healthcare expenditures remains ambiguous. OBJECTIVES: The current study aims to examine the association between DSL, depression and healthcare expenditures as well as catastrophic health expenditures (CHE) among Chinese people aged 45 and above. METHODS: We first utilized the China Health and Retirement Longitudinal Survey (CHARLS) 2018 to obtain data from a total of 13,412 Chinese individuals aged 45 and above to conduct a cross-sectional study. DSL was defined as a combined variable of self-reported vision loss and hearing loss. Depression was measured using The Center for Epidemiologic Studies Depression Scale (CESD-10). The healthcare expenditures, including outpatient out-of-pocket cost and inpatient out-of-pocket cost, were obtained from the Harmonized CHARLS section. CHE were defined as out-of-pocket (OOP) health spending equal to or higher than 40 % of a household's capacity to pay. A Tobit linear regression with three models and a path analysis were conducted to estimate the association between DSL, depression and healthcare expenditures and CHE. Then we utilized 2011CHARLS and 2018CHARLS to present a longitudinal analysis. A path analysis was conducted to estimate the association between 2011DSL, 2018depression and 2018healthcare expenditures and CHE. RESULTS: Depression has a significant mediating effect between DSL and healthcare expenditures. (For outpatient OOP cost: a = 0.453, b = 23.559, c = 25.257, the proportion of mediating effect in total effect = 29.71 %; for inpatient OOP cost: a = 0.453, b = 13.606, c = 15.463, the proportion of mediating effect in total effect = 28.50 %; all P < 0.05). The mediating effect of depression also exists in the association between DSL and CHE (a = 0.453, b = 0.018, c = 0.043, the proportion of mediating effect in total effect = 15.90 %; P < 0.05). The mediation effect of depression on healthcare expenditures and CHE also exists in the longitudinal analysis using CHARLS 2011 and CHARLS 2018 (all P < 0.05). LIMITATIONS: The DSL status were based on self-report and we used 2018CHARLS to conduct the study, which may cause some bias. CONCLUSION: Significant mediating effect of depression exists between DSL and higher healthcare expenditures and CHE. The mental health of elder people with DSL should be focused on, and we should have an overall viewpoint on the topic of healthcare expenditures and CHE.

Radiomics from dual-energy CT-derived iodine maps predict lymph node metastasis in head and neck squamous cell carcinoma.

OBJECTIVE: To develop and validate an iodine maps-based radiomics nomogram for preoperatively predicting cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 278 patients who pathologically confirmed as HNSCC were retrospectively recruited from two medical centers between June 2012 and July 2022. The training set (n = 152) and internal set (n = 67) were randomly selected from medical center A, and the patients from medical center B were enrolled as the external set (n = 69). The minority group in the training set was balanced by the adaptive synthetic sampling (ADASYN) approach. Radiomics features were extracted from dual-energy CT-derived iodine maps at arterial phase (AP) and venous phase (VP), respectively. Three radiomics signatures were constructed to predict the LNM by using a random forest algorithm. The independent clinical predictors for LNM were identified by multivariate analysis and combined with radiomics signatures to establish a radiomic-clinical nomogram. The performance of radiomic-clinical nomogram was evaluated with respect to its discrimination and clinical usefulness. RESULTS: The AP-VP-incorporated radiomics model exhibited a great predictive performance for LNM prediction with an area under curve (AUC) of 0.885 (95% CI, 0.836-0.933) in ADASYN-training set and confirmed in all validation sets. The nomogram that incorporated AP-VP radiomics signatures, CT-reported LN status, and histological grades yielded AUCs of 0.920 (95% CI, 0.881-0.959) in ADASYN-training set, 0.858 (95% CI, 0.771-0.944) in internal validation, and 0.849 (95% CI, 0.752-0.946) in external validation, with good calibration in all cohorts (p > 0.05). Decision curve analyses indicated the nomogram was clinically useful. In addition, the predictive performance of clinical-radiomics nomogram was also validation in combing cohorts. Stratified analysis confirmed the stability of nomogram, particularly in group negative for CT-reported LNM. CONCLUSION: Clinical-radiomics nomogram based on iodine maps exhibited promising performance in predicting LNM and providing valuable information for making individualized therapy decisions.

Multidimensional progressive single-cell sequencing reveals cell microenvironment composition and cancer heterogeneity in lung cancer.

Despite substantial advances in cancer biology and treatment, the clinical outcomes of patients with lung cancer remain unsatisfactory. The tumor microenvironment (TME) is a potential target. Using single-cell RNA sequencing, we could distinguish eight distinct cell types in the lung cancer microenvironment, demonstrating substantial intratumoral heterogeneity in 19 different lung cancer tumor samples. Through the re-dimensional grouping of cancer-associated fibroblasts (CAFs), myeloid cells, epithelial cells, natural killer (NK) cells, and T cells, the difference in the TME of lung cancer was revealed. We discovered SFTPB, SFN, and KRT8 as possible predictive biomarkers for lung cancer by assessing the gene expression patterns in epithelial cells. Examining cell-to-cell communications showed a robust association between the quantity of matrix CAFs, epithelial cells, and macrophages in the thrombospondin signaling pathway. Additionally, we found that the amyloid precursor protein signaling pathway primarily originated from the matrix, and inflammatory cancer-associated endothelial and fibroblast cells showed a co-expression relationship with myeloid cells and B cells. Through cell-to-cell correlation analysis, we found positive regulation between NK cells, regulatory T cells, GZMB-CD8 T cells, and GZMK-CD8 T cells, which could play a role in developing immune TMEs. These findings support studies on cancer heterogeneity and add to our understanding of lung cancer's cellular microenvironment.