Lacticaseibacillus rhamnosus GG alleviates sleep deprivation-induced intestinal barrier dysfunction and neuroinflammation in mice.

Consuming probiotic products is a solution that people are willing to choose to augment health. As a global health hazard, sleep deprivation (SD) can cause both physical and mental diseases. The present study investigated the protective effects of Lacticaseibacillus rhamnosus GG (LGG), a widely used probiotic, on a SD mouse model. Here, it has been shown that SD induced intestinal damage in mice, while LGG supplementation attenuated disruption of the intestinal barrier and enhanced the antioxidant capacity. Microbiome analysis revealed that SD caused dysbiosis in the gut microbiota, characterized by increased levels of Clostridium XlVa, Alistipes, and Desulfovibrio, as well as decreased levels of Ruminococcus, which were partially ameliorated by LGG. Moreover, SD resulted in elevated pro-inflammatory cytokine concentrations in both the intestine and the brain, while LGG provided protection in both organs. LGG supplementation significantly improved locomotor activity in SD mice. Although heat-killed LGG showed some protective effects in SD mice, its overall efficacy was inferior to that of live LGG. In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation.

Progress in research and development of preventive vaccines for children in China.

The infant and child stage is an important stage for the continuation and development of human society. The initial years of life have a lasting impact on a child's future. Children under the age of 5 have an immature immune system, especially infants and young children under 6 months of age. At this stage, the population has a low immunity to pathogen infections, making them vulnerable to bacteria and viruses. Vaccination can enhance the immunity of infants and children to specific diseases, reduce the transmission rate of infectious diseases, and promote the development of global public health. This article summarizes the current application status of Rotavirus (RV) vaccine, Hand-foot -mouth disease (HFMD) vaccine, and Pneumococcal Conjugate Vaccine (PCV) in China, as well as the research progress of clinical trial vaccine, laying a foundation for subsequent vaccine development.

Co-designing interventions to strengthen the primary health care system for the management of hypertension and type 2 diabetes in China.

Background: Policy makers and researchers are tasked with exploring ways to strengthen primary health care (PHC) to address the growing burden of non-communicable diseases (NCDs). This study aims to use a co-design approach (i.e., meaningful involvement of research end users in study planning and design) to develop PHC interventions to improve the management of hypertension and type 2 diabetes (T2DM) in four study sites in China. Methods: The study adopted a three-step co-design approach, including (1) a two-round Delphi panel with health system and NCD professionals to identify prioritised health system challenges, (2) three co-design workshops (in each study site) with local health administrators, PHC providers, and residents with hypertension and/or T2DM, respectively, to develop interventions and identify factors influencing implementation, and (3) another round of co-design workshops with local health administrators to summarise findings and reach consensus. Qualitative synthesis was conducted to analyse results from the workshops. Findings: Thirteen experts were involved in the two-round Delphi panel, which identified three prioritised health system challenges, including limited capacities of PHC providers, suboptimal service quality and evaluation mechanisms, and unreliable health information systems. The co-design workshops involved 116 local stakeholders in 16 sessions (four in each site), and developed three groups of interventions to address the challenges: (1) empowering PHC providers through on-the-job training for capacity building; (2) empowering patient communities through health education on healthy lifestyles and NCD self-management; and (3) empowering health administrators through local health data monitoring and strengthening governance for local PHC programs. Site-specific interventions were also considered to cater for different local contexts. Several recommendations were further identified for the implementation of these interventions, emphasising the importance of local customisation, community participation, and cross-sectoral collaborations. Interpretation: By engaging multiple stakeholders in priority setting and solution generation, this study summarised several key areas for change in health workforce, service delivery, and health information. Future research should examine the effectiveness and implementation of these interventions to improve NCD management in PHC in China. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757) and National Natural Science Foundation of China (72074065). Shangzhi Xiong is supported by University of New South Wales tuition fee scholarship.

BPT-PLR: A Balanced Partitioning and Training Framework with Pseudo-Label Relaxed Contrastive Loss for Noisy Label Learning.

While collecting training data, even with the manual verification of experts from crowdsourcing platforms, eliminating incorrect annotations (noisy labels) completely is difficult and expensive. In dealing with datasets that contain noisy labels, over-parameterized deep neural networks (DNNs) tend to overfit, leading to poor generalization and classification performance. As a result, noisy label learning (NLL) has received significant attention in recent years. Existing research shows that although DNNs eventually fit all training data, they first prioritize fitting clean samples, then gradually overfit to noisy samples. Mainstream methods utilize this characteristic to divide training data but face two issues: class imbalance in the segmented data subsets and the optimization conflict between unsupervised contrastive representation learning and supervised learning. To address these issues, we propose a Balanced Partitioning and Training framework with Pseudo-Label Relaxed contrastive loss called BPT-PLR, which includes two crucial processes: a balanced partitioning process with a two-dimensional Gaussian mixture model (BP-GMM) and a semi-supervised oversampling training process with a pseudo-label relaxed contrastive loss (SSO-PLR). The former utilizes both semantic feature information and model prediction results to identify noisy labels, introducing a balancing strategy to maintain class balance in the divided subsets as much as possible. The latter adopts the latest pseudo-label relaxed contrastive loss to replace unsupervised contrastive loss, reducing optimization conflicts between semi-supervised and unsupervised contrastive losses to improve performance. We validate the effectiveness of BPT-PLR on four benchmark datasets in the NLL field: CIFAR-10/100, Animal-10N, and Clothing1M. Extensive experiments comparing with state-of-the-art methods demonstrate that BPT-PLR can achieve optimal or near-optimal performance.

Brincidofovir inhibits polyomavirus infection in vivo.

Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases, there are no currently approved antivirals for treating polyomavirus infection. Brincidofovir (BCV) is an antiviral approved for the treatment of poxvirus infections and has shown activity against other double-stranded DNA viruses. In this study, we tested the efficacy of BCV against polyomavirus infection in vitro and in vivo using mouse polyomavirus (MuPyV). BCV inhibited virus production in primary mouse kidney cells and brain cortical cells. BCV treatment of cells transfected with MuPyV genomic DNA resulted in a reduction in virus levels, indicating that viral inhibition occurs post-entry. Although in vitro BCV treatment had a limited effect on viral DNA and RNA levels, drug treatment was associated with a reduction in viral protein, raising the possibility that BCV acts post-transcriptionally to inhibit MuPyV infection. In mice, BCV treatment was well tolerated, and prophylactic treatment resulted in a reduction in viral DNA levels and a potent suppression of infectious virus production in the kidney and brain. In mice with chronic polyomavirus infection, therapeutic administration of BCV decreased viremia and reduced infection in the kidney. These data demonstrate that BCV exerts antiviral activity against polyomavirus infection in vivo, supporting further investigation into the use of BCV to treat clinical polyomavirus infections. IMPORTANCE: Widespread in the human population and able to persist asymptomatically for the life of an individual, polyomavirus infections cause a significant disease burden in the immunocompromised. Individuals undergoing immune suppression, such as kidney transplant patients or those treated for autoimmune diseases, are particularly at high risk for polyomavirus-associated diseases. Because no antiviral agent exists for treating polyomavirus infections, management of polyomavirus-associated diseases typically involves reducing or discontinuing immunomodulatory therapy. This can be perilous due to the risk of transplant rejection and the potential development of adverse immune reactions. Thus, there is a pressing need for the development of antivirals targeting polyomaviruses. Here, we investigate the effects of brincidofovir, an FDA-approved antiviral, on polyomavirus infection in vivo using mouse polyomavirus. We show that the drug is well-tolerated in mice, reduces infectious viral titers, and limits viral pathology, indicating the potential of brincidofovir as an anti-polyomavirus therapeutic.

Characterization of Gas-Liquid Two-Phase Slug Flow Using Distributed Acoustic Sensing in Horizontal Pipes.

This article discusses the use of distributed acoustic sensing (DAS) for monitoring gas-liquid two-phase slug flow in horizontal pipes, using standard telecommunication fiber optics connected to a DAS integrator for data acquisition. The experiments were performed in a 14 m long, 5 cm diameter transparent PVC pipe with a fiber cable helically wrapped around the pipe. Using mineral oil and compressed air, the system captured various flow rates and gas-oil ratios. New algorithms were developed to characterize slug flow using DAS data, including slug frequency, translational velocity, and the lengths of slug body, slug unit, and the liquid film region that had never been discussed previously. This study employed a high-speed camera next to the fiber cable sensing section for validation purposes and achieved a good correlation among the measurements under all conditions tested. Compared to traditional multiphase flow sensors, this technology is non-intrusive and offers continuous, real-time measurement across long distances and in harsh environments, such as subsurface or downhole conditions. It is cost-effective, particularly where multiple measurement points are required. Characterizing slug flow in real time is crucial to many industries that suffer slug-flow-related issues. This research demonstrated the DAS's potential to characterize slug flow quantitively. It will offer the industry a more optimal solution for facility design and operation and ensure safer operational practices.

From intramuscular to nasal: unleashing the potential of nasal spray vaccines against coronavirus disease 2019.

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected 700 million people worldwide since its outbreak in 2019. The current pandemic strains, including Omicron and its large subvariant series, exhibit strong transmission and stealth. After entering the human body, the virus first infects nasal epithelial cells and invades host cells through the angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 on the host cell surface. The nasal cavity is an important body part that protects against the virus. Immunisation of the nasal mucosa produces immunoglobulin A antibodies that effectively neutralise viruses. Saline nasal irrigation, a type of physical therapy, can reduce the viral load in the nasal cavity and prevent viral infections to some extent. As a commonly used means to fight SARS-CoV-2, the intramuscular (IM) vaccine can induce the human body to produce a systemic immune response and immunoglobulin G antibody; however, the antibody is difficult to distribute to the nasal mucosa in time and cannot achieve a good preventive effect. Intranasal (IN) vaccines compensate for the shortcomings of IM vaccines, induce mucosal immune responses, and have a better effect in preventing infection. In this review, we discuss the nasal defence barrier, the harm caused by SARS-CoV-2, the mechanism of its invasion into host cells, nasal cleaning, IM vaccines and IN vaccines, and suggest increasing the development of IN vaccines, and use of IN vaccines as a supplement to IM vaccines.

The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.

EpMYB2 positively regulates chicoric acid biosynthesis by activating both primary and specialized metabolic genes in purple coneflower.

Chicoric acid is the major active ingredient of the world-popular medicinal plant purple coneflower (Echinacea purpurea (L.) Menoch). It is recognized as the quality index of commercial hot-selling Echinacea products. While the biosynthetic pathway of chicoric acid in purple coneflower has been elucidated recently, its regulatory network remains elusive. Through co-expression and phylogenetic analysis, we found EpMYB2, a typical R2R3-type MYB transcription factor (TF) responsive to methyl jasmonate (MeJA) simulation, is a positive regulator of chicoric acid biosynthesis. In addition to directly regulating chicoric acid biosynthetic genes, EpMYB2 positively regulates genes of the upstream shikimate pathway. We also found that EpMYC2 could activate the expression of EpMYB2 by binding to its G-box site, and the EpMYC2-EpMYB2 module is involved in the MeJA-induced chicoric acid biosynthesis. Overall, we identified an MYB TF that positively regulates the biosynthesis of chicoric acid by activating both primary and specialized metabolic genes. EpMYB2 links the gap between the JA signaling pathway and chicoric acid biosynthesis. This work opens a new direction toward engineering purple coneflower with higher medicinal qualities.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

[Distribution and Drug Resistance of Pathogens Causing Bloodstream Infection in Patients with Hematological Malignancies].

OBJECTIVE: To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies, in order to provide reference for clinical infection control and treatment. METHODS: The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed. They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation. The types of pathogens and their drug resistance were analyzed. RESULTS: Two hundred and ninety-nine positive strains of pathogenic bacteria were detected. In the transplantation group, Gram-negative bacteria accounted for 68.5% (50/73), Gram-positive bacteria accounted for 6.8% (5/73), and fungi accounted for 24.7% (18/73). The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8%, and 11.5% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0%, and 56.2% to carbapenems. In the non-transplantation group, Gram-negative bacteria accounted for 64.1% (145/226), Gram-positive bacteria accounted for 31.0% (70/226), and fungi accounted for 4.9% (11/226). Gram-positive bacteria were mainly Enterococcus faecium (6.6%, 15/226) and Coagulase-negative Staphylococci (6.2%, 14/226). The fungi were all Candida tropicalis. The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8%, and 10.3% to carbapenems. The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3%, and 26.8% to carbapenems. CONCLUSION: The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied. Gram-negative bacteria is the main pathogenic bacteria. The resistance of pathogenic bacteria to antibiotics is severe. Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Na-Ru bimetallic functional sites promote photo-driven CO2 directed conversion into CH4.

Recently, there has been a significant increase in interest in using photocatalysis for the energy conversion of polluting gases. In this research, sodium and ruthenium bimetallic functional sites co-modified bismuth tungstate (Ru/Na-Bi2WO6) nanoflower photocatalyst was synthesized via the hydrothermal method. The CO2 reduction products on the Bi2WO6 substrate were CO (1.66 µmol/g/h, 68 %) and CH4 (0.78 µmol/g/h, 32 %). After optimization, a significant change in the CO2 products of the Bi2WO6-based composite material was observed, with CO (0.61 µmol/g/h, 3.6 %) and CH4 (16.1 µmol/g/h, 96.4 %). Results showed that the dominance of CH4 as the main product in the Ru/Na-BWO system is attributed to the effective doping of Na, which generates impurity energy levels composed of oxygen vacancies, lowering the conduction band position of Bi2WO6, thereby suppressing CO generation, and enhancing CH4 selectivity by changing the CO2 activation pathway. The remarkable performance is ascribed to the synergized adsorption and activation of CO2 by the tandem Na+ sites and Ru0 sites. Specifically, the doped Na+ sites play a major role in promoting the adsorption CO2 molecules, while the Ru0 sites play a dominant role in facilitating the activation of the intermediates.

Epigenetic Activation of Cytochrome P450 1A2 Sensitizes Hepatocellular Carcinoma Cells to Sorafenib.

Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CYP1A2 CpG island (CGI) and DNA methyltransferase (DNMT) 3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression. Knockdown of DNMT3A by siRNA significantly increased CYP1A2 expression in HCC cells. Additionally, treating HCC cells with decitabine (DAC) resulted in a dose-dependent upregulation of CYP1A2 expression by reducing the methylation level of CYP1A2 CGI. Furthermore, we observed a decreased enrichment of H3K27Ac in the promoter region of CYP1A2 in HCC tissues. Treatment with the trichostatin A (TSA) restored CYP1A2 expression in HCC cells by increasing H3K27Ac levels in the CYP1A2 promoter region. Importantly, combination treatment of sorafenib with DAC or TSA resulted in a leftward shift of the dose-response curve, lower IC50 values, and reduced colony numbers in HCC cells. Our findings suggest that hypermethylation of the CGI at the promoter, mediated by the high expression of DNMT3A, and hypoacetylation of H3K27 in the CYP1A2 promoter region, leads to CYP1A2 repression in HCC. Epigenetic drugs DAC and TSA increase HCC cell sensitivity to sorafenib by restoring CYP1A2 expression. Our study provides new insights into the epigenetic regulation of CYP1A2 in HCC and highlights the potential of epigenetic drugs as a therapeutic approach for HCC. SIGNIFICANCE STATEMENT: This study marks the first exploration of the epigenetic mechanisms underlying cytochrome P450 (CYP) 1A2 suppression in hepatocellular carcinoma (HCC). Our findings reveal that heightened DNA methyltransferase expression induces hypermethylation of the CpG island at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine and trichostatin A emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.

Small-Scale High-Pressure Hydrogen Storage Vessels: A Review.

Nowadays, high-pressure hydrogen storage is the most commercially used technology owing to its high hydrogen purity, rapid charging/discharging of hydrogen, and low-cost manufacturing. Despite numerous reviews on hydrogen storage technologies, there is a relative scarcity of comprehensive examinations specifically focused on high-pressure gaseous hydrogen storage and its associated materials. This article systematically presents the manufacturing processes and materials used for a variety of high-pressure hydrogen storage containers, including metal cylinders, carbon fiber composite cylinders, and emerging glass material-based hydrogen storage containers. Furthermore, it introduces the relevant principles and theoretical studies, showcasing their advantages and disadvantages compared to conventional high-pressure hydrogen storage containers. Finally, this article provides an outlook on the future development of high-pressure hydrogen storage containers.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

Effects of New Psychoactive Substance Esketamine on Behaviors and Transcription of Genes in Dopamine and GABA Pathways in Zebrafish Larvae.

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.

A continuous ultra-narrow impulse synchronizer using a monolithic field programmable gate array for fast deployment and scalability.

Ultra-narrow pulses serve as critical components in numerous applications. These pulses have ultra-fast leading edges that typically function as precision trigger signals to synchronize various instruments. Ultra-narrow pulses inherently exhibit an ultra-wide bandwidth, gaining significant attention in diverse electronic systems encompassing communications, radar imaging, electronic warfare, and others. Although several techniques have been explored for generating ultra-narrow pulses, field programmable gate arrays (FPGAs) offer a promising alternative in terms of flexibility and integration. This study introduces a scalable delay pulse synchronizer method with a resolution of 23 ps. A programmable, successive, narrow pulse sequence operating at a 1-GHz repetition frequency is implemented within a monolithic FPGA. The performance of the proposed method is evaluated using an existing board with a general commercial FPGA in the laboratory. This new method presents a convenient and efficient approach of achieving ultra-narrow pulse synchronization, being applicable across various fields.

The azole biocide climbazole induces oxidative stress, inflammation, and apoptosis in fish gut.

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.

Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.