Electromagnetically induced transparency and quantum enhancement of transmission via dressed bloch photons in an array of three-level Λ-type atoms.

We investigate the interactions between an array of three-level atoms and two photon fields with distinct frequencies employing quantum electrodynamics (QED). The control beam, as expected, has a considerably higher intensity than the probe beam, and the probe photon's eigenstate notably then appears as a distinctive dressed Bloch wave. We calculate the dispersion relation and quantum amplitude of the probe photons for their transmission. At positions predicting electromagnetically induced transparency (EIT) phenomena, we unveil remarkable enhancements in the transmission of the probe beam. Crucially, these enhancements are intricately linked to the unique characteristics of the dressed Bloch wave eigenstate. Moreover, we demonstrate that modulating frequency and intensity of the control beam and the lattice constant would further tune these enhancements. Our study highlights the crucial role of the dressed Bloch wave eigenstate in substantially amplifying targeted light beams, thereby significantly enhancing the detection sensitivity for minute electromagnetic signals and emphasizing its pivotal role in unveiling intriguing phenomena.

MCT Nanoemulsions for the Efficient Delivery of siRNA.

In this study, an oil-in-water (o/w) nanoemulsion is used to deliver siRNA targeting Twist1, a protein that contributes to tumor metastasis in a variety of cancers. The FDA-approved oil, medium chain triglycerides (MCT), is used as the hydrophobic phase for the nanoemulsion. The siRNA is paired with dioleoyl-3-trimethylammonium-propane (DOTAP) to form a hydrophobic salt that is soluble at high concentrations in MCT. The resulting MCT/siRNA-DOTAP solution is formulated into a nanoemulsion with an average particle size of 140 nm. The nanoemulsion displays long term stability over the course of 195 days. In an in vivo murine tumor model, the nanoemulsion facilitates a 46% decrease in Twist1 mRNA after 48 h.

Diagnostic performance of GenBody COVID-19 rapid antigen test for laboratory and non-laboratory medical professionals in real practice: A retrospective study.

Point-of-care tests for coronavirus disease 2019 (COVID-19) antigen detection have been widely used for rapid diagnosis in various settings. However, research on the diagnostic performance of the COVID-19 antigen test performed by non-laboratory personnel is limited. In this study, we aimed to elucidate the diagnostic performance of GenBody COVID-19 rapid antigen between laboratory professionals and non-laboratory staff. We retrospectively analyzed the data of patients who underwent both GenBody COVID-19 rapid antigen testing and reverse transcription polymerase chain reaction (RT-PCR) between November 01, 2021, and June 30, 2022. The diagnostic performance of the antigen test was compared between laboratory and non-laboratory operators, using RT-PCR as the gold standard. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy were calculated and sensitivity analysis was performed based on the PCR cycle threshold (Ct) value. Of the 11,963 patients, 1273 (10.6%) tested positive using real-time RT-PCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy of the GenBody COVID-19 rapid antigen test with 95% confidence interval were 79.92% (77.26%-82.39%), 99.23% (98.73%-99.57%), 103.25 (62.31-171.11), 0.2 (0.18-0.23), 510.18 (299.81-868.18), 98.11% (96.91%-98.85%), 90.75% (89.64%-91.75%) and 92.76% (91.76%-93.67%), respectively, for non-laboratory staff and 79.80% (74.78%-84.22%), 99.99% (99.94%-100.00%), 6983.92 (983.03-49617.00), 0.2 (0.16-0.25), 34566.45 (4770.30-250474.46) 99.58% (97.09%-99.94%), 99.32% (99.15%-99.46%), and 99.33% (99.13%-99.48%), respectively, for laboratory staff. Notably, when the PCR Ct value exceeded 25, the sensitivity of both the groups decreased to < 40%. The diagnostic performance of GenBody COVID-19 rapid antigen performed by non-laboratory staff was comparable to that of laboratory professionals. However, it should be noted that the sensitivity of the antigen tests decreased when the PCR Ct value exceeded 25. Overall, the GenBody COVID-19 antigen test is a viable option for non-laboratory staff during an epidemic.

Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.

Manipulating quantum interference of dressed photon fields.

Through quantum electrodynamics (QED) we investigate the interactions between a three-level atom and two photon fields under perturbation limit. The dispersion relation and (relative) transmission of the probe photons are obtained by calculating the corresponding Feynman diagrams. The quantum interference in this three-level system such as Fano resonance and electromagnetically induced transparency (EIT) can be tuned by varying the intensities of the control and probe beams. Moreover, by considering that the control beam with periodic modulation, that is, the so-called Landau-Zener-Stückelberg (LZS) type source, the accumulated phase after Landau-Zener transitions is found to show the alternating Fano (EIT) lineshapes in the transmission of the probe photons. We further find that the transmissions can become almost stationary in addition to a wide EIT window in time even though the control beam is a LZS-type oscillating source.

Clinical Performance of Rapid Antigen Tests for the Detection of SARS-CoV-2 Infection in the Emergency Department and Community: A Retrospective Study.

Background: Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection have been authorized for emergency use (EUA); however, the performance has not been fully evaluated in clinical contexts. This study aimed to provide evidence regarding the diagnostic performance of SARS-CoV-2 rapid antigen tests compared with the real-time reverse transcription-polymerase chain reaction (RT-PCR) test in the emergency department (ED) and community. Methods: Patients who underwent SARS-CoV-2 rapid antigen tests using the VTRUST COVID-19 Antigen Rapid Test (TD-4531) and real-time RT-PCR on the same day in the ED or community from May 24, 2021, to June 24, 2021, were examined. Results: Paired nasopharyngeal swabs were collected from 4022 suspected COVID-19 patients: 800 in the ED and 3222 in the community. Overall, 62 (1.54%) tested positive, 13 tested indeterminate, and 3947 tested negative by real-time RT-PCR. The sensitivity and specificity of the antigen test were 51.61% and 99.44% (overall), 62.50% and 99.61% (ED), and 31.82% and 99.40% (community), respectively. There were 30 false negatives and 22 false positives. Among the false negatives, 16.67% had a cycle threshold (Ct) value of <25. Conclusion: The VTRUST COVID-19 Antigen Rapid Test showed comparable specificity as real-time RT-PCR for the ED and community, but the sensitivity was relatively low, especially when the Ct value was >25. This test can be useful for the rapid identification of infected subjects in an epidemic situation.

Intratumoral xenogeneic tissue-specific cell immunotherapy inhibits tumor growth by increasing antitumor immunity in murine triple negative breast and pancreatic tumor models.

Low immunogenicity in tumors and the immunosuppressive tumor microenvironment (TME) represent major obstacles to the full success of immunotherapy in cancer patients. A novel intratumoral xenogeneic tissue-specific cell immunotherapeutic approach could overcome the obstacles. Murine 4T1 triple negative breast cancer (TNBC) cells and Pan18 pancreatic ductal adenocarcinoma (PDAC) cells were used for establishing syngeneic graft tumor models to evaluate antitumor effect of intratumoral injection of xenogeneic tissue-specific cells. Responses to treatment were assessed by measuring tumor growth and tumor weight of the tumor-bearing mice. To investigate the mechanisms of action, tumor histology and immunohistochemistry and cytokine gene expression were measured. Splenic lymphocytes proliferation, cytokine production and cytotoxicity activities were also assessed. The findings showed that intratumoral injection of xenogeneic tissue-specific cells in monotherapy and combination with chemotherapy inhibit tumor growth. The therapeutic efficacy of intratumoral xenogeneic cells was significantly enhanced by the addition of cytotoxic chemotherapeutic agents. Mice that received combined treatment showed maximal attenuation in tumor growth rate. The antitumor immunity was explained by altered immune cell infiltration in tumors and immune cell functions. Our findings demonstrate that xenogeneic tissue-specific cells given intratumorally, provide a potent antitumor effect in murine breast and pancreatic tumor models by enhancing recruitment and activation of immune cells in tumors for local and systemic antitumor effects. Moreover, intratumoral xenogeneic cell treatment turns immunologically "cold" tumors to "hot" ones, generates systemic antitumor immunity, and synergizes with chemotherapy. Thus, the intratumoral xenogeneic tissue-specific cell immunotherapy may represent a useful therapeutic option to difficult-to-treat cancers.

Revisiting factors associated with blood culture positivity: Critical factors after the introduction of automated continuous monitoring blood culture systems.

Blood culture is the main tool used to identify causative pathogens. Adequate volume and number of culture sets are considered key to blood culture positivity rate. It is not known whether these factors remain critical to the positivity rate after the introduction of automated continuous blood culture system monitoring. We measured blood volume per bottle and described the distribution of blood volume and number of culture sets. Multivariate logistic regression was performed to determine the independent association of blood volume, number of culture sets, diagnosis of sepsis in a patient, and other covariates with blood culture results. Only 6.9% of the blood culture bottle volumes complied with the guidance (8-10 mL), with the highest culture positivity rate (18%). Of the culture events, only one set of blood was cultured in 60.9% of events. In the multivariate analysis, blood culture volume per event (odds ratio [OR], 1.09 [95% confidence interval [CI], 1.06-1.11]), patients with a diagnosis of sepsis (OR, 2.86 [95% CI, 2.06-3.98]), and samples from the emergency department (OR, 2.29 [95% CI, 1.72-3.04]), but not the number of culture sets (OR, 0.74 [95% CI, 0.50-1.12]), were observed to be statistically significant with respect to blood culture positivity rate. Our results revealed that the total blood culture volume and the diagnosis of sepsis were critical factors affecting blood culture positivity rate. However, the proportion of blood culture bottles with the optimal blood volume was very low, and optimizing blood volume would be key to increasing blood culture positivity rate.

The role of pleural fluid lactate dehydrogenase-to-adenosine deaminase ratio in differentiating the etiology of pleural effusions.

Exudative pleural effusion includes tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). An elevated pleural fluid adenosine deaminase (ADA) typically implies TPE, but the rule may not apply to every individual case. Recent studies proposed that the pleural fluid lactate dehydrogenase (LDH)-to-ADA ratio showed a higher diagnostic power than pleural fluid ADA alone in differentiating the etiology of pleural effusion. Hence, we aimed to investigate the performance of pleural fluid LDH-to-ADA ratio as a biomarker in assistance with the diagnosis of TPE, PPE, and MPE. All patients who underwent thoracentesis for the first time with a pleural fluid ADA >40 U/L were included in this retrospective study. The clinical data including pleural fluid ADA and LDH-to-ADA ratio were analyzed. A total of 311 patients were enrolled during the study interval. The pleural fluid LDH-to-ADA ratio <14.2 (sensitivity: 74.2%; specificity: 90.4%) favored TPE, while the pleural fluid LDH-to-ADA ratio >14.5 (sensitivity: 79.9%; specificity: 78.5%) favored PPE. Besides, the pleural fluid LDH-to-ADA ratio >46.7 (sensitivity: 56.3%; specificity: 78.3%) favored MPE owing to primary lung cancers. In conclusion, the pleural fluid LDH-to-ADA ratio was an effective indicator in differentiating the etiology of pleural effusions in the cases of high ADA level in the pleural fluid.

The abrogated role of premedication in the prevention of transfusion-associated adverse reactions in outpatients receiving leukocyte-reduced blood components.

BACKGROUND AND OBJECTIVES: Although it remains controversial, premedication before transfusion is a common clinical practice to prevent transfusion-associated adverse reactions (TAARs) in Taiwan. Thus, we aimed to investigate whether premedication prevented outpatients from developing TAARs and whether an educational programme could improve the understanding of physicians related to the unnecessary use of premedication, and this could elicit changes in their prescribing activities without affecting the occurrence of TAARs. MATERIALS AND METHODS: Clinical data from outpatients receiving transfusion therapy, including predisposing diseases, histories of transfusion and TAARs, premedication and the occurrence of TAARs in the period April 2017 to October 2018, were retrospectively obtained. The evidence-based transfusion programme implemented to educate physicians was started in January 2018. RESULTS: A total of 5018 blood units were transfused to 803 outpatients, with 2493 transfusion events reported in the study interval. The most frequently transfused component was leukocyte-reduced packed red cells (n = 4338), followed by leukocyte-reduced apheresis platelets (n = 540) and other blood components. The overall premedication rate significantly decreased from 92.4% to 76.7% after the educational programme (p < 0.001). There was no remarkable change in the occurrence of TAARs per patient event between the periods before and after the educational programme (1.11% vs. 1.14%, p = 0.964). Besides, it was shown that the occurrence of TAARs was associated with the history of TAARs and inversely related to multiple transfusions, but not premedication. CONCLUSION: Decreased premedication was not associated with increased incidence of TAARs in outpatients; these findings provide important evidence to support the need to revise clinical practices in the era of leukocyte-reduced blood products.

Exosomal microRNAs miR-30d-5p and miR-126a-5p Are Associated with Heart Failure with Preserved Ejection Fraction in STZ-Induced Type 1 Diabetic Rats.

Exosomal microRNAs (EXO-miRNAs) are promising non-invasive diagnostic biomarkers for cardiovascular disease. Heart failure with preserved ejection fraction (HFpEF) is a poorly understood cardiovascular complication of diabetes mellitus (DM). Little is known about whether EXO-miRNAs can be used as biomarkers for HFpEF in DM. We aimed to investigate the relationship between EXO-miRNAs and HFpEF in STZ-induced diabetic rats. We prepared STZ-induced diabetic rats exhibiting a type 1 DM phenotype with low body weight, hyperglycemia, hyperlipidemia and hypoinsulinemia. Histological sections confirmed atrophy and fibrosis of the heart, with collagen accumulation representing diabetic cardiomyopathy. Significant decreases in end-diastolic volume, stroke volume, stroke work, end-systolic elastance and cardiac output indicated impaired cardiac contractility, as well as mRNA conversion of two isoforms of myosin heavy chain (α-MHC and ß-MHC) and increased atrial natriuretic factor (ANF) mRNA indicating heart failure, were consistent with the features of HFpEF. In diabetic HFpEF rats, we examined a selected panel of 12 circulating miRNAs associated with HF (miR-1-3p, miR-21-5p, miR-29a-5p, miR-30d-5p, miR-34a-5p, miR-126a-5p, miR-143-3p, miR-145-5p, miR-195-5p, miR-206-3p, miR-320-3p and miR-378-3p). Although they were all expressed at significantly lower levels in the heart compared to non-diabetic controls, only six miRNAs (miR-21-5p, miR-30d-5p, miR-126a-5p, miR-206-3p, miR-320-3p and miR-378-3p) were also reduced in exosomal content, while one miRNA (miR-34a-5p) was upregulated. Similarly, although all miRNAs were correlated with reduced cardiac output as a measure of cardiovascular performance, only three miRNAs (miR-30d-5p, miR-126a-5p and miR-378-3p) were correlated in exosomal content. We found that miR-30d-5p and miR-126a-5p remained consistently correlated with significant reductions in exosomal expression, cardiac expression and cardiac output. Our findings support their release from the heart and association with diabetic HFpEF. We propose that these two EXO-miRNAs may be important for the development of diagnostic tools for diabetic HFpEF.

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer.

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival.

External validation of a triage tool for predicting cardiac arrest in the emergency department.

Early recognition and prevention comprise the first ring of the Chain of Survival for in-hospital cardiac arrest (IHCA). We previously developed and internally validated an emergency department (ED) triage tool, Emergency Department In-hospital Cardiac Arrest Score (EDICAS), for predicting ED-based IHCA. We aimed to externally validate this novel tool in another ED population. This retrospective cohort study used electronic clinical warehouse data from a tertiary medical center with approximately 130,000 ED visits per year. We retrieved data from 268,208 ED visits over a 2-year period. We selected one ED visit per person and excluded out-of-hospital cardiac arrest or children. Patient demographics and computerized triage information were retrieved, and the EDICAS was calculated to predict the ED-based IHCA. A total of 145,557 adult ED patients were included. Of them, 240 (0.16%) developed IHCA. The EDICAS showed excellent discrimination with an area under the receiver operating characteristic (AUROC) of 0.88. The AUROC of the EDICAS outperformed those of other early warning scores (0.80 for Modified Early Warning Score [MEWS] and 0.83 for Rapid Emergency Medicine Score [REMS]) in the same ED population. An EDICAS of 6 or above (i.e., high-risk patients) corresponded to a sensitivity of 33%, a specificity of 97%, and a positive likelihood ratio of 12.2. In conclusion, we externally validated a tool for predicting imminent IHCA in the ED and demonstrated its superior performance over other early warning scores. The real-world impact of the EDICAS warning system with appropriate interventions would require a future prospective study.

The impact of the COVID-19 outbreak on activation of the massive transfusion protocol in the emergency department.

BACKGROUND AND OBJECTIVES: An outbreak of coronavirus disease 2019 (COVID-19) occurred in mid-May of 2021 in Taiwan. After 2 months of hard work, transmissions were successfully prevented and the number of newly confirmed COVID-19 cases fell remarkably. We evaluated the impact of this outbreak on the massive transfusion protocol (MTP) in the emergency department (ED) of a trauma centre. MATERIALS AND METHODS: We retrospectively compared the activation and efficacy of MTP before, during and after the outbreak by analysing the clinical data relevant to MTP activations. RESULTS: There was no remarkable change in the average number of MTP triggers per month during the outbreak. The interval from an MTP trigger to the first unit of blood transfused at bedside was significantly increased during the outbreak compared to that before the outbreak (22.4 min vs. 13.9 min, p < 0.001); while the 24-h survival rate decreased (57.1% vs. 71.1%, p = 0.938). There were no remarkable changes in blood unit return or wastage during the outbreak. CONCLUSION: The COVID-19 outbreak limitedly affected MTP activation and waste of blood products, but significantly increased the interval from an MTP trigger to the first unit of blood transfused at bedside.

Automatic segmentation of paravertebral muscles in abdominal CT scan by U-Net: The application of data augmentation technique to increase the Jaccard ratio of deep learning.

ABSTRACT: Sarcopenia, characterized by a decline of skeletal muscle mass, has emerged as an important prognostic factor for cancer patients. Trunk computed tomography (CT) is a commonly used modality for assessment of cancer disease extent and treatment outcome. CT images can also be used to analyze the skeletal muscle mass filtered by the appropriate range of Hounsfield scale. However, a manual depiction of skeletal muscle in CT scan images for assessing skeletal muscle mass is labor-intensive and unrealistic in clinical practice. In this paper, we propose a novel U-Net based segmentation system for CT scan of paravertebral muscles in the third and fourth lumbar spines. Since the number of training samples is limited (i.e., 1024 CT images only), it is well-known that the performance of the deep learning approach is restricted due to overfitting. A data augmentation strategy to enlarge the diversity of the training set to boost the performance further is employed. On the other hand, we also discuss how the number of features in our U-Net affects the performance of the semantic segmentation. The efficacies of the proposed methodology based on w/ and w/o data augmentation and different feature maps are compared in the experiments. We show that the Jaccard score is approximately 95.0% based on the proposed data augmentation method with only 16 feature maps used in U-Net. The stability and efficiency of the proposed U-Net are verified in the experiments in a cross-validation manner.

Cytokine changes in fatal cases of paraquat poisoning.

Cytokine-mediated inflammation is involved in the pathophysiology of paraquat toxicity. Nevertheless, few human studies have examined fluctuations in circulating cytokine levels. Blood samples were obtained from 21 patients with paraquat poisoning and compared to those of 18 healthy controls. All paraquat patients received a standard detoxification protocol composed of hemoperfusion, pulse therapies of methylprednisolone and cyclophosphamide, followed by dexamethasone therapy. Nonsurvivors not only had higher scores for the severity index of paraquat poisoning (P=0.004) but also presented with higher white blood cell counts (P=0.046) than survivors. Multiplex immunoassays revealed higher circulating levels of interleukin 2 (IL-2), interleukin 9 (IL-9), interleukin 10 (IL-10) and macrophage inflammatory protein-1 beta (MIP-1ß) in survivors than in healthy controls. Furthermore, the circulating levels of interleukin 1 beta (IL-1ß), IL-2, interleukin 5 (IL-5), interleukin 8 (IL-8), IL-9, IL-10, interleukin 12 (IL-12 p70), interleukin 17A (IL-17A), eotaxin, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and MIP-1ß were higher in nonsurvivors than in healthy controls. Finally, the circulating levels of IL-1ß and MCP-1 were higher in nonsurvivors than in survivors. Therefore, the observation of cytokine-mediated inflammation is in line with the detoxification protocol because glucocorticoids and cyclophosphamide are potent anti-inflammatory agents. Additionally, circulating levels of IL-1ß and MCP-1 could serve as promising prognostic markers for patients with paraquat poisoning.

Structure-Based Functional Analysis of a Hormone Belonging to an Ecdysozoan Peptide Superfamily: Revelation of a Common Molecular Architecture and Residues Possibly for Receptor Interaction.

A neuropeptide (Sco-CHH-L), belonging to the crustacean hyperglycemic hormone (CHH) superfamily and preferentially expressed in the pericardial organs (POs) of the mud crab Scylla olivacea, was functionally and structurally studied. Its expression levels were significantly higher than the alternative splice form (Sco-CHH) in the POs, and increased significantly after the animals were subjected to a hypo-osmotic stress. Sco-CHH-L, but not Sco-CHH, significantly stimulated in vitro the Na+, K+-ATPase activity in the posterior (6th) gills. Furthermore, the solution structure of Sco-CHH-L was resolved using nuclear magnetic resonance spectroscopy, revealing that it has an N-terminal tail, three α-helices (α2, Gly9-Asn28; α3, His34-Gly38; and α5, Glu62-Arg72), and a π-helix (π4, Cys43-Tyr54), and is structurally constrained by a pattern of disulfide bonds (Cys7-Cys43, Cys23-Cys39, and Cys26-Cys52), which is characteristic of the CHH superfamily-peptides. Sco-CHH-L is topologically most similar to the molt-inhibiting hormone from the Kuruma prawn Marsupenaeus japonicus with a backbone root-mean-square-deviation of 3.12 Å. Ten residues of Sco-CHH-L were chosen for alanine-substitution, and the resulting mutants were functionally tested using the gill Na+, K+-ATPase activity assay, showing that the functionally important residues (I2, F3, E45, D69, I71, and G73) are located at either end of the sequence, which are sterically close to each other and presumably constitute the receptor binding sites. Sco-CHH-L was compared with other members of the superfamily, revealing a folding pattern, which is suggested to be common for the crustacean members of the superfamily, with the properties of the residues constituting the presumed receptor binding sites being the major factors dictating the ligand-receptor binding specificity.

A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.

The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.

The predictive and prognostic role of hematologic and biochemical parameters in the emergency department among coronavirus disease 2019 patients.

Coronavirus disease 2019 (COVID-19) had caused a worldwide pandemic with public health emergencies since 2020. For the symptomatic patients, high mortality rate was observed if without timely and optimized management. In this study, we aimed to investigate the predictive and prognostic roles of hematologic and biochemical parameters obtained in the emergency department (ED) for COVID-19 patients. We conducted a retrospective study in a dedicated COVID-19 medical center, recruiting a total of 228 COVID-19 patients with 86 severe and 142 non-severe cases. Both the hematologic and biochemical parameters obtained in the ED upon arrival were analyzed to evaluate the association of the biomarkers with disease severity and prognosis among COVID-19 patients. Among these parameters, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, and D-dimer were significantly higher in the severe group than the non-severe one, whereas the platelet count and lymphocyte-to-monocyte ratio were significantly lower. Receiver operating characteristic curve analysis revealed that the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the severity of COVID-19 were 0.713, 0.755, 0.763, 0.741, 0.733, and 0.683, respectively, whereas the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the mortality of COVID-19 were 0.678, 0.744, 0.680, 0.676, 0.755, and 0.572, respectively. Logistic regression analysis revealed that CRP, PCT, LDH, ferritin, D-dimer, and NLR were independent indicators for prediction of severe COVID-19, and LDH and ferritin were independent factors associated with the mortality in COVID-19. In conclusion, higher CRP, PCT, LDH, ferritin, D-dimer, and NLR were associated with severe COVID-19, whereas higher LDH and ferritin were associated with the mortality in COVID-19. These findings could help early risk stratification in the ED and contribute to optimized patient management.