Dietary patterns and insomnia symptoms: A systematic review and meta-analysis.

We aimed to systematically review and synthesize the available evidence regarding the link between dietary patterns and insomnia symptoms among the general population using observational studies. We reviewed 16,455 references, of which 37 studies met inclusion criteria with a total sample size of 591,223. There was a significant association of the Mediterranean diet (OR: 0.86; 95 % CI, 0.79, 0.93; P < 0.001; I2 = 32.68 %), a high-quality diet (OR: 0.66; 95 % CI, 0.48, 0.90; P = 0.010; I2 = 84.62 %), and an empirically-derived healthy dietary pattern (OR: 0.91; 95 % CI, 0.85, 0.98; P = 0.010; I2 = 57.14 %) with a decreased risk of insomnia symptoms. Moreover, the dietary glycemic index (OR: 1.16; 95 % CI, 1.08, 1.25; P < 0.001; I2 = 0.0 %), the dietary glycemic load (OR: 1.10; 95 % CI, 1.01, 1.20; P = 0.032; I2 = 74.36 %), and an empirically-derived unhealthy dietary pattern (OR: 1.20; 95 % CI, 1.01, 1.42; P = 0.040; I2 = 68.38 %) were linked with a higher risk of insomnia symptoms. Most individual studies were of good quality (NOS) but provided very low certainty of evidence (GRADE). Consistent data reveals that following healthy diets is associated with decreased insomnia symptoms prevalence, while adherence to an unhealthy pattern is associated with an increased prevalence of insomnia symptoms.

Porphysome Engineered With Specific Protein Binding Sites as a Multimodal Theranostic Nanocarrier for Targeted Protein Delivery.

The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated-porphyrin complex in the porphysome nanocarrier. The conjugated Ni-porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni-porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni-porphyrin, 4 : 1 mole ratio) was formed by supramolecular self-assembly with a diameter of 173±7 nm and zeta potential -8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF-7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1 : 2 mole ratio) show the conjugation efficiency about 80 % and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS-PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin-lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.

Social jetlag and obesity: A systematic review and meta-analysis.

Social jetlag, the weekly variation in sleep timing, is proposed to contribute to increased obesity risk, potentially because of the misalignment of behavioral cycles relative to the endogenous circadian timing system. This systematic review and meta-analysis aim to determine the association between social jetlag and adiposity-related measures using observational studies. We reviewed 477 references, of which 43 studies met inclusion criteria with a total sample size of 231,648. There was a positive association between social jetlag and body mass index (correlation coefficient [r]: 0.12; 95%CI, 0.07, 0.17; P < 0.001; I2  = 94.99%), fat mass (r: 0.10; 95%CI, 0.05, 0.15; P < 0.001; I2  = 0.00%), fat mass index (fat mass divided by height in meter squared, ß: 0.14 kg/m2 ; 95%CI, 0.05, 0.23; P < 0.001; I2  = 56.50%), percent of body fat (r: 0.37; 95%CI, 0.33, 0.41; P < 0.001; I2  = 96.17%), waist circumference (r: 0.15; 95%CI, 0.06, 0.24; P = 0.001; I2  = 90.83%), and the risk of having overweight/obesity (odds ratio: 1.20; 95%CI, 1.02, 1.140; P = 0.039; I2  = 98.25%). Social jetlag is positively and consistently associated with multiple obesity-related anthropometric measures. Further studies are needed to test causality, underlying mechanisms, and whether obesity interventions based on increasing regularity of the sleep/wake cycle can aid in the battle against the obesity pandemic.

Maintaining beneficial alga-associated bacterial communities under heat stress: insights from controlled co-culture experiments using antibiotic-resistant bacterial strains.

Brown algae, like many eukaryotes, possess diverse microbial communities. Ectocarpus-a model brown alga-relies on these communities for essential processes, such as growth development. Controlled laboratory systems are needed for functional studies of these algal-bacterial interactions. We selected bacterial strains based on their metabolic networks to provide optimal completion of the algal metabolism, rendered them resistant to two antibiotics, and inoculate them to establish controlled co-cultures with Ectocarpus under continuous antibiotic treatment. We then monitored the stability of the resulting associations under control conditions and heat stress using 16S metabarcoding. Antibiotics strongly reduced bacterial diversity both in terms of taxonomy and predicted metabolic functions. In the inoculated sample, 63%-69% of reads corresponded to the inoculated strains, and the communities remained stable during temperature stress. They also partially restored the predicted metabolic functions of the natural community. Overall, the development of antibiotic-resistant helper cultures offers a promising route to fully controlled laboratory experiments with algae and microbiota and thus represents an important step towards generating experimental evidence for specific host-microbe interactions in the systems studied. Further work will be required to achieve full control and progressively expand our repertoire of helper strains including those currently 'unculturable'.

Association between the dietary inflammatory index and markers of endothelial and systemic inflammation in hemodialysis patients.

Objectives: The current survey aimed to investigate the link between energy-adjusted dietary inflammatory index (E-DII) and risk factors for CVD including markers of endothelial and systemic inflammation in Iranian hemodialysis patients. Methods: Patients on hemodialysis for at least 6 months prior to enrollment were considered eligible in this cross-sectional study. The usual dietary intakes of the hemodialysis individuals were examined through 4 non-consecutive days including 2 dialysis days and 2 non-dialysis days using a 24-h recall approach to calculate E-DII. Multiple linear regression analysis was utilized to investigate the link between E-DII and selected biomarkers of inflammation and oxidative stress including high-sensitive C reactive protein (hs-CRP), serum intercellular adhesion molecule (sICAM), serum vascular cell adhesion molecule (sVCAM), malondialdehyde, and nitric oxide (NO), sE-selectin, and endothelin-1, and beta (ß) and 95% confidence interval (CI) was reported. Value of p < 0.05 was considered statistically significant. Results: Overall, 291 hemodialysis patients make up our study population. In the crude model, the E-DII score was positively associated with a higher sVCAM-1 (ß = 177.39; 95% CI: 60.51, 294.26; ptrend = 0.003). Further adjustment for potential confounders attenuated the findings in a way that an increase of 128.72 in the sVCAM-1 was observed when the E-DII score increased from -2.68 to -1.14 (95% CI: 13.50, 243.94). After controlling for potential confounders, E-DII was associated with sE-selectin in hemodialysis patients in the highest category of E-DII as compared to the lowest category (ß = 4.11; 95% CI: 0.22, 8.00; ptrend = 0.039). Conclusion: The present findings suggest that adherence to a pro-inflammatory diet among hemodialysis patients is associated with a higher inflammatory status as evidenced by sVCAM-1 and sE-selectin; however, bidirectionality may exist and the role of residual confounders should be taken into account. Therefore, more longitudinal investigations are needed to elucidate the role of diet on the inflammatory status of hemodialysis patients.

Associations between diet quality and migraine headaches: a cross-sectional study.

AIMS: We evaluated associations between diet quality and migraine outcomes. METHODS: The current work represented a cross-sectional study on 262 patients with migraine (20-50 y). Diet quality was assessed using the standard healthy eating index 2015 (HEI-2015) and alternative healthy eating index 2010 (AHEI-2010). A validated 168-item food frequency questionnaire was used to assess dietary intake. Migraine outcomes included clinical factors (severity, duration, frequency, and disability related to migraine) and serum nitric oxide (NO). Associations between diet quality indices and migraine outcomes were evaluated using linear regressions, and ß and 95% corresponding confidence interval (CI) were reported. RESULTS: HEI-2015 was inversely associated with migraine frequency (ß = -4.75, 95% CI: -6.73, -2.76) in patients with the highest HEI scores (third tertile) vs. those with the lowest scores (first tertile) after adjusting for relevant confounders. AHEI-2010 was inversely associated with migraine frequency (ß = -3.67, 95% CI: -5.65, -1.69) and migraine-related disability (ß = -2.74, 95% CI: -4.79, -0.68) in adjusted models. Also, AHEI-2010 was inversely associated with migraine severity in patients in the second vs. first tertile (ß = -0.56; 95% CI: -1.08, -0.05). We detected no associations between diet quality and NO levels (All P > 0.14). CONCLUSIONS: Improved diet quality may be associated with favorable migraine outcomes (lower headache frequency, severity, and migraine-related disability). Future studies are required to confirm and delineate the causal mechanisms of our observations.

Social jetlag and dietary intake: A systematic review.

The objective of the current systematic review was to critically review the available evidence regarding the link between social jetlag and diet among the general population using observational studies. Electronic databases, including PubMed, Scopus, and ISI Web of Sciences were searched systematically. We reviewed 348 references, of which 17 studies met inclusion criteria with a total sample size of 28,905. Qualitative analysis indicated a negative association between social jetlag and adherence to healthy eating habits, including a negative association with empirically-derived healthy dietary patterns, Japanese dietary patterns, Baltic Sea dietary patterns, and the Mediterranean diet, as well as a positive association with Meat and Starchy dietary pattern. On the other hand, the findings on the link of social jetlag with food groups and nutrients were mixed and controversial, except for a more consistent increase in sugar-sweetened beverages, total fat, and saturated fat intake. Our results indicate a possible link between social jetlag and dietary intake. Research suggests that individuals experiencing greater social jetlag exhibit reduced adherence to a healthy eating pattern. However, it is important to note that the reported association lacks consensus, emphasizing the need for additional longitudinal studies to gain further insights into this matter."

Genetic Variants Impacting Angiogenesis Signaling Pathways in Glioblastoma Multiforme: A Systematic Review of Mutations and Polymorphisms.

BACKGROUND: Several signaling pathways are involved in the process of angiogenesis, which is one of the most important hallmarks of glioblastoma multiforme (GBM). Identifying related gene variants can help researchers work out what causes anti-angiogenesis drug resistance. OBJECTIVE: The goal of this systematic analysis was to identify all mutations and polymorphisms involved in angiogenesis pathways in GBM and their impact on clinical outcomes. METHODS: The keywords include glioblastoma, angiogenesis, signaling pathway, mutation, polymorphism, and related terms used to search ISI, PubMed, and Scopus for relevant articles published up to January 2022. The PRISMA protocol was used to conduct our systematic review. The related articles were taken into consideration. The risk of bias in the associated articles was surveyed, as well as the article scoring. Two authors collaborated on data extraction. RESULTS: The inclusion criteria were included in 32 articles out of a total of 787 articles. VEGF, HIF1a, EGFR, PI3K, and MAPK are the pathways that have been studied the most. IDH1, VEGF, VEGFR, EGFR, and HIF1a are the genes with the highest frequency of mutations or polymorphisms. CONCLUSION: In conclusion, this study found that angiogenesis in primary or recurrent GBM is linked to gene changes in eleven signaling pathways. However, some of these gene mutations have been researched numerous times in relation to angiogenesis, while others have only been studied once. Understanding these changes will help us employ combination therapies more effectively for GBM patients' survival and personal medicine.

The effect of cinnamon consumption on lipid profile, oxidative stress, and inflammation biomarkers in adults: An umbrella meta-analysis of randomized controlled trials.

AIMS: Cinnamon is a polyphenol-rich spice that has beneficial effects on markers of cardio metabolic health such as lipid profile, oxidative stress, and inflammation. Despite the accumulating evidence from meta-analyses on the effects of cinnamon on these markers, their findings are controversial. Thus, this umbrella meta-analysis was performed to evaluate the present evidence and provide a conclusive clarification. DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049). CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.

Agent-Based Modelling Reveals the Role of the Tumor Microenvironment on the Short-Term Success of Combination Temozolomide/Immune Checkpoint Blockade to Treat Glioblastoma.

Glioblastoma is the most common and deadly primary brain tumor in adults. All glioblastoma patients receiving standard-of-care surgery-radiotherapy-chemotherapy (i.e., temozolomide (TMZ)) recur, with an average survival time of only 15 months. New approaches to the treatment of glioblastoma, including immune checkpoint blockade and oncolytic viruses, offer the possibility of improving glioblastoma outcomes and have as such been under intense study. Unfortunately, these treatment modalities have thus far failed to achieve approval. Recently, in an attempt to bolster efficacy and improve patient outcomes, regimens combining chemotherapy and immune checkpoint inhibitors have been tested in trials. Unfortunately, these efforts have not resulted in significant increases to patient survival. To better understand the various factors impacting treatment outcomes of combined TMZ and immune checkpoint blockade, we developed a systems-level, computational model that describes the interplay between glioblastoma, immune, and stromal cells with this combination treatment. Initializing our model to spatial resection patient samples labeled using imaging mass cytometry, our model's predictions show how the localization of glioblastoma cells, influence therapeutic success. We further validated these predictions in samples of brain metastases from patients given they generally respond better to checkpoint blockade compared with primary glioblastoma. Ultimately, our model provides novel insights into the mechanisms of therapeutic success of immune checkpoint inhibitors in brain tumors and delineates strategies to translate combination immunotherapy regimens more effectively into the clinic. SIGNIFICANCE STATEMENT: Extending survival times for glioblastoma patients remains a critical challenge. Although immunotherapies in combination with chemotherapy hold promise, clinical trials have not shown much success. Here, systems models calibrated to and validated against patient samples can improve preclinical and clinical studies by shedding light on the factors distinguishing responses/failures. By initializing our model with imaging mass cytometry visualization of patient samples, we elucidate how factors such as localization of glioblastoma cells and CD8+ T cell infiltration impact treatment outcomes.

Is there an association between a plant-based eating pattern and clinical findings of a migraine headache?

Aims: The present study was conducted among Iranian individuals diagnosed with migraine headaches to investigate the association between plant-based eating patterns and the clinical features of a migraine headache. Methods: In total, 262 patients aged 20-50 years who were diagnosed with migraine headaches were included in the current cross-sectional study. Participants' dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). Three versions of the plant-based diet index (PDI) comprising overall PDI, healthy PDI (hPDI), and unhealthy PDI (uPDI) were generated. Headache frequency, duration, and severity were assessed via a 30-day headache diary. Migraine-related disability was assessed with a validated version of the headache impact test (HIT-6) questionnaire. Serum nitric oxide (NO) was measured using the Griess method utilizing serum samples. Results: After controlling for potential confounders, an increase in mean PDI score from 48.22 to 61.67 decreased the frequency of headaches by -2.95 (95% CI: 0.06, 0.53; ptrend = 0.005). PDI was inversely associated with serum levels of NO in those with the highest scores of PDI compared to those with the lowest scores after adjustment for confounders (ß = -7.69; 95% CI: -14.68, -0.69; ptrend = 0.028). After adjustment for potential confounders, an increase in the mean hPDI score from 47.96 to 65.25 decreased serum levels of NO by -11.92 (95% CI: -19.74, -4.10; ptrend = 0.003). Conclusion: Our findings suggest that higher adherence to a plant-based eating style, as evidenced by higher PDI and hPDI values, was significantly associated with lower headache frequency and serum levels of NO.

Molecular Mechanisms of miR-214 Involved in Cancer and Drug Resistance.

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.

CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma.

Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due to their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in T cell content. Orthogonally, spatial imaging mass cytometry shows T cell enrichment in human recurrent tumors compared with matched primary glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak of T cell infiltration post-radiotherapy results in a modest survival benefit compared with concurrent α-PD-1 administration. Following α-PD-1 therapy, CD103+ regulatory T cells (Tregs) with upregulated lipid metabolism accumulate in the tumor microenvironment, and restrain immune checkpoint blockade response by repressing CD8+ T cell activation. Treg targeting elicits tertiary lymphoid structure formation, enhances CD4+ and CD8+ T cell frequency and function and unleashes radio-immunotherapeutic efficacy. These results support the rational design of therapeutic regimens limiting the induction of immunosuppressive feedback pathways in the context of T cell immunotherapy in glioblastoma.

The influential role of parents' socioeconomic status and diet quality on their children's dietary behavior: results from the LIPOKAP study among the Iranian population.

PURPOSE: There is a paucity of evidence regarding the influential factors on Iranian children's diet quality. To assess this issue, we explore the relationship between parental diet quality, socioeconomic status (SES), and nutritional knowledge with their children's diet quality using a cross-sectional sample of the Iranian population. METHODS: In this study, paired parents along with one of their children (aged 6-18 years old) who lived with them were included. Dietary intake was assessed using a food frequency questionnaire (FFQ) and diet quality was determined using an Alternative Healthy Eating Index-2010 (AHEI). Nutritional knowledge and SES were also explored using validated questionnaires. Multiple linear regression analysis was used and beta (ß) and corresponding 95% confidence interval (CI) were reported. RESULTS: After controlling for potential confounders, the parents' AHEI was significantly associated with their children's diet quality (ß = 12.34, 95% CI: 10.75, 13.93; P < 0.001). The nutritional knowledge of parents was significantly associated with children's AHEI after controlling for potential confounders (ß = 1.63, 95% CI: 0.14, 3.11; P = 0.032). Moreover, the parents' SES was inversely associated with the AHEI of children (ß=-3.76, 95% CI: -5.40, -2.11; P < 0.001); however, further adjustment for confounders attenuated this relationship (Model 3: ß = 0.87, 95% CI: -0.76, 2.34; P = 0.269). CONCLUSIONS: We found that the children's diet quality could be influenced by their parents' SES, nutritional knowledge, and diet quality. Our findings suggest that improving the nutritional knowledge of parents not only may improve the healthy eating pattern of parents but also could influence their children's diet quality.

Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity.

BACKGROUND: Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI. METHODS: Here, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade. RESULTS: We resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes. DISCUSSION: Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs.

Effects of Probiotic and Selenium Co-supplementation on Lipid Profile and Glycemia Indices: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

PURPOSE OF REVIEW: The current systematic review and meta-analysis was done to evaluate the effects of selenium and probiotic co-supplementation on lipid profile and glycemia indices of the adult population using randomized controlled clinical trials (RCTs). RECENT FINDINGS: Five studies involving 282 participants with a sample size ranging from 38 to 79 were eligible to be enrolled in the current study. Co-supplementation with probiotic and selenium reduced fasting plasma glucose (WMD = -4.02 mg/dL; 95% CI: -5.87 to -2.18; P < 0.001), insulin (WMD = -2.50 mIU/mL; 95% CI: -3.11 to -1.90; P < 0.001), homeostatic model assessment for insulin resistance (WMD = -0.59; 95% CI: -0.74 to -0.43; P < 0.001), quantitative insulin sensitivity check index (WMD = 0.01; 95% CI: 0.01 to 0.02; P < 0.001), total cholesterol (WMD = -12.75 mg/dL; 95% CI: -19.44 to -6.07; P < 0.001), low-density lipoprotein cholesterol (WMD = -7.09 mg/dL; 95% CI: -13.45 to -0.73; P = 0.029), and triglyceride (WMD = -14.38 mg/dL; 95% CI: -23.13 to -5.62; P = 0.001). The findings of the current systematic review and meta-analysis suggested that co-supplementation with probiotics and selenium may benefit adults in terms of glycemia indices and lipid profile. However, due to the small number of included studies, further trials are needed to confirm our findings.

The effects of royal jelly supplementation on oxidative stress, inflammatory mediators, mental health, cognitive function, quality of life, and clinical outcomes of patients with ischemic stroke: study protocol for a randomized controlled trial.

BACKGROUND: Stroke is a debilitating disease that affects over 15 million people worldwide each year, resulting in the death of one-third of those people and severe disability in two-thirds of survivors. Previous studies reported various health benefits of Royal jelly in the context of its anti-inflammatory properties. We will aim to investigate the effects of royal jelly supplementation on oxidative stress, inflammatory mediators, mental health, cognitive function, quality of life, and clinical outcomes of patients with ischemic stroke. METHODS: The present study will be a triple-blind randomized placebo trial. Patients who meet our eligibility criteria will be assigned to the intervention or the control groups to receive allocated intervention for 12 weeks. Individuals of the intervention group will consume 1000 mg of Royal jelly dragee daily after breakfast. Subjects of the control group will receive a placebo dragee identical to the Royal jelly dragee. The severity of the stroke, cognitive function, mental health, quality of life, clinical outcomes, and biochemical measures will be assessed at baseline and post-intervention. DISCUSSION: The current study is designed to investigate the effectiveness and safety of royal jelly supplementation in a randomized, parallel, two-arms, single-center, triple-blind, placebo-controlled manner. This study will provide evidence as a phase III clinical trial. TRIAL REGISTRATION: IRCT20180818040827N4, registered on 16 October 2021. https://www.irct.ir/trial/59275.

Single-cell spatial landscapes of the lung tumour immune microenvironment.

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution1-9. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm2 tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

Insights into the potential for mutualistic and harmful host-microbe interactions affecting brown alga freshwater acclimation.

Microbes can modify their hosts' stress tolerance, thus potentially enhancing their ecological range. An example of such interactions is Ectocarpus subulatus, one of the few freshwater-tolerant brown algae. This tolerance is partially due to its (un)cultivated microbiome. We investigated this phenomenon by modifying the microbiome of laboratory-grown E. subulatus using mild antibiotic treatments, which affected its ability to grow in low salinity. Low salinity acclimation of these algal-bacterial associations was then compared. Salinity significantly impacted bacterial and viral gene expression, albeit in different ways across algal-bacterial communities. In contrast, gene expression of the host and metabolite profiles were affected almost exclusively in the freshwater-intolerant algal-bacterial communities. We found no evidence of bacterial protein production that would directly improve algal stress tolerance. However, vitamin K synthesis is one possible bacterial service missing specifically in freshwater-intolerant cultures in low salinity. In this condition, we also observed a relative increase in bacterial transcriptomic activity and the induction of microbial genes involved in the biosynthesis of the autoinducer AI-1, a quorum-sensing regulator. This could have resulted in dysbiosis by causing a shift in bacterial behaviour in the intolerant algal-bacterial community. Together, these results provide two promising hypotheses to be examined by future targeted experiments. Although they apply only to the specific study system, they offer an example of how bacteria may impact their host's stress response.