Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

[Ultrafiltration of Angelicae Sinensis Radix and Astragali Radix inhibits ferroptosis and improves pulmonary fibrosis in rats by regulating Nrf2/xCT/GPX4 signaling pathway].

This study aims to investigate the mechanism of ferroptosis mediated by the nuclear factor-E2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11, also known as xCT)/glutathione peroxidase 4(GPX4) signaling pathway in radiationinduced pulmonary fibrosis and the intervention effect of Angelicae Sinensis Radix(ASR) and Astragali Radix(AR) ultrafiltration extract. Fifty Wistar rats were randomly divided into five groups, with 10 rats in each group. Except for the blank group without radiation, the rats in each group were anesthetized and subjected to a single local chest irradiation of 40 Gy X-rays once to establish a rat model of radiation-induced pulmonary fibrosis. After radiation, the rats in the intervention groups were orally administered with ASR-AR ultrafiltration extract at doses of 0. 12, 0. 24, and 0. 48 g·kg~(-1), respectively, once a day for 30 days. After 30 days of continuous administration, the levels of oxidative stress indicators superoxide dismutase(SOD) activity, reduced glutathione(GSH),malondialdehyde(MDA), and ferrous ion(Fe~(2+)) in lung tissues of each group were detected by colorimetry. Immunofluorescence was used to detect reactive oxygen species(ROS) fluorescence expression in lung tissues. Hematoxylin-eosin(HE) and Masson staining were performed to observe pathological changes in lung tissues. Immunohistochemistry and Western blot were used to detect the expression levels of Nrf2/xCT/GPX4 signaling pathway and fibrotic proteins in lung tissues. The results showed that compared with the results in the blank group, the levels of Fe~(2+) and MDA in the model group increased, while SOD activity and GSH levels decreased,and ROS levels increased. HE and Masson staining results showed that the structure of lung tissue was seriously damaged, the pulmonary interstitium was significantly proliferated, the alveoli collapsed and consolidated severely, and there were more inflammatory cell aggregates and collagen fiber deposits. Transmission electron microscopy showed that the degree of lung tissue damage in the model group was relatively high, with increased, smaller, and disorganized damaged mitochondria, irregular morphology, shallow matrix,most mitochondria ruptured and shortened, mildly expanded, some mitochondria with increased electron density of the matrix, partial mitochondrial outer membrane rupture, and characteristic changes of ferroptosis-specific mitochondria. Immunohistochemistry showed that the expression of transferrin receptor protein 1(TFR1) in lung tissues was significantly increased, while the expression of GPX4,ferritin heavy chain 1(FTH1), Nrf2, and xCT was significantly decreased. Western blot showed that the expression of α-smooth muscle actin(α-SMA) and collagen Ⅰ protein increased. Compared with the model group, the intervention group with ASR-AR ultrafiltration extract significantly improved lipid peroxidation and antioxidant-related indicators, decreased Fe~(2+) levels, alleviated fibrosis, and decreased the expression of TFR1, α-SMA, and collagen Ⅰ proteins in lung tissues, while increased the expression of GPX4, FTH1, Nrf2, and xCT proteins. In summary, ASR-AR ultrafiltration extract has an ameliorative effect on radiation-induced pulmonary fibrosis, and its mechanism may involve the inhibition of ferroptosis by regulating the Nrf2/xCT/GPX4 signaling pathway.

[Chemical constituents from stem bark of Aquilaria sinensis and their antibacterial activity against Helicobacter pylori].

The stem bark of Aquilaria sinensis(Thymelaeaceae), with the local name of "Li-Wa-Zi-Xing", is used in traditional Yi medicine for treating chronic gastritis and other diseases. However, its active ingredients remain currently unknown. In this study, Helicobacter pylori(Hp) is used in anti-bacterial experiments to test the active compounds derived from A. sinensis stem bark. Nineteen compounds were isolated from the stem bark of A. sinensis by column chromatography, high-performance liquid chromatography, recrystallization, etc. Aquilaridiester(1) is a new lignan. The other eighteen compounds were reported before, including docosyl caffeate(2), 6-hydroxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(3), qinanone A(4), 6-hydroxy-2-(2-phenylethyl)chromone(5), 6-hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(6), 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-1-benzopyran-4-one(7), 6-hydroxy-2-[2-(3,4-dimethoxyphenyl)ethyl]chromone(8), 6-hydroxy-2-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one(9), genkwanin(10), 5-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one(11), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(12),(+)-syringaresinol(13), zhebeiresinol(14), aquilarin A(15), caruilignan D(16),(-)-ficusal(17), pistaciamide(18), and protocatechuic acid(19). The anti-bacterial results show that compounds 2-7, 10-11, and 13 have inhibitory activity against Hp. Among them, 6-hydroxy-2-(2-phenylethyl)chromone(5) and 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-benzopyran-4-one(7) have superior inhibitory effects on Hp to others, with the same minimum inhibitory concentration(MIC) of 6.25 µmol·L~(-1). The 2-(2-phenylethyl)chromones are the major active ingredients in A. sinensis stem bark.

[Guidelines for traditional dietary care in autumn and winter].

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

Explainability of artificial neural network in predicting career fulfilment among medical doctors in developing nations: Applicability and implications.

BACKGROUND: Career fulfilment among medical doctors is crucial for job satisfaction, retention, and healthcare quality, especially in developing nations with challenging healthcare systems. Traditional career guidance methods struggle to address the complexities of career fulfilment. While recent advancements in machine learning, particularly Artificial Neural Network (ANN) models, offer promising solutions for personalized career predictions, their applicability, interpretability, and impact remain challenging. METHOD: This study explores the applicability, explainability, and implications of ANN models in predicting career fulfillment among medical doctors in developing nations, considering socio-economic, psychological, and professional factors. Box plots visualized data distribution, while Heatmaps assessed data intensity and relationships. Matthew's correlation coefficient and Taylor's chart were used to evaluate model performance. Input feature contributions to ANN predictions were analyzed using permutation importance, SHAP, LIME, and Williams plots. The model was tested on a dataset tailored to medical professionals in Nigeria and China, with evaluation metrics including Mean Absolute Error, Mean Squared Error, Root Mean Squared Error, and R2 Score. RESULTS: The ANN model demonstrates strong predictive accuracy, capturing relationships between input factors and outcomes. For Chinese doctors, it achieved an MSE of 0.0004 and R2 of 0.9994, while for Nigerian doctors, it recorded an MSE of 0.0003 and R2 of 0.9998. Key factors for Chinese doctors' satisfaction were IF1 and IF2, while EF1 and EF3 were crucial in preventing dissatisfaction. For Nigerian doctors, IF2 and IF3 drove satisfaction, while EF1 and EF4 were significant in avoiding dissatisfaction. CONCLUSION: The results highlights the ANN model's effectiveness in predicting career fulfillment among medical doctors in developing nations, offering a valuable tool for career guidance, policymaking, and improving job satisfaction, retention, and healthcare quality.

STING Agonist Delivered by Neutrophil Membrane-Coated Gold Nanoparticles Exerts Synergistic Tumor Inhibition with Radiotherapy.

Radiotherapy (RT) is one of the major treatments for cancers and a promising initiator of immune response. Gold nanoparticles are a promising radiosensitizer. In this study, we sought to optimize the drug delivery efficiency of gold nanoparticles and explore their function in delivering stimulator of interferon genes (STING) agonists with or without RT. Gold nanoparticles covalent to MSA-2 (MSA-Au) were mixed with cRGD-modified neutrophil membranes to obtain M-Au@RGD-NM. We explored the treatment efficiency of M-Au@RGD-NM combined with RT. Immune cell regulation and STING pathway activation were detected. We successfully prepared M-Au@RGD-NM with significant tumor suppression by induction of ROS and the resulting DNA damage. In vivo dynamic imaging showed that M-Au@RGD-NM was mainly targeted to radiated tumors. Tumor-bearing mice showed significant tumor inhibition following a combination therapy. M-Au@RGD-NM significantly activated the STING pathway and regulated the whole-body immune response. Locally radiated tumors showed dendritic cells mature, CD8+ T cells upregulation, and M1 polarization, with systematic immune response demonstrated by CD8+ T cell infiltration in abscopal tumors. In this study, we synthesized M-Au@RGD-NM loading MSA-2. Following characterization, we found that RT-based M-Au@RGD-NM treatment achieved good antitumor effects, tumor RT enhancement, and induction of an immune response via STING activation.

Reactions of Benzyl Phosphine Oxide/Sulfide with (COCl)2: Synthesis of Novel Acyl Chloride-Substituted Chlorophosphonium Ylides.

New reactions of benzyl phosphine oxide/sulfide with oxalyl chloride are presented. The resulting reactive intermediates, acyl chloride-substituted chlorophosphonium ylides, are capable of undergoing esterification and Friedel-Crafts acylation reactions, ultimately yielding either methyl 2-(2-bromophenyl)-2-(diphenylphosphoryl)acetate or ß-carbonyl-diarylphosphine oxide derivatives. Additionally, when an alkynyl group is contained in the acyl chloride-substituted chlorophosphonium ylide, intramolecular cyclization occurs, leading to the formation of a pair of trans- and cis-dichlorophosphonyl benzofulvene isomers. The generation process of acyl chloride-substituted chlorophosphonium ylide was carefully monitored by using 31P{1H} NMR spectroscopy, and a plausible reaction mechanism was proposed.

A signal-on photoelectrochemical aptasensor based on WO3/CdS heterojunction for the ultrasensitive detection of kanamycin.

In this study, a signal-on photoelectrochemical (PEC) aptasensor for the ultrasensitive determination of kanamycin (KANA) was constructed using WO3/CdS heterojunction as photoactive material. Firstly, WO3/CdS heterojunction with excellent photoelectric response was successfully prepared by simple co-precipitation method, resulting in a strong and stable initial photocurrent. In addition, amino modified aptamers were immobilized on the electrode surface by glutaraldehyde as biological recognition components. In the presence of the target KANA, it is specifically recognized and captured by the aptamers. More importantly, KANA can act as a signal amplifier to enhance the photocurrent due to the oxidation of KANA by photogenerated holes. Therefore, a signal-on PEC aptasensor based on WO3/CdS heterojunction with high selectivity was obtained for the detection of KANA. Under optimized experimental conditions, the PEC aptasensor demonstrated a wide linear range of 10 pM to 400 nM, with a detection limit of 6.77 pM. Meanwhile, the designed PEC aptasensor had been successfully utilized for the analytical examination of milk, fish, serum, and water samples.

Is Opioid Consumption Impacted by Study Participation? Maintenance of Fewer Opioid Refills With Reduced Prescription Quantity After Posterior Spinal Fusion in Adolescents With Idiopathic Scoliosis.

BACKGROUND: Opioid overprescribing can lead to nonmedical opioid use. In a previous prospective study (STUDY), we showed that a standardized protocol involving preoperative education and reduced opioid prescription quantity decreased opioid use in idiopathic scoliosis patients following posterior spinal fusion (PSF). A potential limitation was the Hawthorne effect, where participant behavior changes due to observation. At STUDY conclusion, we continued the reduced opioid prescriptions but discontinued the formal preoperative education. This retrospective study (post-STUDY) assessed if opioid refill requests increased outside of a study setting. METHODS: Post-STUDY included patients aged 10 to 17 years who underwent PSF for idiopathic scoliosis between January 2022 and December 2023 and were discharged with a prescription of ≤30 oxycodone doses. Patients were excluded if they had previous spine surgery or were discharged with an opioid other than oxycodone. Demographics, perioperative variables, and opioid refill requests were compared with the data from STUDY, in which patients were aware their opioid use would be tracked. Patient-reported outcomes were collected via Scoliosis Research Society-22r (SRS-22r) surveys. RESULTS: The post-STUDY cohort included 67 patients (69% female). The average age at the time of PSF was 13.9 years (range, 11 to 17 y). The mean number of levels fused was slightly higher (10.9 vs. 10.0, P=0.04), and intraoperative estimated blood loss was lower (211 vs. 303 mL, P<0.01) compared with the STUDY cohort. Demographics, preoperative major curve magnitude, surgery duration, and length of hospital stay were similar. The percentage of patients who requested and received opioid refills between the post-STUDY and STUDY cohorts was also similar [6/67 (9%) vs. 3/49 (6%), P=0.30]. SRS-22r showed improvements in self-image, satisfaction, and mean total score from preoperative to postoperative. CONCLUSIONS: Reduced opioid prescriptions did not result in increased opioid refill requests in adolescents undergoing PSF for idiopathic scoliosis outside of a study setting. While formal preoperative discussions about postoperative pain control are important, other factors likely influence opioid use. Further research should explore characteristics that predispose patients to require higher amounts of postoperative opioids. LEVEL OF EVIDENCE: Level III-therapeutic.

Synthesis of Silver(I) Complexes through In Situ Reactions of dppeda with dmp in the Presence of Silver Halides for Photocatalysis.

Due to the unique photosensitivity of silver compounds, they exhibit good photocatalytic activity as photocatalysts in the degradation of water pollutants. However, silver compounds have poor cycling stability and are prone to decomposition and reaction under light to form metallic silver, which greatly limits their practical application. Herein, a (2-(2-(diphenylphosphaneyl)ethyl)-9-methyl-1.10-phenanthroline (PSNNP)) pincer ligand was designed for stabilizing the central metal. The in situ-formed PSNNP ligand could be readily generated in one pot with the participation of silver halides. The reaction of silver halides with dppeda (N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine) in the presence of dmp (2,9-dimethyl-1,10-phenanthroline) in acetonitrile afforded complexes Ag2X2 (PSNNP)2 (complexes 1, 2) (X = Cl, Br). Single-crystal X-ray diffraction shows that the tridentate coordination of the pincer ligand provides strong binding with metal centers and leads to high stability of the pincer metal unit. The removal rate of rhodamine B (RhB) by complexes 1 and 2 can reach up to 100%, demonstrating an excellent photocatalytic degradation performance for organic dyes. The important effect of PSNNP ligands on photocatalytic properties after coordination with central metals was studied through experiments and discrete Fourier transform (DFT) calculations. The photocatalytic reaction mechanism of complexes 1 and 2 was also studied. This result provides an effective pathway for the first synthesis of PSNNP and interesting insights into photocatalytic degradation chemistry.

Glymphatic System in Preterm Neonates: Developmental Insights Following Birth Asphyxia.

BACKGROUND: Birth asphyxia (BA) and germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are common clinical events in preterm neonates. However, their effects on the glymphatic system (GS) development in preterm neonates remain arcane. PURPOSE: To evaluate the developmental trajectory of the GS, and to investigate the effects of BA and GMH-IVH on GS function in preterm neonates. STUDY TYPE: Prospective. POPULATION: Two independent datasets, prospectively acquired internal dataset (including 99 preterm neonates, 40 female, mean [standard deviation] gestational age (GA) at birth, 29.95 [2.63] weeks) and the developing Human Connectome Project (dHCP) dataset (including 81 preterm neonates, 29 female, median [interquartile range] GA at birth, 32.71 [4.28] weeks). FIELD STRENGTH/SEQUENCE: 3.0 T MRI and diffusion-weighted spin-echo planar imaging sequence. ASSESSMENT: The diffusion-weighted images were preprocessed in volumetric space using the FMRIB Software Library and diffusion along the perivascular space (DTI-ALPS) index was accessed to evaluate GS function. STATISTICAL TESTS: Two sample t tests, one-way analysis of variance followed by least-significant difference (LSD) post hoc analysis, chi-squared tests, and Pearson's correlation analysis. Significance level: P < 0.05. RESULTS: In prospectively acquired internal dataset, preterm neonates with BA exhibited a significant lower DTI-ALPS index than those without BA (0.98 ± 0.08 vs. 1.08 ± 0.07, T = -5.89); however, GMH-IVH did not exert significant influences on the DTI-ALPS index (P = 0.83 and 0.27). The DTI-ALPS index increased significantly at postmenstrual age ranging from 25 to 34 weeks (r = 0.38) and then plateaued after 34 weeks (P = 0.35), which we also observed in the dHCP dataset. DATA CONCLUSION: BA rather than GMH-IVH serves as the major influencing factor in the development of GS in preterm neonates. Moreover, as GS development follows a nonlinear trajectory, we recommend close monitoring of GS development in preterm neonates with a GA less than 34 weeks. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

"Synergistic anticoagulant and endothelial regeneration strategy" based on mussel-inspired phospholipid copolymer coating and bioactive zeolitic imidazolate frameworks-90 to maintain the patency of CoCr stent.

Given the risks of poor patient compliance and bleeding associated with current dual antiplatelet therapies, it is urgent to develop the next generation of cardiovascular stents with anticoagulation and rapid endothelialization capabilities. Inspired by the prominent bioactivity and bioavailability of zeolitic imidazolate framework-90 (ZIF-90) in driving endothelial cell (EC) morphogenesis, this research proposes a "synergistic anticoagulant and endothelial regeneration strategy" depending on mussel-inspired phospholipid copolymer (MIPC) and ZIF-90. Depending on the copolymerization of the catechol with dopamine (Dopa) monomers, Dopa/MIPC coating was immobilized on the surface of CoCr via a one-pot process for resisting the initial thrombosis induced by platelets and fibrinogen. Meanwhile, ZIF-90 was loaded on the coating via coordination effect, aiming to accelerate the proliferation and migration of ECs. Compared with CoCr, the well-designed CoCr-Dopa/MIPC@ZIF-90 not only reduced fibrinogen adhesion by approximately 40 % and platelet adhesion by almost 55 %, but also promoted the proliferation and migration of ECs significantly in vitro. Furthermore, the blood flow velocity of CoCr-Dopa/MIPC@ZIF-90 stent was similar to natural aorta and ECs coverage on it was greatly strengthened after 30 days in a rat aorta vascular stent implantation model. Collectively, CoCr-Dopa/MIPC@ZIF-90 exhibited obvious superiority in reducing the formation of thrombus and promoting endothelial regeneration, which might meet the high requirement for the next generation of vascular stent.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma.

OBJECTIVE: The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. METHODS: A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. RESULTS: Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. CONCLUSION: Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

Association between waist circumference and sleep disorder in the elderly: Based on the NHANES 2005-2018.

The existing data do not consistently support the link between elderly adults' waist circumferences and sleep disorders. This study aimed to evaluate whether waist circumference was connected with sleep disorder in the elderly. This cross-sectional study utilized data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) regarding waist circumference, sleep disorders, and confounding factors. Included in the study were participants older than 60 who completed sleep questionnaires and waist circumference measurements. Using a multivariate logistic regression model and subgroup analyses, the relationship between waist circumference and sleep disorder was evaluated. To explore the non-linear relationship, restricted cubic spline (RCS) with three knots coupled with a logistic regression model to assess the dose-response relationship between waist circumference (continuous variables) and sleep disorder. A total of 2,545 (Weighted 14,682,916.3) elderly participants with complete information were included in the analysis and 312 (Weighted 1,777,137.8) subjects met the definition of sleep disorder. Compared with participants without sleep disorder, those with sleep disorder had a higher waist circumference (100.80 cm vs. 108.96 cm, P< 0.001). The results of the multivariable adjusted logistic regression model suggested that those in quartiles 4 (≥ 75th percentile) for their waist circumference had higher odds of sleep disorder [adjusted odds ratio (AOR) = 2.75, 95% confidence interval (CI) = 1.66-4.54, P < 0.001] compared with those in quartile 1. The RCS result showed that the OR of sleep disorder and waist circumference displayed a linear relationship (P <0.001, Non-linear P = 0.642). Age and gender subgroup analysis revealed comparable relationships between waist circumference and sleep disorder among elderly individuals. Waist circumference was associated with sleep disorders in the elderly. There was a dose-response relationship between waist circumference and the likelihood of sleep disorder. Those with a larger waist circumference were more likely to have a sleep disorder than those with a smaller waist circumference.

Associations of daily eating frequency and nighttime fasting duration with biological aging in National Health and Nutrition Examination Survey (NHANES) 2003-2010 and 2015-2018.

BACKGROUND: Information on the influences of daily eating frequency (DEF) and nighttime fasting duration (NFD) on biological aging is minimal. Our study investigated the potential associations of DEF and NFD with accelerated aging. METHODS: Out of 24212 participants in NHANES 2003-2010 and 2015-2018, 4 predicted age metrics [homeostatic dysregulation (HD), Klemera-Doubal method (KDM), phenoAge (PA), and allostatic load (AL)] were computed based on 12 blood chemistry parameters. Utilizing 24-h dietary recall, DEF was measured by the frequency of eating occurrences, while NFD was determined by assessing the timing of the initial and final meals throughout the day. Weighted multivariate linear regression models and restricted cubic spline (RCS) were utilized to examine the associations. RESULTS: Compared to DEF of ≤ 3.0 times, subjects with DEF ≥ 4.6 times demonstrated lower KDM residual [ß: -0.57, 95% confidence-interval (CI): (-0.97, -0.17)] and PA residual [ß: -0.47, 95% CI: (-0.69, -0.25)]. In comparison to NFD between 10.1 and 12.0 h, individuals with NFD ≤ 10.0 h were at higher HD [ß: 0.03, 95% CI: (0.01, 0.04)], KDM residual [ß: 0.34, 95% CI: (0.05, 0.63)], and PA residual [ß: 0.38, 95% CI: (0.18, 0.57)]. Likewise, those with NFD ≥ 14.1 h also had higher HD [ß: 0.02, 95% CI: (0.01, 0.04)] and KDM residual [ß: 0.33, 95% CI: (0.03, 0.62)]. The results were confirmed by the dose-response relationships of DEF and NFD with predicted age metrics. Lactate dehydrogenase (LDH) and globulin (Glo) were acknowledged as implicated in and mediating the relationships. CONCLUSIONS: DEF below 3.0 times and NFD less than 10.0 or more than 14.1 h were independently associated with higher predicted age metrics.

The influence of widowhood and social engagement on cognitive impairment among Chinese older adults and factors mediating their association.

Background: Prior studies exploring the impact of widowhood on cognitive impairment in later life have been focussed on the USA and Europe. We aimed to explore the mediating role of social engagement, health behaviours, and subjective well-being in the association between widowhood and cognitive impairment in the Chinese population. Methods: We conducted a study on 7796 older individuals enrolled in the 2018 wave of the Chinese Longitudinal Health Longevity Study. We used logistic regression models to analyse the impact of widowhood on cognitive health among older adults and performed mediation analysis to determine possible mediating factors in this relationship. Results: Widows and widowers had a higher risk of having cognitive impairment than married older adults (95% confidence interval (CI) = 1.312, 2.279). The results from structural equation modelling (SEM) provided a good fit to the observed data (χ2 = 24.909; P = 0.00) and indicated that the effect of widowhood on cognitive impairment was partially mediated by social engagement, lifestyle behaviours, and subjective well-being (ß = 0.075; P < 0.01). Conclusions: Our findings contribute to existing research on the mechanisms underlying the association between widowhood and cognitive impairment among older individuals, suggesting a need for policies targeted at the specific needs of this vulnerable population, such as the maintenance of social interactions, adoption of a healthy lifestyle, improvement of subjective well-being, and provision of necessary support systems.

A chimeric mRNA vaccine of S-RBD with HA conferring broad protection against influenza and COVID-19 variants.

Influenza and coronavirus disease 2019 (COVID-19) represent two respiratory diseases that have significantly impacted global health, resulting in substantial disease burden and mortality. An optimal solution would be a combined vaccine capable of addressing both diseases, thereby obviating the need for multiple vaccinations. Previously, we conceived a chimeric protein subunit vaccine targeting both influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilizing the receptor binding domain of spike protein (S-RBD) and the stalk region of hemagglutinin protein (HA-stalk) components. By integrating the S-RBD from the SARS-CoV-2 Delta variant with the headless hemagglutinin (HA) from H1N1 influenza virus, we constructed stable trimeric structures that remain accessible to neutralizing antibodies. This vaccine has demonstrated its potential by conferring protection against a spectrum of strains in mouse models. In this study, we designed an mRNA vaccine candidate encoding the chimeric antigen. The resultant humoral and cellular immune responses were meticulously evaluated in mouse models. Furthermore, the protective efficacy of the vaccine was rigorously examined through challenges with either homologous or heterologous influenza viruses or SARS-CoV-2 strains. Our findings reveal that the mRNA vaccine exhibited robust immunogenicity, engendering high and sustained levels of neutralizing antibodies accompanied by robust and persistent cellular immunity. Notably, this vaccine effectively afforded complete protection to mice against H1N1 or heterosubtypic H5N8 subtypes, as well as the SARS-CoV-2 Delta and Omicron BA.2 variants. Additionally, our mRNA vaccine design can be easily adapted from Delta RBD to Omicron RBD antigens, providing protection against emerging variants. The development of two-in-one vaccine targeting both influenza and COVID-19, incorporating the mRNA platform, may provide a versatile approach to combating future pandemics.

Comparative evaluation of machine learning models in predicting overall survival for nasopharyngeal carcinoma using 18F-FDG PET-CT parameters.

PURPOSE: The objective of this study is to assess the prognostic efficacy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET-CT) parameters in nasopharyngeal carcinoma (NPC) and identify the best machine learning (ML) prognostic model for NPC patients based on these 18F-FDG PET/CT parameters and clinical variables. METHOD: A cohort of 678 patients diagnosed with NPC between 2016 and 2020 was analyzed in this study. The model was constructed using four advanced ML algorithms, namely Random Forest (RF), Extreme Gradient Boosting (XGBoost), Least Absolute Shrinkage and Selection Operator (LASSO), and multifactor COX step-up regression. Statistical significance of the models was assessed using Kaplan-Meier (K-M) curves, with a significance level established at P < 0.05. The prognostic efficacy of the models was evaluated through the analysis of receiver operating characteristic (ROC) curves, with the area under the ROC curve (AUC) serving as a criterion for model selection. The decision curve analysis (DCA) and concordance index (C-index) were employed to assess the precision of the optimal model. RESULTS: Multivariate analysis revealed age, T stage, and metabolic tumor volume (MTV) for the primary nasopharyngeal tumor (MTVT) as significant independent prognostic factors for overall survival (OS) in NPC patients. Additionally, the LASSO model identified six key variables, including peak standardized uptake value (SUV-peak) for the primary nasopharyngeal tumor (SUV-peak(T)), MTVT, heterogeneity index for neck lymph nodes (HIN), age, pathological type, and T stage. Remarkably, the LASSO model demonstrated superior performance with a 5-year AUC of 0.849 compared to other models. Further assessment using the C-index and DCA confirmed the accuracy of the LASSO model. Subgroup analysis revealed notable risk factors, such as a high heterogeneity index (HI) for the primary nasopharyngeal tumor (HIT), MTV values for neck lymph nodes (MTVN), and HIN. CONCLUSIONS: We developed a novel prognostic machine learning model that integrates 18F-FDG PET-CT parameters and clinical characteristics, significantly enhancing prognosis prediction in NPC.