Enhanced and asymmetric signatures of hybridization at climatic margins: Evidence from closely related dioecious fig species.

Hybridization plays a significant role in biological evolution. However, it is not clear whether ecological contingency differentially influences likelihood of hybridization, particularly at ecological margins where parental species may exhibit reduced fitnesses. Moreover, it is unknown whether future ecosystem change will increase the prevalence of hybridization. Ficus heterostyla and F. squamosa are closely related species co-distributed from southern Thailand to southwest China where hybridization, yielding viable seeds, has been documented. As a robust test of ecological factors driving hybridization, we investigated spatial hybridization signatures based on nuclear microsatellites from extensive population sampling across a widespread contact range. Both species showed high population differentiation and strong patterns of isolation by distance. Admixture estimates exposed asymmetric interspecific gene flow. Signatures of hybridization increase significantly towards higher latitude zones, peaking at the northern climatic margins. Geographic variation in reproductive phenology combined with ecologically challenging marginal habitats may promote this phenomenon. Our work is a first systematic evaluation of such patterns in a comprehensive, latitudinally-based clinal context, and indicates that tendency to hybridize appears strongly influenced by environmental conditions. Moreover, that future climate change scenarios will likely alter and possibly augment cases of hybridization at ecosystem scales.

Pollinator sharing and hybridization in a pair of dioecious figs sheds light on the pathways to speciation.

The dynamics and processes underlying the codiversification of plant-pollinator interactions are of great interest to researchers of biodiversity and evolution. Cospeciation is generally considered a key process driving the diversity of figs and their pollinating wasps. Groups of closely related figs pollinated by separate wasps occur frequently and represent excellent opportunities to study ongoing diversification in this textbook mutualism. We study two closely related sympatric dioecious figs (Ficus heterostyla and Ficus squamosa) in Xishuangbanna, southwest China, and aim to document what is likely to be the final stages of speciation between these species using a combination of trait data and experimental manipulation. Volatile profiles at the receptive phase, crucial for attracting pollinators, were analyzed. In total, 37 and 29 volatile compounds were identified from receptive F. heterostyla and F. squamosa figs, respectively. Despite significant interspecific dissimilarity, 25 compounds were shared. Ovipositor lengths lie well within range required for access to heterospecific ovules, facilitating hybridization. Cross introduction of wasps into figs was conducted and hybrid seeds were generated for all donor/recipient combinations. F. heterostyla wasps produce adult offspring in F. squamosa figs. While F. squamosa wasps induce gall development in F. heterostyla figs and their offspring fail to mature in synchrony with their novel host. We record limited geographic barriers, minimal volatile dissimilarity, compatible morphology, complementary reproductive phenologies, and the production of hybrid seeds and wasp offspring. These findings suggest ongoing wasp specialization and reproductive isolation, potentially applicable to other related fig species.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

[Effects of Straw Returning with Lime on SOC and Carbon Pool Management in Acidic Paddy Soil].

Soil acidification and low SOC are the main limiting factors in acidic paddy soils. Straw returning with lime is an effective measure to alleviate soil acidification and improve soil fertility; however, its interaction effects on SOC and carbon pool management are still unclear. To investigate the impact of straw returning with lime on the organic carbon pool of acidic paddy soil, field experiments were conducted on acidic paddy soil in Baiyun District and Huiyang District of Guangdong Province. The changes in soil total organic carbon (TOC), water-soluble organic carbon (DOC), active organic carbon (LOC), particulate organic carbon (POC), microbial biomass carbon (MBC), carbon pool index (CPI), stable organic carbon (IOC), carbon pool activity (L), carbon pool activity index (CPAI), and carbon pool management index (CPMI) were analyzed under three treatments (CK, conventional fertilization; RS, straw returning+conventional fertilization; RS+L straw returning with lime+conventional fertilization). The results demonstrated that compared with that in CK, the TOC, LOC, POC, and MBC in the RS+L treatment were significantly increased by 10.24%-17.79%, 34.49%-44.37%, 19.27%-23.59%, and 33.36%-43.26%, respectively (P<0.05). Compared with that in CK, the RS+L treatment significantly increased the DOC content during the early growth stage (15-45 days after transplanting) of rice (P<0.05) but had no significant influence on the DOC content during the late growth stage of rice. Compared with that in RS, the TOC, LOC, POC, and MBC in the RS+L treatment were increased by 2.15%-6.95%, 1.17%-17.90%, 4.27%-8.65%, and 12.99%-14.53%, respectively. Compared with that in CK, the RS+L treatment significantly increased IOC and CPI by 8.32%-15.57% and 14.00%-20.00%, respectively (P<0.05). Compared with that in the CK treatment, the RS treatment significantly increased CPI by 14.00%-18.00% (P<0.05). No significant differences in L, CPAI, or CPMI were detected among the different treatments. The soil pH in the RS+L treatment was significantly higher than that in the CK treatment (P<0.05). No significant differences in rice yield were detected among the different treatments. Principal component analysis demonstrated that rice yield was primarily correlated with DOC, LOC, CPAI, and CPMI but its contribution to SOC and carbon pool management index was low. Principal component analysis also indicated that straw returning with lime could improve soil pH and nutrient contents of acidic paddy soil, driving the formation and accumulation of organic carbon fraction such as MBC and POC, thus boosting the increase in SOC. In conclusion, straw returning with lime is beneficial to the accumulation of MBC, POC, LOC, and IOC in acidic paddy soil to improve the content and stability of soil total organic carbon, which is an effective way to improve the carbon sequestration of acidic paddy soil.

Association between dietary niacin intake and cognitive function in the elderly: Evidence from NHANES 2011-2014.

Recent studies have shown an inconsistent association between dietary niacin and cognitive function. And this remains unclear in the American outpatient population. The aim of this study was to assess whether there is an association between dietary niacin and cognitive performance in an older American population aged ≥60 years. A total of 2523 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were enrolled. Cognitive function was assessed by the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Cognitive impairment that meets one of the four scoring conditions listed above is defined as low cognitive function. Dietary niacin intake was obtained from 2 days of a 24-h recall questionnaire. Based on the quartiles of dietary niacin intake, they were divided into four groups: Q1 (<15.51 mg), Q2 (15.51-20.68 mg), Q3 (20.69-26.90 mg), and Q4 (>26.91 mg). The stability of the results was assessed using multifactorial logistic regression, restricted cubic spline (RCS) models, and sensitivity stratified analysis. More than half of the participants had cognitive impairment (52.52%). In the fully adjusted model, niacin was associated with a significantly reduced risk of cognitive impairment in Q3 and Q4 compared with the Q1 group (OR: 0.610, 95% CI: 0.403, 0.921, p = .022; OR: 0.592, 95% CI: 0.367, 0.954, p = .034). Meanwhile, niacin was negatively associated with poor cognition as assessed by the CERAD-WL test, CERAD test, AFT, and DSST. An L-shaped dose-response relationship between dietary niacin and cognitive function was observed in all participants (nonlinear p < .001). There were also interactions that existed in populations with different carbohydrate intakes and cholesterol intakes (p for interaction = .031, p for interaction = .005). These findings provide new evidence for the potential role of dietary niacin intake on cognitive function in the elderly.

Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis.

Introduction: Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC. Method: We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software. Results: Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58-1.19, p=0.300 and OR, 1.54; 95%CI 0.89-2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15-0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03-0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02-0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39-4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81-4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33-4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08-2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55-81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06-4.61, p=0.030). Conclusions: Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.

East‒West genetic differentiation across the Indo-Burma hotspot: evidence from two closely related dioecious figs.

BACKGROUND: Understanding biodiversity patterns and their underlying mechanisms is of interest to ecologists, biogeographers and conservationists and is critically important for conservation efforts. The Indo-Burma hotspot features high species diversity and endemism, yet it also faces significant threats and biodiversity losses; however, few studies have explored the genetic structure and underlying mechanisms of Indo-Burmese species. Here, we conducted a comparative phylogeographic analysis of two closely related dioecious Ficus species, F. hispida and F. heterostyla, based on wide and intensive population sampling across Indo-Burma ranges, using chloroplast (psbA-trnH, trnS-trnG) and nuclear microsatellite (nSSR) markers, as well as ecological niche modeling. RESULTS: The results indicated large numbers of population-specific cpDNA haplotypes and nSSR alleles in the two species. F. hispida showed slightly higher chloroplast diversity but lower nuclear diversity than F. heterostyla. Low-altitude mountainous areas of northern Indo-Burma were revealed to have high genetic diversity and high habitat suitability, suggesting potential climate refugia and conservation priority areas. Strong phylogeographic structure and a marked east‒west differentiation pattern were observed in both species, due to the interactions between biotic and abiotic factors. Interspecific dissimilarities at fine-scale genetic structure and asynchronized historical dynamics of east‒west differentiation between species were also detected, which were attributed to different species-specific traits. CONCLUSIONS: We confirm hypothesized predictions that interactions between biotic and abiotic factors largely determine the patterns of genetic diversity and phylogeographic structure of Indo-Burmese plants. The east‒west genetic differentiation pattern observed in two targeted figs can be generalized to some other Indo-Burmese plants. The results and findings of this work will contribute to the conservation of Indo-Burmese biodiversity and facilitate targeted conservation efforts for different species.

Associations between urinary iodine concentration and the prevalence of metabolic disorders: a cross-sectional study.

Background: Few studies have examined the role of iodine in extrathyroidal function. Recent research has shown an association between iodine and metabolic syndromes (MetS) in Chinese and Korean populations, but the link in the American participants remains unknown. Purpose: This study aimed to examine the relationship between iodine status and metabolic disorders, including components associated with metabolic syndrome, hypertension, hyperglycemia, central obesity, triglyceride abnormalities, and low HDL. Methods: The study included 11,545 adults aged ≥ 18 years from the US National Health and Nutrition Examination Survey (2007-2018). Participants were divided into four groups based on their iodine nutritional status(ug/L), as recommended by the World Health Organization: low UIC, < 100; normal UIC, 100-299; high UIC, 300-399; and very high, ≥ 400. The Odds ratio (OR) for MetS basing the UIC group was estimated using logistic regression models for our overall population and subgroups. Results: Iodine status was positively associated with the prevalence of MetS in US adults. The risk of MetS was significantly higher in those with high UIC than in those with normal UIC [OR: 1.25; 95% confidence intervals (CI),1.016-1.539; p = 0.035). The risk of MetS was lower in the low UIC group (OR,0.82; 95% CI: 0.708-0.946; p = 0.007). There was a significant nonlinear trend between UIC and the risk of MetS, diabetes, and obesity in overall participants. Participants with high UIC had significantly increased TG elevation (OR, 1.24; 95% CI: 1.002-1.533; P = 0.048) and participants with very high UIC had significantly decreased risk of diabetes (OR, 0.83; 95% CI: 0.731-0.945, p = 0.005). Moreover, subgroup analysis revealed an interaction between UIC and MetS in participants aged < 60 years and ≥ 60 years, and no association between UIC and MetS in older participants aged ≥ 60 years. Conclusion: Our study validated the relationship between UIC and MetS and their components in US adults. This association may provide further dietary control strategies for the management of patients with metabolic disorders.

Systematic analysis of the cuprotosis in tumor microenvironment and prognosis of gastric cancer.

Cuprotosis is a new programmed cell death related to cancer. However, the characteristics of cuprotosis in gastric cancer (GC) remain unknown. Ten cuprotosis molecules from 1544 GC patients were used to identify three GC molecular genotypes. Cluster A was characterized by the best clinical outcome and was significantly enriched in metabolic signaling pathways. Cluster B exhibited elevated immune activation, high immune stroma scores and was significantly enriched in tumor immune signaling pathways. Cluster C was characterized by severe immunosuppression and poor response to immunotherapy. Notably, the citrate cycle, cell cycle, and p53 signaling pathways were enriched in the differentially expressed genes among the three subtypes, which were critical signaling pathways for cell death. We also developed a cuprotosis signature risk score that could accurately predict the survival, immunity, and subtype of GC. This study presents a systematic analysis of cuprotosis molecules and provides new immunotherapeutic targets for GC patients.

Seasonality in nighttime blood pressure and its associations with target organ damage.

There is some evidence that nighttime blood pressure varies between seasons. In the present analysis, we investigated the seasonal variation in ambulatory nighttime blood pressure and its associations with target organ damage. In 1054 untreated patients referred for ambulatory blood pressure monitoring, we performed measurements of urinary albumin-to-creatinine ratio (ACR, n = 1044), carotid-femoral pulse wave velocity (cfPWV, n = 1020) and left ventricular mass index (LVMI, n = 622). Patients referred in spring (n = 337, 32.0%), summer (n = 210, 19.9%), autumn (n = 196, 18.6%) and winter (n = 311, 29.5%) had similar 24-h ambulatory systolic/diastolic blood pressure (P ≥ 0.25). However, both before and after adjustment for confounding factors, nighttime systolic/diastolic blood pressure differed significantly between seasons (P < 0.001), being highest in summer and lowest in winter (adjusted mean values 117.0/75.3 mm Hg vs. 111.4/71.1 mm Hg). After adjustment for confounding factors, nighttime systolic/diastolic blood pressure were significantly and positively associated with ACR, cfPWV and LVMI (P < 0.006). In season-specific analyses, statistical significance was reached for all the associations of nighttime blood pressure with target organ damage in summer (P ≤ 0.02), and for some of the associations in spring, autumn and winter. The association between nighttime systolic blood pressure and ACR was significantly stronger in patients examined in summer than those in winter (standardized ß, 0.31 vs 0.11 mg/mmol, P for interaction = 0.03). In conclusion, there is indeed seasonality in nighttime blood pressure level, as well as in its association with renal injury in terms of urinary albumin excretion. Our study shows that there is indeed seasonal variability in nighttime blood pressure, highest in summer and lowest in winter, and its association with renal injury in terms of urinary albumin excretion varies between summer and winter as well.

PD-1/PD-L1 inhibitor plus chemotherapy versus standard of care in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor plus chemotherapy vs standard of care (SoC) treatment in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M-SCCHN). METHODS: Randomized controlled trials (RCTs) that investigated PD-1/PD-L1 inhibitor plus chemotherapy vs SoC as first-line treatment for R/M-SCCHN were searched from electronic databases (PubMed, Embase and Cochrane Library). The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: In total, three phase 3 RCTs (KEYNOTE-048, CAPTAIN-1st, and JUPITER-02; n = 1120) with three PD-1 inhibitors (pembrolizumab, camrelizumab and toripalimab) were included in the analysis. Compared with SoC, PD-1 inhibitor plus chemotherapy significantly prolonged PFS (hazard ratio [HR] 0.66, 95% CI 0.40-0.93, p < 0.001) and OS (HR 0.73, 95% CI 0.60-0.86, p < 0.001) of patients. There was no statistical differences in ORR (odds ratio [OR] 1.26; 95% CI 0.97-1.64, p = 0.086), grade 3 or higher AEs (OR 0.77, 95% CI 0.50-1.17, p = 0.221), and treatment-related deaths (OR 1.34, 95% CI 0.60-2.98, p = 0.470) between the two groups. CONCLUSION: PD-1 inhibitor plus chemotherapy showed more survival benefit than SoC in the first-line treatment for R/M-SCCHN, with a similar safety profile.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project.

Objective: This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness. Methods: We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges. Results: Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83). Conclusion: Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

Diversity and metabolic potentials of microbial communities associated with pollinator and cheater fig wasps in fig-fig wasp mutualism system.

Microbial symbionts can influence a myriad of insect behavioral and physiological traits. However, how microbial communities may shape or be shaped by insect interactions with plants and neighboring species remains underexplored. The fig-fig wasp mutualism system offers a unique model to study the roles of microbiome in the interactions between the plants and co-habiting insects because a confined fig environment is shared by two fig wasp species, the pollinator wasp (Eupristina altissima and Eupristina verticillata) and the cheater wasp (Eupristina sp1 and Eupristina sp2). Here, we performed whole genome resequencing (WGS) on 48 individual fig wasps (Eupristina spp.) from Yunnan, China, to reveal the phylogenetic relationship and genetic divergence between pollinator and congeneric cheater wasps associated with the Ficus trees. We then extracted metagenomic sequences to explore the compositions, network structures, and functional capabilities of microbial communities associated with these wasps. We found that the cheaters and pollinators from the same fig species are sister species, which are highly genetically divergent. Fig wasps harbor diverse but stable microbial communities. Fig species dominate over the fig wasp genotype in shaping the bacterial and fungal communities. Variation in microbial communities may be partially explained by the filtering effect from fig and phylogeny of fig wasps. It is worth noting that cheaters have similar microbial communities to their sister pollinators, which may allow cheaters to coexist and gain resources from the same fig species. In terms of metabolic capabilities, some bacteria such as Desulfovibrio and Lachnospiraceae are candidates involved in the nutritional uptake of fig wasps. Our results provide novel insights into how microbiome community and metabolic functions may couple with the fig-wasp mutualistic systems.