UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis.

BACKGROUND: The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis. METHODS: Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1. RESULTS: UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis. CONCLUSIONS: UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.

UBXN9 inhibits the RNA exosome function to promote T cell control of liver tumorigenesis.

BACKGROUND AND AIMS: Liver tumorigenesis encompasses oncogenic activation and self-adaptation of various biological processes in premalignant hepatocytes to circumvent the pressure of cellular stress and host immune control. Ubiquitin regulatory X domain-containing proteins (UBXNs) participate in the regulation of certain signaling pathways. However, whether UBXN proteins function in the development of liver cancer remains unclear. APPROACH AND RESULTS: Here, we demonstrated that UBXN9 (Alveolar Soft Part Sarcoma Chromosomal Region Candidate Gene 1 Protein/Alveolar Soft Part Sarcoma Locus) expression was decreased in autochthonous oncogene-induced mouse liver tumors and ~47.7% of human HCCs, and associated with poor prognosis in patients with HCC. UBXN9 attenuated liver tumorigenesis induced by different oncogenic factors and tumor growth of transplanted liver tumor cells in immuno-competent mice. Mechanistically, UBXN9 significantly inhibited the function of the RNA exosome, resulting in increased expression of RLR-stimulatory RNAs and activation of the retinoic acid-inducible gene-I-IFN-Ι signaling in tumor cells, and hence potentiated T cell recruitment and immune control of tumor growth. Abrogation of the CD8 + T cell response or inhibition of tumor cell retinoic acid-inducible gene-I signaling efficiently counteracted the UBXN9-mediated suppression of liver tumor growth. CONCLUSIONS: Our results reveal a modality in which UBXN9 promotes the stimulatory RNA-induced retinoic acid-inducible gene-I-interferon signaling that induces anti-tumor T cell response in liver tumorigenesis. Targeted manipulation of the UBXN9-RNA exosome circuit may have the potential to reinstate the immune control of liver tumor growth.

APOE2 protects against Aß pathology by improving neuronal mitochondrial function through ERRα signaling.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease and apolipoprotein E (APOE) genotypes (APOE2, APOE3, and APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce the risk of developing AD, which may be attributed to the potential neuroprotective role of APOE2. However, the mechanisms underlying the protective effects of APOE2 is still unclear. METHODS: We analyzed single-nucleus RNA sequencing and bulk RNA sequencing data of APOE2 and APOE3 carriers from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort. We validated the findings in SH-SY5Y cells and AD model mice by evaluating mitochondrial functions and cognitive behaviors respectively. RESULTS: The pathway analysis of six major cell types revealed a strong association between APOE2 and cellular stress and energy metabolism, particularly in excitatory and inhibitory neurons, which was found to be more pronounced in the presence of beta-amyloid (Aß). Moreover, APOE2 overexpression alleviates Aß1-42-induced mitochondrial dysfunction and reduces the generation of reactive oxygen species in SH-SY5Y cells. These protective effects may be due to ApoE2 interacting with estrogen-related receptor alpha (ERRα). ERRα overexpression by plasmids or activation by agonist was also found to show similar mitochondrial protective effects in Aß1-42-stimulated SH-SY5Y cells. Additionally, ERRα agonist treatment improve the cognitive performance of Aß injected mice in both Y maze and novel object recognition tests. ERRα agonist treatment increased PSD95 expression in the cortex of agonist-treated-AD mice. CONCLUSIONS: APOE2 appears to enhance neural mitochondrial function via the activation of ERRα signaling, which may be the protective effect of APOE2 to treat AD.

A Population Study to Identify Candidates for Cytoreductive Nephrectomy in Patients with Metastatic Sarcomatoid Renal Cell Carcinoma from the Surveillance, Epidemiology, and End Results (SEER) Database.

BACKGROUND This population study aimed to identify suitable candidates for cytoreductive nephrectomy in patients with metastatic sarcomatoid renal cell carcinoma (RCC) from the US Surveillance, Epidemiology, and End Results (SEER) database. MATERIAL AND METHODS Demographic and clinical data from 1,229 patients with metastatic sarcomatoid RCC were retrieved from the SEER database. Patients were divided into the cytoreductive nephrectomy group (n=937) and the no surgery group (n=292). Multivariate Cox regression analysis identified factors associated with overall survival (OS) and propensity score matching identified factors that significantly impacted the OS. Survival of propensity score-matched subgroups of patients with metastatic sarcomatoid RCC treated by cytoreductive nephrectomy or no surgery was determined by the Kaplan-Meier method and compared by the log-rank test. RESULTS Of the 1,229 patients with metastatic sarcomatoid RCC retrieved from the SEER database, age, tumor size, T stage, and N stage were independent risk factors for patient survival. There were no significant differences in age, N stage, and tumor size between the cytoreductive nephrectomy-treated and non-surgically treated T stage cases following propensity score matching. OS benefits were found in cases with stage T1 (12 months increase), T2 (7.5 months increase), T3a (2 months increase), and T4 (3 months increase), but not in the T3b or T3c subgroups treated by cytoreductive nephrectomy, compared with patients with no surgical treatment. CONCLUSIONS Data from the SEER database showed that cytoreductive nephrectomy improved OS in patients with T1 and T2 metastatic sarcomatoid RCC with a significant long-term survival benefit of >6 months.

Perioperative risk factors and cumulative duration of "triple-low" state associated with worse 30-day mortality of cardiac valvular surgery.

ABSRACT: Hospital stay and mortality in high-risk patients after noncardiac surgery has been associated with a triple low anesthesia. However, the association between anesthesia-related factors and perioperative outcome after cardiac surgery remains unclear.We tested the effect of a novel triple low state: low mean arterial pressure (MAP) <65 mmHg and low bispectral index (BIS) <45 during a low target effect-site concentration (Ce) <1.5 µg ml-1 of propofol anesthesia on postoperative duration of hospitalization and 30-day mortality in cardiac valvular patients. In this prospective observational study, univariable and multivariable logistic regression analyses were used to determine whether perioperative factors, in particular, cumulative duration of triple low state were independently associated with duration of hospitalization and 30-day mortality among patients who underwent elective valvular replacement. 489 patients were included in the final analysis. After adjusting for related covariates, cumulative duration of the triple-low state was not associated with prolonged hospitalization (multivariable odds ratio: 1.007; 95 % confidence interval 0.997-1.017; P = 0.564), but was a significant predictor of 30-day mortality (multivariable odds ratio: 1.016; 95 % confidence interval 1.002-1.031; P = 0.030). Compared to a triple-low duration of <15 min, a duration >60 min increased the 30-day mortality rate by 8 times. After adjusting for patient- and procedure-related characteristics, the cumulative duration of a triple-low state (intraoperative low MAP, low BIS, and low Ce) was associated with poorer 30-day mortality, but not with prolonged duration of hospital stay.The mortality risk was even greater when a cumulative time >60 min.

Sufentanil attenuates impairment of the endothelium-dependent vasodilation induced by hypoxia-reoxygenation in the rat coronary artery.

Sufentanil has been used broadly in cardiac surgery, but the mechanisms by which it modulates coronary vascular tone after ischemia-reperfusion injury are largely unknown. Effects of sufentanil on coronary tone and on the relaxation of rat coronary arteries (CAs) in response to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxing agents in the presence of hypoxia-reoxygenation (H/R) was studied in an in vitro organ chamber setup. Sufentanil (10-7-10-4 mol/L) relaxed rat CA rings in endothelium-dependent and endothelium-independent manners. In endothelium-intact rings, preincubation of H/R-treated CAs with sufentanil (10-5 mol/L) significantly increased the acetylcholine response, but did not augment sodium nitroprusside-induced relaxation. Sufentanil-mediated potentiation of acetylcholine-induced relaxation was not affected by a nitric oxide synthase inhibitor or by intermediate- or small-conductance Ca2+-activated K+ channel blockers. However, potentiation was abolished by iberiotoxin (100 nmol/L), a selective inhibitor of large-conductance Ca2+-activated K+ channels, as well as Rp-cAMPS (30 µmol/L), a cyclic AMP-dependent protein kinase (PKA) inhibitor. Sufentanil induced endothelium-dependent and endothelium-independent relaxation and attenuated H/R-induced impairment of endothelium-dependent vasodilation in the rat CAs. The potentiating effect of sufentanil may involve activation of large-conductance Ca2+-activated K+ channels via cAMP-dependent mechanisms.

Long non-coding RNA LIP interacts with PARP-1 influencing the efficiency of base excision repair.

In recent years, various long non-coding RNAs (lncRNAs) involved in DNA damage response (DDR) have been identified and studied to deepen our understanding. However, there are rare reports on the association between lncRNAs and base excision repair (BER). Our designed DNA microarray identified dozens of functionally unknown lncRNAs, and their transcription levels significantly increased upon exposure to DNA damage inducers. One of them, named LIP (Long noncoding RNA Interacts with PARP-1), exhibited a significant alteration in transcription in response to methyl methanesulfonate (MMS) and temozolomide (TMZ) treatments. LIP knockdown or knockout cell lines are sensitive to MMS and TMZ, indicating that LIP plays a crucial role in DDR. The loss or insufficiency of LIP significantly influences the efficiency of BER in human cells, and it suggests that LIP participates in the BER pathway. The interaction between LIP and a key factor in BER, poly (ADP-ribose) polymerase 1 (PARP-1), has been confirmed. We identified and characterized LIP, a lncRNA, which is involved in DDR, significantly influences BER efficiency, and interacts with the BER key factor PARP-1. This advances our understanding of the connection between lncRNAs and BER, presenting the potential for the discovery of new drug targets.

Development and evaluation of a disulfidoptosis-related lncRNA index for prognostication in clear cell renal cell carcinoma.

Background: This study introduces a novel prognostic tool, the Disulfidoptosis-Related lncRNA Index (DRLI), integrating the molecular signatures of disulfidoptosis and long non-coding RNAs (lncRNAs) with the cellular heterogeneity of the tumor microenvironment, to predict clinical outcomes in patients with clear cell renal cell carcinoma (ccRCC). Methods: We analyzed 530 tumor and 72 normal samples from The Cancer Genome Atlas (TCGA), employing k-means clustering based on disulfidoptosis-associated gene expression to stratify ccRCC samples into prognostic groups. lncRNAs correlated with disulfidoptosis were identified and used to construct the DRLI, which was validated by Kaplan-Meier and receiver operating characteristic curves. We utilized single-cell deconvolution analysis to estimate the proportion of immune cell types within the tumor microenvironment, while the ESTIMATE and TIDE algorithms were employed to assess immune infiltration and potential response to immunotherapy. Results: The Disulfidoptosis-Related lncRNA Index (DRLI) effectively stratified ccRCC patients into high and low-risk groups, significantly impacting survival outcomes (P < 0.001). High-risk patients, marked by a unique lncRNA profile associated with disulfidoptosis, faced worse prognoses. Single-cell analysis revealed marked tumor microenvironment heterogeneity, especially in immune cell makeup, correlating with patient risk levels. In prognostic predictions, DRLI outperformed traditional clinical indicators, achieving AUC values of 0.779, 0.757, and 0.779 for 1-year, 3-year, and 5-year survival in the training set, and 0.746, 0.734, and 0.750 in the validation set. Notably, while the constructed nomogram showed exceptional predictive capability for short-term prognosis (AUC = 0.877), the DRLI displayed remarkable long-term predictive accuracy, with its AUC value reaching 0.823 for 10-year survival, closely approaching the nomogram's performance. Conclusions: The study introduces the DRLI as a groundbreaking molecular stratification tool for ccRCC, enhancing prognostic precision and potentially guiding personalized treatment strategies. This advancement is particularly significant in the context of long-term survival predictions. Our findings also elucidate the complex interplay between disulfidoptosis, lncRNAs, and the immune microenvironment in ccRCC, offering a comprehensive perspective on its pathogenesis and progression. The DRLI and the nomogram together represent significant strides in ccRCC research, highlighting the importance of molecular-based assessments in predicting patient outcomes.

A biocompatible pea protein isolate-derived bioink for 3D bioprinting and tissue engineering.

Three-dimensional bioprinting is a potent biofabrication technique in tissue engineering but is limited by inadequate bioink availability. Plant-derived proteins are increasingly recognized as highly promising yet underutilized materials for biomedical product development and hold potential for use in bioink formulations. Herein, we report the development of a biocompatible plant protein bioink from pea protein isolate. Through pH shifting, ethanol precipitation, and lyophilization, the pea protein isolate (PPI) transformed from an insoluble to a soluble form. Next, it was modified with glycidyl methacrylate to obtain methacrylate-modified PPI (PPIGMA), which is photocurable and was used as the precursor of bioink. The mechanical and microstructural studies of the hydrogel containing 16% PPIGMA revealed a suitable compress modulus and a porous network with a pore size over 100 µm, which can facilitate nutrient and waste transportation. The PPIGMA bioink exhibited good 3D bioprinting performance in creating complex patterns and good biocompatibility as plenty of viable cells were observed in the printed samples after 3 days of incubation in the cell culture medium. No immunogenicity of the PPIGMA bioink was identified as no inflammation was observed for 4 weeks after implantation in Sprague Dawley rats. Compared with methacrylate-modified gelatin, the PPIGMA bioink significantly enhanced cartilage regeneration in vitro and in vivo, suggesting that it can be used in tissue engineering applications. In summary, the PPIGMA bioink can be potentially used for tissue engineering applications.

Terminally differentiated cytotoxic CD4+ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

BACKGROUND: Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context. MAIN TEXT: Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4+ T cells (CD4+ CTLs), was marked with high expression of cytotoxicity-related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in-depth pseudotime analysis, which simulates the development of CD4+ T cells, we observed that the CD4+ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine-type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time-dependent infiltration of CD4+ T cells, an increase of MHCII+ cells, and the existence of CD4+ CTLs in lesions, along with an elevation of apoptotic-related proteins. Finally, and most crucially, single-cell T-cell receptor sequencing (scTCR-seq) analysis at the patient level determined a large clonal expansion of CD4+ CTLs in lesion tissues of RIBI. Transcriptional factor-encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4+ T cells, suggesting their potential to distinguish RIBI-related CD4+ CTLs from other subsets. CONCLUSION: The present study enriches the understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4+ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.

An Artificial MnWO4 Cathode Electrolyte Interphase Enabling Enhanced Electrochemical Performance of δ-MnO2 Cathode for Aqueous Zinc Ion Battery.

The dissolution of active material in aqueous batteries can lead to a rapid deterioration in capacity, and the presence of free water can also accelerate the dissolution and trigger some side reactions that affect the service life of aqueous batteries. In this study, a MnWO4 cathode electrolyte interphase (CEI) layer is constructed on a δ-MnO2 cathode by cyclic voltammetry, which is effective in inhibiting the dissolution of Mn and improving the reaction kinetics. As a result, the CEI layer enables the δ-MnO2 cathode to produce a better cycling performance, with the capacity maintained at 98.2% (vs. activated capacity at 500 cycles) after 2000 cycles at 10 A g-1. In comparison, the capacity retention rate is merely 33.4% for pristine samples in the same state, indicating that this MnWO4 CEI layer constructed by using a simple and general electrochemical method can promote the development of MnO2 cathodes for aqueous zinc ion batteries.

Enhanced H+ Storage of a MnO2 Cathode via a MnO2 Nanolayer Interphase Transformed from Manganese Phosphate.

The MnO2 cathode has attracted extensive attention in aqueous zinc ion battery research due to its environmental benignity, low cost, and high capacity. However, sluggish kinetics of hydrated zinc ion and manganese dissolution lead to insufficient rate and cycle performances. In this study, a manganese phosphate nanolayer synthesized in situ on a MnO2 cathode can be transformed into a δ-MnO2 nanolayer interphase after activation upon cycling, endowing the interphase with abundant interlayer water. As a result, the δ-MnO2 nanolayer interphase with the function of H+ topochemistry significantly enhances H+ (de)insertion in the MnO2 cathode, which leads to a kinetics conversion from Zn2+-dominated (de)insertion to H+-dominated (de)insertion, thus endowing the MnO2 cathode with superior rate and cycle performances (85.9% capacity retention after 1000 cycles at 10 A g-1). This strategy can be highly scalable for other manganese-based cathodes and provides an insight for developing high-performance aqueous zinc ion batteries.

Tanshinone IIA Facilitates Efficient Cartilage Regeneration under Inflammatory Factors Caused Stress via Upregulating LncRNA NEAT1_2.

(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1ß suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1ß and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.

The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer.

Epigenetic modifications are essential mechanism by which to ensure cell homeostasis. One such modification is lysine methylation of nonhistone proteins by SETD7, a mono-methyltransferase containing SET domains. SETD7 methylates over 30 proteins and is thus involved in various classical pathways. As such, SETD7 has been implicated in both the basic functions of normal tissues but also in several pathologies, such as cancers. In this review, we summarize the current knowledge of SETD7 substrates, especially transcriptional-related proteins and enzymes, and their putative roles upon SETD7-mediated methylation. We focus on the role of SETD7 in cancers, and speculate on the possible points of intervention and areas for future research.

Copper-doped zeolitic imidazolate frameworks-8/hydroxyapatite composite coating endows magnesium alloy with excellent corrosion resistance, antibacterial ability and biocompatibility.

Magnesium (Mg) and its alloys exhibit an excellent prospect for orthopedic clinical application due to their outstanding biodegradability and mechanical adaptability. However, the rapid corrosion rate/latent device-associated infections may lead to a failed internal fixation of Mg-based implants. Herein, a novel composite coating consisted of outer copper-doped zeolitic imidazolate frameworks-8 and inner hydroxyapatite (Cu@ZIF-8/HA) was in situ constructed on AZ31B Mg alloy via a two-step approach of hydrothermal treatment and seeded solvothermal method. The results verified that the electrochemical impedance of the obtained Cu45@ZIF-8/HA composite coating increased by two orders of magnitude to 6.6013 × 104 Ω·cm2 compared to that of bare Mg alloy. This was attributed to the reduced particle size of ZIF-8 nanoparticles due to the doped copper ions, which could be effectively grown in situ on the micro-nano flower-like structure of the HA-coated Mg alloy. Meanwhile, the Cu@ZIF-8/HA coating exhibited excellent antibacterial properties due to the release of copper ions and zinc ions from Cu@ZIF-8 dissolved in bacterial culture solution. The ICP results unraveled that the released concentration of copper and zinc ions could enhance the activity of alkaline phosphatase in the appropriate range during MC3T3-E1 cell culture in vitro for 7 days. This research revealed that the preparation of multifunctional metal-organic frameworks coating doped with antimicrobial metal ions via the seed layer solvothermal method was significant for studying the antimicrobial properties, osteogenic performance and corrosion resistance of Mg-based bioactive coatings.

Boosted H+ Intercalation Enables Ultrahigh Rate Performance of the δ-MnO2 Cathode for Aqueous Zinc Batteries.

H+ intercalation, as a critical battery chemistry, enables electrodes' high rate performance due to the fast diffusion kinetics of H+. In this work, more water molecules are introduced into δ-MnO2 by the protonation of δ-MnO2 with abundant oxygen vacancies. Benefiting from the structure with a close arrangement of water molecules in interlayers, the Grotthuss transport of proton is achieved in the energy storage of the δ-MnO2 cathode. As a result, the δ-MnO2 cathode exhibits an ultrahigh rate performance with a capacity of 368.1 mAh g-1 at 0.5 A g-1 and 83.4 mAh g-1 at 50 A g-1, which has a capacity retention of 73% after 1100 cycles at 10 A g-1. The study of the storage mechanism reveals that the Grotthuss intercalation of proton predominates the storage process, which empowers the cathode with high rate performance.

Comparative Analyses of Rhizosphere Bacteria Along an Elevational Gradient of Thuja sutchuenensis.

Thuja sutchuenensis Franch. is an endangered species in southwestern China, primarily distributed in 800-2,100 m of inaccessible mountainous areas. Rhizosphere soil physicochemical properties and bacterial communities play an essential role in managing plant growth and survival. Nonetheless, the study investigating rhizosphere soil properties and bacterial communities of T. sutchuenensis is limited. The present study investigated soil properties, including soil pH, organic matter, water content, nitrogen, phosphorus, and potassium contents, and bacterial communities in nearly all extant T. sutchuenensis populations at five elevational gradients. Our results demonstrated that the increase in elevation decreased rhizosphere and bulk soil phosphorus content but increased potassium content. In addition, the elevational gradient was the dominant driver for the community composition differentiation of soil bacterial community. Proteobacteria and Acidobacteria were the dominant bacterial phyla distributed in the rhizosphere and bulk soils. Co-occurrence network analysis identified key genera, including Bradyrhizobium, Acidicapsa, Catenulispora, and Singulisphaera, that displayed densely connected interactions with many genera in the rhizosphere soil. The dominant KEGG functional pathways of the rhizosphere bacteria included ABC transporters, butanoate metabolism, and methane metabolism. Further correlation analysis found that soil phosphorus and potassium were the dominant drivers for the diversity of soil bacteria, which were distinctively contributed to the phylum of Planctomycetes and the genera of Blastopirellula, Planctomycetes, and Singulisphaera. Collectively, this comprehensive study generated multi-dimensional perspectives for understanding the soil bacterial community structures of T. sutchuenensis, and provided valuable findings for species conservation at large-scale views.

Contrasting Responses of Rhizosphere Fungi of Scutellaria tsinyunensis, an Endangered Plant in Southwestern China.

Scutellaria tsinyunensis is an endangered species in southwest China, distributed sporadically in mountainous areas at an elevation of approximately 200 to 900 m. Rhizosphere soil properties and fungal communities play critical roles in plant survival and expansion. Nevertheless, understanding of soil properties and fungal communities in the S. tsinyunensis distribution areas is extremely limited. The present study examined soil properties and fungal communities in nearly all extant S. tsinyunensis populations at two altitudinal gradients (low and high groups). Our findings indicated that soil characteristics (i.e., soil pH, water content, and available phosphorus) were affected distinctively by altitudes (P < 0.05). In addition, the low altitude group harbored higher fungal richness and diversity than the high altitude. Co-occurrence network analysis identified six key genera that proved densely connected interactions with many genera. Further analysis represented that the low altitude group harbored three beneficial genera belonging to Ascomycota (Archaeorhizomyces, Dactylella, and Helotiales), whereas the high altitude showed more pathogenic fungi (Apiosporaceae, Colletotrichum, and Fusarium). Correlation analysis found that soil water content was highly correlated with Hydnodontaceae and Lophiostoma. Besides, plants' canopy density was negatively correlated with four pathogenic fungi, indicating that the high abundance of the pathogen at high altitudes probably inhibited the survival of S. tsinyunensis. To sum up, this comprehensive analysis generates novel insights to explore the contrasting responses of S. tsinyunensis rhizosphere fungal communities and provides profound references for S. tsinyunensis habitat restoration and species conservation. IMPORTANCE Our study highlighted the importance of rhizosphere fungal communities in an endangered plant, S. tsinyunensis. Comparative analysis of soil samples in nearly all extant S. tsinyunensis populations identified that soil properties, especially soil water content, might play essential roles in the survival and expansion of S. tsinyunensis. Our findings proved that a series of fungal communities (e.g., Archaeorhizomyces, Dactylella, and Helotiales) could be essential indicators for S. tsinyunensis habitat restoration and protection for the first time. In addition, further functional and correlation analyses revealed that pathogenic fungi might limit the plant expansion into high altitudes. Collectively, our findings displayed a holistic picture of the rhizosphere microbiome and environmental factors associated with S. tsinyunensis.

Sarcomatoid-associated gene risk index for clear cell renal cell carcinoma.

Sarcomatoid renal cell carcinoma is a de-differentiated form of kidney cancer with an extremely poor prognosis. Genes associated with sarcomatoid differentiation may be closely related to the prognosis of renal cell carcinoma. The prognosis of renal cell carcinoma itself is extremely variable, and a new prognostic model is needed to stratify patients and guide treatment. Data on clear cell renal cell carcinoma with or without sarcomatoid differentiation were obtained from TCGA database, and a sarcomatoid-associated gene risk index (SAGRI) and column line graphs were constructed using sarcomatoid-associated genes. The predictive power of the SAGRI and column line graphs was validated using an internal validation set and an independent validation set (E-MTAB-1980). The SAGRI was constructed using four sarcoma-like differentiation-related genes, COL7A1, LCTL, NPR3, ZFHX4, and had a 1-year AUC value of 0.725 in the training set, 0.712 in the internal validation set, and 0.770 in the independent validation set for TCGA training cohort, with high model reliability. The molecular characteristics among the SAGRI subgroups were analyzed by multiple methods, and results suggested that the SAGRI-HIGH subgroup may benefit more from immunotherapy to improve prognosis. SAGRI satisfactorily predicted the prognosis of patients with clear cell renal cell carcinoma with or without sarcomatoid differentiation.

Contrasting Responses of Multispatial Soil Fungal Communities of Thuja sutchuenensis Franch., an Extremely Endangered Conifer in Southwestern China.

Thuja sutchuenensis Franch. is an endangered species in southwest China, distributed sporadically in mountainous areas. Soil property and soil fungal community play a crucial role in plant growth and survival. Nevertheless, understanding soil properties and the soil fungal community in the areas where T. sutchuenensis is distributed is extremely limited. Hence, this study collected a total of 180 soil samples from five altitudinal distribution areas (altitudinal gradients) and three vertical depths throughout four horizontal distances from the base of each tree. The results found that altitudinal gradients and vertical depths altered soil properties, including pH, organic matter content, water content, total nitrogen, phosphorus, and potassium, and available nitrogen, phosphorus, and potassium. The fungal alpha diversity indexes (Chao1 and Shannon) and beta diversity were dramatically decreased with elevation. In addition, high altitudes (2,119 m) harbored the highest relative abundance of ectomycorrhizal fungi (27.57%) and the lowest relative abundance of plant-pathogenic fungi (1.81%). Meanwhile, we identified a series of fungal communities, such as Tomentella, Piloderma, Cortinarius, Sebacina, and Boletaceae, that play an essential role in the survival of T. sutchuenensis. The correlation analysis and random forest model identified that water content and total phosphorus showed strong relationships with fungal characteristics and were the primary variables for Zygomycota and Rozellomycota. Collectively, the findings of this integrated analysis provide profound insights into understanding the contrasting responses of T. sutchuenensis soil fungal communities and provide a theoretical basis for T. sutchuenensis habitat restoration and species conservation from multispatial perspectives. IMPORTANCE The present study highlights the importance of fungal communities in an endangered plant, T. sutchuenensis. Comparative analysis of soil samples in nearly all extant T. sutchuenensis populations identified that soil properties, especially soil nutrients, might play critical roles in the survival of T. sutchuenensis. Our findings prove that a series of fungal communities (e.g., Tomentella, Piloderma, and Cortinarius) could be key indicators for T. sutchuenensis survival. In addition, this is the first time that large-scale soil property and fungal community investigations have been carried out in southwest China, offering important values for exploring the distribution pattern of regional soil microorganisms. Collectively, our findings display a holistic picture of soil microbiome and environmental factors associated with T. sutchuenensis.