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Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O 2 − and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H 2 O into •O 2 − and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O 2 − and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H 2 O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O 2 − and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm −2 . The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT. Conventional photodynamic therapy (PDT) is hindered by oxygen-dependent photosensitization pathways and high-power-density photoexcitation. Here, the authors develop polymer-based organic photosensitizers (PSs) through PS skeleton design and side-chain engineering to allow tumor-specific PDT under oxygen-free conditions using ultralow-power 808 nm photoexcitation.

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O 2 –• ). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O 2 to O 2 –• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance. Developing Type I photosensitizers (PSs) is vital for tackling hypoxic intolerance of photodynamic therapy in the hypoxic microenvironment, but elusive due to the lack of a general molecular design strategy. Here the authors report a universal and simple method to covert traditional Type II PSs to Type I PSs.

Ferroptosis is a necrotic form of iron‐dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density. Furthermore, the facilitatory effect of ferroptosis of osteocytes is verified in the occurrence and development of postmenopausal osteoporosis is associated with over activated osteoclastogenesis using a direct osteocyte/osteoclast coculture system and glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, the nuclear factor erythroid derived 2‐related factor‐2 (Nrf2) signaling pathway is confirmed to be a crucial factor in the ferroptosis of osteocytic cells. Nrf2 regulates the expression of nuclear factor kappa‐B ligand (RANKL) by regulating the DNA methylation level of the RANKL promoter mediated by DNA methyltransferase 3a (Dnmt3a), which is as an important mechanism in osteocytic ferroptosis‐mediated osteoclastogenesis. Taken together, this data suggests that osteocytic ferroptosis is involved in PMOP and can be targeted to tune bone homeostasis. Ferroptosis of osteocytes is a major factor implicated in the pathogenesis of osteoporosis. Ferroptotic osteocytes play a critical role in modulating bone loss through the regulation of osteoclast‐mediated bone resorption. The transcriptional regulation of Dnmt3a by Nrf2 leads to the methylation of the RANKL promoter, serving as a crucial molecular mechanism by which ferroptotic osteocytes promote osteoclast formation and differentiation.

Oil is the “blood” and economic lifeblood of modern industry, but traditional light crude oil has been over-consumed, and it has been difficult to meet human demand for energy, so the exploitation of heavy oil is particularly important. In this paper, an oil-soluble catalyst was synthesized to catalyze the pyrolysis reaction of heavy oil in collaboration with reservoir minerals, so as to achieve efficient viscosity reduction of heavy oil and reduce production costs. The experimental results showed that Zn(II)O + K had the best synergistic viscosity reduction effect after the aquathermolysis of No. 1 oil sample under the reaction conditions of 180 °C, 4 h, 30% of water, and 0.2% of catalyst, respectively, and the viscosity reduction rate was 61.74%. Under the catalysis of the isopropanol system, the viscosity reduction rate was increased to 91.22%. A series of characterizations such as freezing point, thermogravimetric analysis, DSC analysis, component analysis, gas chromatography, wax crystal morphology analysis, and GC-MS analysis of aqueous organic matter were carried out on heavy oil after reaction by different reaction systems, and it could be verified that the viscosity of heavy oil was reduced. Finally, through the study of the reaction mechanism of the model compound, combined with the aqueous phase analysis, it can be clearly found that the depolymerization between macromolecules, the breaking of heteroatom chains, hydrogenation, ring opening, and other effects mainly occur during the reaction, thereby weakening the van der Waals force and hydrogen bond of the recombinant interval, inhibiting the formation of grid structure in heavy oil and effectively reducing the viscosity of heavy oil.

Osteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects. The present study aims to determine whether omaveloxolone has a therapeutic effect on OA. Chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model in vitro . Indicators of cell viability, oxidative stress, inflammation, cell apoptosis and extracellular matrix (ECM) degradation were investigated. Proteins related to the Nuclear factor erythroid derived-2-related factor 2 (Nrf2)/antioxidant response element (ARE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways were assessed using Western blotting. A destabilized medial meniscus surgery-induced OA rat model was used in vivo . Gait analysis, microcomputed tomography analysis, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of omaveloxolone on attenuating osteoarthritis in vivo . The results showed that omaveloxolone exerts antioxidative, anti-inflammatory, antiapoptotic and anti-ECM degradation effects via activation of the Nrf2/ARE signalling pathway and inhibition of the NF-κB signalling pathway in chondrocytes in vitro and attenuates OA progression in vivo , suggesting that omaveloxolone may be a potential therapeutic agent for OA.

In order to study the synergistic effects of exogenous catalysts and in situ minerals in the reservoir during heavy oil aquathermolysis, in this paper, a series of simple supported transition metal complexes were prepared using sodium citrate, chloride salts and bentonite, and their catalytic viscosity reduction performances for heavy oil were investigated. Bentonite complex catalyst marked as B@Zn(II)L appears to be the most effective complex. B@Zn(II)L was characterized by scanning electron microscopy (SEM), Fourier-Transform Infrared (FTIR) spectroscopy, thermo-gravimetric analysis (TGA) and N2 adsorption–desorption isotherms. Under optimized conditions, the viscosity of the heavy oil was decreased by 88.3%. The reaction temperature was reduced by about 70 °C compared with the traditional reaction. The results of the group composition analysis and the elemental content of the heavy oil indicate that the resin and asphaltene content decreases, and the saturated and aromatic HC content increases. The results of TGA and DSC of the heavy oil show that the macromolecular substances in the heavy oil were cracked into small molecules with low boiling points by the reaction. GC-MS examination of water-soluble polar compounds post-reaction indicates that B@Zn(II)L can diminish the quantity of polar substances in heavy oil and lower the aromatic nature of these compounds. Thiophene and quinoline were utilized as model compounds to investigate the reaction mechanism. GC-MS analysis revealed that C-C, C-N and C-S bonds were cleaved during the reaction, leading to a decrease in the viscosity of heavy oil.

Nuclei and mitochondria are the only cellular organelles containing genes, which are specific targets for efficient cancer therapy. So far, several photosensitizers have been reported for mitochondria targeting, and another few have been reported for nuclei targeting. However, none have been reported for photosensitization in both mitochondria and nucleus, especially in cascade mode, which can significantly reduce the photosensitizers needed for maximal treatment effect. Herein, a light‐driven, mitochondria‐to‐nucleus cascade dual organelle cancer cell ablation strategy is reported. A functionalized iridium complex, named BT‐Ir, is designed as a photosensitizer, which targets mitochondria first for photosensitization and subsequently is translocated to a cell nucleus for continuous photodynamic cancer cell ablation. This strategy opens new opportunities for efficient photodynamic therapy. Herein, a functionalized iridium complex, named BT‐Ir, is designed as a light‐driven, mitochondria‐to‐nucleus cascade organelle targeted photosensitizer, which targets mitochondria first for photosensitization and subsequently is translocated to the cell nucleus for continuous photodynamic cancer cell ablation. This strategy opens new opportunities for efficient photodynamic therapy.

Osteoporosis is a common public health problem characterized by decreased bone mass, increased bone brittleness and damage to the bone microstructure. Excessive bone resorption by osteoclasts is the main target of the currently used drugs or treatment for osteoporosis. Effective antiresorptive drugs without side effects following long-term administration have become a major focus of anti-osteoporotic drugs. In the present study, we investigated the effect of berbamine, a small molecule natural product from Berberis amurensis Rupr , a traditional Chinese medicine, on RANKL-induced osteoclast differentiation in vitro and ovariectomy-induced bone loss in vivo . The results demonstrated that berbamine at a safe and effective dose inhibited osteoclastogenesis and bone resorption function in vitro by suppressing the nuclear factor-κB signaling pathway. In addition, berbamine protected against osteoporosis by inhibiting osteoclastogenesis and bone resorption function without affecting osteogenesis in the ovariectomy mouse model. These findings revealed that berbamine has a protective role against osteoporosis and may represent a novel promising treatment strategy for osteoporosis.

In the medical field, the analysis and understanding of human emotions is a key approach to the study of mental diseases. Many psychological or psychiatric disorders exhibit inconsistent and often subtle symptoms, which complicates the prediction of human emotions based on singular traits. Consequently, this study integrates a range of modal cues. The study proposes THRMM, a Transformer-based network for temporal modeling that leverages multiple contextual cues. The THRMM architecture effectively extracts global video features, character traits, and dialogue cues to monitor emotional shifts, capturing the emotional dynamics for timely and accurate emotion predictions. Ablation and comparative studies confirm the effectiveness of THRMM in temporal context modeling, emphasizing the importance of scene, task, and dialogue information in interpreting emotions.

In order to study the synergistic effects of exogenous catalysts and in situ minerals in the reservoir during heavy oil aquathermolysis, in this paper, a series of simple supported transition metal complexes were prepared using sodium citrate, chloride salts and bentonite, and their catalytic viscosity reduction performances for heavy oil were investigated. Bentonite complex catalyst marked as B@Zn(II)L appears to be the most effective complex. B@Zn(II)L was characterized by scanning electron microscopy (SEM), Fourier-Transform Infrared (FTIR) spectroscopy, thermo-gravimetric analysis (TGA) and N2 adsorption–desorption isotherms. Under optimized conditions, the viscosity of the heavy oil was decreased by 88.3%. The reaction temperature was reduced by about 70 °C compared with the traditional reaction. The results of the group composition analysis and the elemental content of the heavy oil indicate that the resin and asphaltene content decreases, and the saturated and aromatic HC content increases. The results of TGA and DSC of the heavy oil show that the macromolecular substances in the heavy oil were cracked into small molecules with low boiling points by the reaction. GC-MS examination of water-soluble polar compounds post-reaction indicates that B@Zn(II)L can diminish the quantity of polar substances in heavy oil and lower the aromatic nature of these compounds. Thiophene and quinoline were utilized as model compounds to investigate the reaction mechanism. GC-MS analysis revealed that C-C, C-N and C-S bonds were cleaved during the reaction, leading to a decrease in the viscosity of heavy oil.