Construction of Switch Modules for CAR-T Cell Treatment Using a Site-Specific Conjugation System.

Chimeric antigen receptor T-cell (CAR-T cell) therapy has become a promising treatment option for B-cell hematological tumors. However, few optional target antigens and disease relapse due to loss of target antigens limit the broad clinical applicability of CAR-T cells. Here, we conjugated an antibody (Ab) fusion protein, consisting of an Ab domain and a SpyCatcher domain, with the FITC-SpyTag (FITC-ST) peptide to form a bispecific safety switch module using a site-specific conjugation system. We applied the safety switch module to target CD19, PDL1, or Her2-expressing tumor cells by constructing FMC63 (anti-CD19), antiPDL1, or ZHER (anti-Her2)-FITC-ST, respectively. Those switch modules significantly improved the cytotoxic effects of anti-FITC CAR-T cells on tumor cells. Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.

Construction of a versatile fusion protein for targeted therapy and immunotherapy.

Antibody (Ab)-based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab-based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag-X (S-X) to form the SpaCC-S-X complex, which binds non-covalently to an Ab to form the Ab-SpaCC-S-X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell-penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab-SpaCC-S-FITC(-TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab-SpaCC-SN3-MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab-DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab-SpaCC-SN3-Ap boosted the tumor-killing function of T-cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.

Photo-Responsive Ascorbic Acid-Modified Ag2S-ZnS Heteronanostructure Dropping pH to Trigger Synergistic Antibacterial and Bohr Effects for Accelerating Infected Wound Healing.

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

CAR-Aptamers Enable Traceless Enrichment and Monitoring of CAR-Positive Cells and Overcome Tumor Immune Escape.

Chimeric antigen receptor (CAR)-positive cell therapy, specifically with anti-CD19 CAR-T (CAR19-T) cells, achieves a high complete response during tumor treatment for hematological malignancies. Large-scale production and application of CAR-T therapy can be achieved by developing efficient and low-cost enrichment methods for CAR-T cells, expansion monitoring in vivo, and overcoming tumor escape. Here, novel CAR-specific binding aptamers (CAR-ap) to traceless sort CAR-positive cells and obtain a high positive rate of CAR19-T cells is identified. Additionally, CAR-ap-enriched CAR19-T cells exhibit similar antitumor capacity as CAR-ab (anti-CAR antibody)-enriched CAR-T cells. Moreover, CAR-ap accurately monitors the expansion of CAR19-T cells in vivo and predicts the prognosis of CAR-T treatment. Essentially, a novel class of stable CAR-ap-based bispecific circular aptamers (CAR-bc-ap) is constructed by linking CAR-ap with a tumor surface antigen (TSA): protein tyrosine kinase 7 (PTK7) binding aptamer Sgc8. These CAR-bc-aps significantly enhance antitumor cytotoxicity with a loss of target antigens by retargeting CAR-T cells to the tumor in vitro and in vivo. Overall, novel CAR-aptamers are screened for traceless enrichment, monitoring of CAR-positive cells, and overcoming tumor cell immune escape. This provides a low-cost and high-throughput approach for CAR-positive cell-based immunotherapy.

Anti-CD79b/CD3 bispecific antibody combined with CAR19-T cells for B-cell lymphoma treatment.

CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b+ CD19- lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b+ CD19- lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR- T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells.

[Quantification of Ozone Pollution Transport Based on Four-dimensional Flux Method in Foshan, China].

Quantifying the contribution of transport processes to air pollution events has been a prominent challenge and an important need in regional air pollution prevention and control. The WRF-Chem model was used to simulate a typical regional ozone (O3) pollution event in Foshan, and the four-dimensional flux method was applied to quantify the transport fluxes of ozone and its precursors from the surrounding areas to Foshan and to clarify the contributions of the direct transport of ozone and transport of precursors. The average ozone flux from the surrounding areas to Foshan was 120.3 t·h-1, the volatile organic compound (VOCs) flux was 30.2 t·h-1, and the corresponding ozone formation potential (OFP) was 114.8 t·h-1. By counting the transport fluxes of each ozone pollution event, it was found that the city with the largest ozone flux into Foshan during the pollution period was Guangzhou (contributed 44%); the city with the largest input VOCs flux was Zhaoqing (contributed 48%). The analysis of ozone generation potential due to transported VOCs emissions found that oxygenated volatile organic compounds (OVOCs) contributed the most to OFP, accounting for 47% of the "maximum input events." OVOCs and aromatic hydrocarbons such as formaldehyde, xylenes, aldehydes, acetone, and phenols were the top five species contributing to the OFP, contributing more than 50% of the total OFP, mainly from industrial solvent sources.

A novel His-tag-binding aptamer for recombinant protein detection and T cell-based immunotherapy.

Screening novel aptamers for recombinant protein detection is of great significance in industrial mass production of antibody drugs. In addition, construction of structurally stable bispecific circular aptamers (bc-apts) may provide a tumor-targeted treatment strategy by simultaneously binding two different cell types. In this study, we obtained a high-affinity hexahistidine tag (His-tag)-binding aptamer 20S and explored its application in recombinant protein detection and T cell-based immunotherapy. We developed a new molecular beacon (MB) 20S-MB to detect His-tagged proteins in vitro and in vivo with high sensitivity and specificity, and the results showed high consistency with the enzyme-linked immunosorbent assay (ELISA). Moreover, we constructed two kinds of bc-apts by cyclizing 20S or another His-tag-binding aptamer, 6H5-MU, with Sgc8, which specifically recognizes protein tyrosine kinase 7 (PTK7) on tumor cells. After forming a complex with His-tagged OKT3, an anti-CD3 antibody for T cell activation, we utilized these aptamer-antibody complexes (ap-ab complex) to enhance cytotoxicity of T cells by linking T cells and target cells together, and 20S-sgc8 exhibited antitumor efficacy superior to that of 6H5-sgc8. In conclusion, we screened a novel His-tag-binding aptamer and used it to construct a new type of MB for rapid detection of recombinant proteins, as well as establish a feasible approach for T cell-based immunotherapy.

Associations of the audited residential neighborhood built-environment attributes with objectively-measured sedentary time among adults: a systematic review.

This study systematically reviewed the relevant studies and summarized the associations of objective measures of residential neighborhood built-environment attributes with sedentary time among adults. Published studies were obtained from PubMed and Scopus, restricting to those published in English language peer-reviewed journals to Oct. 2021. There were nine studies and 48 instances of estimated associations. Most instances showed no statistical-significant associations; by contrast, few instances showed that adults living in a neighborhood characterized by a high density of local destinations and connected intersections were associated with less sedentary time. The findings suggest that a high density of destinations and street intersections around residence may provide opportunities to transfer and access to services, thus reducing the sedentary time. Future research strengthening the research design and measurements are needed to investigate the potential explanations of the associations between residential neighborhood built environments and sedentary time in adults.

A novel aptamer beacon for rapid screening of recombinant cells and in vivo monitoring of recombinant proteins.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

Video-assisted bystander cardiopulmonary resuscitation improves the quality of chest compressions during simulated cardiac arrests: A systemic review and meta-analysis.

BACKGROUND: It remains unclear whether video aids can improve the quality of bystander cardiopulmonary resuscitation (CPR). AIM: To summarize simulation-based studies aiming at improving bystander CPR associated with the quality of chest compression and time-related quality parameters. METHODS: The systematic review was conducted according to the PRISMA guidelines. All relevant studies were searched through PubMed, EMBASE, Medline and Cochrane Library databases. The risk of bias was evaluated using the Cochrane collaboration tool. RESULTS: A total of 259 studies were eligible for inclusion, and 6 randomised controlled trial studies were ultimately included. The results of meta-analysis indicated that video-assisted CPR (V-CPR) was significantly associated with the improved mean chest compression rate [OR = 0.66 (0.49-0.82), P < 0.001], and the proportion of chest compression with correct hand positioning [OR = 1.63 (0.71-2.55), P < 0.001]. However, the difference in mean chest compression depth was not statistically significant [OR = 0.18 (-0.07-0.42), P = 0.15], and V-CPR was not associated with the time to first chest compression compared to telecommunicator CPR [OR = -0.12 (-0.88-0.63), P = 0.75]. CONCLUSION: Video real-time guidance by the dispatcher can improve the quality of bystander CPR to a certain extent. However, the quality is still not ideal, and there is a lack of guidance caused by poor video signal or inadequate interaction.

Platelet rich plasma alleviates OGD/R injury in N2a cell by enhancing autophagy through the miR­223/PAQR3 pathway.

Our study constructed an in vitro model of cerebral ischemia/reperfusion (I/R) injury to evaluate the protective effect of platelet rich plasma (PRP) on I/R injury and uncover the mechanism behind it. Firstly, N2a cells were exposed in the condition of oxygen and glucose deprivation/reperfusion (OGD/R) to construct a model of cerebral I/R in vitro. MTT assay was employed to access the effects of PRP in N2a cell OGD/R injury. Then, we evaluated the role of the expression of miR­223, progestin and adipoQ receptors 3 (PAQR3) and autophagy markers in the neuroprotective effect of PRP by qPCR and western blot. And the effect of miR­223/PAQR3 axis regulated autophagy in the neuroprotection of PRP was verified by overexpressing miR­223 and PAQR3. Finally, the interaction between miR­223 and PAQR3 was analyzed by the luciferase reporter gene. The results showed that after OGD/R treatment of N2a cells, the expression of miR­223 increased and the expression of PAQR3 and autophagy decreased. PRP improved cells damage caused by OGD/R in N2a cell, and reduced the expression of miR­223 in cells, increased PAQR3 and autophagy. The luciferase reporter assay was used to prove that miR­223 could target PAQR3 directly. Overexpression of miR­223 could eliminate the improvement effect of PRP on OGD/R cells, but at the same time, overexpression of PAQR3 restored the protection of PRP from cell damage. Our research found that in the OGD/R injury in vitro model, PRP inhibited the expression of miR­223 and enhanced autophagy to attenuate the injury by increasing the expression of PAQR3.

Controllable preparation and performance of bio-based poly(lactic acid-iminodiacetic acid) as sustained-release Pb2+ chelating agent.

The bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism.

B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL.

Deep-sea bacteria trigger settlement and metamorphosis of the mussel Mytilus coruscus larvae.

Bacteria from coast seawaters are widely known to induce larval recruitment of many invertebrates. However, whether and how deep-sea bacteria, that play crucial roles in the ecological and biogeochemical cycles, promote larval recruitment remains little known. Here, the interaction between deep-sea bacterial biofilms (BFs) and Mytilus coruscus larvae was tested. All these nine deep-sea bacterial isolates triggered planktonic-sessile transition, and the highest percentage of post-larvae was observed in Virgibacillus sp. 1 BF. Except for Pseudomonas sp. 3, Pseudoalteromonas sp. 32 and Bacillus sp. 13, other BF cell  densities were significantly related to their corresponding inductive efficiency. The deep-sea Virgibacillus sp. 1 BF's cue that triggers planktonic-sessile transition was uncovered. Treating Virgibacillus sp. 1 BFs through physic-chemical approaches reduced inducing impact and cell survival. The conditioned water collaborated with formalin-fixed Virgibacillus sp. 1 BF hoisted planktonic-sessile transition efficiency in comparison to each one alone. Thus, two signals derived from deep-sea bacteria trigger planktonic-sessile transition in M. coruscus. This finding firstly demonstrates that deep-sea bacteria has good potential for application in the mussel seed production and provides novel insight to clarify the bacteria-mussel interaction.

Design and topology optimization of air conditioning suspension bracket for metro.

During the operation of subway vehicles, the vibration of air conditioning units is mainly transmitted to the vehicle body through the suspension support, which seriously affects the stability and comfort of the vehicle during operation. Therefore, the design and optimization of the suspension support of air conditioning units has become a hot topic in the research of the dynamic characteristics of subway vehicles. In this paper, the rigid and flexible coupling dynamic model of metro is firstly calculated to simulate the stress of the suspension point of air conditioning of the vehicle body when the vehicle is running. The initial structure design of the suspension support is carried out, and the stress of the air conditioning suspension point is taken as the load input to analyze the stiffness and strength of the initial structure of the suspension support. Then, the fatigue life is taken as the topology constraint, and the variable density method (SIMP) is used to optimize the topology of the suspension bracket. Finally, the optimized suspension support is validated. The results show that after topological optimization, the maximum displacement and maximum stress of the suspension support under vertical, horizontal, and vertical loads are reduced by 80%, 93%, and 99%, respectively, compared with the original structure model, and the maximum stress under vertical loads is reduced by 50%.

[Medication rules of traditional Chinese medicine for the treatment of premature ejaculation: An analysis based on data mining].

OBJECTIVE: To study the medication rules of traditional Chinese medicine (TCM) in the treatment of premature ejaculation. METHODS: We searched the databases of CNKI, Wan Fang, VIP, SinoMed (CBM) and PubMed for studies on the treatment of PE with TCM prescriptions and performed statistical analyses on the data obtained using the TCM inheritance auxiliary platform software. RESULTS: Totally 180 prescriptions were identified, involving 209 TCM drugs. The results of statistical analysis showed that the TCM drugs for the treatment of premature ejaculation were mostly warm, flat or cold in nature, sweet or spicy in taste, and with the kidney, liver and spleen meridian tropisms. The single TCM drugs most commonly used included Lycium barbarum L (Gouqizi), followed by Epimedium brevicornum Maxim (Yinyanghuo), Os draconis (Longgu), Fructus rosae laevigatae (Jinyingzi), and the drugs most frequently used in combination with others in a prescription were Os draconis (Longgu) and Concha ostreae (Muli). Seven newly derived prescriptions were identified in addition. CONCLUSIONS: The compatibility of TCM in the treatment of premature ejaculation is characterized by the combination of the drugs for tonifying the kidney and arresting seminal emission as the main medication strategy, with those for soothing the liver and invigorating the spleen as the adjuvant agents, which has a certain clinical application value.

Cloning and characterization of the putative AFAP1-AS1 promoter region.

Actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1), a cancer-related long non-coding RNA, has been found to be upregulated in multiple types of cancers. AFAP1-AS1 is important for the initiation, progression and poor prognosis of many cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism underlying the regulation of AFAP1-AS1 expression is not well-understood. In our study, the potential promoter region of AFAP1-AS1 was predicted by comprehensive bioinformatics analysis. Moreover, promoter deletion analysis identified the sequence between positions -359 and -28 bp as the minimal promoter region of AFAP1-AS1. The ChIP assay results indicate that the AFAP1-AS1 promoter is responsive to the transcription factor c-Myc, which can promote high AFAP1-AS1 expression. This study is the first to clone and characterize the AFAP1-AS1 promoter region. Our findings will help to better understand the underlying mechanism of high AFAP1-AS1 expression in tumorigenesis and to develop new strategies for therapeutic high expression of AFAP1-AS1 in NPC.

[Interspecific associations of the main tree populations of the Cyclobalanopsis glauca community in Karst hills of Guilin, Southwest China]. / æ¡‚æž—å²©æº¶çŸ³å±±é’å†ˆç¾¤è½ä¸»è¦ä¹”æœ¨æ ‘ç§çš„ç§é—´å ³è”.

Analyzing the interspecific association of major tree populations of Cyclobalanopsis glauca community and revealing the coexistence among the populations would provide theoretical basis for the restoration and reconstruction, management and biodiversity conservation of Karst hills in Gui-lin. Based on field survey, the χ2 test, association coefficient (AC), co-occurrence percentage (PC), Ochiai index (OI), Dice index (DI), and principal component analysis (PCA) were used to investigate the interspecific association and eco-taxonomic classification of the top 22 tree species in Cyclobalanopsis glauca community in Guilin Karst Rocky Mountains. The results showed that there was a significant positive correlation between the interspecific associations of the 22 main tree populations, indicating that this community was in a stable climax stage. The results of χ2 test showed that 108 pairs of 231 species pairs had positive associations, 115 species pairs had negative associations, 8 species pairs were unrelated, with the positive and negative linkage ratio being 93.9%. The vast majority of species pairs showed no significant association. The strong indepen-dence between species might be mainly caused by the higher habitat heterogeneity of the Karst hills in Guilin which led to the differentiation of niches between species. The results of AC, PC, OI and DI were basically consistent with that of χ2 test, indicating that the analysis of interspecific association should be based on the χ2 test and supplemented by AC, PC, OI and DI indices. According to the PCA and evaluation of interspecific relationships, the 22 main tree species were divided into three ecological groups. The species within each group had the same adaptability to habitat but different ecological requirements.