Application of T-cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort-study based on RA patients.

T-cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti-rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease-modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.

Effects of High Pressure Processing and Thermal Treatment on the Interaction between α-Lactalbumin and Pelargonium-3-Glucoside.

In this study, high pressure processing (HPP) and thermal treatment were comparatively evaluated by examining their impacts on the binding behavior and interaction between α-lactalbumin (α-La) and pelargonium-3-glucoside (P3G) under pH values of 6.0, 7.4, and 8.0. The methods of circular dichroism spectroscopy, fluorescence quenching, dynamic light scattering, and molecular simulation were used to characterize the effects of processing-induced changes in protein structure, size distribution, binding site conformation, and residue charges on their binding characteristics between them. The results indicated that the thermal treatments significantly increased the quenching constants of the complex at pH 7.4/8.0 and 60/80 °C, as well as the accessible fraction of protein at pH 8.0/80 °C. Both HPP and thermal treatments increased the random coil content and showed limited effects on the α-helix and ß-sheet contents of α-La and caused the aggregation of the complex to varying degrees. Molecular dynamic simulation and docking analyses revealed that the binding site of the complex did not change under different processing conditions, but the solvent-accessible surface area varied under different conditions.

Performance of 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography in the diagnosis of primary prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. MATERIALS AND METHODS: Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%. CONCLUSIONS: Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.

Effect of high hydrostatic pressure processing on the structure, functionality, and nutritional properties of food proteins: A review.

Proteins are important food ingredients that possess both functional and nutritional properties. High hydrostatic pressure (HHP) is an emerging nonthermal food processing technology that has been subject to great advancements in the last two decades. It is well established that pressure can induce changes in protein folding and oligomerization, and consequently, HHP has the potential to modify the desired protein properties. In this review article, the research progress over the last 15 years regarding the effect of HHP on protein structures, as well as the applications of HHP in modifying protein functionalities (i.e., solubility, water/oil holding capacity, emulsification, foaming and gelation) and nutritional properties (i.e., digestibility and bioactivity) are systematically discussed. Protein unfolding generally occurs during HHP treatment, which can result in increased conformational flexibility and the exposure of interior residues. Through the optimization of HHP and environmental conditions, a balance in protein hydrophobicity and hydrophilicity may be obtained, and therefore, the desired protein functionality can be improved. Moreover, after HHP treatment, there might be greater accessibility of the interior residues to digestive enzymes or the altered conformation of specific active sites, which may lead to modified nutritional properties. However, the practical applications of HHP in developing functional protein ingredients are underutilized and require more research concerning the impact of other food components or additives during HHP treatment. Furthermore, possible negative impacts on nutritional properties of proteins and other compounds must be also considered.

High pressure processing combined with selected hurdles: Enhancement in the inactivation of vegetative microorganisms.

High pressure processing (HPP) as a nonthermal processing (NTP) technology can ensure microbial safety to some extent without compromising food quality. However, for vegetative microorganisms, the existence of pressure-resistant subpopulations, the revival of sublethal injury (SLI) state cells, and the resuscitation of viable but nonculturable (VBNC) state cells may constitute potential food safety risks and pose challenges for the further development of HPP application. HPP combined with selected hurdles, such as moderately elevated or low temperature, low pH, natural antimicrobials (bacteriocin, lactate, reuterin, endolysin, lactoferrin, lactoperoxidase system, chitosan, essential oils), or other NTP (CO2 , UV-TiO2 photocatalysis, ultrasound, pulsed electric field, ultrafiltration), have been highlighted as feasible alternatives to enhance microbial inactivation (synergistic or additive effect). These combinations can effectively eliminate the pressure-resistant subpopulation, reduce the population of SLI or VBNC state cells and inhibit their revival or resuscitation. This review provides an updated overview of the microbial inactivation by the combination of HPP and selected hurdles and restructures the possible inactivation mechanisms.

Topical application of tranexamic acid in primary total hip arthroplasty: a randomized double-blind controlled trial.

So far, studies of topical tranexamic acid (TXA) in total hip arthroplasty (THA) were still lacking and controversial. We conducted this randomized double-blind controlled trial which included 101 patients to assess the effect of a high-dose 3g topical TXA in THA. The results showed that 3g topical TXA could significantly reduce transfusions from 22.4% to 5.7% (P<0.05) without increasing the risk of deep vein thrombosis (DVT), pulmonary embolism (PE) and other complications. In addition, topical TXA significantly reduced total blood loss, reduced drain blood loss, and the drops of HB and HCT in topical TXA group were lower than control group. We concluded that 3g topical TXA was effective and safe in reducing bleeding and transfusions in THA.

High pressure processing plus technologies: Enhancing the inactivation of vegetative microorganisms.

High pressure processing (HPP) is a non-thermal technology that can ensure microbial safety without compromising food quality. However, the presence of pressure-resistant sub-populations, the revival of sub-lethally injured (SLI) cells, and the resuscitation of viable but non-culturable (VBNC) cells pose challenges for its further development. The combination of HPP with other methods such as moderate temperatures, low pH, and natural antimicrobials (e.g., bacteriocins, lactate, reuterin, endolysin, lactoferrin, lactoperoxidase system, chitosan, essential oils) or other non-thermal processes (e.g., CO2, UV-TiO2 photocatalysis, ultrasound, pulsed electric fields, ultrafiltration) offers feasible alternatives to enhance microbial inactivation, termed as "HPP plus" technologies. These combinations can effectively eliminate pressure-resistant sub-populations, reduce SLI or VBNC cell populations, and inhibit their revival or resuscitation. This review provides an updated overview of microbial inactivation by "HPP plus" technologies and elucidates possible inactivation mechanisms.

Metal-free production of natural blue colorants through anthocyanin-protein interactions.

INTRODUCTION: The scarcity of naturally available sources for blue colorants has driven reliance on synthetic alternatives. Nevertheless, growing health concerns have prompted the development of naturally derived blue colorants, which remains challenging with limited success thus far. Anthocyanins (ACNs) are known for providing blue colors in plants, and metal complexation with acylated ACNs remains the primary strategy to generate stable blue hues. However, this approach can be costly and raise concerns regarding potential metal consumption risks. OBJECTIVES: Our study aims to introduce a metal-free approach to achieve blue coloration in commonly distributed non-acylated 3-glucoside ACNs by exploring their interactions with proteins and unveiling the underlying mechanisms. METHODS: Using human serum albumin (HSA) as a model protein, we investigated the structural influences of ACNs on their blue color generation using visible absorption spectroscopy, fluorescence quenching, and molecular simulations. Additionally, we examined the bluing effects of six proteins derived from milk and egg and identified the remarkable roles of bovine serum albumin (BSA) and lysozyme (LYS). RESULTS: Our findings highlighted the importance of two or more hydroxyl or methoxyl substituents in the B-ring of ACNs for generating blue colors. Cyanidin-, delphinidin- and petunidin-3-glucoside, featuring two neighboring hydroxyl groups in the B-ring, exhibited blue coloration when interacting with HSA or LYS, driven primarily by favorable enthalpy changes. In contrast, malvidin-3-glucoside, with two methoxyl substituents, achieved blue coloration through interactions with HSA or BSA, where entropy change played significant roles. CONCLUSION: Our work, for the first time, demonstrates the remarkable capability of widely distributed 3-glucoside ACNs to generate diverse blue shades through interactions with certain proteins. This offers a promising and straightforward strategy for the production of ACN-based blue colorants, stimulating further research in this field.

Exploring high hydrostatic pressure effects on anthocyanin binding to serum albumin and food-derived transferrins.

This study investigated the effects of high hydrostatic pressure (HHP) on the binding interactions of cyanindin-3-O-glucoside (C3G) to bovine serum albumin, human serum albumin (HSA), bovine lactoferrin, and ovotransferrin. Fluorescence quenching revealed that HHP reduced C3G-binding affinity to HSA, while having a largely unaffected role for the other proteins. Notably, pretreating HSA at 500 MPa significantly increased its dissociation constant with C3G from 24.7 to 34.3 µM. Spectroscopic techniques suggested that HSA underwent relatively pronounced tertiary structural alterations after HHP treatments. The C3G-HSA binding mechanisms under pressure were further analyzed through molecular dynamics simulation. The localized structural changes in HSA under pressure might weaken its interaction with C3G, particularly polar interactions such as hydrogen bonds and electrostatic forces, consequently leading to a decreased binding affinity. Overall, the importance of pressure-induced structural alterations in proteins influencing their binding with anthocyanins was highlighted, contributing to optimizing HHP processing for anthocyanin-based products.

Understanding the pH-dependent interaction of anthocyanin with two food-derived transferrins.

The potential binding of cyanidin-3-O-glucoside (C3G) to bovine lactoferrin (BLF) and ovotransferrin (OTF) at pH 3, 5, and 7 was investigated for the first time. Multiple spectroscopic techniques demonstrated pH-dependent alterations in the conformational characteristics of BLF and OTF upon complexation with C3G. Fluorescence quenching assays showed that their highest binding affinity was at pH 7. Hydrophobic interactions and hydrogen bonds were found to be crucial in molecular dynamics simulations but with significantly lower probabilities of formation at pH 3 (p < 0.05). At pH 7, electrostatic attraction can occur for the negatively charged forms of C3G, and the well-maintained native structures of BLF and OTF may be favorable for stabilizing the C3G binding sites. This study sheds light on the stronger interaction of C3G with BLF/OTF at pH 7, which may have implications for future applications such as anthocyanin stabilization or the development of functional food ingredients.

Atypical CT findings of renal neuroblastoma: a case report.

Background: The neuroblastoma (NB) is a highly malignant tumor of the ectoderm of sympathetic nerve cells and one of the most common malignant tumors in children, which can occur in any part of the sympathetic nerve plexus distribution, however it is less common in the kidney. Case Description: Here we present a case of a 4-year-old boy who came to our hospital for medical help because of "abdominal distension for 1 day". Abdominal computed tomography (CT) revealed a huge retroperitoneal soft tissue mass with unclear boundaries with kidneys and adrenal glands, and low-density cystic necrosis areas were seen in the tumor. Contrast-enhanced scan showed that the mass showed mild heterogeneous enhancement. Based on these findings in the patient, he was initially considered to have Wilms tumor, but was finally pathologically confirmed as renal NB. The purpose of this article is to provide the clinicopathological features and CT manifestations of renal NB, and to discuss its differential diagnosis with other renal tumors, in order to better provide clinicians with a better understanding of the rare solid tumor. The renal NB is usually a large lobulated soft tissue mass with unclear boundary and incomplete capsule, which is prone to hemorrhage, necrosis, cystic degeneration and calcification. On CT, the mass is usually isodensity or slightly hypodense, and the cystic degeneration and necrosis area is hypodense, and on contrast-enhanced scan, it can be mildly to significantly enhanced, but the cystic degeneration and necrosis area have no enhancement. Conclusions: The CT findings of our case were atypical and overlapped with those of Wilms, so our case suggests that renal NB should be considered as one of the differential diagnoses of Wilms, the most common malignancy of the kidney in children.

A Moving Meckel Diverticulum on 99mTc-Pertechnetate Imaging in a Patient With Inguinal Hernia.

A boy aged 1 year 8 months underwent Tc-pertechnetate scintigraphy to evaluate the cause of bloody stool. On the initial images, there was an abnormal activity in the right abdomen, which changed location to the right groin in later images. A Meckel diverticulum was identified by histopathology examination. We concluded this case of moving Meckel diverticulum was caused by the synergy between an inguinal hernia and high abdominal pressure.

Gout inheritance in an extended Chinese family analyzed by whole-exome sequencing: A case-report.

INTRODUCTION: Gout is a worldwide chronic disease generally caused by high serum levels of uric acid. Using whole exome sequencing, we aimed to explore genetic alterations in hereditary gout. PATIENTS' CONCERNS: There were 9 direct descendants diagnosed with gout in total in this family. The patients concerned about the high incidence and inheritance of gout. DIAGNOSIS: The youngest propositus was diagnosed as gout in our hospital. Diagnoses of other patients in this family were made on the foundation of history and clinical tests. INTERVENTIONS: Six direct descendants and 3 healthy spouses in 1 family were recruited in our study. Whole-exome sequencing was conducted in all participants. OUTCOMES: Whole-exome sequencing and genetic analysis revealed 2 putative rare inherited deleterious variants, which were detected only in direct descendants. Twelve gout and uric acid (UC)-related nucleotide sequence variants previously reported by GWAS were detected among all subjects. CONCLUSIONS: In the case of this family, the GWAS identified gout and UC-related nucleotide sequence variants may increase the risk of developing gout, but penetrance was not complete. The rare sequence variants in low-density lipoprotein receptor-related protein 1 (LRP1) and oncoprotein induced transcript 3 (OIT3) may have contributed to inheritance of gout within the 5 generations of family members in this study.

Different Faces for Different Places: Heterogeneity of Neutrophil Phenotype and Function.

As the most abundant leukocytes in the circulation, neutrophils are committed to innate and adaptive immune effector function to protect the human body. They are capable of killing intruding microbes through various ways including phagocytosis, release of granules, and formation of extracellular traps. Recent research has revealed that neutrophils are heterogeneous in phenotype and function and can display outstanding plasticity in both homeostatic and disease states. The great flexibility and elasticity arm neutrophils with important regulatory and controlling functions in various disease states such as autoimmunity and inflammation as well as cancer. Hence, this review will focus on recent literature describing neutrophils' variable and diverse phenotypes and functions in different contexts.

Performance of 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography in the diagnosis of primary prostate cancer: a systematic review and meta-analysis

ABSTRACT Objective: To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. Materials and Methods: Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results: According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%. Conclusions: Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.

Effect of Topical Tranexamic Acid in Reducing Bleeding and Transfusions in TKA.

Intravenous tranexamic acid (TXA) has been identified to be effective in total knee arthroplasty (TKA), but the effect of topical application is still unclear. Therefore, the authors conducted a meta-analysis to assess the effect of topical TXA in TKA. Twelve trials with a total of 1179 knees were included. The results revealed that the application of topical TXA in TKA significantly reduced total blood loss by a mean of 280.65 mL and reduced transfusions without increasing the risks of deep venous thrombosis and pulmonary embolism. Topical TXA also reduced postoperative drain output by a mean of 194.59 mL and lowered postoperative hemoglobin drop by a mean of 0.66 g/dL. In addition, subgroup analysis showed that high-concentration TXA may be better at reducing bleeding and transfusions than low-concentration TXA. Therefore, the authors concluded that topical TXA can effectively reduce bleeding and transfusion rate in TKA without increasing the risk of deep venous thrombosis and pulmonary embolism, and high-concentration (20 mg/mL or more) topical TXA is recommended.