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1.
Hemoglobin ; : 1-6, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693050

ABSTRACT

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.

3.
Br J Cancer ; 130(8): 1356-1364, 2024 May.
Article in English | MEDLINE | ID: mdl-38355839

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/genetics , Radiomics , Tumor Microenvironment , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Hypoxia , Magnetic Resonance Imaging
4.
J Med Screen ; 31(1): 53-57, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37439030

ABSTRACT

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.


Subject(s)
alpha-Thalassemia , beta-Thalassemia , Child , Humans , Early Detection of Cancer , beta-Thalassemia/diagnosis , beta-Thalassemia/epidemiology , beta-Thalassemia/genetics , China/epidemiology , Genotype , alpha-Thalassemia/diagnosis , alpha-Thalassemia/epidemiology , alpha-Thalassemia/genetics , Students , Mutation
5.
Front Genet ; 14: 1267892, 2023.
Article in English | MEDLINE | ID: mdl-37928241

ABSTRACT

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.

6.
Clin Cosmet Investig Dermatol ; 16: 2409-2417, 2023.
Article in English | MEDLINE | ID: mdl-37694193

ABSTRACT

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.

7.
Hemoglobin ; 47(1): 21-24, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36866928

ABSTRACT

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.


Subject(s)
beta-Thalassemia , Male , Humans , Adult , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , High-Throughput Nucleotide Sequencing , China , Mutation , beta-Globins/genetics
8.
Opt Express ; 31(3): 4129-4139, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36785388

ABSTRACT

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.

9.
Sci Total Environ ; 857(Pt 1): 159390, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36243072

ABSTRACT

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.


Subject(s)
Climate Change , Ecosystem , Carbon Sequestration , Soil , Machine Learning , Carbon , Carbon Dioxide/analysis
10.
JASA Express Lett ; 2(1): 016001, 2022 01.
Article in English | MEDLINE | ID: mdl-36154222

ABSTRACT

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.

11.
Ying Yong Sheng Tai Xue Bao ; 33(8): 2271-2278, 2022 Aug.
Article in Chinese | MEDLINE | ID: mdl-36043836

ABSTRACT

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.


Subject(s)
Conservation of Natural Resources , Ecosystem , China , Human Activities , Humans
12.
Front Oncol ; 12: 882372, 2022.
Article in English | MEDLINE | ID: mdl-35692750

ABSTRACT

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.

13.
J Int Med Res ; 50(5): 3000605221099013, 2022 May.
Article in English | MEDLINE | ID: mdl-35549527

ABSTRACT

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.


Subject(s)
beta-Globins , beta-Thalassemia , Alleles , Genotype , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation/genetics , Phenotype , beta-Globins/genetics , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics
14.
Nanomaterials (Basel) ; 12(9)2022 May 09.
Article in English | MEDLINE | ID: mdl-35564314

ABSTRACT

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.

15.
Cancer Lett ; 541: 215750, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35609735

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , B7-H1 Antigen , Carcinoma, Hepatocellular , Immune Checkpoint Inhibitors , Liver Neoplasms , Membrane Proteins , Oligonucleotides, Antisense , RNA-Binding Proteins , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Cell Line, Tumor , Humans , Immune Checkpoint Inhibitors/pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Membrane Proteins/genetics , Membrane Proteins/immunology , Oligonucleotides, Antisense/immunology , Programmed Cell Death 1 Receptor/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , Tumor Microenvironment , beta Catenin/genetics , beta Catenin/immunology
16.
iScience ; 25(3): 103893, 2022 Mar 18.
Article in English | MEDLINE | ID: mdl-35243251

ABSTRACT

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.

17.
BMC Pregnancy Childbirth ; 22(1): 172, 2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35236312

ABSTRACT

BACKGROUND: There is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles. METHODS: A total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363). RESULTS: There were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin. CONCLUSIONS: GnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.


Subject(s)
Chorionic Gonadotropin/administration & dosage , Fertility Agents, Female/administration & dosage , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/agonists , Oocytes/drug effects , Ovarian Hyperstimulation Syndrome/chemically induced , Adult , Chorionic Gonadotropin/adverse effects , Cryopreservation , Embryo Transfer/methods , Female , Fertility Agents, Female/adverse effects , Fertilization in Vitro/methods , Hormone Antagonists/administration & dosage , Humans , Pregnancy , Pregnancy Outcome , Pregnancy Rate , Retrospective Studies
18.
Cell Mol Gastroenterol Hepatol ; 13(5): 1413-1447, 2022.
Article in English | MEDLINE | ID: mdl-35158098

ABSTRACT

BACKGROUND & AIMS: Cancer stemness and immune evasion are closely associated and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association. METHODS: The expressions of heterogeneous nuclear ribonucleoprotein M (HNRNPM) in 240 hepatocellular carcinoma (HCC) samples, public databases, and liver development databases were analyzed. Chromatin immunoprecipitation assays were performed to explore the associations between stem-cell transcription factors and HNRNPM. HNRNPM-regulated alternative splicing (AS) and its binding motif were identified by RNA-seq and RIP-seq. HNRNPM-specific antisense oligonucleotides were developed to explore potential therapeutic targets in HCC. CD8+ T cells that were co-cultured with tumor cells were sorted by flow cytometry assays. RESULTS: We identified an elevated oncofetal splicing factor in HCC, HNRNPM, that unifies and regulates the positive association between cancer stemness and immune evasion. HNRNPM knockdown abolished HCC tumorigenesis and diminished cancer stem cell properties in vitro and in vivo. Mechanistically, HNRNPM regulated the AS of MBD2 by binding its flanking introns, whose isoforms played opposing roles. Although MBD2a and MBD2c competitively bound to CpG islands in the FZD3 promoter, MBD2a preferentially increased FZD3 expression and then activated the WNT/ß-catenin pathway. Interestingly, FZD3 and ß-catenin further provided additional regulation by targeting OCT4 and SOX2. We found that HNRNPM inhibition significantly promoted CD8+ T cell activation and that HNRNPM- antisense oligonucleotides effectively inhibited WNT/ß-catenin to enhance anti-programmed cell death protein-1 immunotherapy by promoting CD8+ T cell infiltration. CONCLUSIONS: HNRNPM has a tumor-intrinsic function in generating an immunosuppressive HCC environment through an AS-dependent mechanism and demonstrates proof of the concept of targeting HNRNPM in tailoring HCC immunotherapeutic approaches.


Subject(s)
Carcinoma, Hepatocellular , Heterogeneous-Nuclear Ribonucleoprotein Group M , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , DNA-Binding Proteins/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group M/metabolism , Humans , Liver Neoplasms/pathology , Oligonucleotides, Antisense , beta Catenin/metabolism
19.
Sci China Life Sci ; 65(5): 861-895, 2022 05.
Article in English | MEDLINE | ID: mdl-35146581

ABSTRACT

Enhancing the terrestrial ecosystem carbon sink (referred to as terrestrial C sink) is an important way to slow down the continuous increase in atmospheric carbon dioxide (CO2) concentration and to achieve carbon neutrality target. To better understand the characteristics of terrestrial C sinks and their contribution to carbon neutrality, this review summarizes major progress in terrestrial C budget researches during the past decades, clarifies spatial patterns and drivers of terrestrial C sources and sinks in China and around the world, and examines the role of terrestrial C sinks in achieving carbon neutrality target. According to recent studies, the global terrestrial C sink has been increasing from a source of (-0.2±0.9) Pg C yr-1 (1 Pg=1015 g) in the 1960s to a sink of (1.9±1.1) Pg C yr-1 in the 2010s. By synthesizing the published data, we estimate terrestrial C sink of 0.20-0.25 Pg C yr-1 in China during the past decades, and predict it to be 0.15-0.52 Pg C yr-1 by 2060. The terrestrial C sinks are mainly located in the mid- and high latitudes of the Northern Hemisphere, while tropical regions act as a weak C sink or source. The C balance differs much among ecosystem types: forest is the major C sink; shrubland, wetland and farmland soil act as C sinks; and whether the grassland functions as C sink or source remains unclear. Desert might be a C sink, but the magnitude and the associated mechanisms are still controversial. Elevated atmospheric CO2 concentration, nitrogen deposition, climate change, and land cover change are the main drivers of terrestrial C sinks, while other factors such as fires and aerosols would also affect ecosystem C balance. The driving factors of terrestrial C sink differ among regions. Elevated CO2 concentration and climate change are major drivers of the C sinks in North America and Europe, while afforestation and ecological restoration are additionally important forcing factors of terrestrial C sinks in China. For future studies, we recommend the necessity for intensive and long term ecosystem C monitoring over broad geographic scale to improve terrestrial biosphere models for accurately evaluating terrestrial C budget and its dynamics under various climate change and policy scenarios.


Subject(s)
Carbon Sequestration , Ecosystem , Carbon Cycle , Carbon Dioxide , China , Climate Change
20.
Sensors (Basel) ; 22(3)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35161817

ABSTRACT

The reliability and stability of MEMS electrostatic comb resonators have become bottlenecks in practical applications. However, there are few studies that comprehensively consider the nonlinear dynamic behavior characteristics of MEMS systems and devices in a coupled field so that the related simulation accuracy is low and cannot meet the needs of design applications. In this paper, to avoid the computational complexity and the uncertainty of the results of three-field direct coupling and take into the damping nonlinearity caused by coupled fields, a novel electrostatic-fluid-structure three-field indirect coupling method is proposed. Taking an actual microcomb resonant electric field sensor as an example, an electrostatic-fluid-structure multiphysics coupling 3D finite element simulation model is established. After considering the influence of nonlinear damping concerning the large displacement of the structure and the microscale effect, multifield coupling dynamics research is carried out using COMSOL software. The multiorder eigenmodes, resonant frequency, vibration amplitude, and the distribution of fluid load of the microresonator are calculated and analyzed. The simulated data of resonance frequency and displacement amplitude are compared with the measured data. The results show that the fluid load distribution of the microelectrostatic comb resonator along the thickness direction is high in the middle and low on both sides. The viscous damping of the sensor under atmospheric pressure is mainly composed of the incompressible flow damping of the comb teeth, which is an order of magnitude larger than those of other parts. Compared with the measured data, it can be concluded that the amplitude and resonance frequency of the microresonator considering the nonlinear damping force and residual thermal stress are close to the experimental values (amplitude error: 15.47%, resonance frequency error: 12.48%). This article provides a reference for studies on the dynamic characteristics of electrostatically driven MEMS devices.

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