KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Assessment of Laparoscopic Indocyanine Green Tracer-guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Studies on ICG imaging use in patients with LAGC on NAC are rare. METHODS: Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. RESULTS: Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). CONCLUSIONS: ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

A Mitochondria-Targeted Nitric Oxide Probe for Multimodality Imaging of Macrophage Immune Responses.

Nitric oxide (NO) is a crucial signal molecule closely linked to the biological immune response, especially in macrophage polarization. When activated, macrophages enter a pro-inflammatory state and produce NO, a marker for the M1 phenotype. In contrast, the anti-inflammatory M2 phenotype does not produce NO. We developed a mitochondria-targeted two-photon iridium-based complex (Ir-ImNO) probe that can detect endogenous NO and monitor macrophages' different immune response states using various imaging techniques, such as one- and two-photon phosphorescence imaging and phosphorescence lifetime imaging. Ir-ImNO was used to monitor the immune activation of macrophages in mice. This technology aims to provide a clear and comprehensive visualization of macrophage immune responses.

Predictive Value of a New Muscle Parameter in Patients with Resectable Gastric Cancer: A Pooled Analysis of Three Prospective Trials.

BACKGROUND: Sarcopenia is closely associated with gastric cancer (GC) prognosis. However, its exact definition remains controversial. METHODS: This study included computed tomography images and clinical data of patients from three prospective studies. The skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) were analyzed, and a new muscle parameter, skeletal muscle gauge (SMG), was obtained by multiplying the two parameters. The values of the three indices for predicting the prognosis of patients with GC were compared. RESULTS: The study included 717 patients. The findings showed median values of 42 cm2/m2 (range, 36.8-48.2 cm2/m2) for SMI, 45 HU (range, 41-49 HU) for SMRA, and 1842 (range, 1454-2260) for SMG. Postoperatively, 111 patients (15.5%) experienced complications. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were 74.3%, 68.2%, and 70%, respectively. Univariate logistic analysis showed that postoperative complications were associated with SMI (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.92-0.96), SMRA (OR, 0.87; 95% CI 0.84-0.90), and SMG (OR 0.99; 95% CI 0.98-0.99). After a two-step multivariate analysis, only SMG (OR 0.98, 95% CI 0.97-0.99) was an independent protective factor of postoperative complications. Multivariate analysis showed that SMG also was an independent protective factor of OS, DFS, and RFS. The patients were divided into low-SMG (L-SMG) group and high-SMG (H-SMG) groups. Chemotherapy benefit analysis of the patients with stage II low SMG showed that the OS, DFS, and RFS of the chemotherapy group were significantly better than those of the non-chemotherapy group (p < 0.05). CONCLUSION: The prospective large sample data showed that the new muscle parameter, SMG, can effectively predict the short-term outcome and long-term prognosis of patients with resectable gastric cancer. As a new muscle parameter index, SMG is worthy of further study.

CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.

BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

Trajectories of neutrophil-to-lymphocyte ratios during neoadjuvant chemotherapy correlate with short- and long-term outcomes in gastric cancer: a group-based trajectory analysis.

BACKGROUND: Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported. METHODS: This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups. RESULTS: Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005). CONCLUSION: There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials.

BACKGROUND: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. METHODS: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. RESULTS: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. CONCLUSION: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.

Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. METHODS: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. RESULTS: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). CONCLUSIONS: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. REGISTRATION NUMBER: NCT02327481 ( http://clinicaltrials.gov ).

Appraisal of surgical outcomes and oncological efficiency of intraoperative adverse events in robotic radical gastrectomy for gastric cancer.

BACKGROUND: Surgical quality control is a crucial determinant of evaluating the tumor efficacy. OBJECTIVE: To assess the ClassIntra grade for quality control and oncological outcomes of robotic radical surgery for gastric cancer (GC). METHODS: Data of patients undergoing robotic radical surgery for GC at a high-volume center were retrospectively analyzed. Patients were categorized into two groups, the intraoperative adverse event (iAE) group and the non-iAE group, based on the occurrence of intraoperative adverse events. The iAEs were further classified into five sublevels (ranging from I to V according to severity) based on the ClassIntra grade. Surgical performance was assessed using the Objective Structured Assessment of Technical Skill (OSATS) and the General Error Reporting Tool. RESULTS: This study included 366 patients (iAE group: n = 72 [19.7%] and non-iAE group: n = 294 [80.3%]). The proportion of ClassIntra grade II patients was the highest in the iAE group (54.2%). In total and distal gastrectomies, iAEs occurred most frequently in the suprapancreatic area (50.0% and 54.8%, respectively). In total gastrectomy, grade IV iAEs were most common during lymph node dissection in the splenic hilum area (once for bleeding [grade IV] and once for injury [grade IV]). The overall survival (OS) and disease-free survival of the non-iAE group were significantly better than those of the iAE group (Log rank P < 0.001). Uni- and multi-variate analyses showed that iAEs were key prognostic indicators, independent of tumor stage and adjuvant chemotherapy (P < 0.001). CONCLUSION: iAEs in patients who underwent robotic radical gastrectomy significantly correlated with the occurrence of postoperative complications and a poor long-term prognosis. Therefore, utilization and inclusion of ClassIntra grading as a crucial surgical quality control and prognostic indicator in the routine surgical quality evaluation system are recommended.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Developing a modified textbook outcome for elderly patients with gastric cancer: a multi-center study.

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Multi-functional nanozyme-based colorimetric, fluorescence dual-mode assay for Salmonella typhimurium detection in milk.

Rapid and high-sensitive Salmonella detection in milk is important for preventing foodborne disease eruption. To overcome the influence of the complex ingredients in milk on the sensitive detection of Salmonella, a dual-signal reporter red fluorescence nanosphere (RNs)-Pt was designed by combining RNs and Pt nanoparticles. After being equipped with antibodies, the immune RNs-Pt (IRNs-Pt) provide an ultra-strong fluorescence signal when excited by UV light. With the assistance of the H2O2/TMB system, a visible color change appeared that was attributed to the strong peroxidase-like catalytic activity derived from Pt nanoparticles. The IRNs-Pt in conjunction with immune magnetic beads can realize that Salmonella typhimurium (S. typhi) was captured, labeled, and separated effectively from untreated reduced-fat pure milk samples. Under the optimal experimental conditions, with the assay, as low as 50 CFU S. typhi can be converted to detectable fluorescence and absorbance signals within 2 h, suggesting the feasibility of practical application of the assay. Meanwhile, dual-signal modes of quantitative detection were realized. For fluorescence signal detection (emission at 615 nm), the linear correlation between signal intensity and the concentration of S. typhi was Y = 83C-3321 (R2 = 0.9941), ranging from 103 to 105 CFU/mL, while for colorimetric detection (absorbamce at 450 nm), the relationship between signal intensity and the concentration of S. typhi was Y = 2.9logC-10.2 (R2 = 0.9875), ranging from 5 × 103 to 105 CFU/mL. For suspect food contamination by foodborne pathogens, this dual-mode signal readout assay is promising for achieving the aim of convenient preliminary screening and accurate quantification simultaneously.

Walking Interventions and Sleep Quality of Persons Living With Dementia and Their Family Caregivers: Effects of Different Walking Companions.

PURPOSE: To examine the effect of walking interventions on sleep quality of persons with dementia (PWD) and their caregivers (dyads), and how different companions affect results. METHOD: Forty-five dyads were divided into three groups: a control group and two experimental groups (one with a care attendant, one with a family caregiver). The two experimental groups engaged in 120 minutes of walking per week for 24 weeks. RESULTS: A significant improvement in sleep quality was observed among PWD in the family caregiver group (Wald χ2 = 4.55, p = 0.033), whereas there was no improvement in the care attendant group. A slight improvement in sleep quality of family caregivers was also found. CONCLUSION: Findings suggest the importance of creating individualized walking activity plans for dyads, incorporating trust and rapport-building strategies to improve sleep quality. [Journal of Gerontological Nursing, 50(8), 46-56.].

Relationship of Hearing Loss to Parkinson's Disease, Dementia, and APOE Genotype in Adults.

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE. Results: Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB, p = 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB, p = 0.028) and higher prevalence of dementia (12/14 vs. 18/44, p = 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62, p = 0.036). Conclusions: Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.

A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity.

An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor-immune responses. Research has shown that non-apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP-ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that the Ru(II) complex can initiate the oncosis-associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis promotes dendritic cell maturation and awakens adaptive cytotoxic T lymphocytes but also activates the innate immune by inducing the polarization of macrophages towards an M1 phenotype.

Exploring the relationship between lesion morphology and pathogenesis in acute small subcortical infarction.

Introduction Acute small subcortical infarctions (SSIs) result from occlusions of small penetrating arteries, and the underlying pathological factors can have different clinical implications. The objective of this study was to assess the clinical relevance of acute SSIs based on their sizes and morphologies. Methods This retrospective case-control study analyzed clinical and imaging data of stroke patients with acute SSIs in penetrating artery territories who underwent MRI within 5 days of stroke onset, registered between 2016 and 2020. We categorized these patients into three groups based on size and morphology: diameter < 20mm, diameter ≧ 20mm, and separated lesions. We then evaluated their clinical characteristics and outcomes. Results We analyzed 726 stroke patients with SSIs, among whom 573 had a diameter <20mm, 99 had a diameter ≥20mm, and 54 had separated lesions. The patients had a median age of 70 years and a median National Institutes of Health Stroke Scale (NIHSS) score of 4 on arrival. Patients who experienced early neurological deterioration (END) had a significantly lower chance of good functional outcomes (27.3% vs. 64.4%, p<0.001). Patients with a diameter ≧20mm had the most severe NIHSS on arrival and at day 3, the highest rate of END, and the lowest rate of good outcome at 3 months. The incidence of cardioembolism did not differ between patients with diameters of ≥20mm and <20mm. However, multiple logistic regression analysis revealed that separated lesions were more likely to be associated with cardioembolic stroke (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 2.0-28.5) and parent artery stenosis >50% (aOR, 3.8; 95% CI, 2.1-7.0) than a diameter of <20mm. Moreover, SSIs with a diameter of ≥20mm was found to be associated with an increased risk of END compared to that with a diameter of <20mm (aOR, 2.9; 95% CI, 1.7-5.2). Conclusion Our study suggests that the sizes and morphologies of acute SSIs may indicate different underlying pathologies and be linked to diverse clinical outcomes. Our findings also challenge the current imaging criteria for embolic stroke of undetermined source, as we did not find a link between large subcortical infarction and cardioembolic stroke.