A2AR-mediated CXCL5 upregulation on macrophages promotes NSCLC progression via NETosis.

Tumor-associated macrophages (TAMs) are abundant in tumors and interact with tumor cells, leading to the formation of an immunosuppressive microenvironment and tumor progression. Although many studies have explored the mechanisms underlying TAM polarization and its immunosuppressive functions, understanding of its progression remains limited. TAMs promote tumor progression by secreting cytokines, which subsequently recruit immunosuppressive cells to suppress the antitumor immunity. In this study, we established an in vitro model of macrophage and non-small cell lung cancer (NSCLC) cell co-culture to explore the mechanisms of cell-cell crosstalk. We observed that in NSCLC, the C-X-C motif chemokine ligand 5 (CXCL5) was upregulated in macrophages because of the stimulation of A2AR by adenosine. Adenosine was catalyzed by CD39 and CD73 in macrophages and tumor cells, respectively. Nuclear factor kappa B (NFκB) mediated the A2AR stimulation of CXCL5 upregulation in macrophages. Additionally, CXCL5 stimulated NETosis in neutrophils. Neutrophil extracellular traps (NETs)-treated CD8+ T cells exhibited upregulation of exhaustion-related and cytosolic DNA sensing pathways and downregulation of effector-related genes. However, A2AR inhibition significantly downregulated CXCL5 expression and reduced neutrophil infiltration, consequently alleviating CD8+ T cell dysfunction. Our findings suggest a complex interaction between tumor and immune cells and its potential as therapeutic target.

Dynamic surveillance of lymphocyte subsets in patients with non-small cell lung cancer during chemotherapy or combination immunotherapy for early prediction of efficacy.

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Lymphocytes are the primary executors of the immune system and play essential roles in tumorigenesis and development. We investigated the dynamic changes in peripheral blood lymphocyte subsets to predict the efficacy of chemotherapy or combination immunotherapy in NSCLC. Methods: This retrospective study collected data from 81 patients with NSCLC who received treatments at the First Affiliated Hospital of Zhengzhou University from May 2021 to May 2023. Patients were divided into response and non-response groups, chemotherapy and combination immunotherapy groups, and first-line and multiline groups. We analyzed the absolute counts of each lymphocyte subset in the peripheral blood at baseline and after each treatment cycle. Within-group and between-group differences were analyzed using paired Wilcoxon signed-rank and Mann-Whitney U tests, respectively. The ability of lymphocyte subsets to predict treatment efficacy was analyzed using receiver operating characteristic curve and logistic regression. Results: The absolute counts of lymphocyte subsets in the response group significantly increased after the first cycle of chemotherapy or combination immunotherapy, whereas those in the non-response group showed persistent decreases. Ratios of lymphocyte subsets after the first treatment cycle to those at baseline were able to predict treatment efficacy early. Combination immunotherapy could increase lymphocyte counts compared to chemotherapy alone. In addition, patients with NSCLC receiving chemotherapy or combination immunotherapy for the first time mainly presented with elevated lymphocyte levels, whereas multiline patients showed continuous reductions. Conclusion: Dynamic surveillance of lymphocyte subsets could reflect a more actual immune status and predict efficacy early. Combination immunotherapy protected lymphocyte levels from rapid decrease and patients undergoing multiline treatments were more prone to lymphopenia than those receiving first-line treatment. This study provides a reference for the early prediction of the efficacy of clinical tumor treatment for timely combination of immunotherapy or the improvement of immune status.

Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring.

Liquid biopsy, a novel detection method, has recently become an active research area in clinical cancer owing to its unique advantages. Studies on circulating free DNA, circulating tumor cells, and exosomes obtained by liquid biopsy have shown great advances and they have entered clinical practice as new cancer biomarkers. The metabolism of the body is dynamic as cancer originates and progresses. Metabolic abnormalities caused by cancer can be detected in the blood, sputum, urine, and other biological fluids via systemic or local circulation. A considerable number of recent studies have focused on the roles of metabolic molecules in cancer. The purpose of this review is to provide an overview of metabolic markers from various biological fluids in the latest clinical studies, which may contribute to cancer screening and diagnosis, differentiation of cancer typing, grading and staging, and prediction of therapeutic response and prognosis.

24-Hour movement behaviors and executive functions in preschoolers: A compositional and isotemporal reallocation analysis.

This cross-sectional study explored the relationship between 24-hour movement behaviors and executive function (EF) in preschool children. A total of 426 Han Chinese preschoolers (231 males; 3.8 ± 0.6 years old) from Zhuhai, Guangdong Province, China were selected from October 2021 to December 2021. Accelerometers were used to measure physical activity (PA) and sedentary behavior (SB), while sleep duration was obtained via a parent-report questionnaire. Components of EF (cognitive flexibility, inhibitory control, and working memory) were assessed using computerized behavioral tasks. The daily composition was significantly associated with inhibitory control and working memory. Inhibitory control improvements were linked to the addition of moderate-to-vigorous physical activity (MVPA) at the expense of SB and sleep. The reallocation between MVPA, SB, sleep, and light physical activity yielded a significant association with working memory.

Moral characteristics predicting COVID-19 vaccination.

OBJECTIVE: The current study aims to assess, for the first time, whether vaccination is predicted by different behavioral and cognitive aspects of moral decision-making. BACKGROUND: Studies linking moral factors to vaccination have largely examined whether vaccination decisions can be explained by individual differences in the endorsement of various principles and norms central to deontology-based arguments in vaccination ethics. However, these studies have overlooked whether individuals prioritize norms over other considerations when making decisions, such as maximizing consequences (utilitarianism). METHOD: In a sample of 1492 participants, the current study assessed whether vaccination is explained by individual differences in three aspects of moral decision-making (consequence sensitivity, norm sensitivity, and action tendency), while also considering ethics position (idealism, relativism) and moral identity. RESULTS: Supportive vaccination (vaccine uptake accompanied by a positive attitude toward vaccines) was associated with utilitarianism (increased consequence sensitivity) and increased tolerance to risks and harm toward others. Meanwhile, although those in the non-vaccinated group was associated with higher harm sensitivities, they neither supported nor received the COVID vaccines (when vaccines prevent harm from infection). CONCLUSION: Pro-vaccination messages may be made more effective by addressing perceptions of harms associated with vaccines and infections, respectively.

Not all discounts are created equal: Regional activity and brain networks in temporal and effort discounting.

Reward outcomes associated with costs like time delay and effort investment are generally discounted in decision-making. Standard economic models predict rewards associated with different types of costs are devalued in a similar manner. However, our review of rodent lesion studies indicated partial dissociations between brain regions supporting temporal- and effort-based decision-making. Another debate is whether options involving low and high costs are processed in different brain substrates (dual-system) or in the same regions (single-system). This research addressed these issues using coordinate-based, connectivity-based, and activation network-based meta-analyses to identify overlapping and separable neural systems supporting temporal (39 studies) and effort (20 studies) discounting. Coordinate-based activation likelihood estimation and resting-state connectivity analyses showed immediate-small reward and delayed-large reward choices engaged distinct regions with unique connectivity profiles, but their activation network mapping was found to engage the default mode network. For effort discounting, salience and sensorimotor networks supported low-effort choices, while the frontoparietal network supported high-effort choices. There was little overlap between the temporal and effort networks. Our findings underscore the importance of differentiating different types of costs in decision-making and understanding discounting at both regional and network levels.

Acute stress promotes brain network integration and reduces state transition variability.

Despite the prevalence of stress, how brains reconfigure their multilevel, hierarchical functional organization in response to acute stress remains unclear. We examined changes in brain networks after social stress using whole-brain resting-state functional MRI (fMRI) by extending our recently published nested-spectral partition method, which quantified the functional balance between network segregation and integration. Acute stress was found to shift the brain into a more integrated and less segregated state, especially in frontal-temporal regions. Stress also stabilized brain states by reducing the variability of dynamic transition between segregated and integrated states. Transition frequency was associated with the change of cortisol, and transition variability was correlated with cognitive control. Our results show that brain networks tend to be more integrated and less variable after acute stress, possibly to enable efficient coping.

To learn or to gain: neural signatures of exploration in human decision-making.

Individuals not only take actions to obtain immediate rewards but also to gain more information to guide future choices. An ideal exploration-exploitation balance is crucial for maximizing reward over the long run. However, the neural signatures of exploration in humans remain unclear. Using quantitative meta-analyses of functional magnetic resonance imaging experiments on exploratory behaviors, we sought to identify the concordant activity pertaining to exploration over a range of experiments. The results revealed that exploration activates concordant brain activity associated with risk (e.g., dorsal medial prefrontal cortex and anterior insula), cognitive control (e.g., dorsolateral prefrontal cortex and inferior frontal gyrus), and motor processing (e.g., premotor cortex). These stereotaxic maps of exploration may indicate that exploration is highly linked to risk processing, but is also specifically associated with regions involved in executive control processes. Although this explanation should be treated as exploratory, these findings support theories positing an important role for the prefrontal-insular-motor cortical network in exploration.

The neural underpinnings of allocentric thinking in a novel signaling task.

The ability to adopt the perspectives of others is fundamental to effective communication in social interactions. However, the neural correlates of allocentric thinking in communicative signaling remain unclear. We adapted a novel signaling task in which the signaler was given the target word and must choose a one-word signal to help the receiver guess the target. Behavioral results suggest that speakers can use allocentric thinking to choose signals that are salient from the perspective of the receiver rather than their own point of view. At the neural level, functional magnetic resonance imaging (fMRI) data reveal that the medial prefrontal cortex (mPFC), ventral striatum, and temporal-parietal junction are more activated when signalers engage in allocentric than egocentric thinking. Moreover, functional connectivity between the mPFC and ventral striatum predicted individuals' perspective-taking ability during successful communication. These findings reveal that neural representations in the mPFC-striatum network support perspective-taking in complex social decision making, providing a new perspective on how the brain arbitrates between allocentric thinking and egocentric thinking in communication and social coordination.

Neural correlates of recursive thinking during interpersonal strategic interactions.

To navigate the complex social world, individuals need to represent others' mental states to think strategically and predict their next move. Strategic mentalizing can be classified into different levels of theory of mind according to its order of mental state attribution of other people's beliefs, desires, intentions, and so forth. For example, reasoning people's beliefs about simple world facts is the first-order attribution while going further to reason people's beliefs about the minds of others is the second-order attribution. The neural substrates that support such high-order recursive reasoning in strategic interpersonal interactions are still unclear. Here, using a sequential-move interactional game together with functional magnetic resonance imaging (fMRI), we showed that recursive reasoning engaged the frontal-subcortical regions. At the stimulus stage, the ventral striatum was more activated in high-order reasoning as compared with low-order reasoning. At the decision stage, high-order reasoning activated the medial prefrontal cortex (mPFC) and other mentalizing regions. Moreover, functional connectivity between the dorsomedial prefrontal cortex (dmPFC) and the insula/hippocampus was positively correlated with individual differences in high-order social reasoning. This work delineates the neural correlates of high-order recursive thinking in strategic games and highlights the key role of the interplay between mPFC and subcortical regions in advanced social decision-making.

Age-dependent statistical learning trajectories reveal differences in information weighting.

Statistical learning (SL) is the ability to generate predictions based on probabilistic dependencies in the environment, an ability that is present throughout life. The effect of aging on SL is still unclear. Here, we explore statistical learning in healthy adults (40 younger and 40 older). The novel paradigm tracks learning trajectories and shows age-related differences in overall performance, yet similarities in learning rates. Bayesian models reveal further differences between younger and older adults in dealing with uncertainty in this probabilistic SL task. We test computational models of 3 different learning strategies: (a) Win-Stay, Lose-Shift, (b) Delta Rule Learning, (c) Information Weights to explore whether they capture age-related differences in performance and learning in the present task. A likely candidate mechanism emerges in the form of age-dependent differences in information weights, in which young adults more readily change their behavior, but also show disproportionally strong reactions toward erroneous predictions. With lower but more balanced information weights, older adults show slower behavioral adaptation but eventually arrive at more stable and accurate representations of the underlying transitional probability matrix. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Burden of viral gastroenteritis in children living in rural China: Population-based surveillance.

BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.

Dexmedetomidine Alleviates Postpartum Depressive Symptoms following Cesarean Section in Chinese Women: A Randomized Placebo-Controlled Study.

OBJECTIVES: Few studies have investigated the prophylactic efficacy of dexmedetomidine (DEX) in postpartum depressive symptoms (PDS). A randomized double-blind placebo-controlled trial was conducted to investigate whether the administration of DEX, immediately after delivery and for patient-controlled intravenous analgesia (PCIA), can attenuate PDS. METHODS: A total of 600 parturients scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated into the control group (infusion with 0.9% normal saline after delivery and PCIA with sufentanil) and the DEX group (DEX infusion 0.5 µg/kg after delivery and PCIA with DEX plus sufentanil). The prevalence of postpartum depressive disorders was indicated by the Edinburgh Postnatal Depression Scale (EPDS). Postoperative analgesia, sedation, and sleep quality of parturients were also assessed. RESULTS: Postpartum blues and PDS prevalence in the DEX, versus control, group were significantly lower (5.0% vs 14.1%, p<0.001; 5.7% vs 16.3%, p<0.001, respectively), especially in parturients with antenatal depression or moderate stress during pregnancy. Compared with the control group, the EPDS score at postpartum days 7 and 42 in the DEX group was significantly lower (4.23 ± 4.37 vs 1.93 ± 3.36, p<0.001; 4.68 ± 4.78 vs 1.99 ± 3.18, p<0.001, respectively), as was the incidence of postpartum self-harm ideation at postpartum days 7 and 42 in the DEX group versus the control group (1.1% vs 4.0%, p=0.03; 0.4% vs 2.9%, p=0.04, respectively). The pain score and the sleep quality in the DEX group were better than that in the control group (p<0.001). CONCLUSION: The application of DEX in the early postpartum period can significantly attenuate the incidence of postpartum depressive disorders.

Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai.

Acute infectious gastroenteritis cases in Shanghai, reported over three years, were analyzed. Pathogens were identified in 1031 patients; of these, 725 and 306 were bacterial and viral cases, respectively. Vibrio parahemolyticus and Salmonella were the dominant bacteria, and Caliciviridae and Reoviridae were the dominant viral families in the local area. The acute gastroenteritis epidemic peaks appeared in August and January, which represented the active peak periods of bacteria and viruses, respectively. Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. Pathogen stratification showed that age, vomiting and red cell-positive fecal matter were associated with males with ORs of 0.99, 0.61 and 1.71, respectively, in bacterial gastroenteritis; and the migrant ratio was higher in males with an OR of 2.29 only in viral gastroenteritis. In conclusion, although bacterial and viral gastroenteritis shared many features, epidemiological and clinical factors differed between sexes and pathogens.

Common and distinct neural correlates of self-serving and prosocial dishonesty.

People often anticipate certain benefits when making dishonest decisions. In this article, we aim to dissociate the neural-cognitive processes of (1) dishonest decisions that focus on overall benefits of being dishonest (regardless of whether the benefits are self-serving or prosocial) from (2) those that distinguish between self-serving and prosocial benefits. Thirty-one participants had the opportunity to maximize their monetary benefits by voluntarily making dishonest decisions while undergoing functional magnetic resonance imaging (fMRI). In each trial, the monetary benefit of being dishonest was either self-serving or prosocial. Behaviorally, we found dissociable patterns of dishonest decisions: some participants were dishonest for overall benefits, while others were primarily dishonest for self-serving (compared with prosocial) benefits. When provided an opportunity to be dishonest for either self-serving or prosocial benefits, participants with a stronger overall tendency to be dishonest had stronger vmPFC activity, as well as stronger functional connectivity between the vmPFC and dlPFC. Furthermore, vmPFC activity was associated with decisions to be dishonest both when the benefits of being dishonest were self-serving and prosocial. Conversely, high self-serving-biased participants had stronger striatum activity and stronger functional connectivity between the striatum and middle-mPFC when they had a chance to be dishonest for self-serving (compared with prosocial) benefits. Altogether, we showed that activity in (and functional connectivity between) regions in the valuation (e.g., vmPFC and Str) and executive control (e.g., dlPFC and mmPFC) systems play a key role in registering the social-related goal of dishonest decisions.

Burden of acute gastroenteritis caused by norovirus in China: A systematic review.

BACKGROUND: To understand the epidemiology and disease burden of norovirus (NoVs) gastroenteritis in China, a systematic review was conducted. METHODS: Studies on acute gastroenteritis (AGE) caused by NoVs from mainland China, published before 2017 were searched. All retrieved articles were screened and reviewed by a standardized algorithm. NoVs detection rates as well as strain variations by ages, seasonal variations and geographic locations were analyzed using random-effects model. RESULTS: A total of 225 articles were included in the final analysis. Similar detection rates at 21.0% and 19.8% were obtained from the North and the South, respectively. NoVs infection occurred year round, with a peak between October and January in the North and between August and November in the South. High detection rates (∼29%) of NoVs were found in adults and the elderly and in children aged 6-35 months (∼22%). The predominant strains were GII.4 (70.4%), followed by GII.3 (13.5%). CONCLUSION: NoVs cause significant disease burden in China which warrants development of vaccines against NoVs, particularly for children and the elderly who are vulnerable to gastroenteritis diseases. To achieve a broad protection, continual monitoring NoV epidemics and strain variations for selection of proper vaccine strains is critical.

Decision ambiguity is mediated by a late positive potential originating from cingulate cortex.

People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction.

Variation analysis of norovirus among children with diarrhea in rural Hebei Province, north of China.

To understand the distribution of genotyping, as well as evolution of norovirus circulating among children<5yrs., a population-based diarrhea surveillance targeted children<5yrs. was conducted in rural Zhengding County, Hebei Province, China between October 2011 and March 2012. RT-PCR was used to amplify the capsid-encoding region of GI and GII norovirus to identify norovirus infection. All PCR products were sequenced and analyzed for genotyping and constructing phylogenetic tree. Dynamic distribution network was constructed by TempNet to illustrate the genetic relationships at two different time points. Bayesian evolutionary inference techniques were applied by BEAST software to study the norovirus evolution rate. During the 6-month surveillance period, 1091 episodes of diarrhea were reported from 5633 children under 5years of age lived in catchment area. 115 of 1091 stool specimens were detected as norovirus positive (10.54%). Five genotypes based on capsid gene sequences were identified, including GII.2 (11), GII.3 (52), GII.4 (47), GII.6 (4) and GII.7 (1). An identical haplotype of GII.4 circulated between 2006 and 2011 in Hebei Province. A mean rate of 6.29×10-2 nucleotide substitutions/site/year (s/s/y) was obtained for GII.3 viruses in Hebei, while the GII.4 viruses evolved at a mean rate of 3.67×10-2s/s/y. In conclusions, GII.3 (45.22%) and GII. 4(40.87%) are the predominant strain in Hebei Province in the winter season of 2011 and 2012. Different from the current consensus, our study shows that GII.3 noroviruses in Hebei Province evolved at a faster rate than GII.4 viruses.