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The bay ecosystem plays an important role in maintaining energy flow, material circulation, community stability and ecosystem balance. In the present study, the comprehensive evaluation model for marine ecosystem of Laizhou Bay was established by using index system method, in which, five indicators were selected including water environment, sedimentary environment, marine community, primary productivity and ecological disaster indexes. The relative importance and weight of the evaluation indexes were determined combined using analytic hierarchy process and experts consultation method. By analyzing the survey data obtained, this assessment system was applied to assess and compare the health level of Laizhou Bay in recent ten years. Results showed that the condition of Laizhou Bay was always being sub-health, the main indicators that had given adverse impact on the health level of Laizhou Bay included inorganic nitrogen, phosphate, petroleum hydrocarbon, plankton species and benthic biomass. The results of evaluation model were more sensitive to Laizhou Bay, which could identify the adverse effects of extreme events such as oil spills and typhoons, therefore, the use of interval index and environmental admissible value could avoid disadvantage concealment, information omissions and the overestimation of limit value-based assessment method effectively.

Abstract Background Laparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC. Methods By using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis. Results Among patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss. Conclusion LLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

Abstract Background Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. Methods This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. Results Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. Conclusions A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.

Abstract Background Disordered lipid metabolism plays an essential role in both the initiation and progression of alcoholic fatty liver disease (AFLD), and fatty acid β-oxidation is increasingly considered as a crucial factor for controlling lipid metabolism. Hif-2α is a member of the Hif family of nuclear receptors, which take part in regulating hepatic fatty acid β-oxidation. However, its functional role in AFLD and the underlying mechanisms remain unclear. Results Hif-2α was upregulated in EtOH-fed mice and EtOH-treated AML-12 cells. Inhibition or silencing of Hif-2α led to increased fatty acid β-oxidation and BNIP3-dependent mitophagy. Downregulation of Hif-2α activates the PPAR-α/PGC-1α signaling pathway, which is involved in hepatic fatty acid β-oxidation, by mediating BNIP3-dependent mitophagy, ultimately delaying the progression of AFLD. Conclusions Hif-2α induces liver steatosis, which promotes the progression of AFLD. Here, we have described a novel Hif-2α-BNIP3-dependent mitophagy regulatory pathway interconnected with EtOH-induced lipid accumulation, which could be a potential therapeutic target for the prevention and treatment of AFLD.

Based on the processing and analysis of the fixed-point horizontal deformation data across the fault in the middle and southern part of the Tan-Lu fault zone in recent 20 years, this paper preliminarily analyzes the vertical deformation characteristics of the middle and southern section of the Tan-Lu fault. The research shows that the overall activity level of the middle and southern part of the Tan-Lu fault zone is not high, and the average combining rate is 0.19 mm/a. However, it has obvious characteristics of time-sharing activities: from 2000 to 2010, the activity in Huaibai-Suqian section was large, while the activity in Xinyi-Linyi section was relatively small. There was a relatively closed section between Suqian and Xinyi; The overall activity rate has decreased from 2011 to 2019, but the activity rate of Anqiu station has increased significantly compared with that of 2000 to 2011. There is a certain correspondence between the activitycharacteristics of the fault zone and the seismicity of the region in the past 20 years.

Achieving a sustainable and efficient power systems network and decarbonized environment involves the optimal allocation of multiple distributed energy resource (DERs) unit types and flexible alternating current transmission systems (FACTS) to distribution networks. However, while the most focus is on optimization algorithms and multi-objective techniques, little to no attention is paid to the underlying mechanisms in planning frameworks. This paper goes beyond existing literature by investigating the impact of planning mechanisms in smart grid planning frameworks when considering the allocation of PV distributed generation units, battery energy storage systems, capacitor banks, and electric vehicle charging station facilities. First, a single- and multi-objective planning problem is formulated. Then, we propose a novel adaptive-dynamic planning mechanism that uses a recombination technique to find optimal allocation variables of multiple DER and FACTS types. To cope with the additional complexity resulting from the expanded solution space, we develop a hybrid stochastic optimizer, named cooperative spiral genetic algorithm with differential evolution (CoSGADE) optimization scheme, to produce optimal allocation solution variables. Through numerical simulations, it is seen that the proposed adaptive planning mechanism improves achieves a 12% and 14% improvement to the conventional sequential (multi-stage) and simultaneous mechanisms, on small to large scale distribution networks.

Abstract Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein–protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either not addressed or did not show any decline. Until now, the exact mechanisms for initiating and sustaining this interaction are still unknown. The objective of this study is to use volume overload to induce cardiac hypertrophy and HF in aortocaval fistula (ACF) rat models, and to elucidate how volume overload affects metabolic changes in the kidney, even with normal renal function, in HF. The results showed the metabolic changes between control and ACF rats, including taurine metabolism; purine metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; and histidine metabolism. Increasing the downstream purine metabolism from inosine to uric acid in the kidneys of ACF rats induced oxidative stress through xanthine oxidase. This result was consistent with HK-2 cells treated with xanthine and xanthine oxidase. Under oxidative stress, taurine accumulation was observed in ACF rats, indicating increased activity of the hypotaurine–taurine pathway as a defense mechanism against oxidative stress in the kidney. Another antioxidant, ascorbic acid 2-sulfate, showed lower levels in ACF rats, indicating that the kidneys experience elevated oxidative stress due to volume overload and HF. In summary, metabolic profiles are more sensitive than clinical parameters in reacting to damage to the kidney in HF.

BackgroundMalnutrition is a rising global health issue associated with unfavorable outcomes of a variety of disorders. Currently, the prevalence and prognostic significance of malnutrition to patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remained largely unclear.MethodsA total of 705 patients diagnosed with ACS and CKD in the First Affiliated Hospital of Wenzhou Medical University between 2013 and 2021 were included in this retrospective cohort study. Malnutrition was assessed by the Controlling Nutritional Status (CONUT), the Geriatric Nutritional Risk Index (GNRI), and the Prognostic Nutritional Index (PNI), respectively. The relationships between malnutrition and all-cause mortality and major cardiovascular events (MACEs) were analyzed.ResultsDuring a median follow-up of 31 months, 153 (21.7%) patients died, and 165 (23.4%) had MACEs. The prevalence of malnutrition was 29.8, 80.6, and 89.8% for the PNI, CONUT, and GNRI, respectively. All the malnutrition indexes were correlated with each other (r = 0.77 between GNRI and PNI, r = −0.72 between GNRI and CONUT, and r = −0.88 between PNI and CONUT, all p

The rural industry is the foundation for promoting farmers' income and rural development, and adhering to the green development of the rural industry is the internal requirement for comprehensively promoting Rural Revitalization Strategy (RRS) in China. Firstly, the article explains the three aspects of China's rural eco-industries' development logic: the rural eco-industries have the historical inevitability of action under the Ecological Civilization (EC), academic rationality of development under the theory of urban-rural integration development, and strategic action under ecological poverty alleviation. Secondly, it establishes the six components of the Chinese rural eco-eco-industries' scientific connotation: one guiding concept, three theoretical foundations, three development carriers, two practical paths, a 3*3 development model, and two fundamental goals. Thirdly, Suggestions to encourage the development of rural eco-industry in the three dimensions of ''space, organization, and subject'' from primary mode to advanced mode.

Background The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW−) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW− groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW−group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW− group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW− group (p

Abstract Osimertinib is approved as the first‐line treatment for advanced non‐small cell lung cancer patients with epidermal growth factor (EGFR) mutation and for patients who develop EGFR T790M mutation during EGFR tyrosine kinase inhibitor (TKI) treatment and disease progression. Asymptomatic elevation of aminotransferase levels is commonly observed during TKI treatment; however, significant hepatotoxicity is infrequent. Here, we report a patient with osimertinib‐related drug‐induced liver injury who was successfully managed with osimertinib rechallenge.

Abstract Papillary thyroid cancer (PTC) has attracted much attention due to its high morbidity and severe metastasis. Long noncoding RNA ENST00000504230 (LncRNA ENST00000504230, known as LINC00958) was overexpressed in many cancers and associated with cancer development. However, its underlying mechanism in PTC remains unclear. PTC tissues and corresponding adjacent tissues were collected for measuring the expression of LINC00958 and miR‐627. MiR‐627 and TRIM44 expressions were measured in in vitro cultured PTC cell lines (B‐cpap and IHH4 cells) transfected with sh‐LINC00958 or miR‐627 mimic using RT‐qPCR and western blot. Cell proliferation, migration, and invasion were measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) and Transwell assays, respectively. Dual‐luciferase reporter assay was performed to evaluate the target association between miR‐627 and TRIM44. LINC00958 was up‐regulated in PTC tissues and cells, while the expression of miR‐627 was lowly expressed. Knockdown of LINC00958 inhibited the proliferation, migration, and invasion by elevating miR‐627 expression in PTC cells. TRIM44 was confirmed as a target of miR‐627. Overexpression of miR‐627 in PTC inhibited the proliferation, migration, and invasion by down‐regulating the expression of TRIM44. LINC00958 promoted proliferation, migration, and invasion in PTC by down‐regulating miR‐627 and activating TRIM44, indicating the potential therapeutic effect of LINC00958 on PTC.

Anxiety may contribute to agitation and distress in learners that can influence learning. Along with anxiety, boredom has been the focus of many recent investigations in the context of second language (L2) learning involving young learners. Anxiety and boredom would limit learners' imagination power, and can deter creativity, one of the indispensable skills in the 21st century. Mindfulness is another construct that is in line with creativity and its perspective to control anxiety is assured in literature. The proposed programs of mindfulness can influence creativity positively in the moment and over time. This is made possible by enhancing the level of the person's attention on daily activities which yields creative outcomes. In a world where stress and, often, distress undermine creativity, mindfulness emerges as an essential contributor to learners' success in educational practice. The current review focuses on young English as a foreign language (EFL) learners given that many believe stress and anxiety are commonplace among youth, leading to a decrease in creativity. Research findings reveal that mindfulness enhances creativity. Therefore, the improvement of students' well-being can be achieved by gradually incorporating mindfulness into the educational domain. Considering the important role of these factors in the language learning process, the purpose of this review is to examine the possible interactional effect of mindfulness in relation to creativity, learners' anxiety, and boredom in the context of L2 education among young learners. This is followed by proposing some suggestions for future research, as well as pedagogical implications.

Designing child-friendly streetscapes is a pragmatic and effective approach to addressing the limited outdoor play spaces and social exclusion experienced by migrant children living in vulnerable residential areas. However, the existing research and guidelines on streetscape design lack specificity for migrant workers’ communities and fail to provide full-cycle design process guidance for real-world practices. By taking a social–ecological perspective and synthesizing the existing literature, this paper develops an integrated design framework with seven indicators to guide three stages of child-friendly streetscape regeneration in migrant workers’ communities. The effectiveness of this framework was validated by application in a case project in a typical migrant workers’ community in Ningbo, China. The results show that the social–ecological design framework can help maximize opportunities for various children’s activities on the street with limited spatial resources. It also contributes to creating inclusive streetscapes to promote social cohesion by integrating social and cultural elements, children’s participation, and place-making activities. However, institutional barriers, cultural norms, and limited resources impede children’s participation and sustainable operations, which calls for more attention to be paid to “software” building. The new framework and research findings serve as a valuable guide and reference for practitioners in the field of child-friendly environmental design, especially in the context of marginalized communities in developing countries.

The high peak to average power ratio (PAPR) is the main challenge facing asymmetrically clipped optical (ACO) orthogonal frequency division multiplexing (OFDM). We propose a new hybrid technique that incorporates a modified selective mapping (SLM) and companding called low complexity hybrid selective mapping (LCHSLM) for PAPR mitigation in ACO OFDM systems. It is demonstrated through computer simulations that our proposed system significantly reduces the PAPR compared with the conventional SLM or companding alone. In addition, LCHSLM achieves a significant reduction in complexity compared with conventional SLM without bit error rate (BER) degradation.

Auxin (indole-3-acetic acid, IAA) has a considerable impact on the regulation of plant carbohydrate levels and growth, but the mechanism by which it regulates sugar levels in plants has received little attention. In this study, we found that exogenous IAA altered fructose (Fru), glucose (Glc), and sucrose (Suc) concentrations in shoot tips mainly by regulating MdSUSY1, MdFRK2, MdHxK1 and MdSDH2 transcript levels. Additionally, we used 5-year-old ‘Royal Gala’ apple trees to further verify that these genes play primary roles in regulating sink strength. The results showed that MdSUSY1, MdFRK2, MdHxK1/3 and MdSDH2 might be major contributors to sink strength regulation. Taken together, these results provide new insight into the regulation of the carbohydrate metabolism mechanism, which will be helpful for regulating sink strength and yield.

As the number of wireless applications and devices grows, higher standards for the quality of service and navigation performance of mobile networks are required. Numerous critical applications, including unmanned aerial vehicles, internet of things, digital twin, and military systems, require reliable communication and accurate navigation services. To meet these requirements, the development of the sixth generation (6G) network is necessary. 6G networks provide seamless 3-dimensional coverage in space–air–ground–sea area, as well as deep coupling of communication, sensing, and computation. 6G networks will be combined with low Earth orbit (LEO) satellites to construct a universal and intelligent integrated system of communication, sensing, and computing by utilizing the benefits of LEO satellites, such as miniaturization, modularity, large bandwidth, low latency, and wide area coverage. One of the critical construction tasks in this system is the integration of communication and navigation (ICAN), which can break the limitations of the global navigation satellite system, provide high-precision, robust navigation capability, and enable high-quality communication services. In this article, a comprehensive survey is presented for ICAN technologies toward LEO-enabled 6G networks (LEO-ICAN), including the framework design, system implementation, and key technologies. We also highlight the challenges and opportunities ahead faced by the LEO-ICAN system. Finally, the prospect development and future research trends are discussed, and a few ideas for practical and effective LEO-ICAN solutions are provided. This survey provides a reference for the theoretical design, technological innovation, and system implementation of LEO-ICAN, which is capable of coping with the demand of massive access and global seamless coverage in the upcoming 6G network era.

Aims: Few studies have compared the association between dosing of spironolactone and outcomes in patients with heart failure with preserved ejection fraction (HFpEF), and whether spironolactone dose could significantly affect the prognosis of HFpEF patients combined with chronic kidney disease (CKD) remains unclear. Our aim was to directly compare ‘high vs. low’ doses of spironolactone in an attempt to find a benefit-risk-balanced point, and infer an adequate dose for HFpEF with CKD patients.Methods: Overall, 4,321 symptomatic heart failure inpatients were initially screened from January 2013 to December 2019, and all enrolled patients were followed-up for 36 months; After including patients who meet the diagnostic criteria of HFpEF and CKD with ejection fraction > 45% and estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, a total of 387 patients was selected. Primary outcome was a composite of all-cause death, heart failure (HF) hospitalization and non-fatal stroke. The key safety outcome was hyperkalemia rates during the follow-up period.Results: The primary outcome event rates in patients with or without spironolactone were 12.74 and 21.45 per 100 person-years, respectively. Compared with patients not taking spironolactone, the adjusted hazard ratio (HR) [95% confidence interval (CI)] was 0.55 (0.38–0.79) with spironolactone group for primary outcomes. After grouped by the daily dose of spironolactone, low-dose group (≤ 40 mg) was associated with lower relative risk for the primary efficacy outcome [adjusted HR (95% CI) was 0.43 (0.23–0.81), 0.50 (0.33–0.76) and 0.74 (0.36–2.79) with < 40 mg, 40 mg and >40 mg, respectively]. During 3-year follow-up, the risk for hyperkalemia was amplified in the higher dose group (>40 mg) while showed no significant difference compared with low dose group (p = 0.425).Conclusion: HFpEF with CKD patients using spironolactone had lower risk of adverse cardiovascular outcomes. And the use of low-dose spironolactone (≤ 40 mg) showed the best efficacy and safety, therefore we may recommend ≤ 40 mg as the optimal initial dose for these patients. However, this was a relatively small sample size, retrospective study, and further adequately powered randomized trials are needed to verify these results.

This study aimed to examine the learning progression (LP) model of scientific imagination among undergraduate students using the Scientific Imagination Test-Verbal (SIT-Verbal) and investigated the influence of students’ demographic characteristics including gender, age, and discipline on their scientific imagination. Six hundred and sixteen undergraduates from a university in southern Taiwan participated in this study. The SIT-Verbal covered four key components of the scientific imagination process: brainstorming, association, transformation/elaboration, and conceptualization/organization/formation. The multiple validities of SIT-Verbal were assessed via a Rasch partial credit model. The results indicated that the SIT-Verbal had good model–data fit, supporting that undergraduate students’ scientific imagination in four stages from brainstorming, association and transformation/elaboration to conceptualization/organization/formation. Additionally, the results showed that the SIT-Verbal was suitable for measuring students’ scientific imagination at the university level. The study also provided abundant evidence verifying the SIT-Verbal and supported the learning progression for undergraduate students’ scientific imagination.

IntroductionSubjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture.MethodsCorrelation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well.ResultsAcupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p < 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p < 0.001, cluster p < 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p < 0.05).DiscussionThe findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.

Neonicotinoid (NEO) pesticides have become a potential risk to ecological safety and human health after application. The combined use of biochar and organic fertilizer (OF) is a promising approach to reduce pesticide adverse effects and improve soil fertility in agricultural soils. However, the combined remediation effects of biochar and OF on immobilization and dissipation of NEOs in soils have not previously been systematically investigated. In this study, biochars derived from peanut shell prepared at low/high pyrolysis temperatures (PS400 and PS900) were combined with composted chicken manure (CCM) as an example for OF to remediate contaminated soils toward six typical NEOs, nitenpyram (NIT), thiamethoxam (THIA), clothianidin (CLO), imidacloprid (IMI), acetamiprid (ACE), thiacloprid (THI). Results shown that both biochars and CCM were effective in improving soil sorption capacity and immobilization efficiency. The Freundlich affinity parameters (Kf) of NEOs in soils increased 7.2–12.0 times after the combined remediation of biochar and CCM, and the Kf of six NEOs had negative correlation with their lipophilicity (p ACE ≈ IMI > CLO > THIA > NIT. Meanwhile, NEOs-abiotic degradation was accelerated by biochar, CCM and their combined addition by adjusting soil pH and stimulating hydrolysis action. Biotic degradation was dominant in NEOs dissipation processes in amended soils, and the contribution ratios of biotic degradation (CRbio) were in the range of 25.4–99.0%. The combined use of biochar and CCM selectively stimulated the relative abundance of NEOs-degraders, which simplified abiotic degradation of -NO2-containing NEOs (viz., NIT, THIA, CLO, and IMI), but inhibited -C≡N-containing NEOs (viz., ACE and THI). The combined remediation provided a strategy for immobilizing NEOs and facilitating dissipation of -NO2-containing NEOs in soils. The results in this study provide valuable information for policymakers and decision-makers to choose appropriate soil remediation approaches with respect to the NEO types.

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs.