Association between body mass index and medication-overuse headache among individuals with migraine: a cross-sectional study.

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.

The impact of micropolymorphism in Anpl-UAA on structural stability and peptide presentation.

Micropolymorphism significantly shapes the peptide-binding characteristics of major histocompatibility complex class I (MHC-I) molecules, affecting the host's resistance to pathogens, which is particularly pronounced in avian species displaying the "minimal essential MHC" expression pattern. In this study, we compared two duck MHC-I alleles, Anpl-UAA*77 and Anpl-UAA*78, that exhibit markedly different peptide binding properties despite their high sequence homology. Through mutagenesis experiments and crystallographic analysis of complexes with the influenza virus-derived peptide AEAIIVAMV (AEV9), we identified a critical role for the residue at position 62 in regulating hydrogen-bonding interactions between the peptide backbone and the peptide-binding groove. This modulation affects the characteristics of the B pocket and the stability of the loop region between the 310 helix and the α1 helix, leading to significant changes in the structure and stability of the peptide-MHC-I complex (pMHC-I). Moreover, the proportion of different residues at position 62 among Anpl-UAAs may reflect the correlation between pAnpl-UAA stability and duck body temperature. This research not only advances our understanding of the Anpl-UAA structure but also deepens our insight into the impact of MHC-I micropolymorphism on peptide binding.

Rapid and Non-Destructive Prediction of Moisture Content in Maize Seeds Using Hyperspectral Imaging.

The moisture content of corn seeds is a crucial indicator for evaluating seed quality and is also a fundamental aspect of grain testing. In this experiment, 80 corn samples of various varieties were selected and their moisture content was determined using the direct drying method. The hyperspectral imaging system was employed to capture the spectral images of corn seeds within the wavelength range of 1100-2498 nm. By utilizing seven preprocessing techniques, including moving average, S-G smoothing, baseline, normalization, SNV, MSC, and detrending, we preprocessed the spectral data and then established a PLSR model for comparison. The results show that the model established using the normalization preprocessing method has the best prediction performance. To remove spectral redundancy and simplify the prediction model, we utilized SPA, CASR, and UVE algorithms to extract feature wavelengths. Based on three algorithms (PLSR, PCR, and SVM), we constructed 12 predictive models. Upon evaluating these models, it was determined that the normalization-SPA-PLSR algorithm produced the most accurate prediction. This model boasts high RC2 and RP2 values of 0.9917 and 0.9914, respectively, along with low RMSEP and RMSECV values of 0.0343 and 0.0257, respectively, indicating its exceptional stability and predictive capabilities. This suggests that the model can precisely estimate the moisture content of maize seeds. The results showed that hyperspectral imaging technology provides technical support for rapid and non-destructive prediction of corn seed moisture content and new methods in seed quality evaluation.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Prediction of risk factors for linezolid-induced thrombocytopenia based on neural network model.

Background: Based on real-world medical data, the artificial neural network model was used to predict the risk factors of linezolid-induced thrombocytopenia to provide a reference for better clinical use of this drug and achieve the timely prevention of adverse reactions. Methods: The artificial neural network algorithm was used to construct the prediction model of the risk factors of linezolid-induced thrombocytopenia and further evaluate the effectiveness of the artificial neural network model compared with the traditional Logistic regression model. Results: A total of 1,837 patients receiving linezolid treatment in a hospital in Xi 'an, Shaanxi Province from 1 January 2011 to 1 January 2021 were recruited. According to the exclusion criteria, 1,273 cases that did not meet the requirements of the study were excluded. A total of 564 valid cases were included in the study, with 89 (15.78%) having thrombocytopenia. The prediction accuracy of the artificial neural network model was 96.32%, and the AUROC was 0.944, which was significantly higher than that of the Logistic regression model, which was 86.14%, and the AUROC was 0.796. In the artificial neural network model, urea, platelet baseline value and serum albumin were among the top three important risk factors. Conclusion: The predictive performance of the artificial neural network model is better than that of the traditional Logistic regression model, and it can well predict the risk factors of linezolid-induced thrombocytopenia.

Analyzing ozone formation sensitivity in a typical industrial city in China: Implications for effective source control in the chemical transition regime.

Volatile organic compounds (VOCs) play a major role in O3 formation in urban environments. However, the complexity in the emissions of VOCs and nitrogen oxides (NOx) in industrial cities has made it challenging to identify the key factors influencing O3 formation. This study used observation-based-model (OBM) to analyze O3 sensitivities to VOCs and NOx during summer in a typical industrial city in China. The OBM model results were coupled with a receptor model to analyze the sources of O3. Higher concentrations of O3 precursors were observed during polluted periods indicating that precursor accumulation contributed to the higher maxima of the net ozone formation rate and HOx concentrations. Analyses of ROx· budgets and relative incremental reactivity (RIR) indicated that O3 production is in a chemical transition regime and was sensitive to both VOCs and NOx. Results from Positive Matrix Factorization (PMF) analysis indicated that gasoline vehicle emissions, industrial processes, and coal combustion were major sources of O3 precursors. The sensitivities of O3 production to these sources depend on if both VOC and NOx sensitivities are considered. If only VOCs sensitivity is considered, in contrast, the contribution of anthropogenic sources to O3 production was significantly underestimated. This study highlights the importance of accounting for both VOCs and NOx sensitivities when O3 chemistry is in a transition regime in O3 production attribution studies.

A community-based cross-sectional study of dietary composition and associated factors among tuberculosis patients in China.

To determine the dietary structure and its associated factors of tuberculosis (TB) patients in the community. This cross-sectional study analysed the dietary intake of 300 TB patients in two impoverished counties in China. Food intake was collected by using food frequency and two consecutive 24-h dietary review (24hdr) methods. The dietary composition and dietary structure of TB patients were compared with China's 2022 Dietary Reference Intake (DRIs) and the average reference value of dietary composition (ARC) in China in 2013. Binary logistic regression models were used to explore the factors associated with inadequate intake of animal food, insufficient protein and fat energy supply in patients with TB. The daily intake of various foods in TB patients was measured and the results were as follows: staple foods-median 372.12 g (interquartile range [IQR] 315.87 g); vegetables-median 200.00 g (IQR 205.55 g); fruits-median 20.22 g (IQR 36.82 g); animal foods-median 100.82 g (IQR 180.74 g); dairy products-median 0.00 g (IQR 0.00 g); nuts-median 17.10 g (IQR 29.75 g). The average daily intakes of vegetables, fruits, animal food, dairy products, soy and nuts were lower than those recommended by the DRIs (P < 0.01). Compared to women, men consumed more whole grains and mixed legumes, but less fruit. The dietary structures, including food and nutrient supply for energy, protein and fat, were significantly different in 300 patients compared with DRIs or ARC values. Inadequate rates of animal food intake were observed in 54.85% of men and 59.57% of women. Protein undersupply rates were 66.02% in men and 56.38% in women, while fat undersupply rates were 52.91% in men and 52.13% in women. The study revealed that being 18-49 years old, being the Han nationality, having less than 2 h of physical activity per day on average, and eating twice a day were risk factors for inadequate animal protein intake, protein energy deficiency and fat energy deficiency. TB patients from impoverished counties in China have inadequate intake of several food categories and insufficient protein and fat energy supply, correlating with multiple factors in socio-demographics, behavioral practices, and TB disease. To improve the nutritional status of TB patients, urgent public health actions, especially carrying out nutritional screening and evaluation once diagnosed, developing individualized nutritional support treatment plans, strengthening dietary nutritional health education and intervention, and advocating for enhanced nutritional support, should be taken.

Magnetic resonance imaging-based classification of the myodural bridge complex and its influencing factors.

Cerebrospinal fluid (CSF) circulation is considered the third circulation of the human body. Recently, some scholars have proposed the myodural bridge (MDB) as a novel power source for CSF flow. Moreover, the suboccipital muscles can exert a driving force on the CSF via the MDB. This hypothesis is directly supported by head rotation and nodding movements, which can affect CSF circulation. The MDB has been validated as a normal structure in humans and mammals. In addition, the fusion of MDB fibers of different origins that act in concert with each other forms the MDB complex (MDBC). The MDBC may be associated with several CSF disorder-related neurological disorders in clinical practice. Therefore, the morphology of the MDBC and its influencing factors must be determined. In this study, T2-weighted imaging sagittal images of the cervical region were analyzed retrospectively in 1085 patients, and magnetic resonance imaging (MRI) typing of the MDBC was performed according to the imaging features of the MDBC in the posterior atlanto-occipital interspace (PAOiS) and posterior atlanto-axial interspace (PAAiS). The effects of age and age-related degenerative changes in the cervical spine on MRI staging of the MDBC were also determined. The results revealed four MRI types of the MDBC: type A (no MDBC hyposignal shadow connected to the dura mater in either the PAOiS or PAAiS), type B (MDBC hyposignal shadow connected to the dura mater in the PAOiS only), type C (MDBC hyposignal shadow connected to the dura mater in the PAAiS only), and type D (MDBC hyposignal shadow connected to the dura mater in both the PAOiS and PAAiS). The influencing factors for the MDBC typing were age (group), degree of intervertebral space stenosis, dorsal osteophytosis, and degenerative changes in the cervical spine (P < 0.05). With increasing age (10-year interval), the incidence of type B MDBC markedly decreased, whereas that of type A MDBC increased considerably. With the deepening of the degree of intervertebral space stenosis, the incidence of type C MDBC increased significantly, whereas that of type A MDBC decreased. In the presence of dorsal osteophytosis, the incidence of type C and D MDBCs significantly decreased, whereas that of type A increased. In the presence of protrusion of the intervertebral disc, the incidence of type B, C, and D MDBCs increased markedly, whereas that of type A MDBC decreased considerably, with cervical degenerative changes combined with spinal canal stenosis. Moreover, the incidence of both type C and D MDBCs increased, whereas that of type A MDBC decreased. Based on the MRI signal characteristics of the dural side of the MDBC, four types of the MDBC were identified. MDBC typing varies dynamically according to population distribution, depending on age and cervical degeneration (degree of intervertebral space stenosis, vertebral dorsal osteophytosis formation, simple protrusion of intervertebral disc, and cervical degeneration changes combined with spinal canal stenosis, except for the degree of protrusion of the intervertebral disc and the degree of spinal canal stenosis); however, it is not influenced by sex.

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

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.

[Revealing Driving Factors of Urban O3 Based on Explainable Machine Learning].

Driven by precursor emissions, meteorological conditions, and other factors, atmospheric ozone (O3) has become the main pollutant affecting urban air quality in summer. The current deductive models driven by physical and chemical mechanisms require a large number of parameters for the analysis of O3 pollution, and the calculation timeliness is poor. The data-driven inductive models are efficient but have problems such as poor explanation. In this study, an explainable model of data-driven Correlation-ML-SHAP was established to reveal the strongly correlated influencing factors of O3 concentration. Additionally, the machine learning ML module coupled with the explainable SHAP module was used to calculate the contributions of driving factors to O3 concentration, so as to realize the quantitative analysis of driving factors. The O3 pollution process in the summer of 2021 in Jincheng City was used as an example to carry out the application research. The results showed that the Correlation-ML-SHAP model could reveal and use strong driving factors to simulate O3 concentration and quantify influence contribution, and the ML module used the XGBoost model to achieve the best simulation accuracy. Air temperature, solar radiation, relative humidity, and precursor emission level were the strong driving factors of O3 pollution in Jincheng City in summer 2021, and the contribution weights were 32.1%, 21.3%, 16.5%, and 15.6%. The contribution weights of air temperature, solar radiation, and precursor emission level increased by 3.4%, 1.2%, and 1.2% on polluted days, respectively, and the contribution weights of precursor emission level rose to third place on polluted days. Each driving factor had a nonlinear interaction effect on O3 concentration. When the air temperature exceeded 24℃, or the relative humidity was lower than 70%, there was a 94.9% and 94.1% probability of positive contribution to O3 pollution, respectively. Under such meteorological conditions, ρ(NO2) exceeded 9 µg·m-3, or ρ(CO) exceeded 0.7 mg·m-3, and there was a 94.9% and 99.3% probability of positive contribution to O3 pollution, respectively. The southeast wind speed was lower than 5.8 m·s-1, or the south wind speed was lower than 5.3 m·s-1, both of which contributed positively to O3 pollution. The model quantitatively analyzed the influence contribution of various driving factors on urban O3 concentration, which could provide a basis for the prevention and control of urban atmospheric O3 pollution in summer.

The Epidemiology and Clinical Characteristics of Fungemia in a Tertiary Hospital in Southern China: A 6-Year Retrospective Study.

Knowledge of the epidemiology and clinical characteristics of fungemia in southern China is limited. We conducted a six-year retrospective descriptive study to analyze the epidemiological and clinical characteristics of fungemia at the largest tertiary hospital in Guangxi, southern China. Data were obtained from the laboratory registry of patients with fungemia between January 2014 and December 2019. Demographic characteristics, underlying medical conditions, and outcomes for each case were analyzed. A total of 455 patients with fungemia were identified. Unexpectedly, Talaromyces marneffei (T. marneffei) was the most frequently isolated agent causing fungemia in the region (149/475, 31.4%), and Candida albicans (C. albicans) was the most commonly isolated Candida spp. (100/475, 21.1%). We identified that more than 70% of talaromycosis fungemia developed in AIDS patients, whereas candidemia was most commonly associated with a history of recent surgery. Notably, the total mortality rate of fungemia and the mortality rate in patients with T. marneffei and Cryptococcus neoformans (C. neoformans) fungemia were significantly higher in HIV-uninfected patients than in HIV-infected patients. In conclusion, the clinical pattern of fungemia in Guangxi is different from that in previous studies. Our study may provide new guidance for the early diagnosis and prompt treatment of fungemia in similar geographic regions.

Financial Burden of Tuberculosis Patients - China, 2020.

What is already known about this topic?: Tuberculosis (TB) is often referred to as "a disease of poverty," yet the information regarding the financial burden of TB care is limited and regionally representative. What is added by this report?: This manuscript reported the national representative total and breakdown costs associated with TB care in China. The total cost per patient was 1,185 USD, of which 88% was direct cost and 37% was incurred prior to TB treatment. What are the implications for public health practice?: TB patients experience a significant financial burden, and disparities exist among different regions and populations. Current TB care policies and packages are not sufficient to address this issue.

Micron-Thick Interlocked Carbon Nanotube Films with Excellent Impact Resistance via Micro-Ballistic Impact.

The highest specific energy absorption (SEA) of interlocked micron-thickness carbon nanotube (IMCNT) films subjected to micro-ballistic impact is reported in this paper. The SEA of the IMCNT films ranges from 0.8 to 1.6 MJ kg-1 , the greatest value for micron-thickness films to date. The multiple deformation-induced dissipation channels at the nanoscale involving disorder-to-order transition, frictional sliding, and entanglement of CNT fibrils contribute to the ultra-high SEA of the IMCNT. Furthermore, an anomalous thickness dependency of the SEA is observed, that is, the SEA increases with increasing thickness, which should be ascribed to the exponential growth in nano-interface that further boosts the energy dissipation efficiency as the film thickness increases. The results indicate that the developed IMCNT overcomes the size-dependent impact resistance of traditional materials and demonstrates great potential as a bulletproof material for high-performance flexible armor.

Fiber Crossbars: An Emerging Architecture of Smart Electronic Textiles.

Smart wearables have a significant impact on people's daily lives, enabling personalized motion monitoring, realizing the Internet of Things, and even reshaping the next generation of telemedicine systems. Fiber crossbars (FCs), constructed by crossing two fibers, have become an emerging architecture among the accessible structures of state-of-the-art smart electronic textiles. The mechanical, chemical, and electrical interactions between crossing fibers result in extensive functionalities, leading to the significant development of innovative electronic textiles employing FCs as their basic units. This review provides a timely and comprehensive overview of the structure designs, material selections, and assembly techniques of FC-based devices. The recent advances in FC-based devices are summarized, including multipurpose sensing, multiple-mode computing, high-resolution display, high-efficient power supply, and large-scale textile systems. Finally, current challenges, potential solutions, and future perspectives for FC-based systems are discussed for their further development in scale-up production and commercial applications.

Psyllium seed husk regulates the gut microbiota and improves mucosal barrier injury in the colon to attenuate renal injury in 5/6 nephrectomy rats.

Chronic kidney disease (CKD) can cause gut microbiota dysbiosis and thus impair intestinal barrier function. Disruption of intestinal homeostasis facilitates the production of enterogenic toxins, which exacerbate CKD-induced uremic toxicity and inflammation. Dietary fiber, by targeting the gut-kidney axis, could be used for CKD treatment. Psyllium seed husk (PSH) extracted from the seeds of Plantago ovata contains highly branched, gel-forming arabinoxylan. Positive effects of PSH on host physiology have been demonstrated but whether it also acts on the microbial ecosystem in CKD patients is unknown. In this study, the effects of dietary PSH on the gut microbiota, intestinal barrier function, systemic inflammation, uremic toxins, and renal injury were investigated in 5/6 nephrectomy (5/6Nx) CKD rats. Blood, feces, and kidney and colon tissues were collected from PSH-treated and control rats and subjected to biochemical and histological analyses, enzyme-linked immunosorbent assays, and 16SrRNA sequencing. PSH supplementation reduced serum creatinine and blood urea nitrogen levels, and attenuated renal tubular interstitial injury, in 5/6Nx rats. 16SrRNA sequencing showed that PSH improved the gut microbiota and intestinal barrier function in addition to down-regulating serum interleukin (IL)-1, IL-6, and indoxyl sulfate levels. Together, these results demonstrate the potential of PSH supplementation for treating CKD, including by improving intestinal microecology, reducing uremic toxin levels and systemic inflammation, and delaying disease progression.

Preparation of CoFe2O4-Doped TiO2 Nanofibers by Electrospinning and Annealing for Oxygen Electrocatalysis.

In this paper, catalyst precursor fibers were prepared by a sol gel method combined with an electrospinning method using tetrabutyl titanate as a titanium source, cobalt acetylacetonate as a cobalt source, and iron acetylacetonate as an iron source. CoFe@TiO2 nanofibers (NFs) with a bimetallic spinel structure were formed after thermal annealing, which have dual-functional catalytic activity. With the molar ratio of Co and Fe coming to 1:1, a typical spinel CoFe2O4 structure was generated in Co1Fe1@TiO2 NFs. At a load of only 28.7 µg·cm-2, Co1Fe1@TiO2 NFs not only have a low overpotential (284 mV) and Tafel slope (54 mV·dec-1) in the oxygen evolution reaction but also show a high initial potential (0.88 V) and limiting current density (6.40 mA·cm-2) in the oxygen reduction reaction. Meanwhile, Co1Fe1@TiO2 NFs exhibit good durability, cycle stability, and dual-function catalysis.

Tryptophan intake, not always the more the better.

Objectives: To investigate the effects of excessive tryptophan intake on the body and the effects of tryptophan metabolism-related aryl hydrocarbon receptor (AhR) pathway in healthy rats and chronic kidney disease rats, to study the adverse effects of excess tryptophan. Design: In Part I Experiment, the healthy rats were fed with diet containing 0.6, 1.2 and 1.8% tryptophan for 12 weeks. After the intervention, the blood and kidney tissues were collected. Serum creatinine and blood urea nitrogen were detected. Hematoxylin-eosin (H&E) staining was used to observe renal pathological changes. Enzyme-linked immunosorbent assay was used to detect serum kynurenic acid and AhR levels. The kidney levels of AhR, CyP1A1 and CyP1B1 were detected by western-blot. In Part II Experiment, the chronic kidney disease (CKD) model was induced by intra-gastric gavage with adenine for 4 weeks. Then the CKD rats were given tryptophan at a dose of 100 mg/kg or 500 mg/kg for eight weeks. Rat survival curve, renal function, renal tissue pathology and serum AhR were detected. Tryptophan-targeted ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS) was employed to quantitatively access the tryptophan-targeted metabolites in two parts experiments. Results: In part I experiment, high tryptophan diet can increase the level of blood urea nitrogen (BUN) in healthy rats and induce focal renal tubulointerstitial injury. Tryptophan-targeted analyzes showed that high tryptophan diet feeding can significantly increase the concentration of kynurenine and indole metabolites. The serum AhR level and kidney AhR, CyP1A1 and CyP1B1 were also significantly increased in high tryptophan diet rats. In part II experiment, high tryptophan intervention induced a significant increase in mortality, serum creatinine, urea nitrogen levels, and renal pathological damage in CKD rats. The levels of tryptophan-targeted metabolites, kynurenine, xanthurenate, picolinic acid, 5-hydroxyindole-3-acetic acid, indole-3-lactic acid, indoleacetate and indoxyl sulfate, showed an upward trend in the high-dose tryptophan group (Ade + Trp-H) compared with the adenine group. The serum AhR of Ade + Trp-H rats was significantly higher than those of adenine rats. Conclusion: Moderate tryptophan intake may be beneficial, but excessive tryptophan can lead to accumulation of kynurenine and indole metabolites, activate AhR pathway and induce kidney injury.

Digital adherence technologies to improve tuberculosis treatment outcomes in China: a cluster-randomised superiority trial.

BACKGROUND: Drug-sensitive tuberculosis treatment requires 6 months of therapy, so adherence problems are common. Digital adherence technologies might improve tuberculosis treatment outcomes. We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes. METHODS: We did a cluster-randomised superiority trial across four prefectures in China. 24 counties or districts (clusters) were randomly assigned (1:1) to intervention or control groups. We enrolled patients aged 18 years or older with GeneXpert-positive, rifampicin-sensitive pulmonary tuberculosis, who were receiving daily fixed-dose combination treatment. Patients in the intervention group received a medication monitor for daily drug-dosing reminders, monthly review of adherence data by health-care provider, and management of poor adherence; and patients in the control group received routine care (silent-mode monitor-measured adherence). Only the independent endpoints review committee who assessed endpoint data for some participants were masked to study group assignment. Patients were followed up (with sputum solid culture) at 12 and 18 months. The primary outcome was a composite of death, loss to follow-up, treatment failure, switch to multidrug-resistant tuberculosis treatment, or tuberculosis recurrence by 18 months from treatment start, analysed in the intention-to-treat population. Analysis accounted for study design with multiple imputation for the primary outcome. This trial is now complete and is registered with ISRCTN, 35812455. FINDINGS: Between Jan 26, 2017, and April 3, 2019, 15 257 patients were assessed for eligibility and 3074 were enrolled, 2686 (87%) of whom were included in the intention-to-treat population. 1909 (71%) of 2686 patients were male, 777 (29%) were female, and the median age was 44 years (IQR 29-58). By 18 months from treatment start, using multiple imputation for missing outcomes, 239 (16% [geometric mean of cluster-level proportion]) of 1388 patients in the control group and 224 (16%) of 1298 in the intervention group had a primary composite outcome event (289 [62%] of 463 events were loss to follow-up during treatment and 42 [9%] were tuberculosis recurrence). The intervention had no effect on risk of the primary composite outcome (adjusted risk ratio 1·01, 95% CI 0·73-1·40). INTERPRETATION: Our digital medication monitor intervention had no effect on unfavourable outcomes, which included loss to follow-up during treatment, tuberculosis recurrence, death, and treatment failure. There was a failure to change patient management following identification of treatment non-adherence at monthly reviews. A better understanding of adherence patterns and how they relate to poor outcomes, coupled with a more timely review of adherence data and improved implementation of differentiated care, may be required. FUNDING: Bill & Melinda Gates Foundation.

BJTJ-1837, a novel FXI activation-blocking antibody.

Background: Factor (F)XI contributes to thrombosis development while it plays a limited role in normal hemostasis. FXI targeting has the potential for preventing and treating thrombosis with little bleeding risk. Objectives: The aim of this study was to develop novel antibody therapeutics against FXI for the treatment of thrombosis-related diseases. Methods: Mouse hybridoma technology was applied to screen for anti-FXI antibodies. Surface plasma resonance, enzyme inhibition, activated partial thromboplastin time, and prothrombin time assays were conducted to characterize the binding affinity and activity of antibodies. A cynomolgus monkey arterial venous shunt model was applied to validate the antithrombotic activities. Results: A humanized antibody, BJTJ-1837, reported here bound to the protease domain of FXI and activated FXI with high affinity. BJTJ-1837 fully inhibited the activation of FXI by activated FXII and thrombin. BJTJ-1837 also demonstrated strong anticoagulant activity in human and cynomolgus monkey plasma as measured by activated partial thromboplastin time. Moreover, BJTJ-1837 showed favorable antithrombotic activity with a dose-dependent protection in an arterial venous shunt thrombosis model in cynomolgus monkeys without the bleeding adverse effect. Furthermore, BJTJ-1837 displayed favorable pharmacokinetic and pharmacodynamic properties and good developability. Conclusion: As a potential antithrombotic therapeutic agent with a safe profile, BJTJ-1837 is a very promising FXI activation-blocking antibody candidate.