Multi-source domain adaptive network based on local kernelized higher-order moment matching for rotating machinery fault diagnosis.

Unsupervised domain adaptation has been extensively researched in rotating-machinery cross-domain fault diagnosis. A multi-source domain adaptive network based on local kernelized higher-order moment matching is constructed in this research for rotating-machinery fault diagnosis. Firstly, a multi-branch network is designed to map each source-target pair to a domain-specific shared space and to extract domain-invariant features using domain adversarial thought. Then, a local kernelized higher-order moment matching algorithm is proposed to perform fine-grained matching in shared category subspace. Finally, a feature fusion strategy based on the local domain distribution deviation is applied to synthesize the output features of multiple classifiers to obtain diagnostic results. The experimental validation of two-branch and three-branch networks on two public datasets is carried out and average diagnostic accuracies both exceed 99%. The results demonstrate the effectiveness and superiority of the approach.

Probiotics Pediococcus acidilactici GR-1 promotes the functional strains and remodels gut microbiota to reduce the Cr(VI) toxicity in a dual-chamber simulated intestinal system.

Numerous animal studies have demonstrated the toxicity of hexavalent chromium [Cr(VI)] and the bioremediative effects of probiotics on the composition and functions of gut microbiota. Since the precise mechanisms of Cr(VI) detoxification and its interactions with human gut microbiota were unknown, a novel dual-chamber simulated intestinal (DCSI) system was developed to maintain both the stability of the simulated system and the composition of the gut microbiota. Probiotic GR-1 was found to regulate intestinal gut microbiota, thereby reducing the toxicity of Cr(VI) within the DCSI system. The results indicate that Cr(VI) levels were reduced from 2.260 ± 0.2438 µg/g to 1.7086 ± 0.1950 µg/g in the gut microbiota cell pellet, and Cr(VI) permeability decreased from 0.5521 ± 0.1132 µg/L to 0.3681 ± 0.0178 µg/L after 48 h in simulated gut fluid. Additionally, the removal rate of 1,1-Diphenyl-2-picrylhydrazyl (DPPH), reducibility (Vitamin C), and total antioxidant capacity (T-AOC) increased by 50.83%, 31.70%, and 27.56%, respectively, following probiotic treatment. The increase in antioxidant capacity correlated with total Cr removal (P < 0.05, r from -0.80 to 0.73). 16S rRNA sequencing analysis showed that gut microbiota composition was reshaped by the addition of probiotics, which regulated the recovery of the functional gut microbiota to normal levels, rather than restoring the entire gut microbiota composition for community function. Thus, this study not only demonstrates the feasibility and stability of culturing gut microbiota but also offers a new biotechnological approach to synthesizing functional communities with functional strains for environmental risk management.

Association with pre-pregnancy BMI on early pregnancy loss in infertility patients in first HRT-FET cycles: A retrospective cohort study.

OBJECTIVE: To investigate the association between pre-pregnancy body mass index (BMI) and the early pregnancy loss rate in patients in first hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) cycles and find the threshold. METHODS: A retrospective cohort study was conducted using a total of 14030 HRT-FET cycles at the Reproductive Center from January 2017 to December 2021. The association of pre-pregnancy BMI on early pregnancy loss rate in patients in HRT-FET cycles was assessed by performing univariate analysis, multivariable logistic regression, curve fitting and threshold effect analysis. RESULTS: There were 2076 cycles of early pregnancy loss, and the pregnancy loss rate was 14.80%. After adjusting for confounding factors, the early pregnancy loss rate of the obese group was significantly higher than that of the normal weight group (P < 0.05). The threshold effect analysis showed that as the pre-pregnancy BMI ranged from 21.2 to 25.8 kg/m2, the early pregnancy loss rate came to the plateau phase at the low level. In addition, when the BMI was ≥ 25.8 kg/m2, the early pregnancy loss rate increased by 3% (aOR = 1.03, P = 0.01) with each 1 kg/m2 increment of BMI. CONCLUSION: The early pregnancy loss rate might achieve a low level when the pre-pregnancy BMI was within the range of 21.2- 25.8 kg/m2. The early pregnancy loss rate would increase when pre-pregnancy BMI is more than 25.8 kg/m2. For patients in HRT-FET cycles, adjusting their pre-pregnancy BMI to the optimal level by following a healthy diet and daily exercise may help to reduce the early pregnancy loss.

Spatiotemporal heterogeneity in meteorological and hydrological drought patterns and propagations influenced by climatic variability, LULC change, and human regulations.

This study aims to quantify meteorological-hydrological drought propagations and examine the potential impacts by climatic variability, LULC change (LULC), and human regulations. An integrated observation-modeling framework quantifies drought propagation intervals and assesses mechanisms influencing hydrological droughts. Meteorological droughts are characterized using the Standardized Precipitation Evapotranspiration Index (SPEI), and hydrological droughts are assessed through the Standardized Streamflow Index (SSI) across diverse climatic zones. Cross-correlation analysis between SPEI and SSI time series identifies the lag time associated with the highest correlation as the drought propagation interval. Mechanisms are investigated via a coupled empirical-process modeling framework incorporating the Soil and Water Assessment Tool (SWAT). Discrepancies between simulated and observed SSI time series help quantify the extent of human regulation impacts on hydrological drought characteristics and propagation. The Yellow River Basin (YRB), divided into six subzones based on climate characteristics, is selected as the case study. Key findings include: (1) Meteorological droughts were extremely severe across most YRB during the 1990s, while the 2000s showed some mitigation primarily due to precipitation increases. (2) Hydrological droughts and propagation times from meteorology to hydrology demonstrated substantial spatiotemporal variability. In general, summer propagation times were shorter than other seasons. (3) Propagation times were shorter in arid regions with cropland or built-up land cover versus grassland and woodland, while the reverse held for humid regions. (4) Human regulations prolonged propagation times, likely due to reservoir regulations designed to overcome water deficits. While the YRB is the focus of this paper, the methodologies and findings are applicable to other regions worldwide to enhance drought forecasting and water resource management. In various hydrological and climatic contexts worldwide.

Sleep-phasic heart rate variability predicts stress severity: Building a machine learning-based stress prediction model.

We propose a novel approach for predicting stress severity by measuring sleep phasic heart rate variability (HRV) using a smart device. This device can potentially be applied for stress self-screening in large populations. Using a Holter electrocardiogram (ECG) and a Huawei smart device, we conducted 24-h dual recordings of 159 medical workers working regular shifts. Based on photoplethysmography (PPG) and accelerometer signals acquired by the Huawei smart device, we sorted episodes of cyclic alternating pattern (CAP; unstable sleep), non-cyclic alternating pattern (NCAP; stable sleep), wakefulness, and rapid eye movement (REM) sleep based on cardiopulmonary coupling (CPC) algorithms. We further calculated the HRV indices during NCAP, CAP and REM sleep episodes using both the Holter ECG and smart-device PPG signals. We later developed a machine learning model to predict stress severity based only on the smart device data obtained from the participants along with a clinical evaluation of emotion and stress conditions. Sleep phasic HRV indices predict individual stress severity with better performance in CAP or REM sleep than in NCAP. Using the smart device data only, the optimal machine learning-based stress prediction model exhibited accuracy of 80.3 %, sensitivity 87.2 %, and 63.9 % for specificity. Sleep phasic heart rate variability can be accurately evaluated using a smart device and subsequently can be used for stress predication.

Association of intra-shift nap duration with heart rate variability in medical night shift workers.

Napping during night shifts effectively reduces disease risk and improves work performance, but few studies have investigated the association between napping and physiological changes, particularly in off-duty daily lives. Changes in the autonomic nervous system precede diseases like cardiovascular disease, diabetes, and obesity. Heart rate variability is a good indicator of autonomic nervous system. This study aimed to investigate the link between night shift nap durations and heart rate variability indices in the daily lives of medical workers. As indicators of chronic and long-term alterations, the circadian patterns of heart rate variability indices were evaluated. We recruited 146 medical workers with regular night shifts and divided them into four groups based on their self-reported nap durations. Heart rate variability circadian parameters (midline-estimating statistic of rhythm, amplitude, and acrophase) were obtained by obtaining 24-h electrocardiogram on a day without night shifts, plotting the data of the heart rate variability indices as a function of time, and fitting them into periodic cosine curves. Using clinical scales, depression, anxiety, stress, fatigue, and sleepiness were assessed. Linear regression analysis revealed a positive relationship between 61-120-min naps and 24-h, daytime, and night-time heart rate variability indices, and the parasympathetic activity oscillation amplitude (indexed by high-frequency power, the square root of the mean of the sum of squares of differences between adjacent normal intervals, standard deviation of short-term R-R-interval variability) within one circadian cycle. This study indicated that napping for 61-120 min during night shifts could benefit medical workers' health, providing physiological evidence to promote nap management.

Cerebral protective effect of in situ and remote ischemic postconditioning on ischemic stroke rat via the TGFß1-Smad2/3 signaling pathway.

Patients with acute ischemic stroke achieve inadequate benefit due to the short therapeutic window for thrombolysis and the risk of ischemia/reperfusion (IR) injury. Ischemic postconditioning induces endogenous cerebral protection for acute ischemic stroke, although the protective mechanisms associated with ischemic postconditioning haven't been well clarified. In present study, the rat models of ischemic cerebral stroke with in situ and remote ischemic postconditioning (ISP and RIP) were established successfully. The Zea Longa and the modified neurological severity scoring (mNSS) were carried out to evaluate neurological function in the rats, while the open field test was explored to estimate their autonomic athletic ability. The 2,3,5-riphenyltetrazolium chloride (TTC) staining method was used to measure the size of the infarcts. TUNEL and Nissl's staining were used to detect the apoptosis rate of cells in the ischemic penumbra, with the expression of TGFß1, Smad2, and Smad3 in the ischemic penumbra and serum detected by immunohistochemical staining, qRT-PCR, Western blots, and ELISA analysis. We showed that application of both types of ischemic postconditioning had cerebral protective effects for the ischemic stroke rats, that included effective reduction in the volume of cerebral infarction, alleviation of apoptosis and inflammation in the ischemic penumbra, and promotion of recovery of neurological function. These effects included significantly enriched gene ontology (GO) terms after RIP intervention that were related to TGFß1, increased protein levels of TGFß1 and decreased levels of p-Smad2/3 and smad3 following RIP intervention. We showed that the TGFß1-Smad2/3 signaling pathway was associated with the cerebral protection of ischemic postconditioning.

Risk factors for proliferative vitreoretinopathy after retinal detachment surgery: A systematic review and meta-analysis.

BACKGROUND: To comprehensively investigate risk factors for proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched until May 22, 2023. Risk factors included demographic and disease-related risk factors. Odds ratios (ORs) and weighted mean differences (WMDs) were used as the effect sizes, and shown with 95% confidence intervals (CIs). Sensitivity analysis was conducted. The protocol was registered with PROSPERO (CRD42022378652). RESULTS: Twenty-two studies of 13,875 subjects were included in this systematic review and meta-analysis. Increased age was associated with a higher risk of postoperative PVR (pooled WMD = 3.98, 95%CI: 0.21, 7.75, P = 0.038). Smokers had a higher risk of postoperative PVR than non-smokers (pooled OR = 5.07, 95%CI: 2.21-11.61, P<0.001). Presence of preoperative PVR was associated with a greater risk of postoperative PVR (pooled OR = 22.28, 95%CI: 2.54, 195.31, P = 0.005). Presence of vitreous hemorrhage was associated with a greater risk of postoperative PVR (pooled OR = 4.12, 95%CI: 1.62, 10.50, P = 0.003). Individuals with aphakia or pseudophakia had an increased risk of postoperative PVR in contrast to those without (pooled OR = 1.41, 95%CI: 1.02, 1.95, P = 0.040). The risk of postoperative PVR was higher among patients with macula off versus those with macula on (pooled OR = 1.85, 95%CI: 1.24, 2.74, P = 0.002). Extent of RD in patients with postoperative PVR was larger than that in patients without (pooled WMD = 0.31, 95%CI: 0.02, 0.59, P = 0.036). Patients with postoperative PVR had longer duration of RD symptoms than those without (pooled WMD = 10.36, 95%CI: 2.29, 18.43, P = 0.012). CONCLUSION: Age, smoking, preoperative PVR, vitreous hemorrhage, aphakia or pseudophakia, macula off, extent of RD, and duration of RD symptoms were risk factors for postoperative PVR in patients undergoing RD surgery, which may help better identify high-risk patients, and provide timely interventions.

Research on Two-Stage Semi-Active ISD Suspension Based on Improved Fuzzy Neural Network PID Control.

To better improve the ride comfort and handling stability of vehicles, a new two-stage ISD semi-active suspension structure is designed, which consists of the three elements, including an adjustable damper, spring, and inerter. Meanwhile, a new semi-active ISD suspension control strategy is proposed based on this structure. Firstly, the fuzzy neural network's initial parameters are optimized using the grey wolf optimization algorithm. Then, the fuzzy neural network with the optimal parameters is adjusted to the PID parameters. Finally, a 1/4 2-degree-of-freedom ISD semi-active suspension model is constructed in Matlab/Simulink, and the dynamics simulation is carried out for the three schemes using PID control, fuzzy neural network PID control, and improved fuzzy neural network PID control, respectively. The results show that compared with adopting PID control and fuzzy neural network PID control strategy, the vehicle body acceleration and tire dynamic loads are significantly reduced after using the grey wolf optimized fuzzy neural network PID control strategy, which shows that the control strategy proposed in this paper can significantly improve the vehicle smoothness and the stability of the handling.

Phytoavailability of cadmium in rice amended with organic materials and lime: Effects of rhizosphere chemical changes and cadmium sequestration in iron plaque.

Excessive Cd in rice grains produced with acidic paddy soil is receiving increasingly widespread attention because it endangers human health. Applying organic materials (OM) and lime (L) is a common technique used to reduce Cd concentration in grains (CdG). Nevertheless, the mechanism by which their simultaneous application affects the Cd phytoavailability in soilrice systems remains ambiguous. In the current study, we adopted a rhizobag pot culture test to explore the influences of single application of OM [rice straw (RS), milk vetch (MV)], L, and their co-utilization on Cd phytoavailability and the associated mechanisms. The results showed that the application of RS, MV, L, L + RS (LRS), and L + MV (LMV) significantly decreased CdG by 26.9%, 38.2%, 48.6%, 50.0%, and 53.0%, respectively. Fe plaque (IP) formation was not affected by these treatments; however, Cd sequestration in IP (CdIP) was significantly reduced. CdIP was significantly reduced by 18.3%, 23.6%, 43.8%, 33.1%, and 41.4%, after RS, MV, L, LRS, and LMV treatments, respectively. Additionally, available Cd concentrations in rhizospheric soil (RHS) were significantly reduced by 11.5%, 14.8%, 15.1%, and 18.4%, after MV, L, LRS, and LMV treatments, respectively. Cd availability in RHS was significantly influenced by pH, dissolved organic carbon concentration, and Zn, Fe, and Mn availability. The results of the structure equation mode showed that CdG was mainly affected by CdIP, followed by Cd availability and the pH of RHS. In conclusion, the reduction of CdG by OM, L, and their co-utilization was the results of their combined effects of reducing Cd availability in RHS, CdIP, and Cd uptake by the roots. This study emphasizes that the reduction of CdG is a result of the dual effects of reducing Cd availability in RHS and CdIP after amendments application. L application alone or in conjunction with OM is an efficient practice to reduce CdG in acidic Cd-contaminated paddy fields.

Mixed reality drills of indoor earthquake safety considering seismic damage of nonstructural components.

The damaged indoor nonstructural components in the earthquake often cause casualties. To improve the indoor earthquake safety capacity of occupants, a mixed reality (MR) drill method for indoor earthquake safety considering seismic damage of nonstructural components is proposed. First, an MR device, HoloLens, is used to capture indoor point clouds, and the indoor three-dimensional scene is reconstructed using point clouds. Subsequently, the seismic motion models of indoor components are established, so that the indoor nonstructural seismic damage scene is constructed using the physics engine and displayed using HoloLens. Finally, a guidance algorithm for a safe zone was designed for the drills. Taking a typical office as an example, an indoor earthquake safety drill was performed. The drill results show that the proposed MR method can increase the average efficiency of moving to a safe zone by 43.1%. Therefore, the outcome of this study can effectively improve the earthquake safety ability of occupants, thereby reducing casualties.

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy.

Objective: The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients. Methods: A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves. Results: There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08-0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24-0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival. Conclusion: MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.

Berberine and aspirin prevent traumatic heterotopic ossification by inhibition of BMP signalling pathway and osteogenic differentiation.

Heterotopic ossification (HO) is a pathological process that often occurs in soft tissues following severe trauma. There is no effective therapy for HO. The BMP signalling pathway plays an essential role in the pathogenesis of HO. Our previous study showed that AMPK negatively regulates the BMP signalling pathway and osteogenic differentiation. The present study aims to study the effect of two AMPK activators berberine and aspirin on osteogenic differentiation and HO induced by traumatic injury. The effects of two AMPK activators, berberine and aspirin, on BMP signalling and osteogenic differentiation were measured by western blot, ALP and Alizarin red S staining in C3H10T1/2 cells. A mouse model with Achilles tenotomy was employed to assess the effects of berberine and aspirin on HO using µCT and histological analysis. First, our study showed that berberine and aspirin inhibited phosphorylation of Smad1/5 induced by BMP6 and the inhibition was attributed to the down-regulation of ALK2 expression. Second, the combination of berberine and aspirin yielded more potent effects on BMP signalling. Third, we further found that there was an additive effect of berberine and aspirin combination on osteogenic differentiation. Finally, we found that berberine and aspirin blocked trauma-induced ectopic bone formation in mice, which may be through suppression of phosphorylation of Smad1/5 in injured tissues. Collectively, these findings indicate that berberine and aspirin inhibit osteogenic differentiation in C3H10T1/2 cells and traumatic HO in mice, possibly through the down-regulation of the BMP signalling pathway. Our study sheds a light on prevention and treatment of traumatic HO using AMPK pharmacological activators berberine and aspirin.

Study on Aging Mechanism and High-Temperature Rheological Properties of Low-Grade Hard Asphalt.

In order to investigate the potential application of low-grade hard asphalt in high-temperature and high-altitude areas, various tests were conducted to analyze the performance and high-temperature rheological properties of 30#, 50#, and 70# matrix asphalt under thermo-oxidative aging and ultraviolet aging. The tests utilized for analysis included the examination of basic asphalt properties, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), gel permeation chromatography (GPC), dynamic shear rheology (DSR), and multi-stress creep recovery (MSCR). The results indicate a progressive decrease in asphalt performance with increasing aging time. Prolonged exposure to thermal oxygen aging and ultraviolet irradiation significantly diminishes the plasticity of asphalt. The carbonyl index and sulfoxide index of asphalt increase after thermal oxygen aging and ultraviolet aging. Notably, 30# asphalt demonstrates greater resistance to aging compared to 50# and 70# asphalt under long-term high ultraviolet radiation. The LMS% of 30#, 50#, and 70# asphalt increases by 14%, 15%, and 16%, respectively. Following photothermal oxidative aging, a larger proportion of lighter components in the asphalt transforms into resins and asphaltenes. The high-temperature rheological properties of the three types of asphalt rank as 30# > 50# > 70#, while within the same type of asphalt, the high-temperature rheological properties rank as PAV > UV3 > UV2 > UV1 > RTFOT > virgin. Elevating temperature, stress level, and stress duration negatively impact the high-temperature stability of asphalt. In general, low-grade asphalt demonstrates superior anti-aging ability and high-temperature rheological properties during the aging process.

Crack Detection of Bridge Concrete Components Based on Large-Scene Images Using an Unmanned Aerial Vehicle.

The current method of crack detection in bridges using unmanned aerial vehicles (UAVs) relies heavily on acquiring local images of bridge concrete components, making image acquisition inefficient. To address this, we propose a crack detection method that utilizes large-scene images acquired by a UAV. First, our approach involves designing a UAV-based scheme for acquiring large-scene images of bridges, followed by processing these images using a background denoising algorithm. Subsequently, we use a maximum crack width calculation algorithm that is based on the region of interest and the maximum inscribed circle. Finally, we applied the method to a typical reinforced concrete bridge. The results show that the large-scene images are only 1/9-1/22 of the local images for this bridge, which significantly improves detection efficiency. Moreover, the accuracy of the crack detection can reach up to 93.4%.

YOLOv5s-Fog: An Improved Model Based on YOLOv5s for Object Detection in Foggy Weather Scenarios.

In foggy weather scenarios, the scattering and absorption of light by water droplets and particulate matter cause object features in images to become blurred or lost, presenting a significant challenge for target detection in autonomous driving vehicles. To address this issue, this study proposes a foggy weather detection method based on the YOLOv5s framework, named YOLOv5s-Fog. The model enhances the feature extraction and expression capabilities of YOLOv5s by introducing a novel target detection layer called SwinFocus. Additionally, the decoupled head is incorporated into the model, and the conventional non-maximum suppression method is replaced with Soft-NMS. The experimental results demonstrate that these improvements effectively enhance the detection performance for blurry objects and small targets in foggy weather conditions. Compared to the baseline model, YOLOv5s, YOLOv5s-Fog achieves a 5.4% increase in mAP on the RTTS dataset, reaching 73.4%. This method provides technical support for rapid and accurate target detection in adverse weather conditions, such as foggy weather, for autonomous driving vehicles.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Screening and Bioinformatics Analysis of MicroRNA Biomarkers in Triple-Negative Breast Cancer.

OBJECTIVE: To identify and evaluate the bioinformatics of microRNA (miRNA) biomarkers in triple-negative breast cancer. METHODS: The MDA-MB-231 cell line with stable and low expression of c-Myc was created, and the expression patterns of messenger RNA (mRNA) and miRNA were investigated by cluster analysis. The genes regulated by c-Myc were then screened by transcriptome sequencing and miRNA sequencing. The negative binomial distribution of the DESeq software package was used to test for and determine the differential expression of genes. RESULTS: In the c-Myc deletion group, 276 differently expressed mRNAs were screened out by transcriptome sequencing, of which 152 mRNAs were considerably upregulated and 124 were significantly downregulated in comparison to the control group. One-hundred-seventeen (117) differentially expressed miRNAs were found using miRNA sequencing, of which 47 showed a substantial upregulation and 70 a significant downregulation. According to the Miranda algorithm, 1803 mRNAs could be targeted by 117 differently expressed miRNAs. Comparing the two sets of data, a total of 5 miRNAs were differentially expressed after targeted binding with 21 mRNAs, which were subjected to GO and KEGG enrichment analysis. The genes regulated by c-Myc were mainly enriched in signaling pathways such as extracellular matrix receptors and Hippo. CONCLUSION: Twenty-one target genes and five differential miRNAs in the mRNA-c-Myc-miRNA regulatory network are potential therapeutic targets for triple-negative breast cancer.

Inhibition of NF-κB Signaling-Mediated Crosstalk Between Macrophages and Preosteoblasts by Metformin Alleviates Trauma-Induced Heterotopic Ossification.

Heterotopic ossification (HO) is a pathological condition that occurs in soft tissues following severe trauma. The exact pathogenesis of HO remains unclear. Studies have shown that inflammation predisposes patients to the development of HO and triggers ectopic bone formation. Macrophages are crucial mediators of inflammation and are involved in HO development. The present study investigated the inhibitory effect and underlying mechanism of metformin on macrophage infiltration and traumatic HO in mice. Our results found that abundant levels of macrophages were recruited to the injury site during early HO progression and that early administration of metformin prevented traumatic HO in mice. Furthermore, we found that metformin attenuated macrophage infiltration and the NF-κB signaling pathway in injured tissue. The monocyte-to-macrophage transition in vitro was suppressed by metformin and this event was mediated by AMPK. Finally, we showed that inflammatory mediator's regulation by macrophages targeted preosteoblasts, leading to elevated BMP signaling, and osteogenic differentiation and driving HO formation, and this effect was blocked after the activation of AMPK in macrophages. Collectively, our study suggests that metformin prevents traumatic HO by inhibiting of NF-κB signaling in macrophages and subsequently attenuating BMP signaling and osteogenic differentiation in preosteoblasts. Therefore, metformin may serve as a therapeutic drug for traumatic HO by targeting NF-κB signaling in macrophages.

Insight into mixed chlorine/chloramines conversion and associated water quality variability in drinking water distribution systems.

Mixed chlorine/chloramines are common in drinking water distribution systems (DWDSs); however, their transformation and impact on chemical and microbial characteristics are not well understood. We systematically investigated water quality parameters associated with mixed chlorine/chloramine species conversion in 192 samples (including raw, finished, and tap water) collected throughout the year in a city in East China. Various chlorine/chloramine species (free chlorine, monochloramine [NH2Cl], dichloramine [NHCl2], and organic chloramines [OC]) were detected in both chlorinated and chloraminated DWDSs. NHCl2 + OC increased with transport distance along the pipeline network. The maximum proportion of NHCl2 + OC in over total chlorine in tap water reached 66 % and 38 % from chlorinated and chloraminated DWDSs, respectively. Both free chlorine and NH2Cl showed a rapid decay in the water pipe systems, but NHCl2 and OC were more persistent. Correlations between chlorine/chloramine species and physicochemical parameters were established. Models for predicting the sum of chloroform/TCM, bromodichloromethane/BDCM, chlorodibromomethane/CBDM, and bromoform/TBM (THM4) (R2 = 0.56) and haloacetic acids (HAAs) (R2 = 0.65) exhibited greater accuracy based on machine learning tuned with chlorine/chloramine species, particularly NHCl2 + OC. The predominant bacterial communities in mixed chlorine/chloramine systems were those resistant to chlorine or chloramine such as proteobacteria. NH2Cl was the most significant explanatory factor (28.1 %) for the variation in microbial community assemblage in chloraminated DWDSs. Although residual free chlorine and NHCl2 + OC, accounted for a smaller proportion of chlorine species in chloraminated DWDSs, they played an essential role (12.4 % and 9.1 %, respectively) in the microbial community structure.