The potential roles of salivary biomarkers in neurodegenerative diseases.

Current research efforts on neurodegenerative diseases are focused on identifying novel and reliable biomarkers for early diagnosis and insight into disease progression. Salivary analysis is gaining increasing interest as a promising source of biomarkers and matrices for measuring neurodegenerative diseases. Saliva collection offers multiple advantages over the currently detected biofluids as it is easily accessible, non-invasive, and repeatable, allowing early diagnosis and timely treatment of the diseases. Here, we review the existing findings on salivary biomarkers and address the potential value in diagnosing neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Based on the available research, ß-amyloid, tau protein, α-synuclein, DJ-1, Huntington protein in saliva profiles display reliability and validity as the biomarkers of neurodegenerative diseases.

Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Enzyme-Catalyzed Hydrogen-Deuterium Exchange between Environmental Pollutants and Enzyme-Regulated Endogenous Metabolites.

Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D38-bis(2-ethylhexyl) phthalate (D38-DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A2 (PLA2)], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D38-DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D38-DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA2, and this process mediated H-D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.

TrDosePred: A deep learning dose prediction algorithm based on transformers for head and neck cancer radiotherapy.

BACKGROUND: Intensity-Modulated Radiation Therapy (IMRT) has been the standard of care for many types of tumors. However, treatment planning for IMRT is a time-consuming and labor-intensive process. PURPOSE: To alleviate this tedious planning process, a novel deep learning based dose prediction algorithm (TrDosePred) was developed for head and neck cancers. METHODS: The proposed TrDosePred, which generated the dose distribution from a contoured CT image, was a U-shape network constructed with a convolutional patch embedding and several local self-attention based transformers. Data augmentation and ensemble approach were used for further improvement. It was trained based on the dataset from Open Knowledge-Based Planning Challenge (OpenKBP). The performance of TrDosePred was evaluated with two mean absolute error (MAE) based scores utilized by OpenKBP challenge (i.e., Dose score and DVH score) and compared to the top three approaches of the challenge. In addition, several state-of-the-art methods were implemented and compared to TrDosePred. RESULTS: The TrDosePred ensemble achieved the dose score of 2.426 Gy and the DVH score of 1.592 Gy on the test dataset, ranking at 3rd and 9th respectively in the leaderboard on CodaLab as of writing. In terms of DVH metrics, on average, the relative MAE against the clinical plans was 2.25% for targets and 2.17% for organs at risk. CONCLUSIONS: A transformer-based framework TrDosePred was developed for dose prediction. The results showed a comparable or superior performance as compared to the previous state-of-the-art approaches, demonstrating the potential of transformer to boost the treatment planning procedures.

Flap perfusion assessment with indocyanine green angiography in deep inferior epigastric perforator flap breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: Indocyanine green angiography (ICG-A) has been widely applied for intraoperative flap assessment in DIEP flap breast reconstruction. However, the beneficial effect of ICG-A in DIEP flap breast reconstruction is still uncertain and no standardized protocol is available. This study aims to analyze the clinical outcome and comprehensively review protocols of this field. METHODS: A systematic review was conducted in MEDLINE, EMBASE, and Cochrane CENTRAL databases until September 15, 2022. Studies on the utility of intraoperative ICG-A in DIEP breast reconstruction were included. Data reporting reconstruction outcomes were extracted for pooled analysis. RESULTS: A total of 22 studies were enrolled in the review, among five studies with 1021 patients included in the meta-analysis. The protocols of ICG-A assessment of DIEP flap varied among studies. According to the pooled results, the incidence of postoperative fat necrosis was 10.89% (50 of 459 patients) with ICG-A and 21.53% (121 of 562 patients) with clinical judgment. The risk for postoperative fat necrosis was significantly lower in patients with intraoperative ICG-A than without (RR 0.47 95% CI 0.29-0.78, p = .004, I2 = 51%). Reoperation occurred in 5 of 48 patients (10.42%) in the ICG-A group and in 21 of 64 patients (32.82%) in the control group summarized from reports in two studies. The risk for reoperation was lower in the ICG-A group than in the control group (RR 0.41 95% CI 0.18-0.93, p = .03, I2 = 0%). Other complications, including flap loss, seroma, hematoma, dehiscence, mastectomy skin necrosis, and infection, were comparable between the two groups. Heterogeneities among studies were acceptable. No significant influence of specific studies was identified in sensitivity analysis. CONCLUSIONS: ICG-A is an accurate and reliable way to identify problematic perfusion of DIEP flaps during breast reconstruction. Protocols of ICG-A differed in current studies. Intraoperative ICG-A significantly decreases the rate of fat necrosis and reoperation in patients undergoing DIEP breast reconstruction. The synthesized results should be interpreted sensibly due to the sample size limitation. RCTs on the outcomes and high-quality studies for an optimized ICG-A protocol are still needed in the future.

SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPß/TNF-α signaling axis in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant memory CD4 T cells activation plays a key role in the initiation and perpetuation of the disease. SIGIRR (single immunoglobulin IL-1R-related receptor), a member of the IL-1 receptor (ILR) family, acts as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. The aim of this study was to investigate the potential roles of SIGIRR on memory CD4 T cells in RA and the underlying cellular and molecular mechanisms. METHODS: Single-cell transcriptomics and bulk RNA sequencing data were integrated to predict SIGIRR gene distribution on different immune cell types of human PBMCs. Flow cytometry was employed to determine the differential expression of SIGIRR on memory CD4 T cells between the healthy and RA cohorts. A Spearman correlation study was used to determine the relationship between the percentage of SIGIRR+ memory CD4 T cells and RA disease activity. An AIA mouse model (antigen-induced arthritis) and CD4 T cells transfer experiments were performed to investigate the effect of SIGIRR deficiency on the development of arthritis in vivo. Overexpression of SIGIRR in memory CD4 T cells derived from human PBMCs or mouse spleens was utilized to confirm the roles of SIGIRR in the intracellular cytokine production of memory CD4 T cells. Immunoblots and RNA interference were employed to understand the molecular mechanism by which SIGIRR regulates TNF-α production in CD4 T cells. RESULTS: SIGIRR was preferentially distributed by human memory CD4 T cells, as revealed by single-cell RNA sequencing. SIGIRR expression was substantially reduced in RA patient-derived memory CD4 T cells, which was inversely associated with RA disease activity and related to enhanced TNF-α production. SIGIRR-deficient mice were more susceptible to antigen-induced arthritis (AIA), which was attributed to unleashed TNF-α production in memory CD4 T cells, confirmed by decreased TNF-α production resulting from ectopic expression of SIGIRR. Mechanistically, SIGIRR regulates the IL-1/C/EBPß/TNF-α signaling axis, as established by experimental evidence and cis-acting factor bioinformatics analysis. CONCLUSION: Taken together, SIGIRR deficiency in memory CD4 T cells in RA raises the possibility that receptor induction can target key abnormalities in T cells and represents a potentially novel strategy for immunomodulatory therapy.

A PD-L1 and VEGFR2 dual targeted peptide and its combination with irradiation for cancer immunotherapy.

Although the blockade of immune checkpoint PD-1/PD-L1 has achieved great success, the lack of tumor-infiltrating immune cells and PD-L1 expression in the tumor microenvironment results in a limited response in certain tumor types. Thus, rational and optimal combination strategies were urgently needed. The combination of PD-1/PD-L1 blockade and anti-angiogenic therapy has been reported to have great potential. Here, a chimeric peptide OGS was designed by conjugating the peptides OPBP-1 (8-12) and DA7R targeting PD-L1 and VEGFR2, respectively. OGS could bind to both human and mouse PD-L1 with high affinity and block the PD-1/PD-L1 interaction, and also inhibit the migration and tube formation of HUVEC cells in wound healing and tube formation assays. To further prolong the half-life of OGS, it was modified by coupling with peptide DSP which has a high binding affinity to both human serum albumin (HSA) and mouse serum albumin (MSA) to form the peptide DSPOGS. DSPOGS could not directly affect the viability, apoptosis, and cell cycle of tumor cells in vitro, while significantly inhibiting the tumor growth in the MC38 mouse model. DSPOGS could elicit a potent anti-tumor immune response and inhibit tumor angiogenesis, with the enhancement of tumor infiltrating CD8+ T cells and the IFN-γ secreting CD8+ T cells in the spleen and tumor-draining lymph node. Further, the combination of radiotherapy with DSPOGS could dramatically improve the therapeutic efficacy. Our study could provide a promising paradigm for the combination of immune checkpoint blockade, anti-angiogenesis, and radiotherapy.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

Repositioning liothyronine for cancer immunotherapy by blocking the interaction of immune checkpoint TIGIT/PVR.

BACKGROUND: Inhibitors targeting immune checkpoint were proved effective in cancer immunotherapy, such as PD-1/PD-L1 blockade. The novel immune checkpoint TIGIT/PVR plays critical roles in suppressing the anti-tumor effects of CD8+ T and NK cells, and dual blockade of TIGIT/PVR and PD-1/PD-L1 by antibody can elicit synergistic effects in tumor models and clinical trials. However, small molecules for TIGIT/PVR blockade have not been investigated. METHODS: The expression of PVR in tumors were analyzed by using TCGA, Oncomine and GEO database, and in cancer cell lines examined by flow cytometry. Natural product compounds were docked to PVR for virtual screening by using the software Molecular Operating Environment (MOE). Candidate compounds were further tested by biolayer interferometry-based binding assay, microscale thermophoresis assay and cell based blocking assay. The in vitro activity of the candidate compound was determined by MTT, peripheral blood mononuclear cells (PBMCs) activation assay and coculture assay. The anti-tumor effects and mechanism were also investigated by using MC38 tumor-bearing mice model and immune cell depletion tumor model. RESULTS: PVR was over-expressed in many tumor tissues and cancer cell lines, making it a promising therapeutic target. Through virtual screening, binding, and blocking assay, liothyronine was discovered to bind PVR and block the interaction of TIGIT/PVR. Liothyronine could enhance the function of CD4+ and CD8+ T cells in PBMCs. Besides, in the Jurkat-hTIGIT and CHOK1-hPVR coculture assay, liothyronine could reverse the IL-2 secretion inhibition resulted by TIGIT/PVR ligation. Although had no influence on the proliferation of tumor cells in vitro, liothyronine could significantly inhibit tumor growth when administrated in vivo, by enhancing CD8+ T cell infiltration and immune responses in the tumor bearing mice. The immune cell depletion model showed that the anti-tumor effects of liothyronine depends on CD4+ T cells, CD8+ T cells and NK cells. CONCLUSIONS: A small molecule liothyronine was discovered to serve as a potential candidate for cancer immunotherapy by blocking the immune checkpoint TIGIT/PVR. Video abstract.

Huge fetal hepatic Hemangioma: prenatal diagnosis on ultrasound and prognosis.

BACKGROUND: Although huge fetal hepatic hemangiomas are rare, they can cause fatal complications. The purpose of this study is to describe the imaging features and prognosis of these tumors. METHODS: Imaging data were collected for 6 patients with huge fetal hepatic hemangiomas treated at our hospital. Imaging modalities included prenatal magnetic resonance imaging and ultrasound and postnatal color Doppler ultrasound and contrast-enhanced computed tomography (CT). RESULTS: Among the 93,562 fetuses of 92,126 pregnant women examined at our hospital, 6 had huge hepatic hemangiomas (incidence rate, 0.64/10,000), as confirmed via postnatal color Doppler imaging and contrast-enhanced CT. Five fetuses had solitary lesions, whereas 1 (fetus 2) had multiple lesions. Four fetuses had lesions in the right liver lobe and 1 had a lesion in the left liver lobe, and 1 (fetus 2) had lesions in both lobes. All lesions showed centripetal enhancement on postnatal contrast-enhanced CT, which was more intense peripherally. Following postnatal treatment with oral propranolol, with or without dexamethasone or interventional therapy with the medical sclerosant pingyangmycin, all lesions decreased in size, with calcification plaques appearing 6 months after treatment. CONCLUSIONS: Huge hepatic hemangiomas have typical ultrasonographic features and can be diagnosed prenatally. Treatment with propranolol, with or without dexamethasone, may result in a favorable prognosis.

The risk factors and pattern of cerebral microbleeds in Parkinson's disease.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) in Parkinson's disease (PD) have been reported recently and concerned increasingly. Our aim was to investigate the risk factors and pattern of CMBs in patients with PD, as well as the influence of risk factors on the pattern of CMBs. METHODS: We retrospectively collected medical and imaging data of 247 patients who underwent brain susceptibility-weighted imaging. Logistic regression analyses were performed to determine the risk factors of CMBs. The frequency and amount of CMBs in different locations between patients with and without risk factors were analyzed. RESULTS: Of the 247 patients with PD, 39 (15.79%) had CMBs, 27 (69.23%) had lobar CMBs, 20 (51.28%) had deep CMBs and 17 (43.59%) had infratentorial CMBs. A history of cerebral ischemic events was independently associated with the presence of CMBs (odds ratio (OR) 4.485 [95% CI 2.150-9.356]; p = 0.000), especially with lobar and deep CMBs. Hypertension and Hoehn and Yahr score were also associated with the presence of deep CMBs. Only white matter hyperintensities were independently associated with the presence of infratentorial CMBs. Compared to patients without risk factors, the frequency of deep CMBs was greater in those with a history of cerebral ischemic events (p = 0.013), while the amount of deep CMBs was higher in those with hypertension (p = 0.035). CONCLUSION: CMBs in PD seem to present a lobe-dominant pattern. A history of cerebral ischemic events and hypertension may be two strong risk factors which preferentially influences the pattern of deep CMBs in PD.

GeXP analyzer-based multiplex reverse-transcription PCR assay for the simultaneous detection and differentiation of eleven duck viruses.

BACKGROUND: Duck viral pathogens primarily include the avian influenza virus (AIV) subtypes H5, H7, and H9; duck hepatitis virus (DHV); duck tembusu virus (DTMUV); egg drop syndrome virus (EDSV); duck enteritis virus (DEV); Newcastle disease virus (NDV); duck circovirus (DuCV); muscovy duck reovirus (MDRV); and muscovy duck parvovirus (MDPV). These pathogens cause great economic losses to China's duck breeding industry. RESULT: A rapid, specific, sensitive and high-throughput GeXP-based multiplex PCR assay consisting of chimeric primer-based PCR amplification with fluorescent labeling and capillary electrophoresis separation was developed and optimized to simultaneously detect these eleven viral pathogens. Single and mixed pathogen cDNA/DNA templates were used to evaluate the specificity of the GeXP-multiplex assay. Corresponding specific DNA products were amplified from each pathogen. Other pathogens, including duck Escherichia coli, duck Salmonella, duck Staphylococcus aureus, Pasteurella multocida, infectious bronchitis virus, and Mycoplasma gallisepticum, did not result in amplification products. The detection limit of GeXP was 10(3)copies when all twelve pre-mixed plasmids containing the target genes of eleven types of duck viruses were present. To further evaluate the reliability of GeXP, 150 clinical field samples were evaluated. Comparison with the results of conventional PCR methods for the field samples, the GeXP-multiplex PCR method was more sensitive and accurate. CONCLUSION: This GeXP-based multiplex PCR method can be utilized for the rapid differential diagnosis of clinical samples as an effective tool to prevent and control duck viruses with similar clinical symptoms.

The development of adultoid reproductives and brachypterous neotenic reproductives from the last instar nymphs in Reticulitermes labralis (Isoptera: Rhinotermitidae): a comparative study.

Secondary reproductives develop primarily from nymphs. However, they have been rarely studied; in particular, the development of adultoid reproductives (AR) with floppy wings is still unclear. In this study, the change in juvenile hormone (JH) levels, vitellogenin gene expression, and oogenesis during the development of AR and brachypterous neotenic reproductives (BN) from the last instar nymphs of Reticulitermes labralis are investigated and compared. The results showed that the AR derived from the last instar nymphs by molting, and they were more similar to neotenic reproductives in morphology. In addition, the paired AR were not able to survive in the absence of workers. In R. labralis, the process of the last instar nymphs developing into AR and BN took an increase in JH level as a starting point. The JH level of the last instar nymphs molting into BN was approximately 1.5-fold higher than that of the AR. Additionally, The JHIII level of BN peaked on day 5, and that of AR peaked on day 10, which induced the onset of vitellogenesis in BN and AR, respectively. After molting, the vitellogenin gene expression levels of both BN and AR initially increased and then declined, and the expression levels in the BN were significantly higher than those in the AR. In addition, the oocytes of BN matured earlier than those of the AR, and the number of eggs laid by the BN was higher than the number laid by the AR. Our results demonstrate that, in R. labralis, the last instar nymphs can develop into AR, which are significantly different from BN in their development.

Alkylphenols disrupt estrogen homeostasis via diradical cross-coupling reactions: A novel pathway of endocrine disruption.

Estrogen, being an essential class of sex hormone, is an important target of endocrine disruption chemicals. It is well known that environmental disruptors could activate or inhibit estrogen receptors, acting as agonists or antagonists, and thus affect the circulating estrogen concentrations. Here, we report enzyme-mediated diradical cross-coupling reactions between alkylphenols (e.g., 2,4-di-tert-butylphenol [DBP], 4-nonylphenol [4-NP], and 4-tert-octylphenol [4-t-OP]) and estrogens (e.g., estradiol [E2]) that generate coupling metabolites and disrupt estrogen homeostasis. Among the phenolic xenobiotics, the screening of metabolic products revealed that alkylphenols had the highest reaction activities and generated coupling metabolites with high abundances (DBP-O-E2, 4-t-OP-O-E2, and 4-NP-O-E2). The coupling reactions were catalyzed by cytochrome P450 3A4 (CYP3A4) and verified by the detection of the coupling products in general populations. In vitro and in vivo exposures together with CYP3A4 inhibition demonstrated that cross-coupling reactions of phenols and E2 significantly reduced the normal levels of E2. We further established a unique spin-trapping-based high-throughput screening method to show the existence of diradicals in the coupling reaction. Density functional theory calculations revealed that spin aromatic delocalization was the fundamental cause of the high rebound barrier and sufficient lifetime of phenoxy radicals that enabled phenolic cross-coupling triggered by cytochrome P450. The identified mechanistic details for diradical cross-coupling reactions provide a novel pathway for phenolic chemicals to disrupt estrogen homeostasis.

Changes in the electron paramagnetic resonance spectra of albumin-associated spin-labeled stearic acid as a diagnostic parameter of colorectal cancer.

BACKGROUND: With more than 940,000 new colorectal cancer cases worldwide each year, there is no better way for colorectal cancer routine screening. The aim of this study was to investigate whether the fatty acid binding to albumin is detectably and significantly altered in colorectal cancer patients when compared with healthy people, in order to find a better way for colorectal cancer diagnosis. METHODS: One hundred and forty-one patients operatively treated for colorectal cancer were included in the examination, and 180 healthy people were also enrolled as controls. Commercial 16-doxyl stearic acid was used as spin probe. Serum albumin was analyzed by electron paramagnetic resonance (EPR) with spin probe. Discriminant analysis was carried out using the measured EPR spectra by SPSS 20.0. RESULTS: Of the original grouped cases, 89.4% were correctly classified. Of the cross-validated grouped cases, 86.9% were correctly classified. Using Fisher linear discriminant analysis we were able to develop a mathematical model allowing for identification of colorectal cancer patients based on five values (both relative intensity and peak width) which are obtained from the EPR spectrum. CONCLUSIONS: Cancer-associated alterations to albumin can be assessed by spin-label EPR. The potential applications for this diagnostic technique are significant and represent a cost-effective means for screening patients with cancer. Spin probe for diagnosis of colorectal cancer might be a useful tool and further studies should take place in order to investigate all stages of colorectal cancer patients.

Strategies for the Discovery of Oxazolidinone Antibacterial Agents: Development and Future Perspectives.

Oxazolidinones represent a significant class of synthetic bacterial protein synthesis inhibitors that are primarily effective against Gram-positive bacteria. The commercial success of linezolid, the first FDA-approved oxazolidinone antibiotic, has motivated researchers to develop more potent oxazolidinones by employing various drug development strategies to fight against antimicrobial resistance, some of which have shown promising results. Thus, this Perspective aims to discuss the strategies employed in constructing oxazolidinone-based antibacterial agents and summarize recent advances in discovering oxazolidinone antibiotics to provide valuable insights for potentially developing next-generation oxazolidinone antibacterial agents or other pharmaceuticals.

Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.

[Clinical comparative study of efficacy of Er:YAG laser for debonding different veneers].

PURPOSE: To compare the debonding time of IPS e.max CAD lithium disilicate glass-ceramic veneers in different thickness and transparency using Er:YAG laser, and evaluate the effect of Er:YAG laser on the surface topography of the veneers and the underlying tooth. METHODS: A total of twelve maxillary first premolar teeth were collected and prepared, then veneers were made by computer aided design and computer aided manufacture(CAD/CAM) system. The veneers were divided into four groups according to different thicknesses and transparency: e.max HT with 0.5 mm and 1.0 mm thickness, e.max LT with 0.5 mm and 1.0 mm thickness. Three veneers of each group were cemented to prepared premolar with resin cement and then stored in normal saline solution at room temperature for 7 days. All veneers were debonded with Er:YAG laser and the debonding time of all-ceramic veneers of all groups was recorded. Scanning electron microscopy(SEM) observation was performed to detect the surface topography of the veneers and the underlying tooth. SPSS 19.0 software package was used for statistical analysis. RESULTS: The debonding time of 1.0 mm-thick groups were longer than 0.5 mm-thick groups. When the veneer thickness was 0.5 mm, the average debonding time of e.max LT group was longer than e.max HT. Consistent with the finding of 0.5 mm, the longer debonding time was found in the e.max LT group of 1.0mm. No cracks and crater structure were found in SEM observation of veneers after Er:YAG laser irradiation. Teeth surface was covered with bonding cement with no signs of ablation or damage of the enamel. CONCLUSIONS: Er:YAG laser can completely debond lithium disilicate glass-ceramic veneers, and the debonding time depends on the transparency and thickness of the veneers. The lower translucent porcelain veneers (e.max LT) and thicker ones (1.0 mm-thick) had a longer debonding time. Moreover, Er:YAG laser does not damage the morphology and topography of the veneer and the teeth surface.