SOX9 functionalized scaffolds as a barrier to against cartilage fibrosis.

Hyaline cartilage regeneration will bring evangel to millions of people suffered from cartilage diseases. However, uncontrollable cartilage fibrosis and matrix mineralization are the primary causes of cartilage regeneration failure in many tissue engineering scaffolds. This study presents a new attempt to avoid endochondral ossification or fibrosis in cartilage regeneration therapy by establishing biochemical regulatory area. Here, SOX9 expression plasmids are assembled in cellulose gels by chitosan gene vectors to fabricate SOX9+ functionalized scaffolds. RT-qPCR, western blot and biochemical analysis all show that the SOX9 reinforcement strategy can enhance chondrogenic specific proteins expression and promote GAG production. Notably, the interference from SOX9 has resisted osteogenic inducing significantly, showing an inhibition of COL1, OPN and OC production, and the inhibition efficiency was about 58.4 %, 22.8 % and 76.9 % respectively. In vivo study, implantation of these scaffolds with BMSCs can induce chondrogenic differentiation and resist endochondral ossification effectively. Moreover, specific SOX9+ functionalized area of the gel exhibited the resistance to matrix mineralization, indicating the special biochemical functional area for cartilage regeneration. These results indicate that this strategy is effective for promoting the hyaline cartilage regeneration and avoiding cartilage fibrosis, which provides a new insight to the future development of cartilage regeneration scaffolds.

Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1.

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats.

Surface Molecular Engineering for Fully Textured Perovskite/Silicon Tandem Solar Cells.

Developing large-scale monolithic perovskite/silicon tandem devices based on industrial Czochralski silicon wafers will likely have to adopt double-side textured architecture, given their optical benefits and low manufacturing costs. However, the surface engineering strategies that are widely used in solution-processed perovskites to regulate the interface properties are not directly applicable to micrometric textures. Here, we devise a surface passivation strategy by dynamic spray coating (DSC) fluorinated thiophenethylammonium ligands, combining the advantages of providing conformal coverage and suppressing phase conversion on textured surfaces. From the viewpoint of molecular engineering, theoretical calculation and experimental results demonstrate that introducing trifluoromethyl group provide more effective surface passivation through strong interaction and energy alignment by forming a dipole layer. Consequently, the DSC treatment of this bifunctional molecule enables the tandem cells based on industrial silicon wafers to achieve a certified stabilized power conversion efficiency of 30.89%. In addition, encapsulated devices display excellent operational stability by retaining over 97% of their initial performance after 600 h continuous illumination.

Function Electrical Stimulation Effect on Muscle Fatigue Based on Fatigue Characteristic Curves of Dumbbell Weightlifting Training.

The parameter setting of functional electrical stimulation (FES) is important for active recovery training since it affects muscle health. Among the FES parameters, current amplitude is the most influential factor. To explore the FES effect on the maximum stimulation time, this study establishes a curve between FES current amplitude and the maximum stimulation time based on muscle fatigue. We collect 10 subjects' surface electromyography under dumbbell weightlifting training and analyze the muscle fatigue state by calculating the root mean square (RMS) of power. By analyzing signal RMS, the fatigue characteristic curves under different fatigue levels are obtained. According to the muscle response under FES, the relationship curve between the current amplitude and the maximum stimulation time is established and FES parameters' effect on the maximum stimulation time is obtained. The linear curve provides a reference for FES parameter setting, which can help to set stimulation time safely, thus preventing the muscles from entering an excessive fatigue state and becoming more active to muscle recovery training.

LanCL2 Implicates in Testicular Redox Homeostasis and Acrosomal Maturation.

Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis.

Given the extremely high inter-patient heterogeneity among acute myeloid leukemia (AML), identifying biomarkers for prognostic assessment and therapeutic guidance is crucial. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In this study, we evaluate the prognostic potential of all human CSMs in AML patients based on differential gene expression analysis and univariate Cox regression analysis. Utilizing multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we construct a 9-CSMs prognostic model for risk stratification of AML patients. The predictive value of the 9-CSMs risk score is further confirmed in three independent datasets. Multivariate Cox regression analysis shows that the risk score is an independent prognostic factor for AML patients. AML patients with high 9-CSMs risk scores have shorter overall and event-free survival time than those with lower scores. Notably, our single-cell RNA-seq analysis indicates that patients with high 9-CSMs risk scores exhibit chemotherapy resistance. Further, PI3K inhibitors are identified as potential treatments for these high-risk patients. In conclusion, we construct a 9-CSMs prognostic model which is an independent prognostic factor for the survival of AML patients and has the potential to guide drug therapy.

Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis.

Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown promising results in alleviating inflammation and infection. Here, we aimed to evaluate the therapeutic potential of medical ozone in sepsis-induced ALI using a mouse model, measuring behavioral assessments, lung function, and blood flow. Western blot was used to quantify the levels of protein. In vitro, experiments on BMDM cells examine the impact of AMPK inhibitors and agonists on phagocytic activity. Results indicate that medical ozone can enhance the survival rate, ameliorate lung injury, and improve lung function and limb microcirculation in mice with ALI. Notably, it inhibits NETs formation, a crucial player in ALI development. Medical ozone also counteracts elevated TF, MMP-9, and IL-1ß levels. In ALI mice, the effects of ozone are nullified and BMDMs exhibit impaired engulfment of NETs following Sr-a1 knockout. Under normal physiological conditions, the use of an AMPK antagonist produces similar effects to Sr-a1 knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. On the contrary, AMPK agonists enhance this phagocytic process. In conclusion, medical ozone can alleviate sepsis-induced lung injury via the AMPK/SR-A1 pathway, thereby enhancing phagocytosis of NETs by macrophages.

Electrically Oriented Antibodies on Transistor for Monitoring Several Copies of Methylated DNA.

An antibody transistor is a promising biosensing platform for the diagnosis and monitoring of various diseases. Nevertheless, the low concentration and short half-life of biomarkers require biodetection at the trace-molecule level, which remains a challenge for existing antibody transistors. Herein, we demonstrate a graphene field-effect transistor (gFET) with electrically oriented antibody probes (EOA-gFET) for monitoring several copies of methylated DNA. The electric field confines the orientation of antibody probes on graphene and diminishes the distance between graphene and methylated DNAs captured by antibodies, generating more induced charges on graphene and amplifying the electric signal. EOA-gFET realizes a limit of detection (LoD) of ∼0.12 copy µL-1, reaching the lowest LoD reported before. EOA-gFET shows a distinguishable signal for liver cancer clinical serum samples within ∼6 min, which proves its potential as a powerful tool for disease screening and diagnosis.

Theranostic antibacterial hydrogel based on biopolymers cross-linked and doped with phytic acid from rice bran for wound healing.

Theranostic antibacterial wound dressing is highly recommended in practical applications. The conventional methods of integrating diagnostic and therapeutic functions have the disadvantages of complicated preparation, mutual interference, inability to effectively broad spectrum antibacterial property, and easy to induce drug-resistant bacteria. Herein, a pH and light-responsive theranostic antibacterial hydrogel is developed by biopolymers polyvinyl alcohol (PVA) and polyaniline (PANI), and cross-linking with phytic acid (PA), which is widely present in rice bran. The biological polymer-based conductive hydrogel enables timely diagnosis and photothermal sterilization in-situ for wound healing. Because PANI is highly sensitive to pH changes in the bacterial microenvironment, the hydrogel can detect bacterial infections at concentrations as low as 103 CFU/mL. Subsequently, PANI absorbs near-infrared light to achieve on-demand exothermic sterilization (under 808 nm irradiation for 20 min, the killing ratios for Staphylococcus aureus and Escherichia coli reached almost 100 %). In addition, the hydrogel can monitor the intensity of joint movement to avoid wound re-tearing sensitively. In vitro cytotoxicity and hemocompatibility experiments and in vivo full-thickness infected wound model indicate that the hydrogel has good biocompatibility, antibacterial ability, and can accelerate the wound healing effectively. This work will promote the development of wearable electronic devices and precision medicine.

Exploring the Impact of a Supportive Work Environment on Chinese L2 Teachers' Emotions: A Partial Least Squares-SEM Approach.

Second language (L2) teachers' emotions can influence their well-being and students' performance. However, most of the existing studies have focused on the role of individual factors in affecting L2 teachers' emotions, while leaving environmental factors underexplored. To fill this gap, this study aimed to examine how the four dimensions of a supportive work environment (SWE) (perceived climate, PC; supervisory relationship, SR; peer group interaction, PGI; and perceived organization support, POS) relate to L2 teachers' emotions (enjoyment, anxiety, pride, and anger). A sample of 406 Chinese L2 teachers completed two valid scales to measure their SWE and emotions. The data were analyzed by Partial Least Squares-Structural Equation Modeling (SEM) using Smart PLS 3 software. The results showed that (1) PC, PGI, and POS had a positive and significant effect on enjoyment, while SR had no significant effect; (2) PGI and POS had a negative and significant effect on anxiety, while PC and SR had no significant effect; (3) PGI had a positive and significant effect on pride, while the other three dimensions had no significant effect; and (4) POS had a negative and significant effect on anger, while the other three dimensions had no significant effect. The study concludes with some implications for L2 teachers' education.

A review: Mechanisms and molecular pathways of signaling lymphocytic activation molecule family 3 (SLAMF3) in immune modulation and therapeutic prospects.

The signaling lymphocytic activation molecule (SLAM) family participates in the modulation of various innate and adaptive immune responses. SLAM family (SLAMF) receptors include nine transmembrane glycoproteins, of which SLAMF3 (also known as CD229 or Ly9) has important roles in the modulation of immune responses, from the fundamental activation and suppression of immune cells to the regulation of intricate immune networks. SLAMF3 is mainly expressed in immune cells, such as T, B, and natural killer cells. It has a unique molecular structure, including four immunoglobulin-like domains in the extracellular domain and two immunoreceptor tyrosine-based signaling motifs in the intracellular structural domains. These unique structures have important implications for protein functioning. SLAMF3 is involved in pathogenesis of various disease, particularly autoimmune diseases and cancer. However, despite its potential clinical significance, a comprehensive overview of the current paradigm of SLAMF3 research is lacking. This review summarizes the structure, functional mechanisms, and therapeutic implications of SLAMF3. Our findings highlight the significance of SLAMF3 in both physiological and pathological contexts, and underline its dual role in autoimmunity and malignancies, and including disease progression and prognosis. The review also proposes that future studies on SLAMF3 should explore its context-specific inhibitory and stimulatory effects, expand on its potential in disease mapping, investigate related signaling pathways, and explore its value as a drug target. Research in these areas related to SLAMF3 can provide more precise directions for future therapeutic strategies.

Hybrid surgery for the treatment of lumbar spine surgery complicated with iliac artery pseudoaneurysm, arteriovenous fistula, and lower limb artery embolism: A rare case report.

INTRODUCTION AND IMPORTANCE: Vascular injuries during lumbar surgery are rare, but complications such as false aneurysm of the iliac artery, arteriovenous fistula, and lower limb artery embolism are even rarer. These complications can easily be misdiagnosed and result in the inability to choose an appropriate surgical approach, leading to serious consequences. CASE PRESENTATION: A 36-year-old male patient experienced swelling in both lower limbs, along with numbness, coldness, and dysfunction in his right lower limb, after undergoing a "posterior lumbar discectomy" surgery. On the 20th day post-surgery, a clear diagnosis was established through CTV: 1) Right common iliac artery injury with pseudoaneurysm formation; 2) Right iliac arteriovenous fistula; 3) Right popliteal artery embolism. The patient underwent hybrid surgery to address multiple complications simultaneously and made a good recovery after the procedure. CLINICAL DISCUSSION: Rarely, lumbar spine surgery can concurrently lead to conditions such as pseudoaneurysm, arteriovenous fistula, and lower limb artery embolism. Due to atypical symptoms and signs, it is often misdiagnosed. Hybrid surgery involves incising the femoral artery, using a thrombectomy catheter to remove clots from the iliac artery above and the popliteal artery below, and then re-implanting a covered stent to treat pseudoaneurysm and arteriovenous fistula. CONCLUSION: With a solid clinical knowledge, one can make a timely diagnosis and choose an appropriate surgical method to intervene, thereby improving the prognosis. Hybrid surgery combines the minimally invasive and safe effects of endovascular techniques with the precise effects of open surgery, and it also allows for the simultaneous treatment of multiple comorbidities.

SIRT1 activation ameliorates rhesus monkey liver fibrosis by inhibiting the TGF-ß/smad signaling pathway.

TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.

Coexistence of giant Goos-Hänchen shift and high reflectance in Dirac semimetal based multilayered structure.

Bulk Dirac semimetals (BDSs) possess Fermi energy dependent optical parameters, providing unprecedented opportunities for the study of the controllable Goos-Hänchen (GH) shift. However, the enhancement of GH shifts often comes at the cost of the reflectance in the previous BDS-based structures, which hinders their practical application. In this work, we theoretically present the investigation of the GH shift in a multilayered structure composed of one BDS film and a symmetric one-dimensional photonic crystal (1DPC) with a defect layer. We demonstrate that this well-designed structure supports a large GH shift at the specific working wavelength, whose magnitude can be enhanced up to 3883 times the incident wavelength. In particular, such an enhanced GH shift achieved in this structure is associated with high reflectance (0.94) and these remarkable features can be attributed to the sharp change in the reflective phase and the destructive interference that occurs between the simultaneously excited optical Tamm state (OTS) at the BDS/1DPC interface and the defect state at the 1D defected PC. In addition, we also explore the manipulation of the GH shift by adjusting the Fermi energy of the BDS as well as the geometrical parameter of the multilayered structure. Our results provide a new approach for realizing an enhanced and controllable GH shift in a BDS-based multilayered structure, which endows it with promising prospects for application in optical sensors, optical detectors and beam controllers.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

Selective recovery of metals in spent batteries by electrochemical precipitation to cathode material for sodium-ion batteries.

The recycling of key components in waste lithium-ion batteries (LIBs) is an important route to make up for the shortage of battery materials. Metal separation and purification is an important step. It is of great significance to propose an efficient and green separation technology. In this paper, an electrochemical precipitation method was applied to metal separation from spent LiNi0.5Mn1.5O4 cathode material. The Li and metal elements were effective separated and the precipitates were then used as precursor to synthesize high-performance R-O3-NaNFM cathode material for sodium-ion batteries. The R-O3-NaNFM exhibits excellent electrochemical cycling stability. The capacity retains 71.3 mAh g-1 after a long-term cycling of 200 times at 1 C. This method offers a referable strategy of the recycling for the waste cathode material in spent LIBs.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

An open-cage bis[60]fulleroid as an electron transport material for tin halide perovskite solar cells.

An open-cage bis[60]fulleroid (OC) was applied as an electron transport material (ETM) in tin (Sn) halide perovskite solar cells (PSCs). Due to the reduced offset between the energy levels of Sn-based perovskites and ETMs, the power conversion efficiency (PCE) of Sn-based PSCs with OC reached 9.6% with an open-circuit voltage (VOC) of 0.72 V. Additionally, OC exhibited superior thermal stability and provided 75% of the material without decomposition after vacuum deposition. The PSC using vacuum-deposited OC as the ETM could afford a PCE of 7.6%, which is a big leap forward compared with previous results using vacuum-deposited fullerene derivatives as ETMs.

PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity in Male Mice.

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, and these could be improved in mice with elevated hypothalamic antioxidant defense. We also show that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator, is implicated in regulating hypothalamic LanCL1 transcription, in collaboration with SP1 through a direct interaction, in response to HFD-induced palmitic acid (PA) accumulation. According to our results, when exposed to HFD, mice undergo a process of overwhelming hypothalamic antioxidant defense; short-time HFD exposure induces ROS production to activate PGC-1α and elevate LanCL1-mediated antioxidant defense, while long-time exposure promotes ubiquitin-mediated PGC-1α degradation and suppresses LanCL1 expression. Our findings show the critical importance of the hypothalamic PGC-1α-SP1-LanCL1 axis in regulating HFD-induced obesity, and provide new insights describing the correlations of hypothalamic inflammation and oxidative stress during this process.

Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties.

Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.