Optical biomarker analysis for renal cell carcinoma obtained from preoperative and postoperative patients using ATR-FTIR spectroscopy.

Renal cell carcinoma (RCC) is the most common malignant tumor in the urinary system, accounting for 80 % to 90 % for all renal malignancies. Traditional diagnostic methods like magnetic resonance imaging (MRI) and computed tomography (CT) lack the sensitivity and specificity as they lack specific biomarkers. These limitations impede effective monitoring of tumor recurrence. This study aims to employ Attenuated Total Reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, an optical technology sensitive to molecular groups, to analyze the potential optical biomarkers in urine and plasma samples from RCC patients pre- and post-surgery. The results reveal distinctive spectral information from both plasma and urine samples. Post-surgery urine spectra exhibit complexity compared to plasma, showing reduced content at 1072 cm-1, 1347 cm-1 and 1654 cm-1 bands, while increased content at 1112 cm-1, 1143 cm-1, 1447 cm-1, 3334 cm-1 and 3420 cm-1 bands. Utilizing machine learning models such as eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), and artificial neural network (ANN), the study evaluated plasma and urine samples pre- and post-surgery. Remarkably, the XGBoost method excelled in distinguishing between tumor conditions and recovery, achieving an impressive AUC value of 0.99. These results underscore the potential of ATR-FTIR technology in identifying RCC optical biomarkers, with XGBoost showing promise as a valuable screening tool for RCC recurrence diagnosis.

Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases.

Merkel cell polyomavirus (MCV or MCPyV) is an alphapolyomavirus causing human Merkel cell carcinoma and encodes four tumor (T) antigen proteins: large T (LT), small tumor (sT), 57 kT, and middle T (MT)/alternate LT open reading frame proteins. We show that MCV MT is generated as multiple isoforms through internal methionine translational initiation that insert into membrane lipid rafts. The membrane-localized MCV MT oligomerizes and promiscuously binds to lipid raft-associated Src family kinases (SFKs). MCV MT-SFK interaction is mediated by a Src homology (SH) 3 recognition motif as determined by surface plasmon resonance, coimmunoprecipitation, and bimolecular fluorescence complementation assays. SFK recruitment by MT leads to tyrosine phosphorylation at a SH2 recognition motif (pMTY114), allowing interaction with phospholipase C gamma 1 (PLCγ1). The secondary recruitment of PLCγ1 to the SFK-MT membrane complex promotes PLCγ1 tyrosine phosphorylation on Y783 and activates the NF-κB inflammatory signaling pathway. Mutations at either the MCV MT SH2 or SH3 recognition sites abrogate PLCγ1-dependent activation of NF-κB signaling and increase viral replication after MCV genome transfection into 293 cells. These findings reveal a conserved viral targeting of the SFK-PLCγ1 pathway by both MCV and murine polyomavirus (MuPyV) MT proteins. The molecular steps in how SFK-PLCγ1 activation is achieved, however, differ between these two viruses.

The global/local (limited to some regions) effect of cesarean delivery on the risk of pediatric allergic rhinitis: a systematic review and meta-analysis.

Background: Allergic rhinitis is a chronic and refractory disease that can be affected by a variety of factors. Studies have shown an association between cesarean section and the risk of pediatric allergic rhinitis. Methods: The PubMed, Springer, Embase, Cochrane Library, and Web of Science databases were searched to retrieve all studies published from January 2000 to November 2022, focusing on the relationship between cesarean section and the risk of pediatric allergic rhinitis. A meta-analysis was conducted to find a correlation between cesarean section and the risk of pediatric allergic rhinitis. A subgroup analysis was performed, considering the region and family history of allergy, after adjusting for confounding factors. Pooled odds ratios (ORs) were calculated, publication bias was assessed using a funnel plot, and heterogeneity between study-specific relative risks was taken into account. Results: The results showed that cesarean section was significantly associated with an increased risk of pediatric allergic rhinitis (OR: 1.27, 95% CI: 1.20-1.35). Subgroup analysis stratified by region indicated that cesarean section increased the risk of pediatric allergic rhinitis, with the highest increase in South America (OR: 1.67, 95% CI: 1.10-2.52) and the lowest in Europe (OR: 1.13, 95% CI: 1.02-1.25). The results of the subgroup analysis stratified by family history of allergy indicate that family history of allergy was not associated with the risk of pediatric allergic rhinitis. Conclusion: An association exists between cesarean section as the mode of delivery and the increased risk of pediatric allergic rhinitis, and cesarean section is a risk factor for allergic rhinitis.

Auricular acupressure for adverse events following immunization after COVID-19 vaccine injection: A multicentre, blinded, randomized controlled trial.

BACKGROUND: Some adverse events following immunization (AEFI) were observed in potential corelation with COVID-19 vaccination but without prevention or ongoing trial for it. We aimed to investigate efficacy of auricular acupressure (AuriAc) therapy in preventing AEFI after first dosage of the vaccine. METHODS: We performed a multicentre randomized controlled trial with three arms, including AuriAc, SAuriAc (sham auricular acupressure), and TrAsU (treatment as usual) group, carried out in four medical institutions in Chengdu, China, from March 17th to April 23rd, 2021. We enrolled participants based on eligibility criteria and randomized them into three groups: AuriAc (AEFI-specific auricular points applied, n = 52), SAuriAc (n = 51) or TrAsU (n = 44) group. Primary outcomes were percentages of any AEFI and local pain, and secondary outcomes were percentages who reported other AEFI. They were followed at 1, 3, 5, 7, and 14 days, by phone or online, with severity evaluated. RESULTS: 147 participants (73.47% females) were included with median age as 31 years (25-45, IQR). One day after the injection, participants in AuriAc group reported significant reduction on percentages of any AEFI [intention-to-treat, difference of percentage (DP) = -20.13, 95%CI: - 0.39, - 0.02, p = 0.01; per-protocol, DP = -22.21, 95%CI: - 0.40, - 0.03, P = 0.02] and local pain (per-protocol, DP = -18.40, 95%CI: -0.36, -0.01, P = 0.04), compared with TrAsU group. The effects were slight at other follow-up days and for other outcomes, and with a low percentage of mild local allergic reactions. CONCLUSIONS: We firstly explored potential of AuriAc for preventing AEFI related to COVID-19 vaccine injection, which is beneficial for the vaccine recipients, but evidence is limited. TRIAL REGISTRATION: chictr.org.cn no. ChiCTR2100043210 (http://www.chictr.org.cn/showproj.aspx?proj=121519).

Deciphering the Biochemical Similarities and Differences Among Human Neuroglial Cells and Glioma Cells Using Fourier Transform Infrared Spectroscopy.

BACKGROUND: The use of Fourier transform infrared spectroscopy to identify the peritumoral tissue of gliomas proves the potential of this technique to distinguish normal brain tissues from glioma tissues. However, due to the heterogeneity of gliomas, it is difficult to characterize the representative spectra of normal brain tissues and glioma tissues. The linear spectra of major cellular components, such as microglia, astrocytes, and glioma cells, were obtained to quantify the biochemical changes between healthy cells and tumor cells, and provide supporting data for the final distinction between tumor and normal brain tissue. METHODS: Fourier transform infrared was used to measure human astrocytes, microglia (HM1900), and glioma cells (U87, BT325), and the cellular components of the 4 types of cells were analyzed by means of average spectra, second-derivative spectra, principal component analysis, hierarchical cluster analysis, and difference spectra. RESULTS: The proteomics, lipidomics, genomics, and metabolic statuses of the cells were different. The amide I, lipid, and nuclear acid regions of the spectra are the most obvious regions to use for distinguishing the 4 types of cells. CONCLUSIONS: We conclude that an improved understanding of both similarities and differences in the cellular components of astrocytes, microglia, and glioma cells can help us better understand the heterogeneity of gliomas. We suggest that targeting cellular metabolism (protein, lipid, and nuclear acids) is helpful to distinguish between normal brain tissue and glioma tissue, which has broad application prospects.

Calibration-free, high-precision, and robust terahertz ultrafast metasurfaces for monitoring gastric cancers.

Optical sensors, with great potential to convert invisible bioanalytical response into readable information, have been envisioned as a powerful platform for biological analysis and early diagnosis of diseases. However, the current extraction of sensing data is basically processed via a series of complicated and time-consuming calibrations between samples and reference, which inevitably introduce extra measurement errors and potentially annihilate small intrinsic responses. Here, we have proposed and experimentally demonstrated a calibration-free sensor for achieving high-precision biosensing detection, based on an optically controlled terahertz (THz) ultrafast metasurface. Photoexcitation of the silicon bridge enables the resonant frequency shifting from 1.385 to 0.825 THz and reaches the maximal phase variation up to 50° at 1.11 THz. The typical environmental measurement errors are completely eliminated in theory by normalizing the Fourier-transformed transmission spectra between ultrashort time delays of 37 ps, resulting in an extremely robust sensing device for monitoring the cancerous process of gastric cells. We believe that our calibration-free sensors with high precision and robust advantages can extend their implementation to study ultrafast biological dynamics and may inspire considerable innovations in the field of medical devices with nondestructive detection.

Neighboring mutation-mediated enhancement of dengue virus infectivity and spread.

Frequent turnover of dengue virus (DENV) clades is one of the major forces driving DENV persistence and prevalence. In this study, we assess the fitness advantage of nine stable substitutions within the envelope (E) protein of DENV serotypes. Two tandem neighboring substitutions, threonine to lysine at the 226th (T226K) and glycine to glutamic acid at the 228th (G228E) residues in the DENV2 Asian I genotype, enhance virus infectivity in either mosquitoes or mammalian hosts, thereby promoting clades turnover and dengue epidemics. Mechanistic studies indicate that the substitution-mediated polarity changes in these two residues increase the binding affinity of E for host C-type lectins. Accordingly, we predict that a G228E substitution could potentially result in a forthcoming epidemic of the DENV2 Cosmopolitan genotype. Investigations into the substitutions associated with DENV fitness in hosts may offer mechanistic insights into dengue prevalence, thus providing a warning of potential epidemics in the future.

Identification of hepatocellular carcinoma and paracancerous tissue based on the peak area in FTIR microspectroscopy.

Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies across the world. The annual incidence and death rates have increased at the highest rate of all cancers in recent years. Surgical resection is a potentially curative option for solitary HCC or unilobar disease without evidence of metastases or vascular invasion. This study focuses on the molecular differences between the HCC foci and paracancerous tissues and provides some valuable biomarkers based on the vibrational spectrum. Fourier transform infrared (FTIR) spectroscopy is a non-invasive and qualitative and semi-quantitative analysis technique that has been widely applied for the identification of macromolecular changes in biological tissues. In this study, the FTIR spectra of the HCC foci and the paracancerous tissues were recorded separately, and ten areas under the absorption peaks of all the specimens were calculated. The result demonstrates that the areas of protein-related absorption peaks at 1398 cm-1, 1548 cm-1, 1654 cm-1 and 3070 cm-1 may be the key indicators of the two different regions. After coupling with the classification algorithms of k-nearest neighbor (KNN), random forest (RF) and support vector machine (SVM), it was found that SVM with an RBF kernel performed best with the AUC (area under the ROC curve) reaching 0.997, and the performance was better than the feature based on the full spectrum. This reveals that the peak area-based FTIR spectra combined with the SVM algorithm may be a promising tool in identifying the HCC foci and the paracancerous tissues.

The therapeutic effect of Taijiquan combined with acupoint pressing on the treatment of anxiety insomnia in college students: A study protocol for a randomized controlled trial.

Introduction: Sleep health is an important part of health and has become a common concern of society. For anxiety insomnia, the commonly used clinical therapies have limitations. Alternative and complementary therapy is gradually rising and showing remarkable effect in clinical practice. This is the first study to evaluate the therapeutic effect of Taijiquan combined with acupoint pressing in the treatment of anxiety insomnia in college students and to compare the difference in intervention before and after sleep, to choose the best treatment time. Methods and analysis: This is a multicenter, single-blind, randomized controlled trial. A total of 126 eligible subjects who have passed the psychological evaluation and met inclusion criteria by completing a psychometric scale will be randomly divided into treatment group A (treat before sleep), treatment group B (treat after sleep) and control group C (waiting list group) in a ratio of 1:1:1. All the three groups will receive regular psychological counseling during the trial, and the treatment groups will practice 24-style Taijiquan and do meridian acupuncture at Baihui (DU20), Shenting (DU24), Yintang (EX-HN3), Shenmen (HT7) and Sanyinjiao (SP6). This RCT includes a 2-week baseline period, a 12-week intervention period, and a 12-week follow-up period. The main results will be measured by changes in the Pittsburgh sleep quality index (PSQI) and Hamilton anxiety scale (HAMA). The secondary results will be measured by the generalized anxiety scale (GAD-7) and insomnia severity index (ISI). The safety of the intervention will be evaluated at each assessment. The statistical analysis of data will be carried out by SPSSV.26.0 software. Discussion: We expect this trial to explore the effectiveness of Taijiquan combined with acupoint pressing in the treatment of anxiety insomnia in college students and choose the best treatment time by comparison. Clinical trial registration: [www.ClinicalTrials.gov], identifier [ChiCTR2200057003].

A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness.

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

Grade classification of human glioma using a convolutional neural network based on mid-infrared spectroscopy mapping.

This study proposes a convolutional neural network (CNN)-based computer-aided diagnosis (CAD) system for the grade classification of human glioma by using mid-infrared (MIR) spectroscopic mappings. Through data augmentation of pixels recombination, the mappings in the training set increased almost 161 times relative to the original mappings. The pixels of the recombined mappings in the training set came from all of the one-dimensional (1D) vibrational spectroscopy of 62 (almost 80% of all 77 patients) patients at specific bands. Compared with the performance of the CNN-CAD system based on the 1D vibrational spectroscopy, we found that the mean diagnostic accuracy of the recombined MIR spectroscopic mappings at peaks of 2917 cm-1 , 1539 cm-1 and 1234 cm-1 on the test set performed higher and the model also had more stable patterns. This research demonstrates that two-dimensional MIR mapping at a single frequency can be used by the CNN-CAD system for diagnosis and the research also gives a prompt that the mapping collection process can be replaced by a single-frequency IR imaging system, which is cheaper and more portable than a Fourier transform infrared microscopy and thus may be widely utilized in hospitals to provide meaningful assistance for pathologists in clinics.

Grade diagnosis of human glioma using Fourier transform infrared microscopy and artificial neural network.

The World Health Organization (WHO) grade diagnosis of cancer is essential for surgical outcomes and patient treatment. Traditional pathological grading diagnosis depends on dyes or other histological approaches, and the result interpretation highly relies on the pathologists, making the process time-consuming (>60 min, including the steps of dewaxing to water and H&E staining), resource-wasting, and labor-intensive. In the present study, we report an alternative workflow that combines the Fourier transform infrared (FTIR) microscopy and artificial neural network (ANN) to diagnose the grade of human glioma in a way that is faster (~20 min, including the processes of sample dewaxing, spectra acquisition and analysis), accurate (the prediction accuracy, specificity and sensitivity can reach above 99%), and without reagent. Moreover, this method is much superior to the common classification method of principal component analysis-linear discriminate analysis (PCA-LDA) (the prediction accuracy, specificity and sensitivity are only 87%, 89% and 86%, respectively). The ANN mainly learned the characteristic region of 800-1800 cm-1 to classify the major histopathologic classes of human glioma. These results demonstrate that the grade diagnosis of human glioma by FTIR microscopy plus ANN can be streamlined, and could serve as a complementary pathway that is independent of the traditional pathology laboratory.

Morphological and Biochemical Properties of Human Astrocytes, Microglia, Glioma, and Glioblastoma Cells Using Fourier Transform Infrared Spectroscopy.

BACKGROUND With infiltration, high-grade glioma easily causes the boundary between tumor tissue and adjacent tissue to become unclear and results in tumor recurrence at or near the resection margin according to the incomplete surgical resection. Fourier transform infrared spectroscopy (FTIR) technique has been demonstrated to be a useful tool that yields a molecular fingerprint and provides rapid, nondestructive, high-throughput and clinically relevant diagnostic information. MATERIAL AND METHODS FTIR was used to investigate the morphological and biochemical properties of human astrocytes (HA), microglia (HM1900), glioma cells (U87), and glioblastoma cells (BT325) cultured in vitro to simulate the infiltration area, with the use of multi-peak fitting and principal component analysis (PCA) of amide I of FTIR spectra and the use of hierarchical cluster analysis (HCA). RESULTS We found that the secondary structures of the 4 types of cells were significantly different. The contents of a-helix structure in glial cells was significantly higher than in the glioma cells, but the levels of ß-sheet, ß-turn, and random coil structures were lower. The 4 types of cells could be clearly separated with 85% for PC1 and 12.2% for PC2. CONCLUSIONS FTIR can be used to distinguish between human astrocytes, microglia, glioma, and glioblastoma cells in vitro. The protein secondary structure can be used as an indicator to distinguish tumor cells from glial cells. Further tissue-based and in vivo studies are needed to determine whether FTIR can identify cerebral glioma.

Development of a TEM-cell-integrated CO2 incubator for cell-based transient electromagnetic field bioeffect study.

To facilitate the cell-based experiment for pulsed electromagnetic field biological effect study, a novel TEM-cell-integrated CO2 incubator was developed. The integrated experimental system could simultaneously meet the requirement of standard cell culture condition and the various Transient Electromagnetic Field (TEF) exposure, which made it possible to study the relationship between different electromagnetic pulse exposure and the cellular responses in a reliable way. During the research, a comparison experiment was carried out to evaluate the necessity of the integrated incubator system: firstly, two different types of cell lines, which are the human prostate cancer cell line (PC3) and the pancreatic ß cell line (MIN6) were chosen and exposed in the TEM-cell which located in the open area and the integrated system, respectively, with the same EFT radiation conditions; then, the cells' viability, the cellular ROS level and the mitochondrial membrane potential (MMP) were detected, respectively. The results showed that in the same parameter of the EFT radiation, the processes of the cells had a significant difference and even opposite in the incubator and open area, and all the results could be reproducible. The phenomenon indicated the stability of the TEM-cell-integrated CO2 incubator, and also demonstrated the necessity to strictly control the cell culture condition when carrying out the precise mechanism study of the TEF bioresponse at the cellular levels.