Adenosine Deaminase as a Potential Diagnostic and Prognostic Biomarker for Severe Fever with Thrombocytopenia Syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease caused by the Dabie bandavirus, with a high mortality rate. Currently, there are no effective vaccines or specific treatments for SFTS. Early diagnosis and accurate severity assessment are crucial. METHODS: This study included 171 cases of SFTS, COVID-19, and hepatitis B virus (HBV) patients and healthy controls. We compared the serum adenosine deaminase (ADA) activity across these groups. The diagnostic and prognostic efficiency of serum ADA for SFTS was evaluated by using receiver operating characteristic (ROC) curve analysis. We also examined the correlation between serum ADA in SFTS patients and clinical lab parameters as well as serum cytokines. RESULTS: SFTS patients had significantly higher serum ADA activity than those of COVID-19, HBV patients, and healthy controls. Nonsurvivor SFTS patients had notably higher ADA than survivors. ROC analysis indicated ADA as an effective SFTS diagnostic and prognostic biomarker. ADA correlated with prognosis, viral load, APTT, PT, AST, ferritin, negatively with HDL-c and LDL-c, and positively with cytokines like IL-6, TNF-α, and IL-1ß. Multiorgan failure patients showed significant ADA increase. CONCLUSION: Elevated serum ADA activity in SFTS patients is linked with disease severity and prognosis, showing potential as a diagnostic and prognostic biomarker for SFTS.

[Development of a Three-Wavelength Brain Tissue Oxygen Monitoring System Based on Near Infrared Spectrum].

In the past 20 years, near infrared spectrum technology has been widely used in human body monitoring due to its non-invasive and real-time characteristics. Oxygen, as the main metabolic substance of the human body, is consumed the most in brain tissue. In order to prevent complications caused by a decrease in brain tissue oxygen during treatment, the patient's brain tissue blood oxygen saturation needs to be monitored in real time. Currently, most of the clinically used non-invasive cerebral blood oxygen detection equipments use dual wavelengths. Other substances on the detection path will cause errors in the measurement results. Therefore, this article proposes a three-wavelength method based on the basic principle of non-invasive monitoring of cerebral blood oxygen using near-infrared spectrum. The brain tissue oxygen saturation monitoring method of detecting light sources was initially verified through the built system, laying the foundation for subsequent system engineering.

Electromagnetic heating-assisted metasurface for stably tunable, fast-responding chiroptics.

Herein, a graphene-dielectric metasurface with the function of stably tunable and fast responding on the chiroptics is theoretically investigated and numerically demonstrated. Via utilizing the intrinsic thermo-optical effect of the silicon, the circular dichroism (CD) peak position can be linearly scaled with a spectral sensitivity of up to 0.06 nm/K by artificially adjusting the temperature. Moreover, a perfectly adjusting manipulation with a wavelength shift of full width at half maximum for the resonant spectrum and the simultaneously maintained CD values can be realized by a slight temperature variation of ∼0.8 K. Additionally, we take a graphene layer as the heating source to actually demonstrate the ultra-fast thermal generation. Applying an input voltage of 2 V to the graphene with only 10 µs can rapidly increase the metasurface temperature of up to 550 K. Such performances hold the platform with wide applications in functional chiroptics and optoelectronics.

Elevation of Metrnß and Its Association with Disease Activity in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an auto-immune disease, the pathogenesis of which remains to be fully addressed. Metrnß is a novel cytokine involved in the pathogenesis of inflammatory disease, but its regulatory roles in SLE are unclear. We aimed to comprehensively investigate the clinical value of Metrnß in SLE. A massive elevation of circulating Metrnß levels was observed in SLE, and patients with an active phase displayed higher Metrnß concentrations than those with inactive phases. Additionally, we found that Metrnß expression was positively correlated with clinical indicators of SLE. Longitudinal cytokine and chemokine profiles revealed a disturbed immune response in SLE, with high activity profiles displayed severe pathogenic inflammation, and a positive correlation of the serum Metrnß with CXCL9, IL10, IL18 and IL1RA was observed as well. Moreover, Metrnß expressions exhibited an inverse correlation with Treg and B10. Of note, a significant decrease of ILC2 was found in SLE, and there was a negative correlation of Metrnß with ILC2 as well. Further ROC analysis showed that the area under the curve (AUC) for Metrnß was 0.8250 (95% CI: 0.7379-0.9121), with a cutoff value of 1131 pg/mL to effectively distinguish SLE patients from healthy controls. Our study herein demonstrated for the first time that Metrnß values were increased and were immunologically correlated with SLE activity, which could be utilized as an alternative biomarker for the early identification and predicting of the immuno-response of SLE.

GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner.

GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis. The catalysis of BH4 biosynthesis is tightly regulated for physiological neurotransmission, inflammation, and vascular tone. Paradoxically, BH4 has emerged as an oncometabolite regulating tumor growth, but the effects on tumor development remain controversial. Here, we found that GCH1 potentiated the growth of triple-negative breast cancer (TNBC) and HER2+ breast cancer and transformed nontumor breast epithelial cells. Independent of BH4 production, GCH1 protein induced epithelial-to-mesenchymal transition by binding to vimentin (Vim), which was mediated by HSP90. Conversely, GCH1 ablation impaired tumor growth, suppressed Vim in TNBC, and inhibited EGFR/ERK signaling while activating the p53 pathway in estrogen receptor-positive tumor cells. GCH1 deficiency increases tumor cell sensitivity to HSP90 inhibition and endocrine treatments. In addition, high GCH1 correlated with poor breast cancer survival. Together, this study reveals an enzyme-independent oncogenic role of GCH1, presenting it as a potential target for therapeutic development. SIGNIFICANCE: GTP cyclohydrolase functions as an oncogene in breast cancer and binds vimentin to induce epithelial-to-mesenchymal transition independently of its enzyme activity, which confers targetable vulnerabilities for developing breast cancer treatment strategies.

A colloidal gold test strip based on catalytic hairpin assembly for the clinical detection of influenza a virus nucleic acid.

Influenza A epidemics, which occur annually in varying degrees worldwide, is a global challenge to healthcare facilities owing to several limitations of the current detection methods. Therefore, the development of a rapid, convenient, and economical method for the early diagnosis of influenza A will aid clinical treatment and epidemic control. Currently, most of the commonly used clinical rapid tests utilize colloidal gold test strips that detect specific influenza virus antigens but are limited by low sensitivity. Therefore, this study combined catalytic hairpin assembly (CHA) with colloidal gold immunochromatographic assay (GICA) to develop a highly sensitive and visual CHA-GICA test strip. Clinical sample analysis revealed that the sensitivity of the assay was 81.8% and 74% under optimal (35 °C) and room temperature (25 °C) conditions, respectively. In conclusion, this study developed a rapid nucleic acid assay for detecting influenza A virus with high sensitivity and specificity, which can improve the clinical detection of influenza A.

Dual-targeted and dual-sensitive self-assembled protein nanocarrier delivering hVEGI-192 for triple-negative breast cancer.

Breast cancer is a highly prevalent malignancy worldwide among women with an increasing incidence in recent years. Triple-negative breast cancer (TNBC), a specific type of breast cancer, occurs primarily in young women and exhibits large tumor size, high clinical stage, and extremely poor prognosis with a high rate of lymph node, liver, and lung metastases. TNBC is insensitive to endocrine therapy and trastuzumab treatment, and there is an urgent need for effective therapeutics and treatment guidelines. However, investigations into antiangiogenic agents for the treatment of TNBC are ongoing. In this study, we successfully engineered a self-assembled protein nanocarrier TfRBP9-hVEGI-192-ELP fusion protein (TVEFP) to deliver the therapeutic protein, human vascular endothelial growth inhibitor (hVEGI-192). This was found to be effective in inhibiting tumor angiogenesis in vivo. The protein nanocarrier effectively inhibited the progression of TNBC in vivo and showed the behavior of self-assembly, thermoresponsiveness, enzyme stimulation-responsiveness, tumor-targeting, biocompatibility, and biodegradability. Near-infrared imaging studies showed that fluorescent dye-stained TVEFP effectively aggregated at the tumor site. The TVEFP nanocarrier significantly expands the application of the therapeutic protein hVEGI-192 and improves the imaging and biotherapeutic effects in TNBC, chiefly based on anti-angiogenesis effects.

Addition of dNTPs can improve the detection sensitivity of catalytic hairpin assembly.

Ever since the catalytic hairpin assembly (CHA) circuit has been highlighted as a powerful nucleic acid detection tool, nucleic acid detection methods based on CHA have been widely studied. However, the detection sensitivity of CHA-based methods is insufficient. The relatively high background signals resulting from the spontaneous reaction between the two hairpin probes is one of the major reasons for limiting the sensitivity of CHA. In this study, we established that the addition of deoxynucleotide triphosphates (dNTPs) to the reaction system can significantly reduce the background leakage of CHA. The dNTPs-CHA, coupled with a fluorescence lateral flow assay strip, is used for the rapid and highly sensitive detection of miRNA. It is capable of reliably detecting miRNA in serum samples down to a limit of 100 aM, which is an improvement in the lower detection limit by nearly five orders of magnitude compared to that of the pure CHA.

Oenological characteristics of two indigenous Starmerella bacillaris strains isolated from Chinese wine regions.

To broaden knowledge about the oenological characteristics of Starmerella bacillaris, the influence of two Chinese indigenous S. bacillaris strains on the conventional enological parameters and volatile compounds of Cabernet Sauvignon wines were investigated under different inoculation protocols (single inoculation and simultaneous/sequential inoculation with the commercial Saccharomyces cerevisiae EC1118). The results showed that the two S. bacillaris strains could complete alcohol fermentation alone under high sugar concentrations while increasing the content of glycerol and decreasing the content of acetic acid. Compared with wines fermented by EC1118 single inoculation, S. bacillaris single inoculation and S. bacillaris/EC1118 sequential inoculation increased the contents of isobutanol, ethyl isobutanoate, terpenes, and ketones and decreased the contents of isopentanol, phenylethyl alcohol, fatty acids, acetate esters, and total ethyl esters. Furthermore, for S. bacillaris/EC1118 simultaneous inoculation, the concentrations of ethyl esters were increased, contributing to a higher score of "floral" and "fruity" notes in agreement with sensory analysis. KEY POINTS: • S. bacillaris single and simultaneous/sequential inoculation. • Conventional enological parameters and volatile compounds were investigated. • S. bacillaris/EC1118 simultaneous fermentation increased ethyl esters.

A simple and programmable dual-mode aptasensor for the ultrasensitive detection of multidrug-resistant bacteria.

Accurately identifying multidrug-resistant (MDR) bacteria from clinical samples has long been a challenge. Herein, we report a simple and programmable dual-mode aptasensor called DAPT to reliably detect MDR bacteria. The DAPT method comprises two elements, namely the mode of dynamic light scattering (Mode-DLS) for ultrasensitive detection and the mode of fluorescence (Mode-Flu) for reliable quantification as a potent complement. Benefiting from the states of aptamer-modified gold nanoparticles (AptGNPs) sensitively changing from dispersion to aggregation, the proposed Mode-DLS achieved the rapid, specific, and ultrasensitive detection of methicillin-resistant Staphylococcus aureus (MRSA) at the limit of detection (LOD) of 4.63 CFU mL-1 in a proof-of-concept experiment. Simultaneously, the Mode-Flu ensured the accuracy of the detection, especially at a high concentration of bacteria. Moreover, the feasibility and universality of the DAPT platform was validated with four other superbugs by simply reprogramming the corresponding sequence. Overall, the proposed DAPT method based on a dual-mode aptasensor can provide a universal platform for the rapid and ultrasensitive detection of pathogenic bacteria due to its superior programmability.

[Development of Respiratory Signal Monitoring System Based on Photoplethysmography].

Breathing is of great significance in the monitoring of patients with obstructive sleep apnea hypopnea syndrome, perioperative monitoring and intensive care. In this study, a respiratory monitoring and verification system based on optical capacitance product pulse wave (PPG) is designed, which can synchronously collect human PPG signals. Through algorithm processing, the characteristic parameters of PPG signal are calculated, and the respiratory signal and respiratory frequency can be extracted in real time. In order to verify the accuracy of extracting respiratory signal and respiratory rate by the algorithm, the system adds the nasal airflow respiratory signal acquisition module to synchronously collect the nasal airflow respiratory signal as the standard signal for comparison and verification. Finally, the root mean square error between the respiratory rate extracted by the algorithm from the pulse wave and the standard respiratory rate is only 1.05 times/min.

Novel therapeutic strategies: targeting epithelial-mesenchymal transition in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance apical-basal cell polarity and cell-cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer, EMT has an important role in tumour progression, metastasis, and drug resistance. There has been accumulating evidence from preclinical and early clinical studies that show that EMT markers might serve as outcome predictors and potential therapeutic targets in colorectal cancer. This Review describes the fundamentals of EMT, including biology, newly partial EMT, and associated changes. We also provide a comprehensive summary of therapeutic compounds capable of targeting EMT markers, including drugs in preclinical and clinical trials and those with repurpose potential. Lastly, we explore the obstacles of EMT bench-to-bedside drug development.

Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma.

Oncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-ß-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development.

Deciphering the bacterial composition in the rhizosphere of Baphicacanthus cusia (NeeS) Bremek.

Rhizobacteria is an important ingredient for growth and health of medicinal herbs, and synthesis of pharmacological effective substances from it. In this study, we investigated the community structure and composition of rhizobacteria in Baphicacanthus cusia (NeeS) Bremek via 16S rRNA amplicon sequencing. We obtained an average of 3,371 and 3,730 OTUs for bulk soil and rhizosphere soil samples respectively. Beta diversity analysis suggested that the bacterial community in the rhizosphere was distinctive from that in the bulk soil, which indicates that B.cusia can specifically recruit microbes from bulk soil and host in the rhizosphere. Burkholderia was significantly enriched in the rhizosphere. Burkholderia is a potentially beneficial bacteria that has been reported to play a major role in the synthesis of indigo, which was a major effective substances in B. cusia. In addition, we found that Bacilli were depleted in the rhizosphere, which are useful for biocontrol of soil-borne diseases, and this may explain the continuous cropping obstacles in B. cusia. Our results revealed the structure and composition of bacterial diversity in B. cusia rhizosphere, and provided clues for improving the medicinal value of B. cusia in the future.

Neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase, lipase, high-density lipoprotein as a panel of factors to predict acute pancreatitis in pregnancy.

Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP has common symptoms with acute abdomen. Assessment of an acute abdomen is more complicated during pregnancy because the gravid uterus could mask most of symptomatic signs. It has been a challenge to diagnose APIP by physical examination or diagnostic imaging. Case studies on APIP are also limited for analysis on the risk factors associated with the disease. This retrospective study evaluated a series of risk factors from a relatively substantial number of APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine APIP patients together with 179 random normal pregnant women in Shengjing Affiliated Hospital of China Medical University were included for this retrospective study. Medical parameters of blood test in biochemistry and hematology were compared between 2 groups using t test. Multivariate logistic regression analysis was performed to investigate the relationship between various factors and APIP using Statistical Applied Software (SAS student version).Compared with normal pregnant women, APIP patients have elevated values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low-density lipoprotein cholesterol (LDL-D), and total proteins from their blood tests. In addition, APIP patients have decreased numbers in red cells but increased numbers in white blood cells and increased ratio of neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are significantly associated with APIP. This study suggests that the combination of those factors serve as a panel of indicators for early-onset prognosis of APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP. More case studies are important to further evaluate the predicting power of this panel factors in APIP.

Ultrasmall Pt Nanoclusters as Robust Peroxidase Mimics for Colorimetric Detection of Glucose in Human Serum.

In this work, a new type of ultrasmall Pt nanoclusters (Pt NCs) was prepared via a facile one-pot approach by using yeast extract as the reductant and stabilizer. Besides their excellent water solubility, these yeast extract-stabilized Pt NCs also possess attractive peroxidase mimicking property. They can efficiently catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the coexistence of hydrogen peroxide (H2O2). Catalytic mechanism analysis suggested that the peroxidase mimicking activity of these Pt NCs might originate from their characteristic of accelerating electron transfer between TMB and H2O2, and their enzymatic kinetics followed typical Michaelis-Menten theory. On the basis of these findings, we developed a new highly sensitive colorimetric method for glucose detection, and the limit of detection was calculated as low as 0.28 µM (S/N = 3). Further application of the present system for glucose detection in human serum has been successfully demonstrated, suggesting its promising utilization as robust peroxidase mimics in the clinical diagnosis, pharmaceutical, and environmental chemistry fields.

Paracrine effect of GTP cyclohydrolase and angiopoietin-1 interaction in stromal fibroblasts on tumor Tie2 activation and breast cancer growth.

Cancer-associated fibroblasts (CAFs) play a key role in promoting tumor growth, acting through complex paracrine regulation. GTP cyclohydrolase (GTPCH) expression for tetrahydrobiopterin synthesis in tumor stroma is implicated in angiogenesis and tumor development. However, the clinical significance of GTPCH expression in breast cancer is still elusive and how GTPCH regulates stromal fibroblast and tumor cell communication remains unknown. We found that GTPCH was upregulated in breast CAFs and epithelia, and high GTPCH RNA was significantly correlated with larger high grade tumors and worse prognosis. In cocultures, GTPCH expressing fibroblasts stimulated breast cancer cell proliferation and motility, cancer cell Tie2 phosphorylation and consequent downstream pathway activation. GTPCH interacted with Ang-1 in stromal fibroblasts and enhanced Ang-1 expression and function, which in turn phosphorylated tumor Tie2 and induced cell proliferation. In coimplantation xenografts, GTPCH in fibroblasts enhanced tumor growth, upregulating Ang-1 and alpha-smooth muscle actin mainly in fibroblast-like cells. GTPCH inhibition resulted in the attenuation of tumor growth and angiogenesis. GTPCH/Ang-1 interaction in stromal fibroblasts and activation of Tie2 on breast tumor cells could play an important role in supporting breast cancer growth. GTPCH may be an important mechanism of paracrine tumor growth and hence a target for therapy in breast cancer.

A case-cohort study of postoperative myocardial infarction: impact of anemia and cardioprotective medications.

OBJECTIVE: Postoperative myocardial infarction (poMI) is a serious and costly complication. Multiple risk factors for poMI are known, but the effect of anemia and cardioprotective medications have not been defined in real-world surgical practice. METHODS: Patients undergoing inpatient elective surgery were assessed at 17 hospitals from 2008 to 2011 for the occurrence of poMI (American Heart Association definition). Non-MI control patients were chosen randomly on the basis of case type. Descriptive, univariable, and multivariable statistical analysis were performed for primary outcomes of poMI and death at 30 days. RESULTS: Compared with controls (N = 304), patients with poMI (N = 222) were older (72 ± 11 vs 60 ± 17 years, P < .0001), had a lesser preoperative hematocrit (37 ± 6 vs 39 ± 5, P < .0001), more often were smokers, had a preoperative T-wave abnormality (21% vs 9%, P < .0001), and had a preoperative stress test with a fixed deficit (26% vs 3%; P < .001). Preoperative factors associated with poMI included peripheral vascular disease (odds ratio 2.6; 95% confidence interval 1.3-5.3), tobacco use (1.7; 1.01-2.9), history of percutaneous coronary angioplasty (2.8; 1.6-5.0), and age (1.05; 1.03-1.07), whereas hematocrit >35 (0.51; 0.32-0.82) and preoperative acetylsalicylic acid, ie, aspirin (0.59; 0.4-0.97) were protective. Preoperative ß-blockade, statin, and use of angiotensin-converting enzyme inhibitors were not associated with lesser rates of poMI. Non-MI complication rates were 23-fold greater in the poMI group compared with the control group (P < .0001). Mortality with poMI within 30 days was 11% compared with 0.3% in non-MI control patients (P < .0001). In patients with poMI, factors independently associated with death included use of epidurals (3.5; 1.07-11.4) and bleeding (4.2; 1.1-16), whereas preoperative use of aspirin (0.29; 0.1-0.88), and postoperative ß-blockade (0.18; 0.05-0.63) were protective. Cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting after poMI was performed in 34% of those alive and 20% of those who died (P = .16). CONCLUSION: In the current era, poMI patients have a markedly increased risk of death. This risk is decreased with preoperative use of acetylsalicylic acid and post MI ß-blockade. Further study is warranted to explore the role of anemia and cardiac interventions after poMI.

A statewide colectomy experience: the role of full bowel preparation in preventing surgical site infection.

OBJECTIVE: To assess the utility of full bowel preparation with oral nonabsorbable antibiotics in preventing infectious complications after elective colectomy. BACKGROUND: Bowel preparation before elective colectomy remains controversial. We hypothesize that mechanical bowel preparation with nonabsorbable oral antibiotics is associated with a decreased rate of postoperative infectious complications when compared with no bowel preparation. METHODS: Patient and clinical data were obtained from the Michigan Surgical Quality Collaborative-Colectomy Best Practices Project. Propensity score analysis was used to match elective colectomy cases based on primary exposure variable-full bowel preparation (mechanical bowel preparation with nonabsorbable oral antibiotics) or no bowel preparation (neither mechanical bowel preparation given nor nonabsorbable oral antibiotic given). The primary outcomes for this study were occurrence of surgical site infection and Clostridium difficile colitis. RESULTS: In total, 2475 cases met the study criteria. Propensity analysis created 957 paired cases (n = 1914) differing only by the type of bowel preparation. Patients receiving full preparation were less likely to have any surgical site infection (5.0% vs 9.7%; P = 0.0001), organ space infection (1.6% vs 3.1%; P = 0.024), and superficial surgical site infection (3.0% vs 6.0%; P = 0.001). Patients receiving full preparation were also less likely to develop postoperative C difficile colitis (0.5% vs 1.8%, P = 0.01). CONCLUSIONS: In the state of Michigan, full bowel preparation is associated with decreased infectious complications after elective colectomy. Within this context, the Michigan Surgical Quality Collaborative recommends full bowel preparation before elective colectomy.