The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway.

Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo. Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD.

Advancements in physiologically based pharmacokinetic modeling for fedratinib: updating dose guidance in the presence of a dual inhibitor of CYP3A4 and CYP2C19.

PURPOSE: A physiologically based pharmacokinetic (PBPK) model for fedratinib was updated and revalidated to bridge a gap between the observed drug-drug interaction (DDI) of a single sub-efficacious dose in healthy participants and the potential DDI in patients with cancer at steady state. The study aimed to establish an appropriate dose for fedratinib in patients coadministered with dual CYP3A4 and CYP2C19 inhibitors, providing quantitative evidence to inform dosing guidance. METHODS: The original minimal PBPK model was developed using Simcyp® Simulator v17. The model was updated by substituting a single distribution rate (Qsac) with 2 separate rates (CLin/CLout) and transitioning to v20. Model parameter updates were further informed with 3 clinical studies, and 3 more studies served as independent validation data. The validated model was applied to simulate potential DDIs between fedratinib and a known dual inhibitor of CYP3A4 and CYP2C19 (fluconazole). RESULTS: Coadministration of fedratinib with fluconazole in patients was predicted to increase fedratinib exposure by < 2-fold in all simulated scenarios. For patients with cancer receiving the approved dose of fedratinib 400 mg once daily along with fluconazole 200 mg daily, the model predicted an approximate 50% increase in fedratinib exposure at steady state. CONCLUSIONS: The updated PBPK model improved description of the observed pharmacokinetics and predicted a low risk of clinically significant DDIs between fedratinib and fluconazole. The quantitative evidence serves as a primary foundation for providing dose guidance in clinical practice for the coadministration of fedratinib with dual CYP3A4 and CYP2C19 inhibitors.

Neurocognitive Remediation Therapy: A Promising Approach to Enhance Cognition in Community Living Pilots with Depression and Anxiety.

Depression and anxiety are pervasive mental health issues, affecting millions globally and often accompanied by cognitive impairments with significant repercussions in daily life and professions, particularly in safety-critical roles like community-living pilots. This exploration assesses Neurocognitive Remediation Therapy (NRT) as an innovative solution for addressing cognitive deficits linked to depression and anxiety in these pilots. Theoretical underpinnings of NRT draw from cognitive rehabilitation, neuropsychology, and neuroplasticity principles. Depression and anxiety often manifest as cognitive deficits, impacting attention, memory, executive functions, and decision-making. NRT interventions aim to address these impairments by enhancing cognitive flexibility, attentional control, and memory through training exercises and cognitive restructuring, empowering individuals to regain cognitive functionality and adaptability. Empirical evidence supports NRT's efficacy in enhancing cognitive functioning, showing significant improvements in attention, memory, and executive functions. This review focuses on NRT's potential to improve cognition in community pilots, demonstrating its effectiveness in reducing cognitive deficits and enhancing job performance, even in high-pressure environments like aviation. The practical implications of NRT for pilots are profound. Tailored programs can address specific cognitive challenges, such as maintaining vigilance and decision-making under stress. Integrating NRT into training regimens enhances skill sets and mental resilience, contributing to safety and success. Additionally, NRT positively impacts emotional well-being, reducing stress and improving overall quality of life. In Conclusion, NRT emerges as a promising intervention for enhancing cognitive functioning in community-living pilots with depression and anxiety. Evidence suggests its potential to improve performance, job satisfaction, and overall well-being. Further research and implementation are crucial to fully realize its benefits and ensure pilots' safety and success.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway.

BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear. AIM: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1ß, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1ß, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1ß, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both). CONCLUSION: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.

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.

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.

Exploring factors affecting the acceptance of fall detection technology among older adults and their families: a content analysis.

BACKGROUND: This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur. METHODS: The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke. RESULTS: The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology. CONCLUSIONS: This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Stereoselective Double Spirocyclization of 2-Benzyl-3-alkynyl Chromone with Nitrone via Gold-Catalyzed Cascade Reactions.

A novel, highly stereoselective gold-catalyzed spirocyclization of 2-benzyl-3-alkynyl chromone with nitrone is described. This cascade reaction involves gold-catalyzed cycloisomerization, nitrone-olefin [3 + 2]-annulation, alkene oxidation, and rearrangement for the formation of spirocyclic products. Interestingly, the isoxazolidine ring generated from [3 + 2]-annulation donates oxygen to alkene to generate a new pyran-3(4H)-one and azetidine ring for dispiro-benzofuran formation upon heating. This work demonstrates the one-pot, gold-catalyzed, multiple-step reaction, and the reaction temperature directly affects the formation of spirocyclic products.

Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway.

Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: The authors aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR ≤0.4, and sLNR >0.4. Patients in the D2+No. 10 group were randomly divided into the training ( n =302) and validation ( n =130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate, and high SHLN metastasis burden groups (LMB, MMB, and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) ( P <0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication.

Similar to other RNA viruses, grass carp reovirus, the causative agent of the hemorrhagic disease, replicates in cytoplasmic viral inclusion bodies (VIBs), orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of GCRV VIBs are poorly understood. This work demonstrates that GCRV manipulates grass carp oxysterol binding protein 1 (named as gcOSBP1) and vesicle-associated membrane protein-associated protein A/B (named as gcVAP-A/B), 3 components of cholesterol transport pathway, to generate VIBs. By siRNA-mediated knockdown, we demonstrate that gcOSBP1 is an essential host factor for GCRV replication. We reveal that the nonstructural proteins NS80 and NS38 of GCRV interact with gcOSBP1, and that the gcOSBP1 is recruited by NS38 and NS80 for promoting the generation of VIBs. gcOSBP1 increases the expression of gcVAP-A/B and promotes the accumulation of intracellular cholesterol. gcOSBP1 also interacts with gcVAP-A/B for forming gcOSBP1-gcVAP-A/B complexes, which contribute to enhance the accumulation of intracellular cholesterol and gcOSBP1-mediated generation of VIBs. Inhibiting cholesterol accumulation by lovastatin can completely abolish the effects of gcOSBP1 and/or gcVAP-A/B in promoting GCRV infection, suggesting that cholesterol accumulation is vital for gcOSBP1- and/or gcVAP-A/B-mediated GCRV replication. Thus, our results, which highlight that gcOSBP1 functions in the replication of GCRV via its interaction with essential viral proteins for forming VIBs and with host gcVAP-A/B, provide key molecular targets for obtaining anti-hemorrhagic disease grass carp via gene editing technology.

Medical students' preferences for asynchronous online or face-to-face learning strategies in learning gross anatomy and neuroanatomy during the COVID-19 pandemic.

Gross anatomy and neuroanatomy are fundamental subjects in medical education. However, learning different anatomical terms and understanding the complexity of the subjects are often challenging for medical students. At National Taiwan University, the 2020-2021 cohort adopted a face-to-face (F2F) learning strategy for gross anatomy and neuroanatomy lecture and laboratory courses until May 17, 2021. After the aforementioned date, the same cohort learned the rest of the gross anatomy and neuroanatomy courses via asynchronous online learning. This study aimed to evaluate the benefits of and students' preferences for F2F and asynchronous online learning strategies in learning gross anatomy and neuroanatomy. A survey with closed-ended and open-ended questions was used to quantitatively and qualitatively explore medical students' learning preferences for two teaching strategies in gross anatomy and neuroanatomy. The results identified different learning preferences among students in learning gross anatomy and neuroanatomy-satisfied with both learning strategies, satisfied with only F2F learning strategy, satisfied with only asynchronous online learning strategy, and satisfied with neither learning strategy. The survey results with closed-ended and open-ended questions showed that medical students preferred F2F learning for anatomical laboratory courses but favored asynchronous online learning for neuroanatomical laboratory courses. In addition, medical students considered peer discussion more critical in learning gross anatomy than neuroanatomy. These findings provide valuable information about medical students' preference for gross anatomy and neuroanatomy courses, which anatomy teachers can consider when planning to enhance their curriculum in the future.

Biomechanical effects of posterior lumbar interbody fusion with vertical placement of pedicle screws compared to traditional placement.

BACKGROUND: The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal disorders. However, traditional screw placement methods require the dissection of paraspinal muscles and the insertion of pedicle screws at specific transverse section angles (TSA). Larger TSA angles require more force to pull the muscle tissue, which can increase the risk of surgical trauma and ischemic injury to the lumbar muscles. AIM: To study the feasibility of zero-degree TSA vertical pedicle screw technique in the lumbosacral segment. METHODS: Finite element models of vertebral bodies and pedicle screw-rod systems were established for the L4-S1 spinal segments. A standard axial load of 500 N and a rotational torque of 10 N/m were applied. Simulated screw pull-out experiment was conducted to observe pedicle screw resistance to pull-out, maximum stress, load-displacement ratio, maximum stress in vertebral bodies, load-displacement ratio in vertebral bodies, and the stress distribution in pedicle screws and vertebral bodies. Differences between the 0-degree and 17-degree TSA were compared. RESULTS: At 0-degree TSA, the screw pull-out force decreased by 11.35% compared to that at 17-degree TSA (P < 0.05). At 0-degree and 17-degree TSA, the stress range in the screw-rod system was 335.1-657.5 MPa and 242.8-648.5 MPa, separately, which were below the fracture threshold for the screw-rod system (924 MPa). At 0-degree and 17-degree TSA, the stress range in the vertebral bodies was 68.45-78.91 MPa and 39.08-72.73 MPa, separately, which were below the typical bone yield stress range for vertebral bodies (110-125 MPa). At 0-degree TSA, the load-displacement ratio for the vertebral bodies and pedicle screws was slightly lower compared to that at 17-degree TSA, indicating slightly lower stability (P < 0.05). CONCLUSION: The safety and stability of 0-degree TSA are slightly lower, but the risks of screw-rod system fracture, vertebral body fracture, and rupture are within acceptable limits.

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.

Comparing the Diagnostic Value of FDG PET or PET/CT With FDG PET/MR in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.

BACKGROUND: The aim of this study was to compare the diagnostic value of 18F-FDG PET or PET/CT with FDG PET/MR in patients with inflammatory bowel disease (IBD). METHODS: A comprehensive search was performed in PubMed for studies reporting the diagnostic performance of FDG PET (PET/CT) and FDG PET/MR in IBD from the inception of the database to March 14, 2024, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fourteen studies were included in this systematic review and meta-analysis. Pooled estimates of segment-based sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for FDG PET (PET/CT) and FDG PET/MR were calculated alongside 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were plotted, and the area under the SROC curve was determined alongside the Q* index. RESULTS: The segment-based pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve of FDG PET (PET/CT) for diagnosing IBD (9 studies) were 0.81, 0.86, 5.76, 0.22, 31.92, and 0.92, respectively. Those of FDG PET/MR (5 studies) were 0.78, 0.92, 10.97, 0.25, 51.79, and 0.95. There was no significant difference in the abilities of detecting or excluding IBD between FDG PET (PET/CT) and FDG PET/MR. CONCLUSIONS: For diagnostic value in patients with IBD, there was no significant difference between FDG PET (PET/CT) and FDG PET/MR. Both FDG PET (PET/CT) and FDG PET/MR have demonstrated high diagnostic performance for accurate diagnosing in patients with IBD.

Vacancies-Induced Delocalized States Cobalt Phosphide for Binder-Free Anode Toward Stable and High-Rate Sodium-Ion Batteries.

Metal phosphides with easy synthesis, controllable morphology, and high capacity are considered as potential anodes for sodium-ion batteries (SIBs). However, the inherent shortcomings of metal phosphating materials, such as conductivity, kinetics, volume strain, etc are not satisfactory, which hinders their large-scale application. Here, a CoP@carbon nanofibers-composite containing rich Co─N─C heterointerface and phosphorus vacancies grown on carbon cloth (CoP1-x@MEC) is synthesized as SIB anode to accomplish extraordinary capacity and ultra-long cycle life. The hybrid composite nanoreactor effectively impregnates defective CoP as active reaction center while offering Co─N─C layer to buffer the volume expansion during charge-discharge process. These vast active interfaces, favored electrolyte infiltration, and a well-structured ion-electron transport network synergistically improve Na+ storage and electrode kinetics. By virtue of these superiorities, CoP1-x@MEC binder-free anode delivers superb SIBs performance including a high areal capacity (2.47 mAh cm-2@0.2 mA cm-2), high rate capability (0.443 mAh cm-2@6 mA cm-2), and long cycling stability (300 cycles without decay), thus holding great promise for inexpensive binder-free anode-based SIBs for practical applications.

Exosomal miRNA 16-5p/29a-3p from pancreatic cancer induce adipose atrophy by inhibiting adipogenesis and promoting lipolysis.

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia. MicroRNA sequencing of exosomal components from normal and cancer-derived exosomes revealed enrichment of miR-16-5p, miR-21-5p, miR-29a-3p, and miR-125b-5p in serum exosomes of mice harboring PDAC and patients with PDAC. Further, miR-16-5p and miR-29a-3p inhibited adipogenesis through decreasing Erlin2 and Cmpk1 expression which downregulates C/EBPß and PPARγ. Synergistically, miR-29a-3p promotes lipolysis through increasing ATGL expression by suppressing MCT1 expression. Furthermore, PDAC-exosomes deprived of miR-16-5p and miR-29a-3p fail to induce fat loss. Hence, miR-16-5p and miR-29a-3p exosomal miRs are essential for PDAC-induced fat loss. Thus, we unravel that PDAC induces adipose atrophy via exosomal miRs. This knowledge may provide new diagnostic and therapeutic strategies for PDAC-induced cachexia.

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.

Efficient Compressive Strength Prediction of Alkali-Activated Waste Materials Using Machine Learning.

This study explores the integration of machine learning (ML) techniques to predict and optimize the compressive strength of alkali-activated materials (AAMs) sourced from four industrial waste streams: blast furnace slag, fly ash, reducing slag, and waste glass. Aimed at mitigating the labor-intensive trial-and-error method in AAM formulation, ML models can predict the compressive strength and then streamline the mixture compositions. By leveraging a dataset of only 42 samples, the Random Forest (RF) model underwent fivefold cross-validation to ensure reliability. Despite challenges posed by the limited datasets, meticulous data processing steps facilitated the identification of pivotal features that influence compressive strength. Substantial enhancement in predicting compressive strength was achieved with the RF model, improving the model accuracy from 0.05 to 0.62. Experimental validation further confirmed the ML model's efficacy, as the formulations ultimately achieved the desired strength threshold, with a significant 59.65% improvement over the initial experiments. Additionally, the fact that the recommended formulations using ML methods only required about 5 min underscores the transformative potential of ML in reshaping AAM design paradigms and expediting the development process.