[Research progress on ferroptosis in tumor immunity].

Ferroptosis is a novel form of cell death that is induced by excessive accumulation of ferrous ions and lipid peroxides. It triggers the release of damage-associated molecular patterns through autophagy-dependent mechanisms, serving as an adjunct to immunogenic cell death and activating both adaptive and innate immunity. In the tumor microenvironment, the regulation and influence of tumor cells and immune cells undergoing ferroptosis are regulated by various factors, which plays a crucial role in tumor development, treatment, and prognosis. This article provides an overview of the biological effects of ferroptosis on immune cells such as T cells, macrophages, neutrophils and B cells and tumor cells in the tumor microenvironment.

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle's branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 'Kraken' RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection.

The status and influencing factors of fatigue in kidney transplant recipients based on the theory of unpleasant symptoms: A cross-sectional study in China.

AIMS: This study describes the incidence of fatigue in kidney transplant recipients and analyses the relationship between physiological factors, psychological factors, situational factors and fatigue in kidney transplant recipients. BACKGROUND: Fatigue, as a common symptom after kidney transplantation, is affected by many factors, but the influence of some factors on the fatigue of kidney transplant recipients is still controversial. DESIGN: This cross-sectional study was designed based on the theory of unpleasant symptoms. METHODS: Our survey involved 307 participants attending the kidney transplant outpatient clinic of a tertiary Class A hospital (Changsha, Hunan, China). Data were collected between February and April 2021 using a structured questionnaire and electronic medical records. Data were analysed using IBM SPSS 25.0 (SPSS Inc.) RESULTS: It was found that the incidence of fatigue in kidney transplant recipients was 53.1%. According to the binary logistic regression analysis, sleep quality, hypokalemia, anxiety, depression and education level were independent risk factors for fatigue in kidney transplant recipients. CONCLUSION: The incidence of fatigue in kidney transplant recipients was high and was influenced by physical, psychological and situational factors. Clinical nurses should assess fatigue levels in a timely and multidimensional manner in clinical practice and provide effective and scientific guidance about fatigue self-coping and symptom management for kidney transplant recipients.

Deep Learning-Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aß, this study uses deep learning and a pharmacological approach to elucidate the potential of pyrroloquinoline quinone (PQQ) as a neuroprotective agent for AD. Using deep learning for a comprehensive molecular dataset, blood-brain barrier (BBB) permeability is predicted and the anti-inflammatory and antioxidative properties of compounds are evaluated. PQQ, identified in the Mediterranean-DASH intervention for a diet that delays neurodegeneration, shows notable BBB permeability and low toxicity. In vivo tests conducted on an Aß1₋42-induced AD mouse model verify the effectiveness of PQQ in reducing cognitive deficits. PQQ modulates genes vital for synapse and anti-neuronal death, reduces reactive oxygen species production, and influences the SIRT1 and CREB pathways, suggesting key molecular mechanisms underlying its neuroprotective effects. This study can serve as a basis for future studies on integrating deep learning with pharmacological research and drug discovery.

Hirudin in the Treatment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a common public health concern. The global burden of CKD is increasing due to the high morbidity and mortality associated with it, indicating the shortcomings of therapeutic drugs at present. Renal fibrosis is the common pathology of CKD, which is characterized by glomerulosclerosis, renal tubular atrophy, and renal interstitial fibrosis. Natural hirudin is an active ingredient extracted from Hirudo medicinalis, which has been found to be the strongest natural specific inhibitor of thrombin. Evidence based on pharmacological data has shown that hirudin has important protective effects in CKD against diabetic nephrology, nephrotic syndrome, and renal interstitial fibrosis. The mechanisms of hirudin in treating CKD are mainly related to inhibiting the inflammatory response, preventing apoptosis of intrinsic renal cells, and inhibiting the interactions between thrombin and protease-activated receptors. In this review, we summarize the function and beneficial properties of hirudin for the treatment of CKD, and its underlying mechanisms.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV. Methods: Using data from the 2016-2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype. Results: We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively). Conclusion: AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications.

Intradialytic Hypotension and Mortality in Adolescents and Young Adults With Kidney Failure Receiving Maintenance Hemodialysis.

Rationale & Objective: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults. Study Design: This was a retrospective observational cohort study. Setting & Participants: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included. Exposures: This study used different definitions of IDH. Outcome: The study outcome was 2-year all-cause mortality. Analytical Approach: Several definitions of IDH were selected a priori based on a literature review. Patients were classified as having IDH if it was present in at least 30% of HD treatments during the first 90 days after dialysis initiation. Cox proportional hazards regression was used to test whether IDH associated with 2-year all-cause mortality. Results: Over a 2-year follow-up period, 54 (4.5%) patients died. Dependent on its definition, IDH was present in 2.9%-61.1% of patients. After the multivariable adjustment for sociodemographic and clinical characteristics, we found no association of IDH with mortality. Results were consistent across subgroups stratified by age (aged <18 and 19-21 years) and predialysis systolic blood pressure (<120, 120-150, and >150 mm Hg). We also examined IDH as occurring in <5%, 5%-29%, 30%-50%, and >50% of baseline treatments, and did not find a dose-response association with mortality (P > 0.05). Limitations: Owing to low event rates, our current sample size may have been too small to detect a difference in mortality. Conclusions: Our study found that IDH was not associated with mortality in adolescents and young adults.

Intradialytic hypotension (IDH), or hypotension experienced during dialysis, is common among children and young adults with kidney failure requiring hemodialysis. We examined the association of commonly used definitions of IDH with death in adolescents and young adults with kidney failure receiving hemodialysis. Intradialytic hypotension was present in 2.9%-61.1% of patients, depending on the definition, and over a 2-year follow-up period, 4.5% of the patients died. We found no association of IDH with mortality.

Selection and Validation of Reference Genes for Gene Expression in Bactericera gobica Loginova under Different Insecticide Stresses.

Insecticide resistance has long been a problem in crop pest control. Bactericera gobica is a major pest on the well-known medicinal plants Lycium barbarum L. Investigating insecticide resistance mechanisms of B. gobica will help to identify pesticide reduction strategies to control the pest. Gene expression normalization by RT-qPCR requires the selection and validation of appropriate reference genes (RGs). Here, 15 candidate RGs were selected from transcriptome data of B. gobica. Their expression stability was evaluated with five algorithms (Delta Ct, GeNorm, Normfinder, BestKeeper and RefFinder) for sample types differing in response to five insecticide stresses and in four other experimental conditions. Our results indicated that the RGs RPL10 + RPS15 for Imidacloprid and Abamectin; RPL10 + AK for Thiamethoxam; RPL32 + RPL10 for λ-cyhalothrin; RPL10 + RPL8 for Matrine; and EF2 + RPL32 under different insecticide stresses were the most suitable RGs for RT-qPCR normalization. EF1α + RPL8, EF1α + ß-actin, ß-actin + EF2 and ß-actin + RPS15 were the optimal combination of RGs under odor stimulation, temperature, developmental stages and both sexes, respectively. Overall, EF2 and RPL8 were the two most stable RGs in all conditions, while α-TUB and RPL32 were the least stable RGs. The corresponding suitable RGs and one unstable RG were used to normalize a target cytochrome P450 CYP6a1 gene between adult and nymph stages and under imidacloprid stress. The results of CYP6a1 expression were consistent with transcriptome data. This study is the first research on the most stable RG selection in B. gobica nymphs exposed to different insecticides, which will contribute to further research on insecticide resistance mechanisms in B. gobica.

Characterization of CD8+ T cells in immune-privileged organs of ZIKV-infected Ifnar1-/- mice.

Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E294-302-specific T cells can account for 20-60% of the total CD8+ T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E294-302-specific TCRαßs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αß paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8+ T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs.IMPORTANCEThe immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8+ T cells. Our data show that CD8+ T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/ß clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/ß clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5, was found to be selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8+ T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8+ T cells after ZIKV infection in different IPOs.

Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models.

Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the C. elegans system in the realm of ALS research and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.

Mask-inspired moisture-transmitting and durable thermochromic perovskite smart windows.

Thermochromic perovskite smart windows (TPWs) are a cutting-edge energy-efficient window technology. However, like most perovskite-based devices, humidity-related degradation limits their widespread application. Herein, inspired by the structure of medical masks, a unique triple-layer thermochromic perovskite window (MTPW) that enable sufficient water vapor transmission to trigger the thermochromism but effectively repel detrimental water and moisture to extend its lifespan is developed. The MTPW demonstrates superhydrophobicity and maintains a solar modulation ability above 20% during a 45-day aging test, with a decay rate 37 times lower than that of a pristine TPW. It can also immobilize lead ions and significantly reduce lead leakage by 66 times. Furthermore, a significant haze reduction from 90% to 30% is achieved, overcoming the blurriness problem of TPWs. Benefiting from the improved optical performance, extended lifespan, suppressed lead leakage, and facile fabrication, the MTPW pushes forward the wide applications of smart windows in green buildings.

Dialysis Modality, Transplant Characteristics, and Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using USRDS Data.

Rationale & Objective: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied. Study Design: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation. Setting & Participants: The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it. Exposure: Dialysis modality used before transplant. Outcome: Time to incidence of atrial fibrillation up to 3 years posttransplant. Analytical Approach: Multivariable Cox regression was used to estimate HRs. Results: Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%). Limitations: Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular. Conclusions: Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant. Plain-Language Summary: New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes.

Predicting transfer to haemodialysis using the peritoneal dialysis surprise question.

BACKGROUND: People on peritoneal dialysis (PD) at risk of transfer to haemodialysis (HD) need support to remain on PD or ensure a safe transition to HD. Simple point-of-care risk stratification tools are needed to direct limited dialysis centre resources. In this study, we evaluated the utility of collecting clinicians' identification of patients at high risk of transfer to HD using a single point of care question. METHODS: In this prospective observational study, we included 1275 patients undergoing PD in 35 home dialysis programmes. We modified the palliative care 'surprise question' (SQ) by asking the registered nurse and treating nephrologist: 'Would you be surprised if this patient transferred to HD in the next six months?' A 'yes' or 'no' answer indicated low and high risk, respectively. We subsequently followed patient outcomes for 6 months. Cox regression model estimated the hazard ratio (HR) of transfer to HD. RESULTS: Patients' mean age was 59 ± 16 years, 41% were female and the median PD vintage was 20 months (interquartile range: 9-40). Responses were received from nurses for 1123 patients, indicating 169 (15%) as high risk and 954 (85%) as low risk. Over the next 6 months, transfer to HD occurred in 18 (11%) versus 29 (3%) of the high and low-risk groups, respectively (HR: 3.92, 95% confidence interval (CI): 2.17-7.05). Nephrologist responses were obtained for 692 patients, with 118 (17%) and 574 (83%) identified as high and low risk, respectively. Transfer to HD was observed in 14 (12%) of the high-risk group and 14 (2%) of the low-risk group (HR: 5.56, 95% CI: 2.65-11.67). Patients in the high-risk group experienced higher rates of death and hospitalisation than low-risk patients, with peritonitis events being similar between the two groups. CONCLUSIONS: The PDSQ is a simple point of care tool that can help identify patients at high risk of transfer to HD and other poor clinical outcomes.

A novel fixed-time error-monitoring neural network for solving dynamic quaternion-valued Sylvester equations.

This paper addresses the dynamic quaternion-valued Sylvester equation (DQSE) using the quaternion real representation and the neural network method. To transform the Sylvester equation in the quaternion field into an equivalent equation in the real field, three different real representation modes for the quaternion are adopted by considering the non-commutativity of quaternion multiplication. Based on the equivalent Sylvester equation in the real field, a novel recurrent neural network model with an integral design formula is proposed to solve the DQSE. The proposed model, referred to as the fixed-time error-monitoring neural network (FTEMNN), achieves fixed-time convergence through the action of a state-of-the-art nonlinear activation function. The fixed-time convergence of the FTEMNN model is theoretically analyzed. Two examples are presented to verify the performance of the FTEMNN model with a specific focus on fixed-time convergence. Furthermore, the chattering phenomenon of the FTEMNN model is discussed, and a saturation function scheme is designed. Finally, the practical value of the FTEMNN model is demonstrated through its application to image fusion denoising.

Influence of landform, soil properties, soil Cd pollution and rainfall on the spatial variation of Cd in rice: Contribution and pathway models based on big data.

Landform, soil properties, soil cadmium (Cd) pollution and rainfall are the important factors affecting the spatial variation of rice Cd. In this study, we conducted big data mining and model analysis of 150,000 rice-soil sampling sites to examine the effects by the above four factors on the spatial variation of rice Cd in Hunan Province, China. Specifically, the variable coefficient of rice Cd in space was significantly correlated with the partition scale according to the logistic fitting. The improved random forest results suggested that elevation (DEM) and pH were the two most important factors affecting the spatial variation of rice Cd, followed by relief, soil Cd content and rainfall. Typically, variance partitioning analysis (VPA) revealed that both the soil property and the interactive effects between the soil property and Cd pollution were the principal contributors to the rice-Cd variation, with the respective contributing rates of 30.5 % and 29.0 %. Meanwhile, the partial least square-structural equation modelling (PLS-SEM) elucidated 4 main paths of specific indirect effects on rice-Cd variation. They were landform → physicochemical property → soil acidity → rice-Cd variation, landform → soil acidity → rice-Cd variation, physicochemical property → soil acidity → rice-Cd variation, and soil texture → soil acidity → rice-Cd variation. This work can provide a general guidance for scientific zoning, accurate prediction and prevention of Cd pollution in paddy fields.

Relevance of NAT2 genotype and clinical factors to risk for antituberculosis drug-induced liver injury.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

Quantitative health risk assessment of microbial hazards from water sources for community and self-supply drinking water systems.

In low and medium income countries (LMIC) drinking water sources (wells and boreholes) often contain a high number of pathogenic microorganisms, that can pose significant human and environmental health risks. In this study, a quantitative microbial risk assessment approach based on existing literature was conducted to evaluate and compare the quantitative health risks associated with different age groups using various drinking water supply systems. Results showed that both community-supply and self-supply modes exhibit similar levels of risk. However, the self-supply water source consistently showed higher risks compared to the community-supply one. Borehole water was found to be a more suitable option than well water, consistently showing between 5 and 8 lower health risks for E. coli and fecal coliform levels, respectively. The sensitivity analysis further showed the importance of prioritizing the reduction of E. coli concentration in well water and fecal coliform concentration in borehole water. This study offers a fresh perception on quantifying the impact of exposure concentration and age groups, shedding light on how they affect environmental health risks. These findings provide valuable insights for stakeholders involved in the management and protection of water sources.

Phase I dose-escalation study of nab-paclitaxel combined with cisplatin and capecitabin as induction chemotherapy followed by concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Nab-paclitaxel is a promising albumin-bound paclitaxel with a therapeutic index superior to that of docetaxel, but the optimal dose of nab-paclitaxel combined with cisplatin and capecitabine as induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma remains unknown. MATERIALS AND METHODS: This was an open-label, single-arm study investigating the safety and efficacy of nab-paclitaxel + cisplatin + capecitabin as IC for three cycles, followed by cisplatin CCRT, conducted by using the standard "3 + 3" design in LA-NPC. If more than one-third of the patients in a cohort experienced dose-limiting toxicity (DLT), the dose used in the previous cohort was designated the maximum tolerated dose (MTD). The recommended phase 2 dose (RP2D) was defined as one level below the MTD. RESULTS: From 29 May 2021 to 17 March 2022, 19 patients with LA-NPC were enrolled, one patient withdrew informed consent. Two DLTs occurred in cohort 4 (grade 4 febrile neutropenia and grade 3 peripheral neuropathy), and an MTD was established as 225 mg/m2. The most frequent grade 3 or 4 adverse events were neutropenia (16.7 %), hypertriglyceridemia (16.7 %), leukopenia (5.6 %) and peripheral neuropathy (5.6 %) during IC. CONCLUSION: The RP2D is nab-paclitaxel 200 mg/m2 on day 1, combined with cisplatin 75 mg/mg2 on day 1 and capecitabin1000 mg/m2 on days 1-14, twice a day, every 3 weeks, for three cycles as an IC regimen prior to CCRT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850235.

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.

Alzheimer's disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aß proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD's pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aß1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aß-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aß toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.