DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

Identifying the association between serum urate levels and gout flares in patients taking urate-lowering therapy: a post hoc cohort analysis of the CARES trial with consideration of dropout.

OBJECTIVE: To investigate gout flare rates based on repeated serum urate (SU) measurements in a randomised controlled trial of urate-lowering therapy (ULT), accounting for dropout and death. METHODS: We performed a secondary analysis using data from Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout, which randomised participants to febuxostat or allopurinol, titrated to target SU <6 mg/dL with flare prophylaxis for 6 months. SU was categorised as ≤3.9, 4.0-5.9, 6.0-7.9, 8.0-9.9 or ≥ 10 mg/dL at each 3-6 month follow-up. The primary outcome was gout flare. Poisson regression models, adjusted for covariates and factors related to participant retention versus dropout, estimated gout flare incidence rate ratios by time-varying SU category. RESULTS: Among 6183 participants, the median age was 65 years and 84% were male. Peak gout flare rates for all SU categories were observed in months 0-6, coinciding with the initiation of ULT and months 6-12 after stopping prophylaxis. Flare rates were similar across SU groups in the initial year of ULT. During months 36-72, a dose-response relationship was observed between the SU category and flare rate. Lower flare rates were observed when SU ≤3.9 mg/dL and greater rates when SU ≥10 mg/dL, compared with SU 4.0-5.9 mg/dL (p for trend <0.01). CONCLUSION: Gout flare rates were persistently higher when SU ≥6 mg/dL after the first year of ULT after accounting for censoring. The spike in flares in all categories after stopping prophylaxis suggests a longer duration of prophylaxis may be warranted.

Hypoxia differently regulates the proportion of ALDHhi cells in lung squamous carcinoma H520 and adenocarcinoma A549 cells via the Wnt/ß-catenin pathway.

BACKGROUND: Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self-renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non-small cell lung cancer (NSCLC) remains unclear. METHODS: The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit ß-catenin while pcDNA3-ß-catenin (S33Y) plasmid enhanced the expression of ß-catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real-time PCR. RESULTS: We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, ß-catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by ß-catenin inhibitor or siRNA knockdown, whereas increased after ß-catenin overexpression. Furthermore, hypoxia treatment suppressed E-cadherin expression in H520 cells and enhanced N-cadherin and ß-catenin expression, while this effect was completely opposite in A549 cells. CONCLUSION: The hypoxia-EMT-ß-catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.

Modular development of organelle-targeting fluorescent probes for imaging formaldehyde in live cells.

Formaldehyde (FA) is endogenously generated via fundamental biological processes in living systems. Aberrant FA homeostasis in subcellular microenvironments is implicated in numerous pathological conditions. Fluorescent probes for detecting FA in specific organelles are thus of great research interest. Herein, we present a modular strategy to construct diverse organelle-targeting FA probes by incorporating selective organelle-targeting moieties into the scaffold of a 1,8-naphthalimide-derived FA fluorescent probe. These probes react with FA through the 2-aza-Cope arrangement and exhibit highly selective fluorescence increases for detecting FA in aqueous solutions. Moreover, these organelle-targeting probes, i.e., FFP551-Nuc, FFP551-ER, FFP551-Mito, and FFP551-Lyso, allow selective localization and imaging of FA in the nucleus, endoplasmic reticulum, mitochondria, and lysosomes of live mammalian cells, respectively. Furthermore, FFP551-Nuc has been successfully employed to monitor changes of endogenous FA levels in the nucleus of live mammalian cells. Overall, these probes should represent new imaging tools for studying the biology and pathology associated with FA in different intracellular compartments.

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes.

Importance: The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective: To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants: This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure: Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures: Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results: Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance: This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.

Effects of different light conditions on morphological, anatomical, photosynthetic and biochemical parameters of Cypripedium macranthos Sw.

In this study, the morphological (plant height, leaf length and width, stem diameter and leaf number), anatomical (epidermal cell density and thickness, Stomatal length and width), photosynthetic (net photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2 concentration, relative humidity, leaf temperature and chlorophyll fluorescence parameters) and biochemical parameters (the content of soluble sugar, soluble protein, proline, malondialdehyde and electrical conductivity) of Cypripedium macranthos Sw. in Changbai Mountain were determined under different light conditions (L10, L30, L50, L100). The results showed that morphological values including plant height, leaf area, stem diameter and leaf number of C. macranthos were smaller under the condition of full light at L100. The epidermal cell density and epidermal thickness of C. macranthos were the highest under L30 and L50 treatments, respectively. It had the highest net photosynthetic rate (Pn) and chlorophyll content under L50 treatment. Meanwhile, correlation analysis indicated that photosynthetically active radiation (PAR) and water use efficiency (WUE) were the main factors influencing Pn. C. macranthos accumulated more soluble sugars and soluble proteins under L100 treatment, while the degree of membrane peroxidation was the highest and the plant was severely damaged. In summary, the adaptability of C. macranthos to light conditions is ranked as follows L50 > L30 > L10 > L100. Appropriate light conditions for C. macranthos are 30%-50% of full light, which should be taken into account in protection and cultivation.

Bivariate extreme value analysis of extreme temperature and mortality in Canada, 2000-2020.

Climate change increases the risk of illness through rising temperature, severe precipitation and worst air pollution. This paper investigates how monthly excess mortality rate is associated with the increasing frequency and severity of extreme temperature in Canada during 2000-2020. The extreme associations were compared among four age groups across five sub-blocks of Canada based on the datasets of monthly T90 and T10, the two most representative indices of severe weather monitoring measures developed by the actuarial associations in Canada and US. We utilize a combined seasonal Auto-regressive Integrated Moving Average (ARIMA) and bivariate Peaks-Over-Threshold (POT) method to investigate the extreme association via the extreme tail index χ and Pickands dependence function plots. It turns out that it is likely (more than 10%) to occur with excess mortality if there are unusual low temperature with extreme intensity (all χ > 0.1 except Northeast Atlantic (NEA), Northern Plains (NPL) and Northwest Pacific (NWP) for age group 0-44), while extreme frequent high temperature seems not to affect health significantly (all χ ≤ 0.001 except NWP). Particular attention should be paid to NWP and Central Arctic (CAR) since population health therein is highly associated with both extreme frequent high and low temperatures (both χ = 0.3182 for all age groups). The revealed extreme dependence is expected to help stakeholders avoid significant ramifications with targeted health protection strategies from unexpected consequences of extreme weather events. The novel extremal dependence methodology is promisingly applied in further studies of the interplay between extreme meteorological exposures, social-economic factors and health outcomes.

Inhibitory Impact of Prenatal Exposure to Nano-Polystyrene Particles on the MAP2K6/p38 MAPK Axis Inducing Embryonic Developmental Abnormalities in Mice.

Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area.

In vivo study of chelating agent-modified nano zero-valent iron: Biodistribution and toxicity in mice.

In this study, the distribution and toxicity of nanoscale zero valent iron (nZVI) and nZVIs coated with citric acid and sodium tripolyphosphate (CA-nZVI and STPP-nZVI) in mice were investigated. nZVIs were primarily found in the livers and spleens, followed by the lungs, hearts, and kidneys. Histologic analysis revealed no significant histopathologic abnormalities or lesions in all organs except the liver at 14th d gavage. nZVIs did not have a noticeable impact on the body weight of the mice or the weight of their organs. Compared with the control group, there were no significant changes in hematology indexes in the nZVIs groups. However, the nZVIs groups exhibited varying levels of elevation in alanine aminotransferase, aspartate aminotransferase, and creatinine, suggesting liver and kidney inflammation in mice. The up-regulation of Nuclear Factor erythroid 2-Related Factor 2 and Heme oxygenase 1 in the nZVIs groups may be a response to nZVIs-induced oxidative stress. Immunohistochemical analysis confirmed the inflammatory response induced by the three nZVI groups. Chelating agents did not have a significant impact on the distribution or toxicity of nZVIs in mice. This study contributes to a comprehensive and detailed insight into nZVI toxicity in the environmental field.

Ozone pollution aggravated by mountain-valley breeze over the western Sichuan Basin, Southwest China.

The impact of thermally driven mountain-valley breezes (MVB) on the atmospheric environment remains poorly understood, especially in ozone (O3)-polluted regions with complex underlying topography. To address this knowledge gap, we focused on the western Sichuan Basin (SCB), situated immediately east of the Tibetan Plateau (TP), which is considered susceptible to MVB coupled with severe O3 pollution in southwest China. We revealed the MVB driving diurnal O3 variations and meteorological mechanisms using surface observations and ERA5 reanalysis data. Local MVB days accounted for up to 47% of cases in the summers of 2015-2022. Driven by the MVB, the near-surface O3 concentrations increased by 8.8%, with 12.7% and 50.0% deterioration in the O3 light and moderate exceedance rates, respectively, on the western SCB edge. The daytime upslope valley breeze with 20% higher wind speed drove the westward transport of rich O3 and precursors from the upwind-polluted inner SCB towards its western edge, and the O3 photochemical production, followed by intensifying solar radiation and air temperature, gave rise to 14.8% of surface O3 concentrations over the western SCB edge. The nighttime downward mountain breeze with a 20% increase in wind speed could transport the rich O3 in the mountainous area to the basin edge, causing O3 levels to increase by 2.8%. In summary, we quantitatively assessed the impacts of MVB on changes in O3 concentrations and air quality along with its meteorological mechanisms, facilitating a comprehensive understanding of meteorological drivers in the atmospheric environment.

Energy use in residential buildings for sustainable development: The fifth Solar Decathlon Europe revelations.

This research focuses on achieving sustainable development in residential buildings with energy use. Under the influence of the energy crisis and related problems, research on residential buildings for less energy use has great potential. The literature review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and including VOSviewer analysis, shows the research is increasing and meaningful. Solar Decathlon buildings are used as the main objects in this research. The fifth Solar Decathlon Europe energy use technologies are examined through onsite investigation and online searching. The Analytic Hierarchy Process method for multi-criteria decision analysis is used for sustainability assessment. Moreover, the Ladybug and ClimateStudio plugins simulated respectively the annual solar radiation and the best angle for receiving it. The main findings show that 34 kinds of technologies used in these buildings can be classified into two categories in three directions. Passive technologies should be applied and prioritized, but generating renewable energy is also important. Some infrequently used technologies are not insignificant. The research shows that the combination of technologies decides sustainability performance, but the quantity used does not. Furthermore, energy use also needs to be balanced and coordinated in combination with architectural aesthetics. This research on energy use in residential buildings is beneficial for achieving sustainable development.

Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml (n = 262) and Per/Ind + Aml (n = 269). Overall, the mean (±SD) age was 55.7 ±â€Š8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ±â€Š14.46 mmHg Per/Ind/Aml versus -14.49 ±â€Š12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed (P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Validation of the RBP-9801 oscillometric blood pressure monitor in the general population according to the association for the Advancement of Medical Instrumentation/European Society of Hypertension/ International Organization for Standardization Universal Standard.

The aim of this study was to evaluate the accuracy of the single upper-arm cuff oscillometric blood pressure (BP) monitor RBP-9801 developed for office and home BP measurement in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. A total of 105 subjects were recruited and 85 were analyzed. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.3 ± 6.4/3.1 ± 5.8 mmHg (systolic/diastolic). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 5.24/5.03 mmHg (systolic/diastolic). The conclusion is that the RBP-9801 oscillometric device for office and home BP measurement fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in the general population and can be recommended for clinic and self-use at home.

Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.

Hepatocellular carcinoma (HCC) is a common type of cancer that ranks first in cancer-associated death worldwide. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are the key components of the pyrimidine pathway, which promotes cancer development. However, the function of CAD in HCC needs to be clarified. In this study, the clinical and transcriptome data of 424 TCGA-derived HCC cases were analyzed. The results demonstrated that high CAD expression was associated with poor prognosis in HCC patients. The effect of CAD on HCC was then investigated comprehensively using GO annotation analysis, KEGG enrichment analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT algorithm. The results showed that CAD expression was correlated with immune checkpoint inhibitors and immune cell infiltration. In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Finally, the results from clinical sample suggested that CAD expression increased remarkably in HCC compared with non-cancerous tissues. Loss of function experiments demonstrated that CAD knockdown could significantly inhibit HCC cell growth and migration both in vitro and in vivo. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

Design and Synthesis of Mandelic Acid Derivatives for Suppression of Virulence via T3SS against Citrus Canker.

Citrus canker, a highly contagious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc), poses a substantial threat to citrus crops, leading to serious reductions in fruit yield and economic losses. Most commonly used bactericides against Xcc lead to the rapid development of resistant subpopulations. Therefore, it is imperative to create novel drugs, such as type III secretion system (T3SS) inhibitors, that specifically target bacterial virulence factors rather than bacterial viability. In our study, we designed and synthesized a series of mandelic acid derivatives including 2-mercapto-1,3,4-thiazole. Seven substances were found to reduce the level of transcription of hpa1 without affecting bacterial viability. In vivo bioassays indicated that compound F9 significantly inhibited hypersensitive response and pathogenicity. RT-qPCR assays showed that compound F9 visibly suppressed the expression of Xcc T3SS-related genes as well as citrus canker susceptibility gene CsLOB1. Furthermore, the combination with compound F9 and quorum-quenching bacteria HN-8 can also obviously alleviate canker symptoms.

[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Money grows on green energy: Financing a sustainable power future.

This research aims to estimate the relationship between green bond financing and the OECD nations' performance on the renewable energy indices. The study attempted to quantify the relationship between concepts by analyzing data from OECD countries for 2011-2019. Padroni unit root test, FMOLS, and DOLS method provide evidence for the study's results and convey broad policy implications on this important topic. The robustness is consequently examined through a long-term sensitivity analysis employing the FMOLS, and green bond financing nexus concerning the renewable energy indices is shown for comparison. The study showed that financing of green bonds had a predictable impact on renewable energy indices variables. Green bonds' unequal implications for renewable energy measures across the study period bear out this interpretation. The study's findings call for full suppot from government institutions, energy agencies, and departments to optimize energy efficiency, as green bond financing played a 32% role in OECD nation's renewable energy index constructions and increased per unit improvement in renewable energy sources by 9.6%. The research offers many policy recommendations for improving energy efficiency through renewable energy generation. Recent studies extend and contribute to the existing body of literature, although the scientific discussion on this subject matter still needs to be more detailed and understudied. Financial unpredictability may be transformed into a tremendous opportunity if the renewable energy business is appropriately regulated.

Sybil Attacks Detection and Traceability Mechanism Based on Beacon Packets in Connected Automobile Vehicles.

Connected Automobile Vehicles (CAVs) enable cooperative driving and traffic management by sharing traffic information between them and other vehicles and infrastructures. However, malicious vehicles create Sybil vehicles by forging multiple identities and sharing false location information with CAVs, misleading their decisions and behaviors. The existing work on defending against Sybil attacks has almost exclusively focused on detecting Sybil vehicles, ignoring the traceability of malicious vehicles. As a result, they cannot fundamentally alleviate Sybil attacks. In this work, we focus on tracking the attack source of malicious vehicles by using a novel detection mechanism that relies on vehicle broadcast beacon packets. Firstly, the roadside units (RSUs) randomly instruct vehicles to perform customized key broadcasting and listening within communication range. This allows the vehicle to prove its physical presence by broadcasting. Then, RSU analyzes the beacon packets listened to by the vehicle and constructs a neighbor graph between the vehicles based on the customized particular fields in the beacon packets. Finally, the vehicle's credibility is determined by calculating the edge success probability of vehicles in the neighbor graph, ultimately achieving the detection of Sybil vehicles and tracing malicious vehicles. The experimental results demonstrate that our scheme achieves the real-time detection and tracking of Sybil vehicles, with precision and recall rates of 98.53% and 95.93%, respectively, solving the challenge of existing detection schemes failing to combat Sybil attacks from the root.