Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard.

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.

Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer's disease.

Blood exosomes are emerging as potential biomarkers for diagnosing brain diseases such as Alzheimer's disease (AD). There is currently a lack of an ultrasensitive technology for identifying core AD biomarkers in blood exosomes to optimize the utility of biomarkers in clinical practice. Here, an immunomagnetic exosomal polymerase chain reaction (iMEP) platform was developed using DNA-conjugated antibodies for the rapid detection of amyloid-ß (Aß1-40 and Aß1-42) and phosphorylated tau (p-tau396,404 and p-tau181) in clinical blood exosomes. The toehold shift-mediated DNA affinity pulldown eliminates the high detection background, which allows the detection of biomarkers at concentrations down to 10 femtograms per milliliter. With the iMEP assay, exosomal Aß1-42 was more accurate in differentiating patients with AD from healthy individuals compared with exosomal p-tau181 and p-tau396,404, with a sensitivity of 95.0% and a specificity of 95.0%. The iMEP technique is also adept at quantifying the levels of different exosomal biomarkers associated with disease pathogenesis.

Comprehensive analysis of DNA methylation gene expression profiles in GEO dataset reveals biomarkers related to malignant transformation of sinonasal inverted papilloma.

BACKGROUND: DNA methylation may be involved in the regulation of malignant transformation from sinonasal inverted papilloma (SNIP) to squamous cell carcinoma (SCC). The study of gene methylation changes and screening of differentially methylated loci (DMLs) are helpful to predict the possible key genes in the malignant transformation of SNIP-SCC. MATERIALS AND METHODS: Microarray dataset GSE125399 was downloaded from the Gene Expression Omnibus (GEO) database and differentially methylated loci (DMLs) were analyzed using R language (Limma package). ClusterProfiler R package was used to perform Gene Ontology (GO) analysis on up-methylated genes and draw bubble maps. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and its visualization analysis were analyzed to speculate the possible key Genes in SNIP-SCC malignant transformation. Subsequently, SNIP cases archived in our department were collected, tissue microarray was made, and immunohistochemical staining was performed to analyze the expression levels of UCKL1, GSTT1, HLA-G, MAML2 and NRGN in different grades of sinonasal papilloma tissues. RESULTS: Analysis of dataset GSE125399 identified 56 DMLs, including 49 upregulated DMLs and 7 downregulated DMLs. Thirty-one genes containing upregulated DNA methylation loci and three genes containing downregulated DNA methylation loci were obtained by methylation microarray annotation analysis. In addition, KEGG pathway visualization analysis of 31 up-methylated genes showed that there were four significantly up-methylated genes including UCKL1, GSTT1, HLA-G and MAML2, and one significantly down-methylated gene NRGN. Subsequently, compared with non-neoplasia nasal epithelial tissues, the expression of HLA-G and NRGN was upregulated in grade I, II, III and IV tissues, while the expression of MAML2 was lost. The protein expression changes of MAML2 and NRGN were significantly negatively correlated with their gene methylation levels. CONCLUSIONS: By analyzing the methylation dataset, we obtained four up-regulated methylation genes UCKL1, GSTT1, HLA-G and MAML2 and one down-regulated gene NRGN. MAML2, a tumor suppressor gene with high methylation modification but loss of protein expression, and NRGN, a tumor gene with low methylation modification but upregulated protein expression, can be used as biological indicators to judge the malignant transformation of SNIP-SCC.

Tailored bacteria tackling with environmental mercury: Inspired by natural mercuric detoxification operons.

Mercury (Hg) and its inorganic and organic compounds significantly threaten the ecosystem and human health. However, the natural and anthropogenic Hg environmental inputs exceed 5000 metric tons annually. Hg is usually discharged in elemental or ionic forms, accumulating in surface water and sediments where Hg-methylating microbes-mediated biotransformation occurs. Microbial genetic factors such as the mer operon play a significant role in the complex Hg biogeochemical cycle. Previous reviews summarize the fate of environmental Hg, its biogeochemistry, and the mechanism of bacterial Hg resistance. This review mainly focuses on the mer operon and its components in detecting, absorbing, bioaccumulating, and detoxifying environmental Hg. Four components of the mer operon, including the MerR regulator, divergent mer promoter, and detoxification factors MerA and MerB, are rare bio-parts for assembling synthetic bacteria, which tackle pollutant Hg. Bacteria are designed to integrate synthetic biology, protein engineering, and metabolic engineering. In summary, this review highlights that designed bacteria based on the mer operon can potentially sense and bioremediate pollutant Hg in a green and low-cost manner.

[Big data analysis of coastal illegal fishing from the perspective of compensation of ecological and environmental damage]. / 生态环境损害赔偿视域下的近海非法捕捞大数据分析.

Illegal fishing is one of the sources of marine ecological damage. The implementation of compensation of ecological and environmental damage in this field is poorly understood. In this study, we examined data pertaining to coastal illegal fishing cases during 2018-2022 using the big data publicly made available by China Judgement Online. The main results included: 1) there are numerous types of illegal fishing, and more efforts should focus on the nature and extent of illegal fishing, with electrofishing and trawl being suitable entry points; 2) Special attention should be paid to the variation characteristics of rakes in the range of high illegal catch weight and value. It was suggested to optimize and adjust its management mode to avoid the frequent occurrence of such illegal fishing cases of rake; 3) The varieties of assessment models increased the uncertainty of damages computation, which might be reduced by establishing strong criteria for value quantification and damage assessment; 4) There is limited scientific support for the compensation for releasing the most popular ecological restoration technique for illegal fishing. As a result, the "compensation" design for "restoration" should be implemented, while the potential for additional restoration methods should be investigated.

Effect of sleep ambient music on sleep quality and mental health in college students: a self-controlled study.

To verify the effect of sleep ambient music intervention (SAMI) on sleep quality and mental status of college students, and to further explore the minimum effective duration of SAMI, this study was designed as a pre-and post-intervention self-controlled exploratory study. Participants were subjected to a one-week no-intervention test, then 4 weeks of music intervention followed. Subjective sleep quality data were collected using the Pittsburgh Sleep Quality Index (PSQI); objective sleep quality data were collected with Actigraphy; and mental status data were collected using the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II). Data were analyzed and processed using mixed-effects models and repeated measures. The results showed that compared with the no-intervention week, college students' subjective sleep quality, objective sleep onset latency (SOL), trait anxiety, and depression symptom were reduced at week 1; week 2; week 3; week 4 under SAMI; state anxiety of college students at week 3 and week 4 under SAMI were also reduced. And there were differences in sleep quality among college students of different genders too. Compared with females, males had worse sleep efficiency (SE), shorter total sleep time (TST), and more awaking times (AT). In addition, 3 days was the minimum effective length for SAMI to shorten objective SOL, and 2 days was the minimum effective length to shorten the subjective SOL of college students. The findings of this study suggest that SAMI can improve subjective sleep quality, shorten objective SOL, and reduce anxiety and depression in college students. Interventions for more than 3 days had a significant effect on shortening SOL and long-term effects seemed to emerge after 3 weeks.

Effects of Co-Culture EBV-miR-BART1-3p on Proliferation and Invasion of Gastric Cancer Cells Based on Exosomes.

AIM: EBV encodes at least 44 miRNAs involved in immune regulation and disease progression. Exosomes can be used as carriers of EBV-miRNA-BART intercellular transmission and affect the biological behavior of cells. We characterized exosomes and established a co-culture experiment of exosomes to explore the mechanism of miR-BART1-3p transmission through the exosome pathway and its influence on tumor cell proliferation and invasion. MATERIALS AND METHODS: Exosomes of EBV-positive and EBV-negative gastric cancer cells were characterized by transmission electron microscopy. NanoSight and Western blotting, and miRNA expression profiles in exosomes were sequenced with high throughput. Exosomes with high or low expression of miR-BART1-3p were co-cultured with AGS cells to study the effects on proliferation, invasion, and migration of gastric cancer cells. The target genes of EBV-miR-BART1-3p were screened and predicted by PITA, miRanda, RNAhybrid, virBase, and DIANA-TarBase v.8 databases, and the expression of the target genes after co-culture was detected by qPCR. RESULTS: The exosomes secreted by EBV-positive and negative gastric cancer cells range in diameter from 30 nm to 150 nm and express the exosomal signature proteins CD9 and CD63. Small RNA sequencing showed that exosomes expressed some human miRNAs, among which hsa-miR-23b-3p, hsa-miR-320a-3p, and hsa-miR-4521 were highly expressed in AGS-exo; hsa-miR-21-5p, hsa-miR-148a-3p, and hsa-miR-7-5p were highly expressed in SNU-719-exo. All EBV miRNAs were expressed in SNU-719 cells and their exosomes, among which EBV-miR-BART1-5p, EBV-miR-BART22, and EBV-miR-BART16 were the highest in SNU-719 cells; EBV-miR-BART1-5p, EBV-miR-BART10-3p, and EBV-miR-BART16 were the highest in SNU-719-exo. After miR-BART1-3p silencing in gastric cancer cells, the proliferation, healing, migration, and invasion of tumor cells were significantly improved. Laser confocal microscopy showed that exosomes could carry miRNA into recipient cells. After co-culture with miR-BART1-3p silenced exosomes, the proliferation, healing, migration, and invasion of gastric cancer cells were significantly improved. The target gene of miR-BART1-3p was FAM168A, MACC1, CPEB3, ANKRD28, and USP37 after screening by a targeted database. CPEB3 was not expressed in all exosome co-cultured cells, while ANKRD28, USP37, MACC1, and FAM168A were all expressed to varying degrees. USP37 and MACC1 were down-regulated after up-regulation of miR-BART1-3p, which may be the key target genes for miR-BART1-3p to regulate the proliferation of gastric cancer cells through exosomes. CONCLUSIONS: miR-BART1-3p can affect the growth of tumor cells through the exosome pathway. The proliferation, healing, migration, and invasion of gastric cancer cells were significantly improved after co-culture with exosomes of miR-BART1-3p silenced expression. USP37 and MACC1 may be potential target genes of miR-BART1-3p in regulating cell proliferation.

Is it safe for the spinal metastasis patients with preoperative deep vein thrombosis to use low-molecular-weight heparin before surgery? A prospective study.

Spine surgeons should weigh the risks of anticoagulants against their benefits in preventing deep venous thrombosis (DVT), as they may increase the risk of bleeding. Spinal metastasis patients undergoing decompression with fixation are at a high risk for DVT, which may occur preoperatively. Therefore, anticoagulants should be administered preoperatively. This study aimed to evaluate the safety of the administration of anticoagulants in treating spinal metastasis patients with preoperative DVT. Therefore, we prospectively investigated the prevalence of DVT in these patients. Patients who were diagnosed with preoperative DVT were included in an anticoagulant group. Subcutaneous low-molecular-weight heparin (LMWH) was administered. Patients without DVT were included in a non-anticoagulant group. Data on patient information, clinical parameters, blood test results, and bleeding complications were also collected. Moreover, the safety of anticoagulants was analyzed. The prevalence of preoperative DVT was 8.0%. None of the patients developed pulmonary thromboembolism. Furthermore, no significant differences in blood loss, drainage volume, hemoglobin levels, number of transfusions, or preoperative trans-catheter arterial embolization were observed between the two groups. None of the patients developed major bleeding. However, two patients experienced wound hematoma and one experienced incisional bleeding in the non-anticoagulant group. Therefore, LMWH is safe for spinal metastasis patients. Future randomized controlled trials should be conducted to evaluate the validity of perioperative prophylactic anticoagulation therapy in these patients.

A panel of visual bacterial biosensors for the rapid detection of genotoxic and oxidative damage: A proof of concept study.

The emergence of new compounds during the past decade requires a high-throughput screening method for toxicity assay. The stress-responsive whole-cell biosensor is a powerful tool to evaluate direct or indirect damages of biological macromolecules induced by toxic chemicals. In this proof-of-concept study, nine well-characterized stress-responsive promoters were first selected to assemble a set of blue indigoidine-based biosensors. The PuspA-based, PfabA-based, and PgrpE-based biosensors were eliminated due to their high background. A dose-dependent increase of visible blue signal was observed in PrecA-, PkatG-, and PuvrA-based biosensors, responsive to potent mutagens, including mitomycin and nalidixic acid, but not to genotoxic lead and cadmium. The PrecA, PkatG, and Ppgi gene promoters were further fused to a purple deoxyviolacein synthetic enzyme cluster. Although high basal production of deoxyviolacein is unavoidable, an enhanced visible purple signal in response to mitomycin and nalidixic acid was observed as dose-dependent, especially in PkatG-based biosensors. The study shows that a set of stress-responsive biosensors employing visible pigment as a reporter is pre-validating in detecting extensive DNA damage and intense oxidative stress. Unlike widely-used fluorescent and bioluminescent biosensors, the visual pigment-based biosensor can become a novel, low-cost, mini-equipment, and high-throughput colorimetric device for the toxicity assessment of chemicals. However, combining multiple improvements can further improve the biosensing performance in future studies.

Ada2 and Ada3 Regulate Hyphal Growth, Asexual Development, and Pathogenicity in Beauveria bassiana by Maintaining Gcn5 Acetyltransferase Activity.

The histone acetyltransferase (HAT) Gcn5 ortholog is essential for a variety of fungi. Here, we characterize the roles of Ada2 and Ada3, which are functionally linked to Gcn5, in the insect-pathogenic fungus Beauveria bassiana. Loss of Ada2 and Ada3 led to severe hyphal growth defects on rich and minimal media and drastic decreases in blastospore yield and conidiation capacity, with abnormal conidia-producing structures. ΔAda2 and ΔAda3 exhibited a delay in conidial germination and increased sensitivity to multiple chemical stresses and heat shock. Nearly all their pathogenicity was lost, and their ability to secrete extracellular enzymes, Pr1 proteases and chitinases for cuticle degradation was reduced. A yeast two-hybrid assay demonstrated that Ada2 binds to Ada3 and directly interacts with Gcn5, confirming the existence of a yeast-like Ada3-Ada2-Gcn5 HAT complex in this fungus. Additionally, deletion of the Ada genes reduced the activity of Gcn5, especially in the ΔAda2 strain, which was consistent with the acetylation level of histone H3 determined by Western blotting. These results illustrate the dependence of Gcn5 enzyme activity on Ada2 and Ada3 in fungal hyphal growth, asexual development, multiple stress responses, and pathogenicity in B. bassiana. IMPORTANCE The histone acetyltransferase Gcn5 ortholog contributes significantly to the growth and development of various fungi. In this study, we found that Ada2 and Ada3 have critical regulatory effects on Gcn5 enzyme activity and influence the acetylation of histone H3. Deletion of Ada2 or Ada3 decreased the fungal growth rate and asexual conidial yield and increased susceptibility to multiple stresses in Beauveria bassiana. Importantly, Ada genes are vital virulence factors, and their deletion caused the most virulence loss, mainly by inhibiting the activity of a series of hydrolytic enzymes and the dimorphic transition ability. These findings provide a new perspective on the function of the Gcn5 acetyltransferase complex in pathogens.

Three Chitin Deacetylase Family Members of Beauveria bassiana Modulate Asexual Reproduction and Virulence of Fungi by Mediating Chitin Metabolism and Affect Fungal Parasitism and Saprophytic Life.

As an important chitin-modifying enzyme, chitin deacetylase (CDA) has been characterized in many fungi, but its function in the entomopathogenic fungus Beauveria bassiana remains unclear. Three CDAs with conserved domains of the carbohydrate esterase 4 (CE-4) family were identified in B. bassiana. Disruption of CDA1 resulted in growth restriction of the fungus on medium with chitin as a carbon source or without a carbon source. Deletion of CDA1 and CDA2 led to defects in fungal conidial formation and conidial vitality compared with those of the wild type (WT), and the conidial yield decreased by 25.81% to 47.68%. Inactivation of three CDA genes resulted in a decrease of 20.23% to 27% in the blastospore yield. ΔCDA1 and ΔCDA3 showed 29.33% and 23.34% reductions in cuticular infection virulence, respectively. However, the CDA family may not contribute to hemocoel infection virulence. Additionally, the sporulation of the insect carcass showed that the three gene deletion mutants were 68.45%, 63.84%, and 56.65% less than WT. Penetration experiments with cicada wings and enzyme activity assays were used to further explore the effect of the fungus on chitin metabolism after gene deletion. Although the three gene deletion mutants penetrated the cicada wings successfully and continued to grow on the underlying medium, their colony sizes were reduced by 29.12% to 47.76%. The CDA enzyme activity of ΔCDA1 and ΔCDA3 decreased by 84.76% and 83.04%, respectively. These data showed that members of the CDA family play a different role in fungal growth, conidial quality, and virulence. IMPORTANCE In this study, we report the roles of CDA family in entomopathogenic fungus B. bassiana. Our results indicated that CDA modulates asexual development and regulates fungal virulence by altering chitin deacetylation and metabolic capacity. CDA affected the biological control potential and life history of B. bassiana by affecting its parasitic and saprophytic life. These findings provide novel insights into the roles of multiple CDA paralogues existing in fungal biocontrol agents.

Colorimetric and surface-enhanced Raman scattering dual-mode magnetic immunosensor for ultrasensitive detection of blood phosphorylated tau in Alzheimer's disease.

Phosphorylation of tau at Ser 396, 404 (p-tau396,404) is the earliest phosphorylation event and a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, the detection of blood p-tau is challenging because of its low abundance, easy degradation, and complex formation with various blood proteins or cells, often leading to the underestimation of p-tau levels in conventional plasma-based assays. Herein, we developed a colorimetric and surface-enhanced Raman scattering (SERS) dual-mode magnetic immunosensor for highly sensitive, specific, and robust detection of p-tau396,404 in whole blood samples. The detection assay was based on an immunoreaction between p-tau396,404 proteins, wherein antibody-modified superparamagnetic iron oxide nanoparticles act as recognition elements to capture p-tau396,404 in blood, and then horseradish peroxidase- and Raman tags label the corresponding paired antibody as a reporter to provide high signal-to-noise ratios for the immunosensor. This dual-mode immunosensor achieved identified as low as 1.5 pg/mL of p-tau396,404 in the blood in SERS mode and 24 pg/mL in colorimetric mode by the naked eye. More importantly, this immunosensor rapidly and accurately distinguished AD patients from healthy individuals based on blood p-tau396,404 levels, and also had the potential to distinguish AD patients of different severities. Therefore, the dual-mode immunosensor is promising for rapid clinical diagnosis of AD, especially in large-scale AD screening.

Metabolic engineering of the carotenoid biosynthetic pathway toward a specific and sensitive inorganic mercury biosensor.

The toxicity of mercury (Hg) mainly depends on its form. Whole-cell biosensors respond selectively to toxic Hg(ii), efficiently transformed by environmental microbes into methylmercury, a highly toxic form that builds up in aquatic animals. Metabolically engineered Escherichia coli (E. coli) have successfully produced rainbow colorants. By de novo reconstruction of the carotenoid synthetic pathway, the Hg(ii)-responsive production of lycopene and ß-carotene enabled programmed E. coli to potentially become an optical biosensor for the qualitative and quantitative detection of ecotoxic Hg(ii). The red color of the lycopene-based biosensor cell pellet was visible upon exposure to 49 nM Hg(ii) and above. The orange ß-carotene-based biosensor responded to a simple colorimetric assay as low as 12 nM Hg(ii). A linear response was observed at Hg(ii) concentrations ranging from 12 to 195 nM. Importantly, high specificity and good anti-interference capability suggested that metabolic engineering of the carotenoid biosynthesis was an alternative to developing a visual platform for the rapid analysis of the concentration and toxicity of Hg(ii) in environmentally polluted water.

Validating the accuracy of a multifunctional smartwatch sphygmomanometer to monitor blood pressure.

BACKGROUND: Hypertension is the most modifiable factor associated with cardiovascular events and complications. The conventional blood pressure (BP) meter method is simple but is limited in terms of real-time monitoring abnormal BP. Therefore, the development of a multifunction smartwatch (HUAWEI WATCH D) sphygmomanometer could significantly improve integrated BP monitoring. METHODS: We enrolled 361 subjects from Chinese PLA General Hospital, Beijing, China to validate the accuracy of the smartwatch versatile sphygmomanometer using ISO 81060-2:2018. Resting and ambulatory BP accuracy of the smartwatch were compared with gold standard clinical sphygmomanometers using ISO 81060-2:2018 guidelines, the accuracy of 24 h systolic blood pressure (SBP) circadian rhythm monitoring, and diurnal high SBP alert for this smartwatch were assessed using a confusion matrix approach. Additionally, we analyzed online users of different ages for compliance. RESULTS: Eighty-five subjects underwent resting BP measurements; the mean resting BP differences between two devices were -0.683 ± 6.203 mmHg (SBP) (P = 0.723) and 1.628 ± 5.028 mmHg (diastolic blood pressure, DBP) (P = 0.183). In 35 subjects' ambulatory BP measurements, the mean differences of ambulatory BP were -1.943 ± 5.475 mmHg (SBP) (P = 0.923) and 3.195 ± 5.862 mmHg (DBP) (P = 0.065). All data complied with ISO 81060-2:2018 guidelines (mean ≤ ±5 mmHg and standard deviation ≤ ±8 mmHg) with no significant differences. Positive predictive values (PPV) of resting SBP and DBP were 0.635 and 0.671, respectively. The PPV of ambulatory SBP and DBP were 0.686. Also, 24 h SBP circadian rhythm monitoring was performed in 107 subjects: accuracy = 0.850, specificity = 0.864, precision/PPV = 0.833, sensitivity = 0.833, and F1-measure (F1) = 0.833. The accuracy, specificity, precision, sensitivity, and F1 values in 85 subjects undergoing diurnal high SBP alerting were 0.858, 0.876, 0.706, 0.809, and 0.754, respectively. CONCLUSIONS: When compared with the gold standard clinical sphygmomanometer, smartwatch results were consistent and accurate. Online user feedback showed that elderly individuals cared more about BP monitoring accuracy, with better compliance.

COVID-19 Infection Deteriorates the Clinical Condition and Outcomes of Acute Pancreatitis: A Meta-Analysis.

Backgrounds: The novel coronavirus disease 2019 (COVID-19) has caused a global pandemic. Pancreatic injuries have been reported in COVID-19 patients. The present meta-analysis was conducted to compare the morbidity and outcomes of AP between COVID-19 positive and negative patients. Methods: Databases including Cochrane Library, PubMed, and EMBASE were systematically searched (until July 3rd 2022). Studies with English abstracts comparing the severity and outcomes of AP between COVID-19 positive and negative patients were included. Mean differences or odds ratios with a 95% confidence interval were employed for assess variables. Risk of publication bias was assessed with funnel plots. Results: Data from 7 studies with a total of 2816 AP patients were included. COVID-19 positive was associated with higher incidences of pancreatic necrosis (OR = 1.65; 95% CI: 1.13 to 2.42, P = 0.01; P = 0.82 for heterogeneity) and persistent organ failure (OR = 6.87; 95% CI: 2.37 to 19.98, P = 0.0004; P = 0.12 for heterogeneity), especially cardiovascular failure (OR = 2.92; 95% CI: 1.66 to 5.14, P = 0.0002; P = 0.58 for heterogeneity) and acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) (OR = 3.03; 95% CI: 2.09 to 4.39, P < 0.00001; P = 0.20 for heterogeneity). COVID-19 infection induced a higher level of CRP (MD = 0.40; 95% CI: 0.16 to 0.64, P = 0.001; P < 0.00001 for heterogeneity) as well as coagulation disorders involving platelets, prothrombin time, activated partial thromboplastin time, and D-dimer (all P < 0.05). During hospitalization, COVID-19 positive was associated with higher ICU admission rate (OR = 2.76; 95% CI: 1.98 to 3.85 P < 0.00001; P = 0.47 for heterogeneity). COVID-19 positive AP was associated with a higher mortality rate (OR = 3.70; 95% CI: 2.60 to 5.25, P < 0.00001; P = 0.12 for heterogeneity). Discussion. The number of included studies is limited and none is RCT, thus the risks of publication and selective bias could not be ignored. COVID-19 deteriorated the severity and clinical outcomes of AP, with a high incidence of morbidity and mortality.

Inflammation-based different association between anatomical severity of coronary artery disease and lung cancer.

BACKGROUND: Coronary artery disease (CAD) is associated with cancer. The role of inflammation in the association of CAD with cancer remains unclear. The study investigated whether inflammation could impact the relationship between CAD and lung cancer. METHODS: The study involved 96 newly diagnosed lung cancer patients without receiving anti-cancer therapy and 288 matched non-cancer patients. All the patients underwent coronary angiography and were free from previous percutaneous coronary intervention or coronary artery bypass grafting. SYNTAX score (SXscore) were used to assess severity of CAD. High SXscore (SXhigh) grade was defined as SXscore > 16 (highest quartile). Neutrophil-to-lymphocyte ratio (NLR) served as an inflammatory biomarker. NLR-high grade referred to NLR > 2.221 (median). RESULTS: Among 384 study patients, 380 patients (98.96%) had NLR value (median: 2.221, interquartile range: 1.637-3.040). Compared to non-cancer patients, lung cancer patients had higher rate of SXhigh among total study patients (P = 0.014) and among patients with NLR-high (P = 0.006), but had not significantly higher rate of SXhigh among patients with NLR-low (P = 0.839). Multivariate logistic regression analysis showed that SXhigh was associated with lung cancer [odds ratio (OR) = 1.834, 95% CI: 1.063-3.162, P = 0.029]. Subgroup analysis showed that SXhigh was associated with lung cancer among patients with NLR-high (OR = 2.801, 95% CI: 1.355-5.794, P = 0.005), however, the association between SXhigh and lung cancer was not significant among patients with NLR-low (OR = 0.897, 95% CI: 0.346-2.232, P = 0.823). CONCLUSIONS: Inflammation could lead different association between anatomical severity of CAD and lung cancer. Severity of CAD was significantly associated with increased risk of lung cancer among patients with high inflammation rather than among patients with low inflammation.

Anthocyanin biosynthetic pathway switched by metalloregulator PbrR to enable a biosensor for the detection of lead toxicity.

Environmental lead pollution mainly caused by previous anthropogenic activities continuously threatens human health. The determination of bioavailable lead is of great significance to predict its ecological risk. Bacterial biosensors using visual pigments as output signals have been demonstrated to have great potential in developing minimal-equipment biosensors for environmental pollutant detection. In this study, the biosynthesis pathway of anthocyanin was heterogeneously reconstructed under the control of the PbrR-based Pb(II) sensory element in Escherichia coli. The resultant metabolic engineered biosensor with colored anthocyanin derivatives as the visual signal selectively responded to concentrations as low as 0.012 µM Pb(II), which is lower than the detection limit of traditional fluorescent protein-based biosensors. A good linear dose-response pattern in a wide Pb(II) concentration range (0.012-3.125 µM) was observed. The color deepening of culture was recognized to the naked eye in Pb(II) concentrations ranging from 0 to 200 µM. Importantly, the response of metabolic engineered biosensors toward Pb(II) was not significantly interfered with by organic and inorganic ingredients in environmental water samples. Our findings show that the metabolic engineering of natural colorants has great potential in developing visual, sensitive, and low-cost bacterial biosensors for the detection and determination of pollutant heavy metals.

Dual-targeted magnetic mesoporous silica nanoparticles reduce brain amyloid-ß burden via depolymerization and intestinal metabolism.

Rationale: Active removal of excess peripheral amyloid-ß (Aß) can potentially treat Alzheimer's disease (AD). However, the peripheral clearance of Aß using an anti-Aß monoclonal antibody (mAb) cannot remove PET-detectable Aß within the brain. This may be due to the inability of mAb to cross the blood-brain barrier (BBB) to degrade insoluble brain Aß plaques and block liver dysfunction. Methods: We developed a dual-targeted magnetic mesoporous silica nanoparticle (HA-MMSN-1F12) through surface-coupled Aß42-targeting antibody 1F12 and CD44-targeting ligand hyaluronic acid (HA). Results: HA-MMSN-1F12 had a high binding affinity toward Aß42 oligomers (Kd = 1.27 ± 0.34 nM) and revealed robust degradation of Aß42 aggregates. After intravenous administration of HA-MMSN-1F12 into ten-month-old APP/PS1 mice for three weeks (4 mg/kg/week), HA-MMSN-1F12 could cross the BBB and depolymerize brain Aß plaques into soluble Aß species. In addition, it also avoided hepatic uptake and excreted captured Aß species through intestinal metabolism, thereby reducing brain Aß load and neuroinflammation and improving memory deficits of APP/PS1 mice. Furthermore, the biochemical analysis showed that HA-MMSN-1F12 did not detect any toxic side effects on the liver and kidney. Thus, the efficacy of HA-MMSN-1F12 is associated with the targeted degradation of insoluble brain Aß plaques, avoidance of non-specific hepatic uptake, and excretion of peripheral Aß through intestinal metabolism. Conclusions: The study provides a new avenue for treating brain diseases by excreting disease-causing biohazards using intestinal metabolism.

Relationship between demoralization of the college student with their individual- and social-oriented self.

Demoralization has become increasingly prevalent among college students who have lost motivation in life and feel hopeless about their future. Many college students who demonstrate symptoms of demoralization are neglected because they might fail to typical symptoms of depression. Taiwanese college students are simultaneously influenced by bicultural-self system, such as individual- and social-oriented views of self, which vary considerably in the view of self, achievement motivation, and the value of self-realization, and may even create contradictory expectations and behavioral standard. The purpose of this study was to investigate the extent of the relationship between attitude towards demoralization, individual- and social-oriented views of self. Three-hundred fifty-six college students completed the online questionnaire, which was designed to explore their demoralization status and cultural differences. Four groups were divided into bicultural self, individual-oriented self, social-oriented self, and unintegrated self. Bicultural group demonstrated significantly lower demoralization overall scores than other groups. Moreover, the five dimensions of demoralization in college students were mostly significantly and negatively correlated with individual- and social-oriented views of self, indicating that college students' bicultural views of self may contribute to or prevent demoralization.

Recent progress in nanomaterial-functionalized membranes for removal of pollutants.

Membrane technology has gained tremendous attention for removing pollutants from wastewater, mainly due to their affordable capital cost, miniature equipment size, low energy consumption, and high efficiency even for the pollutants present in lower concentrations. In this paper, we review the literature to summarize the progress of nanomaterial-modified membranes for wastewater treatment applications. Introduction of nanomaterial in the polymeric matrix influences membrane properties such as surface roughness, hydrophobicity, porosity, and fouling resistance. This review also covers the importance of functionalization strategies to prepare thin-film nanocomposite hybrid membranes and their effect on eliminating pollutants. Systematic discussion regarding the impact of the nanomaterials incorporated within membrane, toward the recovery of various pollutants such as metal ions, organic compounds, dyes, and microbes. Successful examples are provided to show the potential of nanomaterial-functionalized membranes for regeneration of wastewater. In the end, future prospects are discussed to develop nanomaterial-based membrane technology.