Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.

Nodal staging score for adequacy of nodal staging in cervical cancer.

Background: Cervical cancer remains the fourth most common female malignancy with increasing newly cases around the world. It is of clinical value to precisely evaluate whether false negative nodal existed and develop a nodal staging model in cervical cancer. Materials and methods: Clinical data of cervical cancer patients was retrieved from the Surveillance, Epidemiology, and End Results database. Probability of missing nodal disease and nodal staging score (NSS) was computed to assess the nodal status of each individual.Prognostic value of NSS was assessed. Results: A total of 9056 individuals were in this study, with 5115 squamous cell carcinoma, 2791 adenocarcinoma, 512 adenosquamous carcinoma, and 638 other type individuals. A beta-binomial model was used to compute the probability of nodal disease in four histological types, respectively. False negative probability drastically decreased as more nodes examined. To reach 0.05 of false negative probability, it required at least 17 lymph nodes in squamous cell carcinoma patients,18 in adenocarcinoma, 12 in adenosquamous carcinoma patients and 14 in other types. To reach 0.95 of NSS, it took 10 lymph nodes in squamous cell carcinoma, 6 in adenocarcinoma, 10 in adenosquamous carcinoma and 7 in other types. Significant prognostic values of NSS quartiles subsets were found in all four histological sets. Conclusion: NSS tool enables adequate nodal staging of cervical cancer with significant prognostic value. Exact number of lymph nodes required for surgery in cervical cancer is specified based on histologic type.

Tris buffer-accelerated ligand exchange rate for instant fluorescence detection of trivalent chromium ion.

Functional nucleic acids (FNAs) have attracted a lot of attention for the rapid detection of metal ions. Cr3+ is one of the major heavy metal ions in natural waters. Due to the slow ligand exchange rate of Cr3+, the FNA-based Cr3+ sensors require long assay times, limiting the on-site applications. In this study, we report that the good's buffers containing amino and polyhydroxy groups greatly increase the ligand exchange rate of Cr3+. Using EDTA as a model coordinate ligand, the Tris buffer (100 mM, pH 7.0) showed the best acceleration effect among the eight buffers. It improved the rate constant ∼20-fold, shorten the half-time 19-fold, and lowered the activation energy ∼70% at 40 °C. The Tris buffer was then applied for sensor based on the Cr3+-binding induced fluorescence quenching of fluorescein (FAM)-labeled and single-stranded DNA (ssDNA), which shortened the assay time from 1 h to 1 min. The Tris buffer also ∼100% enhanced the fluorescence intensity of FAM, achieving the 11.4-fold lower limit of detection (LOD = 6.97 nM, S/N = 3). By the combination use of the Tris buffer and ascorbic acid, the strong interference from Cu2+, Pb2+, and Fe3+ suffered in many previous reported Cr3+ sensors was avoided. The practical application of the sensor for the detection of Cr3+ spiked in the real water samples were demonstrated with high recovery percentages. The Tris buffer could be applied for other metal ions with slow ligand exchange rate (such as V2+, Co3+ and Fe2+) to solve diverse issues such as long assay time and low synthesis yield of metal complexes, without the need of heating treatment.

Sybil Attacks Detection and Traceability Mechanism Based on Beacon Packets in Connected Automobile Vehicles.

Connected Automobile Vehicles (CAVs) enable cooperative driving and traffic management by sharing traffic information between them and other vehicles and infrastructures. However, malicious vehicles create Sybil vehicles by forging multiple identities and sharing false location information with CAVs, misleading their decisions and behaviors. The existing work on defending against Sybil attacks has almost exclusively focused on detecting Sybil vehicles, ignoring the traceability of malicious vehicles. As a result, they cannot fundamentally alleviate Sybil attacks. In this work, we focus on tracking the attack source of malicious vehicles by using a novel detection mechanism that relies on vehicle broadcast beacon packets. Firstly, the roadside units (RSUs) randomly instruct vehicles to perform customized key broadcasting and listening within communication range. This allows the vehicle to prove its physical presence by broadcasting. Then, RSU analyzes the beacon packets listened to by the vehicle and constructs a neighbor graph between the vehicles based on the customized particular fields in the beacon packets. Finally, the vehicle's credibility is determined by calculating the edge success probability of vehicles in the neighbor graph, ultimately achieving the detection of Sybil vehicles and tracing malicious vehicles. The experimental results demonstrate that our scheme achieves the real-time detection and tracking of Sybil vehicles, with precision and recall rates of 98.53% and 95.93%, respectively, solving the challenge of existing detection schemes failing to combat Sybil attacks from the root.

Oxidized DJ-1 activates the p-IKK/NF-κB/Beclin1 pathway by binding PTEN to induce autophagy and exacerbate myocardial ischemia-reperfusion injury.

Patients with myocardial infarction have a much worse prognosis when they have myocardial ischemia-reperfusion (I/R) injury. Further research into the molecular basis of myocardial I/R injury is therefore urgently needed, as well as the identification of novel therapeutic targets and linkages to interventions. Three cysteine residues are present in DJ-1 at amino acids 46, 53, and 106 sites, with the cysteine at position 106 being the most oxidation-prone. This study sought to understand how oxidized DJ-1(C106) contributes to myocardial I/R damage. Rats' left anterior descending branches were tied off to establish a myocardial I/R model in vivo. A myocardial I/R model in vitro was established via anoxia/reoxygenation (A/R) of H9c2 cells. The results showed that autophagy increased after I/R, accompanied by the increased expression of oxidized DJ-1 (ox-DJ-1). In contrast, after pretreatment with NAC (N-acetylcysteine, a ROS scavenger) or Comp-23 (Compound-23, a specific antioxidant binding to the C106 site of DJ-1), the levels of ox-DJ-1, autophagy and LDH release decreased, and cell survival rate increased. Furthermore, the inhibition of interaction between ox-DJ-1 and PTEN could increase PTEN phosphatase activity, inhibit the p-IKK/NF-κB/Beclin1 pathway, reduce injurious autophagy, and alleviate A/R injury. However, BA (Betulinic acid, a NF-κB agonist) was able to reverse the protective effects produced by Comp-23 pretreatment. In conclusion, ox-DJ-1 could activate detrimental autophagy through the PTEN/p-IKK/NF-κB/Beclin1 pathway and exacerbate myocardial I/R injury.

Novel methyltransferase G9a inhibitor induces ferroptosis in multiple myeloma through Nrf2/HO-1 pathway.

Multiple myeloma (MM) is a common malignant hematologic neoplasm, and the involvement of epigenetic modifications in its development and drug resistance has received widespread attention. Ferroptosis, a new ferroptosis-dependent programmed death mode, is closely associated with the development of MM. The novel methyltransferase inhibitor DCG066 has higher cell activity, but its mechanism of action in MM has not been clarified. Here, we found that DCG066 (5µM) inhibited the proliferation and induced ferroptosis in MM cells; the intracellular levels of ROS, iron, and MDA were significantly elevated, and the level of GSH was reduced after the treatment of DCG066; The protein expression levels of SLC7A11, GPX4, Nrf2 and HO-1 were significantly reduced, and these phenomena could be reversed by ferroptosis inhibitor Ferrostatin-1 (Fer-1) and Nrf2 activator Tert-butyl hydroquinone (TBHQ). Meanwhile, the protein expression levels of Keap1 was increased, and heat shock proteins (HSP70, HSP90 and HSPB1) were reduced after DCG066 treatment. In conclusion, this study confirmed that DCG066 inhibits MM proliferation and induces ferroptosis via the Nrf2/HO-1 pathway.

Intestinal organoid modeling: bridging the gap from experimental model to clinical translation.

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name "mini-intestines". Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

Directed Assembly of Ordered Mixed-Spacer Quasi-2D Halide Perovskites through Homomeric Chains of Intermolecular Bonds.

Two-dimensional (2D) halide perovskites (HPs) are of significant interest to researchers because of their natural structural frameworks and intriguing optoelectronic properties. However, the direct fabrication of ordered mixed-spacer quasi-2D HPs remains challenging. Herein, a synthetic strategy inspired by the principle of supramolecular synthons is employed for the self-assembly of a series of ordered mixed-spacer bilayered HPs. The key innovation involves the introduction of intermolecular hydrogen bonds using a bifunctional 3-aminopropionitrile cation. Three homogeneous n = 2 structures are obtained, with a subtly ordered perovskite connected by two distinct types of organic cation layers, resulting in a recurrent ABAB' stacking sequence. These three compounds exhibit attractive semiconducting properties. Moderate bandgaps in the range of 2.70 to 2.76 eV with an absorption wavelength range of 448-459 nm exhibit excellent photoelectric response. Moreover, the ordered structures facilitate excellent polarization-sensitive photodetection, with an impressive on/off ratio of 103. The response speed ranged from 298 to 381 µs, and the out-of-plane polarization-related dichroism ratio is determined to be 1.19. Such ordered mixed-spacer bilayered perovskites have not been reported. These results enrich the HPs system and play a significant role in the direct assembly of novel perovskites with ordered structures.

Epitaxial Strain Enhanced Ferroelectric Polarization toward a Giant Tunneling Electroresistance.

A substantial ferroelectric polarization is the key for designing high-performance ferroelectric nonvolatile memories. As a promising candidate system, the BaTiO3/La0.67Sr0.33MnO3 (BTO/LSMO) ferroelectric/ferromagnetic heterostructure has attracted a lot of attention thanks to the merits of high Curie temperature, large spin polarization, and low ferroelectric coercivity. Nevertheless, the BTO/LSMO heterostructure suffers from a moderate FE polarization, primarily due to the quick film-thickness-driven strain relaxation. In response to this challenge, we propose an approach for enhancing the FE properties of BTO films by using a Sr3Al2O6 (SAO) buffering layer to mitigate the interfacial strain relaxation. The continuously tunable strain allows us to illustrate the linear dependence of polarization on epitaxial strain with a large strain-sensitive coefficient of ∼27 µC/cm2 per percent strain. This results in a giant polarization of ∼80 µC/cm2 on the BTO/LSMO interface. Leveraging this large polarization, we achieved a giant tunneling electroresistance (TER) of ∼105 in SAO-buffered Pt/BTO/LSMO ferroelectric tunnel junctions (FTJs). Our research uncovers the fundamental interplay between strain, polarization magnitude, and device performance, such as on/off ratio, thereby advancing the potential of FTJs for next-generation information storage applications.

Isotope Effect-Enabled Crystal Enlargement in Metal-Organic Frameworks.

Synthesizing large metal-organic framework (MOF) single crystals has garnered significant research interest, although it is hindered by the fast nucleation kinetics that gives rise to numerous small nuclei. Given the different chemical origins inherent in various types of MOFs, the development of a general approach to enhancing their crystal sizes presents a formidable challenge. Here, we propose a simple isotopic substitution strategy to promote size growth in MOFs by inhibiting nucleation, resulting in a substantial increase in the crystal volume ranging from 1.7- to 165-fold. Impressively, the crystals prepared under optimized conditions by normal approaches can be further enlarged by the isotope effect, yielding the largest MOF single crystal (2.9 cm × 0.48 cm × 0.23 cm) among the one-pot synthesis method. Detailed in situ characterizations reveal that the isotope effect can retard crystallization kinetics, establish a higher nucleation energy barrier, and consequently generate fewer nuclei that eventually grow larger. Compared with the smaller crystals, the isotope effect-enlarged crystal shows 33% improvement in the X-ray dose rate detection limit. This work enriches the understanding of the isotope effect on regulating the crystallization process and provides inspiration for exploring potential applications of large MOF single crystals.

TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.

Ovarian cancer is a major cause of death among cancer patients. Recent research has shown that the transmembrane emp24 domain (TMED) protein family plays a role in the progression of various types of cancer. In this study, we investigated the expression of TMED3 in ovarian cancer tumors compared to nontumor tissues using immunohistochemical staining. We found that TMED3 was overexpressed in ovarian cancer tumors, and its high expression was associated with poor disease-free and overall survival. To understand the functional implications of TMED3 overexpression in ovarian cancer, we conducted experiments to knockdown TMED3 using short hairpin RNA (shRNA). We observed that TMED3 knockdown resulted in reduced cell viability and migration, as well as increased cell apoptosis. Additionally, in subcutaneous xenograft models in BALB-c nude mice, TMED3 knockdown inhibited tumor growth. Further investigation revealed that SMAD family member 2 (SMAD2) was a downstream target of TMED3, driving ovarian cancer progression. TMED3 stabilized SMAD2 by inhibiting the E3 ligase NEDD4-mediated ubiquitination of SMAD2. To confirm the importance of SMAD2 in TMED3-mediated ovarian cancer, we performed functional rescue experiments and found that SMAD2 played a critical role in this process. Moreover, we discovered that the PI3K-AKT pathway was involved in the promoting effects of TMED3 overexpression on ovarian cancer cells. Overall, our study identifies TMED3 as a prognostic indicator and tumor promoter in ovarian cancer. Its function is likely mediated through the regulation of the SMAD2 and PI3K-AKT signaling pathway. These findings contribute to our understanding of the molecular mechanisms underlying ovarian cancer progression and provide potential targets for therapeutic intervention.

Advanced glycation end products promote meniscal calcification by activating the mTOR-ATF4 positive feedback loop.

The meniscus is vital for maintaining knee homeostasis and function. Meniscal calcification is one of the earliest radiological indicators of knee osteoarthritis (KOA), and meniscal calcification is associated with alterations in biomechanical properties. Meniscal calcification originates from a biochemical process similar to vascular calcification. Advanced glycation end products (AGEs) and their receptors (RAGEs) reportedly play critical roles in vascular calcification. Herein, we investigated whether targeting AGE-RAGE is a potential treatment for meniscal calcification. In our study, we demonstrated that AGE-RAGE promotes the osteogenesis of meniscal cells and exacerbates meniscal calcification. Mechanistically, AGE-RAGE activates mTOR and simultaneously promotes ATF4 accumulation, thereby facilitating the ATF4-mTOR positive feedback loop that enhances the osteogenic capacity of meniscal cells. In this regard, mTOR inhibits ATF4 degradation by reducing its ubiquitination, while ATF4 activates mTOR by increasing arginine uptake. Our findings substantiate the unique role of AGE-RAGE in the meniscus and reveal the role of the ATF4-mTOR positive feedback loop during the osteogenesis of meniscal cells; these results provide potential therapeutic targets for KOA.

Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination External Rotation Type IV Ankle Injury.

BACKGROUND Lateral malleolus fractures, typically from trauma, sports, or accidents, are common, with supination external rotation (SER) injuries being most prevalent. SER injuries involve complex joint mechanics and often necessitate surgical intervention for instability. This study compares intramedullary nail and plate fixation for fibula fractures in SER type IV ankle injuries, considering their biomechanical properties and influence on fracture healing. MATERIAL AND METHODS A prospective, randomized study was conducted between January 2021 and December 2021. A total of 81 patients with SER injuries were included in the study. Surgical procedures were performed using either intramedullary nails or plates. The following parameters were recorded and analyzed: postoperative complications, operation times, bone healing times, American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores for pain, and ankle range of motion. RESULTS Out of the 81 cases, 42 were treated with intramedullary nails, while 39 received plate fixation. Statistical analysis revealed a significantly lower rate of postoperative complications in the intramedullary nail group than in the the plate fixation group (9.52% vs 30.77%, P<0.0164). However, there were no significant differences between the 2 groups in terms of operation time, bone healing time, AOFAS scores, VAS scores, and functional evaluations (P>0.05). CONCLUSIONS Plate fixation and intramedullary nail fixation are effective techniques for treating fibula fractures in SER type IV injuries. However, intramedullary nail fixation demonstrates a lower rate of complications. Therefore, intramedullary nails may be preferable to plate fixation for the management of fibula fractures in SER type IV ankle injuries.

Synthesis and Properties of Cobalt/Nickel-Iron-Antimony(III, V)-Oxo Tartrate Cluster-Based Compounds.

Two types of isostructural iron-cobalt/nickel-antimony-oxo tartrate cluster-based compounds, namely (H3O)(Me2NH2)[M(H2O)6]2[FeII2SbIII12(µ4-O)3(µ3-O)8(tta)6]·6H2O (M = Co (1); Ni (3)), H5/3[Co2.5FeII4/3FeIII3(H2O)13SbV1/3FeIII2/3(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (2) and H2[Ni2.25FeII1.5FeIII3(H2O)14SbV0.25FeIII0.75(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (4) (H4tta = tartaric acid) were synthesized via simple solvothermal reactions. All the clusters in the structures adopt sandwich configurations, that is, bilayer sandwich configuration in 1 and 3 and monolayer sandwich configuration in 2 and 4. Interestingly, the monolayer sandwiched compounds 2 and 4 represent rare examples of cluster-based compounds containing mixed-valence Sb(III, V), whose center of the intermediate layer is the co-occupied [FexSbV1-x]. This is different from that of previously reported sandwich-type antimony-oxo clusters in which the center position is either occupied by a transition metal ion or a Sb(V) alone. Thus, the discovery of title compounds 2 and 4 makes the evolution of center metal ion more complete, that is, from M, MxSbV1-x to SbV. All the title compounds were fully characterized, and the photocatalysis, proton conduction and magnetism of compounds 2 and 4 were studied.

A Sustainable Retinal Drug Co-Delivery for Boosting Therapeutic Efficacy in wAMD: Unveiling Multifaceted Evidence and Synergistic Mechanisms.

Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age-related macular degeneration (wAMD). Here, a microemulsion-doped hydrogel (Bor/PT-M@TRG) is engineered as an intravitreal depot composing of temperature-responsive hydrogel (TRG) and borneol-decorated paeoniflorin (PF) & tetramethylpyrazine (TMP)-coloaded microemulsions (Bor/PT-M). Bor/PT-M@TRG, functioning as the "ammunition depot", resides in the vitreous and continuously releases Bor/PT-M as the therapeutic "bullet", enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor/PT-M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress-induced damage in vivo. Combinational PF&TMP regulates the "reactive oxygen species/nuclear factor erythroid-2-related factor 2/heme oxygenase-1" pathway and blocks the "hypoxia inducible factor-1α/vascular endothelial growth factor" signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography-mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE-19 cells, in vivo eye balls, and ex vivo section/retina-choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT-M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.

Chronic low salinity stress rescued masculinization effect in farmed Cynoglossus semilaevis population.

Salinity, being an indispensable abiotic factor crucial for the survival of marine organisms, has demonstrated diverse alterations globally in response to the current trend of global warming. In this study, the effect of chronic low salinity stress on teleosts' sex differentiation was investigated using Cynoglossus semilaevis, an economically important fish with both genetic and environmental sex determination system. The cultivation experiment was conducted employing artificially simulated seawater of 20 ppt and ambient sea water of 30 ppt to rear juveniles C. semilaevis. Throughout the experiment, the growth performance was assessed and the histology of gonadal development was examined, a significantly lower masculinization rate was observed in LS group. To gain further insights, transcriptome analysis was conducted using raw reads obtained from 53 libraries derived from gonads of 55 days post fertilization (dpf) and 100 dpf juveniles in both LS and CT groups. GO/KEGG enrichment were further proceeded, Terms and pathways involved in reproduction ability, germ cell proliferation, immune function, steroid metabolism etc., were illuminated and a possible crosstalk between HPI and HPG axis was proposed. WGCNA was conducted and two hub genes, hspb8-like and Histone H2A.V were exhibited to be of great significance in the changes of masculinization rate. Our findings provided solid reference for sex differentiation study of GSD + ESD species in a constantly changing ocean environment, as well as practice guiding significance for the environmental management for the culture of C. semilaevis.

Drug-Loaded Biomimetic Carriers for Non-Hodgkin's Lymphoma Therapy: Advances and Perspective.

Chemotherapy remains the mainstay of treatment for the lymphoma patient population, despite its relatively poor therapeutic results, high toxicity, and low specificity. With the advancement of biotechnology, the significance of drug-loading biomimetic materials in the medical field has become increasingly evident, attracting extensive attention from the scientific community and the pharmaceutical industry. Given that they can cater to the particular requirements of lymphoma patients, drug-loading biomimetic materials have recently become a potent and promising delivery approach for various applications. This review mainly reviews the recent advancements in the treatment of tumors with biological drug carrier-loaded drugs, outlines the mechanisms of lymphoma development and the diverse treatment modalities currently available, and discusses the merits and limitations of biological drug carriers. What is more, the practical application of biocarriers in tumors is explored by providing examples, and the possibility of loading such organisms with antilymphoma drugs for the treatment of lymphoma is conceived.

Nonlinear Optical Switching in a Tin-Based Multilayered Halide Perovskite Activated by Stereoactive Lone Pairs and Confined Rotators.

In recent years, there has been a surge in research enthusiasm on searching for solid-state nonlinear optical (NLO) switching materials in halide perovskites owing to their exceptional structural flexibility, compositional diversity, and broad property tenability. However, the majority of reported halide perovskite NLO switching materials contain toxic elements (e.g., Pb), which raise significant environmental concerns. Herein, we present a novel lead-free multilayered halide perovskite NLO switching material, (BA)2(EA)2Sn3Br10 (1, where BA is butylammonium and EA is ethylammonium). Driven by the stereochemically active lone-pair electrons of the Sn2+ cation and the cage-confined effect of EA rotators, 1 undergoes a phase transition with symmetry breaking from P4/mnc to Cmc21, which gives rise to a highly efficient modulation of the quadratic NLO property (0.7 times that of KH2PO4) at a high temperature of 353 K. Furthermore, crystallographic investigation combined with theoretical calculations reveals that the efficient modulation of NLO properties in 1 stems from the synergistic effects between stereochemically active lone pair-induced octahedral distortions and order/disorder transformation of organic cations. This study opens up an instructive avenue for designing and advancing environmentally friendly solid-state NLO switches in halide perovskites.

SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.

Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.