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Abstract Purpose Respiratory movement, as one of the main challenges in proton therapy for pancreatic cancer patients, could not only lead to harm to normal tissues but also lead to failure of the tumor control, resulting in irreversible consequences. Including respiratory movements into the plan optimization, i.e. 4D robust optimization, may mitigate the interplay effect. However, 4D robust optimization considering images of all breathing phases is time-consuming and less efficient. This work aims to investigate the effect of the breathing phase number on the 4D robust optimization for pancreatic cancer intensity modulated proton therapy (IMPT) by examining plan quality and computational efficiency. Methods A total of 15 pancreatic cancer patients were retrospectively analyzed. In this study, both anterior-fields and posterior-fields plans were created for each patient. For each plan, six four-dimensional (4D) robust treatment planning strategies with different numbers of respiratory phases and one three-dimensional (3D) treatment plan were created. Optimization of the plans were performed on all ten phases (10phase plan), two extreme phases (2phase plan), two extreme phases plus an intermediate state (3phase plan), two extreme phases plus the 3D CT (3Aphase plan), six phases during the exhalation stage (6Exphase plan), six phases during the inhalation stage (6Inphase plan) and 3D Computed Tomography (CT) scan image (3D plan), respectively. 4D dynamic dose (4DDD) was then calculated to access the interplay effect by considering respiratory motion and dynamic beam delivery. Plan quality and dosimetric parameters for the target and organs at risk (OARs) were then analyzed. Results Compared to the 4D plans, 3D plan performed terribly in terms of target coverage and organs at risk. Target dose in anterior-fields plan varied slightly among all six 4D treatment planning strategies. Both the 6Exphase and 6Inphase plans demonstrated performance that was comparable to the 10phase plan in target coverage, outperforming the other five plans for anterior-fields plan. It’s basically the same for the posterior-fields plan. The six strategies showed similar OARs sparing effect for both anterior-fields and posterior-fields plan. Compared with the 10phase plan, the average decline rates of the optimization time of the six plans of 2phase, 3phase, 3Aphase, 6Exphase, 6Inphase, and 3D were 73.26 ± 6.54% vs. 74.48 ± 6.63%, 65.80 ± 7.89% vs. 65.81 ± 9.58%, 54.67 ± 11.52% vs. 65.75 ± 9.58%, 42.14 ± 13.57% vs. 39.63 ± 16.93%, 37.72 ± 11.70% vs. 40.79 ± 13.62% and 75.52 ± 8.21% vs. 80.67 ± 5.62%, respectively (anterior vs. posterior). With the decrease of the number of phases selected for optimization, the decline rates increased, while the other dosimetry parameters generally showed a deterioration trend. Conclusion In this study, a comprehensive evaluation of six 4D robust treatment planning strategies and one 3D treatment planning strategy for pancreatic cancer patients receiving IMPT was performed. The results showed that six 4D robust optimization strategies were comparable in common posterior field therapy. 2phase and 3phase (including 3Aphase) treatment planning strategies could replace the 10phase treatment planning strategy. It should be noted that patients with large motion amplitudes should receive special attention. The dosimetric performance of the 6Exphase and 6Inphase plans closely aligned with that of the 10phase plan in anterior fields. These plans offered a feasible alternative to 10phase treatment planning strategy by reducing optimization time while maintaining dose coverage of the target and protection of OARs. This research provides guidelines to reduce optimization time and improve clinical efficiency for pancreatic cancer IMPT.

Abstract Background & Aims There is no consensus on whether it is worthwhile for young people to undergo lipid screening. An estimate of the national prevalence of lipid screening in this population can serve as a basic parameter in analyses of the utilization and cost-effectiveness of health care services. Previous studies were mostly based on electronic health records or insurance claims data or were restricted to adolescents at younger ages. This study aimed to investigate the prevalence of lipid screening and the factors associated with it in young people aged 16– to 21 years in the United States based on a nationally representative sample. Methods A cross-sectional study of 16- to 21-year-old participants from the National Health and Nutrition Examination Survey (NHANES), 2013–March 2020 (four cycles), was conducted. The prevalence of lipid screening uptake was calculated for each cycle as well as for all four cycles combined, and the associations of lipid screening uptake with the covariates were analysed by logistic regression. An appropriate sample weight was incorporated into the analysis as recommended. Results A total of 3,600 participants were included in the analysis, and 32.02% of them had ever received lipid screening at the time of the survey, with no statistically significant secular changes observed over the four cycles. Among the participants, 28.83% received lipid screening within the past 5 years. In multivariable regression analysis adjusted for all covariates, non-Hispanic black ethnicity (adjusted odds ratio [AOR]: 1.43), having health insurance (AOR: 1.54), obesity (AOR: 1.65) and sufficient physical activity (AOR: 1.36) were significantly associated with a greater chance of ever receiving lipid screening. Conclusions Nearly one-third of young people aged 16– to 21 years in the United States have received lipid screening. Ethnicity, health insurance, weight problems, and physical activity level were associated with the likelihood of lipid screening uptake. These findings could help people understand the current situation of lipid screening in young people in the United States and may serve as fundamental parameters in the assessment of the utilization and cost-effectiveness of related health care services.

Abstract Background Bone metastasis (BM) occurs when colon cancer cells disseminate from the primary tumor site to the skeletal system via the bloodstream or lymphatic system. The emergence of such bone metastases typically heralds a significantly poor prognosis for the patient. This study's primary aim is to develop a machine learning model to identify patients at elevated risk of bone metastasis among those with right-sided colon cancer undergoing complete mesocolonectomy (CME). Patients and methods The study cohort comprised 1,151 individuals diagnosed with right-sided colon cancer, with a subset of 73 patients presenting with bone metastases originating from the colon. We used univariate and multivariate regression analyses as well as four machine learning algorithms to screen variables for 38 characteristic variables such as patient demographic characteristics and surgical information. The study employed four distinct machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), to develop the predictive model. Additionally, the model was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), while Shapley additive explanation (SHAP) was utilized to visualize and analyze the model. Results The XGBoost algorithm performed the best performance among the four prediction models. In the training set, the XGBoost algorithm had an area under curve (AUC) value of 0.973 (0.953–0.994), an accuracy of 0.925 (0.913–0.936), a sensitivity of 0.921 (0.902–0.940), and a specificity of 0.908 (0.894–0.922). In the validation set, the XGBoost algorithm had an AUC value of 0.922 (0.833–0.995), an accuracy of 0.908 (0.889–0.926), a sensitivity of 0.924 (0.873–0.975), and a specificity of 0.883 (0.810–0.956). Furthermore, the AUC value of 0.83 for the external validation set suggests that the XGBoost prediction model possesses strong extrapolation capabilities. The results of SHAP analysis identified alkaline phosphatase (ALP) levels, tumor size, invasion depth, lymph node metastasis, lung metastasis, and postoperative neutrophil-to-lymphocyte ratio (NLR) levels as significant risk factors for BM from right-sided colon cancer subsequent to CME. Conclusion The prediction model for BM from right-sided colon cancer developed using the XGBoost machine learning algorithm in this study is both highly precise and clinically valuable.

The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004–2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem.

Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), possess antioxidant properties and play a crucial role in growth and development. However, the combined effects of ALA, EPA, and DHA at different concentrations have rarely been reported. This work explored the effects of EPA, ALA, and DHA on the viability and antioxidant capacity of mouse hepatocytes, with the objective of enhancing the antioxidant capacity. Within the appropriate concentration range, cell viability and the activity of glutathione S-transferase, superoxide dismutase, and catalase were increased, while the oxidation products of malondialdehyde and the level of intracellular reactive oxygen species were obviously reduced. Thus, oxidative stress was relieved, and cellular antioxidant levels were improved. Finally, response surface optimization was carried out for EPA, ALA, and DHA, and the model was established. The antioxidant capacity of the cells was highest at EPA, ALA, and DHA concentrations of 145.46, 405.05, and 551.52 µM, respectively. These findings lay the foundation for further exploration of the interactive mechanisms of n-3 PUFAs in the body, as well as their applications in nutraceutical food.

In a study of DNA methylation changes in melatonin-deficient rice mutants, mutant plants showed premature leaf senescence during grain-filling and reduced grain yield. Melatonin deficiency led to transcriptional reprogramming, especially of genes involved in chlorophyll and carbon metabolism, redox regulation, and transcriptional regulation, during dark-induced leaf senescence. Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes. Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin. A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been extensively studied for its potential therapeutic effects on various central nervous system (CNS) disorders, including epilepsy, chronic pain, Parkinson’s disease, and stress-related neuropsychiatric disorders. However, the pharmacological mechanisms of CBD have not been fully elucidated due to the complexity of their targets. In this study, we reported that the transient receptor potential canonical 4 (TRPC4) channel, a calcium-permeable, non-selective cation channel, could be inhibited by CBD. TRPC4 is highly abundant in the central nervous system and plays a critical role in regulating axonal regeneration, neurotransmitter release, and neuronal network activity. Here, we used whole-cell electrophysiology and intracellular calcium measurements to identify the inhibitory effects of CBD on TRPC4, in which CBD was found to inhibit TRPC4 channel with an IC50 value of 1.52 μM TRPC4 channels function as receptor-operated channels (ROC) and could be activated by epinephrine (EP) via G proteins. We show that CBD can inhibit EP-evoked TRPC4 current in vitro and EP-evoked neuronal excitability in the medial prefrontal cortex (mPFC). These results are consistent with the action of TRPC4-specific inhibitor Pico145, suggesting that TRPC4 works as a functional ionotropic receptor of CBD. This study identified TRPC4 as a novel target for CBD in the CNS and suggested that CBD could reduce the pyramidal neuron excitability by inhibiting TRPC4-containing channels in the mPFC.

Air pollution significantly impacts lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to common EGFR mutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, and radiomic features. Finally, MAD1 and TPRN were identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers.

BackgroundIrreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE’s clinical application.MethodsThe clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters.ResultsThirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien−Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days.ConclusionIRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver.

Objective Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI).Methods A search was conducted across seven databases, encompassing data from the inception of each database through October 8th, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions.Results This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = −23.31, 95% CI (-28.06, −18.57); p

Microplastics, as a type of anthropogenic pollution in aquatic ecosystems, affect the carbon cycle of organic matter. Although some studies have investigated the effects of microplastics on dissolved organic matter (DOM), the impact of alterations in the chemical properties of microplastics on refractory DOM and carbon release remains unclear. Here, we observed that microplastic treatments (e.g., polystyrene, PS) altered the composition and function of microbial community, notably increasing the abundance of microbial families involved in consuming easily degradable organic matter. During the process in which microbial community decomposed organic matter into DOM, PS underwent surface oxidation. The oxidized PS aggregated with DOM and microorganisms through electrostatic interactions and chemical bonds. Moreover, these interactions between oxidized PS and microbial community affect the utilization of organic matter, resulting in a significant decrease in CO2 emissions. Specifically, total CO2 emissions decreased by approximately 23.76 % with 0.1 mg/L PS treatment and by 44.97 % with 10 mg/L PS treatment compared to those in PS-free treatments over the entire reaction. These findings underscored the significance of the chemical properties of PS in the interactions among DOM and microorganisms, emphasizing the potential impact of PS microplastics on the carbon cycle in ecosystems.

Summary: Background: How often hypertensive patients could achieve remission to normal blood pressure (BP) (i.e.,

Objective: This study aimed to investigate the incidence, treatment status, and impact position of impacted third molars (ITM) and their effects on patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A retrospective analysis was conducted on the medical records of 454 patients who underwent HSCT, out of which 188 patients had ITM. The presence of ITM and its association with transplant-related infections and complications were recorded and analyzed. Results: Patients with ITM were significantly younger. The number of mandibular ITM was notably higher than maxillary ones, and the risk of pericoronitis in mandibular ITM was significantly higher than in maxillary ones. Out of 311 ITM in 188 patients, 25 were extracted before transplantation. The proportion of extraction and treatment for ITM with pericoronitis or caries was significantly higher than that for ITM without such problems. Moreover, patients with a history of pre-transplant pericoronitis had a significantly higher probability of developing tooth-related complications during transplantation, caused by pericoronitis in ITM compared to patients without a history of pericoronitis. Conclusion: Pre-transplant examination and treatment of ITM are essential, especially in cases with a history of pericoronitis. Oral intervention can significantly reduce the occurrence of tooth-related complications related to ITM during transplantation.

The United Nations has proposed Sustainable Development Goal 15 (SDG15), which emphasizes the importance of sustainable land development. This study aims to use remote sensing data to build a spectral index feature dataset based on Google Earth Engine (GEE) platform, dig deep spectral features of ground objects, and use a random forest (RF) algorithm to extract land use type distribution data in the Bohai Rim region from 2000 to 2020. Meanwhile, combined with a land use transfer map and landscape pattern index, the spatio-temporal pattern of land use was quantitatively analyzed. Finally, the sustainable development level of land was evaluated quantitatively from three aspects: forest resource sustainability, wetland resource sustainability, and land system sustainability. The results show that the overall accuracy and kappa coefficient of land use classification achieved by GEE and the RF algorithm were 0.94 and 0.92, respectively. From 2000 to 2020, the main land use type in the study area was cropland, accounting for 33% of the total, and the impervious has significantly expanded, increasing by 9588.01 km2, mainly from cropland, barren, and water. In relation to SDG15, forest resources exhibited poor stability, wetland resources demonstrated a steady recovery, SDG15.3.1 revealed that the problems of land degradation exist in various provinces and cities around the Bohai Sea, and the stability of the land system was poor between 2000 and 2020. This article can provide a valuable reference for land use management and ecological remediation in the Bohai Rim region.

Abstract Background Sarcopenia and frailty are both age‐related declines in functional reserve that are linked to adverse health outcomes. It is critical to know about the outcomes of a combination of these conditions. The study aimed to investigate the effects of sarcopenia and frailty on postoperative recovery in elderly patients and to explore risk factors. Methods This prospective cohort study was conducted among 608 patients aged ≥60 years, American Society of Anesthesiologists I‐III, who were scheduled to undergo thoracic (non‐cardiac) and abdominal surgery from 1 March 2022 to 31 October 2022 at the Affiliated Hospital of Xuzhou Medical University. Frailty was measured by the 28‐item frailty index, and sarcopenia was assessed sarcopenia was assessed by skeletal muscle index in computed tomographic scan, handgrip strength and 6‐m walk. Participants were classified as follows: Group A: both sarcopenia and frailty; Group B: sarcopenia only; Group C: frailty only; and Group D: neither frailty nor sarcopenia. The primary outcome was 90‐day morbidity. Multivariable logistic regression model was used to estimate the association between sarcopenia, frailty and 90‐day morbidity. Results The median (interquartile range) age of participants was 68 (64–72) years, and 62.7% were men. The prevalence rates of sarcopenia and frailty were 32.8% and 47.6%, respectively. The 90‐day morbidity in Group A was 58.5%, in Group B was 46.2%, in Group C was 42.0% and in Group D was 28.8%, and the difference was significant (P

Abstract Piezoelectrets, also called ferroelectrets, can exhibit promising piezoelectric properties and have plenty of applications in wearable health monitoring. Usually, the cellular structure of piezoelectrets is of outstanding importance for their sensing properties, and structure improvement and optimisation would be a possible way to realise high‐performance piezoelectrets. The authors proposed a compound‐structured piezoelectret system, where a layer of polypropylene foam was sandwiched between two layers of solid polytetrafluoroethylene, resulting in a combination of a foam‐structured and a layer‐structured piezoelectrets. The compound systems are thin and flexible, they can exhibit stable electrical outputs, they have relatively broader linear working range under pressure, and promising mechanical sustainability for multiple testing. The results reveal that the compound system can be considered as a simple addition of both components, and each component contributes linearly and independently to the whole system. The application potential of this proposed compound system has been demonstrated by sleep monitoring together with carotid and radial pulse recordings, where many useful physiological information including breath, heartbeat, and pulse details can be extracted from the signals acquired by the compound system. A type of flexible sensor system that is very competitive for future portable and wearable applications may be provided.

Industrial mobile robots easily experience actuator loss of some effectiveness and additive bias faults due to the working scenarios, resulting in unexpected performance degradation. This article proposes a novel adaptive fault-tolerant control (FTC) strategy for nonholonomic mobile robot systems subject to simultaneous actuator lock-in-place (LIP) and partial loss-of-effectiveness (LOE) faults. First, a nominal fractional-order sliding mode controller based on the designed exponential super-twisting reaching law is investigated to reduce the reaching phase time and eliminate the chattering. To address the time-varying LIP faults and uncertainties, a novel barrier function (BF)-based gain is explored to assist the super-twisting law. An estimator is designed to estimate the lower bound of the time-varying partial LOE fault coefficients, thus without requiring the boundary information of faults that is commonly requested in traditional FTC schemes. Combined with the nominal controller clubbed with BF and estimator-based LOE fault compensation term, the fault-tolerant controller is finally constructed. The proposed FTC scheme achieves fast convergence and the sliding variables can be confined in a predetermined neighborhood of the sliding manifold under actuator faults. The results show that the proposed controller has superior tracking performance under faulty conditions compared with other state-of-the-art adaptive FTC approaches.

Objective: This retrospective analysis aimed to evaluate the prevalence of periodontitis in patients undergoing hematopoietic stem cell transplantation, and investigate the effects of various periodontal statuses and risk factors on oral infection incidence. Study design: Medical records of patients pre– and post–hematopoietic stem cell transplantation from June 2019 to October 2021were reviewed. The study examined the effort of different periodontal statuses on oral complications and infections in patients during transplantation. Results: Of 549 transplant patients studied, 363 had periodontitis. Patients with or without periodontitis showed significant differences in mean age, male proportion, and mucositis incidence during transplantation (P

ObjectiveWe examined the effectiveness of three different messages for persuading individuals to get vaccinated against COVID-19, and the role that emotions play in persuasion.MethodsFour hundred-thirty-six participants reported their concern about the COVID-19 pandemic and confidence/hesitancy toward vaccines. Participants were randomly assigned to one of three text conditions: (1) self-interest: a persuasive message that focused on how much of a “serious threat COVID-19 is to you,” and to get vaccinated to “protect yourself”; (2) self-interest + altruistic: a persuasive message that focused on the “threat to you and your community” and to get vaccinated to “protect you and your loved ones”; (3) self-interest + altruistic + normal: a persuasive message that included (2) but added “This is the only way we can get back to a normal life.”; and, (4) a baseline control: no text. After reading, participants reported their emotions toward COVID-19 vaccines and their willingness to get vaccinated.ResultsIndividuals in the self-interest + altruistic + normal condition were more willing to get vaccinated compared to the control condition and self-interest + altruistic condition. However, there were no differences in willingness between the self-interest + altruistic + normal condition and the self-interest condition. Moreover, emotions mediated relations between vaccine confidence/hesitancy and willingness.ConclusionA message that focuses on “getting back to normal” can achieve important public health action by increasing vaccine uptake to protect the population. Future work is needed across multiple countries and contexts (i.e., non-pandemic) to assess message effectiveness.

BackgroundThe triglyceride glucose (TyG) index is an effective method for determining insulin resistance (IR). Limited research has explored the connection between the TyG index and functionally significant stenosis in hypertensive patients. Furthermore, the connections between the TyG index, fat attenuation index (FAI) and atherosclerotic plaque characteristics are also worth exploring.MethodsThe study screened 1622 hypertensive participants without coronary artery disease history who underwent coronary computed tomography angiography. The TyG index was calculated as ln (fasting glucose [mg/dL] * fasting TG [mg/dL]/2). Adverse plaque characteristics (HRPCs), high-risk plaques (HRPs), FAI, and CT-derived fractional flow reserve (FFRCT) were analyzed and measured for all patients. Functionally significant stenosis causing ischemia is defined as FFRCT ≤ 0.80. Two patient groups were created based on the FFRCT: the FFRCT < 0.80 group and the FFRCT > 0.80 group. In hypertensive patients, the association between the TyG index and FFRCT was examined applying a logistic regression model.ResultsThe TyG index was higher for people with FFRCT ≤ 0.80 contrast to those with FFRCT > 0.80. After controlling for additional confounding factors, the logistic regression model revealed a clear connection between the TyG index and FFRCT ≤ 0.80 (OR = 1.718, 95% CI 1.097–2.690, p = 0.018). The restricted cubic spline analysis displayed a nonlinear connection between the TyG index and FFRCT ≤ 0.80 (p for nonlinear = 0.001). The TyG index increased the fraction of individuals with HRPs and HRPCs, FAI raised, and FFRCT decreased (p < 0.05). The multivariate linear regression analysis illustrated a powerfulcorrelation between high TyG index levels and FAI, FFRCT, positive remodeling (PR), and low-attenuation plaque (LAPs) (standardized regression coefficients: 0.029 [p = 0.007], -0.051 [p < 0.001], 0.029 [p = 0.027], and 0.026 [p = 0.046], separately).ConclusionIn hypertensive patients, the TyG index showed an excellent association with a risk of FFRCT ≤ 0.80. Additionally, the TyG index was also linked to FAI, FFRCT, PR, and LAPs.

Abstract Ginger (Zingiber officinale Roscoe) is an important plant used worldwide for medicine and food. The R2R3‐MYB transcription factor (TF) family has essential roles in plant growth, development, and stresses resistance, and the number of genes in the family varies greatly among different types of plants. However, genome‐wide discovery of ZoMYBs and gene responses to stresses have not been reported in ginger. Therefore, genome‐wide analysis of R2R3‐MYB genes in ginger was conducted in this study. Protein phylogenetic relations and conserved motifs and chromosome localization and duplication, structure, and cis‐regulatory elements were analyzed. In addition, the expression patterns of selected genes were analyzed under two different stresses. A total of 299 candidate ZoMYB genes were discovered in ginger. Based on groupings of R2R3‐MYB genes in the model plant Arabidopsis thaliana (L.) Heynh., ZoMYBs were divided into eight groups. Genes were distributed across 22 chromosomes at uneven densities. In gene duplication analysis, 120 segmental duplications were identified in the ginger genome. Gene expression patterns of 10 ZoMYBs in leaves of ginger under abscisic acid (ABA) and low‐temperature stress treatments were different. The results will help to determine the exact roles of ZoMYBs in anti‐stress responses in ginger.

Objectives To explore associations between adverse birth outcomes and childhood overweight at 3–8 years of age.Design A prospective cohort study.Setting Six central urban districts of Tianjin, China.Participants 1681 woman–child pairs.Methods 1681 woman–child pairs were followed up for 8 years in Tianjin, China. Demographic and clinical information including birth outcomes was collected longitudinally, commencing from first antenatal care visit till postpartum period. Offspring height and weight were measured at 3–8 years of age. High and low weight/length ratios (WLR) at birth were, respectively, defined as ≥90th and ≤10th gestational week and sex-specific percentiles. Overweight for children at 3–5 and 6–8 years of age were, respectively, defined as body mass index (BMI)-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO’s child growth standards. Binary logistic regression analysis was used to obtain ORs and 95% CI with a stepwise backward selection method to select independent predictors.Primary outcomes measures Childhood overweight.Results Of 1681 children, 10.7% (n=179) and 27.8% (n=468) developed overweight at 3–5 and 6–8 years of age, respectively. Large for gestational age (LGA) was associated with increased risk of overweight at 3–5 years of age (aOR: 1.86, 95% CI: 1.27 to 2.72) while high WLR at birth was associated with increased risk of overweight at 6–8 years of age (1.82, 1.41 to 2.34). Low WLR at birth was associated with decreased risk of overweight at 6–8 years of age (0.52, 0.30 to 0.90).Conclusions LGA and high WLR at birth predicted childhood overweight at 3–5 and 6–8 years of age, respectively. Low WLR at birth was associated with decreased risk of childhood overweight at 6–8 years of age.

Abstract The role of de novo evolved genes from non-coding sequences in regulating morphological differentiation between species/subspecies remains largely unknown. Here, we show that a rice de novo gene GSE9 contributes to grain shape difference between indica/xian and japonica/geng varieties. GSE9 evolves from a previous non-coding region of wild rice Oryza rufipogon through the acquisition of start codon. This gene is inherited by most japonica varieties, while the original sequence (absence of start codon, gse9) is present in majority of indica varieties. Knockout of GSE9 in japonica varieties leads to slender grains, whereas introgression to indica background results in round grains. Population evolutionary analyses reveal that gse9 and GSE9 are derived from wild rice Or-I and Or-III groups, respectively. Our findings uncover that the de novo GSE9 gene contributes to the genetic and morphological divergence between indica and japonica subspecies, and provide a target for precise manipulation of rice grain shape.

Many people with diagnosed hypertension, high cholesterol, and/or diabetes are not receiving drug treatment, partly because they perceive their cardiovascular disease (CVD) risk as low. This study aimed to quantify the risk for future CVD events, either first or recurrent, in people with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications for any of these conditions. Participants aged 40–79 years who had been diagnosed with hypertension, high cholesterol, and/or diabetes but were not on medications were identified from National Health and Nutrition Examination Surveys cycles 1999 to 2018. Among them, those with known CVD and those without known CVD but with complete data for estimating their 10-year CVD risk were included in this study. The participants were classified as (1) “high-risk” if they had known CVD or a 10-year predicted CVD risk ≥ 7.5% or (2) “low-risk” if they had a 10-year predicted CVD risk < 7.5%. Of the 5187 participants included, 2201 had known major CVD (n = 490, 9.45%) or a 10-year predicted CVD risk ≥ 7.5% (n = 1711, 32.99%), corresponding to a weighted proportion of 34.83% (95% CI: 33.15 to 36.51%) in the US general population. The proportions of high-risk participants were much higher in the elderly (65.50% for 60–69 years and 97.86% for 70–79 years), males (45.13%), and non-Hispanic Blacks (42.15%) than in others (all p < 0.001). These patterns were consistent across survey cycles during 1999–2018. Additional analyses that classified the participants into groups above or below the treatment threshold (rather than high- or low-risk groups) according to current guidelines yielded similar results. A comparison of the 2201 untreated high-risk participants with other participants who had been diagnosed with hypertension, high cholesterol, and/or diabetes and were on medications for these conditions showed that “lower BMI”, “smaller waist circumference”, and a “non-diabetic” status, among others, were associated with a higher likelihood of “not taking medications”. In conclusion, approximately one-third of the US adults aged 40 to 79 years with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications had known CVD or a 10-year predicted CVD risk ≥ 7.5%, and this proportion was little changed over the past two decades. Interventions targeted at the subgroups with particular characteristics identified in this study may help improve the management of CVD and its risk factors.

The development of advanced sensing and control technologies provides increased intelligence and autonomy for robots and enhances the robots’ agility, maneuverability, and efficiency, which has attracted growing attention in various industries and domains [...]

Cuttage is the main propagation method of tea plant cultivars in China. However, some tea softwood cuttings just form an expanded and loose callus at the base, without adventitious root (AR) formation during the propagation period. Meanwhile, exogenous auxin could promote the AR formation of tea plant cuttings, but the regulation mechanism has not yet explained clearly. We conducted this study to elucidate the regulatory mechanism of exogenous auxin-induced adventitious root (AR) formation of such cuttings. The transcriptional expression profile of non-rooting tea calluses in response to exogenous IBA and NAA was analyzed using ONT RNA Seq technology. In total, 56,178 differentially expressed genes (DEGs) were detected, and most of genes were significantly differentially expressed after 12 h of exogenous auxin treatment. Among these DEGs, we further identified 80 DEGs involved in the auxin induction pathway and AR formation. Specifically, 14 auxin respective genes (ARFs, GH3s, and AUX/IAAs), 3 auxin transporters (AUX22), 19 auxin synthesis- and homeostasis-related genes (cytochrome P450 (CYP450) and calmodulin-like protein (CML) genes), and 44 transcription factors (LOB domain-containing protein (LBDs), SCARECROW-LIKE (SCL), zinc finger protein, WRKY, MYB, and NAC) were identified from these DEGs. Moreover, we found most of these DEGs were highly up-regulated at some stage before AR formation, suggesting that they may play a potential role in the AR formation of tea plant cuttings. In summary, this study will provide a theoretical foundation to deepen our understanding of the molecular mechanism of AR formation in tea cuttings induced by auxin during propagation time.

A series of fluorescent molecules with 1,1-dimethylnaphthalene-2(1H)-one as the core were synthesized to overcome aggregation quenching and emit bright green fluorescence. The low molecular weight of these molecules led to them to smoothly pass through the cell membrane and penetrate deep into the nucleus to emit the corresponding fluorescence. Among them, NC-4-Br and NC-5-3O have good optical and in vitro properties and showed potential for use as fluorescent probes.

This study presents the spatio–temporal evolution of the electric and magnetic fields recorded by the China Seismo–Electromagnetic Satellite (CSES) and the thermal infrared remote sensing data observed by the Chinese stationary meteorological satellites Feng Yun–2G (FY–2G) associated with the 2021 Mw7.3 Maduo earthquake. Specifically, we analyzed the power spectrum density (PSD) data of the electric field in the extremely low frequency (ELF) band, the geomagnetic east–west vector data, and the temperature of brightness blackbody (TBB) data to investigate the spatio–temporal evolution characteristics under quiet space weather conditions (Dst > −30 nT and Kp < 3). Results showed that (1) the TBB radiation began to increase notably along the northern fault of the epicenter ~1.5 months prior to the occurrence of the earthquake. It achieved its maximum intensity on 17 May, and the earthquake occurred as the anomalies decreased. (2) The PSD in the 371 Hz–500 Hz and 700 Hz–871 Hz bands exhibited anomaly perturbations near the epicenter and its magnetic conjugate area on May 17, with particularly notable perturbations observed in the latter. The anomaly perturbations began to occur ~1 month before the earthquake, and the earthquake occurred as the anomalies decreased. (3) Both the magnetic –east–west component vector data and the ion velocity Vx data exhibited anomaly perturbations near the epicenter and the magnetic conjugate area on 11 May and 16 May. (4) The anomaly perturbations in the thermal infrared TBB data, CSES electric field, and magnetic field data all occurred within a consistent perturbation time period and spatial proximity. We also conducted an investigation into the timing, location, and potential causes of the anomaly perturbations using the Vx ion velocity data with magnetic field –east–west component vector data, as well as the horizontal –north–south and vertical component PSD data of the electric field with the magnetic field –east–west component vector data. There may be both chemical and electromagnetic wave propagation models for the “lithosphere—atmosphere—ionosphere” coupling (LAIC) mechanism of the Maduo earthquake.

Abstract Background The differences in fat deposition sites exhibit varying degrees of systemic inflammatory responses and organ damage, especially in obese individuals with excessive visceral fat. Visceral fat, which is closely related to an increase in mortality rates related to heart and liver diseases. However, few studies have analysed the differences in heart and liver indicators and their correlation among groups based on the abdominal visceral fat area (AVFA). Objective Clarifying the differences in and correlations of heart and liver indicators among groups with different severities of AVFA by magnetic resonance imaging (MRI). Methods Sixty-nine subjects with obesity were enrolled. The study group consisted of forty-one individuals (AVFA ≥ 150 cm2), and the control group consisted of twenty-eight individuals (100 cm2 ≤ AVFA

Abstract Phase transition and floral induction in citrus requires several years of juvenility after germination. Such a long period of juvenility has been a major hindrance to its genetic improvement program. Studies have shown that miR156 along with its downstream genes SQUAMOSA PROMOTER BINDING PROTEINS (SBP) and SBP-LIKE (SPL) mediate the phase transition and floral induction process in plants. Our current study has systematically analyzed SPLs in 15 different citrus-related species, systematically annotated them based on their close homology to their respective Arabidopsis orthologs, and confirmed the functional attributes of the selected members in floral precocity. The majority of the species harbored 15 SPLs. Their cis-element assessment suggested the involvement of the SPLs in diverse developmental and physiological processes in response to different biotic and abiotic cues. Among all, SPL5, SPL9, and SPL11 stood out as consistently differentially expressed SPLs in the adult and young tissues of different citrus-related species. Independent overexpression of their F. hindsii orthologs (FhSPL5, FhSPL9, and FhSPL11) brought an enhanced expression of endogenous FLOWERING LOCUS T leading to the significantly precocious flowering in transgenic Arabidopsis lines. Future study of the genes in the citrus plant itself is expected to conclude the assessments made in the current study. Graphical Abstract

Cognitive decline has been linked to periodontitis through an undetermined pathophysiological mechanism. This study aimed to explore the mechanism underlying periodontitis-related cognitive decline and identify therapeutic strategies for this condition. Using single-nucleus RNA sequencing we found that changes in astrocyte number, gene expression, and cell‒cell communication were associated with cognitive decline in mice with periodontitis. In addition, activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was observed to decrease the phagocytic capability of macrophages and reprogram macrophages to a more proinflammatory state in the gingiva, thus aggravating periodontitis. To further investigate this finding, lipid-based nanoparticles carrying NLRP3 siRNA (NPsiNLRP3) were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages, restoring the oral microbiome and reducing periodontal inflammation. Furthermore, gingival injection of NPsiNLRP3 reduced the number of Serpina3nhigh astrocytes in the hippocampus and prevented cognitive decline. This study provides a functional basis for the mechanism by which the destruction of periodontal tissues can worsen cognitive decline and identifies nanoparticle-mediated restoration of gingival macrophage function as a novel treatment for periodontitis-related cognitive decline.

Solid tumors, with their intricate cellular architecture and genetic heterogeneity, have long posed therapeutic challenges. The advent of the CRISPR genome editing system offers a promising, precise genetic intervention. However, the journey from bench to bedside is fraught with hurdles, chief among them being the efficient delivery of CRISPR components to tumor cells. Lipid nanoparticles (LNPs) have emerged as a potential solution. This biocompatible nanomaterial can encapsulate the CRISPR/Cas9 system, ensuring targeted delivery while mitigating off-target effects. Pre-clinical investigations underscore the efficacy of LNP-mediated CRISPR delivery, with marked disruption of oncogenic pathways and subsequent tumor regression. Overall, CRISPR/Cas9 technology, when combined with LNPs, presents a groundbreaking approach to cancer therapy, offering precision, efficacy, and potential solutions to current limitations. While further research and clinical testing are required, the future of personalized cancer treatment based on CRISPR/Cas9 holds immense promise.

Objective To explore a newly discovered T cell antigen [the group-specific antigen(Gag)of endogenous retrovirus (ERV)] associated with type 1 diabetes (T1D) and the pathogenesis of T1D. Methods First, to analyze the amino acid sequence of an islet-expressing Gag antigen, Gag 194 and identified one peptide[P193-P210(VSRLRGRRDPPAVDSTTS)], for production of Gag-specific monoclonal antibodies (mAbs). Second, ELISA and Western blot methods were performed to evaluate antigen specificity of the mAbs. Third, the expression of Gag antigen in pancreatic islets of T1D-susceptible non-obese diabetic (NOD) mice and T1D-resistant C57BL/6 mice was examined by immunohistochemical experiments. Results Five mAbs, namely 1F4C8,2D4C6,3C3B9,4D6B3 and 5F9E4 were obtained, and all of them were IgG2b subtype. Their antigen specificity and titer varied slightly. Three mAbs (1F4C8, 2D4C6 and 5F9E4) specifically recognize the ERV Gag antigen expressed in the pancreatic islets of NOD mice and at the age of 3 weeks, the antigen was detectable. Within the islets, the Gag antigen located near β-cells rather than the area infiltrated by lympho- cytes.In contrast, the T1D-resistant C57BL/6 mice do not express the Gag antigen as detected using the same mAb. Conclusions The expression of ERV Gag antigen in pancreatic islets of NOD mice occurs at very young age, suggesting that genetic factors of this diabetes-prone mouse strain may contribute to the expression.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD. Methods We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 7:3. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors. Results In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p

The complexity and fragmentation of people's activity space are challenging to planners. However, the relevant studies are mostly concerned on the relationship between the social attributes and the activity space of residents in a single or several communities, or the spatiotemporal laws of activity space on a macro scale. The research on the spatial characteristics of residents' activity space still needs to be strengthened. The present study analyses the spatial patterns of residents' activity space based on mobile phone signaling data to fill the gap of previous studies that assessed residents' activity space across small geographic areas. First, according to the spatial scope and direction of an activity space and residents' activity coverage rate, spatial patterns can be divided into three types: compact, extended, and directional extension patterns. The CatBoost method is then used to statistically analyze the influencing variables of spatial patterns, and the order of importance of the following influencing factors is determined: the built environment is more influential than social and economic situations. This study aims to strengthen the understanding of residents' activity space at the spatial level and provide a basis for the optimization of communities with different spatial patterns.

Understanding the immunological characteristics of monocytes—including the characteristics associated with fibrosis—in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Objectives: To track the prevalence trends of latent tuberculosis infection (LTBI) at the global, regional, and national levels. Methods: Data on the prevalence of LTBI were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was estimated by joinpoint regression and was used to evaluate the epidemic of the disease. Results: Globally, the prevalence rate of LTBI decreased from 30.66% in 1990 to 23.67% in 2019, with an AAPC of -0.9%. The prevalence rate of LTBI varied from 5.02% (Jordan) to 48.35% (Uganda) in 1990 and from 2.51% (Jordan) to 43.75% (Vietnam) in 2019 at the country level. The prevalence decreased in all the six World Health Organization (WHO) regions and in most countries, with the AAPC ranging from -0.5% in the Western Pacific Region to -2.1% in the European Region and from -4.3% (Bhutan) to -0.1% (Malaysia, Myanmar, South Africa, Tokelau, and Vietnam), respectively. Disparities were also observed among different sex and age groups. Conclusion: The prevalence of LTBI decreased slightly worldwide in the last three decades, but the decrease is slow and not sufficient to meet the targets of WHO tuberculosis elimination. Much more effort and progress should be made in order to decrease the prevalence of LTBI.