C634Y mutation in RET-induced multiple endocrine neoplasia type 2A: A case report.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners. CASE SUMMARY: Herein, we present RET proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the RET proto-oncogene was conducted. The C634Y mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the C634Y mutation, and the corresponding treatments administered based on test results and associated clinical guidelines. CONCLUSION: Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.

The Potential Mechanisms of Arrhythmia in Coronavirus disease-2019.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.

Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis.

Objective: To evaluate the efficacy of different combinations of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: We obtained relevant randomized controlled trials (RCTs) from databases such as PubMed, Embase, Web of Science, and The Cochrane Library up to May 31, 2023. The analysis of clinical prognostic factors was performed using R 4.2.3 and STATA 15.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events of grade 3-5 severity (Grade ≥3 TRAE). Results: A total of 17 randomized controlled trials (RCTs) were conducted between 2012 and 2023, involving 7792 patients. These trials evaluated 11 different treatment methods. The results of these trials showed that in terms of overall survival (OS) and progression-free survival (PFS), the combination of tislelizumab with chemotherapy and the combination of camrelizumab with chemotherapy were particularly effective. Moreover, when compared with other combination therapies, pembrolizumab combined with chemotherapy showed superiority in terms of disease control rate (DCR) and objective response rate (ORR). Subgroup analyses further demonstrated that the addition of immune checkpoint inhibitors (ICIs) to chemotherapy significantly improved PFS and OS in patients without liver metastasis and in those with brain metastasis. Additionally, carboplatin-based combination therapy was found to confer favorable survival benefits in terms of PFS, while cisplatin-based combination therapy showed the most favorable outcomes in terms of OS. The results of subgroup analyses for overall survival (OS) showed that the combination of immunotherapy and chemotherapy yielded positive outcomes in specific subgroups. These subgroups were characterized by PD-L1 Tumor Proportion Score (TPS) of 50 % or higher, usage of anti-PD-1 medications, age below 65, male gender, smoking history, and non-squamous cell carcinoma histology. Superior effectiveness was demonstrated only in extending the progression-free survival (PFS) of female patients and patients with squamous carcinoma. Meanwhile, other patient cohorts did not show the same level of improvement. Conclusions: Tislelizumab, camrelizumab or pembrolizumab combined with chemotherapy may be the optimal first-line treatment strategies for NSCLC.

Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.

The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes of SLC6A13 in liver cancer. The prognostic significance of SLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation of SLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on hepatocellular carcinoma (HCC) cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels of SLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression of SLC6A13 but counteracted by glycine. This study highlighted elevated expression of SLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression of SLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine.

Agreement of ejection fraction measured by coronary computed tomography (CT) and cardiac ultrasound in evaluating patients with chronic heart failure: an observational comparative study.

Background: Cardiac ultrasound is one of the most important examinations in cardiovascular medicine, but the technical requirements for the operator are relatively high, which to some extent affects the scope of its use. This study was dedicated to investigating the agreement of ejection fraction between coronary computed tomography (CT) and cardiac ultrasound and diagnostic performance in evaluating the clinical diagnosis of patients with chronic heart failure. Methods: We conducted a single-center-based retrospective study including 343 consecutive patients enrolled between January 2019 to April 2020, all of whom presented with suspected symptoms of heart failure within one month. All enrolled cases performed cardiac ultrasound and coronary CT scans. The CT images were analyzed using accurate left ventricle (AccuLV) artificial intelligence (AI) software to calculate the ejection fraction-computed tomography (EF-CT) and it was compared with the ejection fraction (EF) obtained based on ultrasound. Cardiac insufficiency was determined if the EF measured by ultrasound was below 50%. Diagnostic performance analysis, correlation analysis and Bland-Altman plot were used to compare agreement between EF-CT and CT. Results: Of the 319 successfully performed patients, 220 (69%) were identified as cardiac insufficiency. Quantitative consistency analysis showed a good correlation between EF-CT and EF values in all cases (R square =0.704, r=0.837). Bland-Altman analysis showed mean bias of 6.6%, mean percentage error of 27.5% and 95% limit of agreement of -17% to 30% between EF and EF-CT. The results of the qualitative diagnostic study showed that the sensitivity and specificity of EF measured by coronary CT reached a high level of 91% [95% confidence interval (CI): 86-94%], and the positive diagnostic value was up to 96% (95% CI: 92-98%). Conclusions: The EF-CT and EF have excellent agreement, and AccuLV-based AI left ventricular function analysis software perhaps can be used as a clinical diagnostic reference.

The Rational Design of Atomically Dispersed Catalysts via Spin Manipulation.

The catalytic activity of transition-metal-based atomically dispersed catalysts is closely related to the spin states. Manipulating the spin state of metal active centers could directly adjust the d orbital occupancy and optimize the adsorption behavior and electron transfer of the intermediates and transition metals, which would enhance the catalytic activity. We summarize the means of manipulating spin states and the spin-related catalytic descriptors. In future work, we will build a quantifiable and accurate prediction intelligent model through artificial intelligence (AI) and machine learning tools. Furthermore, we will develop new spin regulation methods to carry out the directional regulation of atomically dispersed catalysts through this model, providing new insight into the rational design of transition-metal-based atomically dispersed catalysts through spin manipulation.

Interfacial interactions between minerals and organic matter: Mechanisms and characterizations.

Minerals and organic matter are essential components of soil, with minerals acting as the "bone" and organic matter as the "skin". The interfacial interactions between minerals and organic matter result in changes in their chemical composition, structure, functional groups, and physical properties, possessing a significant impact on soil properties, functions, and biogeochemical cycles. Understanding the interfacial interactions of minerals and organic matter is imperative to advance soil remediation technologies and carbon targets. Consequently, there is a growing interest in the physicochemical identification of the interfacial interactions between minerals and organic matter in the academic community. This review provides an overview of the mechanisms underlying these interactions, including adsorption, co-precipitation, occlusion, redox, catalysis and dissolution. Moreover, it surveys various methods and techniques employed to characterize the mineral-organic matter interactions. Specifically, the up-to-date spectroscopic techniques for chemical information and advanced microscopy techniques for physical information are highlighted. The advantages and limitations of each method are also discussed. Finally, we outline future research directions for interfacial interactions and suggests areas for improvement and development of characterization techniques to better understand the mechanisms of mineral-organic matter interactions.

SPINK4 modulates inhibition of glycolysis against colorectal cancer progression.

Dysregulation of glycolysis is frequently linked to aggressive tumor activity in colorectal cancer (CRC). Although serine peptidase inhibitor, Kazal type 4 (SPINK4) has been linked to CRC, its exact linkage to glycolytic processes and gene expression remains unclear. Differentially expressed genes (DEGs) were screened from two CRC-related datasets (GSE32323 and GSE141174), followed by expression and prognostic analysis of SPINK4. In vitro techniques such as flow cytometry, western blotting, transwell assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess SPINK4 expression in CRC cells. Its effects on apoptosis, glycolysis, and the cell cycle were also investigated. Finally, the impact of SPINK4 overexpression on tumor development was assessed using a xenograft model, while histological and immunohistochemical analyses characterized SPINK4 expression patterns in CRC tissues. SPINK4 expression was downregulated in CRC, correlating with poor patient prognosis. In vitro assays confirmed that overexpression of SPINK4 reduced CRC cell proliferation, invasion, and migration, while its knockdown promoted these processes and caused G1 arrest. SPINK4 also regulated apoptosis by altering caspase activation and Bcl-2 expression. Besides, SPINK4 overexpression altered glycolytic activity, reduced 2-Deoxy-D-glucose (2-DG) absorption, and controlled critical glycolytic enzymes, resulting in alterations in metabolic pathways, whereas SPINK4 knockdown reversed this effect. SPINK4 overexpression significantly reduced tumor volume in vivo, indicating its inhibitory role in carcinogenesis. Moreover, high expression of SPINK4, hexokinase 2 (HK2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) was observed in CRC tissues. As a key inhibitor of glycolytic metabolism in CRC, SPINK4 promises metabolic intervention in CRC therapy due to its impact on tumor growth and cell proliferation.

Case report: Experience and insights on the treatment of two cases of cryptococcal meningitis during the later stages of the COVID-19 pandemic.

In the late stages of the COVID-19 pandemic, there's an increasing trend in opportunistic infections, including bacterial and fungal infections. This study discusses the treatment process of two cases of cryptococcal meningitis during the COVID-19 pandemic. It highlights the importance of laboratory testing for these co-infections and stresses the need for vigilance, early diagnosis, and proactive treatment to improve patient outcomes in the post-pandemic era.

Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer.

Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.

Novel BODIPY-based nano-biomaterials with enhanced D-A-D structure for NIR-triggered photodynamic and photothermal therapy.

Near-infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor-acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

Global, regional, national trends of femur fracture and machine learning prediction: Comprehensive findings and questions from global burden of disease 1990-2019.

Background: Femur fracture is a type of fracture with high disability and mortality. There is no comprehensive analysis and prediction of the global distribution of femur fractures, so we conducted this study. Methods: Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and years living with disability (YLDs) of femur fractures (excluding femoral neck) were downloaded from the Global burden of disease database. Trend analysis was performed, and 6 time-series machine learning algorithms were applied to predict the global ASIR, ASPR, and YLDs. Results: ASPR for femur fracture had been increasing in most countries worldwide from 1990 to 2019, with the highest in East Asia (AAPC = 1.25 95%Confidence Interval (1.2, 1.3)) and lowest in Central Latin America (AAPC = -0.74 95%CI (-0.81, -0.67)). However, ASIR showed a significant downward trend worldwide, with East Saharan Africa decreasing the most (AAPC = -4.04 95%CI (-5.56, -2.47)), and East Asia elevating the most (AAPC = 1.11 95%CI (0.87, 1.42)). YLDs were increasing over the world, with East Asia still elevating the most AAPC= (3.9 95%CI (3.85, 3.95)), with the only region of decrease being Eastern Europe (AAPC = -0.28 95%CI (-0.3, -0.26)). Both ASPR and ASIR were higher in women than in men in the >75 year group, whereas YLDs was lower in women than in men in the >60 year group. Globally, the ARIMA model was optimal in the prediction of ASPR, the PROPHET model effected in the prediction of ASIR, and the PROPHET WITH XGBOOST model was the best in the prediction of YLDs. The projections showed increase in both ASPR and YLDs, except for ASIR decreasing by 2030. Conclusions: Our study found a rise in femur fracture ASPR and ASIR from 1990 to 2019 in war conflict areas and East Asia, meanwhile, the YLDs of femur fracture increased in populous countries. In both 1990 and 2019, both ASPR and ASIR were higher in women over 75 years than that in men, but YLDs was higher in men over 60 years than that in women. In 2020-2030, while global femur fracture ASIR might decline, both ASPR and YLDs might rise. The Translational Potential of this article: Femur fracture is a high-energy injury due to direct violence, and in war, conflicting and underdeveloped regions such as East Asia. Accidental injuries may occur due to the rapid development of industry and the frequent traffic accidents. This study suggests that we should focus on elderly women (≥75 years) in the above regions in the future. For older men (>60 years old), more attention should be paid to post-fracture functional rehabilitation and early reintegration into society to reduce the disability rate and lower the socio-economic burden.

Pollution characteristics and quantitative source apportionment of heavy metals within a zinc smelting site by GIS-based PMF and APCS-MLR models.

The abandoned smelters present a substantial pollution threat to the nearby soil and groundwater. In this study, 63 surface soil samples were collected from a zinc smelter to quantitatively describe the pollution characteristics, ecological risks, and source apportionment of heavy metal(loid)s (HMs). The results revealed that the average contents of Zn, Cd, Pb, As, and Hg were 0.4, 12.2, 3.3, 5.3, and 12.7 times higher than the risk screening values of the construction sites, respectively. Notably, the smelter was accumulated heavily with Cd and Hg, and the contribution of Cd (0.38) and Hg (0.53) to ecological risk was 91.58%. ZZ3 and ZZ7 were the most polluted workshops, accounting for 25.7% and 35.0% of the pollution load and ecological risk, respectively. The influence of soil parent materials on pollution was minor compared to various workshops within the smelter. Combined with PMF, APCS-MLR and GIS analysis, four sources of HMs were identified: P1(25.5%) and A3(18.4%) were atmospheric deposition from the electric defogging workshop and surface runoff from the smelter; P2(32.7%) and A2(20.9%) were surface runoff of As-Pb foul acid; P3(14.5%) and A4(49.8%) were atmospheric deposition from the leach slag drying workshop; P4(27.3%) and A1(10.8%) were the smelting process of zinc products. This paper described the distribution characteristics and specific sources of HMs in different process workshops, providing a new perspective for the precise remediation of the smelter by determining the priority control factors.

Bone Regenerative Effect of Injectable Hypoxia Preconditioned Serum-Fibrin (HPS-F) in an Ex Vivo Bone Defect Model.

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.

Based on scRNA-seq and bulk RNA-seq to establish tumor immune microenvironment-associated signature of skin melanoma and predict immunotherapy response.

Skin cutaneous melanoma (SKCM), a form of skin cancer, ranks among the most formidable and lethal malignancies. Exploring tumor microenvironment (TME)-based prognostic indicators would help improve the efficacy of immunotherapy for SKCM patients. This study analyzed SKCM scRNA-seq data to cluster non-malignant cells that could be used to explore the TME into nine immune/stromal cell types, including B cells, CD4 T cells, CD8 T cells, dendritic cells, endothelial cells, Fibroblasts, macrophages, neurons, and natural killer (NK) cells. Using data from The Cancer Genome Atlas (TCGA), we employed SKCM expression profiling to identify differentially expressed immune-associated genes (DEIAGs), which were then incorporated into weighted gene co-expression network analysis (WGCNA) to investigate TME-associated hub genes. Discover candidate small molecule drugs based on pivotal genes. Tumor immune microenvironment-associated genes (TIMAGs) for constructing TIMAS were identified and validated. Finally, the characteristics of TIAMS subgroups and the ability of TIMAS to predict immunotherapy outcomes were analyzed. We identified five TIMAGs (CD86, CD80, SEMA4D, C1QA, and IRF1) and used them to construct TIMAS. In addition, five potential SKCM drugs were identified. The results showed that TIMAS-low patients were associated with immune-related signaling pathways, high MUC16 mutation frequency, high T cell infiltration, and M1 macrophages, and were more favorable for immunotherapy. Collectively, TIMAS constructed by comprehensive analysis of scRNA-seq and bulk RNA-seq data is a promising marker for predicting ICI treatment outcomes and improving individualized therapy for SKCM patients.

Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

Cetuximab inhibits colorectal cancer development through inactivating the Wnt/ß-catenin pathway and modulating PLCB3 expression.

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.

Neural mechanisms of social comparison in subthreshold depression.

Social comparison is a common phenomenon in our daily life, through which people get to know themselves, and plays an important role in depression. In this study, event-related potential (ERP) was used to explore the temporal course of social comparison processing in the subthreshold depression group. Electrophysiological recordings were acquired from 30 subthreshold depressed individuals and 31 healthy individuals while they conducted the adapted dot estimation task. The ERP results revealed that there was a significant difference of feedback-related negativity (FRN) in the process of social comparison. Especially only in the subthreshold depression, the FRN amplitudes of worse off than some, better off than many comparisons were larger than those of upward comparisons and downward comparisons. Our results suggested that the abnormal reward sensitivity for worse off than some, better off than many comparisons might be prodromal symptoms in the subthreshold depression.

Enhancement of nitrogen on core taxa recruitment by Penicillium oxalicum stimulated microbially-driven soil formation in bauxite residue.

Microbially-driven soil formation process is an emerging technology for the ecological rehabilitation of alkaline tailings. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. Herein, a 1-year field-scale experiment was applied to demonstrate the effect of nitrogen input on the structure and function of the microbiome in alkaline bauxite residue. Results showed that the contents of nutrient components were increased with Penicillium oxalicum (P. oxalicum) incorporation, as indicated by the increasing of carbon and nitrogen mineralization and enzyme metabolic efficiency. Specifically, the increasing enzyme metabolic efficiency was associated with nitrogen input, which shaped the microbial nutrient acquisition strategy. Subsequently, we evidenced that P. oxalicum played a significant role in shaping the assemblages of core bacterial taxa and influencing ecological functioning through intra- and cross-kingdom network analysis. Furthermore, a recruitment experiment indicated that nitrogen enhanced the enrichment of core microbiota (Nitrosomonas, Bacillus, Pseudomonas, and Saccharomyces) and may provide benefits to fungal community bio-diversity and microbial network stability. Collectively, these results demonstrated nitrogen-based coexistence patterns among P. oxalicum and microbiome and revealed P. oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. It will aid in promoting soil formation and ecological rehabilitation of bauxite residue. ENVIRONMENT IMPLICATION: Bauxite residue is a highly alkaline solid waste generated during the Bayer process for producing alumina. Attempting to transform bauxite residue into a stable soil-like substrate using low-cost microbial resources is a highly promising engineering. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. In this study, we evidenced the nitrogen-based coexistence patterns among Penicillium oxalicum and microbiome and revealed Penicillium oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. This study can improve the understanding of core microbes' assemblies that affect the microbiome physiological traits in soil formation processes.