Chemical-Chemical Redox Cycle Signal Amplification Strategy Combined with Dual Ratiometric Immunoassay for Surface-Enhanced Raman Spectroscopic Detection of Cardiac Troponin I.

Improving the sensitivity and reproducibility of surface-enhanced Raman spectroscopy (SERS) methods for the detection of bioactive molecules is crucial in biological process research and clinical diagnosis. Herein, we designed a novel SERS platform for cardiac troponin I (cTnI) detection by a chemical-chemical redox cycle signal amplification strategy combined with a dual ratiometric immunoassay. First, ascorbic acid (AA) was generated by enzyme-assisted immunoreaction with a cTnI-anchored sandwich structure. Then, oxidized 4-mercaptophenol (ox4-MP) was reacted with AA to produce 4-mercaptophenol (4-MP). Quantitative analysis of cTnI was realized by a Raman signal switch between ox4-MP and 4-MP. Specifically, AA could be regenerated by reductant (tris(2-carboxyethyl) phosphine, TCEP), which in turn produced more signal indicator 4-MP, causing significant signal amplification for cTnI analysis by SERS immunosensing. Moreover, a dual ratiometric-type SERS method was established with the intensity ratio I1077/I822 and I633/I822, which improved the reproducibility of the cTnI assay. The excellent performance of the chemical-chemical redox cycle strategy and ratio-type SERS assay endows the method with high sensitivity and reproducibility. The linear ranges of cTnI were 0.001 to 50.0 ng mL-1 with detection limits of 0.33 pg mL-1 (upon I1077/I822) and 0.31 pg mL-1 (upon I635/I822), respectively. The amount of cTnI in human serum samples yielded recoveries from 89.0 to 114%. This SERS method has remarkable analytical performance, providing an effective approach for the early diagnosis of cardiovascular diseases, and has great latent capacity in the sensitive detection of bioactive molecules.

T/Myeloid Mixed-Phenotype Acute Leukemia with Basophilia.

BACKGROUND: As a rare heterogeneous kind of acute leukemia, mixed-phenotype acute leukemia (MPAL) co-expresses more than one cell lineage and could contain bilineal, biphenotypic, or a combination. MPAL is classified as T/myeloid, B/myeloid, B/T-lymphoid, and trilineage B/T/myeloid. METHOD: Here, we report a rare case of T/Myeloid bilineage mixed-phenotype acute leukemia with basophilia. RESULT: The puzzling morphological features are due to two distinct kinds of blasts have put hematologists into a dilemma. The diagnosis of T/myeloid MPAL with basophilia was established based on integrated diagnostics. CONCLUSIONS: To date, no case of a patient diagnosed with T/Myeloid bilineage MPAL with basophilia has been reported. The case focuses on the importance of an integrated diagnostic work-up, with a challenging morphological presentation and crucial role for flow cytometry.

Study on superconducting Li-Se-H hydrides.

The structures, stabilities and superconducting properties of LiSeHn (n = 4-10) hydrides at 150-300 GPa were studied by the genetic algorithm (GA) and DFT calculation method. Three stable stoichiometries of LiSeH4, LiSeH6 and LiSeH10 were uncovered under high pressure. Four other metastable stoichiometries of LiSeH5, LiSeH7, LiSeH8, and LiSeH9 were also studied. By analyzing the electronic band structure and electronic density of states, C2 LiSeH4, Pmm2 LiSeH6 and C2 LiSeH10 were all found to be metal phases above 150 GPa. Electron-phonon coupling calculations showed that C2 LiSeH4 and Pmm2 LiSeH6 were promising superconductors. The predicted Tc values of C2 LiSeH4 and Pmm2 LiSeH6 were 77 K at 200 GPa and 111 K at 250 GPa, respectively.

Dual Effect of Tryptamine on Prostate Cancer Cell Growth Regulation: A Pilot Study.

Abnormal tryptophan metabolism is linked to cancer and neurodegenerative diseases, and tryptophan metabolites have been reported as potential prostate cancer (PCa) biomarkers. However, little is known about the bioactivities of tryptophan metabolites on PCa cell growth. In this study, MTT and transwell assays were used to study the cytotoxicities of 13 major tryptophan metabolites on PCa and normal prostate epithelial cell lines. Ultraperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to analyze metabolic changes in cells treated with tryptamine. Flow cytometry, confocal imaging, and Western blot were used to test the apoptosis induced by tryptamine. It was shown that tryptamine had obvious inhibitory effects on PCa cell lines PC-3 and LNCaP, stronger than those on the normal prostate cell line RWPE-1. Tryptamine was further shown to induce apoptosis and inhibit PC-3 cell migration. Metabolic changes including amino acid metabolism related to cell proliferation and metastasis were found in PC-3 cells treated with tryptamine. Furthermore, a PC-3 xenograft mouse model was used to study the effect of tryptamine in vivo. The intratumoral injection of tryptamine was demonstrated to significantly reduce the tumor growth and tumor sizes in vivo; however, intraperitoneal treatment resulted in increased tumor growth. Such dual effects in vivo advanced our understanding of the bioactivity of tryptamine in regulating prostate tumor development, in addition to its major role as a neuromodulator.

TIM-3: An emerging target in the liver diseases.

T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3) is found expression in the surface of terminally differentiated T cells and belongs to the TIM family of type Ⅰ transmembrane proteins. It binds to the ligand Galectin-9 and mediates T cell apoptosis. As the research progresses, TIM-3 is also expressed in Th17, NK, monocyte, which binds to ligand and induce immune peripheral tolerance in both mice and man. Numerous researches have demonstrated that TIM-3 influences liver diseases, including liver-associated chronic viral infection, liver fibrosis, liver cancer et al and suggest new approaches to intervention. Currently, targeted therapy of TIM-3 is a new treatment in the field of immunization. Although many studies have proven that TIM-3 has an inhibitory effect in vivo, the specific mechanism is not clear. Herein, we summarize the important role of TIM-3 in the regulation of liver disease and prospects for future clinical research. TIM-3 will provide new targets for improving clinical liver disease.

Cross-regulation by TLR4 and T cell Ig mucin-3 determines severity of liver injury in a CCl4-induced mouse model.

Acute liver injury is a common pathological basis for a variety of acute liver diseases in the clinic, which can eventually lead to liver fibrosis and even liver failure. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) and TLR4 receptors play important roles in CCl4-induced acute liver injury. Tim-3 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim-3 (anti-Tim-3 Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti-Tim-3 Ab treatment increased interferon-É£ production by concanavalin A (ConA)-stimulated spleen T cells, and we found that the expression level of interleukin (IL)-6 was increased in a macrophage/spleen T cell coculture system, while administration of galectin-9 (Gal-9, a Tim-3 ligand) reduced the IL-6 production. This indicates the importance of the Tim-3/Gal-9 signalling pathway in maintaining hepatic homeostasis. The Tim-3 signalling pathway inhibits TLR4-mediated NF-κB activity, and an anti-Tim-3 Ab does not affect the liver injury in TLR4-deficient mice. Regulation between Tim-3 and TLR4 determines the severity of liver damage. The negative regulation of Tim-3 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.

Theoretical Prediction of Si2-Si33 Absorption Spectra.

The optical absorption spectra of Si2-Si33 clusters were systematically studied by a time-dependent density functional theory approach. The calculations revealed that the absorption spectrum becomes significantly broad with increasing cluster size, stretching from ultraviolet to the infrared region. The absorption spectra are closely related to the structural motifs. With increasing cluster size, the absorption intensity of cage structures gradually increases, but the absorption curves of the prolate and the Y-shaped structures are very sensitive to cluster size. If the transition energy reaches ∼12 eV, it is noted that all the clusters have remarkable absorption in deep ultraviolet region of 100-200 nm, and the maximum absorption intensity is ∼100 times that in the visible region. Further, the optical responses to doping in the Si clusters were studied.

Si78 double cage structure and special optical properties.

We performed first-principles calculations to study the structural stability of Si78 clusters with or without hydrogen passivation. The calculations reveal that an endohedral double cage isomer is more stable than the diamond-like structure, whereas the opposite is found for the hydrogen passivated isomers. In particular, the hydrogenated double cage and diamond-like structure may display blue shifts to the visible and UV regions, respectively. The IR vibration spectra, ionization potential (IP) and electronic density-of-states of the clusters were calculated and discussed.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community.

BACKGROUND: Age is a significant risk factor of diabetes mellitus (DM). With the develop of population aging, the incidence of DM remains increasing. Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM. AIM: To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals. METHODS: A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed. The prevalence of DM among the elderly was calculated. The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure (DBP) and systolic blood pressure (SBP), fasting blood glucose, body mass index (BMI), waist-to-hip ratio (WHR) and incidence of hypertension (HT), coronary heart disease (CHD), and chronic kidney disease (CKD). RESULTS: DM was diagnosed in 32.70% of the 4816 elderly people. The BMI of the DM group (25.16 ± 3.35) was greater than that of the non-DM group (24.61 ± 3.78). The WHR was 0.90 ± 0.04 in the non-DM group and 0.90 ± 0.03 in the DM group, with no significant difference. The left SBP and SBP in the DM group were 137.9 mmHg ± 11.92 mmHg and 69.95 mmHg ± 7.75 mmHg, respectively, while they were 126.6 mmHg ± 12.44 mmHg and 71.15 mmHg ± 12.55 mmHg, respectively, in the non-DM group. These findings indicate higher SBP and lower DBP in DM patients than in those without DM. In the DM group, 1274 patients were diagnosed with HT, accounting for 80.89%. Among the 3241 non-DM patients, 1743 (53.78%) were hypertensive and 1498 (46.22%) were nonhypertensive. The DM group had more cases of HT than did the non-DM group. There were more patients with CHD or CKD in the DM group than in the non-DM group. There were more patients who drank alcohol more frequently (≥ 3 times) in the DM group than in the non-DM group. CONCLUSION: Older adults in the Lugu community are at a greater risk of DM. In elderly individuals, DM is closely related to high BMI and HT, CHD, and CKD. Physical examinations should be actively carried out for elderly people to determine their BMI, SBP, DBP, and other signs, and sufficient attention should be given to abnormalities in the above signs before further diagnosis.

Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis.

OBJECTIVE: Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. METHOD: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. RESULTS: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. CONCLUSION: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.

Structures and electronic properties of the SiAu(n) (n = 17-20) clusters.

The structures and electronic properties of the SiAu(n) (n = 17-20) clusters are systematically investigated using DFT calculations. The result shows that doping with silicon would significantly change the structures of the gold clusters. For the SiAu(n) (n = 17-20) clusters, the lowest-energy structures exhibit shell-like cage configuration in which the dopant Si atom binds to the cage surface and one Au atom skips to the top of the Si atom forming a SiAu5 or SiAu6 subunit except SiAu19, which is a tetrahedron-like structure with a protruding Au atom. The Au atoms of the SiAu(n) (n = 17-20) clusters carry different partial charges due to their different locations.

Clinical effect of antibiotic combined with fiber bronchoscope perfusion in treatment of pneumonia after severe cerebral hemorrhage.

To explore the curative effect of antibiotic combined with mucosolvan perfusion under fiber bronchoscope in treatment of pneumonia after severe cerebral hemorrhage. The clinical data of 120 patients with pneumonia after severe cerebral hemorrhage admitted to our hospital from January 2017 to December 2019 were collected. All patients were divided into the lavage group and perfusion group by random number method, with 60 patients in each group. Patients in the lavage group received antibiotics combined with mucosolvan lavage therapy under fiber bronchoscope, while patients in the perfusion group received antibiotics combined with mucosolvan perfusion therapy under fiber bronchoscope. Clinical pulmonary infection score (CPIS), arterial blood gas index, clinical symptom improvement, and hospitalization costs were compared between the two groups before and after treatment. CPIS scores were improved after treatment in both groups (P < .05), and CPIS scores of patients in the perfusion group were lower than those in the lavage group at 3, 5, and 7 days after treatment (P < .05). The blood oxygen saturation and partial arterial oxygen pressure of the perfusion group were all higher than those of the lavage group (P < .05), while the partial carbon dioxide pressure was lower than that of the lavage group (P < .05). In the perfusion group, the duration of cough, adequacy of fever, disappearance of rhonchus in the lungs, and the length of hospital stay were less than those in the lavage group (P < .05). The hospitalization costs of perfusion group were lower than that of lavage group (P < .05). The combination of antibiotics and mucosolvan infusion therapy under fiber bronchoscope can effectively improve the clinical efficacy, reduce the hospitalization cost, and improve the prognosis of patients with pneumonia after severe cerebral hemorrhage.

Infrared Radiation Characterization of Damaged Coal Rupture Based on Stress Distribution and Energy.

As coal mine production enters the deep mining stage, the impact of coal and rock dynamic hazards is becoming more and more significant. And the coal and rock containing initial damage such as fractures are more susceptible to destabilization damage by disturbance. So, this paper takes coal containing macro-crack with different inclination angles as the research object and uses the RMT-150B rock mechanics system to carry out uniaxial loading rupture tests on the specimens. On this basis, the changes in infrared radiation on the surface are observed using an infrared thermal imaging camera, and it is analyzed and studied according to the stress distribution and energy change of the specimens. The results show that the strain ratio at crack closure after bearing the coal gradually increases with the increase in the macro-crack inclination. When the inclination angle is 0° < α < 90°, there are obvious low-temperature bands on the upper and lower sides after macro-crack closure. The variance of the infrared thermal image of the specimen can reflect its infrared radiation information more effectively and has a good correspondence with the stress-strain curve. With the increase in the specimen macro-crack inclination angle, the linear change of VIRT is more obvious, the rate of change gradually increases, and the inclination angle is the maximum at 90°. The accumulated elastic strain energy U e is the main source of energy for the sudden change in infrared radiation generated during the bursting process that occurs when the specimen is damaged, and U e is linearly and positively correlated with the change in infrared radiation in front of the specimen peak. These will provide some experimental basis and theoretical guidance for the use of infrared radiation precursor characteristics to warn the damaged coal-rock dynamic disaster.

RGB color analysis of formaldehyde in vegetables based on DNA functionalized gold nanoparticles and triplex DNA.

A highly sensitive and selective RGB color analysis for the detection of formaldehyde (FA) was developed by using a DNA functionalized gold nanoparticle (AuNPs-DNA) probe. When complementary oligonucleotides (oligo 2 and oligo 3) and a silver ion (Ag+) were added to the AuNPs-DNA solution, triplex DNA was formed, resulting in the aggregation of AuNPs, and accompanied by a solution color change from red to purple. With the addition of formaldehyde, it reacted with Ag+, decreased the stability of triplex DNA between AuNPs-DNA, induced the dispersion of AuNPs, and the color of AuNPs recovered to red. Therefore, the formaldehyde concentration could be estimated with the RGB (red, green, blue) values of the AuNP solution by using a smartphone application (APP). The R value of the system was proportional to the concentration of formaldehyde within the range of 0.23-4.50 mg L-1, with a detection limit of 0.14 mg L-1. The method has been successfully applied to detect the residues of formaldehyde in vegetable samples and has the potential of the on-site determination of formaldehyde.

Erratum: Corection to "Multiple Sequence Long and Short Memory Network Model for Corner Gas Concentration Prediction on Coal Mine Workings".

[This corrects the article DOI: 10.1021/acsomega.2c05188.].

Multiple Sequence Long and Short Memory Network Model for Corner Gas Concentration Prediction on Coal Mine Workings.

To further improve the accuracy of recurrent neural network in predicting the gas concentration in the upper corner of the mine tunnel, this paper proposes a method to construct a gas concentration prediction model based on multiple sequence long and short memory network, considering the spatial correlation between the gas concentration in the return airway and upper corner. The reliability of the model construction is improved by using the white noise test and smoothness test to verify the interpretability of the data in this paper and constructing supervised learning type data for gas concentration prediction model training and testing by means of data set division and data windowing. Through experimental comparison, grid search, and time series decomposition, the model algorithm, training parameters, and experimental results were combined to make an in-depth analysis of the influence of each parameter on the model training and the prediction. A training model of the spatially fused gas concentration prediction model with a network layer of 1 and a number of neurons of 32 as the model structure, Adam as the optimization algorithm, and a learning rate of 0.001 and a batch size of 32 as the training parameters was finally determined. The gas concentration prediction model trained in this paper performed well in the test set with a mean square error (MSE) of 0.0013, and its superiority was verified by comparing it with other models to provide some experience and basis for subsequent studies on gas concentration prediction in the upper corner.

Competitive diamond-like and endohedral fullerene structures of Si70.

We performed first-principles calculations to study the structure and stability of Si(70) cluster. The results from the density functional theory calculation with the Becke-Lee-Yang-Parr and B3LYP exchange-correlation functionals suggest that a diamond-like Si(70) isomer is the most stable structure, in contrast to endohedral fullerenes of Si(70). On the other hand, an endohedral fullerene of Si(16)@Si(54) was found to be slightly lower in energy than the diamond-like Si(70) if the Predew-Burke-Ernzerhof functional is used. Our calculation results suggest that around n = 70, the endohedral fullerene and diamond-like isomer are expected to be competitive. The calculated IR vibration spectra, ionization potential, and inverse mobilities were also calculated and discussed.

TIM-3: An update on immunotherapy.

T cell immunoglobulin and mucin domain 3 (TIM-3) was originally found to be expressed on the surface of Th1 cells, acting as a negative regulator and binding to the ligand galectin-9 to mediate Th1 cell the apoptosis. Recent studies have shown that TIM-3 is also expressed on other immune cells, such as macrophages, dendritic cells, and monocytes. In addition, TIM-3 ligands also include Psdter, High Mobility Group Box 1 (HMGB1) and Carcinoembryonic antigen associated cell adhesion molecules (Ceacam-1), which have different effects upon biding to different ligands on immune cells. Studies have shown that TIM-3 plays an important role in autoimmune diseases, chronic viral infections and tumors. A large amount of experimental data supports TIM-3 as an immune checkpoint, and targeting TIM-3 is a promising treatment method in current immunotherapy, especially the new combination of other immune checkpoint blockers. In this review, we summarize the role of TIM-3 in different diseases and its possible signaling pathway mechanisms, providing new insights for better breakthrough immunotherapy.

miR-24 protects against ischemia-induced brain damage in rats via regulating microglia polarization by targeting Clcn3.

Microglia and macrophages play important roles in ischemic brain injury. Changes in their M1/M2 polarization phenotypes significantly impact disease progression. The M2 microglia/macrophages are anti-inflammatory and have a protective effect against ischemic injury. The microRNA 24 (miR-24) promotes M2 macrophage polarization and suppresses inflammation. We tested the hypothesis that miR-24 is protective in ischemic brain injury by regulating microglia polarization. We treated rats with miR-24 inhibitor or mimic and subsequently subjected the rats to middle cerebral artery occlusion (MCAO) to induce ischemic brain injury. Neurological deficit and infarct volume were analyzed. Microglia and macrophages were assessed by fluorescence-activated cell sorting. Microglia polarization was determined by genes specific for M1 and M2 both in vivo and in BV-2 cells. The effect of miR-24 target Clcn3 on microglia polarization was examined. We found that miR-24 inhibition aggravated MCAO induced damage, while miR-24 overexpression alleviated brain injury by suppressing microglia/macrophage infiltration. miR-24 suppressed M1 and promoted M2 microglia polarization both in vivo and in vitro. Finally, we showed that miR-24 targeted Clcn3 to regulate microglia polarization. Our study indicates that miR-24 plays a neuroprotective role by promoting anti-proinflammatory microglia polarization during ischemic brain injury.

A novel chemiluminescence imaging immunosensor for prostate specific antigen detection based on a multiple signal amplification strategy.

A novel chemiluminescence (CL) imaging platform was constructed for prostate specific antigen (PSA) detection in a multiple signal amplifying manner. To construct the platform, the primary antibody for PSA was firstly immobilized on a O-ring area of a glass slide for recognizing the PSA. The horseradish peroxidase (HRP) and the secondary antibody of PSA (Ab2) functionalized Au NPs (HRP-Au NPs-Ab2) were modified on the platform through immunoreaction between PSA and Ab2. The excellent catalytic effect of Au NPs and HRP on the HRP-Au NPs-Ab2 to the luminol-H2O2 CL system provided the dual-signal amplification for PSA detection. To further enhance the sensitivity, tyramine signal amplification (TSA) strategy was introduced: tyramine-HRP conjugates were added into the O-ring reservoir and thus tyramine-HRP repeats formed in the presence of H2O2, generating a multiple signal amplification because of the large amounts of HRP on the sensing interface. The excellent performance of HRP-Au NPs-Ab2 and TSA strategy endows the CL platform with high sensitivity. The PSA was detected with a photomultiplier tube (PMT) and visually analyzed by a charge coupled device (CCD), respectively. The linear ranges of PMT and CCD for PSA are 0.1-100.0 ng mL-1 with a detection limit of 0.05 pg mL-1 and 0.5 - 100.0 ng mL-1 with a detection limit of 0.1 pg mL-1, respectively. The levels of PSA in several human serum samples were determined and the recoveries are ranged from 82.5% - 117.0%. This CL immunosensing platform holds great potential for bioactive molecules detection visually and sensitively.