Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer's Disease by Regulating the Akt/mTOR Signaling Pathway.

Alzheimer's disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of ß-amyloid (Aß). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1ß, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aß aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.

Fabrication and characterization of oxidized starch-xanthan gum composite nanoparticles with efficient emulsifying properties.

This study involved the preparation of nanoparticles by combining oxidized starch (OS) with xanthan gum (XG), and emulsions were prepared from this nanoparticle. The physical and chemical characteristics, as well as the emulsification properties of oxidized starch-xanthan gum composite nanoparticles (OGNP), were analyzed. The findings revealed that the OGNP retained spherical shape after the addition of XG, although their diameter increased from approximately 50-150 to 200-400 nm. Zeta potential decreased with XG content. Moreover, emulsions prepared from OGNP exhibited outstanding thermal stability, also showing enhanced storage stability. In addition, emulsions had different rheological properties at different pH values. The apparent viscosity and shear stress of emulsions under alkaline conditions were lower than that of neutral conditions. NaCl increased the apparent viscosity of OGNP-stabilized emulsions while reducing their thermal stability. The nanoparticles prepared in this study have efficient emulsification properties and can extend the application of OS.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Imaging ultra-weak UV light below 100 pW cm-2 using a 4H-SiC photodetector with an Al2O3 interfacial layer.

Weak light detection is crucial in various practical applications such as night vision systems, flame monitoring, and underwater operations. Decreasing the dark current of a photodetector can effectively mitigate noises, consequently enhancing the signal-to-noise ratio and overall weak light detection performance. Herein, we demonstrate a 4H-SiC UV photodetector capable of detecting extremely weak UV light. This device comprises a photosensitive layer of 4H-SiC, two TiN electrodes and an atomically thin Al2O3 interfacial layer between TiN and the C surface of 4H-SiC. Under 360 nm UV light illumination, the proposed Al2O3 device demonstrates an ultra-low dark current of 18 fA, possibly benefiting from the effective passivation of interfacial carriers, and a boosted photo-to-dark current ratio of 6.7 × 107. Consequently, it achieves a weak-light detection limit as low as 31.8 pW cm-2, significantly outperforming the control device lacking Al2O3. When compared to previously reported SiC photodetectors, our Al2O3 device boasts an exceptional large linear dynamic range of 172 dB. Leveraging this, we construct a photodetector array capable of clearly imaging an object under ultra-weak light illumination below the 100 pW cm-2 level. The proposed photodetector represents a significant advancement in the development of highly sensitive image sensors for weak light detection.

CXCL10 and IL15 co-expressing chimeric antigen receptor T cells enhance anti-tumor effects in gastric cancer by increasing cytotoxic effector cell accumulation and survival.

Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.

Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Magnetic levitation system control based on a novel tracking differentiator.

This study proposes a novel tracking differentiator and applies it to the sliding-mode control (SMC) algorithm to address the unsatisfactory disturbance suppression and low tracking accuracy of magnetic levitation (maglev) systems. First, to assess performance in terms of filtering, tracking, and differentiation, an inverse hyperbolic sine function and a two-phase power function are introduced to improve the tracking differentiator. This can accelerate the global convergence speed, ensure smooth convergence at the equilibrium point, reduce system jitter, and enhance the noise-suppression ability of the system. The differentiator parameter-adjustment rules are derived from a system sweep. A comparison of the simulation results show that the proposed differentiator effectively suppresses noise and performs signal tracking and differentiation. Finally, the new differentiator is applied to the SMC of a maglev system. Simulation and experimental results show that the response speed of the maglev system under the SMC based on the new tracking differentiator is high, the jitter is effectively reduced, and the noise-suppression ability is improved.

Challenges and Opportunities Associated with Lifting the Zero COVID-19 Policy in China.

Chinese government lifted its "Zero COVID-19" policy in December 2022. The estimated COVDI-19 new cases and deaths after the policy change are 167-279 million (about 12.0% to 20.1% of the Chinese population) and 0.68-2.1 million, respectively. Recent data also revealed continuous drops in fertility rate and historically lowest growth in gross domestic production in China. Thus, balancing COVID-19 control and economic recovery in China is of paramount importance yet very difficult. Supply chain disruption, essential service reduction and shortage of intensive care units have been discussed as the challenges associated with lifting "Zero COVID-19" policy. The additional challenges may include triple epidemic of COVID-19, respiratory syncytial virus and influenza, mental health issues of healthcare providers, care givers and patients, impact on human mobility, lack of robust genomic and epidemiological data and long COVID-19. However, the policy-associated opportunities and other challenges are largely untouched, but warrant attention of and prompt reactions by the policy makers, healthcare providers, public health officials and other stakeholders. The associated benefits are quick reach of herd immunity, boost of economy and businesses activities and increase in social activities. At this moment, we must embrace the policy change, effectively mitigate its associated problems and timely and effectively maximize its associated benefits.

Emission factors and source profiles of volatile organic compounds from the automobile manufacturing industry.

Controlling volatile organic compounds (VOCs) emitted from the automobile manufacturing industry requires establishing VOCs emission factors (EFs) and source profiles refinedly. In this study, 41 samples involved 32 VOCs discharge links were collected from three factories. The EFs and VOCs source profiles were estimated by the material balance method and weighted average method, respectively. The ozone formation potential (OFP) of the 110 VOCs species were calculated by the maximum incremental reactivity (MIR). According to estimations, the ranges of EFs were 0.23-1.66 kg VOCs/SUV car and 2.14-14.86 g VOCs/m2 painted area. EFs of six materials were firstly estimated, which are electrophoretic primer (152.31 ± 97.39 g VOCs/SUV car, 0.97 ± 0.38 g VOCs/m2 painted area), sealant (48.39 ± 26.20 g VOCs/SUV car, 0.46 ± 0.25 g VOCs/m2 painted area), floating coat (87.40 ± 75.63 g VOCs/SUV car, 0.86 ± 0.74 g VOCs/m2 painted area), colored paint (127.24 ± 168.24 g VOCs/SUV car, 1.25 ± 1.66 g VOCs/m2 painted area), varnish (205.46 ± 218.14 g VOCs/SUV car, 2.01 ± 2.15 g VOCs/m2 painted area), and cleaning solvent (328.54 ± 404.94 g VOCs/SUV car, 3.23 ± 3.98 g VOCs/m2 painted area). OVOCs (37.40-51.60 %) and aromatics (36.40-37.00 %) were the dominant components. n-Butyl acetate, 1,2,4-trimethylbenzene, undecane, n-hexanal, acetone, 1,2,3-trimethylbenzene, 1,3,5 -trimethylbenzene, m/p/o-xylene, 3-ethylbenzene, and 4-ethylbenzene were the major VOCs species, accounting for 68 % of total VOCs in the automobile manufacturing industry. Considering the OFP values of species, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, 1,2,3-trimethylbenzene, m/p-xylene, acetaldehyde, methyl ethyl ketone are the key active species that should be prioritized for control.

Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. METHODS: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). RESULTS: Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred. CONCLUSION: IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management.

Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet).

Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA.

Sleep and circadian biomarkers of postoperative delirium (SLEEP-POD): protocol for a prospective and observational cohort study.

INTRODUCTION: Surgical patients over 70 experience postoperative delirium (POD) complications in up to 50% of procedures. Sleep/circadian disruption has emerged as a potential risk factor for POD in epidemiological studies. This protocol presents a single-site, prospective observational study designed to examine the relationship between sleep/circadian regulation and POD and how this association could be moderated or mediated by Alzheimer's disease (AD) pathology and genetic risk for AD. METHODS AND ANALYSIS: Study staff members will screen for eligible patients (age ≥70) seeking joint replacement or spinal surgery at Massachusetts General Hospital (MGH). At the inclusion visit, patients will be asked a series of questionnaires related to sleep and cognition, conduct a four-lead ECG recording and be fitted for an actigraphy watch to wear for 7 days before surgery. Blood samples will be collected preoperatively and postoperatively and will be used to gather information about AD variant genes (APOE-ε4) and AD-related pathology (total and phosphorylated tau). Confusion Assessment Method-Scale and Montreal Cognitive Assessment will be completed twice daily for 3 days after surgery. Seven-day actigraphy assessments and Patient-Reported Outcomes Measurement Information System questionnaires will be performed 1, 3 and 12 months after surgery. Relevant patient clinical data will be monitored and recorded throughout the study. ETHICS AND DISSEMINATION: This study is approved by the IRB at MGH, Boston, and it is registered with the US National Institutes of Health on ClinicalTrials.gov (NCT06052397). Plans for dissemination include conference presentations at a variety of scientific institutions. Results from this study are intended to be published in peer-reviewed journals. Relevant updates will be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT06052397.

Associations Between Depression Symptom Burden and Delirium Risk: A Prospective Cohort Study.

Background and Objectives: Delirium and depression are prevalent in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer's disease, functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older hospitalized individuals. Research Design and Methods: A total of 319 141 UK Biobank participants between 2006 and 2010 (mean age 58 years [range 37-74, SD = 8], 54% women) reported frequency (0-3) of 4 depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks prior to initial assessment visit and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12 years of median follow-up. 40 451 (mean age 57 ±â€…8; range 40-74 years) had repeat assessment on average 8 years after their first visit. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium. Results: A total of 5 753 (15 per 1 000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR = 1.16, [95% confidence interval (CI): 1.08-1.25], p < .001), modest (scores 3-5, 1.30 [CI: 1.19-1.43], p < .001), and severe (scores ≥ 5, 1.38 [CI: 1.24-1.55], p < .001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across settings (eg, surgical, medical, or critical care) and specialty (eg, neuropsychiatric, cardiorespiratory, or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03-1.88], p = .03) independent of baseline depression burden. The association was strongest in those over 65 years at baseline (p for interaction <.001). Discussion and Implications: Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may aid delirium prevention.

The modulation effects of the mind-body and physical exercises on the basolateral amygdala-temporal pole pathway on individuals with knee osteoarthritis / Los efectos de modulación de la mente-cuerpo y los ejercicios físicos en la vía del polo basolateral amígdala-temporal en personas con osteoartritis de rodilla

Background/Objective: To investigate the modulatory effects of different physical exercise modalities on connectivity of amygdala subregions and its association with pain symptoms in patients with knee osteoarthritis (KOA). Methods: 140 patients with KOA were randomly allocated either to the Tai Chi, Baduanjin, Stationary cycling, or health education group and conducted a 12 week-long intervention in one of the four groups. The behavioral, magnetic resonance imaging (MRI), and blood data were collected at baseline and the end of the study. Results: Compared to the control group, all physical exercise modalities lead to significant increases in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (pain relief) and serum Programmed Death-1 (PD-1) levels. Additionally, all physical exercise modalities resulted in decreased resting state functional connectivity (rsFC) of the basolateral amygdala (BA)-temporal pole and BA-medial prefrontal cortex (mPFC). The overlapping BA-temporal pole rsFC observed in both Tai Chi and Baduanjin groups was significantly associated with pain relief, while the BA-mPFC rsFC was significantly associated with PD-1 levels. In addition, we found increased fractional anisotropy (FA) values, a measurement of water diffusion anisotropy of tissue that responded to changes in brain microstructure, within the mind-body exercise groups' BA-temporal pole pathway. The average FA value of this pathway was positively correlated with KOOS pain score at baseline across all subjects. Conclusions: Our findings suggest that physical exercise has the potential to modulate both functional and anatomical connectivity of the amygdala subregions, indicating a possible shared pathway for various physical exercise modalities.(AU)

Short-term effectiveness and potential factors of ustekinumab based on real-world data in Chinese psoriasis patients.

BACKGROUND: As one of the most effective biologic treatments for psoriasis, the short-term effectiveness of ustekinumab has yet to be studied extensively. OBJECTIVE: The purpose of this study was to evaluate the short-term effectiveness and potential factors within four weeks after the first-dose ustekinumab treatment based on real-world data. METHODS: The study enrolled 98 patients with moderate-to-severe psoriasis, given ustekinumab 45 mg at week 0, week 4, and then every 12 weeks. Based on clinical data collected at baseline and week 4, we investigated the short-term effectiveness of ustekinumab after the first dose and potential factors associated with the treatment. For evaluation, we collected demographic information, body data, medical history, laboratory examination results, Psoriasis Area and Severity Index (PASI), body surface area (BSA), and dermatology life quality index (DLQI). Response rates were calculated based on the number of patients that achieved a 75/90/100% reduction in PASI (PASI 75/90/100), and the primary treatment goal was to achieve PASI 75. RESULTS: The response rates for PASI 75/90/100 at week 4 were 30.5%, 18.9%, and 16.8%, respectively. For PASI 75, the response rate was higher in patients without metabolic syndrome (MS) (without MS vs. with MS: 36.9% vs. 5.9%, p = 0.013); the serum triglyceride (TG) level was significantly lower in patients achieving PASI 75 (expressed as mean ± standard deviation, achieved vs. unachieved: 1.82 ± 1.79 vs. 3.59 ± 8.89, p = 0.010). For PASI 100, the response rates were higher in female patients (female vs. male: 26.3% vs. 10.5%, p = 0.044) and patients with a family history of psoriasis (with family history vs. without family history: 44.4% vs. 13.9%, p = 0.042). In addition, the possibility of achieving PASI 75/90/100 went up along with the serum high-density lipoprotein cholesterol (HDL-C) level (expressed as adjusted odds ratio < 95% confidence interval>: PASI 75: 28.484 < 2.035-248.419>, p = 0.011; PASI 90: 28.226 < 2.828-281.729>, p = 0.004; PASI 100: 12.175 < 1.876-79.028>, p = 0.009). CONCLUSION: In this study, nearly one-third of patients achieved PASI 75 after only the first-dose ustekinumab treatment. Sex, family history of psoriasis, MS, serum TG level might affect the short-term effectiveness, and serum HDL-C level may be a potential factor. The possibility of achieving treatment goals (PASI 75/90/100) at week 4 increased along with serum HDL-C levels.

Comparison between super-responders and non-super-responders in psoriasis under adalimumab treatment: a real-life cohort study on the effectiveness and drug survival over one-year.

BACKGROUND: Data on the characteristics and treatment outcomes of super-responders and non-super-responders in psoriasis under adalimumab treatment are limited. METHODS: A retrospective analysis from psoriatic patients treated with adalimumab was compared to characterize super-responders vs non-super-responders' groups, identify factors associated with super response, and assess treatment outcomes after switching. RESULTS: 15 out of 70 (21.4%) patients were categorized as super-responder. The proportion of patients achieving a PASI 100 response was significantly higher in super-responders than non-super-responders at weeks 12, 24, and 52. Female sex and Charlson Co-morbidity Index were significantly associated with super-responders. A high level of high-density lipoprotein was independently associated with PASI 90 response at weeks 24 and 52. Additionally, nearly 35%-43% of non-super-responders switching to interleukin-17A (IL-17A) inhibitors may achieve a PASI 100 response at week 12. In contrast, all super-responders switching to IL-17A inhibitors achieved a PASI 100 response at week 4. CONCLUSIONS: Super-responders treated with adalimumab have a higher rate of being female and fewer comorbidities. And super-responders have better PASI responses than non-super-responders, whether the patients were treated with adalimumab or switched to IL-17A inhibitors.

Pongamol Prevents Neurotoxicity via the Activation of MAPKs/Nrf2 Signaling Pathway in H2O2-Induced Neuronal PC12 Cells and Prolongs the Lifespan of Caenorhabditis elegans.

Despite tremendous advances in modern medicine, effective prevention or therapeutic strategies for age-related neurodegenerative diseases such as Alzheimer's disease (AD) remain limited. Growing evidence now suggests that oxidative stress and apoptosis are increasingly associated with AD as promising therapeutic targets. Pongamol, a flavonoid, is the main constituent of pongamia pinnata and possesses a variety of pharmacological activities such as antioxidant, anti-aging and anti-inflammatory. In the present study, we investigated the antioxidant effects and mechanisms of pongamol in H2O2-induced PC12 cells and Caenorhabditis elegans (C. elegans). Our findings revealed that pongamol reduced cellular damage and apoptosis in H2O2-induced PC12 cells. Furthermore, pongamol reduced levels of apoptosis-related proteins Bax, Cyto C, Cleaved Caspase-3, and Cleaved PARP1, and increased the level of anti-apoptotic protein Bcl-2. Pongamol also effectively attenuated the level of oxidative stress markers such as glutathione (GSH) and reactive oxygen species (ROS) in H2O2-induced PC12 cells. Additionally, pongamol possessed antioxidant activity in H2O2-induced PC12 cells through the MAPKs/Nrf2 signaling pathway. Furthermore, pongamol exerted neuroprotective and anti-aging effects in C. elegans. All together, these results suggested that pongamol has a potential neuroprotective effect through the modulation of MAPKs/Nrf2 signaling pathway.

Defining the Minimal Important Change and Meaningful Change Value of the Disease Activity Index for Psoriatic Arthritis: A Chinese Longitudinal Study.

OBJECTIVE: To determine the minimal important change (MIC) and meaningful change value (MCV) of the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the effect size (ES) of DAPSA. METHODS: This was a retrospective cohort study, recruiting 106 patients who agreed to participate in the research from the Department of Dermatology, Xiangya Hospital, between November 1, 2019, and April 1, 2023. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs of the DAPSA. The anchor question assessed whether the patient's well-being had changed since their previous visit, employing a 5-point Likert scale that ranged from "much improved" to "much deteriorated." RESULTS: The overall MIC value was 8.4 (95% CI 0.01-16.75). The MIC improvement was 9.5 (95% CI 0.89-18.14) and MIC deterioration was 1.1 (95% CI -9.81 to 12.05). The overall MCV was 10.5 (95% CI 4.34-16.72). MCV improvement was 11.4 (95% CI 5.95-16.95) and MCV deterioration was 1.1 (95% CI -9.81 to 12.05). The ES was 0.6. CONCLUSION: A change in DAPSA of 8.4 is indicative of an MIC, offering physicians an additional means to contextualize the patient's perception of disease activity during treatment, and a change in DAPSA of 10.5 is likely to be regarded as MCV. These values can enhance the utility of DAPSA in psoriatic arthritis clinical trials.