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OBJECTIVES/GOALS: During the pandemic, alcohol related deaths increased by 25%. To help understand how we might mitigate this negative outcome, we sought to examine the association of new diagnosis of alcohol use disorder (AUD) with SARS-CoV2 through two years of the pandemic. METHODS/STUDY POPULATION: Using a non-date-shifted TriNetX database, we conducted a retrospective cohort analysis of electronic health records of patients age ≥12 years who had been diagnosed either with COVID-19 (n=1,359,817) or other respiratory infections with no record of COVID-19 (n=2,013,031). Patients were then matched for propensity score risk for AUD, and results were analyzed by three-month intervals from January 2020 through January 2022, in blocks numbered 1-8. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CI) for diagnosis of AUD from two weeks to six months following COVID-19 diagnosis. RESULTS/ANTICIPATED RESULTS: There was significant excess risk compared to control cohorts of AUD following COVID-19 diagnoses made during the first three months of the pandemic (HR (CI)): block 1: 2.41(1.89,3.08); no excess risk was seen for the remainder of 2020 (blocks 2-4) (HR1.01-1.14, NS). The excess risk increased again in 2021 as the delta and omicron variants emerged (HR and 95% CI): block 5 were: 1.26(1.11, 1.43)); block 6: 1.88(1.62-2.18)); block 7: 1.24(1.10,1.41); block 8: 1.12(1.0-1.25). COVID-19 diagnosis was associated with clinically-evident AUD under some pandemic circumstances. DISCUSSION/SIGNIFICANCE: COVID-19 early in the pandemic (block 1) was associated with substantial excess risk for new diagnosis of AUD, with smaller excess risk after COVID-19 during 2021 (blocks 5-7), and no excess risk otherwise. Diagnosis of COVID-19 and pandemic contextual factors are associated with increased risk for AUD.
Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders.
Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed.
Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network.
These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
Athetis lepigone Möschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1 μM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15 μM] and ten plant volatiles, including (-)-limonene, α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.
The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.
A12-week experiment was conducted to evaluate the influences of thiamine ongrowth performance, and intestinal mitochondrial biogenesis and function of Megalobramaamblycephala fed a high-carbohydrate (HC) diet. Fish (24·73 (sem 0·45) g) were randomly assigned to one of four diets: two carbohydrate (CHO) levels (30 and 45 %) and two thiamine levels (0 and 1·5 mg/kg). HC diets significantly decreased DGC, GRMBW, FIMBW, intestinal activities of amylase, lipase, Na+, K+-ATPase, CK, complexes I, III and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK: T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, mitochondrial transcription factor A, Opa-1, ND-1 and COX-1 and 2, while the opposite was true for ATP, AMP and reactive oxygen species, and the transcriptions of dynamin-related protein-1, fission-1 and mitochondrial fission factor. Dietarythiamine concentrations significantly increased DGC, GRMBW, intestinal activities of amylase, Na+, K+-ATPase, CK, complexes I and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, ND-1, COX-1 and 2, SGLT-1 and GLUT-2. Furthermore, a significant interaction between dietary CHO and thiamine was observed in DGC, GRMBW, intestinal activities of amylase, CK, complexes I and IV, ΔΨm, the AMP:ATP ratio, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, COX-1 and 2, SGLT-1 and GLUT-2. Overall, thiamine supplementation improved growth performance, and intestinal mitochondrial biogenesis and function of M. amblycephala fed HC diets.
Toxoplasma gondii can infect almost all warm-blooded vertebrates with pathogensis being largely influenced by the host immune status. As important epidemiological hosts, rodents are globally distributed and are also commonly found infected with haemoflagellates, such as those in the genus Trypanosoma. We here address whether and how co-infection with trypanosomes can influence T. gondii infection in laboratory models. Rats of five strains, co-infected with T. lewisi and mice of four strains, co-infected with T. musculi, were found to be more or less susceptible to T. gondii infection, respectively, with corresponding increased or decreased brain cyst burdens. Downregulation of iNOS expression and decreased NO production or reverse were observed in the peritoneal macrophages of rats or mice, infected with trypanosomes, respectively. Trypanosoma lewisi and T. musculi can modulate host immune responses, either by enhancement or suppression and influence the outcome of Toxoplasma infection.
Iridium (Ir) has an extremely high melting point (2443 °C), high chemical stability and is one of the most promising high-temperature materials. However, Ir is more difficult to process compared with other face-centered cubic metals, such as Ni and Al, which limits its applications. To solve this problem, we study the effect of 32 alloying elements (X) on stacking fault energy of dilute Ir-based alloys generated by shear deformation using the first-principles calculations. The investigation reveals that there are many alloying elements studied herein decrease the stacking fault energy of face-centered cubic (fcc) Ir, and the most effective element in reducing stacking fault energy of fcc Ir is Zn. The microscopic mechanism is caused by electron redistribution in the local stacking fault area. These results are expected to provide valuable guidance for the further design and application of Ir-based alloys.
We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
We present the experimental optimization of electrons in the several hundred keV energy range originated from laser-irradiated wire targets. Accelerated by a femtosecond laser pulse, an electron pulse emitted from the wire target was collimated immediately along the wire to a filter unit for the manipulation of energy and spatial distributions. It is shown in simulation that with a pair of magnets as the filter unit, the optimized electrons could serve as a compact and tunable electron source. The proposed system was demonstrated in a proof-of-principle experiment where we attained 1 fC bunch charge with transverse coherence length approaching 1 nm based on a 0.2 TW laser platform. This indicates the scheme as a promising candidate for single-shot electron diffraction.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
Energy chirp compensation of the electron bunch (e-bunch) in a laser wakefield accelerator, which is caused by the phase space rotation in the gradient wakefield, has been applied in many schemes for low energy spread e-bunch generation. We report the experimental observation of energy chirp compensation of the e-bunch in a nonlinear laser wakefield accelerator with a negligible beam loading effect. By adjusting the acceleration length using a wedge-roof block, the chirp compensation of the accelerated e-bunch was observed via an electron spectrometer. Apart from this, some significant parameters for the compensation process, such as the longitudinal dispersion and wakefield slope at the bunch position, were also estimated. A detailed comparison between experiment and simulation shows good agreement of the wakefield and bunch parameters. These results give a clear demonstration of the longitudinal characteristics of the wakefield in a plasma and the bunch dynamics, which are important for better control of a compact laser wakefield accelerator.
X-ray Pulsar Navigation (XPNAV) uses the Time Difference of Arrival (TDOA) of the pulsar signal between the spacecraft and Solar System Barycentre (SSB) to determine position. In this paper, a novel method to improve the performance of XPNAV via exploiting the pulsar position vector is proposed. First, the field of view of the collimator is utilised to find the pulsar orientation direction. Then, a searching strategy based on the modified Powell method under given coordinate frames is proposed. We also mathematically prove the existence of the extreme value of the searching strategy. Subsequently, an observation model based on the pulsar radiation vector is presented and applied to formulate the observation function together with pulsar time transfer function. Finally, an Adaptive Divided Difference Filter (ADDF) algorithm is introduced to iteratively estimate the position and velocity of the spacecraft. Numerical simulations show that the vector searching method is feasible and the pulsar radiation direction can improve the navigation performance by 75%. The simulation results also show that the ADDF performs better than Unscented Kalman Filtering (UKF) and DDF in position estimation.
Given the global water challenges, solar-driven steam generation has become a renewed topic recently as an energy-efficient way for clean water production. Here, a hybrid plasmonic structure consisting of a top layer of TiN nanoparticles (NPs) and a bottom layer of mesoporous anodized alumina membrane (AAM) was rationally designed and fabricated. The top TiN NPs with broadband light absorption acted as a plasmonic heating layer, which converted the absorbed light to heat efficiently for interfacial water heating. The AAM acted as the mechanical support layer, guaranteeing the heat isolation and continuous water replenishment. With optimized thickness of the TiN top layer, a solar steam generation efficiency of 87.7% was achieved in this study. This efficiency is comparable or even higher than prior studies. The current work proves the capability of the TiN NPs as an alternative photothermal material.
The accuracy and fault tolerance of filters are directly affected by the filter architecture and algorithm, thus influencing navigation performance. The chi square detection used in the conventional reset federated filter is not sensitive to soft faults, and it is easy to cause the health subsystem to be polluted through information sharing. It is a challenge to design an adaptive reset federated filter to improve the performance of the navigation system. Therefore, taking the Strapdown Inertial Navigation System/Global Positioning System/Celestial Navigation System/Synthetic Aperture Radar (SINS/GPS/CNS/SAR) integrated navigation system as an example, an adaptive federated filter architecture for vector-formed information sharing without a fault isolation module is designed in this paper. The proposed method uses the two-state chi square detection algorithm to calculate the parameters corresponding to each state, making the state with higher accuracy obtain a greater information distribution coefficient. In addition, according to the value of vector-formed information sharing, an adaptive coefficient of measurement noise is designed. This improves the adaptability of the navigation system to soft faults. Simulation results show that the accuracy of the proposed algorithm has the same performance compared with the conventional method under normal circumstances. When the sensor has a soft fault, the adaptive federated filter algorithm proposed in this paper can adaptively adjust the distribution coefficients, eliminate the influence of the fault information and improve the precision of the navigation system. The approach described in this paper can be used in multi-sensor integrated navigation. It will have better performance in engineering applications.