A Fluorescent Probe Containing Triphenylamine-Benzofuranone Moiety for Detecting Cysteine and Imaging in Living Pulmonary Cells Under Hypercapnia.

In this work, a fluorescent probe TPB-Cys derived from triphenylamine-benzofuranone was developed for monitoring the cysteine (Cys) level and imaging in living pulmonary cells under hypercapnia condition. A systematic hypoxia module was tried to cover both the in-solution test and pulmonary cellular imaging. The hypoxia condition did not obviously affect the fluorescence response signal during the in-solution test. The fluorescence signal at 540 enhanced in a dose-dependent enhancement along with the increase of the Cys concentration. The probe showed the advantages including relatively long linear range, high sensitivity, high stability, and high selectivity. With low cyto-toxicity, TPB-Cys achieved the monitoring of the endogenous Cys level in living pulmonary cells. Furthermore, it also realized the visualization of the affection of the hypoxia and hypoxia recovered conditions. This work was informative for both the accurate diagnosis and potential medical techniques.

A novel hollow flower shaped Cu9S8 antibacterial agent for removing sulfonamide in water environment: effects of composite with magnetic biochar, differential adsorption, and mechanism study.

In this study, hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC with adsorption and antibacterial properties was prepared by coprecipitation and solvothermal method, respectively. The adsorption results showed that the Cu9S8 exhibited excellent adsorption performance on sulfonamide antibiotics (SAs), especially for sulfamethoxazole (SMZ). The optimal addition amount of Cu9S8 is 0.2 g, which results in a maximum adsorption capacity of 33.4 mg/g for SMZ within 120 min. The fitting results of adsorption and desorption kinetics and thermodynamics, as well as the conditions such as pH value and ionic strength were compared. It was found that different interactions led to the differential adsorption of SAs by Cu9S8. The desorption experiment further elucidated its adsorption mechanism. The large desorption capacity indicates that SAs on Cu9S8 can be further recovered and treated. The auto-deposition characteristics of Cu9S8 and the hysteresis loop of Cu9S8/Fe3O4@BC were studied to effectively recover Cu9S8 from aquatic environments. Additionally, more than 99% of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were exterminated by Cu9S8 and Cu9S8/Fe3O4@BC within 20 min. The above results suggested that the hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC composite materials can provide a new strategy for solving pollution problems and waste treatment.

A fluorescent probe for monitoring carboxylesterases in pulmonary cells under permissive hypercapnia condition.

Herein, by combining the benzofuranone-derived fluorophore and the carbamate recognition group, a fluorescent probe named BFO-CarE was developed for monitoring the carboxylesterase (CarE) level in pulmonary cells under the permissive hypercapnia condition. It showed a notable fluorescence response towards CarE at 570 nm under the excitation of 510 nm. The in-solution tests revealed the advantages of BFO-CarE including high sensitivity, high specificity, relatively rapid response, and high steadiness. It was also low-toxic upon the pulmonary cell lines. During the intracellular imaging in pulmonary cells, BFO-CarE achieved the monitoring of the CarE level in both inhibition and activation status. In particular, BFO-CarE realized the visualization of the affection of the permissive hypercapnia condition on the CarE level, which indicated the hypoxia tolerance of CarE. This work was informative for investigating the impact of hypoxia in pulmonary cells, and the corresponding anaesthesia-related approaches.

Developing a vanillin-derived imidazo-pyridin-containing fluorescent probe for imaging cysteine in living pulmonary cells under oxygen supply variation.

In this work, derived from vanillin and imidazo-pyridin backbone, a fluorescent probe IPV-Cys was developed for imaging the cysteine (Cys) level in living pulmonary cells under oxygen supply variation. By mimicking the oxygen supply variation in both the solution test and cellular imaging, the optical performance and imaging effect of IPV-Cys was investigated. In the solution system, the oxygen supply variation caused no impact on the reporting signals. The fluorescence reporting signal intensity at 490 nm suggested the enhancement along with the increase of the Cys concentration. The advantages of IPV-Cys included relatively high sensitivity, high stability, and high selectivity. On the basis of the low cyto-toxicity, IPV-Cys achieved the monitoring the endogenous Cys level in in living pulmonary cells and the impact of the oxygen supply variation by reporting fluorescence signals. The information here was meaningful for both the pre-clinical diagnosis and surgical techniques.

CD36-mediated accumulation of MDSCs exerts abscopal immunosuppressive responses in hepatocellular carcinoma after insufficient microwave ablation.

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8+ T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC.

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice.

Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment.

DCDC2 inhibits hepatic stellate cell activation and ameliorates CCl4-induced liver fibrosis by suppressing Wnt/ß-catenin signaling.

Liver fibrosis, as a consequence of chronic liver disease, involves the activation of hepatic stellate cell (HSC) caused by various chronic liver injuries. Emerging evidence suggests that activation of HSC during an inflammatory state can lead to abnormal accumulation of extracellular matrix (ECM). Investigating novel strategies to inhibit HSC activation and proliferation holds significant importance for the treatment of liver fibrosis. As a member of the doublecortin domain-containing family, doublecortin domain containing 2 (DCDC2) mutations can lead to neonatal sclerosing cholangitis, but its involvement in liver fibrosis remains unclear. Therefore, this study aims to elucidate the role of DCDC2 in liver fibrosis. Our findings revealed a reduction in DCDC2 expression in both human fibrotic liver tissues and carbon tetrachloride (CCl4)-induced mouse liver fibrotic tissues. Furthermore, exposure to transforming growth factor beta-1(TGF-ß1) stimulation resulted in a dose- and time-dependent decrease in DCDC2 expression. The overexpression of DCDC2 inhibited the expression of α-smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1α1), and reduced the activation of HSC stimulated with TGF-ß1. Additionally, we provided evidence that the Wnt/ß-catenin signaling pathway was involved in this process, wherein DCDC2 was observed to inhibit ß-catenin activation, thereby preventing its nuclear translocation. Furthermore, our findings demonstrated that DCDC2 could attenuate the proliferation and epithelial-mesenchymal transition (EMT)-like processes of HSC. In vivo, exogenous DCDC2 could ameliorate CCl4-induced liver fibrosis. In summary, DCDC2 was remarkably downregulated in liver fibrotic tissues of both humans and mice, as well as in TGF-ß1-activated HSC. DCDC2 inhibited the activation of HSC induced by TGF-ß1 in vitro and fibrogenic changes in vivo, suggesting that it is a promising therapeutic target for liver fibrosis and warrants further investigation in clinical practice.

The efficacy and safety of PD-1 inhibitor combined with TACE in the first-line treatment of unresectable hepatocellular carcinoma.

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

[Research Progress on the Mechanism of PI3K/AKT/mTOR Signaling Pathway in Multiple Myeloma --Review].

PI3K/AKT/mTOR signaling pathway is of great significance in the development and prognosis of tumors, and is closely related to the pathogenesis of multiple myeloma (MM). PI3K/AKT/mTOR signaling pathway can participate in the regulation of MM through multichannel and multitarget, such as regulating the tumor microenvironment of MM cells survival, affecting tumor development and migration, regulating the proliferation, apoptosis and autophagy of MM cells. It have shown that after the PI3K/AKT/mTOR signaling pathway is inhibited, the apoptosis and autophagy of MM cells are activated, which promote the death of MM cells and inhibit the metastasis and recurrence of MM cells. Therefore, indepth study of the mechanism of PI3K/AKT/mTOR signaling pathway in MM is helpful to elucidate the pathogenesis and prognosis of MM.

[Research Progress on Effect of Bone Marrow Microenvironment Regulated by IL-6/IL-6R/JAK2/STAT3 Pathway on Biological Behavior of Multiple Myeloma--Review].

Multiple myeloma (MM) is a malignant disease with abnormal proliferation of clonal plasma cells. The development of the disease shows a vast heterogeneity, which is closely related to the interaction between MM cells and bone marrow microenvironment (BMM). The interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway can regulate the transcription of related soluble factors in BMM, promote the proliferation, anti-apoptosis, drug resistance and guide related bone destruction of MM cells. This article reviews the research progress on the effect of BMM regulated by IL-6/IL-6R/JAK2/STAT3 pathway on the biological behavior of MM, in order to provide new research ideas for targeted therapy and precise therapy of MM.

A state-of-the-science review of using mitochondrial DNA copy number as a biomarker for environmental exposure.

Mitochondria are bioenergetic, biosynthetic, and signaling organelles in eukaryotes, and contain their own genomes, mitochondrial DNA (mtDNA), to supply energy to cells by generating ATP via oxidative phosphorylation. Therefore, the threat to mitochondria' integrity and health resulting from environmental exposure could induce adverse health effects in organisms. In this review, we summarized the association between mtDNA copy number (mtDNAcn), and environmental exposures as reported in the literature. We conducted a literature search in the Web of Science using [Mitochondrial DNA copy number] and [Exposure] as two keywords and employed three selection criteria for the final inclusion of 97 papers for review. The consensus of data was that mtDNAcn could be used as a plausible biomarker for cumulative exposures to environmental chemical and physical agents. In order to furtherly expand the application of mtDNAcn in ecological and environmental health research, we suggested a series of algorithms aiming to standardize the calculation of mtDNAcn based on the PCR results in this review. We also discussed the pitfalls of using whole blood/plasma samples for mtDNAcn measurements and regard buccal cells a plausible and practical alternative. Finally, we recognized the importance of better understanding the mechanistic analysis and regulatory mechanism of mtDNAcn, in particular the signals release and regulation pathways. We believe that the development of using mtDNAcn as an exposure biomarker will revolutionize the evaluation of chronic sub-lethal toxicity of chemicals to organisms in ecological and environmental health research that has not yet been implemented.

Lotusine ameliorates propionic acid-induced autism spectrum disorder-like behavior in mice by activating D1 dopamine receptor in medial prefrontal cortex.

Autism spectrum disorder (ASD) is a multifaceted neuropsychiatric condition for which effective drug therapy for core clinical symptoms remains elusive. Lotusine, known for its neuroprotective properties in the treatment of neurological disorders, holds potential in addressing ASD. Nevertheless, its specific efficacy in ASD remains uncertain. This study aims to investigate the therapeutic potential of lotusine in ASD and elucidate the underlying molecular mechanisms. We induced an ASD mouse model through intracerebroventricular-propionic acid (ICV-PPA) injection for 7 days, followed by lotusine administration for 5 days. The efficacy of lotusine was evaluated through a battery of behavioral tests, including the three-chamber social test. The underlying mechanisms of lotusine action in ameliorating ASD-like behavior were investigated in the medial prefrontal cortex (mPFC) using whole-cell patch-clamp recordings, western blotting, immunofluorescence staining, molecular docking, and cellular thermal shift assay. The efficacy and mechanisms of lotusine were further validated in vitro. Lotusine effectively alleviated social deficits induced by ICV-PPA injection in mice by counteracting the reduction in miniature excitatory postsynaptic current frequency within the mPFC. Moreover, lotusine enhanced neuronal activity and ameliorated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor dysfunction in ICV-PPA infusion mice by upregulating c-fos, p-GluA1 Ser 845, and p-GluA1 Ser 831 protein levels within the mPFC. Our findings also suggest that lotusine may exert its effects through modulation of the D1 dopamine receptor (DRD1). Furthermore, the rescuing effects of lotusine were nullified by a DRD1 antagonist in PC12 cells. In summary, our results revealed that lotusine ameliorates ASD-like behavior through targeted modulation of DRD1, ultimately enhancing excitatory synaptic transmission. These findings highlight the potential of lotusine as a nutritional supplement in the treatment of ASD.

Pretreatment with low-frequency magnetic fields can improve the functional properties of pea globulin amyloid-like fibrils.

Plant protein fibrils have recently attracted considerable attention due to their superior mechanical and interfacial properties. The objective of this study was to evaluate the feasibility of low-frequency magnetic field (LF-MF) pretreatment in enhancing the conversion and functional characteristics of the amyloid-like fibrils derived from pea globulin (PG), which was considered a sustainable hypoallergenic protein. The results showed that LF-MF-treated PG (MPG) assembled into longer amyloid-like fibrils compared with native PG (NPG). The MPG presented similar gelling, emulsifying, and foaming properties to the NPG, while the fibril samples exhibited significantly improved functional properties. Moreover, the amyloid-like fibrils generated from the MPG (MPGF) showed large aspect ratios accompanied by superior solubility, molecular flexibility, emulsion stability, and gelling properties. The improved functional properties of the amyloid-like fibrils generated from the MPG can provide a promising outlook for expanding the applications of the PG in food, medicine and other fields.

Therapeutic Potential of Kaempferol against Sleep Deprivation-Induced Cognitive Impairment: Modulation of Neuroinflammation and Synaptic Plasticity Disruption in Mice.

Sleep deprivation (SD) has led to a rise in cognitive impairment (CI) cases. Kaempferol (KMP), known for its anti-inflammatory and antiapoptotic properties, holds promise in countering SD-induced CI. Experimental validation using a sleep-deprived CI model confirmed KMP's efficacy in mitigating CI. Immunofluorescence investigations emphasized diminished activation of astrocytes and reduced the proliferation of microglia in the hippocampus of mice subjected to SD. Subsequently, network pharmacological analyses were conducted and found that KMP may be closely related to the mitogen-activated protein kinase (MAPK) pathway in SD-induced CI. The influence of KMP on the MAPK pathway was verified by the observed decrease in the expression of phosphorylated JNK (p-JNK) and p38 (p-p38). Analyzing hippocampal AMPARS and NMDARS expression indicated KMP's ability to enhance GluA1 phosphorylation (Ser831 and Ser845) and GluN2A levels. Patch clamp assays demonstrated heightened excitatory transmitter transmission in the hippocampus, suggesting KMP's positive influence. Overall, KMP combats neuroinflammation via MAPK inhibition, augments synaptic function, and addresses learning and memory dysfunction in sleep-deprived mice.

Development of arachin and basil seed gum composite gels for the encapsulation and controlled release of vitamin D3.

In this study, the textural and rheological properties of arachin and basil seed gum composite gels (ABG) were successfully regulated by the addition of sodium chloride (NaCl) and transglutaminase (TGase). The texture profile analysis (TPA) results showed that the hardness and springiness of the ABG were significantly enhanced by adding TGase (p < 0.05). Particularly, the composite gel added with NaCl first and subsequently crosslinked by TGase (ABG-Na+-TG) showed a higher hardness value of 186.0 ± 6.1 g. ABG-Na+-TG showed a higher amplitude of strain with lower compliance in the creep and recovery test and exhibited a better elastic behavior. These composite gels were employed as new delivery systems to encapsulate and deliver vitamin D3 (VD3). ABG-Na+-TG showed a higher VD3 encapsulation efficiency of 91.7 % and a better protection of VD3 under different temperatures or UV light, as well as an improved storage stability of VD3. Furthermore, the release of VD3 in the simulated gastric digestion could be controlled by ABG-Na+-TG and the bioaccessibility after digestion was 32.9 %. These results suggest that ABG-Na+-TG can be utilized as a promising delivery system of VD3.

Cloning, Heterologous Expression, and Characterization of a Neutral Uricase from Arthrobacter sp. CSAJ-16 in Cangshan Mountain.

Uricase (or Urate oxidase), a key enzyme involved in purine metabolism, is commonly used in treating conditions such as gout, hyperuricemia, and tumor lysis syndrome. In this study, a uricase-producing strain (named CSAJ-16) was isolated from the soil sample of Cangshan Mountain, Yunnan Province, China. This strain was identified as Arthrobacter sp. CSAJ-16. Based on the gene sequence alignment, the uricase gene (named aruox) of Arthrobacter sp. CSAJ-16 was amplified and heterologously expressed. The recombinant uricase (ArUOX) was about 32 kDa. The optimal pH and temperature of ArUOX were pH 7 and 20°C, respectively. The ArUOX remained above 50% relative activity after incubation at 37°C for 100 min or at pH 6.0-8.6 for 24 h. Moreover, metal ions such as K+, Mg2+, Ca2+, Ba2+ and Pb2+ can significantly enhance the activity of ArUOX (> 200%). These enzymatic properties indicate that ArUOX has potential applications in pharmaceutical enzymes and uric acid detection kits.

Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

Luteolin in the Qi Bi Anshen decoction improves propionic acid-induced autism-like behavior in rats by inhibiting LRP1/MMP9.

BACKGROUND: A neurodevelopmental illness with a high frequency and unidentified pathophysiology is known as autism spectrum disorder (ASD). A research hotspot in this field is the identification of disease-specific biomarkers and drug intervention targets. Traditional Chinese medicine (TCM) can eliminate the symptoms of autism by precisely regulating human physiology. The Qi Bi Anshen decoction (QAT) is a commonly used TCM clinical drug commonly-used to treat for treating ASD. However, the primary active ingredients and underlying mechanisms of action of this decoction remain unknown. PURPOSE: This study aimed to investigate the active ingredients and pharmacodynamics of QAT in the treatment of ASD using a Sprague-Dawley rat model that resembled autism. METHODS: Autism-like rat models were established through intracerebroventricular injections of propionic acid (PPA). Subsequently, the rats were treated with QAT, and their efficacy was evaluated using the three-chamber method to analyze social interactions and grooming behavior. Additionally, open-field tests, elevated cross-maze tests, hematoxylin and eosin staining, Nissl staining, and enzyme-linked immunosorbent assays were performed; Western blot analysis was employed to determine the expression of synaptic plasticity-related proteins. Utilizing ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS), the effectiveness of active QAT components was assessed, and potential QAT targets were screened through molecular docking, surface plasmon resonance, and thermal migration experiments. To better understand the precise processes involved in treating ASD with active QAT components, in vivo and in vitro knockdown tests were also performed. RESULTS: QATexhibited a significant improvement in autism-like behavior and a notable increase in the production of proteins associated with synaptic plasticity. Furthermore, luteolin (LUT), identified as a potentially important active ingredient in QAT for treating ASD, reduced matrix metallopeptidase-9 (MMP9) expression. However, this effect was attenuated by the knockdown of low-density lipoprotein receptor-associated protein 1 (LRP1), which is the target binding site for LUT. CONCLUSIONS: LUT emerges as a potentially crucial active component of QAT in the treatment of ASD, with the ability to antagonize LRP1 and subsequently reduce MMP9 expression.

Development and usability of a Mobile Interactive Application (VCPW) for Vascular Crisis Prewarning after Skin Flap Transplantation.

Background: In microsurgical tissue transfer, skin flap transplantation is frequently used to heal the surface of a wound. Effective microcirculation surveillance of the skin flap is crucial. However, with traditional monitoring methods-that is, clinical observation-vascular crisis can still occur, thereby impairing postoperative recovery. A smartphone application is required to assist health care professionals in the standardized collection of flap perfusion parameters for flap management. Methods: The Vascular Crisis Prewarning Application was created using a design science research methodology that prioritizes users and problems. The system usability scale was used to assess the application's usability among medical practitioners. The application was used at the clinic from December 2020 to September 2022. The unplanned return to the operating room, time to diagnose vascular crisis, and flap survival rate were compared with and without the application. Results: The application consisted of 5 modules: patient addition and basic information entry, flap labeling, flap observation, crisis warning, and case archiving. The average rating for the application's usability among medical practitioners was 97.95 score (SD 2.36). With the application, the time to detect vascular crisis reduced from 26.71 to 16.26 h (P < 0.001), the unplanned return to the operation room increased from 8.18% to 10.24% (P = 0.587), and the flap survival rate went from 94.55% to 99.21% (P = 0.083). Conclusions: An easy-to-use flap perfusion monitoring and prewarning application for medical practitioners was produced using a user-centered development method. The application provided a more standardized and accurate platform for data collection in flap management and reduced the time to detect vascular crisis. Larger cohort studies are required in the future to better assess the full potential of the application.

Research review on the pollution of antibiotic resistance genes in livestock and poultry farming environments.

Increasingly serious pollution of antibiotic resistance genes (ARGs) caused by the abuse of antibiotics in livestock and poultry industry has raised worldwide concerns. ARGs could spread among various farming environmental media through adsorption, desorption, migration, and also could transfer into human gut microbiome by hori-zontal gene transfer (HGT), posing potential threats to public health. However, the comprehensive review on the pollution patterns, environmental behaviors, and control techniques of ARGs in livestock and poultry environments in view of One Health is still inadequate, resulting in the difficulties in effectively assessing ARGs transmission risk and developing the efficient control strategies. Here, we analyzed the pollution characteristics of typical ARGs in various countries, regions, livestock species, and environmental media, reviewed the critical environmental fate and influencing factors, control strategies, and the shortcomings of current researches about ARGs in the livestock and poultry farming industry combined with One Health philosophy. In particular, we addressed the importance and urgency of identifying the distribution characteristics and environmental process mechanisms of ARGs, and developing green and efficient ARG control means in livestock farming environments. We further proposed gaps and prospects for the future research. It would provide theoretical basis for the research on health risk assessment and technology exploitation of alleviating ARG pollution in livestock farming environment.