bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microrobotic System Based on Engineered Bacteria for Targeted Self‐Driven Photodynamic Therapy
Authors: Jin Kai , Yu Lin , Zhang Yue , Niu Luqi , Huang Yi , Zhang Yong , Wu Yihan
Published: November 2024

Photodynamic therapy (PDT) has been used clinically to treat superficial tumors for decades. However, its effectiveness against deep‐seated tumors has been limited by the inefficient delivery of the key components ‐light, photosensitizer, and oxygen‐ required for the photochemical reactions in PDT. Here, we present a novel platform that enables the photochemical reaction to occur in a self‐driven manner, eliminating the need for external delivery of these components and instead orchestrating their endogenous generation within tumors. This was achieved by genetically modifying probiotic Escherichia coli to host three modules ‐ Lux, Hem1, and KatG ‐ responsible for light production, photosensitizer biosynthesis, and oxygen generation, respectively. The system is self‐driven, relying solely on substrates within E. coli cells and tumors. The modules exhibited prolonged activity for days within in vivo mouse models, enabling metronomic PDT that induced an immune response. This research holds promise for revolutionizing PDT and overcoming the enduring challenges encountered in its application for treating deep‐seated tumors.
Anomeric Amide‐Enabled Alkene‐Arene and Alkene‐Alkene Aminative Coupling
Authors: Stein Colin , Tyler Jasper L. , Wiener Julius , Boser Florian , Daniliuc Constantin G. , Glorius Frank
Published: November 2024

Despite the prominence of C−N bond forming cross‐coupling reactions as a strategy to assemble molecular fragments, aminative coupling approaches, in which two fragments are assembled directly at the heteroatom, represents a rarely exploited retrosynthetic strategy. Herein, we report the design, synthesis, and implementation of an anomeric amide reagent capable of promoting highly regioselective aminative alkene‐arene and alkene‐alkene coupling reactions. This transformation follows a sequence of catalyst‐free chloroamination, N‐deprotection, and formal nitrene functionalization, all in one‐pot. Due to the simplicity of both the protocol and the building blocks required, high‐throughput experimentation (HTE) was employed, in combination with a full‐scale scope, to rapidly and efficiently explore a wide range of chemical space and determine the limits of reactivity. In addition, alternative reactivity modes from the functionalized intermediates delivered by this protocol demonstrate the divergent nature of this aminative coupling strategy.
Self‐Assembled Monolayer in Hybrid Quasi‐Solid Electrolyte Enables Boosted Interface Stability and Ion Conduction
Authors: Ma Wenyi , Guo Yuxiang , Sun Jianqi , Zhang Chenyi , Zhu Yuwen , Sun Hengda , Huang Liqiang , Hu Zuming , Wang Hongzhi , Zhu Meifang , Wang Gang
Published: November 2024

Complex interactions between the inorganic solid electrolyte (ISE) and the liquid electrolyte (LE) give rise to challenges of achieving durable interface stability in hybrid quasi‐solid electrolytes (HQSE), and the influence on the involved ISE surface ionic conductivity also needs to be investigated. Here, 4‐chlorobenzenesulfonic acid (CBSA) is utilized to establish a self‐assembled monolayer (SAM) on the surface of Li6.4La3Zr1.4Ta0.6O12 (LLZTO), which is then incorporated into PEGDA‐based in situ polymerized HQSE. The results show that the introduction of CBSA significantly improves the LLZTO/LE interface stability with the optimized solvation structure, resulting in a favorable ionic conductivity (1.19 mS⋅cm−1) and an increasing Li+ transference number (0.647). Mechanisms for the promotion of ionic conduction and interfacial stability of SAM‐HQSE are unveiled through the density functional theory (DFT) combined with Raman spectra and 7Li solid‐state nuclear‐magnetic‐resonance. There are no short‐circuits in the Li|SAM‐HQSE|Li cells after 1000 h. The LFP|SAM‐HQSE|Li cells or LFP|SAM‐HQSE|Graphite pouch cells respectively achieve the capacity retention of 91.2 % and 87.0 % with the 0.5.C‐rate for 500 and 300 cycles. This facile and effective strategy proposed in this work make it accessible for constructing the stable surface micro‐environments of LLZTO where boost and homogenize the Li+ conduction in a hybrid quasi‐solid electrolyte system.
Aggregation Induced Emission Based Luminogenic (AIEgenic) Probes for the Biomarker Detection
Authors: Ghosh Saurajit , Adhikari Subhendu , Sarathi Addy Partha
Published: November 2024

Various biomarkers such as proteins play key roles in controlling crucial biochemical processes. The critical concentration of the biomarkers is important to maintain a healthy life. In fact, imbalance in concentration or irregular activity of these can lead to various diseases like Cancer, Alzheimer's etc. Therefore, the disease related biomarkers and their timely detection are key to control the illness. In the literature, a few activity‐based probes for the detection of such biomarkers are available. As per the requirement an ideal probe should be very specific to recognize the target analyte and that could be achieved by virtue of having a robust structure and stimuli responsive nature. In this regard, several fluorescent probes are of great choice. Although these fluorescent probes face certain challenges such as aggregation caused quenching, which heavily affects the sensitivity and photostability is another major concern for many fluorescent probes. To overcome these challenges aggregation‐induced emissive fluorescent probes found to be an excellent alternative. Aggregation induced emissive luminogens (AIEgens) offer higher signal to noise ratios and found to possess better photostability during sensing and imaging. In the present review we have summarized the development of AIEgenic probes for sensing and imaging of disease related biomarkers. We believe this review could be a guide to design efficient AIEgenic probes for the diagnostics development.
Research Progress of Superhydrophobic Coatings Constructed by Arrayed and Non‐Arrayed Carbon Nanotubes for Anti‐Corrosion, Anti‐Icing and Photothermal De‐Icing
Authors: Hao Xiaoru , Xu Longxiang , Cheng Zhihao , Ji Haowen , Dang Chaobin , Zheng Haikun
Published: November 2024

The preparation methods of superhydrophobic nanocomposite surfaces based on carbon nanotubes are reviewed in view of the different arrangement accuracy and various performance differences of the preparation methods of superhydrophobic surfaces of arrayed and non‐arrayed carbon nanotubes. The application progress of superhydrophobic surfaces of non‐arrayed carbon nanotubes in the fields of anti‐corrosion, anti‐icing and photothermal de‐icing is introduced. On the basis of summarizing the basic preparation methods and properties of carbon nanotubes, the advantages of carbon nanotubes as superhydrophobic surface materials are clarified. By analyzing and comparing the preparation methods of superhydrophobic surface of arrayed carbon nanotubes and non‐arrayed carbon nanotubes, it is concluded that the superhydrophobic surface of arrayed carbon nanotubes has some shortcomings compared with the superhydrophobic surface of non‐arrayed carbon nanotubes. The superhydrophobic surface of non‐arrayed carbon nanotubes offers advantages such as excellent long‐term durability and unique functionality, which will become the focus of research on the preparation of superhydrophobic surfaces based on carbon nanotubes. This will provide guidance for future research on the large‐scale preparation of such surfaces.
Catalytic Advancements in NH3 Selective Catalytic Oxidation: The Impact of Cu‐Induced Lattice Distortion in TiO2 Crystal Structure
Authors: Liu Jun , Long Jisheng , Ge Shiwei , Bai Li , Xing Jiaying , Du Hailiang , Song Weiwei , Liu Xiaoqing , Chen Jianjun , Li Junhua
Published: November 2024

A series of x Cu‐TiO2 obtained from the sol‐gel method were tested for NH3 selective catalytic oxidation (NH3‐SCO). Its performance was higher than that of supported Cu/TiO2‐Im and solvent‐free Cu/TiO2‐SF. The catalyst exhibits better water resistance at 300 °C. XRD, Raman, and H2‐TPR proved that the crystal lattice of TiO2 was deformed by Cu doping, which increased the specific surface area of the catalyst. The dispersion of the Cu component is further enhanced. The enhancement of redox potential was the key to improving catalytic activity. The NH3‐TPD results prove that more acidic sites promote more active NH3 species being adsorbed and dissociated on the catalyst surface. The in‐situ DRIFTs results certify that the NH3 species adsorbed on the Lewis acid sites were easier to consume than those on the Brønsted acid sites. The DFT theoretical calculation demonstrates that the doped Cu promotes the TiO2 conduction band to move closer to the Fermi level and enhances the redox performance of the catalyst. The results suggest that the Cu‐TiO2 catalyst was a potential catalyst under actual working conditions, which would provide a technological reserve for the development and diffusion of ammonia slip for both mobile and fixed sources.
Focal therapy of prostate cancer: Use of artificial intelligence to define tumour volume and predict treatment outcomes
Authors: Brisbane Wayne G. , Priester Alan M. , Nguyen Anissa V. , Topoozian Mark , Mota Sakina , Delfin Merdie K. , Gonzalez Samantha , Grunden Kyla P. , Richardson Shannon , Natarajan Shyam , Marks Leonard S.
Published: November 2024

Objectives

The aim of this study is to evaluate new software (Unfold AI) in the estimation of prostate tumour volume (TV) and prediction of focal therapy outcomes.

Subjects/patients and methods

Subjects were 204 men with prostate cancer (PCa) of grade groups 2–4 (GG ≥ 2), who were enrolled in a trial of partial gland cryoablation (PGA) at UCLA from 2017 to 2022. Magnetic resonance imaging (MRI)‐guided biopsy (MRGB) was performed at diagnosis and at 6 and 18 months following PGA. Utilising Unfold AI (FDA‐cleared 2022), which generates a 3D map of GG ≥ 2 PCa margins, we retrospectively estimated TV for each patient. TV was compared against conventional baseline variables as a correlate of a successful primary outcome—defined here as the absence of GG ≥ 2 on follow‐up MRGB at 6 months. Secondary outcomes were MRGB at 18 months and failure‐free survival, that is, lack of metastasis or salvage whole gland therapy. Receiver operating curves and multivariate analysis were used to determine significance.

Results

A successful primary outcome was observed in 77.7% of patients. Significant correlates of a successful ablation were percent pattern 4 and TV; areas under the curve (AUCs) were 0.60 and 0.73, respectively. GG was not a correlate of success (AUC = 0.51). A TV of 1.5 cc provided the optimal combination of sensitivity (55.8%) and specificity (85.7%) at 6 months. TV was also significantly associated with secondary outcomes. In multivariate analysis, TV was the variable most associated with 6‐ and 18‐month biopsy success (adjusted odds ratios [aORs] were 6.1 and 4.2). Utilising TV ≤ 1.5 cc as a PGA criterion would have prevented 72% of failures at the cost of 42% of successes.

Conclusion

The AI‐based software Unfold AI estimates TV, which is significantly associated with biopsy outcomes after focal cryoablation. The rate of treatment success is inversely related to TV.
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

The 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

Background

Pancreatic 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.

Methods

We 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.

Results

Significantly 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.

Conclusions

Met 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

Background

The 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.

Methods

This 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.

Results

After 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.

Conclusion

Our 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

Cell‐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

Reversible 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

Case 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

Developing 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

Reducing 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

Quantifying 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

The 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

Obesity 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

Background

Alcoholic 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.

Methods

We 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.

Results

Compared 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.

Conclusions

This 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

The 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

Biological 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

This 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).
An Interactive Computational Pipeline to Investigate Ventricular Hemodynamics with Real‐Time Three‐Dimensional Echocardiography and Computational Fluid Dynamics
Authors: Thiel Jan‐Niklas , Verhülsdonk Daniel , Steinseifer Ulrich , Linden Katharina , Herberg Ulrike , Friehs Ingeborg , Diaz‐Gil Daniel , Neidlin Michael
Published: November 2024

Blood flow within the ventricle can provide important information on the performance of the heart. The determined blood flow structures are used to extract flow biomarkers to quantify cardiac function. Patient‐specific computational fluid dynamics (CFD) models that import segmented ventricular deformations from noninvasive imaging data for an individualized hemodynamical analysis are often used. However, tedious preprocessing of those geometries is often necessary and decisions on the modeling of the valve and the surrounding vessels have to be made on an individual level. This leads to a lack of reproducibility and usability of the existing computational models. In this work, we introduce IP‐HEART—an interactive and open‐source computational pipeline to perform geometry processing for CFD models of ventricular blood flow. We showcase its use on real‐time three‐dimensional echocardiography data of three patient datasets from two different clinical centers. We outline how different modeling assumptions of the mitral valve can be implemented and quantify their effect on CFD simulations. The results correspond well with clinical data on transvalvular Doppler ultrasound recordings and distinct flow features such as mitral jet and diastolic vortex formation can be observed. The pipeline is accompanied by an extensive video tutorial and freely available code for further use.
Epigenetic Modeling of Jumping Translocations of 1q Heterochromatin in Acute Myeloid Leukemia After 5'‐Azacytidine Treatment
Authors: Lema Fernandez Anair Graciela , Nardelli Carlotta , Pierini Valentina , Crescenzi Barbara , Pellanera Fabrizia , Matteucci Caterina , Crocioni Maria , Arniani Silvia , Di Battista Valeria , Quintini Martina , Mondanelli Giada , Orabona Ciriana , Gorello Paolo , Mecucci Cristina
Published: November 2024

Jumping translocations (JT) are rare cytogenetic abnormalities associated with progression in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Typically, a tri–tetra‐somic 1q chromosome is translocated to two or more recipient chromosomes. In multiple myeloma JT were shown to originate after DNA demethylation and decondensation. Using epigenomics, we investigated sequential samples in an SRSF2‐mutated MDS and AML cohort with normal karyotype at diagnosis and 1qJT at disease evolution after 5′‐azacytidine (AZA). 1qJT breakpoints fell within repetitive DNA at both 1q12 and the translocation partners, namely acrocentrics n. 14, 15, 21, and 22, chromosome 16, and chromosome Y. The global methylome at diagnosis showed hypermethylation at 61% of the differentially methylated regions (DMRs), followed by hypomethylation at 80% of DMRs under AZA, mostly affecting pathways related to immune system, chromatin organization, chromosome condensation, telomere maintenance, rRNA, and DNA repair. At disease evolution, a shift toward hypermethylation, intronic enhancers enrichment and epigenetic involvement of the PI3K/AKT and MAPK signaling emerged. In particular, AKT1 phosphorylation behaved as a hallmark of the progression. Overall, we provided new insights on the characterization of 1qJT in SRSF2‐mutated myeloid neoplasms and first showed that epigenetics is a powerful tool to investigate the molecular landscape of repetitive DNA rearrangements.
LncRNA SNHG14 Facilitates Cisplatin Resistance Through Upregulating Notch2 via Binding to U2AF2 in Nasopharyngeal Carcinoma
Authors: Yan Sijia , Zhang Puhua , Tan Shuai , Mo Haiyun , Yang Yanlin
Published: November 2024

Background

Cisplatin (DDP) is one of the commonly used chemotherapeutic drugs for nasopharyngeal carcinoma (NPC) patients, and the resistance of tumor cells to cisplatin is main obstacle for NPC treatment. This study explored effect and possible mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on drug resistance of NPC cells to cisplatin.

Methods

Levels of SNHG14 and Notch2 in NPC tissues and cells were confirmed using RT‐qPCR. Western blot detected Notch2 and ABCB1 expression in NPC cells. IC50 of cisplatin‐treated NPC cells was tested utilizing 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). Cell proliferation and apoptosis were evaluated utilizing colony formation experiment and flow cytometry, respectively. RNA immunoprecipitation (RIP) assay was utilized to validate the target genes of U2AF2. Notch2 mRNA stability was tested using actinomycin D.

Results

SNHG14 level was increased in both cisplatin‐resistant NPC tissues and cell lines. SNHG14 silencing in HNE1/DDP cells resulted in inhibition of chemoresistance to cisplatin. Conversely, upregulation of SNHG14 in HNE1 cells enhanced their resistance to cisplatin. SNHG14 exhibited an interaction with U2AF2, leading to stabilization of Notch2 mRNA. Finally, Notch2 was involved in SNHG14‐mediated cisplatin resistance in NPC cells.

Conclusion

Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.
Inflammatory pathways and anti‐inflammatory therapies in sickle cell disease
Authors: Tozatto‐Maio Karina , Rós Felipe A. , Weinlich Ricardo , Rocha Vanderson
Published: November 2024

Sickle cell disease (SCD) is a monogenic disease, resulting from a single‐point mutation, that presents a complex pathophysiology and high clinical heterogeneity. Inflammation stands as a prominent characteristic of SCD. Over the past few decades, the role of different cells and molecules in the regulation of the inflammatory process has been elucidated. In conjunction with the polymerization of hemoglobin S (HbS), intravascular hemolysis, which releases free heme, HbS, and hemoglobin‐related damage‐associated molecular patterns, initiates multiple inflammatory pathways that are not yet fully comprehended. These complex phenomena lead to a vicious cycle that perpetuates vaso‐occlusion, hemolysis, and inflammation. To date, few inflammatory biomarkers can predict disease complications; conversely, there is a plethora of therapies that reduce inflammation in SCD, although clinical outcomes vary widely. Importantly, whether the clinical heterogeneity and complications are related to the degree of inflammation is not known. This review aims to further our understanding of the roles of main immune cells, and other inflammatory factors, as potential prognostic biomarkers for predicting clinical outcomes or identifying novel treatments for SCD.
Disparities in childhood leukemia survival for Asian, Native Hawaiian, and Pacific Islanders in the United States
Authors: Hashibe Mia , Herget Kimberly A. , Schiffman Joshua D. , Chang Vivian Y.
Published: November 2024

While some previous studies disaggregated the Asian, Native Hawaiian, and Pacific Islander (ANHPI) population to investigate survival for childhood leukemia, further studies are needed to understand the differences between subpopulations. The aim of our study was to estimate 5‐year relative survival for patients with childhood leukemia and to investigate disparities in prognostic factors with disaggregation of the ANHPI population. We used the Surveillance, Epidemiology, and End Results Program 17 database and included 1881 ANHPI patients with childhood leukemia and 8772 non‐Hispanic White (NHW) patients with childhood leukemia. The Cox proportional hazards model was used to estimate hazard ratios for the risk of death. We observed lower 5‐year relative survival rates for Southeast Asian and East Asian compared to NHW patients with childhood leukemia for acute lymphoid leukemia (ALL). The survival rates were higher for patients diagnosed at 1–9 years of age, more recent years of diagnosis, and patients residing in urban areas. The risk of death was 42% higher for East Asian patients and 50% higher for Southeast Asian patients compared to NHW patients for childhood ALL. For prognostic factors among East Asian patients with childhood leukemia, higher risks of death were observed for patients diagnosed at <12 months old and for acute myeloid leukemia compared to ALL. Further studies are needed to elucidate the reasons behind the disparities in survival rates for Southeast Asian and East Asian patients with childhood leukemia, including socioeconomic and genetic contributions to leukemia risk and clinical responses to different therapeutic modalities.
Does Algorithmic Trading Induce Herding?
Authors: Fu Servanna Mianjun , Alexakis Christos , Pappas Vasileios , Skarmeas Emmanouil , Verousis Thanos
Published: November 2024

Algorithmic trading (AT) plays a major role in the trading activities of developed markets. This research breaks new ground by investigating how AT influences herding behaviour in stock markets. Utilising the implementation of the Markets in Financial Instruments Directive (MiFID II), we show that AT‐induced herding is quantitatively 14 times more pronounced compared to herding triggered by non‐AT elements. Algorithmic traders herd more when international volatility and market uncertainty are high, revealing a heightened sensitivity to global market signals. However, during periods of high local volatility, AT seems to disregard these fluctuations, indicating an ‘inattention effect’. AT‐induced anti‐herding is prominent in the volatile aggressive stocks, while no such behaviour is observed in the more stable defensive stocks. The findings carry critical implications for both regulators and market professionals, as we uncover dual behaviours of AT‐induced herding and anti‐herding in varying market conditions.
Texture Analysis of Fibrous Meningioma Using Label‐Free Multiphoton Microscopy
Authors: Fang Na , Shi Linjing , Su Xiaoli , Chen Rong , Hu Liwen , Li Lianhuang , Wang Xingfu , Wu Zanyi , Chen Jianxin
Published: November 2024

Fibrous meningiomas, a common type of brain tumor, present surgical challenges due to their variable hardness, which is crucial for complete resection and patient prognosis. This study explores the use of label‐free multiphoton microscopy (MPM) for the objective assessment of the texture of fibrous meningiomas. Fresh tumor samples from 20 patients were analyzed using both multichannel and lambda mode MPM, with quantitative image analysis algorithms determining collagen content and multi‐peak spectral fitting providing additional optical collagen metrics. The study compared medium and hard fibrous meningiomas, utilizing receiver operating characteristic analysis to evaluate predictive performance. Microstructural features were clearly visualized, enabling accurate diagnosis. Collagen‐related parameters significantly differentiated between moderate and hard tumors (p < 0.05). High predictive values were observed for collagen content, collagen‐to‐NADH‐free ratio, and collagen‐to‐FAD ratio (AUC = 0.748–0.839). A multivariate logistic model combining these biomarkers significantly improved diagnostic accuracy (AUC = 0.907). The findings suggest that MPM, with its ability to visualize and quantify microstructures such as collagen and cells without the need for staining, holds strong potential for rapid, objective, and accurate assessment of tumor texture during neurosurgery. The integration of MPM with multiphoton endoscopy paves the way for potential in vivo applications in the future.