Development of a multispectral fluorescence LiDAR for point cloud segmentation of plants.

The accelerating development of high-throughput plant phenotyping demands a LiDAR system to achieve spectral point cloud, which will significantly improve the accuracy and efficiency of segmentation based on its intrinsic fusion of spectral and spatial data. Meanwhile, a relatively longer detection range is required for platforms e.g., unmanned aerial vehicles (UAV) and poles. Towards the aims above, what we believe to be, a novel multispectral fluorescence LiDAR, featuring compact volume, light weight, and low cost, has been proposed and designed. A 405 nm laser diode was employed to excite the fluorescence of plants, and the point cloud attached with both the elastic and inelastic signal intensities that was obtained through the R-, G-, B-channels of a color image sensor. A new position retrieval method has been developed to evaluate far field echo signals, from which the spectral point cloud can be obtained. Experiments were designed to validate the spectral/spatial accuracy and the segmentation performance. It has been found out that the values obtained through the R-, G-, B-channels are consistent with the emission spectrum measured by a spectrometer, achieving a maximum R2 of 0.97. The theoretical spatial resolution can reach up to 47 mm and 0.7 mm in the x- and y-direction at a distance of around 30 m, respectively. The values of recall, precision, and F score for the segmentation of the fluorescence point cloud were all beyond 0.97. Besides, a field test has been carried out on plants at a distance of about 26 m, which further demonstrated that the multispectral fluorescence data can significantly facilitate the segmentation process in a complex scene. These promising results prove that the proposed multispectral fluorescence LiDAR has great potential in applications of digital forestry inventory and intelligent agriculture.

Resveratrol protects against high glucose-induced steroidogenesis and apoptosis in murine granulosa cells.

Resveratrol (Res) is a polyphenolic compound that exhibits a diverse array of biological effects. Herein, we detected the ability of Res on murine granulosa cells (GCs) against impaired steroidogenesis and apoptotic death in response to high glucose levels. Ovarian GCs were harvested from C57BL/6 mice and cultured in steroidogenic media supplemented with follicle-stimulating hormone (FSH, 30 ng/mL), Res (50 µmol/L), and low or high glucose concentrations (5 mM or 30 mM). After culture for 24 h, cell supernatants were harvested and the levels of progesterone and estradiol therein were measured. Also, caspase-3 activity and the expression of genes associated with apoptosis and steroidogenesis were assessed. High-glucose treatment suppressed steroidogenesis in this assay system, resulting in the impaired expression of steroidogenesis-related genes including Cyp11a1, Cyp19a1, 3ßHSD, and StAR and a concomitant decrease in progesterone and estradiol production. Cells exposed to high glucose also exhibited apoptotic phenotypes characterized by Bax upregulation, Bcl-2 downregulation, and increased caspase-3 activity levels. However, Res treatment was sufficient to reverse this high glucose level-induced apoptotic and steroidogenic phenotypes with improving progesterone and estradiol production, and these maybe related the effects of Res on Cyp11a1, Cyp19a1, 3ßHSD, and StAR expressions. These data suggested that Res is well suited to overcoming the negative effects of hyperglycemia of GC functionality.

Factors Influencing Professional Identity of Psychiatric Nurses as Second Victims: A Cross-Sectional Study.

The current study aimed to explore the status and influencing factors of professional identity among psychiatric nurses as second victims in China by using a cross-sectional design. We investigated 291 psychiatric nurses from two psychiatric hospitals. Participants were asked to complete a demographic questionnaire, Second Victim Experience and Support Scale, Multidimensional Health Locus of Control Scale, and Professional Identity Scale for Nurses. Scores of professional identity of psychiatric nurses as second victims were moderate. Regression analysis showed that the second victim experience and support and internal control were significant predictors, explaining 34.2% of the variance in professional identity. Identifying risk factors related to the professional identity of psychiatric nurses as second victims will help managers take timely preventive measures to improve the awareness of the self-health responsibility of psychiatric nurses and reduce the adverse effects of patient safety incidents to enhance their professional identity. [Journal of Psychosocial Nursing and Mental Health Services, 61(12), 47-54.].

Pantothenate protects against obesity via brown adipose tissue activation.

Brown adipose tissue (BAT) is the primary site of adaptive thermogenesis, which is involved in energy expenditure and has received much attention in the field of obesity treatment. By screening a small-molecule compound library of drugs approved by the Food and Drug Administration, pantothenic acid was identified as being able to significantly upregulate the expression of uncoupling protein 1 (UCP1), a key thermogenic protein found in BAT. Pantothenate (PA) treatment decreased adiposity, reversed hepatic steatosis, and improved glucose homeostasis by increasing energy expenditure in C57BL/6J mice fed a high-fat diet. PA also significantly increased BAT activity and induced beige adipocytes formation. Mechanistically, the beneficial effects were mediated by UCP1 because PA treatment was unable to ameliorate obesity in UCP1 knockout mice. In conclusion, we identified PA as an effective BAT activator that can prevent obesity and may represent a promising strategy for the clinical treatment of obesity and related metabolic diseases.NEW & NOTEWORTHY PA treatment effectively and safely protected against obesity via the BAT-UCP1 axis. PA has therapeutic potential for treating obesity and type II diabetes.

Prevalence and Clinical and Endoscopic Characteristics of Cervical Inlet Patch (Heterotopic Gastric Mucosa): A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical inlet patch (CIP), also called gastric inlet patch, is a heterotopic columnar mucosal island located in the cervical esophagus, which has been under-recognized by clinicians. AIM: We conducted a systemic review and meta-analysis to explore the prevalence and clinical and endoscopic characteristics of CIP. MATERIALS AND METHODS: Studies were searched through the PubMed, EMBASE, and Cochrane Library databases. The prevalence of CIP with 95% confidence interval (CI) was pooled by using a random-effect model. The association of CIP with demographics, clinical presentations, and endoscopic features was evaluated by odds ratios (ORs). RESULTS: Fifty-three studies including 932,777 patients were eligible. The pooled prevalence of CIP was 3.32% (95% CI=2.86%-3.82%). According to the endoscopic mode, the pooled prevalence of CIP was higher in studies using narrow-band imaging than in those using white light and esophageal capsule endoscopy (9.34% vs. 2.88% and 0.65%). The pooled prevalence of CIP was higher in studies where the endoscopists paid specific attention to the detection of this lesion (5.30% vs. 0.75%). CIP was significantly associated with male (OR=1.24, 95% CI=1.09-1.42, P=0.001), gastroesophageal reflux disease (OR=1.32, 95% CI=1.04-1.68, P=0.03), reflux symptoms (OR=1.44, 95% CI=1.14-1.83, P=0.002), dysphagia (OR=1.88, 95% CI=1.28-2.77, P=0.001), throat discomfort (OR=4.58, 95% CI=1.00-21.02, P=0.05), globus (OR=2.95, 95% CI=1.52-5.73, P=0.001), hoarseness (OR=4.32, 95% CI=1.91-9.78, P=0.0004), cough (OR=3.48, 95% CI=1.13-10.72, P=0.03), Barrett's esophagus (OR=2.01, 95% CI=1.37-2.94, P=0.0003), and esophagitis (OR=1.62, 95% CI=1.27-2.07, P=0.0001). CONCLUSION: CIP appears to be common by using narrow-band imaging, especially if the endoscopists would like to pay attention to the detection of this lesion. CIP is clearly associated with acid-related symptoms and Barrett's esophagus.

CD205+ polymorphonuclear myeloid-derived suppressor cells suppress antitumor immunity by overexpressing GLUT3.

Myeloid-derived suppressor cells (MDSCs) are responsible for antitumor immunodeficiency in tumor-bearing hosts. Primarily, MDSCs are classified into 2 groups: monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs. In most cancers, PMN-MDSCs (CD11b+ Ly6Clow Ly6G+ cells) represent the most abundant MDSC subpopulation. However, the functional and phenotypic heterogeneities of PMN-MDSC remain elusive, which delays clinical therapeutic targeting decisions. In the 4T1 murine tumor model, CD11b+ Ly6Glow PMN-MDSCs were sensitive to surgical and pharmacological interventions. By comprehensively analyzing 64 myeloid cell-related surface molecule expression profiles, cell density, nuclear morphology, and immunosuppressive activity, the PMN-MDSC population was further classified as CD11b+ Ly6Glow CD205+ and CD11b+ Ly6Ghigh TLR2+ subpopulations. The dichotomy of PMN-MDSCs based on CD205 and TLR2 is observed in 4T07 murine tumor models (but not in EMT6). Furthermore, CD11b+ Ly6Glow CD205+ cells massively accumulated at the spleen and liver of tumor-bearing mice, and their abundance correlated with in situ tumor burdens (with or without intervention). Moreover, we demonstrated that CD11b+ Ly6Glow CD205+ cells were sensitive to glucose deficiency and 2-deoxy-d-glucose (2DG) treatment. Glucose transporter 3 (GLUT3) knockdown by siRNA significantly triggered apoptosis and reduced glucose uptake in CD11b+ Ly6Glow CD205+ cells, demonstrating the dependence of CD205+ PMN-MDSCs survival on both glucose uptake and GLUT3 overexpression. As GLUT3 has been recognized as a target for the rescue of host antitumor immunity, our results further directed the PMN-MDSC subsets into the CD205+ GLUT3+ subpopulation as future targeting therapy.

Development of an all-day portable polarization lidar system based on the division-of-focal-plane scheme for atmospheric polarization measurements.

A portable polarization lidar system based on the division-of-focal-plane scheme has been proposed for all-day accurate retrieval of the atmospheric depolarization ratio. The polarization lidar system has been designed as a T-shaped architecture consisting of a closed transmitter and a detachable large focal receiver, which is capable of outdoor unmanned measurements. The lidar system features low cost, low maintenance and short blind range (∼100 m) by utilizing a 450 nm multimode laser diode as the light source and a polarization image sensor with four polarized channels as the detector. Validation measurements have been carried out on a near horizontal path in ten consecutive days. The linear volume depolarization ratio (LVDR) as well as its measurement uncertainty has been theoretically and experimentally evaluated without employing additional optical components and sophisticated online calibrations. The offset angle can also be accurately retrieved (i.e., -0.06°) from the four-directional polarized lidar profiles with a standard deviation of ±0.02° during the whole measurement period, which contributes negligible influence on the retrieval of the LVDR. It has been found out that the uncertainty of the LVDR was mainly originated from the random noise, which was below 0.004 at nighttime and may reach up to 0.008 during daytime owing to the increasing sunlight background. The performance of the polarization lidar system has been further examined through atmospheric vertical measurements. The low-cost low-maintenance portable polarization lidar system, capable of detecting four-directional polarized lidar signals simultaneously, opens up many possibilities for all-day field measurements of dust, cloud, urban aerosol, oriented particles, etc.

Quantitative analysis of differentially expressed milk fat globule membrane proteins between donkey and bovine colostrum based on high-performance liquid chromatography with tandem mass spectrometry proteomics.

This study was designed to provide novel insights into milk fat globule membrane (MFGM) proteins in donkey colostrum (DC) and bovine colostrum (BC) using quantitative proteomics. In total, 179 (DC) and 195 (BC) MFGM proteins were characterized, including 71 shared, 108 DC-specific, and 124 BC-specific proteins. Fifty-one shared proteins were selected as differentially expressed MFGM proteins, including 21 upregulated and 30 downregulated proteins in DC. Gene ontology analysis showed that these proteins were mainly enriched in cellular components, including the extracellular exosome, extracellular space, and plasma membrane. Additionally, they were further involved in metabolic pathways, including cholesterol metabolism, the peroxisome proliferator-activated receptor signaling pathway, and purine metabolism. Furthermore, several key protein factors with high connectivity were identified via protein-protein interaction analysis. These results provide more comprehensive knowledge of differences in the biological properties of MFGM proteins in DC and BC as well as pave the way for future studies of the nutritional and functional requirements of these important ingredients toward the development of dairy products based on multiple milk sources.

Nurses' experiences and support needs following workplace violence: A qualitative systematic review.

AIMS AND OBJECTIVES: To systematically identify, appraise and synthesise existing qualitative studies exploring nurses' lived experiences of workplace violence by patients, families and hospital visitors, identifying their support needs following workplace violence. BACKGROUND: Workplace violence against nurses is a significant concern globally, as it leads to serious negative consequences for nurses, patients and organisations as a whole. Having adequate support is considered significant. While numerous studies have been conducted on workplace violence, few qualitative reviews have focused on identifying nurses' support needs following episodes of workplace violence. METHODS: Four databases (MEDLINE, CINAHL, PsychINFO and Scopus) were systematically searched. Additionally, hand searching of prominent journals, grey literature and reference lists of included studies was also performed to identify additional research. The Critical Appraisal Skills Programme checklist for qualitative studies was used to assess all included articles. Thomas and Harden's three-stage approach to thematic analysis was followed, using the ENTREQ statement for reporting. RESULTS: Ten studies published in English, conducted across eight countries, met the inclusion criteria. Four analytical themes relating to nurses' experiences were identified: "inevitable and unpredictable trauma in the career" "higher tolerance and understanding of unintentional violence," "positive learning or passive adjustment" and "struggle with the role and behaviour conflict." In terms of nurses' support needs, the analysis yielded two themes: "informal support needs" and "formal support needs." CONCLUSION: Nurses experience significant and lasting psychological trauma due to workplace violence; however, the support for nurses remains seriously inadequate. Establishing an effective and robust support system based on nurses' needs must be viewed as a priority for organisations, as well as researchers. RELEVANCE TO CLINICAL PRACTICE: Institutions and managers have a duty to maintain an awareness of nurses' experiences and support needs regarding workplace violence. There is a need for further policymaking and research, based on clinical practice, in order to develop effective preventive and interventive strategies regarding workplace violence.

Risk of Stroke in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Liver cirrhosis can lead to abnormal coagulation, rendering patients at risk for bleeding but also thrombotic complications. We conducted a systematic review and meta-analysis to explore the epidemiology of stroke in liver cirrhosis and the potential association between them. MATERIALS AND METHODS: Studies were searched through the PubMed, EMBASE, and Cochrane Library databases. Incidence and prevalence of unspecific stroke, hemorrhagic stroke, intracranial hemorrhage, subarachnoid hemorrhage, and ischemic stroke were pooled by using a random-effect model. Meta-regression analyses were employed to explore the sources of heterogeneity. As for the cohort studies, hazard ratios (HRs) with 95% CIs were pooled to evaluate the association between liver cirrhosis and stroke. RESULTS: Twenty-seven studies with 93,191 cirrhotic patients were included, of which 23 explored the incidence and 10 explored the prevalence. The pooled incidence of unspecific stroke, hemorrhagic stroke, intracranial hemorrhage, and ischemic stroke was 4.1%, 1.3%, 2.0%, and 3.7%, respectively. The pooled prevalence of unspecific and ischemic stroke was 9.0% and 2.6%, respectively. Heterogeneity among studies was significant in most of meta-analyses. Meta-regression analyses indicated that the sample size might explain the potential source of heterogeneity (P=0.018). Liver cirrhosis significantly increased the risk of subarachnoid (HR=2.36; 95% CI, 1.80-3.09; P=0.000) and intracranial hemorrhage (HR=1.48; 95% CI, 1.06-2.05; P=0.020), but not unspecific (HR=1.02; 95% CI, 0.49-2.14; P=0.960), ischemic (HR=0.79; 95% CI, 0.46-1.35; P=0.380), or hemorrhagic stroke (HR=1.88; 95% CI, 0.52-6.81; P=0.335). CONCLUSIONS: Stroke is uncommon in cirrhotic patients. However, considering a positive relationship of liver cirrhosis with subarachnoid and intracranial hemorrhage, the prophylactic strategy may be selectively adopted in cirrhotic patients.

Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells.

Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium graminearum. It is one of the most common feed contaminants that poses a serious threat to the health and performance of dairy cows. This study investigated the in vitro cytotoxicity of DON on bovine mammary epithelial cells (MAC-T). DON at different concentrations (0.25, 0.3, 0.5, 0.8, 1 or 2 µg/ml) inhibited the growth of MAC-T cells after 24 hr of exposure (p < .001). DON at 0.25 µg/ml increased lactate dehydrogenase (LDH) leakage (p < .05); decreased glutathione (GSH) levels (p < .001), total superoxide dismutase (T-SOD) activity and total antioxidant capacity (T-AOC; p < .01); and increased malondialdehyde (MDA) concentration (p < .01) in MAC-T cells after 24 hr of exposure. We also observed that DON increased reactive oxygen species (ROS) levels in cells incubated for 9, 15 and 24 hr (p < .001). DON at 0.25 µg/ml triggered oxidative damage in MAC-T cells. Furthermore, it induced an inflammatory response in the cells incubated for 9, 15 and 24 hr (p < .05) by increasing the mRNA expression levels of nuclear factor kappa B, myeloid differentiation factor 88 (MyD88), tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, cyclooxygenase-2 and IL-8. We further examined the effect of DON on apoptosis. DON prevented normal proliferation of MAC-T cells by blocked cell cycle progression in 24 hr (p < .001). In addition, the apoptosis rate measured using annexin V-FITC significantly increased (p < .05) with increase in the mRNA expression level of Bax (p < .01) and increase in the Bax/Bcl-2 ratio (p < .01) in cells incubated for 24 hr. In summary, DON exerts toxic effects in MAC-T cells by causing oxidative stress, inducing an inflammatory response, affecting cell cycle and leading to apoptosis.

Effects of adding bile acids to dietary storage japonica brown rice on growth performance, meat quality, and intestinal microbiota of growing-finishing Min pigs.

Introduction: This study investigated the effects of storage japonica brown rice (SJBR) and bile acids (BA) on the growth performance, meat quality, and intestinal microbiota of growing-finishing Min pigs. Methods: A total of 24 healthy Min pigs with a similar body weight of 42.25 ± 2.13 kg were randomly divided into three groups with eight replicates of one pig each. The groups were as follows: CON (50% corn), SJBR (25% corn +25% SJBR), and SJBR + BA (25% corn +25% SJBR +0.025% hyodeoxycholic acid). The experimental period lasted from day 90 (the end of the nursery phase) to day 210 (the end of the finishing phase). Results: The results showed the following: (1) Compared with the CON group, there was no significant difference in the average daily gain (ADG) and average daily feed intake (ADFI) of the SJBR and SJBR + BA groups, and the feed conversion ratio (FCR) was significantly decreased (p < 0.05). (2) Compared with the CON group, the total protein (TP) content in the serum was significantly increased, and the blood urea nitrogen (BUN) content was significantly decreased (p < 0.05) in the SJBR and SJBR + BA groups; moreover, HDL-C was significantly higher by 35% (p < 0.05) in the SJBR + BA group. (3) There were no significant differences in carcass weight, carcass length, pH, drip loss, cooking loss, and shear force among the groups; the eye muscle area was significantly increased in the SJBR group compared with the CON group (p < 0.05); back fat thickness was significantly decreased in the SJBR + BA group compared with the SJBR group (p < 0.05); and the addition of SJBR significantly increased the mRNA expression of MyHC I in the longissimus dorsi (LD) muscle of growing-finishing Min pigs (p < 0.05). (4) The cecal bacteria were detected using 16S rDNA, and the proportion of Lactobacillus was increased gradually at the genus level, but there was no significant difference among the different groups. Conclusion: In conclusion, 25% SJBR can improve the growth performance and increase the abundance of intestinal beneficial bacteria, and based on this, adding bile acids can reduce the back fat thickness of growing-finishing Min pigs.

Salmonella-mediated methionine deprivation drives immune activation and enhances immune checkpoint blockade therapy in melanoma.

BACKGROUND: Although immune checkpoint inhibitor (ICI)-based therapy is advantageous for patients with advanced melanoma, resistance and relapse are frequent. Thus, it is crucial to identify effective drug combinations and develop new therapies for the treatment of melanoma. SGN1, a genetically modified Salmonella typhimurium species that causes the targeted deprivation of methionine in tumor tissues, is currently under investigation in clinical trials. However, the inhibitory effect of SGN1 on melanoma and the benefits of SGN1 in combination with ICIs remain largely unexplored. Therefore, this study aims to investigate the antitumor potential of SGN1, and its ability to enhance the efficacy of antibody-based programmed cell death-ligand 1 (PD-L1) inhibitors in the treatment of murine melanoma. METHODS: The antitumor activity of SGN1 and the effect of SGN1 on the efficacy of PD-L1 inhibitors was studied through murine melanoma models. Further, The Cancer Genome Atlas-melanoma cohort was clustered using ConsensusClusterPlus based on the methionine deprivation-related genes, and immune characterization was performed using xCell, Microenvironment Cell Populations-counter, Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data, and immunophenoscore (IPS) analyses. The messenger RNA data on programmed death-1 (PD-1) immunotherapy response were obtained from the Gene Expression Omnibus database. Gene Set Enrichment Analysis of methionine deprivation-up gene set was performed to determine the differences between pretreatment responders and non-responders. RESULTS: This study showed that both, the intratumoral and the intravenous administration of SGN1 in subcutaneous B16-F10 melanomas, suppress tumor growth, which was associated with an activated CD8+T-cell response in the tumor microenvironment. Combination therapy of SGN1 with systemic anti-PD-L1 therapy resulted in better antitumor activity than the individual monotherapies, respectively, and the high therapeutic efficacy of the combination was associated with an increase in the systemic level of tumor-specific CD8+ T cells. Two clusters consisting of methionine deprivation-related genes were identified. Patients in cluster 2 had higher expression of methionine_deprivation_up genes, better clinical outcomes, and higher immune infiltration levels compared with patients in cluster 1. Western blot, IPS analysis, and immunotherapy cohort study revealed that methionine deficiency may show a better response to ICI therapy CONCLUSIONS：: This study reports Salmonella-based SGN1 as a potent anticancer agent against melanoma, and lays the groundwork for the potential synergistic effect of ICIs and SGN1 brought about by improving the immune microenvironment in melanomas.

Efficacy and regulatory strategies of gut microbiota in immunotherapy: a narrative review.

Background and Objective: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes. Methods: Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy". Key Content and Findings: The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage. Conclusions: The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods: Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results: The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion: This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

Plasmodium falciparum selectively degrades α-spectrin of infected erythrocytes after invasion.

Remodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not ß-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria. IMPORTANCE: Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while ß-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Novel inhibitory effect of black chokeberry (Aronia melanocarpa) from selected eight berries extracts on advanced glycation end-products formation and corresponding mechanism study.

Numerous health hazards have been connected to advanced glycation end products (AGEs). In this investigation, using reaction models including BSA-fructose, BSA- methylglyoxal (MGO), and BSA-glyoxal (GO), we examined the anti-glycation potential of eight different berry species on AGEs formation. Our results indicate that black chokeberry (Aronia melanocarpa) exhibited the highest inhibitory effects, with IC50 values of 0.35 ± 0.02, 0.45 ± 0.03, and 0.48 ± 0.11 mg/mL, respectively. Furthermore, our findings suggest that black chokeberry inhibits AGE formation by binding to BSA, which alleviates the conformation alteration, prevents protein cross-linking, and traps reactive α-dicarbonyls to form adducts. Notably, three major polyphenols, including cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, and procyanidin B2 from black chokeberry, showed remarkably inhibitory effect on MGO/GO capture, and new adducts formation was verified through LC-MS/MS analysis. In summary, our research provides a theoretical basis for the use of berries, particularly black chokeberry, as natural functional food components with potential anti-glycation effects.

A negative emotional context disrupts the framing effect on outcome evaluation in decision making under uncertainty: An ERP study.

The framing effect refers to the phenomenon that different descriptions of the same option lead to a shift in the choice of the decision maker. Several studies have found that emotional contexts irrelevant to a decision in progress still influence the framing effect on decision making. However, little is known about the potential role of emotional contexts in the framing effect on outcome evaluation under uncertainty and the related neural mechanisms. The present study measured event-related potentials (ERPs) to capture the time series of brain activities during the processing of gain- and loss-framed choices and outcomes primed with neutral and negative emotional contexts. The results revealed that in the neutral emotional context, the P300 amplitudes following both positive and negative feedback were greater in the gain-framed condition than those in the loss-framed condition, demonstrating a framing effect, whereas in the negative emotional context, this effect was unstable and observed only following negative feedback. In contrast, regardless of whether the feedback was positive or negative, the framing effect on the feedback-related negativity (FRN) amplitudes was insensitive to neutral and negative emotional contexts. Furthermore, the time-frequency analysis showed that the framing effect on the theta power related to the FRN was also insensitive to neutral and negative emotional contexts. Our findings suggest that brain responses to framing effects on outcome evaluation in a later cognitive appraisal stage of decision making under uncertainty may depend on the emotional context, as the effects were observed only following negative feedback in the negative emotional context.

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice.

Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

Endogenous production of ω-3 polyunsaturated fatty acids mitigates cisplatin-induced myelosuppression by regulating NRF2-MDM2-p53 signaling pathway.

Cisplatin is a chemotherapy medication used to treat a wide range of cancers. A common side effect of cisplatin is myelosuppression. Research suggests that oxidative damages are strongly and consistently related to myelosuppression during cisplatin treatment. ω-3 polyunsaturated fatty acids (PUFAs) can enhance the antioxidant capacity of cells. Herein, we investigated the protective benefit of endogenous ω-3 PUFAs on cisplatin-induced myelosuppression and the underlying signaling pathways using a transgenic mfat-1 mouse model. The expression of mfat-1 gene can increase endogenous levels of ω-3 PUFAs by enzymatically converting ω-6 PUFAs. Cisplatin treatment reduced peripheral blood cells and bone marrow nucleated cells, induced DNA damage, increased the production of reactive oxygen species, and activated p53-mediated apoptosis in bone marrow (BM) cells of wild-type mice. In the transgenics, the elevated tissue ω-3 PUFAs rendered a robust preventative effect on these cisplatin-induced damages. Importantly, we identified that the activation of NRF2 by ω-3 PUFAs could trigger an antioxidant response and inhibit p53-mediated apoptosis by increasing the expression of MDM2 in BM cells. Thus, endogenous ω-3 PUFAs enrichment can strongly prevent cisplatin-induced myelosuppression by inhibiting oxidative damage and regulating the NRF2-MDM2-p53 signaling pathway. Elevation of tissue ω-3 PUFAs may represent a promising treatment strategy to prevent the side effects of cisplatin.