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Abstract Objective The comorbid relationship between migraine and depression has been well recognized, but its underlying pathophysiology is unclear. Here, we aimed to explore the structural changes of the amygdala and the abnormal functional connectivity of the centromedial amygdala (CMA) in migraineurs with depression. Methods High‐resolution T1‐weighted and functional magnetic resonance images were acquired from 22 episodic migraineurs with comorbid depression (EMwD), 21 episodic migraineurs without depression (EM), and 17 healthy controls (HC). Voxel‐based morphometry and resting‐state functional connectivity (rsFC) were applied to examine the intergroup differences in amygdala volume. Results The bilateral amygdala volume was increased in the EMwD and EM groups compared with the HC group, but there were no differences between the EMwD and EM groups. The right CMA exhibited decreased rsFC in the left dorsolateral prefrontal cortex (DLPFC) in the EMwD group compared with the EM group, while rsFC increased between the CMA and the contralateral DLPFC in the EM group compared with the HC group. In addition, the EM group showed decreased rsFC between the left CMA and the left pallidum compared with the HC group. Conclusions Enlarged amygdala is an imaging feature of EM and EMwD. The inconsistency of rsFC between CMA and DLPFC between migraineurs with and without depression might indicate that decreased rsFC between CMA and DLPFC is a neuropathologic marker for the comorbidity of migraine and depression. The core regions might be a potential intervention target for the treatment of EMwD in the future.

Advances in neuroimaging techniques during the past few decades have captured impaired functional brain activity in migraine disorders, yet the molecular mechanisms accounting for its alterations in migraine remain largely unknown. A total of 27 patients with episodic migraine (EM) and 30 matched healthy controls (HCs) underwent resting-state functional and structural magnetic resonance imaging (MRI) scans. Regional homogeneity (ReHo), low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) of fMRI were compared between the two groups. Based on the Allen Human Brain Atlas and risk genes in migraine, we identified gene expression profiles associated with ReHo alterations in EM. Compared with HCs, patients with EM showed increased ReHo in the left orbital part of the superior frontal gyrus (P < 0.05, cluster-level FWE-corrected). The expression profiles of 16 genes were significantly correlated with ReHo alterations in EM (P < 0.05/5,013, Bonferroni corrected). These genes were mainly enriched for transcription regulation, synaptic transmission, energy metabolism, and migraine disorders. Furthermore, the neural activation was positively correlated with Hamilton Rating Scale for Anxiety (HAMA) scores. To test the stability of our results, we repeated our procedure by using ALFF and fALFF and found these results had a high degree of consistency. Overall, these findings not only demonstrated that regional brain activity was increased in patients with EM, which was associated with emotional regulation but also provided new insights into the genetic mechanisms underlying these changes in migraine.

Abstract Background Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. Methods In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. Results The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of “Nervous headache” was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. Conclusions While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a subject of concern. This study aimed to investigate the relationship between NNIs and their metabolites in urine with serum lipid profiles in adults using data from the National Health and Nutrition Examination Survey (NHANES) 2015–2016. The study included 1192 participants aged over 20 years with urinary NNIs levels, serum lipid parameter levels and potential confounders. Urinary concentrations of NNIs, including imidacloprid, acetamiprid, clothianidin, thiacloprid, N-desmethyl-acetamiprid, and 5-hydroxy-imidacloprid, were quantified. Serum lipids profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B), were assessed. Considering the effects of lipid-lowering medications, the censored normal regression model was used to explore the associations between urinary NNIs and TC, TG, HDL-C, LDL-C and Apo-B levels. The results revealed a significant increase of 9.0 mg/dL (95%CI: 2.0, 16.1) in TC levels among participants with detectable N-desmethyl-acetamiprid compared to those with undetectable levels. Stratified analysis indicated that the association between N-desmethyl-acetamiprid and HDL-C levels was more pronounced among participants aged ≥ 46 years compared to those aged between 20 and 45 years with undetectable N-desmethyl-acetamiprid (pinteraction=0.044). Additionally, there were marginal effect modification of BMI on the association between N-desmethyl-acetamiprid and LDL-C (pinteraction=0.097) and Apo-B (pinteraction=0.052) levels. Specifically, participants with BMI ≥ 25 kg/m² and detectable N-desmethyl-acetamiprid tended to have higher LDL-C and Apo-B levels compared to those with BMI

Introduction: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. Methods: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. Results: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. Conclusion: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

[Introduction] The research aims to make full use of the high quality wind resources in the deep sea, solve the problem of wind abandonment of offshore wind power, and provide a possible offshore hydrogen fuel supply for future new energy ships. [Method] The process flow of offshore wind power coupled seawater hydrogen production technology relying on an independent offshore platform was discussed. The key equipment proton exchange membrane water electrolysis hydrogen production system, hydrogen compressor, hydrogen storage tank and some auxiliary equipment process design problems were described, with a brief description of the control scheme of hydrogen production platform, and a preliminary analysis of its economy. [Result] From the angle of process design, the design of offshore wind hydrogen production platform just in a relatively early stage. The supply chain of key equipment is in the initial development period and most of the suppliers did not enter the marine market, suggesting that current process from engineering design to the engineering of offshore floating hydrogen production is not yet mature and the economic benefit of hydrogen production from renewable energy is low. [Conclusion] At the moment, offshore wind power cannot be connected to the grid at a reasonable price, and the application of coupled hydrogen energy of offshore wind power still has a long way to go. Engineering tests are the prerequisite for large-scale engineering.

The study of visualized bubble phenomena during critical heat flux (CHF) and CHF mechanistic models has been a topic of discussion. CHF visualization experiments are needed to explore the CHF phenomena and bubble behavior cocurrently, especially with high spatialresolution near the heated surface area. The visualization experiments can also provide input for CHF mechanistic models. In this study, the boiling crisis phenomenon on the surface of a single heated rod and the influence of grid on bubble behavior were explored by visualized method with R134a as fluid. The main purpose of this study is to visualize flow conditions near or at CHF and the effect of mixingvanes on bubble behavior by a highspeed camera. The comparison was made between the CHF data with and without mixingvanes spacer grid under the same flow condition. The square of the test section was 19 mm×19 mm, and a uniform heating rod with a diameter of 95 mm was placed in the center. The channel box was unheated and well insulated to provide an approximately adiabatic boundary condition on the outer wall of the test section. Two grids with mixingvanes were placed in the channel to form 522 mm spans to reduce vibration and ensure channel geometry. In the experiment, the pressure was in the range of 1827 MPa, the mass flux was 6002 100 kg/(m2·s), and the inlet subcooling was 1040 ℃. A highspeed camera was used to observe the phenomena during boiling crisis and the effect of mixingvanes on bubble behavior. The comparison was made between the CHF values spacer under different grids (with and without mixingvanes). The experimental results show that when boiling crisis occurs, the vapor film formed by local film boiling expands circumferentially until stable film boiling is formed on the rod surface. The transition was completed from nuclear boiling stage to film boiling stage. The effect of grid on bubble behavior is mainly reflected in tearing bubbles by strip and spring, and swirl flow caused by mixingvanes. This effect increases the turbulent mixing between the bubble layer and the core, and the mixing-vanes promote the separation of bubbles and enhance the heat transfer between the heated wall and the fluid, thus CHF increases. The turbulent mixing rate will damp along the flow direction after the strengthening of the mixingvanes. The turbulent mixing rate damps faster at low mass flux condition. Thus, the enhancement of CHF is not obvious at low mass flux condition.

Abstract Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) have not been evaluated sufficiently due to limited data, particularly in China. Methods Patients with SUNCT or SUNA treated in a tertiary headache centre or seven other headache clinics of China between April 2009 and July 2022 were studied; we compared their demographics and clinical phenotypes. Results The 45 patients with SUNCT and 31 patients with SUNA had mean ages at onset of 37.22 ± 14.54 years and 42.45 ± 14.72 years, respectively. The mean ages at diagnosis of SUNCT and SUNA were 41.62 ± 12.70 years and 48.68 ± 13.80 years, respectively (p = 0.024). The correct diagnosis of SUNCT or SUNA was made after an average of 2.5 (0–20.5) years or 3.0 (0–20.7) years, respectively. Both diseases had a female predominance (SUNCT: 1.14:1; SUNA: 2.10:1). The two diseases differed in the most common attack site (temporal area in SUNCT, p = 0.017; parietal area in SUNA, p = 0.002). Qualitative descriptions of the attacks included stabbing pain (44.7%), electric-shock-like pain (36.8%), shooting pain (25.0%), and slashing pain (18.4%). Lacrimation was the most common autonomic symptom in both SUNCT and SUNA patients, while eyelid oedema, ptosis, and miosis were less frequent. Triggers such as cold air and face washing were shared by the two diseases, and they were consistently ipsilateral to the attack site. Conclusions In contrast to Western countries, SUNCT and SUNA in China have a greater female predominance and an earlier onset. The shared core phenotype of SUNCT and SUNA, despite their partial differences, suggests that they are the same clinical entity.

Auxin is a well-known important phytohormone in plant that plays vital roles in almost every development process throughout plant lifecycle. However, the effect of auxin on the metabolism of chlorophyll, one of the most important pigments involved in the photosynthesis, was intertwined and the underlying mechanism remained to be explored. Here, we found the auxin-defective yuc2 yuc6 double mutant displayed dark-green leaf color with higher chlorophyll content than wildtype, suggesting a negative regulatory role of auxin in chlorophyll biosynthesis. The chloroplast number and structure in mesophyll cells were altered and the photosynthetic efficiency was improved in yuc2 yuc6. In addition, the chlorophyll level was significantly improved during seedling de-etiolation in yuc2 yuc6 mutant, and decreased dramatically under IAA treatment, confirming the inhibitory role of auxin in chlorophyll biosynthesis. The analyses of gene expression in mature leaves and de-etiolation seedlings suggested that auxin suppressed the expression of many chlorophyll biosynthesis genes, especially PROTOCHLOROPHYLLIDE OXIDOREDUCTASE A (PORA) and GENOMES UNCOUPLED 5 (GUN5). Yeast-one-hybrid and luciferase assays demonstrated that the AUXIN RESPONSE FACTOR 2 (ARF2) and ARF7 bind to the promoter of PORA and GUN5 to suppress their expression with the help of INDOLE-3-ACETIC ACID14 (IAA14). Collectively, our research explicitly unraveled the direct inhibitory role of auxin in chlorophyll biosynthesis, and provided new insight into the interplay between auxin signaling and chlorophyll metabolism.

Background: Whether endovascular treatment (EVT) is safe and effective for vertebrobasilar artery occlusion (VBAO) is yet incompletely understood. Two RCTs, the endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST) trail and the Basilar Artery International Cooperation Study (BASICS), concentrating on this field were recently reported. Objective: We use real-world registry data of VBAO to compare the outcome of EVT inside and outside the inclusion and exclusion criteria of the BEST and BASICS study to testify the feasibility of the selection paradigms of VBAO in these trials. Methods: Consecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. The safety outcomes [3-month mortality, symptomatic intracranial hemorrhage (sICH), and effectiveness outcomes (the proportion of 3-month functional independence (mRS of 0–2) and favorable outcome (mRS of 0–3)] were compared between VBAO patients who meet or failed to meet the BEST/BASICS selection criteria for EVT. Results: Our study cohort consisted of 577 VBAO patients who underwent EVT. Of them, 446 patients had pc-ASPECTS ≧8. Successful reperfusion (mTICI 2b or 3) was achieved in 85.4% ( n = 493). There were 418 patients fulfilling the BEST criterion for EVT and 194 fulfilling the BASICS criterion. Regression analysis indicated that adherence to BEST or BASICS criterion for EVT was not independently related to most of the safety and effectiveness outcome except that adherence to BEST was significantly associated with the 3-month favorable outcome (OR BEST : 1.742, 95% CI: 1.087–2.790). However, when we put pc-ASPECTS into both criteria with a cut-off value of 8, meeting both BEST criterion plus pc-ASPECTS and BASICS criterion plus pc-ASPECTS was independently related to 3-month functional independence (OR BEST : 1.687, 95% CI: 1.077–2.644; OR BASIC : 1.653, 95% CI: 1.038–2.631) and favorable outcome (OR BEST : 2.280, 95% CI: 1.484–3.502; OR BASIC : 2.153, 95% CI: 1.372–3.378). Conclusion: Our study indicated that, based on real-world data of EVT, adherence to BEST or BASICS criterion for EVT was not independently associated with the safety and effectiveness outcome except that adherence to BEST was significantly related to the 3-month favorable outcome. However, the BEST or BASICS selection criterion and pc-ASPECTS ≧8 might be better paradigms for EVT patient selection.

Laodelphax striatellus is a notorious sap-feeding insect that also serves as a vector of rice stripe virus (RSV) and is responsible for a significant decline in rice yield. Pesticide application remains a crucial strategy for controlling insect pests. In recent years, the utilization of biopesticides has gained attention due to their eco-friendliness and suitability for controlling insect pests and pathogens in agriculture. The present study aimed Figureto evaluate the potential efficacy of a microbial pesticide, decoyinine (DCY), as a seed priming agent in rice against SBPH’s biology, feeding behavior, and RSV transmission ability in the laboratory. Here, we revealed that the body weight of females and males and honeydew extraction of RSV-virulent SBPH were (22.50%, 25.0%, and 23.25%, respectively) significantly lower than non-virulent SBPH. Meanwhile, the fecundity of RSV-virulent SBPH females was significantly higher (8.24%) than non-virulent SBPH. However, nymphal survival and RSV transmission (horizontal and vertical) were found to be non-significantly affected by DCY application. Furthermore, DCY-primed rice seedlings significantly prolonged the time period and frequency of the electrical penetration graph (EPG) feeding waveforms (np, N2, and N3), and also reduced the time period of the waveform (N4-b) for both RSV-virulent and non-virulent SBPH strains with reduced RSV inoculation. The recent study provides new insights for DCY application in rice against SBPH by reducing fecundity, body weight, and honeydew contents, which might contribute to modern integrated pest management.

The brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae) is one of the most destructive rice pests in Asia. The microbial metabolite decoyinine (DCY) has been extracted from Streptomyces hygroscopicus. Recent studies have suggested that treating rice seeds with DCY could improve the growth and yield of rice. To further assess the effects of priming the seeds of different rice varieties with DCY on rice seedling resistance against BPH, an age-stage, two-sex life table and choice test were applied to investigate the individual fitness, population parameters, and preference behavior of BPHs in this study. The results indicated that feeding on rice seedlings grown from seeds primed with DCY significantly affected BPHs’ adult longevity, oviposition period, fecundity, as well as the net reproductive rate (R0), intrinsic rate of increase (rm), finite rate of increase (λ), doubling time (DT), and population size in terms of BPH. The honeydew excretions and the weights of BPHs fed on DCY-pretreated rice plants were remarkably lowered. The two-way ANOVA results also showed that there were significant differences in the biological parameters, honeydew excretions, and of BPH weights owing to DCY treatment, rice variety, and the interactions between DCY treatment and rice variety. Additionally, the feeding and oviposition preferences of BPHs for the pretreated rice plants were reduced. Our results imply that the priming of seeds with DCY can improve rice resistance against BPH, which could facilitate the utilization of seed priming as a new avenue for effective crop protection.

The brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), is a notorious pest in rice production. The microbial secondary metabolite, decoyinine (DCY), is produced by Streptomyces hygroscopicus. Recent studies found that seed priming with DCY could enhance rice resistance to BPH and Laodelphax striatellus; however, the mechanism of enhancing insect resistance in rice remains unclear. Here, an integrated physio-biochemical and transcriptome analysis was performed on rice priming with DCY after BPH infestation. Defense-related enzymes activities such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S transferase (GST), and polyphenol oxidase (PPO), concentrations of hydrogen peroxide (H2O2), callose, and free amino acids in rice priming with DCY were significantly increased than in control plants after BPH infestation. Concentrations of soluble sugars, sucrose, and glucose were higher in rice treated with DCY than in the control after BPH infestation; however, the concentration of malondialdehyde (MDA) was significantly decreased in rice treated with DCY after BPH infestation. In the transcriptome analysis, GO functional annotation and KEGG pathway analysis were enriched in defense response, transcription factors, secondary metabolites, reactive oxygen species, and cell wall organization and these data also support physio-biochemical results. The qRT-PCR results further verified the differential expressed genes related to DCY-treated rice responding to BPH. Meanwhile, it indicated that DCY might enhance the resistance of rice to BPH by regulating the rice WRKY transcription factor genes. Our results provide a basis for further exploring the molecular mechanism of the defense response of rice priming with DCY against BPH infestation and could provide valuable resources to control insect pests.

Monoclonal antibodies binding the EGFR, such as cetuximab and panitumumab, have been extensively used as targeted therapy for the treatment of mCRC. However, in clinical practice, it has been found that these treatment options have some limitations and fail to fully exploit their immunoregulatory activities. Meanwhile, because of the limited effects of current treatments, immunotherapy is being widely studied for patients with mCRC. However, previous immunotherapy trials in mCRC patients have had unsatisfactory outcomes as monotherapy. Thus, combinatorial treatment strategies are being researched. The authors retrieved relevant documents of combination therapy for mCRC from PubMed and Medline. This review elaborates on the knowledge of immunomodulatory effects of anti-EGFR therapy alone and in combination with immunotherapy for mCRC. Although current treatment options have improved median overall survival (OS) for advanced disease to 30 months, the prognosis remains challenging for those with metastatic disease. More recently, the combination of anti-EGFR therapy with immunotherapy has been shown activity with complementary mechanisms. Hence, anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC. [ABSTRACT FROM AUTHOR]

Abstract Introduction Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). Methods Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. Results In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26–50%, 51–75%, 76–90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. Conclusion VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

GLOBOCAN estimates 36 types of cancers in 185 countries based on the incidence, mortality, and prevalence in the year 2019. Nowadays, chemotherapy is the most widely used cancer treatment among immune, radio, hormone, and gene therapies. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nano-assembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic Gemcitabine (GEM) drug. The GEM prodrugs were gifted to impulsively self-assemble into excellent steady nanoparticles size on covalent conjugation of linoleic acid hydrophobic through amide group with ∼100 nm. Newly synthesized GEM-NPs morphology was confirmed by various electron microscopic techniques. After successful synthesis, we have evaluated the anticancer property of GEM and GEM-NPs against B-CPAP (papillary thyroid carcinoma) and FTC-133 (human follicular thyroid carcinoma) cancer cell lines. Further studies such as AO-EB (acridine orange-ethidium bromide), nuclear staining and flow cytometry analyses on cell death mechanism signified that the cytotoxicity was associated with apoptosis in thyroid cancer cells. GEM-NPs show excellent biocompatibility compared to GEM. The present study explained that GEM-NPs as a safe and hopeful strategy for chemotherapeutics of thyroid cancer therapy and deserve for further clinical evaluations.

Evidence supports the potential influence of persistent organic pollutants (POPs) on the pathogenesis and progression of obesity and diabetes. Diet-toxicant interactions appear to be important in diet-induced obesity/diabetes; however, the factors influencing this interaction, especially the early life environmental exposure, are unclear. Herein, we investigated the metabolic effects following early life five-day exposure (24 μg/kg body weight per day) to 3,3′,4,4′,5-pentacholorobiphenyl (PCB 126) at four months after exposure in mice fed with control (CTRL) or high-fat diet (HFD). Activation of aryl hydrocarbon receptor (AHR) signaling as well as higher levels of liver nucleotides were observed at 4 months after PCB 126 exposure in mice, independent of diet status. Inflammatory responses including higher levels of serum cytokines and adipose inflammatory gene expression caused by early life PCB 126 were observed only in HFD-fed mice in adulthood. Notably, early life PCB 126 exposure worsened HFD-induced impaired glucose homeostasis characterized by glucose intolerance and elevated gluconeogenesis and tricarboxylic acid (TCA) cycle flux without worsening the effects of HFD related to adiposity in adulthood. Furthermore, early life PCB 126 exposure resulted in diet-dependent changes in bacterial community structure and function later in life, as indicated by metagenomic and metabolomic analyses. These data contribute to a more comprehensive understanding of the interactions between diet and early life environmental chemical exposure.

Early life exposure to environmental pollutants may have long-term consequences and harmful impacts on health later in life. Here, we investigated the short- and long-term impact of early life 3,3′,4,4′,5-pentacholorobiphenyl (PCB 126) exposure (24 μg/kg body weight for five days) in mice on the host and gut microbiota using 16S rRNA gene sequencing, metagenomics, and 1H NMR- and mass spectrometry-based metabolomics. Induction of Cyp1a1, an aryl hydrocarbon receptor (AHR)-responsive gene, was observed at 6 days and 13 weeks after PCB 126 exposure consistent with the long half-life of PCB 126. Early life, Short-Term PCB 126 exposure resulted in metabolic abnormalities in adulthood including changes in liver amino acid and nucleotide metabolism as well as bile acid metabolism and increased hepatic lipogenesis. Interestingly, early life PCB 126 exposure had a greater impact on bacteria in adulthood at the community structure, metabolic, and functional levels. This study provides evidence for an association between early life environmental pollutant exposure and increased risk of metabolic disorders later in life and suggests the microbiome is a key target of environmental chemical exposure.

Summary: Alicyclobacillus acidoterrestris is a typical endospore‐forming microorganism, whose spores are able to germinate in Not From Concentrate juice causing its spoilage. In this work, dielectric barrier discharge atmospheric cold plasma (DBD‐ACP) at the voltage of 30 kV was used to inactivate Alicyclobacillus acidoterrestris spores in NFC juice (2–8 min). The results showed spores reduced nearly 3‐log CFU mL−1 after 8 min treatment, and the morphology of spores were severely disrupted, causing the release of their contents. Furthermore, proteomic analysis showed totals of 122 and 170 different expression proteins were detected in group C (control)/Ct1 (30 kV, 4 min) and C/Ct2 (30 kV, 8 min), respectively, indicating that metabolic activities of spores including amino acid and energy metabolic, protein biosynthesis, DNA replication and spore germination are inhibited. This study confirms the inactivation of Alicyclobacillus acidoterrestris spores by DBD‐ACP and provides some new perspectives on the inactivation mechanisms of spores by DBD‐ACP. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly common. This retrospective cohort study examined factors associated with outcomes in patients from Shanghai who had NTM pulmonary disease (NTMPD) from January 2014 to December 2018. The causative bacterial species, drug susceptibility test results, treatment outcomes, sputum culture conversion rate, and risk factors associated with treatment failure were determined. The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, p < 0.001) and M. abscessus (36.1%, p < 0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR = 9.355, p < 0.001; MAC: aOR = 2.970, p < 0.001), elevated ESR (>60 mm/h: aOR = 2.658, p < 0.001), receipt of retreatment (aOR = 2.074, p < 0.001), and being middle-aged or elderly (>60 years-old: aOR = 1.739, p = 0.021; 45–60 years-old: aOR = 1.661, p = 0.034). The main bacterial species responsible for NTMPD were MAC, M. abscessus, and M. kansasii. Patients who were infected by M. abscessus or MAC, with elevated ESR, received retreatment, and were middle-aged or elderly had an increased risk of treatment failure.

Organophosphate esters (OPs) are substitutes for polybrominated diphenyl ether (PBDE) flame retardants. China is the largest producer of OPs globally, with the production rate increasing at 15% annually. Since some OPs are neurodevelopmental and/or carcinogenic toxicants, human exposure is a concern. In this study, concentrations of eight OP metabolites (mOPs) were measured in human urine samples collected from 13 cities located in Northern, Eastern, Southern, and Southwestern China. All target mOPs were frequently detected with detection rates of 50% to 100%, indicating widespread human exposure to OPs. Bis(2-chloroethyl) phosphate (BCEP; median: 0.68 ng/mL), bis(1-chloro-2-propyl) phosphate (BCIPP; 0.30 ng/mL), diphenyl phosphate (DPHP; 0.30 ng/mL), and dibutyl phosphate (DBP; 0.29 ng/mL) were the dominant mOPs across all participants. Regional differences in concentrations (ΣmOPs varied from 0.86 to 3.7 ng/mL) and composition profiles (contribution of chlorinated mOPs to ΣmOPs varied from 35% to 95%) of mOPs were observed within China. In comparison to the concentrations reported worldwide, urinary DPHP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) levels in China were lower, whereas BCEP and DBP levels were comparable or higher. The total daily intake (TDI) of tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) were estimated from daily urine excretion rate and the fraction of OP metabolized in human liver microsomes (TDIHLM) or S9 fraction (TDIS9). The intake estimates showed that Chinese residents were exposed to TCEP from 96.9 to 46,700 (or 52.2 to 25,200) ng/kg bw/day. Depending on the reference dose, we found that approximately 5% of the individuals exceeded the limit (i.e., 2200 ng/kg bw/day) for TCEP intake. To our knowledge, this is the first nationwide baseline survey to determine urinary levels of mOPs in Chinese residents. Keywords: Organophosphate esters, Urinary levels, Total daily intake, Health risk

Emerging evidence supports that exposure to persistent organic pollutants (POPs) can impact the interaction between the gut microbiota and host. Recent efforts have characterized the relationship between gut microbiota and environment pollutants suggesting additional research is needed to understand potential new avenues for toxicity. Here, we systematically examined the direct effects of POPs including 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyls (PCB-123 and PCB-156) on the microbiota using metatranscriptomics and NMR- and mass spectrometry-based metabolomics combined with flow cytometry and growth rate measurements (OD600). This study demonstrated that (1) POPs directly and rapidly affect isolated cecal bacterial global metabolism that is associated with significant decreases in microbial metabolic activity; (2) significant changes in cecal bacterial gene expression related to tricarboxylic acid (TCA) cycle as well as carbon metabolism, carbon fixation, pyruvate metabolism, and protein export were observed following most POP exposure; (3) six individual bacterial species show variation in lipid metabolism in response to POP exposure; and (4) PCB-153 (non-coplanar)has a greater impact on bacteria than PCB-126 (coplanar) at the metabolic and transcriptional levels. These data provide new insights into the direct role of POPs on gut microbiota and begins to establish possible microbial toxicity endpoints which may help to inform risk assessment.

Purpose: To assess the feasibility of imaging extremely low birth weight infants, defined as infants born weighing less than 1000 g or before 27 weeks of gestational age, with an arm-mounted optical coherence tomography angiography (OCTA) device. Methods: Cross-sectional case series conducted at a single site in-patient academic center. Subjects included infants who had been born premature and met ROP screening criteria. Birth history such as gestational age and birth weight were collected. Subjects were imaged with OCTA in a supine position during ROP screening and treatment. Segmental errors were manually corrected and FAZ area was calculated from the superficial and deep capillary plexus (SCP, DCP) layers. Main outcomes measures were foveal avascular zone (FAZ) area, ROP stage and treatment. Results: Seven ELBW infants were included with an average gestational age of 25 weeks (range = 23-4/7 to 26 weeks) and average postmenstrual age of 54.7 weeks (range = 43–80 weeks) at the time of imaging. Average birth weight was 615 g (range 500–680 grams). Thirteen eyes had ROP treatment including primary laser, anti-vascular endothelial growth factor injection with delayed laser, and scleral buckle. Six infants were imaged under general anesthesia and one infant was imaged without sedation. Average FAZ area was 0.17 mm2 (range = 0.03 mm2–0.37 mm2) in the SCP and 0.04 mm2 (range 0 mm2–0.09 mm2) in the DCP. FAZ area correlated positively to the ratio of outer retinal layer thickness to inner retinal layer thickness at the foveal center in the SCP and DCP (r2 = 0.48, p = 0.02; r2 = 0.46, p = 0.02) and negatively with inner retinal layer thickness in the SCP (r2 = 0.56, p = 0.008). Conclusions and Importance: Arm-mounted OCTA was feasible in ELBW infants and provided information about the developing fovea. Measurement of FAZ area and retinal thickness using this modality may be used to study the effects of ELBW, peripheral ROP and ROP treatment on foveal development.

The mechanisms by which white button (WB) mushrooms (Agaricus bisporus) may influence health are unclear. WB feeding (1%) resulted in changes in the composition of microbiota in conventional (CV) mice to expand a population of Prevotella that produce propionate and succinate. Microbial propionate and succinate production induced expression of genes important for intestinal gluconeogenesis (IGN) via the gut-brain neural circuit. Reduced hepatic glucose production was a metabolic benefit of IGN that was found in WB fed CV mice. In the absence of microbiota or in mice with disruptions in the ability to sense microbiota there was no WB mediated effect. WB-fed lean mice had a small but significant improvement in glucose sensitivity. WB feeding resulted in shifts in the microbiota that induced IGN and improved glucose homeostasis.

Background: Selenium (Se) plays a key role in controlling several processes in plant development, such as root growth and regulation of enzyme activity. However, research on the effects of Se in Sophora tonkinensis, a medicinal plant, has not been reported. To elucidate the effect of Se on the accumulation of secondary metabolites in tissue-cultured seedlings of S. tonkinensis. Materials and Methods: Tissue culture seedlings of S. tonkinensis was treated with different concentrations of Se in the rooting medium. Agronomic traits of roots and concentrations of hormones and some secondary metabolites were measured from seedlings. Results: The results show that (1) root growth of tissue culture seedlings were stimulated by Se; (2) a specific amount of Se enhanced the activities of peroxidase (POD) and superoxide dismutase (SOD), as well as the production and storage of soluble proteins and chlorophyll; and (3) Se treatment lowered brassinolide (BR) content, and 15 mg/L Se minimized abscisic acid (ABA) content, while 60 mg/L Se enhanced ABA content. The gibberellin (GA3) content in seedlings increased significantly compared with the control under the treatment of 60 mg/L Se. Conclusion: Se concentration of 30 mg/L facilitated matrine and oxymatrine production and accumulation in stem/leaf tissues. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy. Observations: A 65-year-old Caucasian woman presented with acute respiratory distress syndrome and septic shock. After treatment with vasopressors and prolonged prone positioning, she was noted to be bilaterally completely blind on hospitalization day 12. Evaluation revealed evidence of bilateral central retinal artery occlusion and bilateral ischemic optic neuropathy. Magnetic resonance imaging of the orbits demonstrated severe restricted diffusion of both optic nerves consistent with ischemia. Both central retinal artery occlusion and ischemic optic neuropathy have been reported in cases of severe hypotension, blood loss, and prone positioning, most often postoperatively after spinal surgery. Conclusions and importance: To our knowledge, this is the first reported case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy, presumed due to the combination of severe systemic hypotension, hypoxemia due to the respiratory distress syndrome, and prolonged prone positioning.

Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB.

Aim: We investigated the clinical usefulness of mean corpuscular hemoglobin concentration (MCHC) in patients with pneumoconiosis.Methods: We retrospectively investigated the medical records from 52 patients with pneumoconiosis, and erythrocyte parameters were analyzed in pneumoconiosis patients with different stages.Results: Here, we found that the values of MCHC were significantly lower in III stage pneumoconiosis than those with I/II stage (p = 0.024), and there was no significantly difference in MCHC between smoking pneumoconiosis patients and non-smoking pneumoconiosis patients. A negatively correlation between MCHC and disease stage was observed in patients with pneumoconiosis (r = − 0.298, p = 0.032). In multiple linear regression analysis, the MCHC was found to be independently associated with advanced pneumoconiosis in patients with pneumoconiosis (p=0.011). The results of logistic regression analysis indicated that decreased MCHC was an independent risk factor of advanced pneumoconiosis in patients with pneumoconiosis (OR: 0.936, CI95%: 0.877– 0.999, p = 0.046). Receiver operating characteristic curve analysis showed that the optimal cutoff value of MCHC was 330 g/L to identify advanced pneumoconiosis with the area under the curve of 0.694 (CI95%:0.550– 0.839, p = 0.018).Conclusion: The decreased MCHC is associated with advanced pneumoconiosis, and MCHC may be used as a monitoring marker for follow-up of pneumoconiosis patients. [ABSTRACT FROM AUTHOR]