A Combinatorial Single-Molecule Real-Time and Illumina Sequencing Analysis of Postembryonic Gene Expression in the Asian Citrus Psyllid Diaphorina citri.

Huanglongbing (HLB) is a systemic plant disease caused by 'Candidatus Liberibacter asiaticus (CLas)' and transmitted by Diaphorina citri. D. citri acquires the CLas bacteria in the nymph stage and transmits it in the adult stage, indicating that molting from the nymph to adult stages is crucial for HLB transmission. However, the available D. citri reference genomes are incomplete, and gene function studies have been limited to date. In the current research, PacBio single-molecule real-time (SMRT) and Illumina sequencing were performed to investigate the transcriptome of D. citri nymphs and adults. In total, 10,641 full-length, non-redundant transcripts (FLNRTs), 594 alternative splicing (AS) events, 4522 simple sequence repeats (SSRs), 1086 long-coding RNAs (lncRNAs), 281 transcription factors (TFs), and 4459 APA sites were identified. Furthermore, 3746 differentially expressed genes (DEGs) between nymphs and adults were identified, among which 30 DEGs involved in the Hippo signaling pathway were found. Reverse transcription-quantitative PCR (RT-qPCR) further validated the expression levels of 12 DEGs and showed a positive correlation with transcriptome data. Finally, the spatiotemporal expression pattern of genes involved in the Hippo signaling pathway exhibited high expression in the D. citri testis, ovary, and egg. Silencing of the D. citri transcriptional co-activator (DcYki) gene significantly increased D. citri mortality and decreased the cumulative molting. Our results provide useful information and a reliable data resource for gene function research of D. citri.

Impact of butylparaben on growth dynamics and microcystin-LR production in Microcystis aeruginosa.

The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.

Clinical characteristics, treatment and efficacy of calcaneal osteomyelitis: A systematic review with synthesis analysis 1118 reported cases.

BACKGROUND: Calcaneal osteomyelitis (CO) still poses great challenges to orthopaedic surgeons due to unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis. RESULTS: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcer (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately. CONCLUSIONS: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.

High-performance flexible p-type Ce-filled Fe3CoSb12 skutterudite thin film for medium-to-high-temperature applications.

P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 µW m-1 K-2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm-2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value.

Biosynthesis of silver nanoparticles using Burkholderia contaminans ZCC and mechanistic analysis at the proteome level.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

Aggregation induced emission dynamic chiral europium(III) complexes with excellent circularly polarized luminescence and smart sensors.

The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S-Eu-R-1, R = Et/Me; R/S-Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5D0 → 7F1) and 2429 M-1cm-1 of R-Eu-Et-1, achieving a rare double improvement. R-Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

The Effects of Four Different Thawing Methods on Quality Indicators of Amphioctopus neglectus.

Amphioctopus neglectus is a species of octopus that is favored by consumers due to its rich nutrient profile. To investigate the influence of different thawing methods on the quality of octopus meat, we employed four distinct thawing methods: air thawing (AT), hydrostatic thawing (HT), flowing water thawing (FWT), and microwave thawing (MT). We then explored the differences in texture, color, water retention, pH, total volatile basic nitrogen (TVB-N), total sulfhydryl content, Ca2+-ATPase activity, and myofibrillar protein, among other quality indicators in response to these methods, and used a low-field nuclear magnetic resonance analyzer to assess the water migration that occurred during the thawing process. The results revealed that AT had the longest thawing time, leading to oxidation-induced protein denaturation, myofibrillar protein damage, and a significant decrease in water retention. Additionally, when this method was utilized, the content of TVB-N was significantly higher than in the other three groups. HT, to a certain extent, isolated the oxygen in the meat and thus alleviated protein oxidation, allowing higher levels of Ca2+-ATPase activity, sulfhydryl content, and springiness to be maintained. However, HT had a longer duration: 2.95 times that of FWT, resulting in a 9.84% higher cooking loss and a 28.21% higher TVB-N content compared to FWT. MT had the shortest thawing time, yielding the lowest content of TVB-N. However, uneven heating and in some cases overcooking occurred, severely damaging the protein structure, with a concurrent increase in thawing loss, W value, hardness, and shear force. Meanwhile, FWT improved the L*, W* and b* values of octopus meat, enhancing its color and water retention. The myofibrillar protein (MP) concentration was also the highest after FWT, with clearer subunit bands in SDS-PAGE electrophoresis, indicating that less degradation occurred and allowing greater springiness, increased Ca2+-ATPase activity, and a higher sulfhydryl content to be maintained. This suggests that FWT has an inhibitory effect on oxidation, alleviating protein oxidation degradation and preserving the quality of the meat. In conclusion, FWT outperformed the other three thawing methods, effectively minimizing adverse changes during thawing and successfully maintaining the quality of octopus meat.

Design of Excellent Mechanical Performances and Magnetic Refrigeration via In Situ Forming Dual-Phase Alloys.

Magnetic refrigeration technology can achieve higher energy efficiency based on the magnetocaloric effect (MCE). However, the practical application of MCE materials is hindered by their poor mechanical properties, making them challenging to process into devices. Conventional strengthening strategies usually lead to a trade-off with refrigeration capacity reduction. Here, a novel design is presented to overcome this dilemma by forming dual-phase alloys through in situ precipitation of a tough magnetic refrigeration phase within an intermetallic compound with excellent MCE. In the alloy 87.5Gd-12.5Co, incorporating the interconnected tough phase Gd contributes to enhanced strength (≈505 MPa) with good ductility (≈9.2%). The strengthening phase Gd simultaneously exhibits excellent MCE, enabling the alloy to achieve a peak refrigeration capacity of 720 J kg-1. Moreover, the alloy shows low thermal expansion induced by the synergistic effect of the two phases. It is beneficial for maintaining structural stability during heat exchange in magnetic refrigeration. The coupling interaction between the two magnetic phases can broaden the refrigeration temperature range and reduce hysteresis. This study guides the development of new high-performance materials with an excellent combination of mechanical and magnetic refrigeration properties as needed for gas liquefaction and refrigerators.

The dairy-derived peptide Miltin exerts anti-obesity effects by increasing adipocyte thermogenesis.

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.

Different anion (NO3- and OAc-)-controlled construction of dysprosium clusters with different shapes.

The complex hydrolysis process and strong uncertainty of self-assembly rules have led to the precise synthesis of lanthanide clusters still being in the "blind-box" stage and simplifying the self-assembly process and developing reliable regulation strategies have attracted widespread attention. Herein, different anions are used to induce the construction of a series of dysprosium clusters with different shapes and connections. When the selected anion is NO3-, it blocks the coordination of metal sites around the cluster through the terminal group coordination mode, thereby controlling the growth of the cluster. When NO3- was changed to OAc-, OAc- adopted a bridging mode to induce modular units to build dysprosium clusters through an annular growth mechanism. Specifically, we selected 2-amino-6-methoxybenzoic acid, 2-hydroxybenzaldehyde, and Dy(NO3)3·6H2O to react under solvothermal conditions to obtain a pentanuclear dysprosium cluster (1). The five Dy(III) ions in 1 are distributed in upper and lower planes and are formed by the tight connection of nitrogen and oxygen atoms, and µ3-OH- bridges on the ligand. Next, octa-nuclear dysprosium cluster (2) were obtained by only regulating ligand substituents. The eight Dy(III) ions in 2 are tightly connected through ligand oxygen atoms, µ2-OH-, and µ3-OH- bridges, forming an elliptical {Dy/O} cluster core. Furthermore, only by changing NO3- to OAc-, a wheel-shaped tetradeca-nuclear dysprosium cluster (3) was obtained. Cluster 3 is composed of OAc- bridged multiple template Dy3L3 units and pulling of these template units connected by an annular growth mechanism forms a wheel-shaped cluster. The angle of the coordination site on NO3- is ∠ONO = 115°, which leads to the further extension of the metal sites on the periphery of clusters 1 and 2 through the terminal group coordination mode, thereby regulating the structural connection of the clusters. However, the angle of the coordination site on OAc- is ∠OCO = 128°, and a slightly increased angle leads to the formation of a ring-shaped cluster 3 by connecting the template units through bridging. This is a rare example of the controllable construction of lanthanide clusters with different shapes induced by the regulation of different anions, which provides a new method for the precise construction of lanthanide clusters with special shapes.

The effects of ambient temperature and feeding regimens on cecum bacteria composition and circadian rhythm in growing rabbits.

Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

Metal-bonded perovskite lead hydride with phonon-mediated superconductivity exceeding 46 K under ambient pressure.

In the search for high-temperature superconductivity in hydrides, a plethora of multi-hydrogen superconductors have been theoretically predicted, and some have been synthesized experimentally under ultrahigh pressures of several hundred GPa. However, the impracticality of these high-pressure methods has been a persistent issue. In response, we propose a new approach to achieve high-temperature superconductivity under ambient pressure by implanting hydrogen into lead to create a stable few-hydrogen binary perovskite, Pb4H. This approach diverges from the popular design methodology of multi-hydrogen covalent high critical temperature (Tc) superconductors under ultrahigh pressure. By solving the anisotropic Migdal-Eliashberg equations, we demonstrate that perovskite Pb4H presents a phonon-mediated superconductivity exceeding 46 K with inclusion of spin-orbit coupling, which is six times higher than that of bulk Pb (7.22 K) and comparable to that of MgB2, the highestTcachieved experimentally at ambient pressure under the Bardeen, Cooper, and Schrieffer framework. The highTccan be attributed to the strong electron-phonon coupling strength of 2.45, which arises from hydrogen implantation in lead that induces several high-frequency optical phonon modes with a relatively large phonon linewidth resulting from H atom vibration. The metallic-bonding in perovskite Pb4H not only improves the structural stability but also guarantees better ductility than the widely investigated multi-hydrogen, iron-based and cuprate superconductors. These results suggest that there is potential for the exploration of new high-temperature superconductors under ambient pressure and may reignite interest in their experimental synthesis in the near future.

Harmonizing Enzyme-like Cofactors to Boost Nanozyme Catalysis.

Engineering isolated metal sites resembling the primary coordination sphere of metallocofactors enables atomically dispersed materials as promising nanozymes. However, most existing nanozymes primarily focus on replicating specific metallocofactors while neglecting other supporting cofactors within active pockets, leading to reduced electron transfer (ET) efficiency and thus inferior catalytic performances. Herein, we report a metal-organic framework UiO-67 nanozyme with atomically dispersed iron sites, which involves multiple tailored enzyme-like nanocofactors that synergistically drive the ET process for enhanced peroxidase-like catalysis. Among them, the linker-coupled atomic iron site plays a critical role in substrate activation, while bare linkers and zirconia nodes facilitate the ET efficiency of intermediates. The synergy of three nanocofactors results in a 4.29-fold enhancement compared with the single effort of isolated metal site-based nanocofactor, holding promise in immunoassay for sensitive detection of chlorpyrifos. This finding opens a new way for designing high-performance nanozymes by harmonizing various nanocofactors at the atomic and molecular scale.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Spinning a Liquid Wheel and Driving Surface Thermomagnetic Convection with Light.

A typical Tesla thermomagnetic engine employs a solid magnetic wheel to convert thermal energy into mechanical energy, while thermomagnetic convection in ferrofluid is still challenging to observe because it is a volume convection that occurs in an enclosed space. Using a water-based ferrofluid, a liquid Tesla thermomagnetic engine is demonstrated and reports the observation of thermomagnetic convection on a free surface. Both types of fluid motions are driven by light and observed by simply placing ferrofluid on a cylindrical magnet. The surface thermomagnetic convection on the free surface is made possible by eliminating the Marangoni effect, while the spinning of the liquid wheel is achieved through the solid-like behavior of the ferrofluid under a strong magnetic field. Increasing the magnetic field reveals a transition from simple thermomagnetic convection to a combination of the central spin of the spiky wheel surrounded by thermomagnetic convection in the outer region of the ferrofluid. The coupling between multiple ferrofluid wheels through a fluid bridge is further demonstrated. These demonstrations not only unveil the unique properties of ferrofluid but also provide a new platform for studying complex fluid dynamics and thermomagnetic convection, opening up exciting opportunities for light-controlled fluid actuation and soft robotics.

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Research progress of antineoplastic drugs targeting platelets / 中国药理学通报

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

APR-246 increases tumor antigenicity independent of p53.

We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate that APR-246 and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity of tumor cells directly. MQ treatment of murine B16F10 melanoma cells promoted activation of melanoma-specific CD8+ T cells and increased the efficacy of a tumor cell vaccine using MQ-treated cells even when the B16F10 cells lacked p53. We then designed a novel combination of APR-246 with the TLR-4 agonist, monophosphoryl lipid A, and a CD40 agonist to further enhance these immunogenic effects and demonstrated a significant antitumor response. We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor's p53 mutation status.