Mycorrhizal Symbiosis Increases Plant Phylogenetic Diversity and Regulates Community Assembly in Grasslands.

The intricate mechanisms controlling plant diversity and community composition are cornerstone of ecological understanding. Yet, the role of mycorrhizal symbiosis in influencing community composition has often been underestimated. Here, we use extensive species survey data from 1315 grassland sites in China to elucidate the influence of mycorrhizal symbiosis on plant phylogenetic diversity and community assembly. We show that increasing mycorrhizal symbiotic potential leads to greater phylogenetic dispersion within plant communities. Mycorrhizal species predominantly influence deterministic processes, suggesting a role in niche-based community assembly. Conversely, non-mycorrhizal species exert a stronger influence on stochastic processes, highlighting the importance of random events in shaping community structure. These results underscore the crucial but often hidden role of mycorrhizal symbiosis in driving plant community diversity and assembly. This study provides valuable insights into the mechanisms shaping ecological communities and the way for more informed conservation that acknowledges the complex interplay between symbiosis and community dynamics.

Spatial Metabolomics Profiling Reveals Curcumin Induces Metabolic Reprogramming in Three-Dimensional Tumor Spheroids.

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma.

BACKGROUND: The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine- and arginine-rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. METHODS: To identify the key genes associated with immunotherapy resistance, we conducted single-nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co-culture systems, flow cytometry, various tumor-bearing mouse models, and patient-derived organotypic tumor spheroids. RESULTS: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8+ T cell activity. Mechanistically, SRSF10 interacted with the 3'-untranslated region of MYB, enhancing MYB RNA stability, and subsequently upregulating key glycolysis-related enzymes including glucose transporter 1 (GLUT1), hexokinase 1 (HK1), lactate dehydrogenase A (LDHA), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro-tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8+ T cells and the proportion of interferon-γ+CD8+ T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) in both murine and human preclinical models. CONCLUSIONS: The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti-PD-1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti-PD-1 tolerance in HCC.

Association of high fibrinogen to albumin ratio with long-term mortality in patients with spontaneous intracerebral hemorrhage.

Background: The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients. Methods: Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long-term mortality. Results: Out of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31-1.99), 1-year mortality (HR 1.45, 95% CI 1.25-1.67), and long-term mortality (HR 1.45, 95% CI 1.28-1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15-1.88) even after excluding patients with 1-year mortality. Conclusion: A high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation.

A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and ß-globin chains and consequently cause clinical symptoms of ß-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with ß thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous ß0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of ß-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.

Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

Carrier rate of thalassemia among 25,910 high school students in Shaoguan area, China.

OBJECTIVES: As one of the most common hereditary diseases, thalassemia affects a large number of people in China. The aim of this study was to investigate the feasibility of a method based on next-generation sequencing (NGS) for screening of thalassemia carriers among high school students in the Shaoguan area. MATERIALS AND METHODS: The NGS-based method was performed using 25,910 high school students recruited from 38 schools. The screening yield was systematically analyzed. Before screening, a lecture on how the disease is inherited, the symptoms of thalassemia, and how to prevent it was given to 28,780 students. RESULTS: Implying successful delivery of information on the disease, 90.03% (25,910 of 28,780) of the students agreed to join this program for thalassemia screening. A thalassemia carrier rate of 15.99% (4144 of 25,910) was found. Also, 69 rare genotypes (28 of α-thalassemia and 41 of ß-thalassemia) and 9 novel variants were identified. CONCLUSIONS: This NGS-based method provided a feasible platform for high school population thalassemia screening. Combined with a clinical follow-up strategy, it could help eventually to prevent the births of affected children.

Prevalence and genetic analysis of triplicated α-globin gene in Ganzhou region using high-throughput sequencing.

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous ß-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous ß-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous ß-thalassemia. However, they did not differ from the individuals with heterozygous ß-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication.

Application of Adjustable Skin Stretchers in Repairing Wound-Related Defects.

Objective: To explore the application value of adjustable skin stretchers for repairing skin wound defects. Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated. Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities. Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.

Novel Promoter Mutation (HBB:C.-139_-138del) Associated with ß-Thalassemia Trait Detected by Next-Generation Sequencing in Southern China.

Here we report a novel ß-globin gene mutation in the promoter (HBB:c.-139_-138delAC) detected by next-generation sequencing (NGS). The proband was a 28-year-old Chinese male, living in Shenzhen City, Guangdong Province, who originates from Hunan Province. The red cell indices were almost normal, with a slightly decreased Red Cell volume Distribution Width(RDW). Capillary electrophoresis (CE) showed the Hb A (93.1%) value was below normal, while the Hb A2 (4.2%) and Hb F (2.7%) values were both beyond normal. A set of genetic tests of the α and ß-globin genes were then performed to determine whether the subject carried any causative mutations. The results of NGS revealed a two-base pair deletion at position -89 to -88(HBB:c.-139_-138delAC）in the heterozygous state, which was subsequently confirmed by Sanger sequencing.

Experimental demonstration of a 160 Gbit/s 3D-integrated silicon photonics receiver with 1.2-pJ/bit power consumption.

By using the flip-chip bonding technology, a high performances 3D-integrated silicon photonics receiver is demonstrated. The receiver consists of a high-speed germanium-silicon (Ge-Si) photodetector (PD) and a commercial linear transimpedance amplifiers (TIA). The overall 3 dB bandwidth of the receiver is around 38 GHz with appropriate gain. Based on this 3D-integrated receiver, the 56, 64, 90, 100 Gbit/s non-return-to-zero (NRZ) and 112, 128 Gbit/s four-level pulse amplitude (PAM-4) modulation clear openings of eye diagrams are experimentally obtained. The sensitivities of -10, -5.2 dBm and -6.6, -2.7 dBm were obtained for 112 Gbit/s NRZ and 160 Gbit/s PAM-4 at hard-decision forward err correction (HD-FEC,3.8 × 10-3) and KP4 forward err correction (KP4-FEC,2 × 10-4) threshold, respectively. Additionally, the lowest power consumption of this receiver is about 1.2 pJ/bit, which implies its huge potential for short-reach data center applications.

Mapping Chinese annual gross primary productivity with eddy covariance measurements and machine learning.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr-1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes.

Motion compensation using joint-sub-band phase unwrapping for synthetic aperture sonar.

Displaced phase center antenna (DPCA) micro-navigation has been widely applied in the motion compensation of synthetic aperture sonars (SASs). Estimating the time delay is the most important step for DPCA-based motion compensation. However, at present, the existing methods of estimating the time delay in motion compensation are not sufficiently accurate, which limits the improvement of imaging quality of SASs. This paper proposes a time delay estimation method using joint-sub-band phase unwrapping, which achieves much higher estimation accuracy than the reference method. The experimental results demonstrate that the proposed method dramatically improves the SAS imaging quality, compared to the reference method.

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Ecologically fragile areas account for more than 60% of land area in China. Global change and human activities are aggravating ecosystem degradation and reducing the carrying capacity of resources and environment. It is important to accurately quantify the carrying capacity of resources and environment in ecologically fragile areas to deal with the risk and challenge of global change and to speed up the construction of ecological civilization. How-ever, existing methods evaluating carrying capacity of resources and environment are difficult to reflect the transmission effect of ecosystem structures, processes and functions changes among resource, environment and carrying capacity. Therefore, it is essential to establish a field observation network and obtain the comprehensive data set of resource and environment elements-ecosystem structure, function and process-ecosystem carrying capacity for develo-ping the theory and evaluation method. We introduced the collaborative monitoring networks of flux and UAV photographing, including the thoughts, practice, and preliminary results in the study of ecosystem structure, process and function in the fragile ecosystems of China. Based on the achievements and progress, we proposed the application of collaborative monitoring networks in capacity evaluation.

LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia.

Recently, the role of lncRNAs in tumorigenesis and development has received increasing attention, but the mechanism underlying lncRNAs-mediated tumor growth in the hypoxic microenvironment of solid tumors remains obscure. Using RNA sequencing, 25 hypoxia-related lncRNAs were found to be upregulated in HCC, of which lncRNA USP2-AS1 were significantly increased under hypoxia. We further confirmed that USP2-AS1 was significantly upregulated in liver cancer using FISH assay and that USP2-AS1 was associated with advanced liver cancer and increased tumor size. Furthermore, overexpression of USP2-AS1 under hypoxia dramatically increased HCC proliferation and clone formation, whereas the opposite results were observed after USP2-AS1 knockdown. We also found that overexpression of USP2-AS1 increased migration and invasion of HCC cells, while USP2-AS1 knockdown led to the opposite effect. In addition, USP2-AS1 knockdown can increase the efficacy of lenvatinib in our mice tumor xenograft model. Our findings also suggest that USP2-AS1 could increase the protein level of HIF1α by enhancing YBX1 protein binding to HIF1α mRNA under hypoxia and the therapeutic effect of lenvatinib can be enhanced by combination with HIF1α inhibitors in liver cancer.

MTDH antisense oligonucleotides reshape the immunosuppressive tumor microenvironment to sensitize Hepatocellular Carcinoma to immune checkpoint blockade therapy.

Immune checkpoint blockade (ICB) therapy is an important treatment option for individuals with cancer, but it has certain limitations. Identifying a better target that can overcome tumor immune escape and stimulate T cell activity is critical. This research aimed to delve into the molecular mechanism underlying the immunoregulatory function of metadherin (MTDH), which is a novel and potential therapeutic target in hepatocellular cancer (HCC). A small interfering RNA library was screened using the luciferase reporter assay and PD-L1 promoter. The Cancer Genome Atlas database and HCC tissues were used to investigate the relationship between MTDH and PD-L1. The association between MTDH and ß-catenin/lymphoid enhancer binding factor (LEF-1) was discovered by co-immunoprecipitation. The chromatin immunoprecipitation assay was used to investigate the interaction of MTDH with the PD-L1 promoter when LEF-1 expression was silenced. Locked nucleic acid antisense oligonucleotides (ASOs) were used to inhibit MTDH. We utilized in vitro co-cultures and in vivo syngeneic tumor development experiments to confirm the effectiveness of MTDH ASO combined with PD-1 monoclonal antibody (mAb). MTDH was demonstrated to be a PD-L1 modulator. MTDH increased PD-L1 expression and upregulated PD-L1 transcriptional activity through ß-catenin/LEF-1 signaling. More importantly, MTDH ASO improved the anti-PD-1 response and increased cytotoxic T-cell infiltration in PD-1 mAb-treated malignancies. MTDH effectively predicts the therapeutic efficacy of ICB therapy. Our results imply that combining MTDH ASO with PD-1 mAb could be a promising therapeutic strategy for HCC. In addition, MTDH is a potential novel biomarker for predicting the effectiveness of immune checkpoint inhibitor treatment.

Microorganism-Templated Nanoarchitectonics of Hollow TiO2-SiO2 Microspheres with Enhanced Photocatalytic Activity for Degradation of Methyl Orange.

In this study, hollow SiO2 microspheres were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS) according to the Stober process, in which Pichia pastoris GS 115 cells were served as biological templates. The influence of the preprocessing method, the TEOS concentration, the ratio of water to ethanol, and the aging time on the morphology of microspheres was investigated and the optimal conditions were identified. Based on this, TiO2-SiO2 microspheres were prepared by the hydrothermal process. The structures and physicochemical properties of TiO2-SiO2 photocatalysts were systematically characterized and discussed. The photocatalytic activity for the degradation of methyl orange (MO) at room temperature under Xe arc lamp acting as simulated sunlight was explored. The result showed that the as-prepared TiO2-SiO2 microspheres exhibited a good photocatalytic performance.

Characterization of a novel HBB:c.194dup variant of the ß-globin gene combined with six alpha genes.

ß-thalassemia (ß-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel ß-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient's clinical data, this novel mutation was classified as severe ß0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical ß0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel ß-thal variant combined with six α genes. We describe the patient's clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.

Distinctive pattern and mechanism of precipitation changes affecting soil microbial assemblages in the Eurasian steppe.

Precipitation may increase or decrease by different intensities, but the pattern and mechanism of soil microbial community assembly under various precipitation changes remain relatively underexplored. Here, although ±30% precipitation caused a small decrease (∼19%) in the within-treatment taxonomic compositional dissimilarity through the deterministic competitive exclusion process in a steppe ecosystem, ±60% precipitation caused a large increase (∼35%) in the dissimilarity through the stochastic ecological drift process (random birth/death), which was in contrast with the traditional thought that increasing the magnitude of environmental changes (e.g., from +30% to +60%) would elevate the importance of deterministic relative to stochastic processes. The increased taxonomic dissimilarity/stochasticity under ±60% precipitation translated into functional dissimilarity/stochasticity at the gene, protein, and enzyme levels. Overall, our results revealed the distinctive pattern and mechanism of precipitation changes affecting soil microbial community assembly and demonstrated the need to integrate microbial taxonomic information to better predict their functional responses to precipitation changes.