Opposite Outcomes Research Articles

P11.05.B LONGITUDINAL MODIFICATIONS OF GRADIENTS AND GRAPH-THEORY MEASURES OF FUNCTIONAL MRI CONNECTIVITY IN GLIOMA PATIENTS AS POTENTIAL MARKERS OF POST-SURGICAL LONG-TERM COGNITIVE OUTCOME

Abstract BACKGROUND Integrating connectomics and functional brain activity into the study of brain tumors is among neuro-oncology’s challenges. Functional MRI (fMRI) studies showed that gliomas are integrated with brain networks’ activity, exerting effects beyond their margins. We investigated longitudinal modifications of fMRI gradients and graph-theory parameters in glioma patients, assessing their role in cognitive prognostication. MATERIAL AND METHODS Diffuse non-enhancing glioma patients underwent fMRI and cognitive assessments (OCS-Bridge) before, within 72h after, 3 and 12 months after surgery. Cognitive data were normalized and averaged into a global score. Differences between the last and preoperative scores were computed (“cognitive difference”). fMRI data underwent preprocessing, cortical parcellation, computation of timeseries, connectivity matrices, gradients and graph-theory measures. To quantify gradient dispersion, we computed a circularity metric (“CM”) of the hull perimeter of the first two gradients’ distribution. T-tests, partial correlations (correcting for volume and surgery radicality) and linear regression (regressors: age, volume, preoperative cognition, surgery radicality) were used to investigate associations with cognitive difference. RESULTS 17 patients (22-56 years, 8 females) were included, 4 had long-term cognitive worsening. Postoperative circularity metric, especially of the healthy intra- and inter-hemispheric connectivity (“HIIHC”), was higher than the preoperative (0.43 vs 0.32, t=2.4, p=0.03). Month3-postoperative and month3-preoperative differences in HIIHC CM were higher in patients with compared to those without cognitive worsening (0.33 vs -0.06, t=6.9, p<0.0001 and 0.27 vs 0.009, t=4.3, p=0.001). Both were negative predictors of the cognitive difference (the first: R=-0.94 with p=0.0002; β=-1.1 with p=0.001 and regression model’s p=0.003; the second: R=-0.76 with p=0.006; β=-1.1 with p=0.02 and model’s p=0.05). Month3-preoperative network modularity difference correlated with the second metric (R=-0.72, p=0.01) and the cognitive difference (R=0.67, p=0.02), while the preoperative modularity with the first metric (R=0.77, p=0.014). Similar results were obtained using a predetermined number of modules (Yeo’s 7 networks). Month12-preoperative difference in healthy intra-hemispheric connectivity CM also correlated with cognitive difference (R=-0.91, p=0.002). CONCLUSION Functional gradients seem dispersed after glioma surgery. Their recovery or worsening at month 3 could predict opposite long-term cognitive outcomes, putatively due to connectivity changes mainly involving the healthy hemisphere. Low preoperative network modularity and its increase at month 3 are associated with such gradient dispersion. Cognitive rehabilitation might be beneficial in the early post-surgical phase.

MHC class II genotypes are independent predictors of anti-PD1 immunotherapy response in melanoma.

Immune checkpoint blockade is a highly successful anti-cancer immunotherapy. Both CTLA4 and PD1 checkpoint blockers are clinically available for melanoma treatment, with anti-PD1 therapy reaching response rates of 35-40%. These responses, which are mediated via neoantigen presentation by the polymorphic MHC complex, are hard to predict and the tumor mutation burden is currently one of the few available biomarkers. While MHC genotypes are expected to determine therapy responses, association studies have remained largely elusive. We developed an overall MHC genotype binding score (MGBS), indicative of a patient's MHC class I (MHC-I) and class II (MHC-II) neoantigen binding capacity and solely based on the germline MHC-I (MGBS-I) and MHC-II (MGBS-II) genotypes. These scores were then correlated to survival and clinical responses following anti-PD1 immunotherapy in a previously published dataset of 144 melanoma patients. We demonstrate that MGBS scores are TMB-independent predictors of anti-PD1 immunotherapy responses in melanoma. Opposite outcomes were found for both MHC classes, with high MGBS-I and MGBS-II predicting good and bad outcomes, respectively. Interestingly, high MGBS-II is mainly associated with treatment response failure in a subgroup of anti-CTLA4 pretreated patients. Our results suggest that MGBS, calculated solely from the MHC genotype, has clinical potential as a non-invasive and tumor-independent biomarker to guide anti-cancer immunotherapy in melanoma.

The context-dependent epigenetic and organogenesis programs determine 3D vs. 2D cellular fitness of MYC-driven murine liver cancer cells.

3D cellular-specific epigenetic and transcriptomic reprogramming is critical to organogenesis and tumorigenesis. Here we dissect the distinct cell fitness in 2D (normoxia vs. chronic hypoxia) vs 3D (normoxia) culture conditions for a MYC-driven murine liver cancer model. We identify over 600 shared essential genes and additional context-specific fitness genes and pathways. Knockout of the VHL-HIF1 pathway results in incompatible fitness defects under normoxia vs. 1% oxygen or 3D culture conditions. Moreover, deletion of each of the mitochondrial respiratory electron transport chain complex has distinct fitness outcomes. Notably, multicellular organogenesis signaling pathways including TGFb-SMAD specifically constrict the uncontrolled cell proliferation in 3D while inactivation of epigenetic modifiers (Bcor, Kmt2d, Mettl3 and Mettl14) has opposite outcomes in 2D vs. 3D. We further identify a 3D-dependent synthetic lethality with partial loss of Prmt5 due to a reduction of Mtap expression resulting from 3D-specific epigenetic reprogramming. Our study highlights unique epigenetic, metabolic and organogenesis signaling dependencies under different cellular settings.

143 Short- and long-term effects of heat stress in cow-calf pairs adapted to tropical and subtropical regions

Abstract Chronic exposure to high temperatures and humidity can limit beef cattle performance in tropical/subtropical environments, regardless of breed. Despite better heat adaptability compared with Bos taurus cattle, heat-stressed Bos indicus cattle also experience an increase in body temperature above the physiological limit. As body temperature increases, cascades of behavioral and physiological events are triggered to lessen heat load but often at the expense of productive outcomes. Contrary to other species and feedlot beef cattle, the effects of heat stress on physiology and performance of grazing cow-calf pairs have not been evaluated in detail, particularly for Bos indicus cattle. Preliminary data showed opposite outcomes to heat stress in Bos indicus vs. Bos taurus cattle, limiting the implications of the existing data generated from studies using beef and dairy Bos taurus cattle. This presentation will share some nutritional and management practices to mitigate heat stress in grazing beef cattle. Practices mentioned herein include altering the timing of body weight (BW) growth pattern (stair-step, SST) and immunomodulatory feed ingredient (IFI) supplementation for replacement beef heifers, and maternal access to shade to reduce heat load. For 100 d before the breeding season, Bos indicus-influenced beef heifers grazing warm-season grasses received a constant supplementation amount or SST strategy (50 d of low then 50 d of high supplementation), with or without IFI. Under severe heat stress conditions, IFI supplementation reduced heifer vaginal temperature but did not increase their growth and reproduction, whereas the SST strategy lowered internal body temperature, enhanced growth performance and pregnancy success compared with a conventional constant supplementation practice. Our group is also focused on the critical need to determine the specific effects of heat stress mitigation during pre- and postnatal phases on physiology and performance of Bos indicus-influenced cow-calf pairs. Study 1 evaluated the impacts of maternal access to artificial shade from 83 d prepartum until 50 d postpartum on body thermoregulation, performance, and physiology of beef heifers and their first offspring. Removing maternal access to shade led to greater maternal respiration rate, vaginal and body surface temperatures and reduced maternal body condition score and calf BW at birth. Nonetheless, offspring born from cows with no access to shade were remarkably heavier during a 60-d post-weaning period and had decreased plasma indicators of inflammation and positive effects to humoral immune response. Study 2 is a multi-year, USDA/NIFA-funded study designed to capitalize on the ability of cattle to reprogram physiological/immunological systems following exposure to stress during gestation. Study 2 combined gestational and postnatal heat abatement to enhance the overall growth/immune/reproductive performance of grazing Bos indicus-influenced cow-calf pairs. Partial data on long-term growth and reproductive performance, physiology, metabolome, and microbiome of both cows and their female offspring will be shared in this presentation.

Locus Of Control and Job Satisfaction: A Comparative Study Between Male and Female Employees in It Sector Bangalore

The level of job satisfaction is one of the key pushing factors for improving employee productivity and efficiency in every organization. On the other hand job stress is pulling factor of job satisfaction, productivity and efficiency in the long run. Therefore, two are two extreme variables result into two opposite outcomes However, levels of job stress and job satisfaction varies as per the personalities of employees such as internal and external personalities and gender wise. The present study emphasized on the understanding the relationship between job stress, job satisfaction and work locus of control and variation between genders and type of locus of control among the 150 selected IT professionals in Bangalore. The outcome of the study evidence that, internal locus of control leads to higher job satisfaction of the employees in IT sector irrespective of gender variation and external locus of control causes lower job satisfaction. There is existence of negative correlation between job stress and external locus of control on job satisfaction. Besides, the study found insignificant variation in workplace stress, job satisfaction, and work locus of control. The study also observed high job satisfaction of the employees in IT sector with regarding to promotion, supervision, nature of work and support from colleagues and dissatisfaction regarding remuneration and operating conditions.

Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the "MOZART" prospective observational study.

The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations' type, frequency, actionability, and potential correlations with PD-L1 expression. A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P < .05. A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes. We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical.

Multi-generation effects of lead (Pb) on two Daphnia species.

Two monophyletic Daphnia species (Daphnia magna and D. similis) were exposed to a sub-lethal concentration of Pb (50 µg/L) for nine generations under two food regimes (usual and restricted) and analyzed for acetylcholinesterase (AChE) activity, first reproduction delay, lifespan, and net reproductive rate (R0) at the subcellular, individual, and population levels, respectively. In the sixth generation, Pb-acclimated neonates were moved to clean media for three more generations to check for recovery. The net reproductive rate (R0) of D. magna was not affected by Pb. However, Pb stimulated reproduction, reduced lifespan, and decreased AChE activity. First reproduction delay and lifespan did not improve during the recovery process, suggesting a possible genetic adaptation. Food restriction reduced R0, lifespan, delayed hatching, and increased AChE activity; the opposite outcomes were observed for D. similis. The full recovery shown by R0 suggests the physiological acclimation of D. similis. Under food restriction, the animals exhibited a reduction of R0 and lifespan, delayed first reproduction, and increased AChE activity; however, there was no effect of Pb. The recovery process under food restriction showed that D. similis might not cope with Pb exposure, indicating a failed recovery. Such outcomes indicate that one model species' sensitivity may not represent another's sensitivity.

Navigating the inception stage in online peer production communities: a comparative study on community building activities, user roles and interaction dynamics

PurposeThis exploratory, descriptive study examines the factors that might influence the success or failure of online peer production communities during their inception stage. It focuses on community-building activities, the roles of users and the dynamics of user interaction, aiming to shed light on practices that could contribute to a community's success at the inception stage.Design/methodology/approachBy comparing two Stack Exchange Q&amp;A communities with the same timelines but opposite outcomes during their beta testing phases, the research utilizes quantitative methods to categorize community activities, define user roles via k-means cluster analysis and examine interaction networks using social network analysis.FindingsOur findings suggest the successful Mathematics Q&amp;A community exhibited several distinct practices during its inception, such as the utilization of both external and internal tools, the development of community-specific tutorials and the strategic use of flagging functions for moderation. Eight user roles were discerned, with roles like content editors, metadata curators and gatekeepers being particularly prominent in the successful community. Additionally, a more densely interconnected user network characterized by active participation was observed in the successful community.Originality/valueConcentrating on the inception stage of online communities, this study uncovers insights into the dynamics at play in the early life of peer production environments and provides empirical observations that may assist in shaping strategies for new online communities. It stands out by comparing communities within the same period to understand factors that may influence their early success.

A Sociolinguistic Analysis of Ironic Expressions in English and Kurdish

This paper, which is part of the requirements of an MA degree, is entitled "A Sociolinguistic Analysis of Ironic Expressions in English and Kurdish." It provides further insight into the sociolinguistic application of irony. Irony, which is categorized into verbal and situational is when something that was expected to have a specific result instead of results in a completely different or opposite outcome. The paper argues that expressing one thing while implying another is not always irony. In some instances, the ironic statement alludes to the fact that the idea being refuted is what underlies the truth of a situation, a claim, or a previous way of thinking. Data on Kurdish irony are gathered through observation and are explained in English, while data on English ironic expressions are collected from the corpus of English including books and online sources. The investigation of the topic is conducted using a descriptive methodology. Each sort of irony is described and illustrated, and the figurative connotation in both languages is also emphasized. The main objective of the study is to clarify the figurative meaning of irony in the two languages. The most significant findings comprise first, that irony has a positive connotation in literal contexts while it has a negative connotation in figurative contexts. Second, figurative language, which is frequently used in communication, contains irony. Additionally, ironic expressions are italicized in both languages.

Perceptual Resolution of Ambiguity: Can Tuned, Divisive Normalization Account for both Interocular Similarity Grouping and Difference Enhancement.

Our visual system usually provides a unique and functional representation of the external world. At times, however, the visual system has more than one compelling interpretation of the same retinal stimulus; in this case, neural populations compete for perceptual dominance to resolve ambiguity. Spatial and temporal context can guide perceptual experience. Recent evidence shows that ambiguous retinal stimuli are sometimes resolved by enhancing either similarity or differences among multiple percepts. Divisive normalization is a canonical neural computation that enables context-dependent sensory processing by attenuating a neuron's response by other neurons. Experiments here show that divisive normalization can account for perceptual representations of either similarity enhancement (so-called grouping) or difference enhancement, offering a unified framework for opposite perceptual outcomes.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes. Of particular interest, age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Rho-Associated Protein Kinase Activity Is Required for Tissue Homeostasis in the Xenopus laevis Ciliated Epithelium.

Lung epithelial development relies on the proper balance of cell proliferation and differentiation to maintain homeostasis. When this balance is disturbed, it can lead to diseases like cancer, where cells undergo hyperproliferation and then can undergo migration and metastasis. Lung cancer is one of the deadliest cancers, and even though there are a variety of therapeutic approaches, there are cases where treatment remains elusive. The rho-associated protein kinase (ROCK) has been thought to be an ideal molecular target due to its role in activating oncogenic signaling pathways. However, in a variety of cases, inhibition of ROCK has been shown to have the opposite outcome. Here, we show that ROCK inhibition with y-27632 causes abnormal epithelial tissue development in Xenopus laevis embryonic skin, which is an ideal model for studying lung cancer development. We found that treatment with y-27632 caused an increase in proliferation and the formation of ciliated epithelial outgrowths along the tail edge. Our results suggest that, in certain cases, ROCK inhibition can disturb tissue homeostasis. We anticipate that these findings could provide insight into possible mechanisms to overcome instances when ROCK inhibition results in heightened proliferation. Also, these findings are significant because y-27632 is a common pharmacological inhibitor used to study ROCK signaling, so it is important to know that in certain in vivo developmental models and conditions, this treatment can enhance proliferation rather than lead to cell cycle suppression.

The involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway

BackgroundInterferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated. MethodsUsing lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an in vivo and in vitro model was established. In vivo, Sting agonists and inhibitors were administered, while in vitro, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1β, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the in vivo mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both in vivo and in vitro. ResultsIn vitro experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1β), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, in vitro experiments using HUVEC cell lines validated these findings. ConclusionsOur study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.

A new co-infection model for HBV and HIV with vaccination and asymptomatic transmission using actual data from Taiwan

The co-infection of Human Immunodeficiency Virus (HIV) and Hepatitis B virus (HBV) poses a major threat to public health due to their combined negative impacts on health and increased risk of complications. A novel fractional mathematical model of the dynamics of co-infection between HBV and HIV for Taiwan is presented in this paper. Detailed analyses are conducted on the possible impact of HBV vaccination on the dynamics of HBV and HIV co-infection. The next-generation matrix technique is used to calculate the fundamental reproduction number R 0 = max{R 1, R 2}, where R 1 and R 2 are the reproduction numbers for HBV and HIV, respectively. The disease-free and endemic equilibria of the co-infection model are calculated. An extensive investigation is carried out to determine the local and global stability of the disease-free equilibrium point through Rough Hurtwiz criteria and the construction of Lyapunov function, respectively. We demonstrate that when R 1 < 1 < R 2, HBV infection is eradicated, but HIV remains prevalent. If R 2 < 1 < R 1, the opposite outcome occurs. The real data from 2000-2023 for Taiwan is used to fit the model. The fitting results show how effectively our model handles the data. In addition, numerical simulations are run for different scenarios to observe how the vaccine and fractional parameters changed the model state variables, as well as how the solutions behaved and how quickly they reached the model’s equilibrium points. According to the model’s numerical analysis, greater vaccination efforts against HBV have a positive effect on the propagation of co-infection.

Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from −5.6 to −1.7 ms for T1ρ, and −2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

StMAPK10 gene functional identification and analysis in drought resistance of potato crop (Solanum tuberosum L.).

All over the world, potato (Solanum tuberosum L.) production is constrained by several biotic and abiotic factors. Many techniques and mechanisms have been used to overcome these hurdles and increase food for the rising population. In crop plants, the mitogen-activated protein kinase (MAPK) cascade, a significant regulator of the MAPK pathway under various biotic and abiotic stress conditions, is one of the targets to increase productivity. MAPK plays a significant role under drought stress in potato. However, the function of MAPK in drought resistance in potato is poorly understood. In this study, we wanted to identify the function of StMAPK10 in the drought resistance in potato. StMAPK10 was up-regulated under drought conditions and dynamically modulated by abiotic stresses. Over-expression and down-regulation of StMAPK10 revealed that StMAPK10 stimulated potato growth under drought conditions, as demonstrated by changes in SOD, CAT, and POD activity, as well as H2O2, proline, and MDA content. StMAPK10 up-regulation exaggerated the drought resistance of the potato plant by uplifting antioxidant activities and photosynthetic indices. Overexpressed-StMAPK10 potato lines showed highly significant results for physiological and photosynthetic indices in response to drought stress, while knockdown expression showed opposite outcomes. Additionally, subcellular localization and phenotypic analysis of transgenic and non-transgenic plants substantiated the role of the increased expression of StMAPK10 against drought stress. The results could provide novel insights into the functionality of StMAPK10 in drought responses and conceivable mechanisms.

Insights into the assembly process and properties of regenerated cellulose beads prepared in alkali/urea aqueous solutions

Taking the perspective of cellulose molecular chain assembly via the “bottom-top” route, we delve into the influence of both the cellulose solution and the coagulation bath on the assembly process and structure of regenerated cellulose beads (RCBs). The results show that cellulose molecular weight, mass fraction, and the presence of surfactant have an impact on RCBs. Contrary to traditional views where the structures of material are determined by solvent-nonsolvent exchange rate, ion-cellulose binding capacity also affects RCBs. Overall, the influence of ions follows the Hofmeister sequence. Kosmotropes promote the assembly of cellulose chains and elementary fibers, leading to “salting out” effects, reduced pore size of RCBs, increased crystallinity, and enhanced mechanical properties. In contrast, chaotropes induce “salting in” effects, resulting in opposite outcomes. The average pore size of RCBs coagulated in NaSCN solution was approximately 15-folds larger than those prepared in sodium citrate solution. Anions have a greater impact than cations, and both “salting out” and “salting in” effects strengthen with concentration. Temperature variations primarily affect solvent and nonsolvent exchange speed during cellulose regeneration. These findings provide new insights into regulating RCBs, enabling tailored performance for different applications.

Synergistic effects of different ionic surfactants and temperature on rheological behavior and air-void structure of cement mortar

The influence of air entrainment on rheological behavior of fresh cementitious materials has attracted a lot of attention in the past years, but the results are still in controversy. In this research, cement mortars were prepared with equivalent air contents using different air-entraining admixtures (AEAs) to measure their fresh-state performance and hardened air-void system at variable temperature conditions, which aimed to clarify and unveil the coupled effects of different surfactants and temperature for the first time. The adsorption amount of AEA, zeta potential of cement, along with hydration kinetics of mixtures were evaluated to characterize the interaction of air bubbles with cement grains. It was found that for mixture without superplasticizer (SP), the impact of air entrainment on rheological parameters was dependent on the interaction intensity of AEA molecules with cement. For SP-plasticized mixture, air entrainment tended to cause a shear-thinning behavior with decreased plastic viscosity, while its influence on yield stress was in accordance with the situation without SP. The hardened samples with anionic surfactant contained more small voids and lacked big voids, whereas the samples with cationic surfactant showed opposite outcomes. With temperature decreasing, both the average chord length and the spacing factor of air voids increased owing to the reduced yield stress of mixture. The results will provide in-depth illustrations for understanding how air bubbles change the rheological behavior of mixture, and more importantly it will explain the seemingly inconsistent findings reported by previous literatures.

Matrix metalloproteinase-1 as a potential biomarker for early gastric cancer detection and its effect on gastric cancer cell proliferation and migration

The present study aimed to investigate the association between matrix metalloproteinase-1 (MMP-1) and early gastric cancer (EGC), while also evaluating the effect of MMP-1 on gastric cancer cell proliferation and migration. Transcriptome RNA sequencing and database analysis were conducted to assess the relationship between MMP-1 expression and EGC. Differences in MMP-1 expression between clinical EGC samples and paracancerous tissues were detected using fluorescence quantitative polymerase chain reaction (PCR). In N87 gastric cancer cells, changes in proliferation- and migration-related indicator expression were determined. Gene sequencing revealed differential expression of MMP-1 in early and advanced gastric cancers. Furthermore, enhanced MMP-1 expression was observed in early and advanced gastric cancer tissues, exhibiting a positive correlation with the malignant phenotype in gastric cancer cell lines. Fluorescence quantitative PCR revealed considerably higher MMP-1 expression in EGC tissues than in paracancerous tissues. CCK8 and EdU assays demonstrated a significant increase in N87 cell proliferation on MMP-1 upregulation and a decrease on its downregulation. The scratch assay results demonstrated a corresponding enhancement in N87 cell migratory capacity with MMP-1 upregulation, which was attenuated on its downregulation. Western blot experiments revealed a decrease in the expression of the epithelial-mesenchymal transition-related protein E-cadherin after MMP-1 upregulation, while vimentin expression significantly increased. Conversely, the downregulation of MMP-1 led to opposite outcomes. Overall, MMP-1 emerges as a potential biomarker for EGC diagnosis and plays a crucial role in the regulation of N87 gastric cancer cell proliferation and migration.

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice.

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.