Proteomics appending a complementary dimension to precision oncotherapy.

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.

Low-intensity pulsed ultrasound protects from inflammatory dilated cardiomyopathy through inciting extracellular vesicles.

AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. METHODS AND RESULTS: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. CONCLUSION: Our findings revealed that LIPUS uses an EV-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.

Structure and Chemical Reactivity of Y-Stabilized ZrO2 Surfaces: Importance for the Water-Gas Shift Reaction.

The surface structure and chemical properties of Y-stabilized zirconia (YSZ) have been subjects of intense debate over the past three decades. However, a thorough understanding of chemical processes occurring at YSZ powders faces significant challenges due to the absence of reliable reference data acquired for well-controlled model systems. Here, we present results from polarization-resolved infrared reflection absorption spectroscopy (IRRAS) obtained for differently oriented, Y-doped ZrO2 single-crystal surfaces after exposure to CO and D2O. The IRRAS data reveal that the polar YSZ(100) surface undergoes reconstruction, characterized by an unusual, red-shifted CO band at 2132 cm-1. Density functional theory calculations allowed to relate this unexpected observation to under-coordinated Zr4+ cations in the vicinity of doping-induced O vacancies. This reconstruction leads to a strongly increased chemical reactivity and water spontaneously dissociates on YSZ(100). The latter, which is an important requirement for catalysing the water-gas-shift (WGS) reaction, is absent for YSZ(111), where only associative adsorption was observed. Together with a novel analysis Scheme these reference data allowed for an operando characterisation of YSZ powders using DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy). These findings facilitate rational design and tuning of YSZ-based powder materials for catalytic applications, in particular CO oxidation and the WGS reaction.

Reactivation of methylation-silenced PAX1 inhibits cervical cancer proliferation and migration via the WNT/TIMELESS pathway.

Although aberrant methylation of PAX1 is closely associated with cervical cancer (CC), PAX1 methylation (PAX1m) and its role in CC remain to be elucidated. Here, we clarified the biological function of PAX1 in CC. First, PAX1m in ThinPrep cytologic test samples was measured via quantitative methylation-specific PCR. The results showed that PAX1 promoter methylation levels were significantly increased in CC patients (p < 0.001). We also found that PAX1 promoter methylation levels were positively correlated with tumor purity but negatively correlated with immune-infiltration via public databases. Then, CRISPR-based methylation perturbation tools (dCas9-Tet1) were constructed to further demonstrate that DNA methylation participates in the regulation of PAX1 expression directly. Gain- and loss-of-function experiments were used to show that PAX1 overexpression restrained proliferation, migration and improved cisplatin sensitivity by interfering with the WNT/TIMELESS axis in CC cells. Additionally, Co-immunoprecipitation assays further confirmed the interaction between PAX1 and TCF7L2. Taken together, our results suggested that a tumor suppressor role of PAX1 in CC and that CRISPR-based PAX1 demethylation editing might be a promising therapeutic strategy for CC.

Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study.

Background: Primary ovarian insufficiency (POI) is a common clinical endocrine disorder with a high heterogeneity in both endocrine hormones and etiological phenotypes. However, the etiology of POI remains unclear. Herein, we unraveled the causality of genetically determined metabolites (GDMs) on POI through Mendelian randomization (MR) study with the overarching goal of disclosing underlying mechanisms. Methods: Genetic links with 486 metabolites were retrieved from GWAS data of 7824 European participants as exposures, while GWAS data concerning POI were utilized as the outcome. Via MR analysis, we selected inverse-variance weighted (IVW) method for primary analysis and several additional MR methods (MR-Egger, weighted median, and MR-PRESSO) for sensitivity analyses. MR-Egger intercept and Cochran's Q statistical analysis were conducted to assess potential heterogeneity and pleiotropy. In addition, genetic variations in the key target metabolite were scrutinized further. We conducted replication, meta-analysis, and linkage disequilibrium score regression (LDSC) to reinforce our findings. The MR Steiger test and reverse MR analysis were utilized to assess the robustness of genetic directionality. Furthermore, to deeply explore causality, we performed colocalization analysis and metabolic pathway analysis. Results: Via IVW methods, our study identified 33 metabolites that might exert a causal effect on POI development. X-11437 showed a robustly significant relationship with POI in four MR analysis methods (P IVW=0.0119; P weighted-median =0.0145; PMR-Egger =0.0499; PMR-PRESSO =0.0248). Among the identified metabolites, N-acetylalanine emerged as the most significant in the primary MR analysis using IVW method, reinforcing its pivotal status as a serum biomarker indicative of an elevated POI risk with the most notable P-value (P IVW=0.0007; PMR-PRESSO =0.0022). Multiple analyses were implemented to further demonstrate the reliability and stability of our deduction of causality. Reverse MR analysis did not provide evidence for the causal effects of POI on 33 metabolites. Colocalization analysis revealed that some causal associations between metabolites and POI might be driven by shared genetic variants. Conclusion: By incorporating genomics with metabolomics, this study sought to offer a comprehensive analysis in causal impact of serum metabolome phenotypes on risks of POI with implications for underlying mechanisms, disease screening and prevention.

Dynamic impact of delivery modes on gut microbiota in preterm infants hospitalized during the initial 4 weeks of life.

Preterm infants face a high risk of various complications, and their gut microbiota plays a pivotal role in health. Delivery modes have been reported to affect the development of gut microbiota in term infants, but its impact on preterm infants remains unclear. Here, we collected fecal samples from 30 preterm infants at five-time points within the first four weeks of life. Employing 16 S rRNA sequencing, principal coordinates analysis, the analysis of similarities, and the Wilcoxon rank-sum test, we examined the top dominant phyla and genera, the temporal changes in specific taxa abundance, and their relationship with delivery modes, such as Escherichia-Shigella and Enterococcus based on vaginal delivery and Pluralibacter related to cesarean section. Moreover, we identified particular bacteria, such as Taonella, Patulibacter, and others, whose proportions fluctuated among preterm infants born via different delivery modes at varying time points, as well as the microbiota types and functions. These results indicated the influence of delivery mode on the composition and function of the preterm infant gut microbiota. Importantly, these effects are time-dependent during the early stages of life. These insights shed light on the pivotal role of delivery mode in shaping the gut microbiota of preterm infants and have significant clinical implications for their care and management.

Polydopamine-modified black phosphorus nanosheet drug delivery system for the treatment of ischemic stroke.

Black phosphorus (BP), as a representative metal-free semiconductor, has been extensively explored. It has a higher drug loading capacity in comparison to conventional materials and also possesses excellent biocompatibility and biodegradability. Furthermore, BP nanosheets can enhance the permeability of the blood-brain barrier (BBB) upon near-infrared (NIR) irradiation, owing to their photothermal effect. However, the inherent instability of BP poses a significant limitation, highlighting the importance of surface modification to enhance its stability. Ischemic stroke (IS) is caused by the occlusion of blood vessels, and its treatment is challenging due to the hindrance caused by the BBB. Therefore, there is an urgent need to identify improved methods for bypassing the BBB for more efficient IS treatment. This research devised a novel drug delivery approach based on pterostilbene (Pte) supported by BP nanosheets, modified with polydopamine (PDA) to form BP-Pte@PDA. This system shows robust stability and traverses the BBB using effective photothermal mechanisms. This enables the release of Pte upon pH and NIR stimuli, offering potential therapeutic advantages for treating IS. In a middle cerebral artery occlusion mouse model, the BP-Pte@PDA delivery system significantly reduced infarct size, and brain water content, improved neurological deficits, reduced the TLR4 inflammatory factor expression, and inhibited cell apoptosis. In summary, the drug delivery system fabricated in this study thus demonstrated good stability, therapeutic efficacy, and biocompatibility, rendering it suitable for clinical application.

Computational Study on Interlocked-Ferroelectricity-Contributed High-Performance Memristors Based on Two-Dimensional van der Waals Ferroelectric Semiconductors.

In order to realize the prevailing artificial intelligence technology, memristor-implemented in-memory or neuromorphic computing is highly expected to break the bottleneck of von Neumann computers. Although high-performance memristors have been vigorously developed in labs or in industry, systematic computational investigations on memristors are seldom. Hence, it is urgent to provide theoretical or computational support for the exploration of memristor operating mechanisms or the screening of memristor materials. Here, a computational method based on the main input parameters learned from the first-principles calculations was developed to measure resistance switching of two-terminal memristors with sandwiched metal/ferroelectric semiconductor/metal architectures, which strikingly agrees with the experimental measurements. Based on our developed method, the diverse multiterminal memristors were designed to fully exploit the application of interlocked ferroelectricity of a ferroelectric semiconductor and realize their heterosynaptic plasticity, and their heterosynaptic behaviors can still be well described. Our developed method can provide a paradigm for the emulation of ferroelectric memristors and inspire subsequent computational exploration. Furthermore, our study also supplies a device optimization strategy based on the interlocked ferroelectricity and easy processing of two-dimensional van der Waals ferroelectric semiconductors, and our proposed heterosynaptic memristors still await further experimental exploration.

Small extracellular vesicle-based delivery of interleukin-10 improves treatment of experimental autoimmune uveitis.

Non-infectious uveitis is an intraocular autoimmune disease mainly characterized by immune dysregulation of the eye, which may cause blindness if not well treated. Interleukin 10 (IL-10) is a potent cytokine with multiple immunoregulatory functions. However, it's in vivo activity is unstable owing to its inherent protein instability and short plasma half-life. Therefore, our previous research tried to establish IL-10-overexpressing MSC-sEVs (sEVs-IL10) using lentiviral transfection. While this approach indeed improved drug delivery, it also suffered from tedious procedures and limited loading efficiency. Accordingly, we constructed a novel MSC-sEVs-based delivery system for IL-10 (IL-10@sEVs) by sonication. The obtained formulation (IL-10@sEVs) had relatively higher loading efficiency and exerted a more profound immunomodulatory effect than sEVs-IL10 in vitro. Furthermore, IL-10@sEVs had significant therapeutic effects in a mouse model of experimental autoimmune uveitis (EAU) by decreasing the percentage of Th17 cells, increasing regulatory T cells in the eye, and draining lymph nodes. In summary, sonication outperforms conventional transfection methods for loading IL-10 into MSC-sEVs.

CD276 regulates the immune escape of esophageal squamous cell carcinoma through CXCL1-CXCR2 induced NETs.

BACKGROUND: CD276 (B7-H3), a pivotal immune checkpoint, facilitates tumorigenicity, invasiveness, and metastasis by escaping immune surveillance in a variety of tumors; however, the underlying mechanisms facilitating immune escape in esophageal squamous cell carcinoma (ESCC) remain enigmatic. METHODS: We investigated the expression of CD276 in ESCC tissues from patients by using immunohistochemistry (IHC) assays. In vivo, we established a 4-nitroquinoline 1-oxide (4NQO)-induced CD276 knockout (CD276wKO) and K14cre; CD276 conditional knockout (CD276cKO) mouse model of ESCC to study the functional role of CD276 in ESCC. Furthermore, we used the 4NQO-induced mouse model to evaluate the effects of anti-CXCL1 antibodies, anti-Ly6G antibodies, anti-NK1.1 antibodies, and GSK484 inhibitors on tumor growth. Moreover, IHC, flow cytometry, and immunofluorescence techniques were employed to measure immune cell proportions in ESCC. In addition, we conducted single-cell RNA sequencing analysis to examine the alterations in tumor microenvironment following CD276 depletion. RESULTS: In this study, we elucidate that CD276 is markedly upregulated in ESCC, correlating with poor prognosis. In vivo, our results indicate that depletion of CD276 inhibits tumorigenesis and progression of ESCC. Furthermore, conditional knockout of CD276 in epithelial cells engenders a significant downregulation of CXCL1, consequently reducing the formation of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, while simultaneously augmenting natural killer (NK) cells. In addition, overexpression of CD276 promotes tumorigenesis via increasing NETs' formation and reducing NK cells in vivo. CONCLUSIONS: This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.

Role of Carotid Ultrasonography Combined with Monocyte/HDL Ratio in Internal Carotid Artery Stenosis.

BACKGROUND: Carotid duplex ultrasonography (DUS) is the primary screening tool for carotid artery stenosis, but has low reliability. MHR, which is the ratio of monocytes to high-density lipoprotein cholesterol (HDL-C), can be a marker for the degree and distribution of extracranial and intracranial atherosclerotic stenosis. OBJECTIVE: We determined the diagnostic value of DUS+MHR for internal carotid artery (ICA) stenosis. METHODS: We divided 273 hospitalized patients into non-stenosis (<50%) and ICA stenosis (≥50%) groups based on Digital Subtraction Angiography (DSA). We determined the peak systolic velocity (PSV) in the ICA on DUS, calculated the MHR, and investigated their relationship with ICA stenosis. RESULTS: On DSA, 34.1% (93/273) patients had moderate-to-severe ICA stenosis. DUS and DSA showed low concordance for detecting ICA stenosis (kappa = 0.390). With increasing age, the incidence of moderate-to-severe ICA stenosis increased. PSV, monocyte count, and MHR were significantly greater in the stenosis group than in the non-stenosis group (P < 0.001), while the HDL-C level was significantly lower (P = 0.001). PSV (OR: 1.020, 95% CI: 1.011-1.029, P < 0.001) and MHR (OR: 5.662, 95% CI: 1.945-16.482, P = 0.002) were independent risk factors for ICA stenosis. The area under the receiver operating characteristic curve of PSV+MHR (0.819) was significantly higher than that of PSV or MHR alone (77.42% sensitivity, P = 0.0207; 73.89% specificity, P = 0.0032). CONCLUSION: The combination of ICA PSV on DUS and MHR is better than PSV alone at identifying ICA stenosis and is well-suited to screen high-risk patients.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

Tooth whitening: current status and prospects.

As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects.

A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

The Impact of Delirium after Radical Prostatectomy on Cognitive Function and Health Perception during the Recovery Period.

OBJECTIVE: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. METHODS: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients' mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. RESULTS: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). CONCLUSIONS: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception. A significant correlation exists between postoperative delirium and cognitive function as well as health perception.

CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

An endogenous promoter LpSUT2 discovered in duckweed: a promising transgenic tool for plants.

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35S promoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher initiation activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg.L-1 G418 and 6.18 times at 500 mg.L-1 G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFP were weakened, while the LpSUT2:eGFP only changed slightly. This is because, under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This is a previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.

Maillard reaction intermediates in Chinese Baijiu and their effects on Maillard reaction related flavor compounds during aging.

This study investigated the Maillard reaction in Baijiu and the effects of extended aging in the presence of Maillard reaction intermediates (MRIs) on aromatic compounds, particularly focusing on heterocyclic changes. MRIs with different aroma types in Baijiu aged 1-18 years and force-aged for 6 weeks were determined. Results revealed that MRIs in soy sauce aroma-type Baijiu were significantly more abundant than those in other types of Baijiu. Changes in MRIs were observed and compared in aging and forced-aging Baijiu. Additionally, the distribution and variation of heterocycles in Baijiu were examined, which revealed an increase in N-heterocycle levels but a decrease in S- and O-heterocycle levels to a certain extent. The results of this study demonstrate that the Maillard reaction during the aging of Baijiu influences heterocycle concentrations, thereby improving flavor of aged Baijiu. Research into heterocycles and the Maillard reaction may help elucidate the aromatic evolution of Baijiu with aging and provide guidance for Baijiu storage.