Immune-related mechanisms and immunotherapy in extragonadal germ cell tumors

Purpose of reviewExtragonadal germ cell tumors (EGCTs) are relatively rare tumors, accounting for 1%–5% of all GCTs. In this review, we summarize the current research progress regarding the pathogenesis, diagnosis, and treatment of EGCTs from an immunology perspective.Recent findingsThe histological origin of EGCTs is related to a gonadal origin, but they are located outside the gonad. They show great variation in morphology and can occur in the cranium, mediastinum, sacrococcygeal bone, and other areas. The pathogenesis of EGCTs is poorly understood, and their differential diagnosis is extensive and challenging. EGCT behavior varies greatly according to patient age, histological subtype, and clinical stage.SummaryThis review provides ideas for the future application of immunology in the fight against such diseases, which is a hot topic currently

Diagnostic and prognostic value of serum S100B in sepsis-associated encephalopathy: A systematic review and meta-analysis

BackgroundIn sepsis, brain dysfunction is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Our systematic review and meta-analysis aimed to explore the diagnostic and prognostic value of serum S100 calcium-binding protein B (S100B) in SAE patients.MethodsWe conducted a systematic search of the databases PubMed, Web of Science, Embase, Cochrane databases, CNKI, VIP, and WFSD from their inception dates until August 20, 2022. A Meta-analysis of the included studies was also performed using Review Manager version 5.4 and Stata16.0.ResultsThis meta-analysis included 28 studies with 1401 serum samples from SAE patients and 1591 serum samples from no-encephalopathy septic (NE) patients. The Meta-Analysis showed that individuals with SAE had higher serum S100B level than NE controls (MD, 0.49 [95% CI (0.37)-(0.60), Z =8.29, P < 0.00001]), and the baseline level of serum S100B in septic patients with burn was significantly higher than average (1.96 [95% CI (0.92)-(2.99), Z =3.71, P < 0.0002]) In addition, septic patients with favorable outcomes had lower serum S100B levels than those with unfavorable outcomes (MD, -0.35 [95% CI (-0.50)-(-0.20), Z =4.60, P < 0.00001]).ConclusionOur Meta-Analysis indicates that higher serum S100B level in septic patients are moderately associated with SAE and unfavorable outcomes (The outcomes here mainly refer to the mortality). The serum S100B level may be a useful diagnostic and prognostic biomarker of SAE

Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine

INTRODUCTION: Glucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors. We elaborated on the glutamine-derived PET tracers by developing two novel probes, namely [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine MATERIALS AND METHODS: Both tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [(3)H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model. RESULTS: The radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18 % (n=10) ([(18)F]fluorophenylglutamine) and 8.05 ± 3.25 % (n=5) ([(18)F]fluorobiphenylglutamine). In vitro inhibition experiments showed a moderate and low affinity of fluorophenylglutamine and fluorobiphenylglutamine, respectively, towards the human ASCT-2 transporter. Both compounds had a low affinity towards the rat ASCT-2 transporter. These results were endorsed by the in vivo experiments with low uptake of both tracers in the F98 rat xenograft, low uptake of [(18)F]FBPG in the mice PC-3 xenograft and a moderate uptake of [(18)F]FPG in the PC-3 tumors. CONCLUSION: We investigated the imaging potential of two novel PET radiotracers [(18)F]FPG and [(18)F]FBPG. [(18)F]FPG is the first example of a glutamine radiotracer derivatized with a phenyl group which enables the exploration of further derivatization of the phenyl group to increase the affinity and imaging qualities. We hypothesize that increasing the affinity of [(18)F]FPG by optimizing the substituents of the arene ring can result in a high-quality glutamine-based PET radiotracer. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: We hereby report novel glutamine-based PET-tracers. These tracers are tagged on the arene group with fluorine-18, hereby preventing in vivo defluorination, which can occur with alkyl labelled tracers (e.g. (2S,4R)4-[(18)F]fluoroglutamine). [(18)F]FPG shows clear tumor uptake in vivo, has no in vivo defluorination and has a straightforward production. We believe this tracer is a good starting point for the development of a high-quality tracer which is useful for the clinical visualization of the glutamine transport

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease

IntroductionObesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.MethodsDiagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data.Results and discussionThe results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population

Spin-Orbital Coupling in All-Inorganic Metal-Halide Perovskites: the Hidden Force that Matters

Highlighted with improved long-term thermal and environmental stability, all-inorganic metal halide perovskites exhibit tunable physical properties, cost-effective synthesis, and satisfactory optoelectronic performance, attracting increasing research interests worldwide. However, a less explored feature of these materials is their strong spin-orbit coupling (SOC), which is the hidden force influencing not only band structure but also properties including magnetoresistance, spin lifetime and singlet-triplet splitting. This review provides an overview of the fundamental aspects and the latest progress of the SOC and debate regarding Rashba effects in all-inorganic metal halide perovskites, providing critical insights into the physical phenomena and potential applications. Meanwhile, crystal structures and photophysics of all-inorganic perovskite are discussed in the context of SOC, along with the related experimental and characterization techniques. Furthermore, a recent understanding of the band topology in the all-inorganic halide perovskites is introduced to push the boundary even further for the novel applications of all-inorganic halide perovskites. Finally, an outlook is given on the potential directions of breakthroughs via leveraging the SOC in halide perovskites.Comment: 44 pages, 5 figure

Integrated System Built for Small-Molecule Semiconductors via High-Throughput Approaches

High-throughput synthesis of solution-processable structurally variable small-molecule semiconductors is both an opportunity and a challenge. A large number of diverse molecules provide a possibility for quick material discovery and machine learning based on experimental data. However, the diversity of molecular structure leads to the complexity of molecular properties, such as solubility, polarity, and crystallinity, which poses great challenges to solution processing and purification. Here, we first report an integrated system for the high-throughput synthesis, purification, and characterization of molecules with a large variety. Based on the principle of Like dissolves like, we combine theoretical calculations and a robotic platform to accelerate the purification of those molecules. With this platform, a material library containing 125 molecules and their optical-electric properties was built within a timeframe of weeks. More importantly, the high repeatability of recrystallization we design is a reliable approach to further upgrading and industrial production

Integrated System Built for Small-Molecule Semiconductors via High-Throughput Approaches

High-throughput synthesis of solution-processable structurally variable small-molecule semiconductors is both an opportunity and a challenge. A large number of diverse molecules provide a possibility for quick material discovery and machine learning based on experimental data. However, the diversity of the molecular structure leads to the complexity of molecular properties, such as solubility, polarity, and crystallinity, which poses great challenges to solution processing and purification. Here, we first report an integrated system for the high-throughput synthesis, purification, and characterization of molecules with a large variety. Based on the principle “Like dissolves like,” we combine theoretical calculations and a robotic platform to accelerate the purification of those molecules. With this platform, a material library containing 125 molecules and their optical-electronic properties was built within a timeframe of weeks. More importantly, the high repeatability of recrystallization we design is a reliable approach to further upgrading and industrial production

Microwave Synthesis and High‐Mobility Charge Transport of Carbon‐Nanotube‐in‐Perovskite Single Crystals

Organolead trihalide perovskites have emerged as a new class of competitive solution-processed semiconductors due to their unique optoelectronic properties. However, poor ambient stability and charge transport are the Achilles’ heel of hybrid perovskites, thus limiting their applications. In this work, microwave-assisted synthesis is applied for the first time to rapidly grow perovskite single crystals embedded with single-wall carbon nanotubes. These nanotube-in-perovskite single crystals are endowed with a carrier mobility one order of magnitude higher than the pure counterpart and the related photodetectors show an ultrafast photo-response speed (5 and 80 ns for rise and decay time, respectively). The fast and uniform heating of microwave irradiation facilitates the synthesis of ambient-stable crystals with nanoscale additives, paving the way to creating a wide range of mixed-dimensional perovskite-based nanocomposites with optimal properties and device performance

Reducing Implicit Racial Preferences: II Intervention Effectiveness Across Time

Implicit preferences are malleable, but does that change last? We tested 9 interventions (8 real and 1 sham) to reduce implicit racial preferences over time. In 2 studies with a total of 6,321 participants, all 9 interventions immediately reduced implicit preferences. However, none were effective after a delay of several hours to several days. We also found that these interventions did not change explicit racial preferences and were not reliably moderated by motivations to respond without prejudice. Short-term malleability in implicit preferences does not necessarily lead to long-term change, raising new questions about the flexibility and stability of implicit preferences. (PsycINFO Database Recor