In Vitro and In Vivo Evaluation of Virus-Induced Innate Immunity in Mouse.

The innate immune system is the first line of host defense against infection by pathogenic microorganisms, among which macrophages are important innate immune cells. Macrophages are widely distributed throughout the body and recognize and eliminate viruses through pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs). In the present chapter, we provide detailed protocols for vesicular stomatitis virus (VSV) amplification, VSV titer detection, isolation of mouse primary peritoneal macrophages, in vitro and in vivo VSV infection, detection of interferon-beta (IFN-ß) expression, and lung injury. These protocols provide efficient and typical methods to evaluate virus-induced innate immunity in vitro and in vivo.

FUBP3 mediates the amyloid-ß-induced neuronal NLRP3 expression.

JOURNAL/nrgr/04.03/01300535-202507000-00028/figure1/v/2024-09-09T124005Z/r/image-tiff Alzheimer's disease is characterized by deposition of amyloid-ß, which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from amyloid-ß deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3 in vitro and in vivo, and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-ß is present. In the brains of aged wild-type mice and a mouse model of Alzheimer's disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5' end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-ß-to-phospho-tau transition than microglial NLRP3, and that amyloid-ß fundamentally alters the regulatory mechanism of NLRP3 expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Levels, enrichment characteristics, and health risks of halogenated and parent polycyclic aromatic hydrocarbons in traditional smoked pork.

Chinese traditional smoked pork was contaminated with polycyclic aromatic hydrocarbons (PAHs) and chlorinated and brominated PAHs (ClPAHs and BrPAHs; XPAHs) during the smoking process. Therefore, our study investigated the concentrations, enrichment characteristics, and health risks associated with PAHs, as well as ClPAHs and BrPAHs in Chinese traditional smoked pork. The total concentrations of PAHs, ClPAHs and BrPAHs in traditional smoked pork ranged from 90.0 to 79200 ng/g fat weight (fw), 23.6-2340 pg/g fw and 0.550-200 pg/g fw, respectively, which were significantly higher than their levels found in raw pork. Additionally, the concentrations of PAHs and XPAHs in the surface of smoked pork were higher than those in the inner parts. High-ring PAHs exhibited a greater enrichment compared to low-ring PAHs, and BrPAHs exhibited greater enrichment ability than ClPAHs in smoked pork. Furthermore, the ability of individual congeners to migrate from the surface to the inner parts of the smoked pork were varied. When the smoking fuels were similar, a longer smoking time resulted in higher concentrations of PAHs and XPAHs in smoked pork, while casing effectively reduced their concentrations. The correlation between XPAH and parent PAH concentrations indicated that chlorination of PAHs was one of the primary formation mechanisms of some monochlorinated PAHs. Over half of the smoked pork samples posed a potential carcinogenic risk, particularly the surface samples. It is recommended to remove the surface parts when consuming smoked pork and to improve traditional smoking methods to mitigate the health risks.

Target Fitting Method for Spherical Point Clouds Based on Projection Filtering and K-Means Clustered Voxelization.

Industrial computed tomography (CT) is widely used in the measurement field owing to its advantages such as non-contact and high precision. To obtain accurate size parameters, fitting parameters can be obtained rapidly by processing volume data in the form of point clouds. However, due to factors such as artifacts in the CT reconstruction process, many abnormal interference points exist in the point clouds obtained after segmentation. The classic least squares algorithm is easily affected by these points, resulting in significant deviation of the solution of linear equations from the normal value and poor robustness, while the random sample consensus (RANSAC) approach has insufficient fitting accuracy within a limited timeframe and the number of iterations. To address these shortcomings, we propose a spherical point cloud fitting algorithm based on projection filtering and K-Means clustering (PK-RANSAC), which strategically integrates and enhances these two methods to achieve excellent accuracy and robustness. The proposed method first uses RANSAC for rough parameter estimation, then corrects the deviation of the spherical center coordinates through two-dimensional projection, and finally obtains the spherical center point set by sampling and performing K-Means clustering. The largest cluster is weighted to obtain accurate fitting parameters. We conducted a comparative experiment using a three-dimensional ball-plate standard. The sphere center fitting deviation of PK-RANSAC was 1.91 µm, which is significantly better than RANSAC's value of 25.41 µm. The experimental results demonstrate that PK-RANSAC has higher accuracy and stronger robustness for fitting geometric parameters.

Modified dorsal recumbent position versus lithotomy position for flexible ureteroscopic lithotomy: a multicenter prospective randomized controlled clinical trial.

Background: The lithotomy position (LP) may pose limitations and discomfort for elderly patients and those with a history of lower limb surgery, potentially leading to an increased risk of complications. And the LP is the conventional position during flexible ureteroscopic lithotomy for the treatment of ureteral calculi. However, it has some disadvantages, such as peripheral nerve injury and deep venous thrombosis in the lower limbs, etc. Therefore, we performed a new approach, which is named as modified dorsal recumbent position (MDRP). Currently, there is a lack of systematic analysis and standardization regarding the surgical positioning for flexible ureteroscopic lithotripsy. The objective of the study was to assess whether there were any disparities in the overall duration of the procedure when comparing the MDRP with the LP. The investigation of the optimal position for flexible ureteroscopic lithotomy is essential for enhancing patient safety and comfort. Methods: This is a prospective, multicenter, randomized clinical trial. A total of 144 patients with renal or ureteral calculi from April 2021 to June 2022 were enrolled. Eligible patients were randomized to the MDRP group (n=72) or LP group (n=72). The patient's demographics, the placement of the surgical position (time of position placement, time of disinfection and towel laying, time of position return, degree of medical fatigue) and the operation safety (time of operation, time of ureteroscope from bladder neck to ureteral orifice, heart rate, blood pressure) of two groups were compared and analyzed. Results: Between the two groups, the body positioning time (93.8±31.6 vs. 134.8±40.1 s, P=0.02), operation time (71.8±36.7 vs. 77.7±48.6 min, P=0.04), the time from the bladder neck to the ureteral orifice of the flexible ureteroscope spent by the doctors (3.4±4.7 vs. 10.3±14.7 s, P<0.001) and incidence rate of patient's lower limb soreness (19.4% vs. 49.7%, P=0.01) in the MDRP group were significantly shorter than those in the LP group. However, there was no significant difference in the stone removal rate (87.6% vs. 85.4%, P=0.09) or postoperative hospitalization days (4.3±1.4 vs. 4.1±1.6 d, P=0.08) between the two groups. Conclusions: This trial showed that the MDRP could not only effectively shorten the operation time, shorten the time from the bladder neck to the ureteral orifice of the ureteroscopic lithotripsy, but also place the patient's body in a functional position, stabilize the blood pressure during the operation, improve the comfort of the patient. Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2100053416).

SrHPO4-coated Mg alloy implant attenuates postoperative pain by suppressing osteoclast-induced sensory innervation in osteoporotic fractures.

Osteoporotic fractures have become a common public health problem and are usually accompanied by chronic pain. Mg and Mg-based alloys are considered the next-generation orthopedic implants for their excellent osteogenic inductivity, biocompatibility, and biodegradability. However, Mg-based alloy can initiate aberrant activation of osteoclasts and modulate sensory innervation into bone callus resulting in postoperative pain at the sequential stage of osteoporotic fracture healing. Its mechanism is going to be investigated. Strontium hydrogen phosphate (SrHPO4) coating to delay the Mg-based alloy degradation, can reduce the osteoclast formation and inhibit the growth of sensory nerves into bone callus, dorsal root ganglion hyperexcitability, and pain hypersensitivity at the early stage. Liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis of bone marrow-derived macrophages (BMMs) treated with SrHPO4-coated Mg alloy extracts shows the potential effect of increased metabolite levels of AICAR (an activator of the AMPK pathway). We demonstrate a possible modulated secretion of AICAR and osteoclast differentiation from BMMs, which inhibits sensory innervation and postoperative pain through the AMPK/mTORc1/S6K pathway. Importantly, supplementing with AICAR in Mg-activated osteoclasts attenuates postoperative pain. These results suggest that Mg-induced postoperative pain is related to the osteoclastogenesis and sensory innervation at the early stage in the osteoporotic fractures and the SrHPO4 coating on Mg-based alloys can reduce the pain by upregulating AICAR secretion from BMMs or preosteoclasts.

Rapid determination for tyrosine isomers in food based on N-acetyl-L-cysteine/Upconversion nanomaterials target-induced quench by chiral Electrochemiluminescence sensor.

Rapid determination of amino acid isomer is very important for the evaluation of the amino acid nutrition in different foods, so a fast and sensitive electrochemiluminescence (ECL) sensor was innovatively fabricated for the determination of tyrosine isomers in foods based on N-Acetyl-L-cysteine/upconversion nanomaterials possessed a good particular selectivity to L-tyrosine. Under the optimal conditions, for L-tyrosine, the limit of detection (LOD) of the sensor for L-tyrosine was 2.87 × 10-6 M, detection range of 5.5 × 10-5-5.5 × 10-3 M, for D-tyrosine, LOD was 2.56 × 10-5 M, detection range was from 5.5 × 10-4 to 5.5 × 10-3 M. The developed chiral sensor was used to determinate the tyrosine isomers in foods successfully, which provided a convenient method to quickly evaluate the nutritional value of amino acids in food.

The rs3918188 and rs1799983 loci of eNOS gene are associated with susceptibility in patients with systemic lupus erythematosus in Northeast China.

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.

Characterization of volatile aroma compounds in pak choi.

Aroma is a key sensory factor in the flavor evaluation of pak choi (Brassica rapa L. ssp. chinensis var. Makino). The pak choi varieties Xiangqingcai (XQC) and Xiuhuajin (XHJ) have unique aroma characteristics, but the chemical profiles of these aromas are unknown. Here, the aroma profiles of three varieties of pak choi including XQC, XHJ, and Suzhouqing (CK, non-aromatic) were determined using gas chromatography-mass spectrometry (GC-MS) and relative odor activity values (rOAV). A total of 15 categories of 716 volatile metabolites were detected in the three pak choi varieties, with terpenoid metabolites identified as the major components, although in each sample the identity of the major terpenoid metabolite varied. There were 53 aroma components in XQC and 54 aroma components in XHJ with rOAV >1, which contribute to rice aroma and fishy odor of these varieties, respectively.

Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors.

Background: Patients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option. Objectives: This study aimed to evaluate the safety and efficacy of TARFACT. Methods: Five patients with cardiac tumors (mucinous liposarcoma, myocardial hypertrophy with inflammatory cell infiltration mass, fibrous tissue tumor hyperplasia, myocardial clear cell sarcoma, and cardiac rhabdomyoma) were included. All patients underwent TARFACT and were assessed with electrocardiogram, echocardiographic imaging, biochemical analysis, and pathological confirmation. Results: The median follow-up for all patients was 9 (range 4-12) months. Three surviving patients were alive at their last follow-up (9, 12, and 12 months, respectively), whereas 2 patients with late-stage tumors survived 6 months and 13 months after TARFACT, respectively. After TARFACT, all patients showed significant reductions in tumor size: the mean length decreased from 6.7 ± 2.0 cm to 4.7 ± 1.8 cm (P = 0.007); and the mean width decreased from 5.0 ± 2.1 cm to 2.5 ± 0.7 cm (P = 0.041). NYHA functional class also improved: median (IQR) decreased from 3.0 (1.5) to 2.0 (1.0) (P = 0.038), Peak E-wave on echocardiography showed a mean increase from 64.4 ± 15.7 cm/s to 76.6 ± 18.6 cm/s (P = 0.008), and NT-pro BNP levels had a median (IQR) reduction from 115.7 (252.1) pg/mL to 55.0 (121.6) pg/mL (P = 0.043). Conclusions: TARFACT is a novel palliative treatment option for cardiac tumors, reducing accessible tumors and improving clinical symptoms in a preliminary group of patients. (Cardiac Tumors Interventional [Radio Frequency/Laser Ablation] Therapy [CTIH]; NCT02815553).

The relationship between future time perspective and suicide ideation in college students: Multiple mediating effects of anxiety and depression.

Background: Suicide ideation has high prevalence in adolescents, better future time perspective is considered a protective role for anxiety, depression, and suicide ideation. However, the impact of future time perspective on suicide ideation remains unclear, especially when anxiety and depression as mediating roles. Methods: A cross-sectional study of college students was performed in Chongqing, China. There are 851 students enrolled in this study and we distribute questionnaires through the WeChat platform to obtain data in 2023. We conducted Pearson correlation analysis and descriptive statistics. Model 6 in PROCESS 4.0 was used to test the multiple mediating effect. Results: College students who have higher future time perspective are associated with a lower risk of anxiety, depression, and suicide ideation. Future time perspective not only affects suicide ideation directly, but also influence it by means of two mediating pathways: ①depression, the mediation effect is 37.41 %; ②the multiple mediating effects of anxiety and depression with a mediating effect of 29.68 %. Conclusion: Higher future time perspective functions as a protective role in anxiety, depression, and suicide ideation; future time perspective can affect and predict the occurrence of suicide ideation by influencing anxiety and depression in college students. This conclusion will be a novel and insightful part of adolescent mental health research, and provide a new perspective to prevent college students from committing suicide in the future.

Rapid flowing cells localization enabled by spatiotemporal manipulation of their holographic patterns.

Lab-on-a-Chip microfluidic devices present an innovative and cost-effective platform in the current trend of miniaturization and simplification of imaging flow cytometry; they are excellent candidates for high-throughput single-cell analysis. In such microfluidic platforms, cell tracking becomes a fundamental tool for investigating biophysical processes, from intracellular dynamics to the characterization of cell motility and migration. However, high-throughput and long-term cell tracking puts a high demand on the consumption of computing resources. Here, we propose a novel strategy to achieve rapid 3D cell localizations along the microfluidic channel. This method is based on the spatiotemporal manipulation of recorded holographic interference fringes, and it allows fast and precise localization of cells without performing complete holographic reconstruction. Conventional holographic tracking is typically based on the phase contrast obtained by decoupling the calculation of optical axial and transverse coordinates. Computing time and resource consumption may increase because all the frames need to be calculated in the Fourier domain. In our proposed method, the 2D transverse positions are directly located by morphological calculation based on the hologram. The complex-amplitude wavefronts are directly reconstructed by spatiotemporal phase shifting to calculate the axial position by the refocusing criterion. Only spatial calculation is considered in the proposed method. We demonstrate that the computational time of transverse tracking is only one-tenth of the conventional method, while the total computational time of the proposed method decreases up to 54% with respect to the conventional approach. The proposed approach can open the route for analyzing flow cytometry in quantitative phase microscopy assays.

The combined internal and external fixation surgery is effective and safe in treating posterior lateral tibial plateau fractures: An observational study.

To investigate the treatment outcomes of combined internal and external fixation surgery for patients with posterior lateral tibial plateau fractures and explore its safety. The study was conducted from February 2020 to February 2023 and included a total of 77 patients with Schatzker IV and Schatzker V type posterior lateral tibial plateau fractures. Patients were divided into control group and treatment group according to different treatment methods: the control group with 38 cases received treatment with dual-support plates, and the study group with 39 cases received treatment with internal fixation using medial plates combined with lateral locking plates. Clinical indicators during treatment, immediate postoperative and 12-month postoperative radiographic indicators, Rasmussen knee joint function scores before and 3 months after surgery, knee joint function recovery, quality of life, and postoperative complications were recorded and compared between the 2 groups. The inter-group comparisons were made for intraoperative blood loss, surgical duration, and the time to start weight-bearing postoperatively (P > .05). The study group had shorter postoperative hospital stays and fracture healing times compared to the control group (P < .05). Immediately postoperatively, the medial tilt angle and posterior tilt angle in both groups were compared (P > .05). At 12 months postoperatively, the medial tilt angle decreased and the posterior tilt angle increased in both groups compared to immediately postoperative values (P < .05), with no significant difference between the groups (P > .05). However, at 3 months postoperatively, the scores for various dimensions in both groups increased compared to preoperative values, and the study group had higher scores than the control group (P < .05). However, at 3 months postoperatively, the quality of life scores were higher than preoperative values in both groups, with the study group having higher scores (P < .05). The occurrence of complications during the treatment period was compared between the 2 groups (P > .05). The medial and lateral combined plate fixation has a good clinical effect in the treatment of posterolateral tibial plateau fractures, which can shorten the fracture healing time, help the recovery of knee joint function and improve the quality of life of patients after operation, and has high safety in the treatment process.

A novel shockwave-driven nano-motor composite microneedle transdermal delivery system for the localized treatment of osteoporosis: a basic science study.

BACKGROUND: Clinical protocols in osteoporosis treatment could not meet the requirement of increasing local bone mineral density. A local delivery system was brought in to fix this dilemma. The high-energy extracorporeal shock wave (ESW) can travel into the deep tissues with little heat loss. Hence, ESW-driven nanoparticles could be used for local treatment of osteoporosis. MATERIALS AND METHODS: An extracorporeal shock wave (ESW)--actuated nanomotor (NM) sealed into microneedles (MN) (ESW-NM-MN) was constructed for localized osteoporosis protection. The NM was made of calcium phosphate nanoparticles with a high Young's modulus, which allows it to absorb ESW energy efficiently and convert it into kinetic energy for solid tissue penetration. Zoledronic (ZOL), as an alternative phosphorus source, forms the backbone of the NM (ZOL-NM), leading to bone targeting and ESW-mediated drug release. RESULTS: After the ZOL-NM is sealed into hyaluronic acid (HA)--made microneedles, the soluble MN tips could break through the stratum corneum, injecting the ZOL-NM into the skin. As soon as the ESW was applied, the ZOL-NM would absorb the ESW energy to move from the outer layer of skin into the deep tissue and be fragmented to release ZOL and Ca2+ for anti-osteoclastogenesis and pro-osteogenesis. In vivo, the ZOL-NM increases localized bone parameters and reduces fracture risk, indicating its potential value in osteoporotic healing and other biomedical fields. CONCLUSION: The ESW-mediated transdermal delivery platform (ESW-NM-MN) could be used as a new strategy to improve local BMD and protect local prone-fracture areas.

Ultrahigh Electrostrictive Effect in Lead-Free Sodium Bismuth Titanate-Based Relaxor Ferroelectric Thick Film.

In recent years, the development of environmentally friendly, lead-free ferroelectric films with prominent electrostrictive effects have been a key area of focus due to their potential applications in micro-actuators, sensors, and transducers for advanced microelectromechanical systems (MEMS). This work investigated the enhanced electrostrictive effect in lead-free sodium bismuth titanate-based relaxor ferroelectric films. The films, composed of (Bi0.5Na0.5)0.8-xBaxSr0.2TiO3 (BNBST, x = 0.02, 0.06, and 0.11), with thickness around 1 µm, were prepared using a sol-gel method on Pt/TiO2/SiO2/Si substrates. By varying the Ba2+ content, the crystal structure, morphology, and electrical properties, including dielectric, ferroelectric, strain, and electromechanical performance, were investigated. The films exhibited a single pseudocubic structure without preferred orientation. A remarkable strain response (S > 0.24%) was obtained in the films (x = 0.02, 0.06) with the coexistence of nonergodic and ergodic relaxor phases. Further, in the x = 0.11 thick films with an ergodic relaxor state, an ultrahigh electrostrictive coefficient Q of 0.32 m4/C2 was achieved. These findings highlight the potential of BNBST films as high-performance, environmentally friendly electrostrictive films for advanced microelectromechanical systems (MEMS) and electronic devices.

High-Extraction-Rate Ta2O5-Core/SiO2-Clad Photonic Waveguides on Silicon Fabricated by Photolithography-Assisted Chemo-Mechanical Etching (PLACE).

We demonstrate high-extraction-rate Ta2O5-core/SiO2-clad photonic waveguides on silicon fabricated by the photolithography-assisted chemo-mechanical etching technique. Low-confinement waveguides of larger than 70% coupling efficiency with optical fibers and medium propagation loss around 1 dB/cm are investigated in the experiment. Monolithic microring resonators based on Ta2O5 waveguides have shown the quality factors to be above 105 near 1550 nm. The demonstrated Ta2O5 waveguides and their fabrication method hold great promise in various cost-effective applications, such as optical interconnecting and switching.

The causal and mediation effect of chronic obstructive pulmonary disease on lung cancer subtypes: a two-sample mendelian randomization study.

PURPOSE: This study aims to determine the causal effect of chronic obstructive pulmonary disease (COPD) on different subtypes of lung cancer and to investigate the mediation effects of COPD between smoking and the subtypes of lung cancer. METHODS: The study utilized summary level data from genome-wide association studies. It extracted independent single nucleotide polymorphisms (SNP) to serve as instrumental variables (IV). We conducted two-sample MR analyses primarily using inverse-variance weighting, as well as MR-Egger and MR-PRESSO to establish and validate the causal impact of COPD on lung cancer subtypes. Additionally, multivariable MR analysis was employed to ascertain the mediating role of COPD between smoking and lung cancers. RESULTS: The two-sample MR analysis demonstrated that COPD is linked to an elevated risk of lung adenocarcinoma (OR: 1.48, 95% CI 1.35-1.61, p = 0.009) and squamous cell carcinoma (OR: 1.78, 95% CI 1.62-1.93, p = 0.001). Further, using multivariable MR, it was established that COPD mediates the causal effects of smoking on lung adenocarcinoma by 56.52% (95% CI 17.51-95.52%) and 63.61% (95% CI 38.31-88.92%) in lung squamous cell carcinoma. CONCLUSION: Our study found that COPD was a risk factor for developing both lung adenocarcinoma and squamous cell carcinoma. COPD also played a crucial role in mediating the causal effects of smoking on these two subtypes of lung cancer.

The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats.

Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.