Trajectory patterns and predictors of cancer-related fatigue in postoperative lung cancer patients receiving chemotherapy.

PURPOSE: Cancer-related fatigue (CRF) is a chronic symptom that can affect the overall functioning of lung cancer patients throughout the course of the disease. However, there is limited research on the trajectory and predictors of CRF specifically in lung cancer patients. Furthermore, few studies have investigated the predictive role of positive psychological and social factors in relation to CRF. This study aimed to explore the trajectory of CRF and its predictors in postoperative chemotherapy patients with lung cancer. METHODS: A total of 202 lung cancer patients who underwent surgery and received adjuvant chemotherapy were recruited for this study. Baseline questionnaires were completed, covering sociodemographic information, disease details, CRF levels, personality traits, psychological resilience, and social support. CRF was assessed at three time points: first chemotherapy (T1), 3 months after chemotherapy (T2), and 6 months after chemotherapy (T3). Latent class growth modeling (LCGM) was used to identify distinct developmental trajectories of CRF. Logistic regression analysis was employed to examine predictors of CRF within different patient groups. RESULTS: The LCGM analysis revealed three distinct CRF trajectories: persistent high fatigue group (30.7%), rising fatigue group (30.7%), and no fatigue group (38.6%). Cancer stage (OR = 7.563, 95% CI = 2.468-23.182, P < 0.001), melancholic personality (OR = 6.901, 95% CI = 1.261-37.764, P = 0.026), and high psychological resilience (OR = 0.171, 95% CI = 0.041-0.706, P = 0.015) were associated with the CRF trajectory. On the other hand, sanguine personality (OR = 0.254, 95% CI = 0.071-0.916, P = 0.036) and high social support (OR = 0.168, 95% CI = 0.045-0.627, P = 0.008) were associated with the increasing fatigue trajectory. CONCLUSIONS: This study demonstrated that 60% of lung cancer patients experienced persistent fatigue throughout the assessment period. Moreover, it confirmed the heterogeneity of CRF trajectories among lung cancer patients. The severity of CRF was found to be higher in patients with advanced clinical stages, depressive personality traits, and lower psychological resilience.

Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis.

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 knockout (MyD88-/-) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88-/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed. Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.

Interaction effects between sleep-related disorders and depression on hypertension among adults: a cross-sectional study.

BACKGROUND: Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. METHODS: This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. RESULTS: Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37-1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95-2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02-1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08-3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. CONCLUSIONS: Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.

Optimized Adsorption-Catalytic Conversion for Lithium Polysulfides by Constructing Bimetallic Compounds for Lithium-Sulfur Batteries.

Although lithium-sulfur batteries possess the advantage of high theoretical specific capacity, the inevitable shuttle effect of lithium polysulfides is still a difficult problem restricting its application. The design of highly active catalysts to promote the redox reaction during charge-discharge and thus reduce the existence time of lithium polysulfides in the electrolyte is the mainstream solution at present. In particular, bimetallic compounds can provide more active sites and exhibit better catalytic properties than single-component metal compounds by regulating the electronic structure of the catalysts. In this work, bimetallic compounds-nitrogen-doped carbon nanotubes (NiCo)Se2-NCNT and (CuCo)Se2-NCNT are designed by introducing Ni and Cu into CoSe2, respectively. The (CuCo)Se2-NCNT delivers an optimized adsorption-catalytic conversion for lithium polysulfide, benefitting from adjusted electron structure with downshifted d-band center and increased electron fill number of Co in (CuCo)Se2 compared with that of (NiCo)Se2. This endows (CuCo)Se2 moderate adsorption strength for lithium polysulfides and better catalytic properties for their conversion. As a result, the lithium-sulfur batteries with (CuCo)Se2-NCNT achieve a high specific capacity of 1051.06 mAh g-1 at 1C and an enhanced rate property with a specific capacity of 838.27 mAh g-1 at 4C. The work provides meaningful insights into the design of bimetallic compounds as catalysts for lithium-sulfur batteries.

Aluminum causes irreversible damage to the development of hippocampal neurons by regulating m6A RNA methylation.

The underlying mechanism of the aluminum (Al) on neurotoxicity remains unclear. We explored whether the impairment of hippocampal neurons induced by developmental Al exposure was associated with the m6A RNA modification in mice. In this study, the pregnant female mice were administered 4 mg/mL aluminum-lactate from gestational day (GD) 6 to postnatal day (PND) 21. On PND 21, 10 offsprings per group were euthanized by exsanguination from the abdominal aorta after deep anesthetization. The other offsprings which treated with aluminum-lactate on maternal generation were divided into two groups and given 0 (PND60a) and 4 mg/mL (PND60b) aluminum-lactate in their drinking water until PND 60. Significant neuronal injuries of hippocampus as well as a reduction in the m6A RNA modification and the expression of methylase were observed at PND 21 and PND 60a mice. The results indicated that Al-induced developmental neurotoxicity could persist into adulthood despite no sustained Al accumulation. m6A RNA modification had a crucial role in developmental neurotoxicity induced by Al. In addition, Al exposure during the embryonic to adult stages can cause more severe nerve damage and decline of m6A RNA modification. Collectively, these results suggest that the mechanism underlying Al-induced neurotoxicity appears to involve m6A RNA modification.

A novel photoreduction deposition induced AuNPs/COFs composite for SERS detection of macrolide antibiotics.

As we all know, SERS (Surface-enhanced Raman spectroscopy) is widely used in sensing, analysis and detection. The covalent organic frameworks (COFs) have performed well as a material for supporting metal nanoparticles and facilitating analyte adsorption in SERS, which may greatly enhance the detection sensitivity and reproducibility. The synthesis of traditional metal/COFs composites involved chemical reduction methods, however, the resulting metallic NPs exhibited reduced capacity to enhance SERS due to their small particle sizes (usually <20 nm). This paper presented a novel photoreduction method for the facile growth of AuNPs (diameters: 75 nm) on COFs matrix under light control, which represents the first report of such synthesis on COF. Subsequently, the photoreduction deposition induced AuNPs/COFs composites, which served as highly sensitive and reproducible SERS-active substrates for capturing the spectral information of four types of macrolide antibiotics. The detection limits for the four macrolide antibiotics were determined to be 3.30 × 10-11, 3.43 × 10-10, 1.10 × 10-10 and 5.78 × 10-11 M, respectively, exhibiting excellent linear relationships within the concentration range of 10-10 to 10-3 M. Therefore, our proposed SERS method opens up a new idea for the development of SERS substrates and environmental safety monitoring, and it has great potential for ensuring food safety in the future.

Combined toxicity of abamectin and carbendazim on enzymatic and transcriptional levels in the soil-earthworm microcosm.

To reveal the toxicological mechanisms of pesticide mixtures on soil organisms, this study concentrated on evaluating enzymatic activity and gene expression changes in the earthworm Eisenia fetida (Savigny 1826). Despite being frequently exposed to multiple pesticides, including the common combination of abamectin (ABA) and carbendazim (CAR), environmental organisms have primarily been studied for the effects of individual pesticides. Acute toxicity results exhibited that the combination of ABA and CAR caused a synergistic impact on E. fetida. The levels of MDA, ROS, T-SOD, and caspase3 demonstrated a significant increase across most individual and combined groups, indicating the induction of oxidative stress and cell death. Additionally, the expression of three genes (hsp70, gst, and crt) exhibited a significant decrease following exposure to individual pesticides and their combinations, pointing toward cellular damage and impaired detoxification function. In contrast, a noteworthy increase in ann expression was observed after exposure to both individual pesticides and their mixtures, suggesting the stimulation of reproductive capacity in E. fetida. The present findings contributed to a more comprehensive understanding of the potential toxicity mechanisms of the ABA and CAR mixture, specifically on oxidative stress, cell death, detoxification dysfunction, and reproductive capacity in earthworms. Collectively, these data offered valuable toxicological insights into the combined effects of pesticides on soil organisms, enhancing our understanding of the underlying risks associated with the coexistence of different pesticides in natural soil environments.

Patchouli alcohol alleviates metabolic dysfunction-associated steatohepatitis via inhibiting mitochondria-associated endoplasmic reticulum membrane disruption-induced hepatic steatosis and inflammation in rats.

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs.

Interleukin-17A Promotes Airway Remodeling in Chronic Obstructive Pulmonary Disease by Activating C-X-C Motif Chemokine Ligand 12 Secreted by Lung Fibroblasts.

Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and secretion of inflammatory mediators, which promotes epithelial mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling. Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using one-way ANOVA and Tukey's test or Bonferroni's test for post-hoc test. A p-value < 0.05 was considered statistically significant. Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist (AMD3100) could reverse the degree of EMT in lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated (p-)ERK pathways. Conclusion: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

The Effectiveness and Safety of Intrapartum or Postpartum Catheterization in the Prevention of Postpartum Urinary Retention: A Scoping Review.

INTRODUCTION AND HYPOTHESIS: Catheterization is a common treatment for postpartum urinary retention (PUR); however, its application before diagnosis of PUR remains unclear. The aim was to give an overview of the existing literature on the effectiveness and safety of intrapartum or postpartum catheterization in the prevention of PUR. METHODS: This scoping review followed a methodological framework. PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, WanFang, the China Science and Technology Journal Database, and the China Biomedical Literature Database were searched from the inception of each database to 21 May 2023. RESULTS: The search revealed 16 studies examining three different catheterization methodologies, including 12 intrapartum studies. Ten studies concluded that intrapartum or postpartum catheterization prevented PUR, two of which were only for overt or covert PUR. In 4 out of 13 experimental studies, no significant difference was found: one for intrapartum catheterization versus routine nursing, the other for intrapartum or postpartum intermittent versus indwelling catheterization. However, one found that postpartum disposable catheterization after ineffective targeted care reduced the incidence of PUR compared with indwelling catheterization. One out of the 3 case-control studies concluded that prenatal catheterization ≥2 times was a risk factor for PUR. CONCLUSIONS: Based on the findings in this scoping review, catheterization prior to the diagnosis of PUR appears to play a role in preventing PUR and is safe. Preliminary evidence is accumulating on the effectiveness of three types of catheterization methods in preventing PUR, but more comprehensive studies are needed to establish these findings.

A review of botany, phytochemistry, pharmacology, and applications of the herb with the homology of medicine and food: Ligustrum lucidum W.T. Aiton.

Ligustrum lucidum W.T. Aiton is an outstanding herb with the homology of medicine and food. Its ripe fruits are traditionally used as an important tonic for kidneys and liver in China. Ligustrum lucidum W.T. Aiton is rich in nutritional components and a variety of bioactive ingredients. A total of 206 compounds have been isolated and identified, they mainly include flavonoids, phenylpropanoids, iridoid glycosides, and triterpenoids. These compounds exert anti-osteoporosis, anti-tumor, liver protective, antioxidant, anti-inflammatory, and immunomodulatory effects. Ligustrum lucidum W.T. Aiton has been traditionally used to treat many complex diseases, including osteoporotic bone pain, rheumatic bone, cancer, related aging symptoms, and so on. In the 2020 Edition of Chinese Pharmacopoeia, there are more than 100 prescriptions containing L. lucidum W.T. Aiton. Among them, some classical preparations including Er Zhi Wan and Zhenqi fuzheng formula, are used in the treatment of various cancers with good therapeutic effects. Additionally, L. lucidum W.T. Aiton has also many excellent applications for functional food, ornamental plants, bioindicator of air pollution, algicidal agents, and feed additives. Ligustrum lucidum W.T. Aiton has rich plant resources. However, the application potential of it has not been fully exploited. We hope that this paper provides a theoretical basis for the high-value and high-connotation development of L. lucidum W.T. Aiton in the future.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

The interaction between estimated glomerular filtration rate and dietary magnesium intake and its effect on stroke prevalence: a cross-sectional study spanning 2003-2018.

Background: Despite the known associations of dietary magnesium intake and estimated glomerular filtration rate (eGFR) with cardiovascular diseases, their combined effects on stroke risk remain unclear. Therefore, this study aims to explore the associations of dietary magnesium intake and eGFR with stroke risk. Methods: The National Health and Nutrition Examination Survey (NHANES) data of 37,637 adult participants (≥18 years) from 2003 to 2018 was analyzed. Dietary magnesium intake was categorized as low (≤ 254 mg/day) and normal (> 254 mg/day) based on experimental data. Multiple logistic regression analyses and interaction tests were conducted to assess the associations of dietary magnesium intake and eGFR with stroke risk, with a focus on the interaction between different chronic kidney disease (CKD) stages based on eGFR levels and dietary magnesium intake. Additional analyses included multiplicative interaction analysis, restricted cubic spline analysis, and subgroup evaluations by age, sex, and ethnicity. Results: Dietary magnesium intake and eGFR were inversely correlated with the risk of stroke. Participants with low dietary magnesium intake had a higher stroke risk than those with normal magnesium intake (odds ratio [OR] 1.09, 95% confidence interval [CI]: 1.03-1.42). Likewise, low eGFR was associated with an elevated stroke risk compared with normal eGFR (OR 1.56, 95% CI: 1.15-2.13). Furthermore, the two factors showed a multiplicative interaction effect on stroke risk (OR 1.05, 95% CI: 1.01-1.09). We observed a significant interaction between stage G3 CKD and low dietary magnesium intake (OR 1.05, 95% CI: 1.01-1.09), suggesting a potential association with stroke risk. However, similar associations were not observed for stages G4 and G5, possibly due to the smaller number of participants with G4 and G5 CKD. The restricted cubic spline analysis revealed a non-linear relationship between dietary magnesium intake, eGFR, and stroke risk. The interaction between magnesium deficiency and low eGFR persisted in participants aged >60 years, as well as in females, non-Hispanic Black people, and people of other races. Conclusion: Dietary magnesium intake and eGFR correlate negatively with stroke prevalence. Moreover, there was an interaction between dietary magnesium intake and stroke prevalence across different CKD stages. Further large-scale prospective studies are needed to analyze the potential relationship between dietary magnesium intake, eGFR, and stroke.

Aloesin ameliorates hypoxic-ischemic brain damage in neonatal mice by suppressing TLR4-mediated neuroinflammation.

BACKGROUND: At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult. MATERIALS AND METHODS: Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking. RESULTS: ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4. CONCLUSION: ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.

Microplastics in the human body: A comprehensive review of exposure, distribution, migration mechanisms, and toxicity.

Microplastics (MPs) are pervasive across ecosystems, presenting substantial risks to human health. Developing a comprehensive review of MPs is crucial due to the growing evidence of their widespread presence and potential harmful effects. Despite the growth in research, considerable uncertainties persist regarding their transport dynamics, prevalence, toxicological impacts, and the potential long-term health effects they may cause. This review thoroughly evaluates recent advancements in research on MPs and their implications for human health, including estimations of human exposure through ingestion, inhalation, and skin contact. It also quantifies the distribution and accumulation of MPs in various organs and tissues. The review discusses the mechanisms enabling MPs to cross biological barriers and the role of particle size in their translocation. To ensure methodological rigor, this review adheres to the PRISMA guidelines, explicitly detailing the literature search strategy, inclusion criteria, and the quality assessment of selected studies. The review concludes that MPs pose significant toxicological risks, identifies critical gaps in current knowledge, and recommends future research directions to elucidate the prolonged effects of MPs on human health. This work aims to offer a scientific framework for mitigating MP-related hazards and establishes a foundation for ongoing investigation.

Border cells without theta rhythmicity in the medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is a key brain structure for higher cognitive functions such as decision-making and goal-directed behavior, many of which require awareness of spatial variables including one's current position within the surrounding environment. Although previous studies have reported spatially tuned activities in mPFC during memory-related trajectory, the spatial tuning of mPFC network during freely foraging behavior remains elusive. Here, we reveal geometric border or border-proximal representations from the neural activity of mPFC ensembles during naturally exploring behavior, with both allocentric and egocentric boundary responses. Unlike most of classical border cells in the medial entorhinal cortex (MEC) discharging along a single wall, a large majority of border cells in mPFC fire particularly along four walls. mPFC border cells generate new firing fields to external insert, and remain stable under darkness, across distinct shapes, and in novel environments. In contrast to hippocampal theta entrainment during spatial working memory tasks, mPFC border cells rarely exhibited theta rhythmicity during spontaneous locomotion behavior. These findings reveal spatially modulated activity in mPFC, supporting local computation for cognitive functions involving spatial context and contributing to a broad spatial tuning property of cortical circuits.

An Adaptive Sampling Algorithm with Dynamic Iterative Probability Adjustment Incorporating Positional Information.

Physics-informed neural networks (PINNs) have garnered widespread use for solving a variety of complex partial differential equations (PDEs). Nevertheless, when addressing certain specific problem types, traditional sampling algorithms still reveal deficiencies in efficiency and precision. In response, this paper builds upon the progress of adaptive sampling techniques, addressing the inadequacy of existing algorithms to fully leverage the spatial location information of sample points, and introduces an innovative adaptive sampling method. This approach incorporates the Dual Inverse Distance Weighting (DIDW) algorithm, embedding the spatial characteristics of sampling points within the probability sampling process. Furthermore, it introduces reward factors derived from reinforcement learning principles to dynamically refine the probability sampling formula. This strategy more effectively captures the essential characteristics of PDEs with each iteration. We utilize sparsely connected networks and have adjusted the sampling process, which has proven to effectively reduce the training time. In numerical experiments on fluid mechanics problems, such as the two-dimensional Burgers' equation with sharp solutions, pipe flow, flow around a circular cylinder, lid-driven cavity flow, and Kovasznay flow, our proposed adaptive sampling algorithm markedly enhances accuracy over conventional PINN methods, validating the algorithm's efficacy.

Disulfidptosis-related lncRNAs signature predicting prognosis and immunotherapy effect in lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma (LUAD) is a prevalent malignant tumor worldwide, with high incidence and mortality rates. However, there is still a lack of specific and sensitive biomarkers for its early diagnosis and targeted treatment. Disulfidptosis is a newly identified mode of cell death that is characteristic of disulfide stress. Therefore, exploring the correlation between disulfidptosis-related long non-coding RNAs (DRGs-lncRNAs) and patient prognosis can provide new molecular targets for LUAD patients. METHODS: The study analysed the transcriptome data and clinical data of LUAD patients in The Cancer Genome Atlas (TCGA) database, gene co-expression, and univariate Cox regression methods were used to screen for DRGs-lncRNAs related to prognosis. The risk score model of lncRNA was established by univariate and multivariate Cox regression models. TIMER, CIBERSORT, CIBERSORT-ABS, and other methods were used to analyze immune infiltration and further evaluate immune function analysis, immune checkpoints, and drug sensitivity. Real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of DRGs-lncRNAs in LUAD cell lines. RESULTS: A total of 108 lncRNAs significantly associated with disulfidptosis were identified. A prognostic model was constructed by screening 10 lncRNAs with independent prognostic significance through single-factor Cox regression analysis, LASSO regression analysis, and multiple-factor Cox regression analysis. Survival analysis of patients through the prognostic model showed that there were obvious survival differences between the high- and low-risk groups. The risk score of the prognostic model can be used as an independent prognostic factor independent of other clinical traits, and the risk score increases with stage. Further analysis showed that the prognostic model was also different from tumor immune cell infiltration, immune function, and immune checkpoint genes in the high- and low-risk groups. Chemotherapy drug susceptibility analysis showed that high-risk patients were more sensitive to Paclitaxel, 5-Fluorouracil, Gefitinib, Docetaxel, Cytarabine, and Cisplatin. Additionally, RT-PCR analysis demonstrated differential expression of DRGs-lncRNAs between LUAD cell lines and the human bronchial epithelial cell line. CONCLUSIONS: The prognostic model of DRGs-lncRNAs constructed in this study has certain accuracy and reliability in predicting the survival prognosis of LUAD patients, and provides clues for the interaction between disulfidptosis and LUAD immunotherapy.

IL-17A-induced cancer-associated fibroblasts releases CXCL12 to promote lung adenocarcinoma progression via Wnt/ß-Catenin signaling pathway.

BACKGROUND: Cancer-associated fibroblasts (CAFs) and their secretion, C-X-C motif chemokine ligand 12 (CXCL12), play an important role in the development of lung adenocarcinoma (LUAD). Interleukin 17A (IL-17A) is also crucial in regulating tumor progression. Herein, we explored the specific relationships between these two factors and their mechanisms in the progression of LUAD. METHODS: Immunohistochemistry was utilized to assess the differential expression levels of IL-17A and CXCL12 in tumor versus normal tissues of LUAD patients, followed by gene correlation analysis. Cell counting kit-8 (CCK8), wound-healing and transwell assays were performed to investigate the effect of IL-17A on the function of LUAD cells. qPCR, immunofluorescence, immunohistochemistry and western blot analyses were conducted to elucidate the potential mechanism by which IL-17A facilitates the development of LUAD via CXCL12. Male BALB-C nude mice were used to explore the role of IL-17A in subcutaneous LUAD mouse models. RESULTS: Elevated expression levels of IL-17A and CXCL12 were observed in LUAD tissues, exhibiting a positive correlation. Further studies revealed that IL-17A could stimulate CAFs to enhance the release of CXCL12, thereby facilitating the growth, proliferation, and metastasis of LUAD. The binding of CXCL12 to its specific receptor influences the activation of the Wnt/ß-Catenin pathway, which in turn affects the progression of LUAD. In vivo experiments have demonstrated that IL-17A enhances the growth of LUAD tumors by facilitating the secretion of CXCL12. Conversely, inhibiting CXCL12 has been demonstrated to impede tumor growth. CONCLUSIONS: We discovered that IL-17A promotes the release of CAFs-derived CXCL12, which in turn facilitates the development of LUAD via the Wnt/ß-Catenin signaling pathway.

Erjingpill bionic cerebrospinal fluid alleviates LPS-induced inflammatory response in BV2 cells by inhibiting glycolysis via mTOR.

ETHNOPHARMACOLOGICAL RELEVANCE: Erjingpill, a well-known prescription documented in the classic Chinese medical text "Shengji Zonglu," has been proven to have effective alleviating effects on neuroinflammation in Alzheimer's disease (AD). Although the alterations in microglial cell glycolysis are known to play a crucial role in the development of neuroinflammation, it remains unclear whether the anti-neuroinflammatory effects of Erjingpill are associated with its impact on microglial cell glycolysis. AIM OF THE STUDY: This study aims to determine whether Erjingpill exerts anti-neuroinflammatory effects by influencing microglial cell glycolysis. MATERIALS AND METHODS: Firstly, Erjingpill decoction was prepared into an Erjingpill bionic cerebrospinal fluid (EBCF) through a process of in vitro intestinal absorption, hepatocyte incubation, and blood-brain barrier (BBB) transcytosis. Subsequently, UPLC/Q-TOF-MS/MS technology was used to analyze the compounds in Erjingpill and EBCF. Next, an in vitro neuroinflammation model was established by LPS-induced BV2 cells. The impact of EBCF on BV2 cell proliferation activity was evaluated using the CCK-8 assay, while the NO release was assessed using the Griess assay. Additionally, mRNA levels of pro-inflammatory factors (IL-1ß, IL-6, TNF-α, and COX-2), anti-inflammatory factors (IL-10, IL-4, Arg-1, and TGF-ß), M1 microglial markers (iNOS, CD86), M2 microglial markers (CD36, CD206), and glycolytic enzymes (HK2, GLUT1, PKM, and LDHA) were measured using qPCR. Furthermore, protein expression of microglial activation marker Iba-1, M1 marker iNOS, and M2 marker CD206 were identified through immunofluorescence, while concentrations of pro-inflammatory cytokines IL-1ß and TNF-α were measured using ELISA. Enzymatic activity of glycolytic enzymes (HK, PK, and LDH) was assessed using assay kits, and the protein levels of pro-inflammatory factors (IL-1ß, iNOS, and COX-2), anti-inflammatory factors (IL-10 and Arg-1), and key glycolytic proteins GLUT1 and PI3K/AKT/mTOR were detected by Western blot. RESULTS: Through the analysis of Erjingpill and EBCF, 144 compounds were identified in Erjingpill and 40 compounds were identified in EBCF. The results demonstrated that EBCF effectively inhibited the elevation of inflammatory factors and glycolysis levels in LPS-induced BV2 cells, promoted polarization of M1 microglial cells towards the M2 phenotype, and suppressed the PI3K/AKT/mTOR inflammatory pathway. Moreover, EBCF alleviated LPS-induced BV2 cell inflammatory response by modulating mTOR to inhibit glycolysis. CONCLUSIONS: EBCF exhibits significant anti-neuroinflammatory effects, likely attributed to its modulation of mTOR to inhibit microglial cell glycolysis. This study furnishes experimental evidence supporting the clinical utilization of Erjingpill for preventing and treating AD.