Psychometrics of the modified family-centered care assessment short version for childhood obesity.

BACKGROUND: Incorporating principles of family-centered care into pediatric weight management interventions can improve the effectiveness and quality of treatment and reduce attrition rates. To assess the family-centeredness of interventions, reliable, valid, and easy-to-administer scales are needed. The purpose of the study was to develop a shortened version of the modified Family Centered Care Assessment (mFCCA) and assess its psychometric properties. METHODS: The mFCCA, a scale to assess the family-centeredness of interventions for childhood obesity, was administered to families following the Connect for Health randomized control trial evaluating the effectiveness of a primary care-based pediatric weight management intervention. We iteratively removed items from the mFCCA and used Rasch modeling to examine the reliability and validity of the shortened scale. RESULTS: We included data from 318 parents and the exploratory factor analysis showed the presence of a single factor. The results of the Rasch modeling demonstrated acceptable internal consistency of the scale (0.7) and strong validity as evidenced by the overall model fit and range of item difficulty. Following the psychometric analyses, we reduced the number of items from 24 to 8 items. CONCLUSION: The mFCCA short version demonstrates good psychometrics and can be used to evaluate the family-centeredness of childhood obesity interventions with reduced participant burden, thereby improving outcomes for children with obesity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02124460 registered on April 24, 2014.

Preparation of Thin-Layered Hexagonal Boron Nitride Nanosheet with Oxygen Doping.

Hexagonal boron nitride nanosheet (h-BNNS), a structural analogue of graphene, possesses remarkable properties such as exceptional electrical insulation, great resistance to corrosion, excellent mechanical strength, and thermal conductivity. Nonetheless, its continued development is still hampered by the lack of a preparation technique with an easy-to-follow procedure and reliable composition and structure control. In this study, we investigated a two-step protocol for uniform size production of thin-layered h-BNNS. By carefully manipulating the crystallization degree during synthesis of h-BN powder and employing subsequent hydrothermal treatment, we successfully obtained h-BNNS with an even thickness of only a few atomic layers. Compared with the broadly used liquid-phase exfoliation process, not only is the thickness significantly decreased but also the yield is considerably elevated to several grams. Moreover, the in-plane O doping content can be adjusted within a relatively wide range. Overall, our finding demonstrates the potential of this approach in facilitating the exploration and utilization of h-BNNS.

LncRNA FAISL Inhibits Calpain 2-Mediated Proteolysis of FAK to Promote Progression and Metastasis of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive subtype in breast tumors. When re-analyzing TCGA breast cancer dataset, we found cell adhesion molecules are highly enriched in differentially expressed genes in TNBC samples, among which Focal Adhesion Kinase (FAK) is most significantly associated with poor survival of TNBC patients. FAK is precisely modulated in the focal adhesion dynamics. To investigate whether lncRNAs regulate FAK signaling, we performed RNA immunoprecipitation sequencing and found FAISL (FAK Interacting and Stabilizing LncRNA) abundantly enriched in FAK-interacting lncRNAs and frequently overexpressed in TCGA TNBC tissues. FAISL promotes TNBC cell adhesion, cytoskeleton spreading, proliferation, and anchor-independent survival. FAISL doesn't affect FAK mRNA but positively regulates FAK protein level by blocking Calpain 2-mediated proteolysis. FAISL interacts with the C-terminus domain of FAK, whereby masks the binding site of Calpain 2 and prevents FAK cleavage. High level of FAISL correlates with FAK expression in tumor tissues and poor prognosis of TNBC patients. A siRNA delivery system targeting FAISL using reduction-responsive nanoparticles effectively inhibits tumor growth and metastasis in TNBC mouse models. Together, these findings uncover a lncRNA-mediated mechanism of regulating FAK proteolysis in the TNBC progression, and highlight the potential of targeting lncRNA FAISL for TNBC treatment.

Dual-responsive two-photon probe for specific lipid droplets near-infrared fluorescence imaging in the brain of epileptic mice.

Abnormal lipid metabolism in glial cells is a key pathological feature of epilepsy. The identification of lipid droplets (LDs) is essential for investigating lipid metabolism, disease progression, and potential therapeutic interventions. Two-photon imaging technology enables real-time visualization of the spatial distribution and temporal dynamics of LDs in epilepsy models. In this study, we developed a novel two-photon excited dual-responsive near-infrared fluorescent probe, CabA, based on viscosity and polarity, to monitor dynamic changes in LDs. The fluorescence of CabA at 670 nm exhibits a significant increase in response to low polarity and high viscosity due to the twisted intramolecular charge transfer and intramolecular charge transfer mechanisms. The LDs-targeting capability of CabA at the cellular level and the process of LDs generation between neurons and astrocytes during the pathological advancement of epilepsy have been validated. In situ synchronous imaging experiments in epileptic and normal mice using CabA revealed abnormal LDs accumulation in the brain during seizures. Two-photon fluorescence imaging further demonstrated LDs accumulation in the brains of epileptic mice at a penetration depth of 100 µm. This study offers a valuable tool for enhancing the understanding of LDs in physiological and pathological processes, potentially aiding in the early diagnosis of epilepsy.

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OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Perceived Discrimination Among Food Pantry Clients in Massachusetts.

Introduction: Food insecurity is defined as inconsistent access to enough food to meet nutritional needs. Discrimination is associated with food insecurity and poor health, especially among racial and ethnic minoritized and sexual or gender minoritized groups. We examined the demographic associations of perceived everyday discrimination and food pantry discrimination in Massachusetts. Methods: From December 2021 through February 2022, The Greater Boston Food Bank conducted a cross-sectional, statewide survey of Massachusetts adults. Of the 3,085 respondents, 702 were food pantry clients for whom complete data on food security were available; we analyzed data from this subset of respondents. We used the validated 10-item Everyday Discrimination Scale to measure perceived everyday discrimination and a 10-item modified version of the Everyday Discrimination Scale to measure perceived discrimination at food pantries. Logistic regression adjusted for race and ethnicity, age, gender identity, sexual orientation, having children in the household, annual household income, and household size assessed demographic associations of perceived everyday discrimination and discrimination at food pantries. Results: Food pantry clients identifying as LGBTQ+ were more likely than those identifying as non-LGBTQ+ to report perceived everyday discrimination (adjusted odds ratio [AOR] = 2.44; 95% CI, 1.24-4.79). Clients identifying as Hispanic (AOR = 1.83, 95% CI, 1.13-2.96) were more likely than clients identifying as non-Hispanic White to report perceived discrimination at food pantries. Conclusion: To equitably reach and serve households with food insecurity, food banks and pantries need to understand experiences of discrimination and unconscious bias to develop programs, policies, and practices to address discrimination and create more inclusive interventions for food assistance.

What's driving girls' adolescent marriage decline in Rakai, Uganda? The interplay between adolescent pregnancies and social determinants, 1999 - 2018.

Few studies have sought to untangle the influence of social determinants and pregnancy on adolescent marriage declines. Using longitudinal data from 15- to 17-year-old girls in the Rakai Community Cohort Survey, we assessed how education, socio-economic status, orphanhood and pregnancy contributed to trends in adolescent marriage. We examined descriptive trends and logistic regressions of the associations between social determinants and adolescent marriage, and conducted causal mediation analysis to assess the extent that pregnancy mediated the effect of education on marriage. Between 1999-2018, adolescent marriages and pregnancies dropped substantially (24%-6% and 28%-8%). Girls' secondary schooling was strongly associated with lower marriage risk (aOR marriage=0.09; 95%CI=0.07-0.12), accounting for time. Lower pregnancy rates partially explained the effect of secondary schooling on lower adolescent marriage (aOR indirect effect=0.55; 95%CI=0.421-0.721). Findings affirm the importance of education in preventing adolescent marriages but call attention to the role of pregnancies in influencing adolescent marriages.

Automated Extraction of Patient-Centered Outcomes After Breast Cancer Treatment: An Open-Source Large Language Model-Based Toolkit.

PURPOSE: Patient-centered outcomes (PCOs) are pivotal in cancer treatment, as they directly reflect patients' quality of life. Although multiple studies suggest that factors affecting breast cancer-related morbidity and survival are influenced by treatment side effects and adherence to long-term treatment, such data are generally only available on a smaller scale or from a single center. The primary challenge with collecting these data is that the outcomes are captured as free text in clinical narratives written by clinicians. MATERIALS AND METHODS: Given the complexity of PCO documentation in these narratives, computerized methods are necessary to unlock the wealth of information buried in unstructured text notes that often document PCOs. Inspired by the success of large language models (LLMs), we examined the adaptability of three LLMs, GPT-2, BioGPT, and PMC-LLaMA, on PCO tasks across three institutions, Mayo Clinic, Emory University Hospital, and Stanford University. We developed an open-source framework for fine-tuning LLM that can directly extract the five different categories of PCO from the clinic notes. RESULTS: We found that these LLMs without fine-tuning (zero-shot) struggle with challenging PCO extraction tasks, displaying almost random performance, even with some task-specific examples (few-shot learning). The performance of our fine-tuned, task-specific models is notably superior compared with their non-fine-tuned LLM models. Moreover, the fine-tuned GPT-2 model has demonstrated a significantly better performance than the other two larger LLMs. CONCLUSION: Our discovery indicates that although LLMs serve as effective general-purpose models for tasks across various domains, they require fine-tuning when applied to the clinician domain. Our proposed approach has the potential to lead more efficient, adaptable models for PCO information extraction, reducing reliance on extensive computational resources while still delivering superior performance for specific tasks.

Probing rotaxane dynamics with 19F NMR/MRI: Unveiling the roles of mechanical bond and steric hindrance.

BACKGROUND: Deciphering the molecular dynamics (MD) of rotaxanes is crucial for designing and refining their applications in molecular devices. This study employed fluorine-19 nuclear magnetic resonance (19F NMR) and magnetic resonance imaging (MRI) to unveil the interplay between mechanical bonds and steric hindrance in a series of fluorinated rotaxanes. RESULTS: 1H/19F NMR revealed stable "Z"-shaped wheel conformations minimizing steric clashes and favoring π-π interactions with the axle. Utilizing fluorines and axle protons as reporters, 1H/19F relaxation rates and solid-state 19F NMR studies demonstrated that mechanical bond primarily governs wheel motion, while steric hindrance dictates axle movement. Intriguingly, mechanical bond mainly affects local axle groups, leaving distant ones minimally impacted. MD simulations corroborated these findings. Temperature-dependent 19F NMR indicated that energy input enhances rotational motion and wheel conformational transitions. Furthermore, the drastic increase in 19F relaxation rates upon mechanical bond formation and steric hindrance enables sensitive and selective 19F MRI visualization of MD changes. SIGNIFICANCE: This study, by elucidating the roles of internal and external factors on rotaxane molecular dynamics using 19F NMR/MRI, offers valuable insights that can advance the field of rotaxane-based molecular devices.

ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance.

The ATR-Chk1 pathway is essential in cellular responses to DNA damage and replication stress, whereas the role of long noncoding RNAs (lncRNAs) in regulating this pathway remains largely unknown. In this study, we identify an ATR and Chk1 interacting lncRNA (ACIL, also known as LRRC75A-AS1 or SNHG29), which promotes the phosphorylation of Chk1 by ATR upon DNA damages. High ACIL levels are associated with chemoresistance to DNA damaging agents and poor outcome of breast cancer patients. ACIL knockdown sensitizes breast cancer cells to DNA damaging drugs in vitro and in vivo. ACIL protects cancer cells against DNA damages by inducing cell cycle arrest, stabilizing replication forks and inhibiting unscheduled origin firing, thereby guarding against replication catastrophe and contributing to DNA damage repair. These findings demonstrate a lncRNA-dependent mechanism of activating the ATR-Chk1 pathway and highlight the potential of utilizing ACIL as a predictive biomarker for chemotherapy sensitivity, as well as targeting ACIL to reverse chemoresistance in breast cancer.

Association Between Vitamin Intake and Colorectal Cancer: Evidence from NHANES Data.

PURPOSE: This study aims to investigate the associations between vitamins and colorectal cancer (CRC) based on a national sample of US adults. METHODS: A total of 6200 samples were collected from the National Health and Nutrition Examination Survey to explore the relationship between vitamins (specifically, A, C, and D) and CRC. Logistic regression models were employed to assess the associations between dietary vitamin intake and CRC. RESULTS: Our findings indicate a negative association between vitamin C intake and CRC. However, the associations of vitamin A and vitamin D with CRC were not statistically significant. For vitamin C, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 0.91 (0.76-0.97) for the second tertile and 0.81 (0.64-0.95) for the third tertile (P < 0.01). Conversely, for vitamin A, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.02 (0.82-1.22) for the second tertile and 1.04 (0.75-1.25) for the third tertile (P < 0.01). For vitamin D, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 0.96 (0.84-1.06) for the second tertile and 1.01 (0.83-1.15) for the third tertile (P < 0.01). Additionally, the negative association between vitamin C and CRC was more pronounced among females (0.76, 0.67-0.92), individuals aged 60 and above (0.75, 0.69-0.95), and those with a BMI > 30 (0.78, 0.67-0.93). CONCLUSION: Our findings suggest that higher vitamin C intake is associated with a reduced prevalence of CRC. However, further large-scale prospective cohort studies are warranted to validate our results.

The role of physical activity in mitigating stress-induced internet addiction among Chinese college students.

BACKGROUND: This study addresses the nexus of stress, physical exercise, and internet addiction in college students, aiming to unravel their complex interactions. With prior research hinting at correlations, this study seeks deeper insights into the optimal exercise duration and the mediating role of physical activity in the stress-internet addiction relationship. METHODS: We examined 2892 Chinese college students, assessing psychosocial traits via established scales: the Chinese Internet Addiction Scale (CIAS-R), International Physical Activity Questionnaire (IPAQ), and DASS-21 for stress. We adopted a questionnaire survey method to collect data, and through convenience sampling, participants were selected. Analysis involved Structural Equation Model (SEM) and restricted cubic splines (RCS). RESULTS: Among participants, 22.0 % self-reported internet addiction symptoms. Notably, a non-linear correlation between moderate (MPA) and vigorous physical activity (VPA) and internet addiction was evident (P < 0.001), while light physical activity (LPA) showed no significant association (P = 0.182). MPA initially reduced internet addiction as activity hours increased, but its efficacy lessened after 0.8 h/day. Conversely, VPA's impact fluctuated, declining from 0 to 0.18 h/day, then stabilizing. SEM analysis highlighted VPA and MPA's partial mediation in the stress-internet addiction relationship. Specifically, the path coefficient from stress to MPA was -0.037 (P < 0.05), and the path coefficient from MPA to internet addiction was -0.056 (P < 0.01). Additionally, the path coefficient from stress to VPA was -0.067 (P < 0.001), and the path coefficient from VPA to internet addiction was -0.102 (P < 0.001). CONCLUSION: This study unveils the intricate interplay between physical activity, stress, and internet addiction among college students. With 22.0 % reporting addiction symptoms, urgent interventions tailored to promoting healthy physical activity levels are imperative to mitigate internet addiction risks. LIMITATIONS: The cross-sectional nature of our design precludes the establishment of causal relationships between psychological stress and internet addiction.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

The long non-coding RNA CCAT1 promotes erlotinib resistance in cholangiocarcinoma by inducing epithelial-mesenchymal transition via the miR-181a-5p/ROCK2 axis.

Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.

Cigarette smoking decline among US young adults from 2000 to 2019, in relation to state-level cigarette price and tobacco control expenditure.

OBJECTIVE: To investigate the association of state-level cigarette price and tobacco control expenditure with the large 2000-2019 decline in cigarette smoking among US 18-24 year-olds. METHODS: Smoking behaviour was assessed in the 24 most populous US states using the 1992-2019 Tobacco Use Supplements to the Current Population Survey; association with price and expenditure was tested using adjusted logistic regression. States were ranked by inflation-adjusted average price and tobacco control expenditure and grouped into tertiles. State-specific time trends were estimated, with slope changes in 2001/2002 and 2010/2011. RESULTS: Between 2000 and 2010, the odds of smoking among US young adults decreased by a third (adjusted OR, AOR 0.68, 95% CI 0.56 to 0.84). By 2019, these odds were one-quarter of their 2000 level (AOR 0.24, 95% CI 0.19 to 0.31). Among states in the lowest tertile of price/expenditure tobacco control activity, initially higher young adult smoking decreased by 13 percentage points from 2010 to 2018-2019, to a prevalence of 5.6% (95% CI 4.5% to 6.8%), equal to that in the highest tobacco-control tertile of states (6.5%, 95% CI 5.2% to 7.8%). Neither state tobacco control spending (AOR 1.0, 95% CI 0.999 to 1.002) nor cigarette price (AOR 0.96, 95% CI: 0.92 to 1.01) were associated with young adult smoking in statistical models. In 2019, seven states had prevalence over 3 SDs higher than the 24-state mean. CONCLUSION: National programmes may have filled a gap in state-level interventions, helping drive down the social acceptability of cigarette smoking among young adults across all states. Additional interventions are needed to assist high-prevalence states to further reduce smoking.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Advancements and Challenges in the Integration of Indium Arsenide and Van der Waals Heterostructures.

The strategic integration of low-dimensional InAs-based materials and emerging van der Waals systems is advancing in various scientific fields, including electronics, optics, and magnetics. With their unique properties, these InAs-based van der Waals materials and devices promise further miniaturization of semiconductor devices in line with Moore's Law. However, progress in this area lags behind other 2D materials like graphene and boron nitride. Challenges include synthesizing pure crystalline phase InAs nanostructures and single-atomic-layer 2D InAs films, both vital for advanced van der Waals heterostructures. Also, diverse surface state effects on InAs-based van der Waals devices complicate their performance evaluation. This review discusses the experimental advances in the van der Waals epitaxy of InAs-based materials and the working principles of InAs-based van der Waals devices. Theoretical achievements in understanding and guiding the design of InAs-based van der Waals systems are highlighted. Focusing on advancing novel selective area growth and remote epitaxy, exploring multi-functional applications, and incorporating deep learning into first-principles calculations are proposed. These initiatives aim to overcome existing bottlenecks and accelerate transformative advancements in integrating InAs and van der Waals heterostructures.

Alternative splicing in parallel evolution and the evolutionary potential in sticklebacks.

Repeatability of adaptation to similar environments provides opportunity to evaluate the predictability of natural selection. While many studies have investigated gene expression differences between populations adapted to contrasting environments, the role of post-transcriptional processes such as alternative splicing has rarely been evaluated in the context of parallel adaptation. To address the aforementioned knowledge gap, we reanalysed transcriptomic data from three pairs of threespine stickleback (Gasterosteus aculeatus) ecotypes adapted to marine or freshwater environment. First, we identified genes with repeated expression or splicing divergence across ecotype pairs, and compared the genetic architecture and biological processes between parallelly expressed and parallelly spliced loci. Second, we analysed the extent to which parallel adaptation was reflected at gene expression and alternative splicing levels. Finally, we tested how the two axes of transcriptional variation differed in their potential for evolutionary change. Although both repeated differential splicing and differential expression across ecotype pairs showed tendency for parallel divergence, the degree of parallelism was lower for splicing than expression. Furthermore, parallel divergences in splicing and expression were likely to be associated with distinct cis-regulatory genetic variants and functionally unique set of genes. Finally, we found that parallelly spliced genes showed higher nucleotide diversity than parallelly expressed genes, indicating splicing is less susceptible to genetic variation erosion during parallel adaptation. Our results provide novel insight into the role of splicing in parallel adaptation, and underscore the contribution of splicing to the evolutionary potential of wild populations under environmental change.

Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression.

The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.