The role of lysosomes as intermediates in betacoronavirus PHEV egress from nerve cells.

IMPORTANCE: Betacoronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and mouse hepatitis virus (MHV), exploit the lysosomal exocytosis pathway for egress. However, whether all betacoronaviruses members use the same pathway to exit cells remains unknown. Here, we demonstrated that porcine hemagglutinating encephalomyelitis virus (PHEV) egress occurs by Arl8b-dependent lysosomal exocytosis, a cellular egress mechanism shared by SARS-CoV-2 and MHV. Notably, PHEV acidifies lysosomes and activates lysosomal degradative enzymes, while SARS-CoV-2 and MHV deacidify lysosomes and limit the activation of lysosomal degradative enzymes. In addition, PHEV release depends on V-ATPase-mediated lysosomal pH. Furthermore, this is the first study to evaluate ßCoV using lysosome for spreading through the body, and we have found that lysosome played a critical role in PHEV neural transmission and brain damage caused by virus infection in the central nervous system. Taken together, different betacoronaviruses could disrupt lysosomal function differently to exit cells.

Flex Meta-Storms elucidates the microbiome local beta-diversity under specific phenotypes.

MOTIVATION: Beta-diversity quantitatively measures the difference among microbial communities thus enlightening the association between microbiome composition and environment properties or host phenotypes. The beta-diversity analysis mainly relies on distances among microbiomes that are calculated by all microbial features. However, in some cases, only a small fraction of members in a community plays crucial roles. Such a tiny proportion is insufficient to alter the overall distance, which is always missed by end-to-end comparison. On the other hand, beta-diversity pattern can also be interfered due to the data sparsity when only focusing on nonabundant microbes. RESULTS: Here, we develop Flex Meta-Storms (FMS) distance algorithm that implements the "local alignment" of microbiomes for the first time. Using a flexible extraction that considers the weighted phylogenetic and functional relations of microbes, FMS produces a normalized phylogenetic distance among members of interest for microbiome pairs. We demonstrated the advantage of FMS in detecting the subtle variations of microbiomes among different states using artificial and real datasets, which were neglected by regular distance metrics. Therefore, FMS effectively discriminates microbiomes with higher sensitivity and flexibility, thus contributing to in-depth comprehension of microbe-host interactions, as well as promoting the utilization of microbiome data such as disease screening and prediction. AVAILABILITY AND IMPLEMENTATION: FMS is implemented in C++, and the source code is released at https://github.com/qdu-bioinfo/flex-meta-storms.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Research and Optimization of High-Performance Front-End Circuit Noise for Inertial Sensors.

An inertial sensor is a crucial payload in China's Taiji program for space gravitational wave detection. The performance of the capacitive displacement sensing circuit in the low-frequency band (0.1 mHz to 1 Hz) is extremely important because it directly determines the sensitivity of the space gravitational wave detection missions. Therefore, significant, yet challenging, tasks include decreasing the low-frequency noise in capacitive displacement sensing circuits and improving the capacitive sensing resolution. This study analyzes the noise characteristics of the pre-amplifier circuit within the capacitive sensing circuit, achieves precise tuning of the transformer bridge, and examines how transformer parameters affect noise. In addition, this study introduces a method using a discrete JFET to reduce the operational amplifier current noise and analyzes how feedback resistance and capacitance in TIA circuits affect the overall circuit noise. The proportional relationship between different transformer noises and TIA noise before and after optimization was analyzed and experimentally verified. Finally, an optimized TIA circuit and a superior transformer were utilized to achieve an increase in the capacitive sensing resolution from 1.095 aF/rtHz @ 10 mHz to 0.84 aF/rtHz @ 10 mHz, while improving the performance by 23%. These findings provide valuable insights into further decreasing circuit noise and increasing the capacitive sensing resolution.

Research on High-Precision Resonant Capacitance Bridge Based on Multiple Transformers.

The Taiji program is dedicated to the detection of middle and low-frequency gravitational waves, targeting the 0.1 mHz to 1 Hz frequency band. The project requires an acceleration residual sensitivity of 3 × 10-15 ms-2/Hz1/2, which necessitates a capacitance sensing resolution of 1 aF/Hz1/2 for the capacitive sensing system within the specified frequency range. The noise level of the resonant bridge significantly influences the resolution. Addressing the challenges in enhancing transformer performance parameters in existing resonant capacitance bridges and the constraints on improving the characteristics of resonant capacitance bridges, this study introduces a novel approach to reduce bridge thermal noise without optimizing existing parameters. The simulation results demonstrate that this scheme can reduce the noise to 0.7 times the original level and further reduce bridge thermal noise when other parameters affecting noise are optimized. This not only mitigates the demands for other performance parameters but also increases the range of maximum acceptable resonant frequency deviations and reduces its sensitivity to such variations. Experimental validation confirms that the proposed scheme effectively reduces noise by 0.7 times and improves the resolution of capacitance sensing to 0.6 aF/Hz1/2, thereby advancing the Taiji program gravitational wave detection capabilities.

Association of cardio-renal biomarkers and mortality in the U.S.: a prospective cohort study.

OBJECTIVE: Diabetes poses a significant threat to human health. There is a lack of large-scale cohort studies to explore the association between mortality risk and indicators beyond blood glucose monitoring in diabetic populations. METHODS: Multivariable Cox proportional hazards regression models were performed to investigate the association of 13 blood biomarkers with mortality risk in the National Health and Nutrition Examination Survey (NHANES) and biomarker levels were log-transformed and correlated with mortality. RESULTS: During a median follow-up of 7.42 years, 1783 diabetic patients were enrolled. Compared to traditional risk factors, the addition of hs-cTnT, hs-cTnI, NT-proBNP, creatinine, cystatin C, and ß-2 microglobulin biomarkers increased the predictive ability for all-cause mortality by 56.4%, 29.5%, 38.1%, 18.8%, 35.7%, and 41.3%, respectively. However, the inclusion of blood glucose monitoring had no impact on the prediction of all-cause mortality. Compared with the 1st quartiles of creatinine and Cystatin C, the risk of diabetes mortality were higher in the highest quartiles (HR: 5.16, 95% CI: 1.87-14.22; HR: 10.06, 95% CI: 4.20-24.13). CONCLUSIONS: In the diabetic population, elevated plasma levels of hs-cTnT, hs-cTnI, NT-proBNP, creatinine, cystatin C, and ß-2 microglobulin serve as robust and straightforward predictors of long-term mortality compared to blood glucose levels and HbA1c values. Creatinine and cystatin C stand out as more precise markers for predicting diabetes mortality prior to blood glucose monitoring.

Research and Implementation of a Demodulation Switch Signal Phase Alignment System in Dynamic Environments.

In the space gravitational wave detection mission, inertial sensors play the role of providing an inertial reference for the laser interferometric measurement system. Among them, the capacitance sensor serves as the core key technology of the inertial sensor, used to measure the relative position of the test mass (TM) in the electrode cage. The capacitance sensor utilizes synchronous demodulation technology to extract signals from the AC induction signal. When the phase of the demodulation switch signal is aligned, the synchronous demodulator can most effectively filter out noise, thus directly influencing the performance of the capacitance sensor. However, since the TM is in a suspended state, the information read by the capacitance sensor is dynamic, which increases the difficulty of demodulation phase alignment. In light of this, a method is proposed for achieving the phase alignment of the demodulation switch signal in a dynamic environment. This is accomplished by adjusting the phase of the demodulation switch signal, and subsequently computing the phase difference between the AC induction signal and the demodulation switch signal. At the same time, a measurement and evaluation method for phase deviation is also proposed. Ultimately, an automatic phase alignment system for the demodulation switch signal in dynamic environments is successfully implemented on an FPGA platform, and tests are conducted on a hexapod PI console platform to simulate dynamic environments. The experimental results demonstrate that the system accurately achieves phase alignment in the static environment, with a phase deviation of 0.1394 rad. In the simulated dynamic environment, the phase deviation is 0.1395 rad.

[Dietary micronutrient intake of children aged 2-5 years in China in 2019-2021].

OBJECTIVE: To describe dietary intake of calcium, iron, zinc, selenium, vitamin A, vitamin B_1, vitamin B_2 and vitamin C and compare the intake between urban and rural areas among preschool children aged 2-5 years based on the data from the National Nutrition and Health Systematic Survey for Children 0-17 Years of Age in China. METHODS: Children from 14 provinces were selected by multi-stage stratified random cluster sampling, and the dietary data of preschool children aged 2-5 years were recorded using the 3 day 24-hour weighted food records method. SAS 9.4 was used to calculate dietary intake of these micronutrients based on the Chinese Food Composition Table and to compare the intake between urban and rural areas. The risk of insufficient or excessive intake of micronutrients among Chinese children aged 2-5 years was assessed according to the Chinese Dietary Reference Intakes(DRIs) 2013 edition. RESULTS: A total of 820 children aged 2 to 5 years were selected. The median daily dietary calcium intake of children aged 2-5 years in China was 433.7, 338.9, 356.4 and 347.4 mg, respectively. The median daily dietary intake of vitamin B_1 of children aged 2-5 years was 0.5 mg for all age groups. The median daily dietary vitamin B_2 intake of children aged 2-5 years was 0.7, 0.6, 0.6 and 0.6 mg, respectively. The median daily dietary intake of vitamin C of children aged 2-5 years was 37.9, 37.4, 44.0 and 40.0 mg, respectively. The median daily dietary selenium intake of children aged 2-5 years was 17.1, 20.5, 22.7 and 22.3 µg, respectively. Dietary calcium intake for aged 2-5 years, dietary vitamin B_2 intake for aged 2-4 years, dietary iron, selenium, zinc and vitamin B_1 intake for aged 2-3 years was significantly greater in urban children than rural children. Among all nutrients, the proportion of dietary calcium intakes below the estimated average requirement(EAR) was the highest in aged 2-5 years(61.4%, 76.4%, 91.4% and 91.5%, respectively). The proportions of dietary vitamin B_1, vitamin C and selenium intake lower than EAR of children aged 2-5 years in China were 52.4%-63.2%, 42.8%-50.2% and 46.6%-58.7%, respectively. COUCLUSION: The dietary calcium intake of children aged 2-5 years in China remains insufficient for these children, especially for rural children. Dietary vitamin B_1, vitamin C and selenium intake should be improved.

Analysis of a Capacitive Sensing Circuit and Sensitive Structure Based on a Low-Temperature-Drift Planar Transformer.

In space gravitational-wave-detection missions, inertial sensors are used as the core loads, and their acceleration noise needs to reach 3×10−15 ms−2/Hz at a frequency of 0.1 mHz, which corresponds to the capacitive sensing system; the capacitive sensing noise on the sensitive axis needs to reach 1 aF/Hz. Unlike traditional circuit noise evaluation, the noise in the mHz frequency band is dominated by the thermal noise and the 1/f noise of the device, which is a challenging technical goal. In this paper, a low-frequency, high-precision resonant capacitor bridge method based on a planar transformer is used. Compared with the traditional winding transformer, the developed planar transformer has the advantages of low temperature drift and low 1/f noise. For closed-loop measurements of capacitive sensing circuits and sensitive structures, the minimum capacitive resolution in the time domain is about 3 aF, which is far lower than the scientific measurement resolution requirement of 5.8 fF for gravitational wave detection. The capacitive sensing noise is converted to 1.095 aF/Hz in the frequency band of 10 mHz−1 Hz. Although there is a gap between the closed-loop measurement results and the final index, the measurement environment is an experimental condition without temperature control on the ground; additionally, in China, the measurement integrity and actual measurement results of the capacitive sensing function have reached a domestic leading level. This is the realization of China's future space gravitational wave exploration.

Potential Antiviral Strategy Exploiting Dependence of SARS-CoV-2 Replication on Lysosome-Based Pathway.

The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as "garbage disposals" for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.

Chronic restraint stress promotes the mobilization and recruitment of myeloid-derived suppressor cells through ß-adrenergic-activated CXCL5-CXCR2-Erk signaling cascades.

Myeloid-derived suppressor cells (MDSCs) play an important role in tumor immune escape. Recent studies have shown that MDSCs contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth, as well as the mobilization of MDSCs to spleen and tumor sites from bone marrow. Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. In vitro, the treatments of MDSCs with epinephrine (EPI) and norepinephrine (NE) but not corticosterone (CORT)-treated H22 conditioned medium obviously inhibited T-cell proliferation, as well as enhanced CXCR2 expression and extracellular signal-regulated kinase (Erk) phosphorylation. In vivo, ß-adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress and inactivated CXCL5-CXCR2-Erk signaling pathway. Our findings support the crucial role of ß-adrenergic signaling cascade in the mobilization and recruitment of MDSCs under chronic restraint stress.

Salty Biofluidic Sample Clean-Up and Preconcentration with a Paper-Based Ion Concentration Polarization Interface.

Charged species from complex media could be separated and enriched taking advantage of ion concentration polarization (ICP) effect; thus, ICP can be used for sample purification and improvement of detection sensitivity. In this paper, a novel and reliable ICP interface was established on a paper-based analytical device (PAD) by using ion exchange membrane, and electrokinetic stacking of target analytes from salty media was successfully demonstrated. Steady ICP effect was well observed in aqueous solution with up to 400 mM NaCl as shown by a fluorescent probe, which makes it possible to directly process salty physiological samples such as blood and urine with this type of PAD. Application of this method was demonstrated by direct online stacking of total protein from urine samples and image-based colorimetric detection by a smartphone camera. The linear response was in the range of 50-350 mg/L (R2 = 0.99), with recovery rate in the range of 94.8-107.6% and relative standard deviation below 7.1%. The obtained results were consistent with that of the clinical method. As an off-line sample pretreatment method, the feasibility for rapid tandem mass spectrometry detection of amino acids from serum samples was also investigated, and promising results were obtained. This PAD method is of low cost, easy to operate, and reliable. As a disposable PAD, it is useful not only for sensitive point-of-care testing but also for direct purification and concentration of complex and highly conductive physiological samples for fast and accurate detection with advanced analytical instruments.

[Comparative study on anti-depressant effect of Zhizichi Decoction and its solid fermentation product on CUMS rats].

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.

Inlet Effect Caused by Multichannel Structure for Molecular Electronic Transducer Based on a Turbulent-Laminar Flow Model.

The actual fluid form of an electrolyte in a molecular electronic converter is an important factor that causes a decrease in the accuracy of a molecular electronic transducer (MET) liquid motion sensor. To study the actual fluid morphology of an inertial electrolyte in molecular electron transducers, an inlet effect is defined according to the fluid morphology of turbulent-laminar flow, and a numerical simulation model of turbulent-laminar flow is proposed. Based on the turbulent-laminar flow model, this paper studies the variation of the inlet effect intensity when the thickness of the outermost insulating layer is 50 µm and 100 µm, respectively. Meanwhile, the changes of the inlet effect intensity and the error rate of central axial velocity field are also analyzed when the input signal intensity is different. Through the numerical experiment, it verifies that the thickness of the outermost insulating layer and the amplitude of the input signal are two important factors which can affect the inlet effect intensity and also the accuracy of the MET. Therefore, this study can provide a theoretical basis for the quantitative study on the performance optimization of a MET liquid sensor.

Characterization of Ethyl Acetate and Trichloromethane Extracts from Phoebe zhennan Wood Residues and Application on the Preparation of UV Shielding Films.

In this work, ethyl acetate (EA) and trichloromethane (TR) extracts were extracted from Phoebe zhennan wood residues and the extracts were then applied to the preparation of UV shielding films (UV-SF). The results revealed that substances including olefins, phenols and alcohols were found in both EA and TR extracts, accounting for about 45% of all the detected substances. The two extracts had similar thermal stability and both had strong UV shielding ability. When the relative percentage of the extract is 1 wt% in solution, the extract solution almost blocked 100% of the UV-B (280-315 nm), and UV-A (315-400 nm). Two kinds of UV-SF were successfully prepared by adding the two extracts into polylactic acid (PLA) matrix. The UV-SF with the addition of 24 wt% of the extractive blocked 100% of the UV-B (280-315 nm) and more than 80% of the UV-A (315-400 nm). Moreover, the UV shielding performance of the UV-SF was still stable even after strong UV irradiation. Though the addition of extracts could somewhat decrease the thermal stability of the film, its effect on the end-use of the film was ignorable. EA extracts had less effect on the tensile properties of the films than TR extracts as the content of the extract reached 18%. The results of this study could provide fundamental information on the potential utilization of the extracts from Phoebe zhennan wood residues on the preparation of biobased UV shielding materials.

Analyzing functional status and its correlates in Chinese centenarians: A cross-sectional study.

Factors affecting independence in basic and instrumental activities of daily living have been established in older adults, but not centenarians. The purpose of this study was to examine the state and factors affecting activities of daily living independence in centenarians who resided in Guangxi Province, China. A cross-sectional design was used. Activities of daily living, physical activity, mobility, and physical performance were measured by the Population Study of ChINese Elderly study instruments, and demographics and cognition were assessed. Of the 228 participants, 57% were independent in basic activities of daily living and 5.7% in instrumental activities of daily living. Stepwise regression showed physical activity, cognition, calf circumference, and self-reported health were associated with basic activities of daily living. Physical activity, mobility, cognition, and physical performance were correlated with instrumental activities of daily living. In conclusion, the Chinese centenarians showed impaired instrumental activities of daily living but mostly maintained basic functioning. Physical activity and cognition were associated with activities of daily living independence.

Small auxin upregulated RNA (SAUR) gene family in maize: identification, evolution, and its phylogenetic comparison with Arabidopsis, rice, and sorghum.

Small auxin-up RNAs (SAURs) are the early auxin-responsive genes represented by a large multigene family in plants. Here, we identified 79 SAUR gene family members from maize (Zea mays subsp. mays) by a reiterative database search and manual annotation. Phylogenetic analysis indicated that the SAUR proteins from Arabidopsis, rice, sorghum, and maize had divided into 16 groups. These genes were non-randomly distributed across the maize chromosomes, and segmental duplication and tandem duplication contributed to the expansion of the maize SAUR gene family. Synteny analysis established orthology relationships and functional linkages between SAUR genes in maize and sorghum genomes. We also found that the auxin-responsive elements were conserved in the upstream sequences of maize SAUR members. Selection analyses identified some significant site-specific constraints acted on most SAUR paralogs. Expression profiles based on microarray data have provided insights into the possible functional divergence among members of the SAUR gene family. Quantitative real-time PCR analysis indicated that some of the 10 randomly selected ZmSAUR genes could be induced at least in maize shoot or root tissue tested. The results reveal a comprehensive overview of the maize SAUR gene family and may pave the way for deciphering their function during plant development.

Intracoronary microcatheter indwelling for continuous pumping of low-dose thrombolytic drugs: A new approach to reperfusion in acute myocardial infarction.

Reperfusion therapy of acute myocardial infarction (AMI) refers to physical or chemical recanalization and restoration of blood flow to an occluded coronary artery, and current techniques for reperfusion therapy include intravenous thrombolysis, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The number of patients receiving emergency CABG in the real world is decreasing due to the disadvantages of CABG and the improvement in PCI procedures. Thrombolytic therapy has some disadvantages such as low recanalization rate, high risk of reocclusion and bleeding, and short time window. On the other hand, intracoronary interventional therapy may meet the requirements of "early, complete and persistent" patency of coronary arteries at different time points. However, in the emergency PCI, although thrombus aspiration via a catheter or balloon dilation is performed, residual thrombus with heavy or low TIMI (thrombolysis in myocardial infarction) myocardial perfusion grading is still observed in some patients, suggesting disordered microcirculation. Currently, the treatment of microcirculatory disturbance in emergency PCI mainly employed injection of tirofiban, adenosine, thrombolytic agent or other drugs into the local area via a microcatheter in a short time, all of which can significantly reduce the thrombus load and improve TIMI perfusion. Herein, we report that a microcatheter was indwelled in the coronary artery for continuous pumping of low-dose thrombolytic drugs as reperfusion therapy in 12 patients with acute and subacute MI.

Genetic associations and potential mediators between psychiatric disorders and irritable bowel syndrome: a Mendelian randomization study with mediation analysis.

Objective: Potential causal associations between psychiatric disorders and irritable bowel syndrome have been demonstrated in observational studies; however, these studies are susceptible to underlying confounding and reverse causation biases. We aimed to assess the causal effects of psychiatric disorders on irritable bowel syndrome (IBS) and the potential mediators from a genetic perspective by conducting a Mendelian randomization (MR) study with mediation analysis. Method: Genetic instruments associated with psychiatric disorders, potential mediators, and IBS were obtained from large-scale genome-wide association studies (GWAS). Three MR methods - the inverse-variance weighted (IVW) method, MR-Egger method, and weighted median method, were used to investigate causal association estimates. Heterogeneity among different genetic instrumental variables (IVs) was assessed using Q tests. Additionally, the MR-PRESSO and MR-Pleiotropy methods were used to verify horizontal pleiotropy and detect outliers that might bias the results, which were removed from further analysis. Consequently, we used MR mediation analysis to investigate potential mediators in the causal associations between psychiatric disorders and IBS. Results: MR provided evidence of the causal effects of genetically predicted broad depression, major depressive disorder (MDD), anxiety disorder, post-traumatic stress disorder (PTSD), and schizophrenia on IBS. The results of MR mediation analysis demonstrated that the reduction in acetate levels mediated 12.6% of the effects of broad depression on IBS; insomnia mediated 16.00%, 16.20%, and 27.14% of the effects of broad depression, MDD, and PTSD on IBS, respectively; and the increase in blood ß-hydroxybutyrate levels mediated 50.76% of the effects of schizophrenia on IBS. Conclusion: Our study confirmed the brain-gut axis involvement and potential modulators in the pathophysiology of psychiatric disorder-induced IBS from a genetic perspective, and suggests potential therapeutic targets for the disrupted brain-gut axis.