bluuebunny/crossref_metadata_2025 huggingface dataset:
PARP inhibitors enhance antitumor immune responses by triggering pyroptosis via TNF–caspase 8–GSDMD/E axis in ovarian cancer
Authors: Xia Yu , Huang Pu , Qian Yi-yu , Wang Zanhong , Jin Ning , Li Xin , Pan Wen , Wang Si-Yuan , Jin Ping , Drokow Emmanuel Kwateng , Li Xiong , Zhang Qi , Zhang Zhengmao , Li Pingfei , Fang Yong , Yang Xiang-Ping , Han Zhiqiang , Gao Qing-lei
Published: October 2024

Background

In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses.

Methods

To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 editedGsdme−/−ID8 tumor cells into C57BL/6 mice.

Results

Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1–caspase 8 cascade. Impeding pyroptosis through the depletion ofGsdmesignificantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model.

Conclusions

PARPis induce a specific type of ICD called pyroptosis via TNF–caspase 8–GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions.

Trial registration number

NCT04507841.
Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control
Authors: Detrés Román Carlos R , Erwin Megan M , Rudloff Michael W , Revetta Frank , Murray Kristen A , Favret Natalie R , Roetman Jessica J , Roland Joseph T , Washington Mary K , Philip Mary
Published: October 2024

Background

Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiated in mice with early sporadic lesions as compared with late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, impact TST function and liver cancer progression.

Methods

Mice with a germline floxed allele of the SV40 large T antigen (TAG) undergo spontaneous recombination and activation of the TAG oncogene, leading to rare early cancerous TAG-expressing lesions that inevitably progress to established liver cancer. We assessed the immunophenotype (CD44, PD1, TCF1, and TOX expression) and function (TNFα and IFNγ cytokine production) of tumor/TAG-specific CD8 T cells in mice with early and late liver lesions by flow cytometry. We vaccinated mice, either alone or in combination with ICB, to test whether these immunotherapeutic interventions could stop liver cancer progression and improve survival.

Results

In mice with early lesions, a subset of TST were PD1+TCF1+TOX−and could produce IFNγ while TST present in mice with late liver cancers were PD1+TCF1lo/−TOX+and unable to make effector cytokines. Strikingly, vaccination with attenuated TAG epitope-expressingListeria monocytogenes(LMTAG) blocked liver cancer development and led to a population of TST that were PD1-heterogeneous, TCF1+TOX−and polyfunctional cytokine producers. Vaccine-elicited TCF1+TST could self-renew and differentiate, establishing them as progenitor TST. In contrast, ICB administration did not slow cancer progression or improve LMTAGvaccine efficacy.

Conclusion

Vaccination, but not ICB, generated a population of functional progenitor TST and halted cancer progression in a clinically relevant model of sporadic liver cancer. In patients with early cancers or at high risk of cancer recurrence, immunization may be the most effective strategy.
Toripalimab in combination with HBM4003, an anti-CTLA-4 heavy chain-only antibody, in advanced melanoma and other solid tumors: an open-label phase I trial
Authors: Tang Bixia , Chen Yu , Jiang Yu , Fang Meiyu , Gao Quanli , Ren Xiubao , Yao Li , Huang Gang , Chen Jing , Zhang Xiaoshi , Li Rongqing , Zhao Shuai , Gao Meijuan , Luo Ruixuan , Qi Meng , Li Feng , Zheng Fei , Lee Michael , Tao Xiaolu , Duan Rong , Guo Jun , Chi Zhihong , Cui Chuanliang
Published: October 2024

Background

HBM4003 is a novel anti-CTLA-4 heavy chain-only antibody, designed to enhance Treg ablation and antibody-dependent cell-mediated cytotoxicity while ensuring a manageable safety profile. This phase I trial investigated the safety, pharmacokinetics, immunogenicity and preliminary efficacy of HBM4003 plus with anti-PD-1 antibody toripalimab in patients with advanced solid tumors, especially focusing on melanoma.

Methods

The multicenter, open-label phase I trial was divided into two parts: dose-escalation phase (part 1) and dose-expansion phase (part 2). In part 1, HBM4003 was administered at doses of 0.03, 0.1, 0.3 mg/kg in combination with toripalimab with fixed dosage of 240 mg every 3 weeks. The recommended phase II dose (RP2D) was used in the expansion phase. Primary endpoints were safety and RP2D in part 1 and objective response rate (ORR) in part 2. Biomarkers based on cytokines and multiplex immunofluorescence staining were explored.

Results

A total of 40 patients received study treatment, including 36 patients treated with RP2D of HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week. 36 participants (90.0%) experienced at least one treatment-related adverse event (TRAE), of which 10 (25.0%) patients experienced grade ≥3 TRAEs and 5 (12.5%) experienced immune-mediated adverse events (irAEs) with maximum severity of grade 3. No grade 4 or 5 irAEs occurred. Efficacy analysis set included 32 melanoma patients treated with RP2D and with available post-baseline imaging data. The ORRs of anti-PD-1/PD-L1 treatment-naïve subgroup and anti-PD-1/PD-L1 treatment-failed subgroup were 33.3% and 5.9%, respectively. In mucosal melanoma, the ORR of the two subgroups were 40.0% and 10.0%, respectively. Baseline high Treg/CD4+ratio in the tumor serves as an independent predictive factor for the efficacy of immunotherapy.

Conclusions

HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week demonstrated manageable safety in solid tumors and no new safety signal. Limited data demonstrated promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma.

Trial registration number

NCT04727164.
Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells
Authors: Qi Changsong , Liu Dongqun , Liu Chang , Wei Xiaofei , Ma Mingyang , Lu Xinan , Tao Min , Zhang Cheng , Wang Xicheng , He Ting , Li Jian , Dai Fei , Ding Yanping , Shen Lin
Published: October 2024

Background

Chimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen for targeted therapy due to its intestinal-restricted expression pattern in normal tissues and steady overexpression in gastrointestinal tumors, especially colorectal cancer. An antigen-sensitive and long-lasting CAR-T cell targeting GUCY2C was investigated in this study.

Methods

Using constructed tumor cell lines with various GUCY2C expression densities, we screened out an antigen-sensitive single chain variable fragment (scFv) that enabled CAR-T cells to efficiently eradicate the GUCY2C lowly expressed tumor cells. CAR-T cells with different compositions of the hinge, transmembrane and costimulatory domains were also constructed for selection of the long-lasting CAR-T format with durable antitumor efficacy in vitro and in tumor-bearing mice. The underlying mechanism was further investigated based on mutation of the hinge and transmembrane domains.

Results

We found that the composition of the antigen-sensitive scFv, CD8α hinge, CD8α transmembrane, and CD28 costimulatory domains boosted CAR-T cells to rapidly kill tumors, maintain high expansion capacity, and long-term efficacy in various colorectal cancer models. The durable antitumor function was attributed to the optimal CAR tonic signaling that conferred CAR-T cells with autonomous activation, proliferation, survival and cytokine release in the absence of antigen stimulation. The tonic signaling was associated with the length and the cysteine residues in the CD8α hinge and transmembrane domains.

Conclusions

This study demonstrated a potent GUCY2C-targeted CAR-T cell for gastrointestinal tumor therapy and highlights the importance of adequate tonic signaling for effective CAR-T cell therapy against solid tumors.
Decoding Continuous Tracking Eye Movements from Cortical Spiking Activity
Authors: Noneman Kendra K. , Patrick Mayo J.
Published: October 2024

Eye movements are the primary way primates interact with the world. Understanding how the brain controls the eyes is therefore crucial for improving human health and designing visual rehabilitation devices. However, brain activity is challenging to decipher. Here, we leveraged machine learning algorithms to reconstruct tracking eye movements from high-resolution neuronal recordings. We found that continuous eye position could be decoded with high accuracy using spiking data from only a few dozen cortical neurons. We tested eight decoders and found that neural network models yielded the highest decoding accuracy. Simpler models performed well above chance with a substantial reduction in training time. We measured the impact of data quantity (e.g. number of neurons) and data format (e.g. bin width) on training time, inference time, and generalizability. Training models with more input data improved performance, as expected, but the format of the behavioral output was critical for emphasizing or omitting specific oculomotor events. Our results provide the first demonstration, to our knowledge, of continuously decoded eye movements across a large field of view. Our comprehensive investigation of predictive power and computational efficiency for common decoder architectures provides a much-needed foundation for future work on real-time gaze-tracking devices.
INVESTIGATION ON THE STRENGTH OF E-GLASS FIBER/AA5052-H32 FIBER METAL LAMINATES CONNECTED USING RIVETED JOINTS
Authors: RAJESH M. ESAI , ESAKKIMUTHU S. , MOSHI A. ARUL MARCEL , LOGESH K.
Published: October 2024

Fiber metal laminates (FMLs) belong to a class of composite materials comprising layers of metal sheets and fiber-reinforced polymers (FRP), configured in a specific sequence. This study investigates the tensile strength of FML specimens joined by riveted joints. FML plates were fabricated using AA5052 aluminium alloy, E-glass fibers, epoxy resin, and layered double hydroxide (LDH) via a hand layup process. The experimental parameters included the pattern of rivets, type of rivet materials, and rivet size. Tensile strength, the output response, was evaluated using Taguchi’s L9 orthogonal array design, followed by testing on a universal testing machine. The main effect plot and 3D surface plots were employed to analyze the tensile test results. Maximum tensile strength was held by the test specimen which was connected by the rivets made up of mild steel. From the ANOVA results presented in Table  6 , it was inferred that the number of rivets used for joining the FML specimens (pattern) played a major role in deciding the tensile strength of the specimens (57.25%). A regression equation, derived from Design Expert software, established the relationship between input variables and the tensile strength of FML specimens. ANOVA was conducted to assess the impact of each process variable on achieving optimal tensile strength.

This research contributes novelty by integrating LDH into FML fabrication and demonstrates practical significance through systematic optimization of riveting parameters to enhance tensile strength. Quantitative and qualitative analyses underscore the effectiveness of the proposed FML configuration, validating its potential for structural applications.
EDM SURFACE ANALYSIS OF MOSI2–SIC INTERMETALLIC CERAMIC COMPOSITE WITH ENHANCED FORM AND ORIENTATION TOLERANCES
Authors: BABU MANIKAM , SELVARAJAN L. , VENKATARAMANAN K. , SENTHILKUMAR T. S.
Published: October 2024

Electrical discharge machining (EDM) was performed on a copper electrode and the implications of changing factors such as current, pulse on time, pulse-off time, spark gap voltage and speed have been investigated in this research. The process used an intermetallic MoSi2–SiC ceramic composite. Multiple performance characteristics, including material removal rate, electrode degradation rate and surface roughness, run out, radial overcut, circularity, cylindricity and perpendicularity were considered when optimizing these parameters using the Taguchi-based [Formula: see text]Orthogonal Array with Design of Experiments (DoE). For this purpose, techniques such as analysis of variance (ANOVA), Response Surface Methodologies (RSM) and graphical analysis were utilized. The outcomes revealed that geometric tolerances were decreased as a consequence of significant improvements in the rates of material removal, tool degradation, form tolerance, and orientation tolerance. The optimal machining settings for producing high-quality holes and electrodes in the conductive MoSi2–SiC composite were determined by scanning electron microscopy (SEM) testing the anomalies of the machined composite for various holes of trials. The experimental results suggest that the precision, presence of microvoids and surface roughness of the copper electrode can be enhanced through selecting an appropriate optimal combination.
MULTIDIRECTIONAL FORGING OF Mg–Zn–Ca BIODEGRADABLE ALLOYS; INVESTIGATING MICROSTRUCTURE, MECHANICAL, AND CORROSION BEHAVIORS
Authors: KUDVA S. ADITYA , ANNE GAJANAN , RAMESH S. , KUMAR PRAKASH , PRASHANTH B. H. MARUTHI , SUDHIR  , PATIL NARAHARI S. , SINGH YASHVARDHAN , YADAV CHANDRA BHUSHAN KUMAR
Published: October 2024

This study examined the microstructural, mechanical, and corrosion behaviors of a multidirectional-forged (MDF) Mg–Zn–Ca alloy. The results showed significant grain refinement of the alloy after 5 passes of the MDF process from 378[Formula: see text][Formula: see text]m to 23[Formula: see text][Formula: see text]m. X-ray diffraction analysis (XRD) revealed the presence of finer Mg7Zn3 phases and [Formula: see text]-Mg and Ca5Zn3 phases after the MDF process and peak shift and broadening. Higher hardness ([Formula: see text]) was noticed in the MDF 3 pass sample due to grain refinement; further hardness slightly decreased due to texture softening. Moreover, the results of the in vitro corrosion experiments conducted in SBF solution showed that the corrosion current densities of the alloys move in a noble direction as the number of MDF passes increases. MDF 3 pass sample (0.00523[Formula: see text]mm/y) showed the lowest degradation rates compared to the as-cast sample (0.01154[Formula: see text]mm/y), attributed to refining and redistributing the second phases.
Comparative Study of Semi-Active Control Effectiveness of Structures on Soft Soil Using MR Damper: Shaking Table Investigation
Authors: Lv Yang , Wu Mukai , Li Fangfang
Published: October 2024

The effect of soil-structure interaction (SSI) cannot be neglected in semi-active vibration control of structures located on soft soil. To investigate the mitigating effect of magnetorheological (MR) damper on the semi-active control of structures considering the SSI, shaking table tests were conducted to evaluate the performance of the MR damper-based semi-active control system for structures on soft soil. In addition to a novel fuzzy control method based on online learning deep neural network (OL-DFNN), various control strategies, including passive OFF, passive ON, ON–OFF and deep neural network fuzzy control (DFNN) were systematically evaluated. The test results showed that the OL-DFNN control method exhibited superior adaptability to varying ground motion and structural dynamic characteristics compared to the other control methods. In particular, the OL-DFNN controller effectively mitigated the peak displacement and root mean square displacement, outperforming the passive OFF, passive ON, ON–OFF and DFNN control strategies. The test results highlight the effectiveness of the OL-DFNN control method in addressing the challenges posed by dynamic and time-varying characteristics in structural vibration control systems considering SSI.
Large Amplitude Dynamic Instability of a Graphene-Reinforced Pipe Conveying Pulsating Flow
Authors: Zhang Peijun , Lan Tianhui , Arvin Hadi
Published: October 2024

In many industries’ applications, one deals with pipes conveying fluid. Besides, the implementation of advanced materials in manufacturing of new-brand structures is developing. Consequently, in this paper, one of the most important dynamics analyzes that an advanced pipe conveying fluid may meet it is addressed. For the first time, linear and nonlinear dynamics of a pipe reinforced with graphene nanoplatelets (GPL pipe) that conveys pulsating flow is presented. The Euler–Bernoulli beam model follows the plug flow model in order to formulate the problem. The method of multiple scales (MMS) applied to the discretized couple nonlinear gyroscopic governing equations with the aim of specifying the instability region and the steady-state response of the GPL pipe subjected to the principal parametric resonance of one of its modes, as a consequence of pulsating flow. Respectively, the Floquet theory and the Runge–Kutta fourth-order (RK4) method are applied to the linear governing equations and nonlinear governing equations for the sake of confirming the current MMS results. It is deduced that a small amount usage of GPL reinforcement phase improves substantially the resistance against static instability, and the critical fluid excitation amplitude fraction, meanwhile declines the instability region bandwidth, and the steady-state response of the pipe. In contrary, it is confirmed that a heavier fluid makes reverse the preceding statements with respect to a lighter fluid. The aforementioned findings shed light on the essential design keys that outstandingly affect the mechanics of the GPL pipe conveying pulsating fluid that lead and conduct forthcoming studies and open new horizons for designers in industry implementations.
Influence of External Clearance Variation on Vibration Characteristics of Ship Electrically Assisted Turbocharger Rotor Bearing System
Authors: Duan Baoyin , Yang Chuanlei , Shen Hua , Wang Hechun , Wang Yinyan
Published: October 2024

Electrically assisted turbocharging (EAT) technology is an important technical means to effectively solve the problems of insufficient intake air and poor transient response of traditional turbocharged engines at low speed or acceleration, and to realize the electrification of marine internal combustion engine power system. In the EAT design stage, the original rotor model of a marine turbocharger was established and verified. Subsequently, the EAT rotor dynamics design and analysis were carried out, and the influence of the unbalanced phase and external clearance on rotor vibration was discussed. The results show that when the external clearance is small, extensive sub-synchronous vibration occurs and bifurcation occurs at high speed. When the external clearance is large, the sub-synchronous vibration component almost disappears but high synchronous vibration occurs at a high speed. At the same time, the shaft is significantly affected by the gravity load at low speeds, and the rotor makes a balanced motion on the critical limit cycle at high speed. In order to minimize the vibration and noise of the same type of EAT, it is recommended to control the outer clearance of the EAT bearing in the range of 0.30–0.36[Formula: see text]mm. The research content provides a reference for the dynamic design and analysis of the EAT, which effectively helps the development of the original engine of the ship electric auxiliary turbocharger and improves the operation stability of the EAT.
Modal Frequency Shifts Measured on Xinjiang Bridge Excited by Traveling Vehicles
Authors: Li Q. S. , He J. Y. , Sun Zhen , Cheng Xiao-Xiang
Published: October 2024

To excite sufficient vibrations of bridges for more effective modal experiments to take place, traveling vehicles were utilized in many bridge field inspection campaigns in history. However, the dynamics of a bridge subjected to the traveling vehicles are of changed resonant properties compared with those of the same structure with the ambient excitation in nature. Therefore, the field modal experiments employing vehicle excitations might unfavorably lead to shifted measurement results of low-order natural frequencies for long-span bridges of large mass. Using Xinjiang Bridge (a single-tower pre-stressed concrete cable-stayed bridge with spans [Formula: see text]) as the engineering background, this paper validates this technical notion based on reliable physical experiments and numerical simulations and seeks a practical approach to deal with the issue. It is found that the maximum deviation between the low-order modal frequencies measured on Xinjiang Bridge for the vehicle excitation case and those measured for the ambient excitation case (the accurate values) reaches 0.65[Formula: see text]Hz, and the deviation between the lower limit of the usual vehicle excitation’s energy band and the modal frequency measured (factor 1) and the traveling vehicles’ speed (factor 2) are the two key factors influencing the modal frequency shifts. An empirical model to compensate for modal frequencies’ deviations is formulated considering the two key factors accordingly, which is of high-practical significance in future applications of the modal experiments using vehicle excitations to other long-span bridges.
Fusion rings over Drinfeld doubles
Authors: Li Wenqi
Published: October 2024

The fusion rules in [Formula: see text] for a finite group [Formula: see text] can be computed in terms of character inner products. Using an explicit formula (Theorem 3.2) for these fusion rules, we show that [Formula: see text] is multiplicity free for two infinite families of finite groups: the Dihedral groups and the Dicyclic groups. In fact, we will compute all fusion rules in these categories. Multiplicity freeness is a desired property for modular tensor categories, since it greatly simplifies the computation of [Formula: see text]-matrices. Furthermore, we observe that the fusion rules for Dihedral groups [Formula: see text] with [Formula: see text] odd are extremely similar to the fusion rules of type-B level-[Formula: see text] fusion algebras of Wess–Zumino–Witten conformal field theories. Moreover, we give a proof of the fusion rule formula by using Mackey theory.
Hamiltonian cycles for finite Weyl groupoids
Authors: Inoue Takato , Yamane Hiroyuki
Published: October 2024

Let [Formula: see text] be the Cayley graph of a finite Weyl groupoid [Formula: see text]. In this paper, we show an existence of a Hamiltonian cycle of [Formula: see text] for any [Formula: see text]. We exactly draw a Hamiltonian cycle of [Formula: see text] for any (resp. some) irreducible [Formula: see text] of rank three (resp. four). Moreover for the irreducible [Formula: see text] of rank three, we give a second largest eigenvalue of the adjacency matrix of [Formula: see text], and know if [Formula: see text] is a bipartite Ramanujan graph or not.
A Fast Time-Discontinuous Peridynamic Method for Stress Wave Propagation Problems in Saturated Porous Media
Authors: Zheng Yonggang , Liu Zhenhai , Qiu Yisong , Sun Wei , Ye Hongfei , Zhang Hongwu
Published: October 2024

When employing numerical methods to simulate the behavior of saturated porous media under impact load, the Gibbs phenomenon often occurs, significantly compromising the accuracy of numerical calculations. To improve the accuracy of numerical solutions, this study introduces a fast time-discontinuous peridynamic (TDPD) method for simulating the propagation of fluid pressure and solid stress waves within saturated porous media. In this method, the classical u–p and u–U models are reformulated from spatial differential equations into integral equations to facilitate the simulation of fracture problems. Subsequently, the basic field variables are independently interpolated in the temporal domain, with the introduction of jump terms representing the discontinuities of variables between adjacent time steps. Then an integral weak form in the temporal domain of the spatially discrete governing equations is constructed and the basic formula of the TDPD is derived. Additionally, an efficient approximation method that directly uses the internal force to calculate its time derivative is further proposed. These characteristics ensure that the TDPD can effectively and efficiently capture the inherent sharp gradient features of wave propagation in solid phase and fluid while controlling spurious numerical oscillations. Several representative numerical examples demonstrate that the TDPD can obtain more accurate results compared with conventional peridynamic solution schemes. Moreover, the TDPD can also be viewed as a novel time integration technique, holding substantial potential for high-precision numerical solutions of hyperbolic equations in diverse physical contexts.
Photoelectric activity evaluation of surface-loaded ferroferric oxide/titanium dioxide composite prepared from ilmenite
Authors: Zhang Kun , Wang Daoxin , Wu Shuangquan , Wang Chengeng , Yu Zhengguang , Zhang Lei
Published: October 2024

This work demonstrates a surface-loaded Fe3O4/TiO2 composite with the magnetic Fe3O4 deposited on the surface of anatase TiO2 nanocrystal which can be directly prepared from the ilmenite using the coprecipitation method. After the acidolysis treatment with the 95% dissolution rate, the ilmenite will be first transformed into H2TiO3 and FeCl2, and the photoactive anatase TiO2 nanocrystals are obtained from the calcined H2TiO3 at 500[Formula: see text]C. Then a surface-loaded Fe3O4/TiO2 composite TF is finally achieved by the coprecipitation method, which is carefully elaborated to balance the magnetism and photoactivity of Fe3O4/TiO2 composite by the optimal contents of Fe3O4 and TiO2. It is encouraging to note that Fe3O4/TiO2 composite TF shows a good comprehensive performance in serial photodegradation experiments of Rhodamine B. The degradation rate of Rhodamine B is more than 99% during 60 min under the irradiation of both xenon lamp and sunlight. During at least six cycles, the composite TF can show stable photocatalytic activity and good durability together with the recovery and recycling potentials by using an external magnet.
Optical, Structural and Biological Properties of Reduced Silver Oxide Nanoparticles from Anethum Graveolens Leaf Extract by Nonthermal Plasma
Authors: Ahmed Rasha S. , Dahham Abdulkader Makki , Abdalameer Nisreen Kh. , Mohammed Raghad S.
Published: October 2024

This research aims to develop a novel approach, employing cold plasma technology for preparing nanoparticles of silver oxide by Anethum graveolens (dill) leaf extract as a natural reducing agent. This investigation evaluated the properties of antibacterial and antibiofilm-prepared nanoparticles. Initially, dill leaf extract was prepared to stabilize and reduce the size of silver oxide nanoparticles. Improved synthesis and optimal conditions for nanoparticle formation were achieved through the application of cold plasma technology. The results obtained showed that the prepared silver oxide nanoparticles have strong antibacterial properties and that they have antibacterial activity against a different group of bacteria that cause diseases such as Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results also showed the effectiveness of nanoparticles in preventing the formation of bacterial biofilms, as the highest rate of inhibition was for gram-positive bacteria S. aureus. This study demonstrated the effectiveness of plant extracts and cold plasma technology when combined in producing nanoparticles with improved properties, which may push toward the employment of these materials in developing innovative and sustainable solutions in various scientific and applied fields.
Microemulsion of Medicago marina Essential Oil: In Vitro Evaluation of Antimicrobial, Antibiofilm, Anticoagulant Effects, and In Silico Studies Involving Molecular Docking and ADME Prediction
Authors: Melliti Marwa , Noumi Emira , Horchani Mabrouk , Mastouri Maha , Snoussi Mejdi , Jannet Hichem Ben , Zafar Muhammad , de Oliveira Mozaniel Santana , Edziri Hayet
Published: October 2024

This work characterizes microemulsions of Medicago marina essential oil and evaluates their antimicrobial, antibiofilm, and anticoagulant effects. Medicago marina L. aerial parts essential oil was hydro-distilled and analyzed by gas chromatography-FID and gas chromatography/mass spectrometry (GC/MS) for the first time from the Tunisian chemotype. The microemulsion was prepared using an oil/water formulation with a biopolymer (Arabic gum) and surfactant (Tween 20). Antibacterial and antifungal activities were evaluated using the microbroth dilution method, while anticoagulant activity was tested in vitro using prothrombin time (PT) and aPTT tests. Eventually, the binding affinities and molecule’s interactions of the main chemicals with the operational locations of C (30) carotenoid dehydrosqualene synthase and cytidine deaminase were explored. The essential oil contained 71 compounds of which 87.6% were identified. Major compounds were [Formula: see text]-ionone (17.67%), 1-methyleugenol (10.75%), eugenol (8.86%), [Formula: see text]-damascenone (4.33%), and [Formula: see text]-humulene (4.32%). A microemulsion with a diameter of 1.63 [Formula: see text] m, a polydispersity index of 0.17, a zeta potential of –40.8 mV and a pH of 6 was obtained and it showed the highest antibacterial potential against a multitude of microbes, with low MICs varying between 0.406 mg/mL and 3.25 mg/mL. Significant antibiofilm activity was observed with over 80% inhibition at 4 × MIC concentration. It showed better anticoagulant activity than heparin, with PT and aPTT values of 19.5 s and 57 s, respectively, at 10 mg/mL. Molecular docking showed that “([Formula: see text]-[Formula: see text]-ionone” had the highest binding scores. Notable pharmacokinetic and drug-like qualities were found in the obtained molecules after establishing ADME profiling. As a result, Medicago marina L. Essential oil microemulsion can be used in food processing as a preservative.
Action Mechanism of Bioactive Compounds from Plants and Spices Mixture as Promising Anticancer Agents: In Silico Drug Design Predictions Targeting Cancer Cell Proliferation Through Cell Cycle Arrest Pathway
Authors: Benarba Bachir , Belhouala Khadidja , Pandiella Atanasio
Published: October 2024

Although cancer has been the main reason for death for decades, until now, no safe certified drugs have been discovered to efficiently inhibit its progression. Currently, we aim to employ an in-silico model to predict the action mechanism of phenolic components that we previously demonstrated as inhibitors of colon, prostate and lung cancer. The work was performed by testing pharmacokinetics and pharmacodynamics proprieties of selected molecules. Four compounds: Kaempferol, chrysin, vanillin and p-hydroxybenzoic acid widely obeyed the five rules and the ADME/T criteria with minimum toxicity. Docking prediction recorded an intense affinity between kaempferol-CDK1(−17.72 ± 0.02 kcal/mol), chrysin-CDK1 (−17.61 ± 0.01 kcal/mol) and kaempferol-caspase 8 (−9.30 ± 0.00 kcal/mol), chrysin-caspase 8 (−8.18 ± 0.12 kcal/mol), vanillin-MMP9 (−9.83 ± 0.04 kcal/mol) and p-hydroxybenzoic acid-Ca2 (−8.91 ± 0.01 kcal/mol). Likewise, MMGBSA results demonstrated that these compounds are evidently bound to the targets’ active sites with solid interactions. The passed compounds might target the responsible factors for transcription as inactivators. The molecular mechanism based on kaempferol and vanillin actions was predicted to target CDK1 and MMP9 via cell cycle arrest and apoptosis. All results were confirmed through RMSD analysis suggesting that kaempferol and vanillin are the best ligands to suppress cancer cell proliferation. Thus, these findings allowed us to imagine a potential molecular mechanism of these binaries, phenolic compounds/target proteins to lead further trails on cancer, of which the synergistic activity between phenolic compounds could promote the therapeutic capacity.
Paleozoic tectonothermal history of the amalgamation of the Tarim–North China and Mongolian collages
Authors: Soldner Jérémie , Schulmann Karel , Štípská Pavla , Jiang Yingde
Published: October 2024

In the Mongolian Collage, metamorphic pressure–temperature (
P
–
T
) and timing reveal a one-stage evolution defined by a duality of late Neoproterozoic–Ordovician subduction-related low
T
/
P
metamorphism and suprasubduction high
T
/
P
metamorphism recorded in the Mongolia–Manchuria and Baikal–Sayan belts. This was followed by gradual prevalence of suprasubduction high
T
/
P
metamorphism towards the late Paleozoic corresponding to the Altai and South Altai cycles. In the Tarim–North China Collage, metamorphic
P
–
T
and timing reveal a two-stage evolution, from dominant intermediate
T
/
P
metamorphism possibly resulting from Ordovician–Devonian amalgamation and Andean-type evolution of the collage, to dual low and high
T
/
P
metamorphism in the Carboniferous–Permian reflecting subduction–collision processes along the South Tianshan suture in the west and a suprasubduction evolution along the Solonker suture in the east. Altogether, the Paleozoic tectonometamorphic evolution of the two collages in the Central Asian Orogenic Belt shows remarkable differences, with the Mongolian Collage displaying features typical of peripheral accretionary style reflecting recurrent tectonic switches that can be regarded as a single orogenic system, and a two-stage evolution of the Tarim–North China Collage with features of both peripheral–accretionary and interior–collisional orogenic cycles, but mostly related to recurrent subductions of interior oceans.
Context-Aware Adversarial Graph-Based Learning for Multilingual Grammatical Error Correction
Authors: Kumar Naresh , Kumar Parveen , Tripathy Sushreeta , Samal Neelamani , Gountia Debasis , Gatla Praveen , Singh Teekam
Published: October 2024

Correcting grammatical errors in various language contexts is a crucial and challenging task in the field of natural language processing, commonly referred to as Multilingual Grammatical Error Correction. This paper elaborates the Adversarial Temporal Graph Convolution Model (AT-GCM), which combines the capabilities of MT-5, adversarial learning, and temporal graph convolutional neural network (t-GCN) to achieve accurate progress in multilingual grammatical error correction. The inherent capability of MT-5 to process multiple languages simultaneously serves as a powerful embedding generator for the purpose of multilingual error correction. The t-GCN is employed for the purpose of navigating the temporal context and interdependencies present within words. The assumption that modeling the dynamic interactions among words within the context of temporal relationships improves precision, particularly in languages with complex sentence structures, is supported by research. The utilization of adversarial learning techniques can enhance the generalization capabilities of the model across various language pairings, effectively addressing the challenges associated with low-resource languages. A comprehensive analysis is carried out on a diverse, multilingual dataset comprising various languages, viz. English, Russian, German, Czech, Arabic, and Romanian. The experimental results present significant improvements in grammatical error correction performance compared to state-of-the-art models. Our approach effectively resolves grammatical errors in various linguistic contexts by utilizing a combination of MT-5, adversarial learning, and t-GCN.
USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality
Authors: Jean-Charles Pierre-Yves , Roy Bipradas , Yu Samuel Mon-Wei , Pironti Gianluigi , Nagi Karim , Mao Lan , Kaur Suneet , Abraham Dennis M. , Maudsley Stuart , Rockman Howard A. , Shenoy Sudha K.
Published: October 2024

We identify ubiquitin-specific peptidase 20 (USP20) as an important enzyme that is required for cardiac homeostasis and function, particularly during myocardial pressure overload. USP20 regulates protein stability of cardiac MYH7, an essential molecular motor protein expressed in sarcomeres; loss-of-function mutations of MYH7 are associated with human hypertrophic cardiomyopathy, cardiac failure, and sudden death. Enhancing USP20 activity could be a potential therapeutic approach to prevent the development of maladaptive state of eccentric hypertrophy and heart failure.
Apparent Protein Digestibility and Growth Performance of Nile Tilapia (Oreochromis niloticus L.) Fed on Sunflower and Cotton Seed Meal as Substitutes for Freshwater Shrimp Meal (Caridina nilotica)
Authors: Maundu Anne , Munguti Jonathan , Sharma Rekha , Kasozi Nasser , Liti David , Muthoka Mavindu , Kirimi James , Mutiso Joshua
Published: October 2024

Fish feed is critical in aquaculture production, accounting for over 60% of operational costs, with protein being the most expensive component. Traditionally, fish meal (FM) has been the primary protein source. However, due to declining capture fisheries and high demand, FM has become scarce and costly, necessitating the search for alternative, low‐cost, and nutritionally balanced protein sources. A 180‐day feeding experiment was conducted to evaluate the effects of replacing FM with a combination of cottonseed and sunflower meal (SFM) in Nile tilapia diets on growth performance, protein digestibility, and economic returns. Freshwater shrimp meal was replaced at 25%, 50%, 75%, and 100% (diets D1, D2, D3, and D4) and compared to the control diet (D0) containing only FM. Monosex Nile tilapia fingerlings (25 ± 0.01 g) were allocated to 15 cages within an 800 m2 earthen pond. Fish on diets D0 and D1 showed superior growth performance metrics, including final mean body weight, weight gain, daily weight gain, specific growth rate, feed conversion ratio, and survival rate (p > 0.05), compared to diets D2, D3, and D4. Growth performance declined significantly with increasing levels of the plant protein mixture (p < 0.05). Diet D0 had the highest apparent protein digestibility, while D4 had the lowest. Cost‐benefit analysis revealed that diet D0 had the highest production cost, followed by diets D1, D2, D3, and D4, with no significant cost difference between D0 and D1 (p > 0.05). Thus, the plant protein mixture can effectively replace FM at a 25% inclusion level in Nile tilapia diets.
Measuring and Modifying Threat‐Related Attention Bias in Posttraumatic Stress Disorder: An Attention Bias Modification Study
Authors: Rubin Mikael , Niles Andrea , Evans Travis , Tripp Paige , Neylan Thomas C. , Woolley Joshua , O’Donovan Aoife
Published: October 2024

Background: Dominant models of posttraumatic stress disorder (PTSD) implicate threat‐related attention biases in both the development and maintenance of posttraumatic stress symptoms. However, the ability to better understand and modify threat‐related attention biases in PTSD has been hampered by the low reliability of attention bias measures more generally.

Methods: The current study adopts a new approach to calculate attention bias from a dot‐probe task, response‐based attention bias (RB‐AB) computation, in a sample of 689 individuals reporting significantly elevated PTSD symptoms who participated in a clinical trial of threat‐related attention bias modification training.

Results: RB‐AB is a reliable strategy for deriving threat‐related attention bias scores that correlate with both PTSD severity and anxiety. On the other hand, scores from the traditional approach were unreliable and not associated with clinical symptoms. Attention training led to reductions in RB‐AB indices of attention bias, but not the traditional index, although attention bias training conditions did not appear to moderate these effects.

Conclusions: Taken together, these findings support evidence that threat‐related attention biases may be a feature of PTSD and that RB‐AB computation is a more reliable and valid approach for studying reaction‐time‐based attentional processes. Using the RB‐AB approach to assess attention bias could allow us to better understand threat‐related attention biases in PTSD and to ultimately develop more precise interventions to reduce threat‐related attentional biases in PTSD and other disorders.
Numerical Simulation of the Influence of Long‐Term Deformation of a Water‐Rich Goaf on Highway Stability: A Case Study in Jixi
Authors: Fan Xiaojiang , Wang Hai , Sang Qiwen , Zheng Junquan
Published: October 2024

With the continuous development of transportation construction in China, an increasing number of transportation projects must pass through large‐scale goafs formed by mining activities. Because of the complex structure of the overlying rock in the goaf area, large‐scale and lasting deformation occurs on the surface. Moreover, most goaf areas are in a water‐rich state, and the deformation characteristics of the rock mass are significantly affected by water, which poses a great challenge to the stability of the surface. Based on the Burgers model, a parameter selection method suitable for describing the creep characteristics of water‐rich rock mass compaction is proposed in this research, and the parameter calculation formula for the creep model of water‐rich rock mass under different pressures is given. Then, taking a highway in Jixi as an example, FLAC3D software is used to simulate the long‐term deformation characteristics of a water‐rich goaf, and the influence of long‐term deformation on the stability of the surface highway structure is analyzed. The results show that severe highway pavement deformation will occur after 50 years of operation in the study area. In particular, due to passing through the subsidence area of the goaf, the 0–150 m and 250–400 m sections of the highway are significantly greater than those of the other sections. The above research findings provide important references for the formulation of subsequent highway operation and maintenance programs.
Utilization of Anal Cytology Screening among Sexual and Gender Minority Populations in Pennsylvania
Authors: Bennis Sarah L. , Arsoniadis Elliot G. , Wheldon Christopher W.
Published: October 2024

Background:

Despite the risk of anal cancer in sexual and gender minority (SGM) populations, anal cancer screening remains infrequent and inconsistent in these populations. The objective of this analysis was to identify factors associated with anal cancer screenings among SGM populations using the Andersen’s behavioral model of health services use.

Methods:

Secondary analyses of two cross-sectional surveys from the 2020 (N = 1,125) and 2022 (N = 630) Pennsylvania LGBTQ Health Needs Assessment. Multiple logistic regression analyses were used to identify correlates of anal cytology screening.

Results:

Average age was 37.7 (SD = 13.3) and 39.7 (SD = 13.6) in 2020 and 2022, respectively. Approximately 16% to 18% reported living with human immunodeficiency virus (HIV). A minority of respondents reported past year screening (14.0%, 2020 and 13.6%, 2022). Enabling and need-based factors consistently associated with screening included sexually transmitted infection treatment, living with HIV, preexposure prophylaxis use, and multiple sex partners. Robust factors associated with ever being screened were age and living with HIV.

Conclusions:

Anal cytology screening is being done in Pennsylvania at a small but not insignificant rate. In accordance with existing guidelines, SGM populations living with HIV were most likely to be screened, but still at a low rate. Predictive factors associated with screening in this study can inform future interventions to implement guideline-specific anal cancer prevention.

Impact:

Factors that reflect consistent connection to healthcare are associated with increased rates of screening via anal cytology testing, indicating there are opportunities to implement anal cancer screening as part of a larger, more comprehensive SGM-focused care pathway.
Supplementary Table S4 from Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer
Authors: van de Haar Joris , Mankor Joanne M. , Hummelink Karlijn , Monkhorst Kim , Smit Egbert F. , Wessels Lodewyk F.A. , Cuppen Edwin , Aerts Joachim G.J.V. , Voest Emile E.
Published: October 2024

Actionable EGFR alterations, TMB and DCB in the validation cohort.
Vitamin A Metabolism and Resistance of Hepatic Metastases to Immunotherapy
Authors: Jones Peter C. , Von Hoff Daniel D.
Published: October 2024

The liver is an immune-tolerant organ, allowing for organ transplantation with less immune suppression compared with other organs. It also provides fertile soil for tumor metastases, which tend to be more resistant to checkpoint blockade immunotherapy than metastases in other organs. This resistance may result from the sum of incremental evolutionary adaptions in various cell types to prevent overaction to antigens absorbed from the gut into the portal circulation or it might involve a central mechanism. Here, we propose that metabolism of vitamin A, which is highly concentrated in the liver, is a root source of tolerance and resistance of hepatic metastases to checkpoint blockade. Suppression of retinoic acid synthesis from vitamin A with disulfiram may mitigate tolerance and produce enhanced immunotherapy treatment results for patients with liver metastases.