Global distribution pattern of soil phosphorus-cycling microbes under the influence of human activities.

Human activities have profoundly altered the Earth's phosphorus (P) cycling process and its associated microbial communities, yet their global distribution pattern and response to human influences remain unclear. Here, we estimated the abundances of P-cycling genes from 3321 global soil metagenomic samples and mapped the global distribution of five key P-cycling processes, that is, organic phosphoester hydrolysis, inorganic phosphorus solubilization, two-component system, phosphotransferase system, and transporters. Structural equation modeling and random forest analysis were employed to assess the impact of anthropogenic and environmental factors on the abundance of P-cycling genes. Our findings suggest that although less significant than the climate and soil profile, human-related factors, such as economic activities and population, are important drivers for the variations in P-cycling gene abundance. Notably, the gene abundances were increased parallel to the extent of human intervention, but generally at low and moderate levels of human activities. Furthermore, we identified critical genera, such as Pseudomonas and Lysobacter, which were sensitive to the changes in human activities. This study provides insights into the responses of P-cycling microbes to human activities at a global scale, enhancing our understanding of soil microbial P cycling and underscoring the importance of sustainable human activities in the Earth's biogeochemical cycle.

LanCL2 Implicates in Testicular Redox Homeostasis and Acrosomal Maturation.

Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity in Male Mice.

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, and these could be improved in mice with elevated hypothalamic antioxidant defense. We also show that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator, is implicated in regulating hypothalamic LanCL1 transcription, in collaboration with SP1 through a direct interaction, in response to HFD-induced palmitic acid (PA) accumulation. According to our results, when exposed to HFD, mice undergo a process of overwhelming hypothalamic antioxidant defense; short-time HFD exposure induces ROS production to activate PGC-1α and elevate LanCL1-mediated antioxidant defense, while long-time exposure promotes ubiquitin-mediated PGC-1α degradation and suppresses LanCL1 expression. Our findings show the critical importance of the hypothalamic PGC-1α-SP1-LanCL1 axis in regulating HFD-induced obesity, and provide new insights describing the correlations of hypothalamic inflammation and oxidative stress during this process.

Global biogeography and ecological implications of cobamide-producing prokaryotes.

Cobamides, a class of essential coenzymes synthesized only by a subset of prokaryotes, are model nutrients in microbial interaction studies and play significant roles in global ecosystems. Yet, their spatial patterns and functional roles remain poorly understood. Herein, we present an in-depth examination of cobamide-producing microorganisms, drawn from a comprehensive analysis of 2862 marine and 2979 soil metagenomic samples. A total of 1934 nonredundant metagenome-assembled genomes (MAGs) potentially capable of producing cobamides de novo were identified. The cobamide-producing MAGs are taxonomically diverse but habitat specific. They constituted only a fraction of all the recovered MAGs, with the majority of MAGs being potential cobamide users. By mapping the distribution of cobamide producers in marine and soil environments, distinct latitudinal gradients were observed: the marine environment showed peak abundance at the equator, whereas soil environments peaked at mid-latitudes. Importantly, significant and positive links between the abundance of cobamide producers and the diversity and functions of microbial communities were observed, as well as their promotional roles in essential biogeochemical cycles. These associations were more pronounced in marine samples than in soil samples, which suggests a heightened propensity for microorganisms to engage in cobamide sharing in fluid environments relative to the more spatially restricted soil environment. These findings shed light on the global patterns and potential ecological roles of cobamide-producing microorganisms in marine and soil ecosystems, enhancing our understanding of large-scale microbial interactions.

Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.

Evaluation of the Time Difference Method in Identifying Hepatocellular Carcinoma in Current CEUS LR-M Category Nodules.

OBJECTIVE: The aim of the work described here was to explore a potential method for improving the diagnostic detection of hepatocellular carcinoma (HCC) based on the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) Version 2017. METHODS: We retrospectively evaluated 585 liver nodules in 427 patients at risk for HCC from December 2020 to March 2023. The nodules were categorized as LR-1 to LR-M based on CEUS LI-RADS Version 2017 and were randomly subclassified into a developmental cohort (DC) and a validation cohort (VC) at 3:1. In the DC, the cutoff value of the time difference (∆T) for differentiating HCC from other malignancies by LR-M was calculated and used to reclassify nodules in the VC. The diagnostic effect on HCC detection before and after reclassification was further assessed. RESULTS: According to the current CEUS LI-RADS, 140 of 426 (32.9%) confirmed HCC nodules were misclassified as LR-M. In the DC (439 nodules), the receiver operating characteristic (ROC) curve revealed that the cutoff value of ∆T (wash-out onset time minus contrast arrival time) recommended for HCC diagnosis was greater than 21 s. In the VC (146 nodules), 34 HCCs were correctly categorized as LR-5 according to the cutoff value, and after reclassification, LR-5 had higher accuracy (67.1% vs. 89.0%, p < 0.001) and sensitivity (56.0% vs. 87.2%, p < 0.001) for HCC diagnosis with high specificity (100% vs. 94.6%, p = 0.500). CONCLUSION: Using the time difference method could identify HCC nodules misdiagnosed as LR-M and improve the diagnostic performance of current CEUS LI-RADS.

Prognostic value and model construction of preoperative inflammatory markers in patients with metastatic renal cell carcinoma.

BACKGROUND: Inflammation is considered to be one of the driving factors of cancer, and chronic inflammation plays a crucial role in tumor growth and metastasis. The aim of this study was to examine the predictive value of preoperative inflammatory biomarkers for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), including preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and aspartate aminotransferase-to-lymphocyte ratio (ALR), a novel inflammatory biomarker. METHOD: This study included 198 patients with mRCC from a single center from 2006 to 2022. The optimal cut-off levels for the three biomarkers were derived using the receiver operating characteristic curve (ROC). Cox univariate and multivariate analyses were used to assess independent prognostic inflammatory biomarkers. Finally, independent prognostic inflammatory biomarkers were incorporated into the prognostic model to establish a nomogram to predict the postoperative survival of patients with mRCC. RESULT: The area under the ROC curve for NLR, LMR, and ALR, respectively, is 0.71 (CI: 0.635-0.784), 0.68 (CI: 0.604-0.755), and 0.75 (CI: 0.680-0.819). The optimal LMR, NLR, and ALR cut-off levels as evaluated by the ROC curve were 3.836, 3.106, and 68.056, respectively. Patients with NLR and ALR higher than the cut-off level and LMR lower than the cut-off level had a significant relationship with OS. Multivariate analysis revealed that tumor necrosis, lower LMR, and higher ALR were independent risk factors for OS. In addition, a nomogram that includes independent prognostic inflammatory biomarkers can accurately predict the OS in patients with mRCC. CONCLUSION: ALR and LMR are independent risk factors for the prognosis of individuals with mRCC. By monitoring ALR and LMR postoperatively, the prognosis of patients with mRCC can be better evaluated.

Metagenomic Evidence for Cobamide Producers Driving Prokaryotic Co-occurrence Associations and Potential Function in Wastewater Treatment Plants.

Cobamides are required by most organisms but are only produced by specific prokaryotic taxa. These commonly shared cofactors play significant roles in shaping the microbial community and ecosystem function. Wastewater treatment plants (WWTPs) are the world's most common biotechnological systems; knowledge about sharing of cobamides among microorganisms is predicted to be important to decipher the complex microbial relationships in these systems. Herein, we explored prokaryotic potential cobamide producers in global WWTP systems based on metagenomic analyses. A set of 8253 metagenome-assembled genomes (MAGs) were recovered and 1276 (15.5%) of them were identified as cobamide producers, which could potentially be used for the practical biological manipulation of WWTP systems. Moreover, 8090 of the total recovered MAGs (98.0%) contained at least one enzyme family dependent on cobamides, indicating the sharing of cobamides among microbial members in WWTP systems. Importantly, our results showed that the relative abundance and number of cobamide producers improved the complexity of microbial co-occurrence networks and most nitrogen, sulfur, and phosphorus cycling gene abundances, indicating the significance of cobamides in microbial ecology and their potential function in WWTP systems. These findings enhance the knowledge of cobamide producers and their functions in WWTP systems, which has important implications for improving the efficiency of microbial wastewater treatment processes.

Nano-Nd2O3 reduced soil bacterial community function by altering the relative abundance of rare and sensitive taxa.

Nanoparticulate-Nd2O3 (nano-Nd2O3) has been excessively utilized in agriculture, industry, and medicine. Hence, nano-Nd2O3 can have environmental implications. However, the impact of nano-Nd2O3 on alpha diversity, composition, and function of soil bacterial communities has not been thoroughly evaluated. We amended soil to achieve different concentrations of nano-Nd2O3 (0, 10, 50, and 100 mg kg-1 soil) and incubated the mesocosms for 60 days. On days 7 and 60 of the experiment, we measured the effect of nano-Nd2O3 on alpha diversity and composition of soil bacterial community. Further, the effect of nano-Nd2O3 on the function of soil bacterial community was assessed based on changes in the activities of the six potential enzymes that mediate the cycling of nutrients in the soil. Nano-Nd2O3 did not alter the alpha diversity and composition of the soil bacterial community; however, it negatively affected community function in a dose-dependent manner. Specifically, the activities of ß-1,4-glucosidase and ß-1,4-n-acetylglucosaminidase that mediate soil carbon and nitrogen cycling, respectively, were significantly affected on days 7 and 60 of the exposure. The effect of nano-Nd2O3 on the soil enzymes correlated with changes in relative abundances of the rare and sensitive taxa, viz., Isosphaerales, Isosphaeraceae, Ktedonobacteraceae, and Streptomyces. Overall, we provide information for the safe implementation of technological applications that use nano-Nd2O3.