Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Platelet-Derived Growth Factor C Facilitates Malignant Behavior of Pancreatic Ductal Adenocarcinoma by Regulating SREBP1 Mediated Lipid Metabolism.

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.

The new pattern for dual NOTCH pathway involving nuclear transcription and mitochondrial regulation supports therapeutic mechanism of 4-butyl benzophenone derivatives against SIRS.

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFß, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1ß). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway.

The proactive and reactive mechanisms of learned spatial suppression.

Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Supporting data-enhanced hybrid ordinary differential equation model for phosphate dynamics in municipal wastewater treatment.

A parallel hybrid ordinary differential equation (ODE) integrating the Activated Sludge Model No. 2d (ASM2d) and an artificial neural network (ANN) was developed to simulate biological phosphorus removal (BPR) with high accuracy and interpretability. Two novelties were introduced; first, the involved supporting data (i.e., phosphate-release activity) were incorporated as an input in the ANN. Second, the outputs of the ANN were selective. Three models were implemented using different ANN outputs, and all three outperformed ASM2d in phosphate estimation for anaerobic/aerobic sequencing batch reactor operation. In particular, the incorporation of four variables responsible for BPR into the ANN enabled the highest performance (R2 = 0.93) owing to the capture of increasing phosphate-accumulating organisms (PAOs). The ANN with the supporting data worked satisfactorily to compensate for ASM2d by adding proper PAOs, resulting in improvement in phosphate estimation. The novel parallel hybrid ODE can simulate BPR while maintaining physical meaning.

The clinical value of inflammation index in predicting ICU mortality of critically ill patients with intracerebral hemorrhage.

Background: The inflammatory response holds paramount significance in the context of intracerebral hemorrhage (ICH) and exhibits a robust correlation with mortality rates. Biological markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI) play crucial roles in influencing the systemic inflammatory response following ICH. This study aims to compare the predictive efficacy of NLR, PLR, LMR, SII, and SIRI concerning the risk of mortality in the intensive care unit (ICU) among critically ill patients with ICH. Such a comparison seeks to elucidate their early warning capabilities in the management and treatment of ICH. Methods: Patients with severe ICH requiring admission to the ICU were screened from the Medical Information Marketplace for Intensive Care (MIMIC-IV) database. The outcomes studied included ICU mortality and 30 day ICU hospitalization rates, based on tertiles of the NLR index level. To explore the relationship between the NLR index and clinical outcomes in critically ill patients with ICH, we utilized receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and multivariate logistic regression analysis. Results: A total of 869 patients (51.9% male) were included in the study, with an ICU mortality rate of 22.9% and a 30 day ICU hospitalization rate of 98.4%. Among the five indicators examined, both the ROC curve and DCA indicated that NLR (AUC: 0.660, 95%CI: 0.617-0.703) had the highest predictive ability for ICU mortality. Moreover, this association remained significant even after adjusting for other confounding factors during multivariate analysis (HR: 3.520, 95%CI: 2.039-6.077). Based on the results of the multivariate analysis, incorporating age, albumin, lactic acid, NLR, and GCS score as variables, we developed a nomogram to predict ICU mortality in critically ill patients with ICH. Conclusion: NLR emerges as the most effective predictor of ICU mortality risk among critically ill patients grappling with ICH when compared to the other four indicators. Furthermore, the integration of albumin and lactic acid indicators into the NLR nomogram enhances the ability to promptly identify ICU mortality in individuals facing severe ICH.

The computational and neural substrates of individual differences in impulsivity under loss framework.

Numerous neuroimaging studies have identified significant individual variability in intertemporal choice, often attributed to three neural mechanisms: (1) increased reward circuit activity, (2) decreased cognitive control, and (3) prospection ability. These mechanisms that explain impulsivity, however, have been primarily studied in the gain domain. This study extends this investigation to the loss domain. We employed a hierarchical Bayesian drift-diffusion model (DDM) and the inter-subject representational similarity approach (IS-RSA) to investigate the potential computational neural substrates underlying impulsivity in loss domain across two experiments (n = 155). These experiments utilized a revised intertemporal task that independently manipulated the amounts of immediate and delayed-loss options. Behavioral results demonstrated positive correlations between the drift rate, measured by the DDM, and the impulsivity index K in Exp. 1 (n = 97) and were replicated in Exp. 2 (n = 58). Imaging analyses further revealed that the drift rate significantly mediated the relations between brain properties (e.g., prefrontal cortex activations and gray matter volume in the orbitofrontal cortex and precuneus) and K in Exp. 1. IS-RSA analyses indicated that variability in the drift rate also mediated the associations between inter-subject variations in activation patterns and individual differences in K. These findings suggest that individuals with similar impulsivity levels are likely to exhibit similar value processing patterns, providing a potential explanation for individual differences in impulsivity within a loss framework.

Comparative Proteomic Analysis Reveals the Effect Mechanisms of Glucose on the Biomass and Phenolic Glycoside Esters Synthesis Activity of Candida Parapsilosis ACCC 20221 Whole-Cell Catalyst.

A new Candida parapsilosis ACCC 20221 (C. parapsilosis ACCC 20221) whole-cell catalyst with a high phenolic glycoside esters synthesis activity and large biomass was obtained after culture with glucose. The possible mechanisms were revealed by using comparative proteomics. It found the expression of proteins involved in post-translational modification, protein turnover, and chaperone, and RNA processing and modification was upregulated, which ensured the metabolic balance and accurate translation, correct folding, and post-translational modification of proteins, thus enhancing the production of lipases in C. parapsilosis ACCC 20221 cultured with glucose. Moreover, the glycolysis pathway, tricarboxylic acid cycle, and fatty acids synthesis were enhanced, while the ß-oxidation of fatty acids was weakened in C. parapsilosis ACCC 20221 cells cultured with glucose, which led to an increase in energy generation and cell membrane synthesis; thus, large biomass was obtained. In addition, CCE40476.1 and CAC86400.1, which were likely to exert arbutin esters synthesis activity in C. parapsilosis ACCC 20221, were screened, and it was found that vinyl propionate could easily enter the catalytic pocket of CCE40476.1 and form hydrogen bonding interactions with Leu191 and Ser266.

A case report of small intestinal volvulus caused by lipomatosis of the small intestine successfully treated with enterectomy.

Small intestinal lipomatosis is a rare condition that presents a diagnostic challenge due to the absence of identifiable clinical symptoms and limitations of small intestine examination methods. Consequently, preoperative diagnosis is difficult and only a limited number of cases have been documented in the scientific literature. Here, we report a rare case of volvulus caused by small intestinal lipomatosis. A 58-year-old female patient was tentatively diagnosed with acute ileus. The whirl sign was detected using abdominal three-dimensional enhanced computed tomography, along with marked local intestinal dilation and multiple irregular fat-like containing lesions. During surgery, abnormal dilation of the small intestine between 80 and 220 cm from the ileocecal valve was detected and the affected intestine displayed a folded and twisted configuration. Examination of the resected intestine showed that the inner wall of the diseased intestinal lumen was covered with more than 100 lipomas of different sizes, the largest of which measured ~8.0 cm in diameter. Based on clinical symptoms alone, it was difficult to identify the cause of intestinal volvulus before surgery. Complete resection of the affected small intestine and subsequent pathological analysis yielded a definitive diagnosis of small intestinal lipomatosis. While small intestinal lipomatosis is a rare condition, prognosis is favorable if diagnosed early and treated appropriately. The application of three-dimensional enhanced computed tomography imaging can aid in accurate diagnosis, while complete resection of the affected small intestine is crucial to improve patient prognosis.

Soil moisture alters the responses of alpine ecosystem productivity to environmental factors, especially VPD, on the Qinghai-Tibetan Plateau.

Water availability, which can be represented by soil water content (SWC), plays a crucial role in plant growth and productivity across the cold and arid Qinghai-Tibetan Plateau. However, the indirect effects of SWC are less well understood, and a more comprehensive understanding of its regulating effects may enhance the recognition of its importance, as this factor is pivotal for accurately predicting the future response of alpine ecosystems to climate change. In this study, in situ eddy covariance observation data from typical alpine ecosystems and satellite data covering the Qinghai-Tibetan region were used to comprehensively reveal the effects of SWC on ecosystem productivity. The results indicated that SWC played an important role in regulating the responses of gross primary productivity (GPP) to other environmental factors over both time and space, especially in terms of the responses of GPP to vapor pressure deficit (VPD). The regulating effect can be summarized as follows: there was a specific SWC value (SWC = 0.24 m3 m-3 on the Qinghai-Tibetan Plateau) above which SWC was no longer the primary limiting factor. The responses of GPP to certain environmental factors shifted from negative to positive when the SWC increased above this value. The responses of GPP to VPD exhibited the highest sensitivity to the regulating effects of SWC, with a general response pattern found across different temporal and spatial scales. The findings revealed divergent responses of GPP to environmental factors under different SWC conditions and between arid and humid regions, emphasizing the importance of soil water conditions. These findings suggest that water conditions should be given primary consideration in global change studies.

Metabolic Engineering of Escherichia coli for Bioproduction of (R)-3-Hydroxybutyric Acid through a Three-Pronged Approach.

(R)-3-Hydroxybutyric acid (R-3HB) is an important chiral chemical with extensive applications in the agricultural, food, and chemical industries. The synthesis of R-3HB by microbial fermentation is of interest due to its remarkable stereoselectivity and economy. However, the low production of R-3HB failed to meet the needs of large-scale industrial production. In this study, an engineered strain for the efficient biosynthesis of R-3HB was constructed through a three-pronged approach encompassing biosynthetic pathway optimization, engineering of NADPH regenerators, and central metabolism regulation. The engineered strain Q5081 produced 75.7 g/L R-3HB, with a productivity of 1.26 g/L/h and a yield of 0.34 g/g glucose in fed-batch fermentation, showing the highest reported titer and productivity of R-3HB to date. We also performed transcriptome sequencing and annotation to illustrate the mechanism underlying the enhanced R-3HB production. The systematic metabolic engineering by a three-pronged approach demonstrated the feasibility of improving the biosynthesis, and the engineered strain Q5081 has the potential for widespread applications in the industrial production of R-3HB.

Acute kidney injury after intracerebral hemorrhage: a mini review.

Intracerebral hemorrhage (ICH) stands as a prevalent and pivotal clinical condition. The potential cooccurrence of acute kidney injury (AKI) among afflicted individuals can profoundly influence their prognosis. In recent times, there has been a growing focus among clinical practitioners on researching the relationship between ICH and AKI. AKI occurring concurrently with ICH predominantly arises from both hemodynamic and non-hemodynamic mechanisms. The latter encompasses neurohumoral regulation, inflammatory response, oxidative stress, and iatrogenic factors such as contrast agents, dehydrating agents, antibiotics, and diuretics. Moreover, advanced age, hypertension, elevated baseline creatinine levels, chronic kidney disease, and larger hematomas predispose patients to AKI. Additionally, the current utilization of biomarkers and the development of predictive models appear promising in identifying patients at risk of AKI after ICH. This article aims to underscore the potential of the aforementioned insights to inspire novel approaches to early clinical intervention.

Comprehensive assessment of multiple biomarker mechanisms in the brackish water clam Corbicula japonica exposed to polystyrene microplastics using structural equation modeling.

Using structural equation modeling (SEM), we investigated multiple biomarker mechanisms in terms of biochemical and individual marker responses in the brackish water clam Corbicula japonica following acute exposure to polystyrene microplastic (PS-MP). This study is the first to comprehensively explore multiple biomarker responses in bivalves using SEM. The model revealed that PS-MP accumulation was an independent biomarker, exhibiting significant direct effects on superoxide dismutase (SOD) and catalase (CAT) among the biochemical markers. Although CAT generally interacts closely with SOD, no significant relationship was identified between them, indicating that CAT may have independently responded to PS-MP stress. Among individual markers, significant indirect effects were observed on clearance rate (CR), reflecting feeding activity and valve open rate, indicating excretion activity via SOD and CAT. Finally, the carbon-based scope for growth was significantly influenced by CR. SEM is efficient and useful for identifying significant direct and indirect pathway relationships and for uncovering uncommon relationships in unified multiple biomarker mechanisms in aquatic studies.

The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage.

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079-0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Adaptive Evolution for the Efficient Production of High-Quality d-Lactic Acid Using Engineered Klebsiella pneumoniae.

d-Lactic acid serves as a pivotal platform chemical in the production of poly d-lactic acid (PDLA) and other value-added products. This compound can be synthesized by certain bacteria, including Klebsiella pneumoniae. However, industrial-scale lactic acid production in Klebsiella pneumoniae faces challenges due to growth inhibition caused by lactic acid stress, which acts as a bottleneck in commercial microbial fermentation processes. To address this, we employed a combination of evolutionary and genetic engineering approaches to create an improved Klebsiella pneumoniae strain with enhanced lactic acid tolerance and production. In flask fermentation experiments, the engineered strain achieved an impressive accumulation of 19.56 g/L d-lactic acid, representing the highest production yield observed in Klebsiella pneumoniae to date. Consequently, this strain holds significant promise for applications in industrial bioprocessing. Notably, our genome sequencing and experimental analyses revealed a novel correlation between UTP-glucose-1-phosphate uridylyltransferase GalU and lactic acid resistance in Klebsiella pneumoniae. Further research is warranted to explore the potential of targeting GalU for enhancing d-lactic acid production.

Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment.

The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.

Happy people are always similar: The evidence from brain morphological and functional inter-subject correlations.

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance.

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.