A chitosan-camouflaged nanomedicine triggered by hierarchically stimuli to release drug for multimodal imaging-guided chemotherapy of breast cancer.

Breast cancer remains one of the most intractable diseases, especially the malignant form of metastasis, with which the cancer cells are hard to track and eliminate. Herein, the common known carbohydrate polymer chitosan (CS) was innovatively used as a shelter for the potent tumor-killing agent. The designed nanoparticles (NPs) not only enhance the solubility of hydrophobic paclitaxel (PTX), but also provide a "hide" effect for cytotoxic PTX in physiological condition. Moreover, coupled with the photothermal (PTT) properties of MoS2, results in a potent chemo/PTT platform. The MoS2@PTX-CS-K237 NPs have a uniform size (135 ± 17 nm), potent photothermal properties (η = 31.5 %), and environment-responsive (low pH, hypoxia) and near infrared (NIR) laser irradiation-triggered PTX release. Through a series of in vitro and in vivo experiments, the MoS2@PTX-CS-K237 showed high affinity and specificity for breast cancer cells, impressive tumor killing capacity, as well as the effective inhibitory effect of metastasis. Benefit from the unique optical properties of MoS2, this multifunctional nanomedicine also exhibited favorable thermal/PA/CT multimodality imaging effect on tumor-bearing mice. The system developed in this work represents the advanced design concept of hierarchical stimulus responsive drug release, and merits further investigation as a potential nanotheranostic platform for clinical translation.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

The Effect of Different Factors on Poly(lactic-co-glycolic acid) Nanoparticle Properties and Drug Release Behaviors When Co-Loaded with Hydrophilic and Hydrophobic Drugs.

Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are versatile drug nanocarriers with a wide spectrum of applications owing to their extensive advantages, including biodegradability, non-toxic side effects, and low immunogenicity. Among the numerous nanoparticle preparation methods available for PLGA NPs (the hydrophobic polymer), one of the most extensively utilized preparations is the sonicated-emulsified solvent evaporation method, owing to its simplicity, speed, convenience, and cost-effectiveness. Nevertheless, several factors can influence the outcomes, such as the types of concentration of the surfactants and organic solvents, as well as the volume of the aqueous phase. The objective of this article is to explore the influence of these factors on the properties of PLGA NPs and their drug release behavior following encapsulation. Herein, PLGA NPs were fabricated using bovine serum albumin (BSA) as a surfactant to investigate the impact of influencing factors, including different water-soluble organic solvents such as propylene carbonate (PC), ethyl acetate (PA), and dichloromethane (DCM). Notably, the size of PLGA NPs was smaller in the EA group compared to that in the DCM group. Moreover, PLGA NPs showed excellent stability, ascribed to the presence of the BSA surfactant. Furthermore, PLGA NPs were co-loaded with varying concentrations of hydrophilic drugs (doxorubicin hydrochloride) and hydrophobic drugs (celecoxib), and exhibited pH-sensitive drug release behavior in PBS with pH 7.4 and pH 5.5.

Conformal Engineering of Both Electrodes Toward High-Performance Flexible Quasi-Solid-State Zn-Ion Micro-Supercapacitors.

The severe Zn-dendrite growth and insufficient carbon-based cathode performance are two critical issues that hinder the practical applications of flexible Zn-ion micro-ssupercapacitors (FZCs). Herein, a self-adaptive electrode design concept of the synchronous improvement on both the cathode and anode is proposed to enhance the overall performance of FZCs. Polypyrrole doped with anti-expansion graphene oxide and acrylamide (PPy/GO-AM) on the cathode side can exhibit remarkable electrochemical performance, including decent capacitance and cycling stability, as well as exceptional mechanical properties. Meanwhile, a robust protective polymeric layer containing reduced graphene oxide and polyacrylamide is self-assembled onto the Zn surface (rGO/PAM@Zn) at the anode side, by which the "tip effect" of Zn small protuberance can be effectively alleviated, the Zn-ion distribution homogenized, and dendrite growth restricted. Benefiting from these advantages, the FZCs deliver an excellent specific capacitance of 125 mF cm-2 (125 F cm-3) at 1 mA cm-2, along with a maximum energy density of 44.4 µWh cm-2, and outstanding long-term durability with 90.3% capacitance remained after 5000 cycles. This conformal electrode design strategy is believed to enlighten the practical design of high-performance in-plane flexible Zn-based electrochemical energy storage devices (EESDs) by simultaneously tackling the challenges faced by Zn anodes and capacitance-type cathodes.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis.

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

Hydrogen-rich solution alleviates acute radiation pneumonitis by regulating oxidative stress and macrophages polarization.

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway.

Hollow Metal-Organic Framework/MXene/Nanocellulose Composite Films for Giga/Terahertz Electromagnetic Shielding and Photothermal Conversion.

With the continuous advancement of communication technology, the escalating demand for electromagnetic shielding interference (EMI) materials with multifunctional and wideband EMI performance has become urgent. Controlling the electrical and magnetic components and designing the EMI material structure have attracted extensive interest, but remain a huge challenge. Herein, we reported the alternating electromagnetic structure composite films composed of hollow metal-organic frameworks/layered MXene/nanocellulose (HMN) by alternating vacuum-assisted filtration process. The HMN composite films exhibit excellent EMI shielding effectiveness performance in the GHz frequency (66.8 dB at Ka-band) and THz frequency (114.6 dB at 0.1-4.0 THz). Besides, the HMN composite films also exhibit a high reflection loss of 39.7 dB at 0.7 THz with an effective absorption bandwidth up to 2.1 THz. Moreover, HMN composite films show remarkable photothermal conversion performance, which can reach 104.6 °C under 2.0 Sun and 235.4 °C under 0.8 W cm-2, respectively. The unique micro- and macro-structural design structures will absorb more incident electromagnetic waves via interfacial polarization/multiple scattering and produce more heat energy via the local surface plasmon resonance effect. These features make the HMN composite film a promising candidate for advanced EMI devices for future 6G communication and the protection of electronic equipment in cold environments.

Bio-Polyethylene and Polyethylene Biocomposites: An Alternative toward a Sustainable Future.

Polyethylene (PE), a highly prevalent non-biodegradable polymer in the field of plastics, presents a waste management issue. To alleviate this issue, bio-based PE (bio-PE), derived from renewable resources like corn and sugarcane, offers an environmentally friendly alternative. This review discusses various production methods of bio-PE, including fermentation, gasification, and catalytic conversion of biomass. Interestingly, the bio-PE production volumes and market are expanding due to the growing environmental concerns and regulatory pressures. Additionally, the production of PE and bio-PE biocomposites using agricultural waste as filler materials, highlights the growing demand for sustainable alternatives to conventional plastics. According to previous studies, addition of ≈50% defibrillated corn and abaca fibers into bio-PE matrix and a compatibilizer, results in the highest Young's modulus of 4.61 and 5.81 GPa, respectively. These biocomposites have potential applications in automotive, building construction, and furniture industries. Moreover, the advancement made in abiotic and biotic degradation of PE and PE biocomposites is elucidated to address their environmental impacts. Finally, the paper concludes with insights into the opportunities, challenges, and future perspectives in the sustainable production and utilization of PE and bio-PE biocomposites. In summary, production of PE and bio-PE biocomposites can contribute to a cleaner and sustainable future.

Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

Latent Profiles of Coronavirus-Related Health Literacy in Chinese Residents and Its Related Predictors.

OBJECTIVES: This study aimed to explore the latent profiles of coronavirus-related health literacy among Chinese residents and investigate whether some predictive factors are linked with different latent subgroups of coronavirus-related health literacy. DESIGN/SETTING: This study was a cross-sectional survey conducted among Chinese residents beginning in April 2020. PARTICIPANTS: A total of 1610 Chinese residents aged 15 to 69 years were involved and were asked to complete the questionnaire about coronavirus-related health literacy, demographic information, and COVID-19 pandemic-related information. MAIN OUTCOME MEASURE: Examined the latent profiles of coronavirus-related health literacy and explored the influencing factors of different profiles of coronavirus-related health literacy. RESULTS: The results showed that there were 3 latent subgroups, namely, high coronavirus-related health literacy (45.53%), medium coronavirus-related health literacy (47.76%), and low coronavirus-related health literacy (6.71%). Logistic regression analysis showed that gender, education, and the frequency of exposure to news about the pandemic could predict group membership. CONCLUSIONS: Most Chinese residents have medium coronavirus-related health literacy. Education is an important factor that has a long-term stable influence on coronavirus-related health literacy, and the frequency of exposure to news about the pandemic is a factor that can improve coronavirus-related health literacy in a short time.

Remote Ischemic Postconditioning-Mediated Neuroprotection against Stroke by Promoting Ketone Body-Induced Ferroptosis Inhibition.

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis. In terms of energy metabolism, RIPostC enhanced ATP levels, suppressed lactate content, and increased the production of ketone bodies (KBs). In the ferroptosis assay, RIPostC protected against lipoperoxidation, reversed the reduction of glutathione peroxidase 4 (GPX4), and mitigated the excessive expression of long-chain acyl-CoA synthetase family member 4 (ACSL4). In oxygen-glucose deprivation/reoxygenation-treated HT22 cells, KBs maintained GPX4 levels, suppressed ACSL4 expression, and preserved the mitochondrial cristae number. However, the effect of KBs on the expression of GPX4, ACSL4, and the number of mitochondrial cristae was blocked by erastin. Moreover, both RIPostC and KBs reduced total iron and ferrous ion content by repressing iron transporters both in vitro and in vivo. In conclusion, KBs-induced mitigation of ferroptosis could represent a new therapeutic mechanism for RIPostC in treating stroke.

Evaluating public opinions: informing public health policy adaptations in China amid the COVID-19 pandemic.

Public concern regarding safety policies serious consequences is anticipated to persist over an extended duration. A study examining a case of rapid public health policy adaptation in China during the COVID-19 epidemic was conducted by gathering public opinion data from major social media platforms. A systematic approach to comprehend public opinion was developed. Five fundamental elements and four dimensions were delineated. An indicator system was established utilizing the K-means text clustering model. Public prediction, expectation, and their evolution underlying public concern were elucidated employing TF-IDF text mining models. The HMM elucidated the way public opinion influences policy adjustments. The findings underscore that public concern regarding enduring events undergoes temporal shifts, mirroring the evolution of public opinion towards policy. Public opinion aroused by both the original event and derived events collaboratively influence policy adjustments. In China, public opinion serves as a mechanism for policy feedback and oversight; notably, negative public sentiment plays a pivotal role in expediting policy transitions. These findings aid in refining policies to mitigate emergencies through a feedback loop, thereby averting the emergence of safety risks such as social unrest prompted by public opinion.

The hippocampal salt-inducible kinase 2-CREB-regulated transcription co-activator 1 system mediates the antidepressant actions of paroxetine in mice.

The hippocampal salt-inducible kinase 2 (SIK2)-CREB-regulated transcription co-activator 1 (CRTC1) system has been demonstrated to participate in not only the pathogenesis of depression but also the antidepressant mechanisms of several antidepressant medications including fluoxetine, paroxetine, and mirtazapine. Like fluoxetine, paroxetine is also a widely used selective serotonin (5-HT) reuptake inhibitor (SSRI). Recent studies have indicated that paroxetine also modulates several pharmacological targets other than the 5-HT system. Here, we speculate that paroxetine regulates the hippocampal SIK2-CRTC1 system. Chronic stress models of depression, various behavioral tests, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription PCR, and genetic knockdown were used together in the present study. Our results show that the antidepressant actions of paroxetine in mice models of depression were accompanied by its preventing effects against chronic stress on hippocampal SIK2, CRTC1, and CRTC1-CREB binding. In contrast, genetic knockdown of hippocampal CRTC1 notably abrogated the antidepressant effects of paroxetine in mice. In summary, regulating hippocampal SIK2 and CRTC1 participates in the antidepressant mechanism of paroxetine, extending the knowledge of its pharmacological targets.

The arrival time and energy of FRBs traverse the time-energy bivariate space like a Brownian motion.

The origin of fast radio bursts (FRBs), the brightest cosmic explosion in radio bands, remains unknown. We introduce here a novel method for a comprehensive analysis of active FRBs' behaviors in the time-energy domain. Using "Pincus Index" and "Maximum Lyapunov Exponent", we were able to quantify the randomness and chaoticity, respectively, of the bursting events and put FRBs in the context of common transient physical phenomena, such as pulsar, earthquakes, and solar flares. In the bivariate time-energy domain, repeated FRB bursts' behaviors deviate significantly (more random, less chaotic) from pulsars, earthquakes, and solar flares. The waiting times between FRB bursts and the corresponding energy changes exhibit no correlation and remain unpredictable, suggesting that the emission of FRBs does not exhibit the time and energy clustering observed in seismic events. The pronounced stochasticity may arise from a singular source with high entropy or the combination of diverse emission mechanisms/sites. Consequently, our methodology serves as a pragmatic tool for illustrating the congruities and distinctions among diverse physical processes.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

OBJECTIVE: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. METHODS: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. RESULTS: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. CONCLUSION: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

A One-Step RPA-CRISPR Assay Using crRNA Based on Suboptimal Protospacer Adjacent Motif for Vibrio vulnificus Detection.

Vibrio vulnificus is a hazardous foodborne pathogen responsible for approximately 95% of seafood-related deaths. This highlights the urgent requirement for specialized detection tools to be developed and used by food enterprises and food safety authorities. The DETECTR (DNA endonuclease targeted CRISPR trans reporter) system that combines CRISPR/Cas and recombinase polymerase amplification (RPA) has been utilized to develop a molecular detection assay for V. vulnificus. However, because the incompatibility between RPA and Cas12a cleavage has not been addressed, it is a two-step assay that lacks convenience and presents contamination risk. Here, we developed a one-step RPA-CRISPR assay for V. vulnificus using a special crRNA targeting a sequence with a suboptimal protospacer adjacent motif (PAM). The entire assay, conducted at 37°C, takes only 40-60 min, yields results visualized under blue light, and exhibits exceptional specificity and sensitivity (detecting 4 pathogen genome copies per reaction). This study offers a valuable tool for detecting V. vulnificus, aiding in foodborne infection prevention, and exemplifies one-step RPA-CRISPR assays managing Cas-cleavage activity through PAM adjustments.

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.