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Abstract Due to the cancer therapy-related cardiovascular toxicity, heart failure following cancer therapy has a significant mortality rate. Gene-targeted therapy promotes the re-entry of existing cardiomyocytes into the cell cycle to achieve myocardial regeneration, which is a promising strategy for preventing and treating heart failure after myocardial infarction. Circular RNAs (circRNAs) are considered as potential targets for myocardial regeneration due to their strong stability, resistance to degradation, and potential role in heart development and cardiovascular diseases. By comparing the myocardial tissue of mice in the sham operation group and the Doxorubicin therapy group (DOX), we observed a significant decrease in Cirsorbs expression in the DOX group. Cirsorbs was predominantly localized in cardiomyocytes and exhibited high conservation. Subsequent investigations revealed that Cirsorbs could promote myocardial proliferation and inhibit myocardial apoptosis. Mechanistic studies further demonstrated that Cirsorbs could bind to miR99 and reduce its expression level. Meanwhile, miR99 was found to bind to GATA4 mRNA and decrease its expression level. The binding of Cirsorbs to miR99 alleviated the repression of miR99, thereby enhancing GATA4 expression and the transcription of downstream cyclin A2 and cyclin E1. This, in turn, increased cardiomyocyte proliferation and reduced apoptosis. In conclusion, Cirsorbs holds promise as an effective target for myocardial regeneration in reducing cancer therapy-related cardiovascular toxicity.

Summary: Background: Vascular dysfunction is closely associated with the progression of Alzheimer's disease (AD). A critical research gap exists that no studies have explored the in vivo temporal changes of cerebrovascular alterations with AD progression in mouse models, encompassing both structure and flow dynamics at micron-scale resolution across the early, middle, and late stages of the disease. Methods: In this study, ultrasound localisation microscopy (ULM) was applied to image the cerebrovascular alterations of the transgenic female 5×FAD mouse model across different stages of disease progression: early (4 months), moderate (7 months), and late (12 months). Age-matched non-transgenic (non-Tg) littermates were used as controls. Immunohistology examinations were performed to evaluate the influence of disease progression on the β-amyloid (Aβ) load and microvascular alterations, including morphological changes and the blood–brain barrier (BBB) leakage. Findings: Our findings revealed a significant decline in both vascular density and flow velocity in the retrosplenial cortex of 5×FAD mice at an early stage, which subsequently became more pronounced in the visual cortex and hippocampus as the disease progressed. Additionally, we observed a reduction in vascular length preceding diminished flow velocities in cortical penetrating arterioles during the early stages. The quantification of vascular metrics derived from ULM imaging showed significant correlations with those obtained from vascular histological images. Immunofluorescence staining identified early vascular abnormalities in the retrosplenial cortex. As the disease advanced, there was an exacerbation of Aβ accumulation and BBB disruption in a regionally variable manner. The vascular changes observed through ULM imaging exhibited a negative correlation with amyloid load and were associated with the compromise of the BBB integrity. Interpretation: Through high-resolution, in vivo imaging of cerebrovasculature, this study reveals significant spatiotemporal dysfunction in cerebrovascular dynamics accompanying disease progression in a mouse model of AD, enhancing our understanding of its pathophysiology. Funding: This study is supported by grants from National Key Research and Development Program of China (2020YFA0908800), National Natural Science Foundation of China (12074269, 82272014, 82327804, 62071310), Shenzhen Basic Science Research (20220808185138001, JCYJ20220818095612027, JCYJ20210324093006017), STI 2030-Major Projects (2021ZD0200500) and Guangdong Natural Science Foundation (2024A1515012591, 2024A1515011342).

In modern society, the improvement of women’s education level has become one of the important indicators of national development and social progress. Although there are many useful explorations on the relationship between education and subjective well-being, the research on women’s years of education and subjective well-being is very limited. The article focuses on women’s years of education to determine whether and how to affect subjective well-being. This study is based on the China general social survey in 2021. The ordered Logit model was used to analyze the impact of women’s years of education on subjective well-being, and a binary coupling coordination model was constructed to test the above two variables. The results show that the longer the education years of women, the stronger the subjective well-being. The benchmark regression results show that women’s years of education have positive and negative effects on subjective well-being through economic status, physical and mental health, ecological environment, social cognition and personal cognition. The analysis of coupling coordination degree shows that the coupling between the years of education and subjective well-being of women in coastal areas and economically developed areas is the strongest, and the subjective well-being is better realized by increasing the years of education. Based on the above research results, this paper provides some practical suggestions for improving women’s subjective well-being, and provides some valuable references for women to effectively balance husband-wife relationship, family relationship and work relationship, improve women’s years of education and better obtain happiness.

Abstract Background Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population. Methods We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs. Results In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD. Conclusion There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.

Objectives: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6.Methods: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy.Results: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/μL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/μL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow.Conclusions: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.

Objectives To evaluate changes in health outcomes between years 2 and 3 after discharge following COVID-19 and to identify risk factors for poor health 3-year post-discharge.Design This is a multicentre observational cohort study.Setting This study was conducted in two centres from Wuhan, China.Participants Eligibility screening has been performed in 3988 discharged laboratory-confirmed adult COVID-19 patients. Exclusion criteria were refusal to participate, inability to contact and death before follow-up. The WHO COVID-19 guidelines on defining disease severity were adopted.Results 1594 patients participated in the 1-year, 2-year and 3-year follow-ups, including 796 (49.9%) male patients, and 422 (26.5%) patients were classified in the severe disease group. 3 years after discharge, 182 (11.4%) patients still complained of at least one symptom. The most common symptoms were fatigue, myalgia, chest tightness, cough, anxiety, shortness of breath and expectoration. Fatigue or myalgia, the most common symptom cluster, frequently coexisted with chest symptoms and anxiety. Symptom persistence between years 2 and 3 was reported in 70 patients (4.4%) for which intensive care unit (ICU) admission was a risk factor (p=0.038). Of the 1586 patients who completed the chronic obstructive pulmonary disease assessment test (CAT), 97 (6.1%) scored ≥10, with older age being associated with CAT ≥10 (p=0.007).Conclusions Between years 2 and 3 after SARS-CoV-2 infection, most patients returned to an asymptomatic state, and only a few were still symptomatic. ICU admission was a risk factor for symptom persistence.

Within a growing drug discovery company, scientists acquire (either through in house synthesis or purchase) then store, retrieve, and ship solid compound samples daily between multiple locations. The efficient management and tracking of this entire process to support drug discovery is a significant challenge. This article describes a decentralized and cost-effective inventory facility that simplifies the solid compound storage and retrieval process. Standardized storage cabinets from the market are utilized, providing a cost-effective physical infrastructure. The cabinets can be distributed across storage rooms at multiple sites and arranged into spaces with a variety of dimensions, allowing the system to be retrofitted into existing facilities and scaled up easily. We can provide storage close to work areas at each location, minimizing both unnecessary movement of staff and transportation of substances. We have applied a systematic barcoding method to the compound batch identifier that correlates with its compound location. This simplifies the compound registration process as well as the process of finding and returning compounds. Additionally, a centralized electronic platform has been employed to store, update and track solid compound information, such as properties, location and quantity. Compound shipment may be initiated from different sites, and a centralized electronic platform assists the information retrieval process, ensuring each location possesses up-to-date information. The electronic platform we present streamlines the management of compound registration, location tracking, weight updates and shipment information, facilitating seamless record sharing among all stakeholders. Every step of the process can be tracked in real time by the project team. The platform can be flexibly configured to adapt to an evolving set of storage locations, with all information and processes being audited.

In the event of a fault in the AC/DC distribution network with modular multilevel converter (MMC), the current will surge and have a large amplitude, which seriously threatens the secure and reliable operation of the distribution network. In order to handle the fault, this paper presents an integrated control and protection strategy for AC/DC distribution network, which is based on the active current limiting control (ACLC) and single-terminal fault identification and protection principle. Firstly, an ACLC technique utilizing virtual reactance is introduced to reduce the rising rate of fault current by real-time monitoring of fault current slope. Then, taking into account the impact of ACLC, the characteristics and dynamic deviation value of single terminal current are analyzed, and a fast fault area identification method is designed. Through the cooperation of circuit breakers, this method achieves the goal of fast fault isolation. Finally, the simulation model of AC/DC distribution network is built in PSCAD/EMTDC, where the ACLC described in this paper can reduce the average rising rate of fault current by 38.4%. Moreover, the efficacy of the suggested plan is verified under different fault situations.

With the popularity of edge computing devices and increasing complexity of convolutional neural network (CNN) models, the need for model compression and acceleration has become increasingly urgent. As an effective model compression technique, CANDECOMP/PARAFAC (CP) decomposition relies heavily on the preset rank for its compression effectiveness. However, no direct algorithm is currently available for determining the optimal tensor rank. Therefore, a novel method for CP rank selection based on deep reinforcement learning is proposed. This method utilizes the DecG single-player game framework based on the Deep Deterministic Policy Gradient (DDPG) algorithm to achieve automation and intelligence in rank selection. In this process, a pre-trained model is introduced, which fuses and reshapes several historical tensors as network inputs. Additionally, a hybrid greedy strategy based on singular value decomposition (SVD) was designed in the exploration phase to enhance the efficiency of finding ideal rank selection results. This method can automatically determine the rank according to the weight tensor characteristics of the convolution layer and optimize the compression efficiency and performance of the model. In addition, a compression efficiency index is developed to visually demonstrate the performance of the various compression methods. Finally, on the CIFAR-10 and CIFAR-100 datasets, CP decomposition experiments are conducted on various convolutional neural network models, and the decomposed models undergo iterative fine-tuning for retraining. The experimental results show that the rank values determined by the DecG method achieve significant optimization and enhancement in the compression efficiency of the models compared to other methods, exhibiting strong robustness.

Abstract Purpose The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. Methods This case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. Results As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). Conclusion This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

The subjective well-being of Chinese college students has always been a topic of concern. Subjective well-being is an overall evaluation of the quality of life according to the standards set by individuals, which is of great significance to the development of college students. Based on the data published in the past 5 years of China’s comprehensive social survey, this study uses panel model and adversarial explanatory structure model to analyze the influencing factors of subjective well-being of Chinese college students from five dimensions: social equity attitude, parental education, use of network, social interaction and physical health. The results show that social justice attitude, parents’ education, network use, social interaction and physical health have a positive impact on the subjective well-being of Chinese college students. Among them, the use of the network and the education of parents mainly affect the social justice attitude, social interaction attitude, physical health status, and ultimately affect the subjective well-being of college students. Based on the above conclusions, this study proposes strategies to improve the subjective well-being of college students, which has certain reference and guiding significance for educators and decision makers, and has reference significance for developing countries.

Diabetic kidney disease is one of the complications of diabetes mellitus, which can eventually progress to end-stage kidney disease. The increasing prevalence of diabetic kidney disease has brought huge economic burden to society and seriously jeopardized public health. Ferroptosis is an iron-dependent, non-apoptosis-regulated form of cell death. The regulation of ferroptosis involves different molecular mechanisms and multiple cellular metabolic pathways. In recent years, ferroptosis has been proved to be closely related to the occurrence and development of diabetic kidney disease, and can interact with pathological changes such as fibrosis, inflammation, oxidative stress, and disorders of glucose and lipid metabolism, destroying the structure, form and function of the inherent cells of the kidney, and promoting the progression of the disease. Traditional Chinese medicine has a long history of treating diabetic kidney disease with remarkable curative effect. Current scholars have shown that the oral administration of traditional Chinese medicine and the external treatment of Chinese medicine can regulate GPX4, Nrf2, ACSL4, PTGS2, TFR1 and other key signaling molecules, curb ferroptosis, and prevent the progressive deterioration of diabetic kidney disease. In this paper, the mechanism of ferroptosis and diabetic kidney disease and the prevention and treatment of traditional Chinese medicine are analyzed and summarized, in order to provide new ideas and new plans for the treatment of diabetic kidney disease.

Background: Prenatal diagnosis and genetic counseling play an important role in preventing and controlling birth defects. No reports were found of prenatal diagnosis of couples carrying both the thalassemia and deafness genes. In this study, we presented the prenatal screening and diagnosis of a couple with both thalassemia and deafness genes, contributing to better genetic counseling.Case Report: A couple visited our hospital for a routine prenatal examination. As required by the policy in our region, they underwent screening and genetic diagnosis for thalassemia. Meanwhile, they did not accept the recommendation to test for spinal muscular atrophy and deafness genes. The female was confirmed to be a Hb Quong Sze (Hb QS) carrier (αQSα/αα, βN/βN), and the male had Hb H disease combined with β-thalassemia (--SEA/αCSα, βCDs41-42 (-TTCT)/βN). A prenatal diagnosis of the fetus revealed a Hb CS heterozygote. Subsequent complementary testing showed that the male was a double heterozygote of the GJB2 gene c.299_300delAT combined with c.109G>A, and Sanger sequencing confirmed that the female was a carrier of c.508_511dup in the GJB2. Fortunately, the chorionic villi results indicated that the fetus was only a carrier of deafness.Conclusion: Since both partners carried thalassemia and deafness genes, the couple required prenatal diagnosis for the respective mutations. Expanded carrier screening (ECS) is a more advanced technology that can detect multiple disease genes simultaneously.

Aeromonas hydrophila can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting A. hydrophila is urgently required. Emodin, a naturally occurring anthraquinone compound, was exploited as a photo-antimicrobial agent against A. hydrophila. At the minimum inhibitory concentration of emodin (256 mg/L) to inactivate A. hydrophilia in 30 min, an 11.32% survival rate was observed under 45 W white compact fluorescent light irradiation. In addition, the antibacterial activity under natural sunlight (0.78%) indicated its potential for practical application. Morphological observations demonstrated that the cell walls and membranes of A. hydrophila were susceptible to damage by emodin when exposed to light irradiation. More importantly, the photoinactivation of A. hydrophila was predominantly attributed to the hydroxyl radicals and superoxide radicals produced by emodin, according to the trapping experiment and electron spin resonance spectroscopy. Finally, a light-dependent reactive oxygen species punching mechanism of emodin to photoinactivate A. hydrophila was proposed. This study highlights the potential use of emodin in sunlight-mediated applications for bacterial control, thereby providing new possibilities for the use of Chinese herbal medicine in aquatic diseases prevention.

Objectives To report the hematolgocial and molecular features of a nove β-globin variant in a Chinese fimaly.Methods The proband was a 19-year-old Chinese man whose Hb analysis by HPLC for thalassemia revealed an abnormal peak. Hb analysis was performed by HPLC and CE. Gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB) were used to detect the common mutations in Chinese population. DNA sequencing was used to determine the Hb variant.Results The Hb variant and Hb A can be separated but co-elutes with Hb F by the CE method. However, the variant can be separated from Hb A0, Hb F, and Hb A2 using HPLC. DNA sequencing showed a mutation of codon 3 in the β-globin gene. His wife’s HPLC revealed a high value of Hb A2, which proved to be the Hb E using PCR-RDB.Conclusion It was the first report of the mutation, so we named it Hb Jiangnan according to the place of residence of the proband. It can be separated by HPLC but not CE. Hb Jiangnan can cause an increased level of Hb A2.

Ischemic stroke is one of the main causes of mortality and disability worldwide. However, the majority of patients are currently unable to benefit from intravenous thrombolysis or intravascular mechanical thrombectomy due to the limited treatment windows and serious complications. Silent mating type information regulation 2 homolog 1 (Sirt1), a nicotine adenine dinucleotide-dependent enzyme, has emerged as a potential therapeutic target for ischemic stroke due to its ability to maintain brain homeostasis and possess neuroprotective properties in a variety of pathological conditions for the central nervous system. Animal and clinical studies have shown that activation of Sirt1 can lessen neurological deficits and reduce the infarcted volume, offering promise for the treatment of ischemic stroke. In this review, we summarized the direct evidence and related mechanisms of Sirt1 providing neuroprotection against cerebral ischemic stroke. Firstly, we introduced the protein structure, catalytic mechanism and specific location of Sirt1 in the central nervous system. Secondly, we list the activators and inhibitors of Sirt1, which are primarily divided into three categories: natural, synthetic and physiological. Finally, we reviewed the neuroprotective effects of Sirt1 in ischemic stroke and discussed the specific mechanisms, including reducing neurological deficits by inhibiting various programmed cell death such as pyroptosis, necroptosis, ferroptosis, and cuproptosis in the acute phase, as well as enhancing neurological repair by promoting angiogenesis and neurogenesis in the later stage. Our review aims to contribute to a deeper understanding of the critical role of Sirt1 in cerebral ischemic stroke and to offer novel therapeutic strategies for this condition.

Within a growing drug discovery company, hundreds of scientists take and move reagent chemicals on a daily basis. Conveniently updating the locations of tens of thousands of chemical containers in an electronic system is a big challenge. We have an electronic inventory system, but keeping the chemical records up to date relied on scientists finding an available computer in the lab and logging into a system whenever they took or moved a chemical container, taking several minutes. It was all too easy to think that the task could be deferred until later, but the scientist may then forget all about it, leaving the database inaccurate. As a result, searching for the chemicals we need can take a frustratingly long time if they are not where they should be. We have developed an efficient and reliable system, namely ScanStation, to solve this issue. It relies on a low-cost Raspberry Pi attached to a touch screen connected with a barcode scanner. This equipment is always on and placed in strategic locations around all our labs and chemical stores. This new process is much easier. There is no need to remove gloves to log into the computer, and it is just a scan on the barcode and is done. Now when we check the database for a chemical, we get an instant answer that reliably tells us where to find it. All the time we save have a real benefit in our productivity and our scientists can focus on discovering new medicines.

Abstract Driven by the urgent need for adaptive infrared (IR) electrochromic devices, the improvement in electrochromic performance based on polyaniline (PANI) conducting polymers has become an outstanding challenge. In recent years, the acid doping strategy has been proven to increase the IR modulation ability of PANI, in particular for the Bronsted acid doping. Herein, the effects of copper ions, a Lewis acid, on the structure and electrochromic properties of polyaniline were investigated. Compared to pure polyaniline, the Cu-doped PANI porous films show better IR modulation ability. With the increasing concentration of copper ions, the Cu-doped PANI porous films exhibit a trend in volcanic patterns for the emittance variation (∆ε), depending on the number of polarons and bipolarons. The optimal IR emissivity (ε) modulation obtained on Cu-doped PANI films shows the ∆ε modulation of 0.35 and 0.3 in the wavelength range of 8–14 µm and 2.5–25 µm, superior to previously reported pure sulfuric acid-doped PANI. Furthermore, a flexible IR electrochromic device was fabricated with the present Cu-doped PANI porous films. The modulation of the emittance variation varied between 0.513 and 0.834 (∆ε = 0.32 in ranges of wavelength 8–12 µm), suggesting the great potential for applications in military camouflage and intelligent IR thermal management. We believe that the results in this work will provide a novel perspective and avenue for improving the IR modulation ability of electrochromic devices based on polyaniline conducting polymers.

Aeromonas hydrophila is a significant pathogen to freshwater farmed animals, and antibiotics are usually used to control the bacterial septicemia caused by A. hydrophila. Due to the severe situation of development and spread of antibiotic resistance, there are stricter restrictions on antibiotics used in aquaculture. To evaluate the feasibility of glycyrrhetinic acid β (GA) as an alternative therapy against bacterial infection, in this study, an A. hydrophila isolated from diseased fish is used to test the antibacterial, anti-virulence activity and therapeutic effect of GA in vitro and in vivo, respectively. Results showed that GA did not affect the growth of A. hydrophila in vitro, while it could down-regulate (p

Bacterial quorum sensing (QS) plays a crucial role in chemical communication between bacteria involving autoinducers and receptors and controls the production of virulence factors in bacteria. Therefore, reducing the concentration of signaling molecules in QS is an effective strategy for mitigating the virulence of pathogenic bacteria. In this study, we demonstrated that carvacrol at 15.625 μg/mL (1/4 MIC), a natural compound found in plants, exhibits potent inhibitory activity against QS in Chromobacterium violaceum, as evidenced by a significant reduction (62.46%) in violacein production. Based on its impressive performance, carvacrol was employed as a natural QS inhibitor to suppress the pathogenicity of Aeromonas hydrophila NJ-35. This study revealed a significant reduction (36.01%) in the concentration of N-acyl-homoserine lactones (AHLs), a QS signal molecular secreted by A. hydrophila NJ-35, after 1/4 MIC carvacrol treatment. Moreover, carvacrol was found to down-regulate the expression of ahyR/I, two key genes in the QS system, which further inhibited the QS system of A. hydrophila NJ-35. Finally, based on the above results and molecular docking, we proposed that carvacrol alleviate the pathogenicity of A. hydrophila NJ-35 through QS inhibition. These results suggest that carvacrol could serve as a potential strategy for reducing the virulence of pathogenic bacteria and minimizing the reliance on antibiotics in aquaculture.

Aeromonas hydrophila is a Gram-negative bacterium that widely exists in various aquatic environments and causes septicemia in fish and humans. Resveratrol, a natural polyterpenoid product, has potential chemo-preventive and antibacterial properties. In this study, we investigated the effect of resveratrol on A. hydrophila biofilm formation and motility. The results demonstrated that resveratrol, at sub-MIC levels, can significantly inhibit the biofilm formation of A. hydrophila, and the biofilm was decreased with increasing concentrations. The motility assay showed that resveratrol could diminish the swimming and swarming motility of A. hydrophila. Transcriptome analyses (RNA-seq) showed that A. hydrophila treated with 50 and 100 μg/mL resveratrol, respectively, presented 230 and 308 differentially expressed genes (DEGs), including 90 or 130 upregulated genes and 130 or 178 downregulated genes. Among them, genes related to flagellar, type IV pilus and chemotaxis were significantly repressed. In addition, mRNA of virulence factors OmpA, extracellular proteases, lipases and T6SS were dramatically suppressed. Further analysis revealed that the major DEGs involved in flagellar assembly and bacterial chemotaxis pathways could be regulated by cyclic-di-guanosine monophosphate (c-di-GMP)- and LysR-Type transcriptional regulator (LTTR)-dependent quorum sensing (QS) systems. Overall, our results indicate that resveratrol can inhibit A. hydrophila biofilm formation by disturbing motility and QS systems, and can be used as a promising candidate drug against motile Aeromonad septicemia.

The activation of artemisinin and its derivatives (ARTs) to generate ROS and other free radicals is mainly heme- or ferrous iron-dependent. ARTs induce ferroptosis in tumor cells, although the involvement of ferroptosis in malaria remains unclear. We found that three typical inducers of ferroptosis (erastin, RSL3 and sorafenib) could effectively mimic DHA inhibition on the growth of blood-stage parasites, which exhibited synergistic or nearly additive interactions in vitro with DHA, while the combination of DHA with ferroptosis inhibitors (deferoxamine, liproxstatin-1) had an obvious antagonistic effect. DHA, similar to ferroptosis inducers, can simultaneously induce the accumulation of ferroptosis-associated cellular labile iron and lipid peroxide. However, deferoxamine and liproxstatin-1 reduced the increase in ferrous iron and lipid peroxide caused by DHA. These results suggested that ferroptosis might be an effective way to induce cell death in parasites and could be a primary mechanism by which DHA kills parasites, with almost 50% contribution at low concentrations. These results provide a new strategy for antimalarial drug screening and clinical medication guidance.

Atmospheric ducting is an anomalous atmospheric structure that affects electromagnetic wave propagation. In the context of global warming, the navigation capacity of the Arctic is increased, and the atmospheric duct can affect communication and navigation in the Arctic. In this study, based on the European Centre for Medium-Range Weather Forecasts reanalysis data (ERA-interim), the climate characteristics and their variations of atmospheric ducts over the Arctic polar region (north of 60° N) from 1989 to 2018 were analyzed, including the occurrence frequency, spatial distribution, thickness and intensity of the atmospheric ducts. The results show that the overall frequency of atmospheric ducts in the Arctic is low, with the average frequency of all types of ducts being less than 10% throughout the year. The frequency of surface ducts is 2~3 times that of elevated ducts. More than 90% of the atmospheric ducts in the Arctic have a trapped layer with a thickness of less than 100 m, and the average thickness of surface ducts is higher than that of the elevated ducts. The intensity of the Arctic surface ducts is stronger than that of the elevated ducts, with an average intensity of 2.1 M (±2.3 M) to 4.5 M (±4.5 M) for the surface ducts and 1.7 M (±2 M) to 2.5 M (±2.9 M) for the elevated ducts. There is a positive correlation between the ducts’ trapped layer thickness and duct intensity. The variation in atmospheric ducts is responsive to the changes in atmospheric circulation and the sea ice extent. This anomalous circulation changes surface wind in the Arctic, which affects the formation and maintenance of the ducts. The trends of ducts in the Arctic Ocean are consistent with those of the Arctic Sea ice extent, while the Arctic continental and coastal ducts show the opposite trend.

Aeromonas hydrophila is a ubiquitous Gram-negative opportunistic pathogen in the freshwater environment and the most common cause of bacterial septicemia in aquaculture. In this study, we investigated the impact of carvacrol, a natural monoterpenoid found in herbs, on the virulence of A. hydrophila in vitro and the antibacterial effect in combination with antibiotics. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of carvacrol against A. hydrophila NJ-35 were 125 µg/mL and 250 µg/mL, respectively. Carvacrol could inhibit the virulence factors (biofilm, protease, exopolysaccharide, and hemolysin) of A. hydrophila, and the antibiofilm potential of carvacrol was further verified by microscopic detection. Transcriptional analyses showed that the gene expression of flaB, ompA, aha, ahp, ela, act, aerA, AhyR, and hly were marked as downregulated. The checkerboard assay results showed that carvacrol did not have an antagonistic effect in combination with antibiotics (florfenicol, enrofloxacin, thiamphenicol, or doxycycline hydrochloride) commonly used in aquaculture but possessed an additive-synergistic effect with neomycin sulfate. In vivo studies demonstrated that carvacrol protected grass carp (Ctenopharyngodon idella) from A. hydrophila infection. Our results indicated that carvacrol possessed significant anti-bacterial and anti-virulence effects on A. hydrophila.

The RNA-binding protein tristetraprolin (TTP) is an anti-inflammatory factor that prompts the mRNA decay of target mRNAs and is involved in inflammatory diseases such as rheumatoid arthritis (RA). TTP is regulated by phosphorylation, and protein phosphatase 2A (PP2A) can dephosphorylate TTP to activate its mRNA-degrading function. Some small molecules can enhance PP2A activation. Short interfering RNA (siRNA) targeting TTP expression or PP2A agonist (Arctigenin) was administered to monosodium urate (MSU) crystal-induced J774A.1 cells, and the expression of inflammatory related genes was detected by RT-PCR and Western blot assays. The effects of Arctigenin in mouse models of acute inflammation induced by MSU crystals, including peritonitis and arthritis, were evaluated. The data indicated that TTP expression levels and endogenous PP2A activity were increased in MSU-crystal treated J774A.1 cells. TTP knockdown exacerbated inflammation-related genes expression and NLRP3 inflammasome activation. However, PP2A agonist treatment (Arctigenin) suppressed MSU crystal-induced inflammation in J774A.1 cells. Arctigenin also relieved mitochondrial reactive oxygen species (mtROS) production and improved lysosomal membrane permeability in MSU crystal-treated J774A.1 cells. Moreover, TTP knockdown reversed the anti-inflammatory and antioxidant effects of Arctigenin. Oral administration of Arctigenin significantly alleviated foot pad swelling, the number of inflammatory cells in peritoneal lavage fluids and the production of IL-1β in the mouse model of inflammation induced by MSU crystals. Collectively, these data imply that targeting TTP expression or functional activity may provide a potential therapeutic strategy for inflammation caused by MSU crystals.

For large-area electronic applications, the mechanism of the leakage current in oxide-semiconductor thin-film transistors (TFTs) has become a critical issue. In this work, the impact of the irradiation location on the photo-leakage current of zinc oxide (ZnO) TFTs is investigated. The photo-leakage current of the ZnO TFTs is not only dependent on the light irradiation but it is also dependent on the parasitic capacitance between the drain electrode and the floating gate metal. The photo-leakage current of the source-half irradiation TFT is larger than that of the drain-half irradiation TFT. To explain this phenomenon, the profile of the electric potential and the electron concentration is analyzed by two-dimensional device simulation. It is found that the floating gate metal plays the dominant role in the photo-leakage current. This research provides insight into TFT structure optimization and high-performance TFT process development.

Tooth brushing is necessary to maintain oral health. Little research has been carried out to explore microbial diversity in toothbrushes and to study the potential impact of these bacteria on human health. In the present study, 20 participants were enrolled, and the microbial diversity in their oral cavity and toothbrushes was investigated using high-throughput sequencing. Our results indicate that 1,136 and 976 operational taxonomic units (OTUs) were obtained from groups CB (samples from toothbrushes of participants using traditional Chinese medicinal toothpaste) and AB (samples from toothbrushes of those using antibacterial toothpaste), respectively. The pathogens Acinetobacter baumannii, Staphylococcus aureus, and Candida albicans were identified on toothbrushes. The presence of these pathogens increases the chance for the host to get infectious diseases, neurodegenerative diseases, cardiovascular diseases, and cancers. Moreover, our in vitro results indicate that traditional Chinese medicinal toothpaste and antibacterial toothpaste can not only inhibit the growth of pathogens but also markedly inhibit the growth of probiotics Lactobacillus salivarius and Streptococcus salivarius. Therefore, the inhibitory effect of toothpaste on probiotics, together with the existence of pathogens in toothbrushes, indicates a potential risk of tooth brushing for people in a sub-healthy state.

Flavobacterium columnare is a Gram-negative bacterium that causes columnaris disease in freshwater fish worldwide. Many studies have focused on the identification of protective antigens to aid in the development of novel vaccines against the disease. In this study, an immunoblotting approach was employed to identify immunogenic outer membrane proteins (OMPs) from F. columnare in two-dimensional electrophoresis (2-DE) map gels using antibacterial sera obtained from grass carp (Ctenopharyngodon idella), and anti-grass carp-recombinant Ig (rIg) monoclonal antibodies. Five unique immunogenic proteins, including the gliding motility lipoprotein GldJ (GldJ), hypothetical protein FCOL_13420 (Fco1), lipoprotein (Lip), F0F1 ATP synthase subunit beta (F0f1) and outer membrane efflux protein precursor (Omep), were characterized. Over-expression of these proteins in Escherichia coli DE3, and their immunogenicity and protective efficacy were evaluated in grass carp. The relative percent survival (RPS) of the groups immunized separately with recombinant GldJ, Lip and Omep was 72%, 64% and 68%, respectively when compared to control fish. Up-regulation of immuno-related genes and specific antibodies were detected in immunized fish and sera of immunized fish inhibited the growth of F. columnare. The results suggest that GldJ, Lip and Omep are major protective antigens and may be considered as novel candidates in the development of vaccines against columnaris disease in fish.

Abstract Stress is an important contributing factor in the outbreak of infectious fish diseases. To comprehensively understand the impact of catecholamine stress hormone norepinephrine (NE) on the pathogenicity of Aeromonas hydrophila, we assessed variations in bacterial growth, virulence‐related genes expression and virulence factors activity after NE addition in serum‐SAPI medium. Further, we assessed the effects of NE on A. hydrophila virulence in vivo by challenging fish with pathogenic strain AH196 and following with or without NE injection. The NE‐associated stimulation of A. hydrophila strain growth was not linear‐dose‐dependent, and only 100 μM, or higher concentrations, could stimulate growth. Real‐time PCR analyses revealed that NE notably changed 13 out of the 16 virulence‐associated genes (e.g. ompW, ahp, aha, ela, ahyR, ompA, and fur) expression, which were all significantly upregulated in A. hydrophila AH196 (p

Inter-annual variation of meteorological conditions and their effects on snow and ice thickness in an Arctic lake Unari (67.14° N, 25.73° E) were investigated for winters 1980/1981–2012/2013. The lake snow and ice thicknesses were modelled applying a thermodynamic model, and the results were compared with observations. Regression equations were derived for the relationships between meteorological parameters and modelled snow and ice properties. The composite differences of large-scale atmospheric circulation patterns between seasons of thin and thick ice were analysed. The air temperature had an increasing trend (statistical significance p