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O6-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment. For better blood-brain barrier (BBB) penetration and GBM targeting, we conjugated Angiopep-2 (ANG) targeting modules to each end of the FNN. Nucleolin (NCL)-responsive locks were engineered along the sides of the six-helix DNA bundle, which safeguard siMGMT before tumor entry. Upon interaction with tumor-overexpressed NCL, these locks unlock, exposing siMGMT, this allows for effective suppression of MGMT, resulting in a significant improvement of TMZ therapeutic efficacy in GBM. This innovative strategy has the potential to transform the current treatment landscape for GBM.
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Antineoplásicos Alquilantes , Barreira Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Temozolomida , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Temozolomida/farmacologia , Temozolomida/administração & dosagem , Temozolomida/uso terapêutico , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Nanopartículas/química , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Metilases de Modificação do DNA/metabolismo , Nucleolina , Fosfoproteínas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , RNA Interferente Pequeno/administração & dosagem , Ácidos Nucleicos , PeptídeosRESUMO
Hydrogen energy with its advantages of high calorific value, renewable nature, and zero carbon emissions is considered an ideal candidate for clean energy in the future. The electrochemical decomposition of water, powered by renewable and clean energy sources, presents a sustainable and environmentally friendly approach to hydrogen production. However, the traditional electrochemical overall water-splitting reaction (OWSR) is limited by the anodic oxygen evolution reaction (OER) with sluggish kinetics. Although important advances have been made in efficient OER catalysts, the theoretical thermodynamic difficulty predetermines the inevitable large potential (1.23 V vs. RHE for the OER) and high energy consumption for the conventional water electrolysis to obtain H2. Besides, the generation of reactive oxygen species at high oxidation potentials can lead to equipment degradation and increase maintenance costs. Therefore, to address these challenges, thermodynamically favorable anodic oxidation reactions with lower oxidation potentials than the OER are used to couple with the cathodic hydrogen evolution reaction (HER) to construct new coupling hydrogen production systems. Meanwhile, a series of robust catalysts applied in these new coupled systems are exploited to improve the energy conversion efficiency of hydrogen production. Besides, the electrochemical neutralization energy (ENE) of the asymmetric electrolytes with a pH gradient can further promote the decrease in application voltage and energy consumption for hydrogen production. In this review, we aim to provide an overview of the advancements in electrochemical hydrogen production strategies with low energy consumption, including (1) the traditional electrochemical overall water splitting reaction (OWSR, HER-OER); (2) the small molecule sacrificial agent oxidation reaction (SAOR) and (3) the electrochemical oxidation synthesis reaction (EOSR) coupling with the HER (HER-SAOR, HER-EOSR), respectively; (4) regulating the pH gradient of the cathodic and anodic electrolytes. The operating principle, advantages, and the latest progress of these hydrogen production systems are analyzed in detail. In particular, the recent progress in the catalytic materials applied to these coupled systems and the corresponding catalytic mechanism are further discussed. Furthermore, we also provide a perspective on the potential challenges and future directions to foster advancements in electrocatalytic green sustainable hydrogen production.
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The boom of aqueous Zn-based energy storage devices, such as zinc-iodine (Zn-I2) batteries, is quite suitable for safe and sustainable energy storage technologies. However, in rechargeable aqueous Zn-I2 batteries, the shuttle phenomenon of polyiodide ions usually leads to irreversible capacity loss resulting from both the iodine cathode and the zinc anode, and thus impinges on the cycle lifespan of the battery. Herein, a nontoxic, biocompatible, and economical polymer of polyvinyl alcohol (PVA) is exploited as an electrolyte additive. Based on comprehensive analysis and computational results, it is evident that the PVA additive, owing to its specific interaction with polyiodide ions and lower binding energy, can effectively suppress the migration of polyiodide ions towards the zinc anode surface, thereby mitigating adverse reactions between polyiodide ions and zinc. Simultaneously, the hydrogen bond network of water molecules is disrupted due to the abundant hydroxyl groups within the PVA additive, leading to a decrease in water activity and mitigating zinc corrosion. Further, because of the preferential adsorption of PVA on the zinc anode surface, the deposition environment for zinc ions is adjusted and its nucleation overpotential increases, which is favorable for the dense and uniform deposition of zinc ions, thus ensuring the improvement of the performance of the Zn-I2 battery. This investigation has inspired the development of a user-friendly and high-performance Zn-I2 battery.
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Aim: This research aimed to explore the causal impact of blood metabolites on oral cancer using a two-sample Mendelian randomization (MR) analysis. The study endeavored to identify potential biomarkers for oral cancer's clinical management. Materials and methods: Based on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we first constructed genetic risk scores (GRSs) of 486 human blood metabolites and evaluated the effect on oral cancer. Various statistical methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, among others, were employed to analyze the potential causal relationship between blood metabolites and oral cancer. The sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. Results: 29 metabolites met the stringent selection criteria. Out of these, 14 metabolites demonstrated a positive association with oral cancer risk, while 15 metabolites indicated a protective effect against oral cancer. The IVW-derived estimates were significant, and the results were consistent across different statistical methodologies. Both the Cochran Q test and the MR-Egger intercept test indicated no heterogeneity and pleiotropy. Conclusion: This MR study offers evidence of the role specific blood metabolites play in oral cancer, pinpointing several with potential risk or protective effects. These findings could be helpful for new diagnostic tools and treatments for oral cancer. While the results are promising, additional research is necessary to fully validate and refine these conclusions. This study serves as a foundational step towards more comprehensive understandings in the future.
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Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post-translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2-mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ-resistant cells, and is mainly concentrated in histone H3K9. Combined multi-omics analysis, including CUT&Tag, SLAM-seq, and RNA-seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2 transcription to promote its expression. LUC7L2 mediates intron 7 retention of MLH1 to reduce MLH1 expression, and thereby inhibit mismatch repair (MMR), ultimately leading to GBM TMZ resistance. Of note, it is identified that a clinical anti-epileptic drug, stiripentol, which can cross the blood-brain barrier and inhibit lactate dehydrogenase A/B (LDHA/B) activity, acts as a lactylation inhibitor and renders GBM cells more sensitive to TMZ in vitro and in vivo. These findings not only shed light on the mechanism of lactylation in GBM TMZ resistance but also provide a potential combined therapeutic strategy for clinical GBM treatment.
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Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Histonas , Íntrons , Proteína 1 Homóloga a MutL , Temozolomida , Animais , Humanos , Camundongos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Histonas/metabolismo , Histonas/genética , Íntrons/genética , Camundongos Nus , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Temozolomida/farmacologia , FemininoRESUMO
The Calocybe species possess notable economic and medicinal value, demonstrating substantial potential for resource utilization. The taxonomic studies of Calocybe are lacking in quality and depth. Based on the specimens collected from northeast China, this study provides a detailed description of two newly discovered species, namely Calocybebetulicola and Calocybecystidiosa, as well as two commonly found species, Calocybedecolorata and Calocybeionides. Additionally, a previously unrecorded species, C.decolorata, has recently been discovered in Jilin Province, China. The two newly discovered species can be accurately distinguished from other species within the genus Calocybe based on their distinct morphological characteristics. The primary distinguishing features of C.betulicola include its grayish-purple pileus, grayish-brown to dark purple stipe, smaller basidiomata, absence of cellular pileipellis, and its habitat on leaf litter within birch forests. Calocybecystidiosa is distinguished by its growth on the leaf litter of coniferous forests, a flesh-pink pileus, a fibrous stipe with a white tomentose covering at the base, non-cellular pileipellis, larger basidiospores, and the presence of cheilocystidia. The reconstruction of phylogenetic trees using combined ITS, nLSU, and tef1-α sequences, employing maximum likelihood and Bayesian inference analyses, showed that C.betulicola formed a cluster with C.decurrens, while C.cystidiosa clustered with C.vinacea. However, these two clusters formed separate branches themselves, which also supported the results obtained from our morphological studies. A key to the Calocybe species reported from northeast China is provided to facilitate future studies of the genus.
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Sun trap: Pure WS2 nanosheets are prepared that exhibit excellent photosensitive properties. After functionalization with WO3 nanoparticles, abnormal photocurrent responses, enhanced photocatalytic activity, and induced photoluminescence is observed.
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The use of gel thermoelectric chemical cells to capture low-grade heat for conversion to electricity is an attractive approach. However, there are few studies on whether the distribution of redox species in the electrolyte has an effect on the performance of cells. Herein, this concern was discussed by constructing a novel gel thermoelectric chemical cell (Cu-C-cg). Using cellulose-like rice paper as a separator, a concentration gradient of electrolyte was carefully constructed, so that the concentration of potassium ferrocyanide gradually decreased from the hot electrode to the cold electrode while the concentration of potassium ferricyanide gradually increased. Through electrochemical measurement and analysis, it was found that the thermoelectric performance of this cell outperformed the cell without electrolyte concentration gradients. Meanwhile, this performance could be enhanced by the use of asymmetric electrodes composed of copper foil and carbon electrodes. After optimizing the conditions, the open-circuit voltage, output power, and Seebeck coefficient of the Cu-C-cg cell at 12â K temperature difference were 0.450â V, 183â µW, and 7.82â mV K-1 , respectively. This work not only provides a novel idea in gel-based cell design but also an excellent thermoelectric chemical cell.
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The prognosis of glioblastoma (GBM) patients is poor, and temozolomide (TMZ) resistance has become an important obstacle to its treatment effect. A growing number of researches have revealed the special characteristics of iron metabolism in GBM chemosensitivity. Iron regulatory protein 1 (IRP1) is an important protein for maintaining intracellular iron homeostasis. IRP1 has been indicated to have additional vital roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we unprecedentedly demonstrated that amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growth in vivo via inhibiting NFKB2 in the noncanonical NF-κB signaling pathway. In addition, we identified that NFKB2 affected TMZ sensitivity of GBM by modulating the expression of LCN2 and FPN1. Taken together, this study established a role for the IRP1/NFKB2 pathway in regulating LCN2/FPN1 signaling axis among the progression of TMZ resistance, suggesting a potential innovative GBM therapeutic strategy.
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The exploration of high-performance electrocatalysts for the oxygen evolution reaction (OER) is crucial and urgent for the fast development of green and renewable hydrogen energy. Herein, an ultra-fast and energy-efficient preparation strategy (microwave-assisted rapid in-situ pyrolysis of organometallic compounds induced by carbon nanotube (CNT)) is developed to obtain iron/carbon (Fe/C) heterogeneous materials (Fe/Fe3C particles wrapped by carbon coating layer). The thickness of the carbon coating layer can be adjusted by changing the content and form of carbon in the metal sources during the fast preparation process. Fe/Fe3C-A@CNT using iron acetylacetonate as metal sources possesses unique Fe/C heterogeneous, small Fe/Fe3C particles encapsulated by the thin carbon coating layer (1.77 nm), and obtains the optimal electron penetration effect. The electron penetration effect derives from the redistribution of charge between the surface carbon coating layer and inner Fe/Fe3C nanoparticles efficiently improving both catalytic activity and stability. Therefore, Fe/Fe3C-A@CNT shows efficient OER catalytic activity, just needing a low overpotential of 292 mV to reach a current density of 10 mA cm-2, and long-lasting stability. More importantly, the unique control strategy for carbon thickness in this work provides more opportunity and perspective to prepare robust metal/carbon-based catalytic materials at the nanoscale.
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Based on the first-principles calculations, we investigate the magnetic and electronic properties of α-graphyne nanoribbons (NRs). We show that all the armchair α-graphyne NRs are nonmagnetic semiconductors with band gaps as a function of ribbon widths. The zigzag α-graphyne NRs are found to have magnetic semiconducting ground state with ferromagnetic ordering at each edge and opposite spin orientation between the two edges. Under the application of transverse electric field, we further predict the existence of half-metallicity in the zigzag NRs which strongly depends on the width of the ribbon.
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The search for ultrafast and simple methods to fabricate non-noble metal catalysts to boost electrocatalytic oxygen reduction reaction (ORR) is still ongoing. Herein, we demonstrate a one-step microwave-assisted heating method to prepare copper nitride/iron/iron carbide nanoparticle hybrids (CuNC/Fe/Fe3C/CNT). This ultrafast heating method induces plentiful carbon-wrapped metal and Fe3C nanoparticles that are attached to the surface of CNT and scattered nanosheets. The CuNC/Fe/Fe3C/CNT exhibit a half-wave potential (E1/2) of 0.886 V toward the ORR in alkaline solution, with 220 mV more positive E1/2 than that of CuNC/CNT and Fe/Fe3C/CNT respectively. The activity of as-prepared catalysts is discussed by investigating their structures and compositions and their relationship with the ORR performance. Detailed analysis results disclose that the high activity of the CuNC/Fe/Fe3C/CNT catalysts could be attributed to the interaction of CuNC and Fe/Fe3C species. To be specific, as the electron donor, Fe/Fe3C nanoparticles induce electron localization and promote the formation of Cu (δ + )-NC (0 < δ < 2), therefore leading to the improvement of the ORR performance. This work may offer an ultrafast way to construct efficient catalysts with enhanced ORR performance.
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Carbono , Cobre , Catálise , OxigênioRESUMO
Understanding the mechanisms of how urbanization influences the evolution of native species is vital for urban wildlife ecology and conservation in the Anthropocene. With thousands of years of agriculture-dominated historical urbanization followed by 40 years of intensive and rapid urbanization, Shanghai provides an ideal environment to study how the two-stage urbanization process influences the evolution of indigenous wildlife, especially of anuran species. Therefore, in this study, we used mitochondrial Cyt-b gene, microsatellite (SSR), and single nucleotide polymorphism (SNP) data to evaluate the demographic history and genetic structure of the eastern golden frog (Pelophylax plancyi), by sampling 407 individuals from 15 local populations across Shanghai, China. All local populations experienced bottlenecks during historical urbanization, while the local populations in urban areas maintained comparable contemporary effective population sizes (N e) and genetic diversity with suburban and rural populations. Nevertheless, the rapid modern urbanization has already imposed significant negative effects to the integrity of populations. The 15 local populations were differentiated into eight genetic clusters, showing a spatial distribution pattern consistent with the current urbanization gradient and island-mainland geography. Although moderate gene flow still occurred from the rural peripheral cluster to urban and suburban clusters, population fragmentation was more serious in the urban and suburban populations, where higher urbanization levels within 2-km radius areas showed significant negative relationships to the N e and genetic diversity of local populations. Therefore, to protect urban wildlife with limited dispersal ability, improving conditions in fragmented habitat remnants might be most essential for local populations living in more urbanized areas. Meanwhile, we highlight the need to preserve large unfragmented rural habitats and to construct corridor networks to connect discrete urban habitat remnants for the long-term wildlife conservation in intensively urbanizing environments.
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Van der Waals (vdW) heterostructures consisting of graphene and other two-dimensional materials provide good opportunities for achieving desired electronic and optoelectronic properties. Here, we focus on vdW heterostructures composed of graphene and gallium nitride (GaN). Using density functional theory, we perform a systematic study on the structural and electronic properties of heterostructures consisting of graphene and GaN. Small band gaps are opened up at or near the Γ point of the Brillouin zone for all of the heterostructures. We also investigate the effect of the stacking sequence and electric fields on their electronic properties. Our results show that the tunability of the band gap is sensitive to the stacking sequence in bilayer-graphene-based heterostructures. In particular, in the case of graphene/graphene/GaN, a band gap of up to 334 meV is obtained under a perpendicular electric field. The band gap of bilayer graphene between GaN sheets (GaN/graphene/graphene/GaN) shows similar tunability, and increases to 217 meV with the perpendicular electric field reaching 0.8 V Å(-1).
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Transition metal dichalcogenides (TMDCs) have recently been the focus of extensive research activity owing to their fascinating physical properties. As a new member of TMDCs, Mo doped ReSe2 (Mo:ReSe2) is an octahedral structure semiconductor being optically biaxial and highly anisotropic, different from most of hexagonal layered TMDCs with optically uniaxial and relatively high crystal symmetry. We investigated the effects of physisorption of gas molecule on the few-layer Mo:ReSe2 nanosheet based photodetectors. We compared the photoresponse of the as-exfoliated device with annealed device both in air or ammonia (NH3) environment. After annealing at sub-decomposition temperatures, the Mo:ReSe2 photodetectors show a better photoresponsivity (~55.5â A/W) and higher EQE (10893%) in NH3 than in air. By theoretical investigation, we conclude that the physisorption of NH3 molecule on Mo:ReSe2 monolayer can cause the charge transfer between NH3 molecule and Mo:ReSe2 monolayer, increasing the n-type carrier density of Mo:ReSe2 monolayer. The prompt photoswitching, high photoresponsivity and different sensitivity to surrounding environment from the few-layer anisotropic Mo:ReSe2 can be used to design multifunctional optoelectronic and sensing devices.
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The ability to control the appropriate layer thickness of transition metal dichalcogenides (TMDs) affords the opportunity to engineer many properties for a variety of applications in possible technological fields. Here we demonstrate that band-gap and mobility of ReSe2 nanosheet, a new member of the TMDs, increase when the layer number decreases, thus influencing the performances of ReSe2 transistors with different layers. A single-layer ReSe2 transistor shows much higher device mobility of 9.78 cm(2) V(-1) s(-1) than few-layer transistors (0.10 cm(2) V(-1) s(-1)). Moreover, a single-layer device shows high sensitivity to red light (633 nm) and has a light-improved mobility of 14.1 cm(2) V(-1) s(-1). Molecular physisorption is used as "gating" to modulate the carrier density of our single-layer transistors, resulting in a high photoresponsivity (Rλ) of 95 A W(-1) and external quantum efficiency (EQE) of 18 645% in O2 environment. This work highlights the fact that the properties of ReSe2 can be tuned in terms of the number of layers and gas molecule gating, and single-layer ReSe2 with appropriate band-gap is a promising material for future functional device applications.
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: Using first-principles calculations, we investigate the adsorption of various gas molecules (H2, O2, H2O, NH3, NO, NO2, and CO) on monolayer MoS2. The most stable adsorption configuration, adsorption energy, and charge transfer are obtained. It is shown that all the molecules are weakly adsorbed on the monolayer MoS2 surface and act as charge acceptors for the monolayer, except NH3 which is found to be a charge donor. Furthermore, we show that charge transfer between the adsorbed molecule and MoS2 can be significantly modulated by a perpendicular electric field. Our theoretical results are consistent with the recent experiments and suggest MoS2 as a potential material for gas sensing application.
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We report on the first-principles calculations of bandgap modulation in armchair MoS(2) nanoribbon (AMoS(2)NR) by transverse and perpendicular electric fields respectively. In the monolayer AMoS(2)NR case, it is shown that the bandgap can be significantly reduced and be closed by transverse field, whereas the bandgap modulation is absent under perpendicular field. The critical strength of transverse field for gap closure decreases as ribbon width increases. In the multilayer AMoS(2)NR case, in contrast, it is shown that the bandgap can be effectively reduced by both transverse and perpendicular fields. Nevertheless, it seems that the two fields exhibit different modulation effects on the gap. The critical strength of perpendicular field for gap closure decreases with increasing number of layers, while the critical strength of transverse field is almost independent of it.
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Rapid cold hardening can enhance the cold tolerance of some insects. To explore the effects of different cold hardening induction temperature on the cold tolerance of Arma chinensis and related physiological mechanisms, the 3rd generation A. chinensis adults reared indoor were treated with cooling at 15, 10, and 4 degrees C for 4 h, respectively, or with gradual cooling from 15 degrees C for 4 h to 10 degrees C for 4 h, and finally to 4 degrees C for 4 h. The super-cooling point, water content, and the contents of low molecular carbohydrates, glycerol, and amino acids of the adults after cooling and the adults cold tolerance at 0, -5, and -10 degrees C were measured by thermocouple, high performance liquid chromatography, and other analytical techniques. When exposed at -10 degrees C after cooling, the survival rate of the adults treated with gradual cooling or treated with cooling at 4 degrees C for 4 h was averagely 58.3%, while that of the adults reared at room temperature (25 degrees C +/- 2 degrees C) or treated with cooling at 15 degrees C or 10 degrees C for 4 h decreased significantly, with an average of 8.9%. The super-cooling point of the adults treated with gradual cooling or with cooling at 4 degrees C for 4 h was -15.6 degrees C, which was averagely 1.3 degrees C lower than that of the other treatments. The water content of the adults had no significant difference among all treatments, with an average of 61.8%, but the glucose, sorbitolum, glycerol, Ala, and Glu contents in treatments gradual cooling and cooling at 4 degrees C for 4 h increased by 2.82-fold, 2.65-fold, 3.49-fold, 51.3%, and 80.2%, while the fucose, mannose, and Pro contents decreased by 68.4%, 52.2%, and 30.2%, respectively, as compared with the other treatments. The fructose content showed no significant difference among all treatments. It was suggested that rapid cool hardening had a critical temperature to induce the physiological metabolism process of adult A. chinensis, and gradual cooling hardening could not further increase the cold tolerance of adult A. chinensis on the basis of rapid cool hardening.