Heat-tolerant intertidal rock pool coral Porites lutea can potentially adapt to future warming.

The growing threat of global warming on coral reefs underscores the urgency of identifying heat-tolerant corals and discovering their adaptation mechanisms to high temperatures. Corals growing in intertidal rock pools that vary markedly in daily temperature may have improved heat tolerance. In this study, heat stress experiments were performed on scleractinian coral Porites lutea from subtidal habitat and intertidal rock pool of Weizhou Island in the northern South China Sea. Thermotolerance differences in corals from the two habitats and their mechanisms were explored through phenotype, physiological indicators, ITS2, 16S rRNA, and RNA sequencing. At the extremely high temperature of 34°C, rock pool P. lutea had a stronger heat tolerance than those in the subtidal habitat. The strong antioxidant capacity of the coral host and its microbial partners was important in the resistance of rock pool corals to high temperatures. The host of rock pool corals at 34°C had stronger immune and apoptotic regulation, downregulated host metabolism and disease-infection-related pathways compared to the subtidal habitat. P. lutea, in this habitat, upregulated Cladocopium C15 (Symbiodiniaceae) photosynthetic efficiency and photoprotection, and significantly increased bacterial diversity and coral probiotics, including ABY1, Ruegeria, and Alteromonas. These findings indicate that rock pool corals can tolerate high temperatures through the integrated response of coral holobionts. These corals may be 'touchstones' for future warming. Our research provides new insights into the complex mechanisms by which corals resist global warming and the theoretical basis for coral reef ecosystem restoration and selection of stress-resistant coral populations.

A Multifunctional Nanocarrier System for Highly Efficient and Targeted Delivery of Ketamine to NMDAR Sites for Improved Treatment of Depression.

Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)-ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC-RM@HA-MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA-loaded NPs (AC-RM@HA-MS-KA) are constructed with a multilayer core-shell structure. KA-loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC-membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang-2-Con-G, AC) to achieve specific targeting. One peptide (Ang-2) is acted as a guide to facilitate the crossing of the blood-brain barrier (BBB), while the other (Con-G) is functioned as a ligand for the targeted delivery of KA to the N-methyl-D-aspartate receptor sites. Animal experiments reveal that AC-RM@HA-MS-KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.

Diselenide-triggered hydroxyethyl starch conjugate nanoparticles with cascade drug release properties for potentiating chemo-photodynamic therapy.

A novel type of diselenide bond-bridged hydroxyethyl starch-doxorubicin conjugate, HES-SeSe-DOX, was synthesized via a specially designed multistep synthetic route. The optimally achieved HES-SeSe-DOX was further combined with photosensitizer, chlorin E6 (Ce6), to self-assemble into HES-SeSe-DOX/Ce6 nanoparticles (NPs) for potentiating chemo-photodynamic anti-tumor therapy via diselenide-triggered cascade actions. HES-SeSe-DOX/Ce6 NPs were observed to disintegrate through the cleavage or oxidation of diselenide-bridged linkages in response to the stimuli arising from glutathione (GSH), hydrogen peroxide and Ce6-induced singlet oxygen, respectively, as evidenced by the enlarged size with irregular shapes and cascade drug release. In vitro cell studies exhibited that HES-SeSe-DOX/Ce6 NPs in combination with laser irradiation effectively consumed intracellular GSH and promoted a large rise in levels of reactive oxygen species in tumor cells, actuating the disruption of intracellular redox balance and the enhanced chemo-photodynamic cytotoxicity against tumor cells. The in vivo investigations revealed that HES-SeSe-DOX/Ce6 NPs were inclined to accumulate in tumors with persistent fluorescence emission, inhibited tumor growth with high efficacy and had good safety. These findings demonstrate the potential of HES-SeSe-DOX/Ce6 NPs for use in chemo-photodynamic tumor therapy and suggest their viability for clinical translation.

Multi-Crosslinked Strong and Elastic Bioglass/Chitosan-Cysteine Hydrogels with Controlled Quercetin Delivery for Bone Tissue Engineering.

Chitosan-cysteine (CH-CY) conjugate with an optimal content of thiol groups was synthesized and combined with amino-functionalized mesoporous bioglass (ABG) nanoparticles (NPs) with radially-porous architecture to build multi-crosslinked ABG/CH-CY composite hydrogels. Besides the network formed by self-crosslinking of thiol groups in CY-derived side chains, difunctionalized PEG (DF-P) crosslinkers with varying lengths of PEG segments were used to crosslink amino groups on CH-CY or ABG NPs to form other networks in the composite gels. Quercetin (Que) was loaded into ABG NPs before these NPs were incorporated into the hydrogel, intending to achieve sustainable and controllable Que release from so-built ABG/CH-CY gels. The lengths of PEG segments in DF-P were found to impose remarkable impacts on the strength or elasticity of multi-crosslinked ABG/CH-CY hydrogels. Some ABG/CH-CY hydrogels had their elastic modulus of around 8.2 kPa or higher along with yielding strains higher than 70%, specifying their mechanically strong and elastic characteristics. In addition, these gels showed the ability to release Que and Si or Ca ions in controllable ways for various durations. The optimally achieved ABG/CH-CY hydrogels were injectable and also able to support the growth of seeded MC3T3-E1 cells as well as the specific matrix deposition. The obtained results suggest that these ABG/CH-CY gels have promising potential for bone repair and regeneration.

An Evaluation Model of English Normal Students' Informatization Teaching Ability Based on Technical Pedagogical Content Knowledge and Few-Shot Learning.

Information-based instruction is the most important and recently altered sort of instruction. Numerous changes in educational techniques have emerged from the ongoing growth of science and technology. Teachers must also grasp and enhance their capacity to educate with information on a regular basis. The goal of this research is to look at how to use the TPACK model and computational intelligence to build and explain a model for evaluating English normal students' informatization teaching skills. To measure information-based teaching competence, this research recommends using the Technical Pedagogical Content Knowledge model and Few-Shot Learning technology. As a result, this paper covers the principles and related algorithms of both, as well as constructing and assessing the case design and analysis of the information-based teaching ability evaluation model. According to the experimental data, the average CK of normal students' subject material knowledge is 3.522, which is the highest among the seven dimensions. The subject content is well-understood by ordinary students. When compared with teaching abilities, the competence level is low, and the performance of the integration of technology and teaching content needs to be improved.

Periodicity and stationary distribution of two novel stochastic epidemic models with infectivity in the latent period and household quarantine.

Two types of stochastic epidemic models are formulated, in which both infectivity in the latent period and household quarantine on the susceptible are incorporated. With the help of Lyapunov functions and Has'minskii's theory, we derive that, for the nonautonomous periodic version with white noises, it owns a positive periodic solution. For the other version with white and telephone noises, we construct stochastic Lyapunov function with regime switching to present easily verifiable sufficient criteria for the existence of ergodic stationary distribution. Also, we introduce a series of numerical simulations to support our analytical findings. At last, a brief discussion of our theoretical results shows that the stochastic perturbations and household quarantine measures can significantly affect both periodicity and stationary distribution.

Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy.

BACKGROUND: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy. METHODS: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety. RESULTS: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice. CONCLUSION: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.

Dextran-polylactide micelles loaded with doxorubicin and DiR for image-guided chemo-photothermal tumor therapy.

Image-guided chemo-photothermal therapy based on near-infrared (NIR) theranostic agents has found promising applications in treating tumors. In this multimodal treatment, it is of critical importance to image real-time distribution of photothermal agents in vivo and to monitor therapeutic outcomes for implementing personalized treatment. In this study, an optimally synthesized dextran-polylactide (DEX-PLA) copolymer was assembled with doxorubicin (DOX) and DiR, a kind of NIR dye, to construct desirable micelles ((DiR + DOX)/DEX-PLA) for performing image-guided chemo-photothermal therapy. These (DiR + DOX)/DEX-PLA micelles had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. Based on the H22-tumor-bearing mouse model, (DiR + DOX)/DEX-PLA micelles were found to accumulate inside tumors sustainably and to emit strong fluorescence signals for more than three days. The (DiR + DOX)@DEX-PLA micelles together with NIR laser irradiation were able to highly inhibit tumor growth or even eradicate tumors with one injection and two dose-designated 5-minute laser irradiations at the tumor site during 14 days of treatment. Furthermore, they showed almost no impairment to the body of the treated mice. These (DiR + DOX)@DEX-PLA micelles have confirmative translational potential in clinical tumor therapy on account of their persistent image-guided capacity, high antitumor efficacy and good in vivo safety.

A stochastic epidemic model with infectivity in incubation period and homestead-isolation on the susceptible.

A stochastic epidemic model with infectivity rate in incubation period and homestead-isolation on the susceptible is developed with the aim of revealing the effect of stochastic white noise on the long time behavior. A good understanding of extinction and strong persistence in the mean of the disease is obtained. Also, we derive sufficient criteria for the existence of a unique ergodic stationary distribution of the model. Our theoretical results show that the suitably large noise can make the disease extinct while the relatively small noise is advantageous for persistence of the disease and stationary distribution.

Hydroxyethyl starch and its derivatives as nanocarriers for delivery of diagnostic and therapeutic agents towards cancers.

Many types of drugs and agents used for cancer diagnosis and therapy often have low bioavailability and insufficient efficacy, as well as causing various side effects due to their nonspecific delivery. Nanocarriers with purposely-designed compositions and structures have shown varying degrees of abilities to deliver these compounds towards cancers in passive or active manners. Despite the availability of a variety of materials for the construction of nanocarriers, natural polymers with good biocompatibility and biodegradability are preferable for such usage because of their high in vivo safety as well as easy removal of degradation products. Among the natural polymers intended for building nanocarriers, hydroxyethyl starch and its derivatives have gained tremendous attention in the field of drug delivery in the form of nanomedicines over the last decade. There is growing optimism that ever more hydroxyethyl starch-based nanomedicines will be a significant addition to the armoury currently used for cancer diagnosis and therapy.

Highly Fluorescent Non-Conventional Boron-Difluoride-Based π Organogel with Gelation-Assisted Piezochromism.

Triphenylamine-functionalized boron 2-(2'-pyridyl)imidazole complex bearing no alkyl chains or H-bond unit was found to be able to gelate a series of solvents, and the balanced intermolecular π-π interactions play an important role in its supramolecular self-assembly. The gelator molecule is piezochromic, and the dried gel responded to pressure more sensitively than regular crystalline powder.