Deciphering microbial metabolic interactions and their implications for community dynamics in acid mine drainage sediments.

The microbially-mediated reduction processes have potential for the bioremediation of acid mine drainage (AMD), which represents a worldwide environment problem. However, we know little about the microbial interactions in anaerobic AMD sediments. Here we utilized genome-resolved metagenomics to uncover the nature of cooperative and competitive metabolic interactions in 90 AMD sediments across Southern China. Our analyses recovered well-represented prokaryotic communities through the reconstruction of 2625 population genomes. Functional analyses of these genomes revealed extensive metabolic handoffs which occurred more frequently in nitrogen metabolism than in sulfur metabolism, as well as stable functional redundancy across sediments resulting from populations with low genomic relatedness. Genome-scale metabolic modeling showed that metabolic competition promoted microbial co-occurrence relationships, suggesting that community assembly was dominated by habitat filtering in sediments. Notably, communities colonizing more extreme conditions tended to be highly competitive, which was typically accompanied with increased network complexity but decreased stability of the microbiome. Finally, our results demonstrated that heterotrophic Thermoplasmatota associated with ferric iron and sulfate reduction contributed most to the elevated levels of competition. Our study shed light on the cooperative and competitive metabolisms of microbiome in the hazardous AMD sediments, which may provide preliminary clues for the AMD bioremediation in the future.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

The T120P or M172V mutation on rv2172c confers high level para-aminosalicylic acid resistance in Mycobacterium tuberculosis.

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in M. tuberculosis. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed rv2172c mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on rv2172c could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of rv2172c T120P or M172V mutation on methionine production and PAS resistance was determined in M. tuberculosis. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in M. tuberculosis clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in M. tuberculosis, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.

Unraveling the habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses across China.

BACKGROUND: Soil giant viruses are increasingly believed to have profound effects on ecological functioning by infecting diverse eukaryotes. However, their biogeography and ecology remain poorly understood. RESULTS: In this study, we analyzed 333 soil metagenomes from 5 habitat types (farmland, forest, grassland, Gobi desert, and mine wasteland) across China and identified 533 distinct giant virus phylotypes affiliated with nine families, thereby greatly expanding the diversity of soil giant viruses. Among the nine families, Pithoviridae were the most diverse. The majority of phylotypes exhibited a heterogeneous distribution among habitat types, with a remarkably high proportion of unique phylotypes in mine wasteland. The abundances of phylotypes were negatively correlated with their environmental ranges. A total of 76 phylotypes recovered in this study were detectable in a published global topsoil metagenome dataset. Among climatic, geographical, edaphic, and biotic characteristics, soil eukaryotes were identified as the most important driver of beta-diversity of giant viral communities across habitat types. Moreover, co-occurrence network analysis revealed some pairings between giant viral phylotypes and eukaryotes (protozoa, fungi, and algae). Analysis of 44 medium- to high-quality giant virus genomes recovered from our metagenomes uncovered not only their highly shared functions but also their novel auxiliary metabolic genes related to carbon, sulfur, and phosphorus cycling. CONCLUSIONS: These findings extend our knowledge of diversity, habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses. Video Abstract.

Quantitative Monitoring of GPCR-Mediated Spatiotemporal IP3 Dynamics Using Confocal Fluorescence Microscopy.

Activation of G protein-coupled receptors upon chemoattractant stimulation induces activation of multiple signaling pathways. To fully understand how these signaling pathway coordinates to achieve directional migration of neutrophils, it is essential to determine the dynamics of the spatiotemporal activation profile of signaling components at the level of single living cells. Here, we describe a detailed methodology for monitoring and quantitatively analyzing the spatiotemporal dynamics of 1,4,5-inositol trisphosphate (IP3) in neutrophil-like HL60 cells in response to various chemoattractant fields by applying Förster resonance energy transfer (FRET) fluorescence microscopy.

The Influence of Piriform Recess Instillation with Lidocaine Before Bronchoscopy on Post-General Anesthesia Cough: A Randomized Controlled Trial.

Background and Importance: Postoperative cough is a common complication of general anesthesia after bronchoscopy. The aim of the present study was to determine the safety profile and efficacy of piriform recess instillation with lidocaine in reducing the incidence of coughing. Objective: To what extent could piriform recess instillation with lidocaine decrease the incidence of cough at 10min after extubation? Outcome Measures and Analysis: Eighty-eight consecutive patients were equally randomized to a lidocaine group receiving piriform recess instillation with 2mL 2% lidocaine, and a normal saline group receiving piriform recess instillation with 2mL saline. The primary outcome was the incidence of cough after extubation, and the secondary outcomes were throat score at 10 min and 6 h after extubation assessed by the numerical rating scale, cough severity at 10 min and 6 h after extubation assessed by the Visual Analog Scale (VAS), 24 h 40-item Quality of Recovery Score (QoR-40), and subject-rated satisfaction score on a VAS. Main Results: Compared with saline group, the incidence of cough in lidocaine group was significantly lower (63.6% vs 86.4%, P=0.014). The sore throat score at 10 min after extubation was significantly lower (0[0,0] vs 1[0,2], P<0.001). The subject-rated overall anesthesia satisfaction score was significantly higher (84.8[±6.2] vs 76.6[±8.6], P<0.001). The severity of cough at 10 min after extubation was significantly lower (Mild: 36.4% vs 11.4%, P=0.006; Severe: 9.1% vs 43.2%, P<0.001). There was no significant difference in the sore throat score at 6 h after extubation, severity of cough at 6 h after extubation, or QoR-40 at 24 h after extubation between the two groups. Conclusion: Piriform recess instillation with lidocaine before bronchoscopy is a simple and effective method for reducing early cough intensity and alleviating early sore throat. At 6 hours, there were no differences observed between the groups. Clinical Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2200067087).

The rv2820c K114N mutation is related with capreomycin tolerance.

As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 Mycobacterium tuberculosis clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the rv2820c gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%). However, the mutation was also observed in capreomycin-sensitive isolates (10/394, 2.53%). In most cases (31/42, 73.81%), the rv2820c K114N mutation occurred in isolates with the known capreomycin resistance conferring mutation rrs A1401G. In contrast, the general frequency of the rv2820c K114N mutation was low in 7061 genomes downloaded from the National Center for Biotechnology Information database. To determine the impact of this mutation on the antimycobacterial activity of capreomycin, the intact rv2820c gene and the rv2820c K114N mutant were over-expressed in Mycobacterium smegmatis (Ms), and the results of susceptibility tests showed that the rv2820c K114N mutation did not affect the minimum inhibition concentration (MIC) of capreomycin. Subsequently, the data of time-kill assays showed that, it took only 2 h of capreomycin treatment (40 µg/ml, 5 × MIC) to kill 99.9% bacterial cells of Ms MC2155 pMV261::rv2820cH37Rv, while it took 6 h to achieve that for Ms MC2155 pMV261::rv2820cK114N. Taken together, these data suggested that the rv2820c K114N mutation is related with capreomycin tolerance, which merits further investigation.

A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.

Domestication of rice may have changed its arbuscular mycorrhizal properties by modifying phosphorus nutrition-related traits and decreasing symbiotic compatibility.

Modern cultivated rice (Oryza sativa) typically experiences limited growth benefits from arbuscular mycorrhizal (AM) symbiosis. This could be due to the long-term domestication of rice under favorable phosphorus conditions. However, there is limited understanding of whether and how the rice domestication has modified AM properties. This study compared AM properties between a collection of wild (Oryza rufipogon) and domesticated rice genotypes and investigated the mechanisms underlying their differences by analyzing physiological, genomic, transcriptomic, and metabolomic traits critical for AM symbiosis. The results revealed significantly lower mycorrhizal growth responses and colonization intensity in domesticated rice compared to wild rice, and this change of AM properties may be associated with the domestication modifications of plant phosphorus utilization efficiency at physiological and genomic levels. Domestication also resulted in a decrease in the activity of the mycorrhizal phosphorus acquisition pathway, which may be attributed to reduced mycorrhizal compatibility of rice roots by enhancing defense responses like root lignification and reducing carbon supply to AM fungi. In conclusion, rice domestication may have changed its AM properties by modifying P nutrition-related traits and reducing symbiotic compatibility. This study offers new insights for improving AM properties in future rice breeding programs to enhance sustainable agricultural production.

Association between Hepatitis B virus infection and liver metastasis in colorectal cancer.

The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ (n = 1696) and HBV- (n = 4175) groups and further within HBV+ subgroups of chronic (CHB, n = 474) and occult (OHB, n = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

Non-telecentric photoacoustic microscopy for multi-scale imaging.

Optical-resolution photoacoustic microscopy (OR-PAM) excels in precisely imaging a biological tissue based on absorption contrast. However, existing OR-PAMs are confined by fixed compromises between spatial resolution and field of view (FOV), preventing the integration of large FOV and local high-resolution within one system. Here, we present a non-telecentric OR-PAM (nTC-PAM) that empowers efficient adaptation of FOV and spatial resolution to match the multi-scale requirement of diverse biological imaging. Our method allows for a large-scale transformation in FOV and even surpassing the nominal FOV of the objective with minimal marginal degradation of the lateral resolution. We demonstrate the advantage of nTC-PAM through multi-scale imaging of the leaf phantom, mouse ear, and cortex. The results reveal that nTC-PAM can switch the FOV and spatial resolution to meet the requirements of different biological tissues, such as large-scale imaging of the whole cerebral cortex and high-resolution imaging of microvascular structures in local brain regions.

Endoscopic submucosal dissection versus surgery for T1b esophageal carcinoma: a single-center retrospective study.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC. METHODS: We reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people. RESULTS: In the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan-Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments. CONCLUSION: ESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.

Lemneolemnanes A-D, Four Uncommon Sesquiterpenoids from the Soft Coral Lemnalia sp.

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

High spatiotemporal mapping of cortical blood flow velocity with an enhanced accuracy.

Cerebral blood flow velocity is one of the most essential parameters related to brain functions and diseases. However, most existing mapping methods suffer from either inaccuracy or lengthy sampling time. In this study, we propose a particle-size-related calibration method to improve the measurement accuracy and a random-access strategy to suppress the sampling time. Based on the proposed methods, we study the long-term progress of cortical vasculopathy and abnormal blood flow caused by glioma, short-term variations of blood flow velocity under different anesthetic depths, and cortex-wide connectivity of the rapid fluctuation of blood flow velocities during seizure onset. The experimental results demonstrate that the proposed calibration method and the random-access strategy can improve both the qualitative and quantitative performance of velocimetry techniques and are also beneficial for understanding brain functions and diseases from the perspective of cerebral blood flow.

Phellintremulins A-C, antinociceptive sesquiterpenoids from the medicinal fungus Phellinus tremulae.

Phellintremulin A (1), a rearranged sesquiterpenoid with an unprecedented bicyclic backbone, and two previously unreported illudane-type sesquiterpenoids, namely phellintremulin B (2) and phellintremulin C (3), together with two known analogues (±)‒4 and (±)‒5, were isolated from cultures of the medicinal fungus Phellinus tremulae. Their structures and absolute configurations were established by means of spectroscopic data and HRESIMS analyses, as well as ECD and NMR calculations. A plausible biogenesis for 1 was discussed. The electrophysiological experiments showed that phellintremulins (A‒C) can inhibit Nav current in DRG neuron cells at 10 µM, with percentage inhibitions of 23.2%, 49.3%, and 31.7%, respectively. The antinociceptive activities of phellintremulins (A‒C) were evaluated via the acetic acid-induced writhing test in mice at a dose of 3 mg/kg. They showed significant antinociceptive effects with percentages of inhibition of 43.8%, 54.4%, and 50.6%, respectively, and phellintremulin B and C expressed more potent analgesic effect than lidocaine.

3M: Measuring Vital Signs With Markov-Gauss Model.

Measuring vital signs (VS) contained in the echoes is crucial to the analyses of breathing and heartbeat signals using medical radar. Although many advanced signal processing algorithms have been developed for radar-based VS measurement and make some improved progress, existing schemes cannot achieve a good estimation of echo phases modulated by the respiratory and cardiac activities with high accuracy or low computation, and thus resulting in serious performance degradation on the subsequent separation of breathing and heartbeat patterns as well as the assessment of breathing rate (BR), heart rate (HR), and heart rate variability (HRV). In this paper, we propose a simple yet effective method to measure VS for medical radar, named 3M method. Specifically, our method firstly introduces the Markov-Gauss model to obtain the recursive expression of the echo phases carrying VS, and secondly derive a simple observation equation (SOE) to reflect the relationship between the observed signal and VS of radar measurement. Thirdly, the aforementioned Markov-Gauss model and SOE are fused by Kalman filter to measure VS with accurate estimation. The 3M method demonstrates an elegant structure, low complexity and excellent features introduced by Kalman filter. Simulation results show the superiority of 3M over other methods. Then, we conduct extensive experiments with insightful visualizations to validate the effectiveness of the 3M method. Comparative results on different scenarios illustrate that the 3M method not only achieves state-of-the-art VS measurement performance but also expresses robust properties to HRV analysis.

CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages.

Background: CLEC4E has been reported to promote lung cancer progression. Tumor-associated macrophages (TAMs) play an important role in tumorigenesis. Whether the expression of CLEC4E in TAMs is associated with gastric carcinogenesis remains unclear. Methods: The TIMER, UALCAN, UCSC Xena, and KM plotter databases are used to examine the expression of CLEC4E and its prognostic significance in gastric cancer (GC). Additionally, GO, KEGG, and GSEA analysis were conducted, and single-cell RNA-seq (scRNA-seq) datasets were utilized. The Coremine medical database was used to predict therapeutic drugs, and molecular docking was performed. Human GC samples were obtained, and co-culture models were constructed to evaluate the effects of CLEC4E in TAMs on tumor growth, migration, and invasion in vitro. Results: CLEC4E was significantly upregulated in GC, and high CLEC4E expression was associated with poor prognosis. Western blotting and immunostaining showed increased protein levels of CLEC4E in GC. GO, KEGG, and GSEA results indicated that CLEC4E is involved in immune response. Immune infiltration analysis demonstrated that CLEC4E expression positively correlated with multiple immune cell types. scRNA-seq analyses revealed that CLEC4E was predominantly expressed in myeloid cells specifically TAMs, in GC. In vitro experiments confirmed that MFC induced CLEC4E expression in TAMs to mediate tumor progression. Specifically targeting CLEC4E by si-CLEC4E or stigmasterol inhibited cancer cell migration and invasion. Conclusion: CLEC4E is a potential prognostic biomarker and new therapeutic target for GC that can be specifically targeted by stigmasterol.

Comparison of postoperative survival between early-onset and late-onset adenocarcinoma of esophagogastric junction: a population-based study.

BACKGROUND AND AIM: The prognosis of early-onset adenocarcinoma of esophagogastric junction (AEG) remains unclear. This research aimed at comparing the prognosis between early-onset and late-onset AEGs. METHODS: We extracted eligible patients with surgically resected, pathologically confirmed, nonmetastatic AEG from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The cutoff age of early-onset AEG was set at ≤50 years old. Univariate and multivariate Cox analysis as well as competing risk model were adopted for comparing overall survival (OS) and cancer-specific survival (CSS) between early-onset and late-onset AEGs. In addition, multiple imputation and propensity score matching (PSM) were also carried out for sensitivity analysis. RESULTS: In total, 4610 eligible AEG patients were collected in this study, including 610 early-onset AEGs and 4000 late-onset AEGs. Kaplan-Meier curves revealed significantly better survival in early-onset AEGs than late-onset AEGs. After interpolating missing data by multiple imputation, multivariate Cox regression analysis similarly showed better OS and CSS in early-onset AEGs. By using PSM analysis at a ratio of 1:1, we matched 610 early-onset AEG patients with 610 late-onset AEG patients. After PSM, univariate Cox regression model still revealed favorable prognosis in early-onset AEGs. Similar results were confirmed by performing PSM analysis at a ratio of 1:2 and 1:3. In addition, competing risk model demonstrated significantly lower cancer-specific death in early-onset AEGs compared to late-onset AEGs before and after matching. CONCLUSION: By applying several effective sensitivity analyses, we reported significantly favorable OS and CSS in early-onset AEGs compared to late-onset AEGs.