bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of colorectal cancer growth: Interplay between curcumin and metformin through DMT1 downregulation and ROS‐mediated pathways
Authors: Chuang Hui‐Yen , Chan Hui‐Wen , Shih Kuang‐Chung 
Published: November 2024

AbstractThe rising incidence of colorectal cancer (CRC) poses significant healthcare challenges. This study explored the therapeutic potential of combined curcumin (CUR) and metformin (MET) treatment in CRC models. Our findings indicate that the combination treatment (COMB) effectively downregulates the expression of divalent metal transporter‐1 (DMT‐1), leading to a reduction in cell proliferation aligned with suppression of the pAKT/mTOR/Cyclin D1 signaling pathway. The COMB increased reactive oxygen species (ROS) production, triggering activation of the NRF2/KEAP1 pathway. This pathway elicits an antioxidant response to manage oxidative stress in CRC cell lines. Interestingly, the response of NRF2 varied between CT26 and HCT116 cells. Moreover, our study highlights the induction of apoptosis and autophagy, as evidenced by upregulations in Bax/Bcl‐2 ratios and autophagy‐related protein expressions. Notably, the COMB promoted lipid peroxidation and downregulated xCT levels, suggesting the induction of ferroptosis. Ferroptosis has been shown to activate autophagy, which helps eliminate cells potentially damaged by the increased oxidative stress. Furthermore, the COMB effectively diminished the migratory ability of CRC cells. In vivo experiments using CRC‐bearing mouse models, the results confirmed the anti‐tumor efficacy of the COMB, leading to substantial inhibition of tumor growth without inducing general toxicity. In conclusion, our study suggests that combining CUR with MET holds promise as a potential option for CRC treatment, with critical mechanisms likely involving ROS elevation, autophagy, and ferroptosis.
Metformin Inhibits the Progression of Pancreatic Cancer Through Regulating miR‐378a‐3p/VEGFA/RGC‐32 Axis
Authors: He Jinli , Luo Yixing , Ding Ying , Zhu Liang 
Published: November 2024

ABSTRACTBackgroundPancreatic cancer (PC) is a major contributor to global cancer‐related mortality. While the inhibitory effect of metformin (Met) on PC has been reported, the underlying mechanism remains elusive.MethodsWe established BxPC‐3 cell models with miR‐378a‐3p and VEGFA knockdown. The expression of miR‐378a‐3p, VEGFA, and RGC‐32 in PC and normal tissues was analyzed using GEPIA, TCGA databases. Cell proliferation, invasion, migration, and apoptosis were assessed through CCK8, Transwell, wound healing, and flow cytometry.ResultsSignificantly lower expression of miR‐378a‐3p was observed in PC tissues and cells. Knockdown of miR‐378a‐3p reversed the impact of Met on cell viability in PANC‐1 and BxPC3. VEGFA emerged as a potential regulator in PC and a downstream target of miR‐378a‐3p. The interaction between VEGFA and RGC‐32 played a crucial role in PC regulation. Knockdown of VEGFA substantially reversed the impact of miR‐378a‐3p inhibitor on tumor growth and the epithelial‐mesenchymal transition (EMT) process. Moreover, knockdown of VEGFA effectively countered the influence of miR‐378a‐3p inhibitor on cell viability and the EMT process in BxPC3 cells.ConclusionsMet exerted inhibitory effects on PC through the miR‐378a‐3p/VEGFA/RGC‐32 pathway. Strategies targeting the miR‐378a‐3p/VEGFA/RGC‐32 axis represent a novel avenue for the prevention and treatment of PC.
Body Roundness Index Trajectories and the Risk of Cancer: A Cohort Study
Authors: Chen Yue , Wang Yiming , Zheng Xin , Liu Tong , Liu Chenan , Lin Shiqi , Xie Hailun , Shi Jinyu , Liu Xiaoyue , Ma Xiangming , Deng Li , Wu Shouling , Shi Hanping 
Published: November 2024

ABSTRACTBackgroundThe body rounds index (BRI), an innovative obesity indicator integrating waist circumference (WC) and height, offers a two‐dimensional assessment of obesity. The relationship between BRI trajectories and cancer has been overlooked in previous studies. This study aims to explore the association between BRI trajectories and the incidence of cancer.MethodsThis study included 42,022 participants with a median age of 48.91 years. Based on the changes in participants' BRI during the period from 2006 to 2010, three BRI trajectory patterns were identified: low‐stable, medium‐stable, and high‐stable. The primary outcome was cancer incidence and the secondary outcome was cancer‐specific deaths. The association between BRI trajectories and cancer incidence and death was explored by cox regression analysis in the total, sex‐specific and age‐specific populations, respectively. Additionally, we further investigated the relationship between BRI and site‐specific cancer incidence. Sensitivity analyses were applied to exclude interferences and ensure the stability of the results.ResultsAfter a median follow‐up time of 11.04 years, high‐stable BRI trajectory was significantly associated with increased risk of cancer occurrence compared to low‐stable BRI trajectory. This association was more pronounced in middle‐aged men (men: HR = 1.46, 95% CI = 1.21–1.77, p < 0.001; age < 65: HR = 11.38, 95% CI = 1.15–1.66, p = 0.001). Additionally, high‐stable BRI trajectory was significantly associated with a substantial increase in the risk of site‐specific uterine cancers (HR = 4.92, 95% CI = 1.69–14.33, p = 0.004). Sensitivity analysis confirmed the stability of the results.ConclusionOur study identified a significant association between a high‐stable BRI trajectory and cancer incidence, with this association being most pronounced in middle‐aged men. Moreover, the high‐stable BRI trajectory was strongly associated with uterine site‐specific cancer development. Our findings underscore the importance of implementing lifestyle modifications and monitoring BRI values and their changes to provide effective health guidance.
Development of a Highly Selective NanoBRET Probe to Assess MAGL Inhibition in Live Cells
Authors: Gazzi Thais , Brennecke Benjamin , Olikauskas Valentas , Hochstrasser Remo , Wang Haiyan , Keen Chao Suzan , Atz Kenneth , Mostinski Yelena , Topp Andreas , Heer Dominik , Kaufmann Isabelle , Ritter Martin , Gobbi Luca , Hornsperger Benoit , Wagner Bjoern , Richter Hans , O'Hara Fionn , Wittwer Matthias B. , Jul Hansen Dennis , Collin Ludovic , Kuhn Bernd , Benz Joerg , Grether Uwe , Nazaré Marc 
Published: November 2024

AbstractCell‐free enzymatic assays are highly useful tools in early compound profiling due to their robustness and scalability. However, their inadequacy to reflect the complexity of target engagement in a cellular environment may lead to a significantly divergent pharmacology that is eventually observed in cells. The discrepancy that emerges from properties like permeability and unspecific protein binding may largely mislead lead compound selection to undergo further chemical optimization. We report the development of a new intracellular NanoBRET assay to assess MAGL inhibition in live cells. Based on a reverse design approach, a highly potent, reversible preclinical inhibitor was conjugated to the cell‐permeable BODIPY590 acceptor fluorophore while retaining its overall balanced properties. An engineered MAGL‐nanoluciferase (Nluc) fusion protein provided a suitable donor counterpart for the facile interrogation of intracellular ligand activity. Validation of assay conditions using a selection of known MAGL inhibitors set the stage for the evaluation of over 1’900 MAGL drug candidates derived from our discovery program. This evaluation enabled us to select compounds for further development based not only on target engagement, but also on favorable physicochemical parameters like permeability and protein binding. This study highlights the advantages of cell‐based target engagement assays for accelerating compound profiling and progress at the early stages of drug discovery programs.
Reversible Cerebral Vasoconstriction Syndrome Following Blood Transfusion in a Patient With Chronic Anemia: A Case Report
Authors: Verma Amogh , Sharma Govind , Singh Ajeet , Gupta Harshit , Singh Deependra Pratap , Gaidhane Abhay M. , Khatib Mahalaqua Nazli , Bushi Ganesh , Sah Sanjit , Ndabashinze Rodrigue 
Published: November 2024

ABSTRACTReversible cerebral vasoconstriction syndrome (RCVS) is a rare neurological disorder characterized by transient constriction and dilation of cerebral arteries, leading to severe headaches and neurological deficits. This case report describes a 41‐year‐old woman with chronic anemia, acute chronic kidney disease, type 2 diabetes mellitus, and rheumatoid arthritis who developed RCVS following transfusion of packed red blood cells (PRBCs). She experienced sudden‐onset seizures and a thunderclap headache 5 days post‐transfusion. Diagnostic imaging, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed the characteristic features of vasogenic edema. The patient was treated with blood pressure control and symptomatic relief for pain, resulting in gradual improvement. This case highlights the importance of recognizing RCVS as a potential complication of blood transfusions, particularly in patients with significant comorbidities. Understanding the possible mechanisms, including rapid hemoglobin correction, and the effects of residual plasma and storage lesions in transfused blood, is essential to prevent and manage this rare but serious condition.
Co‐Existing Non‐Occlusive Splenic Vein and Superior Mesenteric Vein Thrombosis in an Acute Necrotic Pancreatitis Patient—A Case Report
Authors: Ghiță Andreea Irina , Gheorghe Arina Ilinca , Beteringhe Georgiana Elena , Treteanu Andreea Ramona , Pahomeanu Mihai Radu 
Published: November 2024

ABSTRACTCase report of a case of acute pancreatitis (AP) at a patient previously known with essential thrombocytosis (ET). The most redoubtable complications of AP in this case were: pancreatic necrosis and splahnic vein thrombosis (SVT). Patient was followed‐up for 3 months with complete resolution of SVT under anticoagulation. As far as we know this is the first case ever published suffering simultaneously from AP and ET, both conditions known for their increased risk of developing thrombi.
High‐Throughput Screening of Co‐Fe‐Ni Electrocatalysts for High‐Current‐Density Water Electrolysis
Authors: Antony Rajini P. , Zerdoumi Ridha , Saddeler Sascha , Krysiak Olga A. , Banko Lars , Ludwig Alfred , Schuhmann Wolfgang 
Published: November 2024

AbstractDeveloping oxygen evolution reaction (OER) catalysts with optimum composition and highly active catalytic centres is a challenge during electrode scale‐up. We show a selection strategy for the optimum composition of Co‐Fe‐Ni catalyst systems through a scanning droplet cell‐based high‐throughput screening on thin‐film materials libraries, followed by fabrication and testing of the selected compositions in the form of catalyst‐coated porous electrodes for the OER in alkaline media. The electrode with optimum composition (Co17Fe25Ni58_Ni foam) exhibits a high current density of 1 A cm−2 during water electrolysis at an operating potential of ∼1.9 V.
In situ techniques for Li‐rechargeable battery analysis
Authors: Lee Seongeun , Park Sangbin , Lee Wontae , Seok Jangwhan , Kim Jae‐Uk , Kim Jongsoon , Yoon Won‐Sub 
Published: November 2024

AbstractReducing our carbon footprint is one of the most pressing issues facing humanity today. The technology of Li‐rechargeable batteries is permeating every corner of our lives as a result of our efforts to reduce the use of carbon energy. Batteries can be seen metaphorically as “living cells”, and approaching the future of that technology requires observing and understanding the real‐time phenomena that occur inside battery systems during (electro)chemical reactions. In this regard, in situ analysis techniques have made significant progress toward understanding the basic science of battery systems and finding better performance‐improving factors. There are various analysis methods utilizing electromagnetic waves, electrons, and neutrons to perform multifaceted analyses of battery systems from the atomic to the macroscopic scale. Now is the opportune moment to construct a comprehensive guide that facilitates the design of advanced Li‐rechargeable battery systems, adopting a highly discerning and all‐encompassing approach toward these cutting‐edge technologies. In this review article, we discuss and organize the key components such as capabilities, limitations, and practical tips with a comprehensive perspective on various in situ techniques. Moreover, this article covers a wide range of information from the nano to the micrometer scale, such as electronic, atomic, crystal, and morphological structures, from stereoscopic perspectives considering the probing depth.
Critical Evaluation of Childs Method for the NMR Spectroscopic Scaling of Effective Lewis Acidity: Limitations and Resolution of Earlier Discrepancies
Authors: Erdmann Philipp , Schmitt Manuel , Janus Lara , Greb Lutz 
Published: November 2024

AbstractQuantifying Lewis acidity is essential for understanding and optimizing the performance of Lewis acids in diverse applications. Next to the widely accepted Gutmann‐Beckett (GB) method, using triethyl phosphine oxide (TEPO) as a probe, the Childs method—employing trans‐crotonaldehyde (TCA)—gained attention as an NMR‐based technique for measuring effective Lewis acidity (eLA). Despite its steady use, the robustness of Childs method and its correlation with other measures remain underexplored. Previous comparisons between the GB and Childs scales revealed significant discrepancies, suggesting that hard and soft acid/base (HSAB) characteristics may be operative. In this study, we compare thermodynamic data for TCA binding to 117 Lewis acids (representing global Lewis acidity, gLA) with their corresponding NMR‐induced chemical shifts in TCA. Our findings showcase notable deviations that reinforce key distinctions between eLA and gLA perspectives. Moreover, we identify significant limitations in the Childs method. First, the weak donor strength of TCA limits its applicability to only the strongest Lewis acids. Second, the exposed protons of TCA are prone to secondary interactions, obscuring the measurement of true Lewis acidity. Finally, our analysis reconciles discrepancies, refuting earlier assumptions that these arise from HSAB effects.
Nickel‐Catalyzed O‐Arylation of N‐Protected Amino Alcohols with (Hetero)aryl Chlorides
Authors: Morrison Kathleen M. , Jackson Emily C. , Elliott Erika M. H. , Stradiotto Mark 
Published: November 2024

AbstractThe aryloxyamine motif is a prominent pharmacophore in drug design and development. While these biologically relevant structures could in principle be sustainably assembled from the base metal‐catalyzed O‐arylation of inexpensive and abundant amino alcohols with (hetero)aryl chlorides, reports of such challenging C−O bond formations with useful scope are lacking. In response, we report herein the hitherto unknown Ni‐catalyzed C−O cross‐coupling of N‐protected amino alcohols (primary, secondary, and tertiary) with (hetero)aryl chlorides. Also presented are chemoselective sequential/telescoped C−N and C−O cross‐couplings of the unprotected amino alcohol prolinol to afford an unsymmetrical diarylated product.
The gut microbiota‐derived metabolite indole‐3‐propionic acid enhances leptin sensitivity by targeting STAT3 against diet‐induced obesity
Authors: Wang Zhiwei , Yang Shaying , Liu Liangju , Mao Aiqin , Kan Hao , Yu Fan , Ma Xin , Feng Lei , Zhou Tingting 
Published: November 2024

AbstractObesity is associated with the gut microbiome. Here, we report that gut commensal Clostridia bacteria regulate host energy balance through the tryptophan‐derived metabolite indole‐3‐propionic acid (IPA). IPA acts as an endogenous leptin sensitiser to counteract obesity. Mechanistically, IPA is secreted from the gut into the circulation, and then targets to the STAT3 in the hypothalamic appetite regulation centre, promoting its phosphorylation and nuclear translocation, which enhances the body's response to leptin, and regulates the balance between appetite and energy metabolism. The in vitro pull‐down assays involving site‐directed mutagenesis demonstrate that Trp623 in the SH2 domain is the key binding site for STAT3‐IPA interaction. High‐fat diet (HFD), rather than genetic factors, induces excessive secretion of antimicrobial peptides by Paneth cells, inhibiting the growth of Clostridia in the gut and resulting in decreased production of the beneficial metabolite IPA. IPA or Clostridium sporogenes supplement effectively controls weight gain, improves glucose metabolism, and reduces inflammation in DIO mice. IPA fails to achieve such effects in ob/ob mice, while exogenous leptin administration restores the therapeutic effect of IPA. Our study suggests that the IPA‐based gut‐brain axis regulates host metabolism, and supplementation with microbiome‐derived IPA could be a promising intervention strategy for treating obesity.
NLRP3 activation maintains intestinal epithelial barrier and reduces liver injury in alcoholic liver disease mice
Authors: Li Shi‐Qing , Wang Ya‐Ru , Xie Zhong‐Liang , Wang Yan , Feng Zi‐Han , Xu Jian‐Hao , Yuan Bing , Zhang Yi‐Tong , Yang Guan , Wang Jing‐Lin , Yuan Yuan 
Published: November 2024

AbstractBackgroundAlcoholic liver disease (ALD) patients with bacterial infections usually exhibit high mortality rates. Infections frequently involve bacteria such as Vibrio vulnificus and Enterococcus faecalis. Nevertheless, the mechanisms predisposing ALD patients to bacterial infections and the role of the NLRP3 inflammasome in the intestinal epithelial barrier in ALD remain unclear.MethodsWe established ALD mice models of WT, Nlrp3−/− and Gsdmd−/− through chronic alcohol consumption feeding and acute alcohol induction. We compared alterations in gut microbiota, ileitis, and adhesion protein expression, to analyze the role and potential mechanism of NLRP3 in the early onset of ALD. Concurrently, we examined the changes in inflammation and liver damage in the ileum of ALD and healthy mice following foodborne infection with V. vulnificus.ResultsCompared with the control group, the expression levels of ZO‐1, Claudin‐1 and E‐cadherin were reduced in the ileum of ALD mice, while those of NLRP3, caspase‐1(p20), GSDMD‐N and IL‐1β were elevated. Nlrp3−/− and Gsdmd−/− ALD mice showed an increased gut bacterial load, decreased ileal expression of E‐cadherin, more severe ileitis, pronounced liver damage, steatosis and higher plasma levels of FITC‐dextran, D‐LA and ZO‐1 compared with WT mice. Notably, Nlrp3−/− ALD mice exhibited a higher presence of Deferribacterota and Enterobacteriaceae. Furthermore, ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.ConclusionsThis study indicated that NLRP3 activation in the ileum of ALD mice stabilizes the inflammation‐related gut microbiota, preserves the intestinal epithelial barrier, and diminishes inflammation and liver injury. Furthermore, the compromised immune defence in ALD mice may contribute to their heightened susceptibility to bacterial pathogens.Key points
Activation of the NLRP3‐GSDMD pathway in the ileum of Alcoholic liver disease (ALD) mice.
NLRP3 activation maintains homeostasis of gut microbiota and intestinal epithelial barrier in ALD mice.
ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.
Insights of the Population Structure and Breeding Biology of a Xanthid Crab Etisus laevimanus Randall, 1840, on the Rocky Intertidal Region of the Gujarat Coast
Authors: Shrimali Bhavesh R. , Patel Krupal J. , Patel Ashish , Sahoo Dipak Kumar , Shrahili Mansour , Ansari Mohammad Javed , Trivedi Jigneshkumar N. 
Published: November 2024

ABSTRACTThe population structure and breeding biology of a Xanthid crab, Etisus laevimanus Randall, 1840, a commonly occurring species on the rocky intertidal region of Saurashtra coast of Gujarat State, India, were investigated. Samples were collected from the intertidal region for 12 consecutive months during low tide using catch per unit effort in a 500 m2 area. The individuals were categorized into male, non‐ovigerous female, or ovigerous female. For fecundity estimation, the total number of eggs, size of eggs, and weight of egg mass were measured along with the carapace width and body weight of the respective ovigerous females. Sexual dimorphism was evident in the collected samples, with males being significantly larger than females. The overall as well as monthly sex ratio was female‐biased. Size frequency distribution showed a bimodal frequency distribution in males while being unimodal in females. The occurrence of ovigerous females throughout the year suggests that the species has a continuous breeding pattern with peaks from December to April. The total number of eggs, size of eggs, and weight of the egg mass showed a significantly positive correlation with the carapace width of the ovigerous females.
Effect of Host Pupae Cryogenic, Anesthesia, Parasitoid‐to‐Host Ratios to Scleroderma sichuanensis the Percentage Parasitism and Numbers of Output
Authors: Zheng Jiangwei , Li Ke , Li Wei , Xia Wensheng , Zhao Yao , Liu Tao , Peng Yu 
Published: November 2024

ABSTRACTBiological control is one of the effective means of controlling forestry burrowing pests in a low‐cost and efficient way. Scleroderma sichuanensis, an ectoparasitic wasp, exhibits significant potential in managing burrowing pests. Currently, the mealworm Tenebrio molitor pupae are mainly used to many insects large‐scale indoor breeding of diet. Therefore, this study focused on the effects of cryogenically treated the mealworm T. molitor pupae for different times and anesthesia treatment on the percentage parasitism and the number of emergence of S. sichuanensis, optimum parasitism and emergence were achieved in the wasp with a parasitoid‐to‐host ratio of 2:1, anesthesia treatment of T. molitor pupae with ethyl ether fumigation for 1.5 h, and cold treatment of them at a temperature of −10°C. As a result, various methods of treating T. molitor pupae indoors were explored, and optimal conditions for indoor rearing were explored for the expansion of S. sichuanensis.
Short Communication: Ultralow Voltage Electrokinetic Particle Trapping in DC‐iEK Devices Using 9 V Alkaline Batteries as Power Supply
Authors: Santos‐Ramirez J. Martin de los , Martinez‐Gonzalez Vania G. , Mendiola‐Escobedo Carlos A. , Cotera‐Sarabia Jose M. , Gallo‐Villanueva Roberto C. , Martinez‐Duarte Rodrigo , Perez‐Gonzalez Victor H. 
Published: November 2024

ABSTRACTThis contribution describes direct current insulator‐based electrokinetic (DC‐iEK) microfluidic devices stimulated by 9 V alkaline batteries for the trapping of 2‐µm diameter fluorescent polystyrene particles. These devices featured two triangular insulating posts within the fluidic channel. Particle trapping was clearly observed at 18 V (two 9 V batteries connected in series), but only intermittent particle trapping was observed with a single 9 V battery. Particle trapping was determined by measuring the increase in relative fluorescence intensity at the gap region between the single pair of triangular posts. Results demonstrate that the use of low stimulating voltages (deemed as ultralow) in DC‐iEK systems may be more suitable for accurate and precise electrokinetic characterization of particles—by exhibiting a very well‐localized trapping region with negligible particle oscillations therein, respectively—than for high‐performance and high‐throughput particle manipulation (i.e., concentration, separation, filtering, or isolation).