Comprehensive analysis of PHF5A as a potential prognostic biomarker and therapeutic target across cancers and in hepatocellular carcinoma.

OBJECTIVE: Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment. METHODS: This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC). RESULTS: PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group. CONCLUSIONS: This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets.

A Lycium barbarum extract inhibits ß-amyloid toxicity by activating the antioxidant system and mtUPR in a Caenorhabditis elegans model of Alzheimer's disease.

Lycium barbarum, a traditional Chinese medicine, has been shown to have antioxidant properties and has a protective effect in many diseases related to oxidative stress, such as neurodegenerative diseases, cardiovascular diseases, and cancer. Although the neuroprotective effects of L. barbarum extract (LBE) have been reported in several studies, the underlying molecular mechanisms are still unclear. In this study, the transgenic Caenorhabditis elegans strain CL2006 was used to investigate the function and molecular mechanism of an LBE in Alzheimer's disease (AD). LBE had high antioxidant potential and effectively delayed Aß-induced paralysis in the CL2006 strain. LBE inhibited the production of excessive reactive oxygen species by inducing the SKN-1-mediated antioxidant system, thereby inhibiting the generation of Aß and inhibiting mitochondrial damage. Importantly, LBE reduced Aß levels by inducing FSHR-1-mediated activation of the mtUPR. Therefore, our study not only reveals a new mechanism of LBE in the treatment of AD but also identifies a novel strategy for the treatment of AD by enhancing the mtUPR.

Effect of ß-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy.

Background and Objectives: A prognosis for kids with pediatric dilated cardiomyopathy (PDCM) is urgently needed to identify high-risk patients. This study aimed to determine the association of levels and soluble suppression of tumorigenicity 2 (sST2) and medical therapy of ß-blocker inhibitors with the risk of adverse events in PDCM. Materials and Methods: A total of 124 patients with PDCM were enrolled after admission from 2 centers in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). Based on a median sST2 level and the usage of ß-blocker inhibitors, patients were divided into four groups. The Cox proportional hazard model was used to assess the risk of incident adverse events. Results: The median level of sST2 was 23.77 ng/mL, and 53 (42.7%) patients received ß-blocker treatment. Over a median follow-up of 678 days, 37 (29.8%) adverse events occurred. Compared with patients with sST2 < median and without ß-blocker, patients with sST2 ≥ median and without ß-blocker (HR: 7.01; 95% CI: 1.21−40.45), followed by those with sST2 ≥ median and use of ß-blocker had the highest risk of adverse events (hazard ratio (HR): 5.51; 95% confidence interval (CI): 1.17−25.84). However, a significant association was not observed in patients with sST2 < median and use of ß-blocker. These associations were consistent across different subgroups. Conclusions: A higher level of sST2 was associated with a higher risk of adverse events in patients with PDCM, and ß-blocker treatment for children with high levels of sST2 can effectively avoid adverse events.

An extract of Lycium barbarum mimics exercise to improve muscle endurance through increasing type IIa oxidative muscle fibers by activating ERRγ.

Lycium barbarum berry (gouqi, Goji, goji berry, or wolfberry), a traditional medicine and functional food, has a wide range of biological effects, including immuno-modulation, anti-aging, antitumor, neuro-protection, and hepato-protection. However, thus far, little is known about the traditional effects of L. barbarum on strengthening muscles. Therefore, this study focused on the effects of an extract of L. barbarum on skeletal muscles. First, the extract of L. barbarum significantly increased the mass of the tibial anterior muscle and gastrocnemius muscle and improved the average running distance of mice. Then, in vivo and in vitro experiments showed that the extract enhanced muscle endurance by increasing the proportion of type IIa oxidative muscle fibers and aerobic respiration. In an in-depth study of the molecular mechanism of these effects, we found that the extract upregulated the proportion of type IIa oxidative muscle fibers by activating ERRγ and that the PKA-CREB signaling pathway was involved in its activation. This study is the first to show that L. barbarum extract modulates skeletal muscle remodeling and has mimetic effects on skeletal muscles in a manner similar to exercise. It provides a scientific explanation based on modern biological technologies and concepts for the traditional function of L. barbarum in improving muscle fitness. This study lays a theoretical foundation for the application of L. barbarum in skeletal muscles as an exercise mimetic.

Long-term outcomes of percutaneous closure of patent ductus arteriosus associated with unilateral absence of a pulmonary artery.

OBJECTIVE: This study aimed to evaluate the long-term outcomes of patients with patent ductus arteriosus (PDA) associated with unilateral absence of a pulmonary artery (UAPA). METHODS: Patients diagnosed with PDA associated with UAPA between January 2005 and June 2019 were retrospectively enrolled in this study. Demographic and clinical characteristics, treatments, and follow-up information were evaluated. RESULTS: A total of 11 patients were diagnosed with PDA associated with UAPA. Percutaneous closure was successfully conducted in nine patients. The mean diameters of the PDA measured by aortogram and occluders were 5.3 ± 1.8 mm and 11.5 ± 3.9 mm, respectively. The median pulmonary systemic flow ratio (Qp:Qs) in five patients was 1.41, and the median total lung resistance was 12 Wood Units. The mean systolic pulmonary artery (PA) pressure was 68.3 ± 19.1 mmHg. In five patients with pre- and postprocedure catheter data, the systolic pulmonary arterial pressure decreased significantly after closure (from 77.0 ± 20.2 to 58.8 ± 17.5 mmHg; p = .024), as did the mean pulmonary arterial pressure (from 58.2 ± 14.6 to 39.0 ± 14.1 mmHg; p = .18). The PA pressure and heart size gradually decreased to normal levels in eight patients, and their quality of life was significantly improved. The ratio of lung to systemic circulation pressure was less than 0.75. CONCLUSIONS: In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve PA hypertension. A ratio of lung to systemic circulation pressure less than 0.75 may be an important reference index for predicting whether PA pressure can be reduced to a normal level after occlusion.

Plastome phylogenomic study of Gentianeae (Gentianaceae): widespread gene tree discordance and its association with evolutionary rate heterogeneity of plastid genes.

BACKGROUND: Plastome-scale data have been prevalent in reconstructing the plant Tree of Life. However, phylogenomic studies currently based on plastomes rely primarily on maximum likelihood inference of concatenated alignments of plastid genes, and thus phylogenetic discordance produced by individual plastid genes has generally been ignored. Moreover, structural and functional characteristics of plastomes indicate that plastid genes may not evolve as a single locus and are experiencing different evolutionary forces, yet the genetic characteristics of plastid genes within a lineage remain poorly studied. RESULTS: We sequenced and annotated 10 plastome sequences of Gentianeae. Phylogenomic analyses yielded robust relationships among genera within Gentianeae. We detected great variation of gene tree topologies and revealed that more than half of the genes, including one (atpB) of the three widely used plastid markers (rbcL, atpB and matK) in phylogenetic inference of Gentianeae, are likely contributing to phylogenetic ambiguity of Gentianeae. Estimation of nucleotide substitution rates showed extensive rate heterogeneity among different plastid genes and among different functional groups of genes. Comparative analysis suggested that the ribosomal protein (RPL and RPS) genes and the RNA polymerase (RPO) genes have higher substitution rates and genetic variations among plastid genes in Gentianeae. Our study revealed that just one (matK) of the three (matK, ndhB and rbcL) widely used markers show high phylogenetic informativeness (PI) value. Due to the high PI and lowest gene-tree discordance, rpoC2 is advocated as a promising plastid DNA barcode for taxonomic studies of Gentianeae. Furthermore, our analyses revealed a positive correlation of evolutionary rates with genetic variation of plastid genes, but a negative correlation with gene-tree discordance under purifying selection. CONCLUSIONS: Overall, our results demonstrate the heterogeneity of nucleotide substitution rates and genetic characteristics among plastid genes providing new insights into plastome evolution, while highlighting the necessity of considering gene-tree discordance into phylogenomic studies based on plastome-scale data.

Construction and validation of a prognostic and therapeutic cuproptosis- and immune-related gene signature in hepatocellular carcinoma.

Background: Abnormal accumulation of copper could induce cell death and tumor growth, and affect tumor immune escape by regulating programmed cell death ligand 1 (PD-L1) expression. This study aims to establish and verify a risk signature based on cuproptosis- and immune-related genes (CIRGs) for hepatocellular carcinoma (HCC) management. Methods: HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature's value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically. Results: A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model's risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors. Conclusions: The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.

A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study.

Background: Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method: This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results: Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion: Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Fenofibrate Recognition and Gq Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1.

The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-Gi complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-Gq complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.

Elevated MPP6 expression correlates with an unfavorable prognosis, angiogenesis and immune evasion in hepatocellular carcinoma.

Background: Membrane palmitoylated proteins (MPPs) are engaged in various biological processes, such as cell adhesion and cell polarity. Dysregulated MPP members have different effects on hepatocellular carcinoma (HCC) development. However, the role of MPP6 in HCC has been unknown. Method: HCC transcriptome and clinical data from different public databases were downloaded and analyzed, and the results were further validated by qRT-PCR, Western blotting and immunohistochemistry (IHC) using HCC cell lines and tissues. The association between MPP6 and prognosis, potential pathogenic mechanisms, angiogenesis, immune evasion, tumor mutation burden (TMB) and treatment response in HCC patients was analyzed by bioinformatics and IHC staining. Results: MPP6 was significantly overexpressed in HCC, and its expression was related to T stage, pathologic stage, histologic grade and adverse prognosis in HCC patients. Gene set enrichment analysis revealed that differentially expressed genes were mainly enriched in the synthesis of genetic materials and the WNT signaling pathway. GEPIA database analysis and IHC staining suggested that MPP6 expression had a positive correlation with angiogenesis. Single-cell dataset analysis indicated that MPP6 was associated with features of the tumor microenvironment. Additional analyses discovered that MPP6 expression was inversely related to immune cell infiltration and was involved in tumor immune evasion. MPP6 expression was positively associated with TMB, and patients with high TMB had an adverse prognosis. Immunotherapy was more effective in HCC patients with low MPP6 expression, whereas those with high MPP6 expression responded better to sorafenib, gemcitabine, 5-FU, and doxorubicin. Conclusions: Elevated MPP6 expression is associated with an unfavorable prognosis, angiogenesis and immune evasion in HCC. Moreover, MPP6 has the potential to be used to assess TMB and treatment response. Therefore, MPP6 might serve as a novel prognostic biomarker and therapeutic target for HCC.

Redox-stress response resistance (RRR) mediated by hyperoxidation of peroxiredoxin 2 in senescent cells.

Aging is closely related to redox regulation. In our previous work, we proposed a new concept, "redox-stress response capacity (RRC)," and found that the decline in RRC was a dynamic characteristic of aging. However, the mechanism of RRC decline during aging remains unknown. In this study, using the senescent human fibroblast cell model and Caenorhabditis elegans model, we identified that peroxiredoxin 2 (PRDX2), as a hydrogen peroxide (H2O2) sensor, was involved in mediating RRC. PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C. elegans also showed decreased RRC. The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells. Moreover, the level of PRDX2 hyperoxidation also increased in old C. elegans. Simultaneous overexpression of both PRDX2 and sulfiredoxin (SRX) rescued the reduced RRC and delayed senescence. The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity, resulting in the decreased cellular response to H2O2, which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity. Treatment of young cells with a high level of H2O2 to induce a higher level of PRDX2-SO3 resulted in mimicking the RRC decline in senescent cells, which is also similar to a model of insulin resistance induced by high levels of insulin. All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells, we named it redox-stress response resistance, RRR. RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.

LBP1C-2 from Lycium barbarum maintains skeletal muscle satellite cell pool by interaction with FGFR1.

Muscle stem cells, called satellite cells (SCs), are employed to repair and rebuild muscle. SC-based therapeutic strategies are urgently needed. In this study, we showed that Lycium barbarum extract (LBE) improved the number of SCs and enhanced muscle regeneration by promoting SC activation and self-renewal in both adult and aging mice. L. barbarum polysaccharide (LBP), the main component of LBE, also played a similar role. More importantly, LBP1C-2, a homogeneous polysaccharide isolated from LBP, was uncovered to be an active component in regulating SC function. Mechanism study revealed that LBP1C-2 might bind to FGFR1 to activate SCs and promote SC self-renewal through Spry1 upregulation. This might be the first study to show that LBE participated in the regulation of SCs, and the active components and targets of LBE were identified. This study lays a theoretical foundation for the medicinal or auxiliary medicinal use of L. barbarum in skeletal muscle.

Porous fiber materials can alleviate the risk of farmland drought and flooding disasters and prompt crop growth.

Floods and droughts on farmland seriously damage agricultural production. Porous fiber materials (PFM) made from mineral rocks have high porosity, permeability, and water retention and are utilized widely in green roofs and agricultural production. Therefore, studying the impact of PFM on the improvement of farmland is of great importance for soil and water conservation. We set 64 extreme rainfalls to analyze the impact of PFM on soil water content (SWC), runoff, nutrient loss, microorganism, and plant growth. The results showed that PFM can effectively reduce runoff and improve soil water distribution, and enhance the soil water holding capacity. Furthermore, PFM reduced the loss of nitrogen and phosphorus by 18.3% to 97% in the runoff, and the soil erosion of summer corn was more strongly influenced by lower vegetation cover, compared with winter wheat. Finally, when PFM was buried in the soil, the wheat yield increased by -6.7%-20.4%, but the corn yield in some PFM groups decreased by 5.1% to 42.5% under short-duration irrigation conditions. Our study emphasizes that the effectiveness of PFM depends mainly on the following: First, PFM with high porosity can increase soil water holding capacity and timely replenish the water lost from the surrounding soil. Second, PFM with high permeability can increase infiltration during rainfall and decrease runoff and nutrient loss, reducing the risk of farmland flooding and pollution. Finally, PFM consists of gold ions and alkali metal oxides, which can stabilize agglomerates and improve soil enzyme activity, thereby increasing the relative abundance of some microbial strains and promoting crop growth. However, when the rainfall amount was low or PFM volume was large, PFM could not store water sufficiently during rainfall, which seriously reduced the maximum saturated moisture content and water absorption performance. Meanwhile, the PFM could not release water in time and replenish the soil water deficit, which increased drought risk. In conclusion, the appropriate volume of PFM and irrigation system may enhance soil water storage capacity, minimize agricultural pollution, and promote crop production.

Naringenin improves muscle endurance via activation of the Sp1-ERRγ transcriptional axis.

Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy.

Identification of the redox-stress signaling threshold (RST): Increased RST helps to delay aging in C. elegans.

Reactive oxygen species (ROS) play a dual role since they can be either beneficial or harmful to living systems. With increasing ROS concentrations, the roles of ROS change from advantageous to detrimental. There seems to be a concentration threshold that determines the transition from their advantageous to detrimental effects. If we purposefully increase the threshold, that is, increase the range of ROS that plays an advantageous role, it should be beneficial for individuals. To test this hypothesis, in C. elegans, the effects of oxidative challenge induced by different concentrations of paraquat (PQ) on nematode lifespan were evaluated. We found that there is a maximum level below which redox stress has benefits and named this threshold as "Redox-stress Signaling Threshold (RST)". Furthermore, we found that starvation (or heat stress or exercise) stimuli at early stage in C. elegans could increase the RST, indicating that this value is not fixed and can be increased by the adaptive response. More intriguingly, we found that increasing RST could improve Redox-stress Response Capacity (RRC) and healthspan, suggesting that increasing the RST value through early stimulation will be an effective strategy to delay aging.

Oreocharis xieyongii, an unusual new species of Gesneriaceae from western Hunan, China.

A new species, Oreocharis xieyongii T. Deng, D.G. Zhang & H. Sun, from Hunan Province, central China, is described. The combination of purple zygomorphic corolla with longer adaxial lobes and exserted stamens defines the species and discriminates it from all other current Oreocharis species. Morphological traits of the new species were compared to those of two similar species, Oreocharis xiangguiensis and O. rubrostriata. Phylogenetic analysis indicates that the new species is nested within the Oreocharis. Although only half of Oreocharis species were included in our study, evolutionary character analysis indicates that the ancestral states of the genus are likely the purple corolla, longer abaxial lip and inserted stamens. The longer adaxial lip is perhaps an apomorphy and only present in O. xieyongii and O. rubrostriata. Both morphological and molecular evidence suggest that O. xieyongii is a taxon new to science.

ER reductive stress caused by Ero1α S-nitrosation accelerates senescence.

Oxidative stress in aging has attracted much attention; however, the role of reductive stress in aging remains largely unknown. Here, we report that the endoplasmic reticulum (ER) undergoes reductive stress during replicative senescence, as shown by specific glutathione and H2O2 fluorescent probes. We constructed an ER-specific reductive stress cell model by ER-specific catalase overexpression and observed accelerated senescent phenotypes accompanied by disrupted proteostasis and a compromised ER unfolded protein response (UPR). Mechanistically, S-nitrosation of the pivotal ER sulfhydryl oxidase Ero1α led to decreased activity, therefore resulting in reductive stress in the ER. Inhibition of inducible nitric oxide synthase decreased the level of Ero1α S-nitrosation and decreased cellular senescence. Moreover, the expression of constitutively active Ero1α restored an oxidizing state in the ER and successfully rescued the senescent phenotypes. Our results uncover a new mechanism of senescence promoted by ER reductive stress and provide proof-of-concept that maintaining the oxidizing power of the ER and organelle-specific precision redox regulation could be valuable future geroprotective strategies.

A data set of distributed global population and water withdrawal from 1960 to 2020.

Population and water withdrawal data sets are currently faced with difficulties in collecting, processing and verifying multi-source time series, and the spatial distribution characteristics of long series are also relatively lacking. Time series is the basic guarantee for the accuracy of data sets, and the production of long series spatial distribution is a realistic requirement to expand the application scope of data sets. Through the time-consuming and laborious basic processing work, this research focuses on the population and water intake time series, and interpolates and extends them to specific land uses to ensure the accuracy of the time series and the demand of spatially distributed data sets. This research provides a set of population density and water intensity products from 1960 to 2020 distributed to the administrative units or the corresponding regions. The data set fills the gaps in the multi-year data set for the accuracy of population density and the intensity of water withdrawal.

How do tree species characteristics affect the bacterial community structure of subtropical natural mixed forests?

The effects of tree species on bacterial community structure have attracted much attention, but few studies have been done in natural mixed forests. In this study, we selected 12 sampling sites in the subtropical natural mixed forest (mainly distributed by Chinese sweet gum, chestnut, Oriental oak, Masson pine, Chinese fir, etc.). The fermentation layer (OF) and humified layer (OH) were mixed as forest floor samples, and the topsoil samples (0-10 cm) were taken. Bacterial composition was studied by 16S rRNA gene sequencing. Coniferous canopy area ratio (Pc), broadleaved and shrubby canopy area ratio (Phwd), elevation, soil properties were tested. The objective is to reveal which soil properties are significantly affected by tree species characteristics, which soil properties significantly affect bacterial community structure, and whether the bacterial community structure is the same in forest floor and topsoil samples at the same sampling site. The results showed that: (1) Pc and Phwd could be used to represent tree species characteristics of natural mixed forests, and they significantly (P=0.05) affected the soil C/N ratio; (2) the soil C/N ratio was the main factor affecting the soil bacterial community composition, especially for the dominant heterotrophic bacteria (Acidothermus, Variibacter, Candidatus Solibacter, Acidibacter, and Bryobacter). The relative abundance (1.11-26.27%) of the dominant heterotrophic bacteria increases with an increase in the C/N ratio (6.33-10.76) within a certain range; (3) the dominant bacteria in topsoil samples were Nitrospira, Acidothermus, Arthrobacter, Bradyrhizobium, and Variibacter, while that in forest floor samples were Jatrophihabitans, Acidothermus, Burkholderia-Paraburkholderia, and Bradyrhizobium. Although the forest floor bacteria came from the topsoil at the same sampling site, the bacterial community structure had changed significantly. This study indicated that tree species drive the change of soil bacterial community by changing the soil C/N ratio, which may provide a new perspective for maintaining the stability of regional ecosystem structure.

Precision Redox: The Key for Antioxidant Pharmacology.

Significance: The redox balance of cells provides a stable microenvironment for biological macromolecules to perform their physiological functions. As redox imbalance is closely related to the occurrence and development of a variety of diseases, antioxidant therapies are an attractive option. However, redox-based therapeutic strategies have not yet shown satisfactory results. To find the key reason is of great significance. Recent Advances: We emphasize the precise nature of redox regulation and elucidate the importance and necessity of precision redox strategies from three aspects: differences in redox status, differences in redox function, and differences in the effects of redox therapy. We then propose the "5R" principle of precision redox in antioxidant pharmacology: "Right species, Right place, Right time, Right level, and Right target." Critical Issues: Redox status must be considered in the context of species, time, place, level, and target. The function of a biomacromolecule and its cellular signaling role are closely dependent on redox status. Accurate evaluation of redox status and specific interventions are critical for the success of redox treatments. Precision redox is the key for antioxidant pharmacology. The precise application of antioxidants as nutritional supplements is also key to the general health of the population. Future Directions: Future studies to develop more accurate methods for detecting redox status and accurately evaluating the redox state of different physiological and pathological processes are needed. Antioxidant pharmacology should consider the "5R" principle rather than continuing to apply global nonspecific antioxidant treatments. Antioxid. Redox Signal. 34, 1069-1082.