Prediction of anxious depression using multimodal neuroimaging and machine learning.

Anxious depression is a common subtype of major depressive disorder (MDD) associated with adverse outcomes and severely impaired social function. It is important to clarify the underlying neurobiology of anxious depression to refine the diagnosis and stratify patients for therapy. Here we explored associations between anxiety and brain structure/function in MDD patients. A total of 260 MDD patients and 127 healthy controls underwent three-dimensional T1-weighted structural scanning and resting-state functional magnetic resonance imaging. Demographic data were collected from all participants. Differences in gray matter volume (GMV), (fractional) amplitude of low-frequency fluctuation ((f)ALFF), regional homogeneity (ReHo), and seed point-based functional connectivity were compared between anxious MDD patients, non-anxious MDD patients, and healthy controls. A random forest model was used to predict anxiety in MDD patients using neuroimaging features. Anxious MDD patients showed significant differences in GMV in the left middle temporal gyrus and ReHo in the right superior parietal gyrus and the left precuneus than HCs. Compared with non-anxious MDD patients, patients with anxious MDD showed significantly different GMV in the left inferior temporal gyrus, left superior temporal gyrus, left superior frontal gyrus (orbital part), and left dorsolateral superior frontal gyrus; fALFF in the left middle temporal gyrus; ReHo in the inferior temporal gyrus and the superior frontal gyrus (orbital part); and functional connectivity between the left superior temporal gyrus(temporal pole) and left medial superior frontal gyrus. A diagnostic predictive random forest model built using imaging features and validated by 10-fold cross-validation distinguished anxious from non-anxious MDD with an AUC of 0.802. Patients with anxious depression exhibit dysregulation of brain regions associated with emotion regulation, cognition, and decision-making, and our diagnostic model paves the way for more accurate, objective clinical diagnosis of anxious depression.

Mass Spectrometry-Based Method to Measure Aflatoxin B1 DNA Adducts in Formalin-Fixed Paraffin-Embedded Tissues.

Aflatoxin B1 (AFB1) is a potent human liver carcinogen produced by certain molds, particularly Aspergillus flavus and Aspergillus parasiticus, which contaminate peanuts, corn, rice, cottonseed, and ground and tree nuts, principally in warm and humid climates. AFB1 undergoes bioactivation in the liver to produce AFB1-exo-8,9-epoxide, which forms the covalently bound cationic AFB1-N7-guanine (AFB1-N7-Gua) DNA adduct. This adduct is unstable and undergoes base-catalyzed opening of the guanine imidazolium ring to form two ring-opened diastereomeric 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy-aflatoxin B1 (AFB1-FapyGua) adducts. The AFB1 formamidopyrimidine (Fapy) adducts induce G → T transversion mutations and are likely responsible for the carcinogenic effects of AFB1. Quantitative liquid chromatography-mass spectrometry (LC-MS) methods have shown that AFB1-N7-Gua is eliminated in rodent and human urine, whereas ring-opened AFB1-FapyGua adducts persist in rodent liver. However, fresh frozen biopsy tissues are seldom available for biomonitoring AFB1 DNA adducts in humans, impeding research advances in this potent liver carcinogen. In contrast, formalin-fixed paraffin-embedded (FFPE) specimens used for histopathological analysis are often accessible for molecular studies. However, ensuring nucleic acid quality presents a challenge due to incomplete reversal of formalin-mediated DNA cross-links, which can preclude accurate quantitative measurements of DNA adducts. In this study, employing ion trap or high-resolution accurate Orbitrap mass spectrometry, we demonstrate that ring-opened AFB1-FapyGua adducts formed in AFB1-exposed newborn mice are stable to the formalin fixation and DNA de-cross-linking retrieval processes. The AFB1-FapyGua adducts can be detected at levels comparable to those in a match of fresh frozen liver. Orbitrap MS2 measurements can detect AFB1-FapyGua at a quantification limit of 4.0 adducts per 108 bases when only 0.8 µg of DNA is assayed on the column. Thus, our breakthrough DNA retrieval technology can be adapted to screen for AFB1 DNA adducts in FFPE human liver specimens from cohorts at risk of this potent liver carcinogen.

Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics.

Air pollution, tobacco smoke, and red meat are associated with renal cell cancer (RCC) risk in the United States and Western Europe; however, the chemicals that form DNA adducts and initiate RCC are mainly unknown. Aristolochia herbaceous plants are used for medicinal purposes in Asia and worldwide. They are a significant risk factor for upper tract urothelial carcinoma (UTUC) and RCC to a lesser extent. The aristolochic acid (AA) 8-methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I), a component of Aristolochia herbs, contributes to UTUC in Asian cohorts and in Croatia, where AA-I exposure occurs from ingesting contaminated wheat flour. The DNA adduct of AA-I, 7-(2'-deoxyadenosin-N6-yl)-aristolactam I, is often detected in patients with UTUC, and its characteristic A:T-to-T:A mutational signature occurs in oncogenes and tumor suppressor genes in AA-associated UTUC. Identifying DNA adducts in the renal parenchyma and pelvis caused by other chemicals is crucial to gaining insights into unknown RCC and UTUC etiologies. We employed untargeted screening with wide-selected ion monitoring tandem mass spectrometry (wide-SIM/MS2) with nanoflow liquid chromatography/Orbitrap mass spectrometry to detect DNA adducts formed in rat kidneys and liver from a mixture of 13 environmental, tobacco, and dietary carcinogens that may contribute to RCC. Twenty DNA adducts were detected. DNA adducts of 3-nitrobenzanthrone (3-NBA), an atmospheric pollutant, and AA-I were the most abundant. The nitrophenanthrene moieties of 3-NBA and AA-I undergo reduction to their N-hydroxy intermediates to form 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) adducts. We also discovered a 2'-deoxycytidine AA-I adduct and dA and dG adducts of 10-methoxy-6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-III), an AA-I isomer and minor component of the herbal extract assayed, signifying AA-III is a potent kidney DNA-damaging agent. The roles of AA-III, other nitrophenanthrenes, and nitroarenes in renal DNA damage and human RCC warrant further study. Wide-SIM/MS2 is a powerful scanning technology in DNA adduct discovery and cancer etiology characterization.

Click-Chemistry-Mediated Cell Membrane Glycopolymer Engineering to Potentiate Dendritic Cell Vaccines.

Dendritic cell vaccine (DCV) holds great potential in tumor immunotherapy owing to its potent ability in eliciting tumor-specific immune responses. Aiming at engineering enhanced DCV, we report the first effort to construct a glycopolymer-engineered DC vaccine (G-DCV) via metabolicglycoengineering and copper-free click-chemistry. Model G-DCV was prepared by firstly delivering tumor antigens, ovalbumin (OVA) into dendritic cells (DC) with fluoroalkane-grafted polyethyleneimines, followed by conjugating glycopolymers with a terminal group of dibenzocyclooctyne (DBCO) onto dendritic cells. Compared to unmodified DCV, our G-DCV could induce stronger T cell activation due to the enhanced adhesion between DCs and T cells. Notably, such G-DCV could more effectively inhibit the growth of the mouse B16-OVA (expressing OVA antigen) tumor model after adoptive transfer. Moreover, by combination with an immune checkpoint inhibitor, G-DCV showed further increased anti-tumor effects in treating different tumor models. Thus, our work provides a novel strategy to enhance the therapeutic effectiveness of DC vaccines.

Metal-Free Atom Transfer Radical Polymerization to Prepare Recylable Micro-Adjuvants for Dendritic Cell Vaccine.

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro-adjuvants grafted with copolymers of 2-(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal-free surface-initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer-sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non-metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro-ligand-mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod-like and spherical micro-adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo-carrying "micro-shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery.

Multifunctional Nanocrystalline-Assembled Porous Hierarchical Material and Device for Integrating Microwave Absorption, Electromagnetic Interference Shielding, and Energy Storage.

Multifunctional applications including efficient microwave absorption and electromagnetic interference (EMI) shielding as well as excellent Li-ion storage are rarely achieved in a single material. Herein, a multifunctional nanocrystalline-assembled porous hierarchical NiO@NiFe2 O4 /reduced graphene oxide (rGO) heterostructure integrating microwave absorption, EMI shielding, and Li-ion storage functions is fabricated and tailored to develop high-performance energy conversion and storage devices. Owing to its structural and compositional advantages, the optimized NiO@NiFe2 O4 /15rGO achieves a minimum reflection loss of -55 dB with a matching thickness of 2.3 mm, and the effective absorption bandwidth is up to 6.4 GHz. The EMI shielding effectiveness reaches 8.69 dB. NiO@NiFe2 O4 /15rGO exhibits a high initial discharge specific capacity of 1813.92 mAh g-1 , which reaches 1218.6 mAh g-1 after 289 cycles and remains at 784.32 mAh g-1 after 500 cycles at 0.1 A g-1 . In addition, NiO@NiFe2 O4 /15rGO demonstrates a long cycling stability at high current densities. This study provides an insight into the design of advanced multifunctional materials and devices and provides an innovative method of solving current environmental and energy problems.

Functional role of a novel zinc finger protein, AoZFA, in growth and kojic acid synthesis in Aspergillus oryzae.

Kojic acid (KA) is a valuable secondary metabolite that is regulated by zinc finger proteins in Aspergillus oryzae. However, only two such proteins have been characterized to function in kojic acid production of A. oryzae to date. In this study, we identified a novel zinc finger protein, AoZFA, required for kojic acid biosynthesis in A. oryzae. Our results showed that disruption of AozfA led to increased expression of kojA and kojR involved in kojic acid synthesis, resulting in enhanced kojic acid production, while overexpression of AozfA had the opposite effect. Furthermore, deletion of kojR in the AozfA disruption strain abolished kojic acid production, whereas overexpression of kojR enhanced it, indicating that AoZFA regulates kojic acid production by affecting kojR. Transcriptional activation assay revealed that AoZFA is a transcriptional activator. Interestingly, when kojR was overexpressed in the AozfA overexpression strain, the production of kojic acid failed to be rescued, suggesting that AozfA plays a distinct role from kojR in kojic acid biosynthesis. Moreover, we found that AozfA was highly induced by zinc during early growth stages, and its overexpression inhibited the growth promoted by zinc, whereas its deletion had no effect, suggesting that AoZFA is non-essential but has a role in the response of A. oryzae to zinc. Overall, these findings provide new insights into the roles of zinc finger proteins in the growth and kojic acid production of A. oryzae.IMPORTANCEKojic acid (KA) is an economically valuable secondary metabolite produced by Aspergillus oryzae due to its vast biological activities. Genetic modification of A. oryzae has emerged as an efficient strategy for enhancing kojic acid production, which is dependent on the mining of genes involved in kojic acid synthesis. In this study, we have characterized a novel zinc-finger protein, AoZFA, as a negative regulator of kojic acid production by affecting kojR. AozfA is an excellent target for improving kojic acid production without any effects on the growth of A. oryzae. Furthermore, the simultaneous modification of AozfA and kojR exerts a more significant promotional effect on kojic acid production than the modification of single genes. This study provides new insights for the regulatory mechanism of zinc finger proteins in the growth and kojic acid production of A. oryzae.

Hyper-inflammation of astrocytes in patients of major depressive disorder: Evidence from serum astrocyte-derived extracellular vesicles.

Astrocyte-derived extracellular vesicles (ADEs) allow the in vivo probing of the inflammatory status of astrocytes practical. Serum sample and ADEs were used to test the inflammatory hypothesis in 70 patients with major depressive disorder (MDD) and 70 matched healthy controls (HCs). In serum, tumor necrosis factor α (TNF-α) and interleukin (IL)-17A were significantly increased, where as IL-12p70 was significantly reduced in the MDD patients compared with HCs. In ADEs, all inflammatory markers (Interferon-γ, IL-12p70, IL-1ß, IL-2, IL-4, IL-6, TNF-α, and IL-17A) except IL-10 were significantly increased in the MDD patients, the Hedge's g values of elevated inflammatory markers varied from 0.48 to 1.07. However, there were no differences of all inflammatory markers whether in serum or ADEs between MDD-drug free and medicated subgroups. The association of inflammatory biomarkers between ADEs and serum did not reach statistically significance after multi-comparison correction neither in the HCs nor MDD patients. The spearman coefficients between inflammatory factors and clinical characteristics in the MDD patients, such as onset age, disease course, current episode duration, and severity of depression, were nonsignificant after multi-comparison correction. In the receiver operating characteristic curves analysis, the corrected partial area under the curve (pAUC) of each inflammatory markers in ADEs ranged from 0.522 to 0.696, and the combination of these inflammatory factors achieved a high pAUC (>0.9). Our findings support the inflammatory glial hypothesis of depression, and suggests that in human ADEs could be a useful tool to probe the in vivo astrocyte status.

Psychosocial factors of insomnia in depression: a network approach.

BACKGROUND: Insomnia symptoms in patients with major depressive disorder (MDD) are common and deleterious. Childhood trauma, personality traits, interpersonal distress, and social support contribute to insomnia, but how they interact to affect insomnia remains uncertain. METHODS: A total of 791 patients with MDD completed the Insomnia Severity Index, Eysenck Personality Questionnaire, Interpersonal Relationship Comprehensive Diagnostic Scale, Childhood Trauma Questionnaire, Social Support Rating Scale and Hamilton Depression Scale-17. This study utilized network analyses to identify the central symptoms of insomnia and their associations with psychosocial factors. RESULTS: Worrying about sleep was identified as the central symptom in the insomnia network, insomnia and associated personality network, insomnia and associated interpersonal disturbance network, insomnia and associated childhood trauma network, insomnia and associated social support network, and the integrated network of insomnia symptoms and associated psychosocial factors. In the networks of insomnia symptoms and individual psychosocial factors, most psychosocial factors (other than childhood trauma) were directly or indirectly related to insomnia symptoms; however, neuroticism was the only factor directly associated with insomnia symptoms before and after controlling for covariates. In the final integrated network of insomnia symptoms and psychosocial factors, neuroticism was a bridge node and mediated the relationships of social support and interpersonal disturbances with insomnia symptoms, which is clearly presented in the shortest pathways. CONCLUSIONS: Worrying about sleep and neuroticism were prominent in the integrated network of insomnia symptoms and associated psychosocial factors, and the edge between them connected psychosocial factors and insomnia symptoms in MDD patients.

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment-resistant depression following electroconvulsive therapy.

AIM: The current study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti-inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma. METHODS: A total of 40 patients with treatment-resistant depression (TRD) and 35 matched healthy controls were recruited at baseline, and 34 patients with TRD completed the post-ECT visits. Blood samples were collected at baseline and post-ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein [GFAP] and S100ß), an extracellular vesicle marker cluster of differentiation 81 (CD81), and nine inflammatory markers in ADEVs were measured as main analyses. In addition, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis. RESULTS: At baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100ß, as well as CD81 compared with the healthy controls. Inflammatory markers interferon γ (IFN-γ), interleukin (IL) 1ß, IL-4, IL-6, tumor necrosis factor α, IL-10, and IL-17A were also significantly higher in the TRD group. After ECT, there was a significant reduction in the levels of GFAP, S100ß, and CD81, along with a significant decrease in the levels of IFN-γ and IL-4. Furthermore, higher levels of GFAP, S100ß, CD81, and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function. CONCLUSION: This study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert an anti-inflammatory effect through inhibition of such activation of astrocytes.

Analysis of Hypoxia Inducible Factor-1α Expression and Its Effects on Glycolysis of Esophageal Carcinoma.

We investigated the regulatory effects of hypoxia-inducible factor-1a (HIF-1α) on glycolysis metabolism in esophageal carcinoma (ESCA) cells. A series of bioinformatics databases and tools were used to investigate the expression and role of HIF-1α in ESCA. The expression of HIF-1a in ESCA tissues and adjacent tissues was validated by real-time PCR. Small interfering RNA (siRNA) was used to inhibit HIF-1α-related genes in human ESCA cells (Eca109 and KYSE150). Cell proliferation was detected by the CCK-8 assay. The expression of HIF-1α and glycolytic enzymes were investigated by real-time PCR and Western blot. HIF-1α is highly expressed in ESCA and is involved in many biological processes such as cell hypoxia reaction, glucose metabolic process. Further in vitro experiments showed that expression of HIF-1α in Eca109 and KYSE150 significantly increased under hypoxia compared with normoxia conditions. Also, the glucose uptake and lactate production under hypoxia were higher. The expression levels of hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1), glycolysis-related genes, were significantly increased under hypoxia. After siRNA knockdown of HIF-1a in Eca109 and KYSE150, the glucose uptake and lactate production, as well as cell proliferation were significantly decreased under hypoxia, and HK2 and PDK1 were significantly downregulated. HIF-1α promotes glycolysis of ESCA cells by upregulating the expression of HK2 and PDK1 under hypoxia.

Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage.

Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. There is a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum. We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. AP sites were quantitated following derivatization with O-(pyridin-3-yl-methyl)hydroxylamine. DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. Limits of quantitation ranged from 0.1 to 1.1 adducts per 108 bases using 3 µg of DNA. Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. Endogenous lipid peroxide-derived 3-(2-deoxy-ß-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology.

The Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Hair Dosimeter, DNA Adductomics Discovery, and Associations with Prostate Cancer Pathology Biomarkers.

Well-done cooked red meat consumption is linked to aggressive prostate cancer (PC) risk. Identifying mutation-inducing DNA adducts in the prostate genome can advance our understanding of chemicals in meat that may contribute to PC. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic aromatic amine (HAA) formed in cooked meat, is a potential human prostate carcinogen. PhIP was measured in the hair of PC patients undergoing prostatectomy, bladder cancer patients under treatment for cystoprostatectomy, and patients treated for benign prostatic hyperplasia (BPH). PhIP hair levels were above the quantification limit in 123 of 205 subjects. When dichotomizing prostate pathology biomarkers, the geometric mean PhIP hair levels were higher in patients with intermediate and elevated-risk prostate-specific antigen values than lower-risk values <4 ng/mL (p = 0.03). PhIP hair levels were also higher in patients with intermediate and high-risk Gleason scores ≥7 compared to lower-risk Gleason score 6 and BPH patients (p = 0.02). PC patients undergoing prostatectomy had higher PhIP hair levels than cystoprostatectomy or BPH patients (p = 0.02). PhIP-DNA adducts were detected in 9.4% of the patients assayed; however, DNA adducts of other carcinogenic HAAs, and benzo[a]pyrene formed in cooked meat, were not detected. Prostate specimens were also screened for 10 oxidative stress-associated lipid peroxidation (LPO) DNA adducts. Acrolein 1,N2-propano-2'-deoxyguanosine adducts were detected in 54.5% of the patients; other LPO adducts were infrequently detected. Acrolein adducts were not associated with prostate pathology biomarkers, although DNA adductomic profiles differed between PC patients with low and high-grade Gleason scores. Many DNA adducts are of unknown origin; however, dG adducts of formaldehyde and a series of purported 4-hydroxy-2-alkenals were detected at higher abundance in a subset of patients with elevated Gleason scores. The PhIP hair biomarker and DNA adductomics data support the paradigm of well-done cooked meat and oxidative stress in aggressive PC risk.

3D Hierarchical Porous and N-Doped Carbonized Microspheres Derived from Chitin for Remarkable Adsorption of Congo Red in Aqueous Solution.

A novel adsorbent of N-doped carbonized microspheres were developed from chitin (N-doped CM-chitin) for adsorption of Congo red (CR). The N-doped CM-chitin showed spherical shape and consisted of carbon nanofibers with 3D hierarchical architecture. There were many micro/nano-pores existing in N-doped CM-chitin with high surface area (455.703 m2 g-1). The N element was uniformly distributed on the carbon nanofibers and formed with oxidize-N graphitic-N, pyrrolic-N, and pyridinic-N. The N-doped CM-chitin showed excellent adsorption capability for CR and the maximum adsorption amount was approximate 954.47 mg g-1. The π-π/n-π interaction, hydrogen-bond interactions, and pore filling adsorption might be the adsorption mechanisms. The adsorption of N-doped CM-chitin was considered as a spontaneous endothermic adsorption process, and which well conformed to the pseudo-second-order kinetic and Langmuir isotherm model. The N-doped CM-chitin exhibited an effective adsorption performance for dynamic CR water with good reusability. Therefore, this work provides new insights into the fabrication of a novel N-doped adsorbent from low-cost and waste biomasses.

Overall trend towards headache remission during the COVID-19 pandemic among Chinese patients with pre-existing headache highlights the role of family support.

BACKGROUND: The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China. METHODS: A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire. RESULTS: Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P<0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P<0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P<0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches. CONCLUSIONS: Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches.

Antibiotic resistance genes are enriched with prolonged age of refuse in small and medium-sized landfill systems.

Landfills are sites for the disposal of waste over decades. The dynamics of contaminants during landfill treatment influence the functions and environmental risks of the landfill systems, but the patterns of these dynamics are not fully characterized, especially for antibiotic resistant genes (ARGs), an emerging contaminant of global concern. Here, seventeen typical ARG subtypes were quantitatively investigated in refuse samples from small and medium-sized landfills with ages of <3 years, ~5 years, and 8-10 years. The abundance of ARGs, including tetM, tetX, blaPER, emrB, sul1 and sul2, increased significantly (p < 0.05), approaching 8- to 304-fold on average, from refuse of < 3years to that of 8-10 years, while there was no obvious change (p > 0.05) in abundance for other ARGs, including tetQ, tetW, ampC, blaCTX-M, blaSHV, emrA, mefA, qnrD, qnrS, and mexF. Accordingly, resistance to tetracyclines, macrolides, and sulfonamides increased with landfill age, while resistance to ß-lactams and quinolones remained unchanged. The increase in ARG abundance with increasing refuse age was probably related with the increased horizontal gene transfer (HGT) (indicated by the increased abundance of mobile gene elements) and the enhanced co-selective pressure (suggested by the increased contents of heavy metals). These results indicated a potential risk from ARG enrichment with an increase in refuse age in small and medium-sized landfills, which should be managed to ensure landfill safety.

Ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in mediastinal mass resection by median sternotomy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Ultrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection. METHODS: This randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18-65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h. RESULTS: There were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 µg vs. 67.67 ± 8.92 µg, P < 0.001). In addition, pain numerical rating scale (NRS) scores were significantly lower in the PSI group compared with control patients, both at rest and upon coughing within 24 postoperative hours. Postoperative adverse events were generally reduced in the PSI group compared with controls. CONCLUSIONS: USG bilateral parasternal intercostal nerve block effectively reduces postoperative pain and adjuvant analgesic requirement, with good patient satisfaction, therefore constituting a good option for mediastinal mass resection by median sternotomy.

The Interaction Effects of Suicidal Ideation and Childhood Abuse on Brain Structure and Function in Major Depressive Disorder Patients.

Suicidal ideation (SI) is a direct risk factor for suicide in patients with depression. Regarding the emergence of SI, previous studies have discovered many risk factors, including childhood abuse as the major public problem. Previous imaging studies have demonstrated that SI or childhood abuse has effects on brain structure and function, respectively, but the interaction effects between them have not been fully studied. To explore the interaction effect between SI and childhood abuse, 215 patients with major depressive disorder completed the Childhood Trauma Questionnaire to evaluate childhood abuse and Beck's Scale for Suicidal Ideation to evaluate SI. Then, they completed magnetic resonance imaging (MRI) within one week after completing questionnaires. Respectively, we preprocessed the structural and functional images and analyzed gray matter volumes (GMV) and mean fractional amplitude of low-frequency fluctuation (mfALFF) values. Results showed that the changes of GMV in the cuneus, precuneus, paracentric lobule, inferior frontal gyrus, and caudate nucleus and local activity in cuneal and middle temporal gyrus are in relation with SI and childhood abuse. And in left caudate, SI and childhood abuse interact with each other on the influence of GMV. That is, the influence of SI in GMV was related to childhood abuse, and the influence of childhood abuse in GMV was also related to SI. Therefore, the combination of SI and childhood abuse based on imaging should help us better understand the suicide ideation developing mechanism and propose more effective targeted prevention strategies for suicide prevention.

Decreased ANGPTL4 impairs endometrial angiogenesis during peri-implantation period in patients with recurrent implantation failure.

Insufficient endometrial angiogenesis during peri-implantation impairs endometrial receptivity (ER), which contributes to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). Angiopoietin-like protein 4 (ANGPTL4) acts as a multifunctional secretory protein and is involved in the regulation of lipid metabolism and angiogenesis in various tissues including the endometrium. Herein, we found decreased ANGPTL4 expression in endometrial tissue and serum during peri-implantation period in 18 RIF-affected women with elevated uterine arterial impedance (UAI) compared with the pregnancy controls. ANGPTL4 and peroxisome proliferator-activated receptor gamma (PPARγ) expression were up-regulated upon decidualization on human endometrial stromal cells (HESCs). Rosiglitazone promoted the expression of ANGPTL4 in HESCs and human umbilical vein endothelial cells (HUVECs) via PPARγ. ANGPTL4 promoted the proliferation, migration and angiogenesis of HUVECs in vitro. Our results suggest that decreased abundance of ANGPTL4 in endometrial tissues impairs the endometrial receptivity via restraining endometrial angiogenesis during decidualization; while rosiglitazone-induced ANGPTL4 up-regulation in hESCs and HUVECs through PPARγ. Therefore, ANGPTL4 could be a potential therapeutic approach for some RIF-affected women with elevated UAI.

Kinetics of DNA Adducts and Abasic Site Formation in Tissues of Mice Treated with a Nitrogen Mustard.

Nitrogen mustards (NM) are an important class of chemotherapeutic drugs used in the treatment of malignant tumors. The accepted mechanism of action of NM is through the alkylation of DNA bases. NM-adducts block DNA replication in cancer cells by forming cytotoxic DNA interstrand cross-links. We previously characterized several adducts formed by reaction of bis(2-chloroethyl)ethylamine (NM) with calf thymus (CT) DNA and the MDA-MB-231 mammary tumor cell line. The monoalkylated N7-guanine (NM-G) adduct and its cross-link (G-NM-G) were major lesions. The cationic NM-G undergoes a secondary reaction through depurination to form an apurinic (AP) site or reacts with hydroxide to yield the stable ring-opened N5-substituted formamidopyrimidine (NM-Fapy-G) adduct. Both of these lesions are mutagenic and may contribute to secondary tumor development, a major clinical limitation of NM chemotherapy. We established a kinetic model with NM-treated female mice and measured the rates of formation and removal of NM-DNA adducts and AP sites. We employed liquid chromatography-mass spectrometry (LC-MS) to measure NM-G, G-NM-G, and NM-Fapy-G adducts in liver, lung, and spleen over 168 h. NM-G reached a maximum level within 6 h in all organs and then rapidly declined. The G-NM-G cross-link and NM-FapyG were more persistent with half-lives over three-times longer than NM-G. We quantified AP site lesions in the liver and showed that NM treatment increased AP site levels by 3.7-fold over the basal levels at 6 h. The kinetics of AP site repair closely followed the rate of removal of NM-G; however, AP sites remained 1.3-fold above basal levels 168 h post-treatment with NM. Our data provide new insights into NM-induced DNA damage and biological processing in vivo. The quantitative measurement of the spectrum of NM adducts and AP sites can serve as biomarkers in the design and assessment of the efficacy of novel chemotherapeutic regimens.