Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma.

Purpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib. Patients and Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics. Results: The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate (p = 0.028) and multivariate (p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS (p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group. Conclusion: Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.

The study provides significant evidence that an increase in spleen volume is associated with better treatment outcomes in advanced hepatocellular carcinoma patients undergoing immunotherapy. These findings offer oncologists a new potential biomarker for optimizing treatment strategies. Specifically, increased spleen volume could be used to predict higher rates of disease control and durable clinical benefits, allowing for more personalized care.

Amelioration of walnut, peony seed and camellia seed oils against D-galactose-induced cognitive impairment in mice by regulating gut microbiota.

Diet adjustment will affect the health of gut microbiota, which in turn influences the development and function of the organism's brain through the gut-brain axis. Walnut oil (WO), peony seed oil (PSO) and camellia seed oil (CSO), as typical representatives of woody plant oils, have been shown to have the potential to improve cognitive impairment in mice, but the function mechanisms are not clear. In this study, we comparatively investigated the neuroprotective effects of these three oils on D-galactose (D-gal)-induced cognitive impairment in mice, and found that the ameliorative effect of WO was more prominent. During the behavioral experiments, supplementation with all three oils would improve spatial learning and memory functions in D-gal mice, with a significant reduction in the error times (p < 0.001) and a significant increase in step-down latency (p < 0.001); walnut oil supplementation also significantly increased the number of hidden platform traversals, the target quadrant spent times and percentage of distance (p < 0.05). The results of biomarker analysis showed that WO, in addition to significantly inhibiting D-gal-induced oxidative stress and neuroinflammation as did PSO, significantly increased the ACh content in the mouse brain (p < 0.05) and modulated neurotransmitter levels. The results of further microbiota diversity sequencing experiments also confirmed that dietary supplementation with all three oils affected the diversity and composition of the gut microbiota in mice. Among them, WO significantly restored the balance of the mouse gut microbiota by increasing the abundance of beneficial bacteria (Bacteroidetes, Actinobacteria, Firmicutes) and decreasing the abundance of harmful bacteria (Clostridium, Shigella, Serratia), which was consistent with the results of behavioral experiments and biomarker analyses. Based on the analysis of the fatty acid composition of the three oils and changes in the gut microbiota, it is hypothesized that there is a correlation between the fatty acid composition of the dietary supplement oils and neuroprotective effects. The superiority of WO over PSO and CSO in improving cognitive impairment is mainly attributed to its balanced composition of omega-6 and omega-3 fatty acids.

Most total pancreatectomies for ductal adenocarcinoma potentially can Be replaced by whipple over the splenic artery: a before and after study.

INTRODUCTION: Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA) which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for a complete resection. Spiked by Warshaw's procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), we developed a new procedure "Whipple over the splenic artery (WOTSA)" to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique "Whipple over the splenic artery (WOTSA)" as a treatment for PDAC which traditionally requires total pancreatectomy (TP) for a complete excision. METHODS: The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019. RESULTS: None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. DM medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and number of harvested positive lymph nodes, but higher rate of adjuvant chemotherapy completion and a trend toward better median disease free survival (14 vs. 7.5 mo, P=0.023). CONCLUSIONS: Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.

Construction of a nomogram model to predict technical difficulty in performing laparoscopic sphincter-preserving radical resection for rectal cancer.

BACKGROUND: Colorectal surgeons are well aware that performing surgery for rectal cancer becomes more challenging in obese patients with narrow and deep pelvic cavities. Therefore, it is essential for colorectal surgeons to have a comprehensive understanding of pelvic structure prior to surgery and anticipate potential surgical difficulties. AIM: To evaluate predictive parameters for technical challenges encountered during laparoscopic radical sphincter-preserving surgery for rectal cancer. METHODS: We retrospectively gathered data from 162 consecutive patients who underwent laparoscopic radical sphincter-preserving surgery for rectal cancer. Three-dimensional reconstruction of pelvic bone and soft tissue parameters was conducted using computed tomography (CT) scans. Operative difficulty was categorized as either high or low, and multivariate logistic regression analysis was employed to identify predictors of operative difficulty, ultimately creating a nomogram. RESULTS: Out of 162 patients, 21 (13.0%) were classified in the high surgical difficulty group, while 141 (87.0%) were in the low surgical difficulty group. Multivariate logistic regression analysis showed that the surgical approach using laparoscopic intersphincteric dissection, intraoperative preventive ostomy, and the sacrococcygeal distance were independent risk factors for highly difficult laparoscopic radical sphincter-sparing surgery for rectal cancer (P < 0.05). Conversely, the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance was identified as a protective factor (P < 0.05). A nomogram was subsequently constructed, demonstrating good predictive accuracy (C-index = 0.834). CONCLUSION: The surgical approach, intraoperative preventive ostomy, the sacrococcygeal distance, and the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance could help to predict the difficulty of laparoscopic radical sphincter-preserving surgery.

Using U-Net convolutional neural network to model pixel-based electrostatic potential distributions in GaN power MIS-HEMTs.

This study demonstrates a novel use of the U-Net convolutional neural network (CNN) for modeling pixel-based electrostatic potential distributions in GaN metal-insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with various gate and source field plate designs and drain voltages. The pixel-based images of the potential distribution are successfully modeled from the developed U-Net CNN with an error of less than 1% error relative to a TCAD simulated reference of a 500-V electrostatic potential distribution in the AlGaN/GaN interface. Furthermore, the modeling time of potential distributions by U-Net takes about 80 ms. Therefore, the U-Net CNN is a promising approach to efficiently model the pixel-based distributions characteristics in GaN power devices.

PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.

Gut microbiome and brain transcriptome analyses reveal the effect of walnut oil in preventing scopolamine-induced cognitive impairment.

Walnut Oil (WO) is recognized for its potential to improve cognition, but the mechanisms of its action related to improving cognitive impairment are not yet clear. In this study, the components of walnut oil were measured, and it was found that WO supplementation for 8 weeks could significantly prevent cognitive behavioral deficits and synaptic dysfunction induced by intraperitoneal injection of scopolamine (SCOP) in mice. By comparing and analyzing the changes in the hippocampal synaptic structure, oxidative stress, neurotransmitter fluctuations, brain transcriptome, inflammatory factors and gut microbiota in mice from different treatment groups, we observed a significant correlation between synaptic transmission genes, gut microbiota and neurotransmission in the WO supplemented group. It was found that WO supplementation could influence the secretion of neurotransmitters Ach and 5-HT by modulating the gut microbiota in vivo, thereby improving cognitive impairment through the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis regulation.

The subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles.

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

Artificial intelligence assisted pterygium diagnosis: current status and perspectives.

Pterygium is a prevalent ocular disease that can cause discomfort and vision impairment. Early and accurate diagnosis is essential for effective management. Recently, artificial intelligence (AI) has shown promising potential in assisting clinicians with pterygium diagnosis. This paper provides an overview of AI-assisted pterygium diagnosis, including the AI techniques used such as machine learning, deep learning, and computer vision. Furthermore, recent studies that have evaluated the diagnostic performance of AI-based systems for pterygium detection, classification and segmentation were summarized. The advantages and limitations of AI-assisted pterygium diagnosis and discuss potential future developments in this field were also analyzed. The review aims to provide insights into the current state-of-the-art of AI and its potential applications in pterygium diagnosis, which may facilitate the development of more efficient and accurate diagnostic tools for this common ocular disease.

A machine learning model for distinguishing Kawasaki disease from sepsis.

KD is an acute systemic vasculitis that most commonly affects children under 5 years old. Sepsis is a systemic inflammatory response syndrome caused by infection. The main clinical manifestations of both are fever, and laboratory tests include elevated WBC count, C-reactive protein, and procalcitonin. However, the two treatments are very different. Therefore, it is necessary to establish a dynamic nomogram based on clinical data to help clinicians make timely diagnoses and decision-making. In this study, we analyzed 299 KD patients and 309 sepsis patients. We collected patients' age, sex, height, weight, BMI, and 33 biological parameters of a routine blood test. After dividing the patients into a training set and validation set, the least absolute shrinkage and selection operator method, support vector machine and receiver operating characteristic curve were used to select significant factors and construct the nomogram. The performance of the nomogram was evaluated by discrimination and calibration. The decision curve analysis was used to assess the clinical usefulness of the nomogram. This nomogram shows that height, WBC, monocyte, eosinophil, lymphocyte to monocyte count ratio (LMR), PA, GGT and platelet are independent predictors of the KD diagnostic model. The c-index of the nomogram in the training set and validation is 0.926 and 0.878, which describes good discrimination. The nomogram is well calibrated. The decision curve analysis showed that the nomogram has better clinical application value and decision-making assistance ability. The nomogram has good performance of distinguishing KD from sepsis and is helpful for clinical pediatricians to make early clinical decisions.

Orexin recruits non-selective cationic conductance and endocannabinoid to dynamically modulate firing of caudal pontine reticular nuclear neurones.

The neuropeptide orexin is involved in motor circuit function. However, its modulation on neuronal activities of motor structures, integrating orexin's diverse downstream molecular cascades, remains elusive. By combining whole-cell patch-clamp recordings and neuropharmacological methods, we revealed that both non-selective cationic conductance (NSCC) and endocannabinoids (eCBs) are recruited by orexin signalling on reticulospinal neurones in the caudal pontine reticular nucleus (PnC). The orexin-NSCC cascade provides a depolarizing force that proportionally enhances the firing-responsive gain of these neurones. Meanwhile, the orexin-eCB cascade selectively attenuates excitatory synaptic strength in these neurones by activating presynaptic cannabinoid receptor type 1. This cascade restrains the firing response of the PnC reticulospinal neurones to excitatory inputs. Intriguingly, non-linear or linear interactions between orexin postsynaptic excitation and presynaptic inhibition can influence the firing responses of PnC reticulospinal neurones in different directions. When presynaptic inhibition is in the lead, non-linear interactions can prominently downregulate or even gate the firing response. Conversely, linear interactions occur to promote the firing response, and these linear interactions can be considered a proportional reduction in the contribution of depolarization to firing by presynaptic inhibition. Through the dynamic employment of these interactions, adaptive modulation may be achieved by orexin to restrain or even gate the firing output of the PnC to weak/irrelevant input signals and facilitate those to salient signals. KEY POINTS: This study investigated the effects of orexin on the firing activity of PnC reticulospinal neurones, a key element of central motor control. We found that orexin recruited both the non-selective cationic conductances (NSCCs) and endocannabinoid (eCB)-cannabinoid receptor type 1 (CB1R) system to pontine reticular nucleus (PnC) reticulospinal neurones. The orexin-NSCC cascade exerts a postsynaptic excitation that enhances the firing response, whereas the orexin-eCB-CB1R cascade selectively attenuates excitatory synaptic strength that restrains the firing response. The postsynaptic and presynaptic actions of orexins occur in an overlapping time window and interact to dynamically modulate firings in PnC reticulospinal neurones. Non-linear interactions occur when presynaptic inhibition of orexin is in the lead, and these interactions can prominently downregulate or even gate firing responses in PnC reticulospinal neurones. Linear interactions occur when postsynaptic excitation of orexin is in the lead, and these interactions can promote the firing response. These linear interactions can be considered a proportional reduction of the contribution of depolarization to firing by presynaptic inhibition.

The diagnostic and prognostic value of SAA1 as a novel biomarker for acute aortic dissection.

BACKGROUND AND AIMS: Acute aortic dissection (AAD) is a serious life-threatening cardiovascular condition. It is necessary to find rapid and accurate biomarkers for the diagnosis of AAD. This study aimed to determine the efficacy of serum amyloid A1 (SAA1) in the diagnosis and prediction of long-term adverse events in AAD. MATERIALS AND METHODS: Four-dimensional label-free quantification (4D-LFQ) technique was used to identify the differentially expressed proteins (DEPs) in aortic tissues of AAD. After comprehensive analysis, SAA1 was identified as a potential biomarker of AAD. ELISA was used to confirm the expression of SAA1 in serum of AAD patients. Moreover, the source of SAA1 in serum was explored by constructing AAD mouse model. RESULTS: A total of 247 DEPs were identified, of which 139 were upregulated while 108 were downregulated. SAA1 was nearly 6.4-fold and 4.5-fold upregulated in AAD tissue and serum. ROC curve and Kaplan-Meier survival curve confirmed the good efficacy of SAA1 for the diagnosis and prediction of long-term adverse events in AAD. In vivo experiments revealed that SAA1 was mainly derived from the liver when AAD occurred. CONCLUSION: SAA1 can be used as a potential biomarker for AAD with effective diagnostic and prognostic value. SIGNIFICANCE: Despite the advances in medical technology in recent years, the mortality rate of acute aortic dissection (AAD) is still high. It is still challenging for clinicians to diagnose AAD patients on time and reduce the mortality rate. In this study, 4D-LFQ technology was used to identify serum amyloid A1 (SAA1) as a potential biomarker of AAD and was verified in subsequent work. The results of this study determined the efficacy of SAA1 in the diagnosis and prediction of long-term adverse events in patients with AAD.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

Epidemiological characteristics and spatiotemporal analysis of mumps at township level in Wuhan, China, 2005-2019.

The resurgence and outbreaks of mumps occur frequently in many countries worldwide in recent years, even in countries with high vaccination coverage. In this study, a descriptive and spatiotemporal clustering analysis at the township level was conducted to explore the dynamic spatiotemporal aggregation and epidemiological characteristics of mumps in Wuhan. During 2005 and 2019, there were 40 685 cases reported in Wuhan, with an average annual morbidity of 28.11 per 100 000 populations. The morbidity showed a fluctuating tendency, and peaked in 2010 and 2018. Bimodal seasonality was found, with a large peak between May and July, and a mild peak from November to January in the following year. Male students aged 5-9-year-old were the main risk group of mumps infection. Significant global spatial auto-correlation was detected except in 2007, 2009 and 2015. The spatial and temporal scan statistics indicated that the hot-spots mainly located at the western and southern areas of Wuhan with variations almost every year. Our findings could assist the public health authorities to develop and improve targeted health strategies, and allocate health resources rationally.

Resonance-Enhanced Emission Effects toward Dual-State Emissive Bright Red and Near-Infrared Emitters.

Resonance-enhanced emission (REE) effect was discovered and lead to a novel dye family of hydrostyryl pyridinium derivatives in our recent work. Herein, the REE effect was employed to design a red and near-infrared dual-state emissive fluorophore family of SW-OH-NO2 derivatives which were easily synthesized by coupling an electron-withdrawing group (W) onto nitro(hydroxyl)styryl (S-OH-NO2 ) through a C=C double bond as π-bridge. The deprotonation of a phenolic hydroxyl group promoted by a nitro group and the electron-withdrawing group (W) on the other side of the π-bridge triggered resonance, resulting in significantly red-shifted emission. All the resultant SW-OH-NO2 compounds showed excellent dual-state emission behavior. Remarkably, hydrostyryl quinolinium (SQ-OH-NO2 ) is one of the smallest NIR emitter molecular skeleton (λem =725 nm, MW<400) and showed dual-state emission characteristics and obvious viscosity-depended fluorescent behaviors. In addition to constructing electron donor-acceptor structures and prolonging π-bridges, the REE effect promises a reliable strategy toward novel fluorophores with small size, long emissive wavelength, and dual-emission characteristics, and importantly, feasible industrial manufactures and applications due to their easy and low-cost synthesis strategy.

Design of biomass-based N, S co-doped porous carbon via a straightforward post-treatment strategy for enhanced CO2 capture performance.

Biomass-based adsorbents are considered to have great potential for CO2 capture due to their low cost, high efficiency and exceptional sustainability. The aim of this work is to design a simple method for preparing biomass-based adsorbents with abundant active sites and large numbers of narrow micropores, so as to enhance CO2 capture performance. Herein, N, S co-doped porous carbon (NSPC) was created utilizing walnut shell-based microporous carbon (WSMC) as the main framework and thiourea as N/S dopant through physical grinding and post-treatment process at a moderate temperature without any other reagents and steps. By altering the post-treatment parameters, a series of porous carbons with varying physico-chemical properties were prepared to discuss the roles of microporosity and N/S functional groups in CO2 adsorption. NSPC with narrow micropore volume of 0.74 cm3 g-1, N content of 4.89 % and S contents of 0.71 % demonstrated the highest CO2 adsorption capacity of 7.26 (0 °C) and 5.51 mmol g-1 (25 °C) at 1 bar. Meanwhile, a good selectivity of binary gas mixture CO2/N2 (15/85) of 29.72 and outstanding recyclability after ten cycles of almost 100 % adsorption capacity retention were achieved. The proposed post-treatment method was beneficial in maintaining the narrow micropores and forming N/S active sites, which together improve the CO2 adsorption performance of NSPC. The novel NSPC displays amazing CO2 adsorption characteristics, and the practical, affordable synthetic approach exhibits significant potential to produce highly effective CO2 adsorbents on a broad scale.

Amelioration of walnut-derived novel peptides against D-galactose-induced cognitive impairment by modulating the gut microbiota composition.

In this work, RLWPF (Arg-Leu-Trp-Pro-Phe) and VLRLF (Val-Leu-Arg-Leu-Phe) were investigated for the effects against D-galactose (D-gal) induced cognitive impairment by modulating the gut microbiota composition. The effects on serum metabolite production were further investigated. The two novel peptides derived from walnut protein alkaline protease hydrolysates were predicted by docking to acetylcholinesterase (AChE) with the highest binding affinities, -10.3 and -9.9 kcal mol-1, considered as the potential neuroprotective peptides. In behavioral experiments, RLWPF and VLRLF treatment significantly restored spatial learning and memory impairment induced by D-gal. The results showed that RLWPF and VLRLF could alleviate cholinergic dysfunction, oxidative stress, and inflammation to varying degrees caused by D-gal-induced aging. Furthermore, 16S rRNA analysis revealed that RLWPF and VLRLF treatment improved cognitive impairment by regulating the composition of the gut microbiota and the abundance of harmful bacteria, including the ratio of Firmicutes to Bacteroidetes, Helicobacter, Allobaculum, Alistipes, Mucispirillum, and Odoribacter. In addition to the same regulation, RLWPF and VLRLF had their marker and regulatory flora. Studies based on the gut microbiota would allow a better understanding of the neuroprotective effects of walnut-derived peptides, supporting that walnut-derived peptides could be potential functional ingredients in foods and nutraceuticals or drug candidates in the treatment of cognitive dysfunction.

Detection of walnut oil adulterated with high-linoleic acid vegetable oils using triacylglycerol pseudotargeted method based on SFC-QTOF-MS.

Authentication of walnut oil (WO) is challenging due to the adulteration of high-linoleic acid vegetable oils (HLOs) with similar fatty acid composition. To allow the discrimination of WO adulteration, a rapid, sensitive and stable scanning method based on supercritical fluid chromatography quadrupole time-of-flight mass spectrometry (SFC-QTOF-MS) was established to profile 59 potential triacylglycerol (TAGs) in HLOs samples within 10 min. Limit of quantitation of the proposed method is 0.002 µg mL-1 and the relative standard deviations range from 0.7% to 12.0%. TAGs profiles of WO samples from various varieties, geography origins, ripeness, and processing methods were used to construct orthogonal partial least squares-discriminant analysis (OPLS-DA) and OPLS models that were highly accurate in both qualitative and quantitative prediction at adulteration levels as low as 5% (w/w). This study advances the TAGs analysis to characterize vegetable oils and holds promise as an efficient method for oil authentication.

Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments.

Rheumatoid arthritis (RA) is a systemic immune disease characterized by synovial inflammation. Patients with RA commonly experience significant damage to their hand and foot joints, which can lead to joint deformities and even disability. Traditional treatments have several clinical drawbacks, including unclear pharmacological mechanisms and serious side effects. However, the emergence of antibody drugs offers a promising approach to overcome these limitations by specifically targeting interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that are closely related to the onset of RA. This approach reduces the incidence of adverse effects and contributes to significant therapeutic outcomes. Furthermore, combining these antibody drugs with drug delivery nanosystems (DDSs) can improve their tissue accumulation and bioavailability.Herein, we provide a summary of the pathogenesis of RA, the available antibody drugs and DDSs that improve the efficacy of these drugs. However, several challenges need to be addressed in their clinical applications, including patient compliance, stability, immunogenicity, immunosupression, target and synergistic effects. We propose strategies to overcome these limitations. In summary, we are optimistic about the prospects of treating RA with antibody drugs, given their specific targeting mechanisms and the potential benefits of combining them with DDSs.