Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action.

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative disease that occurs due to aging. Currently, effective drugs to mitigate or treat AD remain unavailable. AD is associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, and defects in cholesterol metabolism. Amp-activated protein kinase (AMPK) is an important serine/threonine protein kinase that regulates the energy status of cells. AMPK is widely present in eukaryotic cells and can sense and regulate energy metabolism to maintain energy supply and demand balance, making it a promising target for energy metabolism-based AD therapy. Therefore, this review aimed to discuss the molecular mechanism of AMPK in the pathogenesis of AD to provide a theoretical basis for the development of new anti-AD drugs. To review the mechanisms of phytochemicals in the treatment of AD via AMPK pathway regulation, we searched PubMed, Google Scholar, Web of Science, and Embase databases using specific keywords related to AD and phytochemicals in September 2023. Phytochemicals can activate AMPK or regulate the AMPK pathway to exert therapeutic effects in AD. The anti-AD mechanisms of these phytochemicals include inhibiting Aß aggregation, preventing Tau hyperphosphorylation, inhibiting inflammatory response and glial activation, promoting autophagy, and suppressing anti-oxidative stress. Additionally, several AMPK-related pathways are involved in the anti-AD mechanism, including the AMPK/CaMKKß/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, and PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin A, berberine, stigmasterol, arctigenin, and rutaecarpine are promising AMPK agonists with anti-AD effects. Several phytochemicals are effective AMPK agonists and may have potential applications in AD treatment. Overall, phytochemical-based drugs may overcome the barriers to the effective treatment of neurodegenerative diseases.

A Chromosome-Level Genome Assembly of the Non-Hematophagous Leech Whitmania pigra (Whitman 1884): Identification and Expression Analysis of Antithrombotic Genes.

Despite being a non-hematophagous leech, Whitmania pigra is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high quality genome of W. pigra and based on which, we performed a systematic identification of the potential antithrombotic genes and their corresponding proteins. We identified twenty antithrombotic gene families including thirteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. Unexpectedly, a total of 79 antithrombotic genes were identified, more than a typical blood-feeding Hirudinaria manillensis, which had only 72 antithrombotic genes. In addition, combining with the RNA-seq data of W. pigra and H. manillensis, we calculated the expression levels of antithrombotic genes of the two species. Five and four gene families had significantly higher and lower expression levels in W. pigra than in H. manillensis, respectively. These results showed that the number and expression level of antithrombotic genes of a non-hematophagous leech are not always less than those of a hematophagous leech. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a non-hematophagous leech to date and will significantly enhance the investigation and utilization of leech derivatives in thrombosis therapy research and pharmaceutical applications.

Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors.

Targeted and controllable drug release at lesion sites with the aid of visual navigation in real-time is of great significance for precise theranostics of cancers. Benefiting from the marvelous features (e.g., bright emission and phototheranostic effects in aggregates) of aggregation-induced emission (AIE) materials, constructing AIE-based multifunctional nanocarriers that act as all-arounders to integrate multimodalities for precise theranostics is highly desirable. Here, an intelligent nanoplatform (P-TN-Dox@CM) with homologous targeting, controllable drug release, and in vivo dual-modal imaging for precise chemo-photothermal synergistic therapy is proposed. AIE photothermic agent (TN) and anticancer drug (Dox) are encapsulated in thermo-/pH-responsive nanogels (PNA), and the tumor cell membranes are camouflaged onto the surface of nanogels. Active targeting can be realized through homologous effects derived from source tumor cell membranes, which advantageously elevates the specific drug delivery to tumor sites. After being engulfed into tumor cells, the nanogels exhibit a burst drug release at low pH. The near-infrared (NIR) photoinduced local hyperthermia can activate severe cytotoxicity and further accelerate drug release, thus generating enhanced synergistic chemo-photothermal therapy to thoroughly eradicate tumors. Moreover, P-TN-Dox@CM nanogels could achieve NIR-fluorescence/photothermal dual-modal imaging to monitor the dynamic distribution of therapeutics in real-time. This work highlights the great potential of smart P-TN-Dox@CM nanogels as a versatile nanoplatform to integrate multimodalities for precise chemo-photothermal synergistic therapy in combating cancers.

Spatiotemporal evolution of dissolved organic matter (DOM) and its response to environmental factors and human activities.

The South-to-North Water Diversion East Project (SNWDP-E) is an effective way to realize the optimal allocation of water resources in China. The North Dasha River (NDR) is the reverse recharge section that receives water from the Yufu River to the Wohushan Reservoir transfer project line in the SNWDP. However, the dissolved organic matter (DOM) evolution mechanism of seasonal water transfer projects on tributary waters has not been fully elucidated. In this paper, the NDR is the main object, and the changes in the composition and distribution of spectral characteristics during the winter water transfer period (WT) as well as during the summer non-water transfer period (NWT) are investigated by parallel factor analysis (PARAFAC). The results showed that the water connectivity caused by water transfer reduces the environmental heterogeneity of waters in the basin, as evidenced by the ammonia nitrogen (NH4+-N) and total phosphorus (TP) in the water body were significantly lower (p<0.05, p<0.01) during the water transfer period than the non-water transfer period. In addition, the fluorescence intensity of DOM was significantly lower in the WT than the NWT (p<0.05) and was mainly composed of humic substances generated from endogenous sources with high stability. While the NWT was disturbed by anthropogenic activities leading to significant differences in DOM composition in different functional areas. Based on the redundancy analysis (RDA) and multiple regression analysis, it was found that the evolution of the protein-like components is dominated by chemical oxygen demand (COD) and NH4+-N factors during the WT. While the NWT is mainly dominated by total nitrogen (TN) and TP factors for the evolution of the humic-like components. This study helps to elucidate the impact of water transfer projects on the trunk basin and contribute to the regulation and management of inter-basin water transfer projects.

[Herbal-moxa plaster for diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24+), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION: On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.

Expression of CAD and SOX2 in Postoperative Intestinal Tissues of Children with Hirschsprung's Disease and Their Interrelationship.

Objective: To investigate the expression and significance of intestinal Cathepsin D (CAD) and sex-determining region Y-frame protein 2 (SOX2) in children with Hirschsprung's disease (HD) after surgery. Methods: Immunohistochemistry and Western blot techniques were employed to examine the expression of CAD and SOX2 in colonic tissues obtained from 56 children with HD (HD group) and 23 colonic tissues obtained from fistulas for intestinal obstruction or perforation (control group). Pearson linear correlation analysis was conducted to analyze the relationship between CAD and SOX2 expression, the diameter of the intermuscular plexus, and the number of ganglion cells in the diseased intestinal segment. Results: The positive expression rates of CAD protein and SOX2 protein in the intestinal tissues of children with HD were lower than those in the control group (P < .05). Furthermore, the positive expression rates of CAD protein and SOX2 protein in the narrow intestinal tissue of HD children were lower than those in the transitional colon tissue (P < .05). The diameter of the intramuscular plexus and the number of ganglion cells in the intestinal tissue of the stenosis and transitional segments in HD children were lower than those in the control group (P < .05). There was a significant positive correlation between the diameter of the intermuscular plexus and the number of ganglion cells in the intestinal tissue of HD children and the expression intensity of CAD protein and SOX2 protein (P < .05). Conclusions: The down-regulated expression intensity of CAD protein and SOX2 protein in the diseased colon of children with HD may be associated with a decrease in the diameter of the intermuscular plexus and the number of ganglion cells.

AIEgens for synergistic anticancer therapy.

Cancer is a mortal disease that can invade other parts of the body and cause severe complications. Despite their continuous progress, conventional cancer therapies including surgery, chemotherapy, and radiation therapy have their inherent limitations. To improve the precision of cancer treatment, maximize the therapeutic effect and minimize mortality, synergistic therapies combining imaging guiding technologies, phototherapy, and other therapies have emerged due to the mutually strengthening therapeutic efficacy. However, traditional organic phototherapeutic agents are limited since their aggregation in aqueous media usually affects both their luminescence behavior and therapeutic effect. In contrast, aggregate-induced emission luminogens (AIEgens) provide an ideal solution to develop phototherapy with bright fluorescence and a significant treatment effect in the aggregate state. Combining AIE-based phototherapy and conventional therapies benefits from synergistic effects and extends the potential of developing accurate cancer therapy. AIE-based synergistic therapy has been popularly discussed with such unexplored potential in recent years. This review will introduce the most recent progress of AIE-based synergistic cancer therapy.

Supercritical CO2-assisted fabrication of CM-PDA/SF/nHA nanofibrous scaffolds for bone regeneration and chemo-photothermal therapy against osteosarcoma.

Concurrent treatment of tumor recurrence and bone defects after surgical resection of osteosarcoma remains a clinical challenge. Combination therapy based on local drug delivery systems shows great promise in the treatment of osteosarcoma. In this study, curcumin modified polydopamine nanoparticle loaded silk fibroin doped with nano-hydroxyapatite (CM-PDA/SF/nHA) nanofibrous scaffolds were developed to induce bone defect regeneration and chemo-photothermal synergistic effects against osteosarcoma. These scaffolds exhibited good photothermal conversion efficiency and photostability. Moreover, the results of ALP staining and alizarin red S (ARS) staining indicated that the CM-PDA/SF/1%nHA scaffolds had the most obvious promotion effect on early osteogenic differentiation. The results of in vitro and in vivo anti-osteosarcoma activity showed that the CM-PDA/SF/1%nHA scaffolds exhibited higher anti-osteosarcoma activity compared to the control and SF scaffolds. In addition, the CM-PDA/SF/1%nHA scaffolds could promote the proliferation and differentiation of bone marrow mesenchymal stem cells in vitro and new bone production in vivo. Thus, these results suggested that the CM-PDA/SF/1%nHA scaffolds could improve bone defect regeneration and achieve chemo-photothermal synergistic effects against osteosarcoma.

Xue-Jie-San prevents the early development of colitis-associated intestinal fibrosis by blocking Notch1 and FGL1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Xue-Jie-San (XJS), as a traditional Chinese herb prescription, has satisfactory effects on improving clinical symptoms and facilitating the healing of intestinal ulcers in patients with Crohn's disease (CD). This motivates the application of XJS on CD-associated complications. AIM OF THE STUDY: Intestinal fibrosis is a debilitating complication of CD. Currently, there is no effective medication available for preventing or reversing CD-related intestinal fibrosis. This study aimed to assess the efficacy and underlying mechanisms of XJS in the treatment of colitis-associated intestinal fibrosis. MATERIALS AND METHODS: A rat model of CD-related intestinal fibrosis was induced by 2,4,6-trinitrobenzene sulfonic acid administration and treated with XJS. The pathological changes of intestinal fibrosis were evaluated using Masson staining. Collagen deposition and epithelial-to-mesenchymal transition (EMT) were verified by immunohistochemical staining and Western blot analysis. Endothelial-to-mesenchymal transition (EndoMT) was assessed with immunofluorescence and immunohistochemical staining as well as Western blot analysis. Transmission electron microscopy was utilized to observe autophagosomes. The levels of autophagy-related proteins were detected via immunofluorescence staining and Western blot. Finally, the mTOR/ULK1 signaling pathway regulated by Notch1 or FGL1 was analyzed by Western blot. RESULTS: The results found that XJS ameliorated intestinal fibrosis through reducing the deposition of collagens such as Collagen 1 and Collagen 3. XJS inhibited the EMT process by increasing E-cadherin levels and decreasing the expressions of N-cadherin, Vimentin and Snail, which played a crucial role in collagen secretion and intestinal fibrosis. In addition, XJS also repressed the EndoMT process as reflected by the upregulation of CD31 and VE-cadherin levels and the downregulation of FSP1 and α-SMA expressions. Autophagy was activated following XJS treatment via suppression of the mTOR/ULK1 signaling pathway. Furthermore, XJS acted as an inhibitor of Notch1 and FGL1 signals, both of which regulated the mTOR signaling. CONCLUSIONS: Our findings validated that XJS prevented the early development of CD-related intestinal fibrosis by blocking the Notch1 and FGL1 signaling pathways to activate autophagy and thereby inhibit EMT and EndoMT.

Aggregation-induced emission biomaterials for anti-pathogen medical applications: detecting, imaging and killing.

Microbial pathogens, including bacteria, fungi and viruses, greatly threaten the global public health. For pathogen infections, early diagnosis and precise treatment are essential to cut the mortality rate. The emergence of aggregation-induced emission (AIE) biomaterials provides an effective and promising tool for the theranostics of pathogen infections. In this review, the recent advances about AIE biomaterials for anti-pathogen theranostics are summarized. With the excellent sensitivity and photostability, AIE biomaterials have been widely applied for precise diagnosis of pathogens. Besides, different types of anti-pathogen methods based on AIE biomaterials will be presented in detail, including chemotherapy and phototherapy. Finally, the existing deficiencies and future development of AIE biomaterials for anti-pathogen applications will be discussed.

Natural Coumarin Isomers with Dramatically Different AIE Properties: Mechanism and Application.

Aggregation-induced emission luminogens (AIEgens) are of great importance in optoelectronics and biomedical fields. However, the popular design philosophy by combining rotors with traditional fluorophores limits the imagination and structural diversity of AIEgens. Inspired by the fluorescent roots of the medicinal plant Toddalia asiatica, we discovered two unconventional rotor-free AIEgens, 5-methoxyseselin (5-MOS) and 6-methoxyseselin (6-MOS). Interestingly, a slight structural difference of the coumarin isomers leads to completely contrary fluorescent properties upon aggregation in aqueous media. Further mechanism investigation indicates that 5-MOS forms different extents of aggregates with the assistance of protonic solvents, leading to electron/energy transfer, which is responsible for its unique AIE feature, i.e., reduced emission in aqueous media but enhanced emission in crystal. Meanwhile, for 6-MOS, the conventional restriction of the intramolecular motion (RIM) mechanism is responsible for its AIE feature. More interestingly, the unique water-sensitive fluorescence property of 5-MOS enables its successful application for wash-free mitochondria imaging. This work not only demonstrates an ingenious tactic to seek new AIEgens from natural fluorescent species but also benefits the structure design and application exploration of next-generation AIEgens.

Multifunctional nanoparticles for the treatment and diagnosis of osteosarcoma.

Osteosarcoma (OS) is a common primary malignant bone tumor in adolescents. Currently, the commonly used treatment strategies for OS include surgery, chemotherapy and radiotherapy. However, these methods have some problems that cannot be ignored, such as postoperative sequelae and severe side effects. Therefore, in recent years, researchers have been looking for other means to improve the treatment or diagnosis effect of OS and increase the overall survival rate of patients. With the development of nanotechnology, nanoparticles (NPs) have presented excellent properties in improving the therapeutic efficacy of drugs for OS. Nanotechnology makes it possible for NPs to combine various functional molecules and drugs to achieve multiple therapeutic effects. This review presents the important properties of multifunctional NPs for the treatment and diagnosis of OS and focuses on the research progress of common NPs applied for drug or gene delivery, phototherapy and diagnosis of OS, such as carbon-based quantum dots, metal, chitosan and liposome NPs. Finally, the promising prospects and challenges of developing multifunctional NPs with enhanced efficacy are discussed, which lays the foundation and direction for improving the future therapeutic and diagnostic methods of OS.

Enhancement of CdS resistance to photocorrosion and photocatalytic removal of uranyl by complexation with N-deficient g-C3N4under aerobic conditions.

The effect of oxygen on the reduction of uranyl and photocorrosion of CdS remains a pressing issue when CdS is used as a photocatalyst for the removal of uranyl in uranium-containing wastewater. In this study, composites (CdS/PCN) were prepared by designing N-deficient g-C3N4 composite with CdS for efficient photocatalytic reduction of uranyl under aerobic condition. Meanwhile, a series of characterizations of the CdS/PCN composites were carried out by XRD, FT-IR, XPS, EDS and UV-vis. Surprisingly, the CdS/PCN not only showed very high photocatalytic reduction activity for uranyl under aerobic condition, but also the photocorrosion of CdS by oxygen and h+ was inhibited. With a starting uranium (VI) concentration of 20 ppm, the uranium (VI) removal efficiency could reach 97.33% (dark: 30 min, light: 10 min). Interestingly, the removal efficiency was better in air condition than in pure nitrogen or 30% oxygen atmosphere, i.e. a proper amount of oxygen has accelerated the reduction reaction, while excess oxygen weakened the reduction. Finally, a new mechanism of reduction of uranyl by CdS/PCN photocatalyst was given under aerobic condit ions. This work presents a novel strategy for reduction of U(VI) by photocatalysis and the inhibition of photocorrosion of photocatalysts under aerobic conditions.

The distinct plastisphere microbiome in the terrestrial-marine ecotone is a reservoir for putative degraders of petroleum-based polymers.

Research into plastic-degrading bacteria and fungi is important for understanding how microorganisms can be used to address the problem of plastic pollution and for developing new approaches to sustainable waste management and bioplastic production. In the present study, we isolated 55 bacterial and 184 fungal strains degrading polycaprolactone (PCL) in plastic waste samples from Dafeng coastal salt marshes, Jiangsu, China. Of these, Jonesia and Streptomyces bacteria also showed potential to degrade other types of petroleum-based polymers. The metabarcoding results proved the existence of plastisphere as a distinct ecological niche regardless of the plastic types where 27 bacterial and 29 fungal amplicon sequence variants (ASVs) were found to be significantly (p < 0.05) enriched, including some belonging to Alternaria (Ascomycota, Fungi) and Pseudomonas (Gammaproteobacteria, Bacteria) that were also mined out by the method of cultivation. Further assembly analyses demonstrated the importance of deterministic processes especially the environmental filtering effect of carbon content and pH on bacteria as well as the carbon and cation content on fungi in shaping the plastisphere communities in this ecosystem. Thus, the unique microbiome of the plastisphere in the terrestrial-marine ecotone is enriched with microorganisms that are potentially capable of utilizing petroleum-based polymers, making it a valuable resource for screening plastic biodegraders.

Excitatory Crossmodal Input to a Widespread Population of Primary Sensory Cortical Neurons.

Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience- or activity-induced plasticity. Given the potential role in brain function as indicated by previous reports, crossmodal connectivity in the sensory cortex needs to be further explored. Using perforated whole-cell recording in anesthetized adult rats, we found that almost all neurons recorded in the primary somatosensory, auditory, and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation, as recorded when brain activity states were pharmacologically down-regulated in light anesthesia. These crossmodal cortical responses were excitatory and subthreshold, and further seemed to be relayed primarily by the sensory thalamus, but not the sensory cortex, of the stimulated modality. Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs, which might play roles in brain functions involving crossmodal information processing or plasticity.

Organic photosensitizers for antimicrobial phototherapy.

Microbial infectious diseases, especially those caused by new and antibiotic-resistant pathogenic microbes, have become a significant threat to global human health. As an antibiotic-free therapy, phototherapy is a promising approach to treat microbial infections due to its spatiotemporal selectivity, non-invasiveness, minimal side effects, and broad antimicrobial spectrum. Although organic photosensitizer-based antimicrobial phototherapy has been extensively studied over the last decade, there has been no specific review article on this topic yet. It is important and timely to summarize recent research progress in this field. This tutorial review highlights the concept and significance of phototherapy and summarizes innovative types of organic photosensitizers with design strategies to deal with microbial infections. In addition, examples of organic antimicrobial photosensitizers, including antibacterial photosensitizers, antiviral photosensitizers, and antifungal photosensitizers are discussed. Finally, current challenges and future directions of organic photosensitizer-based phototherapy for clinical antimicrobial applications are presented. We believe that this tutorial review will provide general guidance for the future development of efficient photosensitizers and encourage preclinical and clinical studies for phototherapy-mediated antimicrobial treatments.

Evoking Highly Immunogenic Ferroptosis Aided by Intramolecular Motion-Induced Photo-Hyperthermia for Cancer Therapy.

Immunogenic cell death (ICD) through apoptosis or necroptosis is widely adopted to improve the therapeutic effect in cancer treatment by triggering a specific antitumor immunity. However, the tumor resistance to apoptosis/necroptosis seriously impedes the therapeutic effect. Recently, ferroptosis featured with excessive lipid peroxidation is demonstrated capable of bypassing the apoptosis/necroptosis resistance to kill cancer cells. To date, numerous efficient ferroptosis inducers are developed and successfully utilized for sensitizing cancer cells to ferroptosis. Unfortunately, these inducers can hardly generate adequate immunogenicity during induction of ferroptotic cancer cell death, which distinctly attenuates the efficacy of triggering antitumor immune response, therefore leads to unsatisfactory therapeutic effect. Herein, a novel high-performance photothermal nanoparticle (TPA-NDTA NP) is designed by exploiting energy via excited-state intramolecular motion and employed for immensely assisting ferroptosis inducer to evoke highly efficient ICD through ferroptosis pathway. Tumor models with poor immunogenicity are used to demonstrate the tremendously enhanced therapeutic effect endowed by highly enhanced immunogenic ferroptosis in vitro and in vivo by virtue of the NPs. This study sheds new light on a previously unrecognized facet of boosting the immunogenicity of ferroptosis for achieving satisfactory therapeutic effect in cancer therapy.

Arsenic Trioxide Cooperate Cryptotanshinone Exerts Antitumor Effect by Medicating Macrophage Polarization through Glycolysis.

Hepatocellular carcinoma (HCC) is an often-fatal malignant tumor with high lethality. Despite advances and significant efficacy in monotherapy, cancer therapy continues to pose several challenges. Novel combination regimens are an emerging strategy for anti-HCC and have demonstrated to be effective. Here, we propose a potential combination for HCC treatment named arsenic trioxide cooperate cryptotanshinone (ACCS). A remarkable synergistic therapeutic effect has been achieved compared with drugs alone in both in vivo and in vitro experiments. Mechanism study indicated that ACCS exerts its therapeutic actions by regulating macrophage-related immunity and glycolysis. ACCS potentiates the polarization of M1 macrophages and elevates the proportion of M1/M2 to remodel tumor immunity. Further molecular mechanism study revealed that ACCS intensifies the glucose utilization and glycolysis in the macrophage by increasing the phosphorylation of AMPK to activating the AMPK singling pathway. In conclusion, ACCS is a highly potential combination regimen for HCC treatment. The therapeutic potential of ACCS as a candidate option for anticancer drugs in restoring the balance of immunity and metabolism deserves further investigation.

Neural circuit control of innate behaviors.

All animals possess a plethora of innate behaviors that do not require extensive learning and are fundamental for their survival and propagation. With the advent of newly-developed techniques such as viral tracing and optogenetic and chemogenetic tools, recent studies are gradually unraveling neural circuits underlying different innate behaviors. Here, we summarize current development in our understanding of the neural circuits controlling predation, feeding, male-typical mating, and urination, highlighting the role of genetically defined neurons and their connections in sensory triggering, sensory to motor/motivation transformation, motor/motivation encoding during these different behaviors. Along the way, we discuss possible mechanisms underlying binge-eating disorder and the pro-social effects of the neuropeptide oxytocin, elucidating the clinical relevance of studying neural circuits underlying essential innate functions. Finally, we discuss some exciting brain structures recurrently appearing in the regulation of different behaviors, which suggests both divergence and convergence in the neural encoding of specific innate behaviors. Going forward, we emphasize the importance of multi-angle and cross-species dissections in delineating neural circuits that control innate behaviors.

Biomimetic Polydopamine-Modified Silk Fibroin/Curcumin Nanofibrous Scaffolds for Chemo-photothermal Therapy of Bone Tumor.

The simultaneous therapy of tumor recurrence and bone defects resulting from surgical resection of osteosarcoma is still a challenge in the clinic. Combination therapy based on a localized drug-delivery system shows great promise in the treatment of osteosarcoma. Herein, bifunctional polydopamine (PDA)-modified curcumin (CM)-loaded silk fibroin (SF) composite (SF/CM-PDA) nanofibrous scaffolds, which combined photothermal therapy with chemotherapy to synergistically enhance osteosarcoma therapy, were prepared by PDA coating of the SF/CM nanofibrous scaffolds fabricated by supercritical carbon dioxide (SC-CO2) technology. The PDA coating improved hydrophilicity and mechanical strength of the SF/CM scaffolds. The SF/CM-PDA scaffolds present good photothermal conversion capacity and excellent photostability. The low pH and near-infrared (NIR) irradiation could effectively accelerate release of CM in the SF/CM-PDA scaffolds. The in vitro anticancer results indicated that the biocompatible SF/CM-PDA scaffolds had a long-term, stable, and superior anticancer effect compared to pure CM. Furthermore, the SF/CM-PDA scaffolds significantly increased the growth inhibition of osteosarcoma MG-63 cells under NIR irradiation (808 nm and 1.3 W/cm2). Besides, the SF/CM-PDA scaffolds could enhance osteoblast MC3T3-E1 cell proliferation in vitro when the mass ratio of CM was 0.05-0.5%. This work has therefore demonstrated that the bifunctional SF/CM-PDA scaffolds provide a competitive strategy for local osteosarcoma therapy and bone regeneration.