Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

Tumor Promoting Effect of Long Non-Coding RNA RP11-556E13.1 and its Clinical Significance in Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to reveal the function of the long non-coding RNA (lncRNA) RP11-556E13.1 (RP11) and its clinical significance in hepatocellular carcinoma (HCC). METHODS: LncRNA and mRNA expression profiling was performed using lncRNA and mRNA microarrays in HCC and adjacent tissues. Human tissue samples were analyzed by semiquantitative real-time polymerase chain reaction (sqRT-PCR) to evaluate the expression of RP11. Smart silencer RNA (siRNA) was used to knockdown the expression of RP11 in HCC cells. The function of RP11 was determined by some cell function experiments in HCC cells. Western blotting (WB) was performed to detect proteins that were presumably associated with these function changes. An Affymetrix Human HTA2.0 microarray was used to detect the underlying mechanism of RP11 in HCC. RESULTS: lncRNA RP11 was the most significantly upregulated lncRNA in HCC tissues compared with the adjacent tissues (p < 0.05, fold change = 20.24). The expression of RP11 was significantly higher in HCC tissues compared to adjacent tissues in 112 tissue pairs (p < 0.05). The higher the expression of RP11 in HCC tissues, the bigger the tumor size, the poorer the histological differentiation, and the lower the overall survival rate of the patients (all p < 0.05). After the knockdown of RP11, HCC cells displayed inhibited proliferation, increased apoptosis rate, and G1/S arrest. Moreover, the expression of cleaved PARP1 and cleaved caspase-3 was increased. GO enrichment and KEGG pathway enrichment analysis showed some important pathways that might be related to the knockdown of RP11 in HCC cells. CONCLUSIONS: lncRNA RP11 is an HCC-promoting gene and a potential prognostic predictor of HCC.

Phase-Inversion Induced 3D Electrode for Direct Acidic Electroreduction CO2 to Formic acid.

Direct electrochemical CO2 reduction to formic acid (FA) instead of formate is a challenging task due to the high acidity of FA and competitive hydrogen evolution reaction. Herein, 3D porous electrode (TDPE) is prepared by a simple phase inversion method, which can electrochemically reduce CO2 to FA in acidic conditions. Owing to interconnected channels, high porosity, and appropriate wettability, TDPE not only improves mass transport, but also realizes pH gradient to build higher local pH micro-environment under acidic conditions for CO2 reduction compared with planar electrode and gas diffusion electrode. Kinetic isotopic effect experiments demonstrate that the proton transfer becomes the rate-determining step at the pH of 1.8; however, not significant in neutral solution, suggesting that the proton is aiding the overall kinetics. Maximum FA Faradaic efficiency of 89.2% has been reached at pH 2.7 in a flow cell, generating FA concentration of 0.1 m. Integrating catalyst and gas-liquid partition layer into a single electrode structure by phase inversion method paves a facile avenue for direct production of FA by electrochemical CO2 reduction.

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

Deep brain stimulation of fornix in Alzheimer's disease: From basic research to clinical practice.

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition-related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition-related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD.

Catalytic Oxidation Mechanism of Toluene over CexMn1-xO2: The Role of Oxygen Vacancies in Adsorption and Activation of Toluene.

Catalytic oxidation has been extensively studied as a promising technology for the removal of toluene from industrial waste gases and indoor air. However, the debate regarding the oxidation mechanism is far from resolved. CexMn1-xO2 catalysts with different mixing ratios are prepared by the sol-gel method and found to exhibit better catalytic activities for toluene oxidation than a single oxide. Characterizations and theoretical calculations reveal that the doped Mn increases the number of oxygen vacancies and the ability of oxygen vacancies to activate aromatic rings, which promotes the rate-determining step of toluene oxidation, i.e., ring-opening reactions. The oxidation products detected by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and Vocus proton transfer reaction mass spectrometry (Vocus-PTR-MS) show that the doped Mn significantly improves the ring-opening efficiency and subsequently yields more short-chain products, such as pyruvic acid and acetic acid. A comprehensive oxidation pathway of toluene is refined in this work.

Transport of neonicotinoid insecticides in a wetland ecosystem: Has the cultivation of different crops become the major sources?

Extensive application of neonicotinoid insecticides (NNIs) in agricultural production has resulted in widespread contamination of multiple environmental media. To investigate the occurrence and fate of NNIs in the largest marsh distribution area in Northeast China, an integrated ecosystem covering farmlands, rivers, and marshes, referred to as the farmland-river-marsh continuum in this study, was chosen for soil, water, and sediment sampling. Five NNIs were detected, with imidacloprid (IMI), thiamethoxam (THM), and clothianidin (CLO) being the most frequently detected ones in different samples. Concentrations of target NNIs in soil, surface water, and sediment samples were 2.23-136 ng/g dry weight (dw), 3.20-51.7 ng/L, and 1.53-8.40 ng/g dw, respectively. In soils, NNIs were detected more often and at higher concentrations in upland fields, while the concentration of NNIs in the soybean-growing soils (71.5 ng/g dw) was significantly higher than in the rice-growing soils (18.5 ng/g dw) (p < 0.05). Total concentration of NNIs in surface water was lower in the Qixing River channel than inside the marsh, while that in sediments showed an opposite trend. Total migration mass of IMI from approximately 157,000 ha of farmland soil by surface runoff was estimated to be 2636-3402 kg from the application time to the sampling period. The storage of NNIs in sediments was estimated to range from 45.9 to 252 ng/cm2. The estimated environmental risks, calculated as the risk quotients (RQs), revealed low risks to aquatic organisms (RQs <0.1) from the residual concentrations of NNIs in water.

Electrocatalytic oxidation of gaseous toluene in an all-solid cell using a foam Ti/Sb-SnO2/ß-PbO2 anode.

Mineralization of benzene, toluene, and xylene (BTX) with high efficiency at room temperature is still a challenge for the purification of indoor air. In this work, a foam Ti/Sb-SnO2/ß-PbO2 anode catalyst was prepared for electrocatalytically oxidizing gaseous toluene in an all-solid cell at ambient temperature. The complex Ti/Sb-SnO2/ß-PbO2 anode, which was prepared by sequentially deposing Sb-SnO2 and ß-PbO2 on a foam Ti substrate, shows high electrocatalytic oxidation efficiency of toluene (80%) at 7 hr of reaction and high CO2 selectivity (94.9%) under an optimized condition, i.e., a cell voltage of 2.0 V, relative humidity of 60% and a flow rate of 100 mL/min. The better catalytic performance can be ascribed to the high production rate of ⋅OH radicals from discharging adsorbed water and the inhibition of oxygen evolution on the surface of foam Ti/Sb-SnO2/ß-PbO2 anode when compared with the foam Ti/Sb-SnO2 anode. Our results demonstrate that prepared complex electrodes can be potentially used for electrocatalytic removal of gaseous toluene at room temperature with a good performance.

Stress-Induced Inversion of Linear Dichroism by 4,4'-Bipyridine Rotation in a Superelastic Organic Single Crystal.

The molecular crystals that manifest unusual mechanical properties have attracted growing attention. Herein, we prepared an organic single crystal that shows bidirectional superelastic transformation in response to shear stress. Single-crystal X-ray diffractions revealed this crystal-twinning related shape change is owed to a stress-controlled 90° rotation of 4,4'-bipyridine around the hydrogen bonds of a chiral organic trimer. As a consequence of the 90° shift in the aromatic plane, an interconversion of crystallographic a-, b-axes (a→b' and b→a') was detected. The molecular rotations changed the anisotropic absorption of linearly polarized light. Therefore, a stress-induced inversion of linear dichroism spectra was demonstrated for the first time. This study reveals the superior mechanical flexibilities of single crystals can be realized by harnessing the molecular rotations and this superelastic crystal may find applications in optical switching and communications.

When immunotherapy meets liver transplantation for hepatocellular carcinoma: A bumpy but promising road.

Liver transplantation (LT) is a highly curative therapy for patients with hepatocellular carcinoma (HCC). However, due to the shortage of donor livers and rapid progression of HCC, a majority of patients are dropped out from the waitlist. Recently, immunotherapy has shown great promise in the treatment of advanced HCC. However, the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection. One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host. Besides, the safety, availability, and costs of immunotherapy are other challenges that need to be addressed. Here, we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis. Statistically, the incidence of rejection was 25.0% pre-transplant and 18.5% post-transplant. Based on the review of these clinical studies, we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence. To date, the clinical experience on the use of immunotherapy before or after LT comes from individual case studies. Although some of the reported results are promising, they are not sufficient to support the standardized use of immunotherapy in clinical practice.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence.

Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.

Circ_0008500 Knockdown Improves Radiosensitivity and Inhibits Tumorigenesis in Breast Cancer Through the miR-758-3p/PFN2 Axis.

Breast cancer is one of the most common malignancies worldwide. Circular RNAs (CircRNAs) were revealed to be implicated in the development of breast cancer. In this research, we aimed to investigate the role and underlying mechanism of circ_0008500 in the development and radiosensitivity of breast cancer. Using real-time quantitative PCR (RT-qPCR) and western blot, we found that hsa_circ_0008500 (circ_0008500) and profilin 2 (PFN2) were increased, while microRNA-758-3p (miR-758-3p) was decreased in breast cancer tissues and cells. Cell viability, the number of colonies, proliferation and apoptosis were detected using CCK-8, colony formation, EdU assays and flow cytometry, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were devoted to test the interaction between miR-758-3p and circ_0008500 or PFN2. The results showed that circ_0008500 knockdown inhibited cell growth, and facilitated cell apoptosis and radiosensitivity in breast cancer cells in vitro. Moreover, circ_0008500 regulated PFN2 expression by sponging miR-758-3p. Functionally, circ_0008500 knockdown regulated cell behaviors and radiosensitivity by targeting miR-758-3p to downregulate PFN2 expression in vitro. Additionally, in vivo tumor formation assay and immunohistochemistry (IHC) assay demonstrated that circ_0008500 knockdown enhanced the radiosensitivity and repressed tumor growth in vivo. In conclusion, circ_0008500 inhibition promoted the radiosensitivity and restrained the development of breast cancer by downregulating PFN2 expression via targeting miR-758-3p.

A 59-Electron Non-Magic-Number Gold Nanocluster Au99(C≡CR)40 Showing Unexpectedly High Stability.

An atomically resolved gold nanocluster Au99(C≡CC6H3-2,4-F2)40 (Au99) with an unusual 59 valence electrons has been synthesized. Single-crystal X-ray diffraction reveals that its Au79 kernel is a Au49 Marks decahedron capped by two Au15 units. The surface structure of Au99 consists of 20 linear Au(C≡CR)2 staples. Intercluster interactions are observed between these D5 symmetric clusters. The existence of an unpaired electron is verified by magnetic measurement. Interestingly, this open-shell gold cluster Au99 stays intact in toluene solution at 80 °C for more than a week, and it has good charging-discharging capability under electrochemical conditions. The compact ligand shell protection around the symmetric core accounts for the high stability. This work suggests that geometric factors may play a crucial role in determining the stability of a metal nanocluster, even though the cluster has an open-shell electronic structure.

Combination of NSAIDs with donepezil as multi-target directed ligands for the treatment of Alzheimer's disease.

To search for multi-target directed ligands for the treatment of Alzheimer's disease (AD), eight hybrid compounds from the combination of non-steroidal anti-inflammatory drugs with donepezil were designed and synthesized. The enzyme test revealed that the synthesized compounds had remarkable inhibitory activity towards both AChE and BChE. The IC50 values of the most active compound 3a reached 0.015 and 0.80 µM for AChE and BChE, respectively, much lower than that of donepezil. Besides, the anti-inflammatory assays showed that the target compounds could effectively inhibit COX-1 and COX-2, and prevent the secretion of proinflammatory cytokines (TNF-α and IL-1ß) induced by LPS. Moreover, the target compound could also protect the neuron cells from the damage caused by Aß42 in vitro. All the results suggest that the hybrid compounds, in particular compound 3a, can be considered as potential candidates for the treatment of AD.

Two-Dimensional Coordination Polymer Showing Spin-Crossover Behavior with a 64 K Wide Hysteresis Loop.

A two-dimensional grid-like coordination polymer, [Fe(NCBH3)2(Py2ttz)2]·4CHCl3 (1·4CHCl3, Py2ttz = 2,5-di(pyridin-4-yl)thiazolo[5,4-d]thiazole), showed one-step complete spin crossover with unexpectedly large hysteresis loop of 64 K wide and temperature-induced excited spin-state trapping effect below 91 K.

Small-Molecule-Selective Organosilica Nanoreactors for Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions in Cellular and Living Systems.

We reported the synthesis of a tris(triazolylmethyl)amine (TTA)-bridged organosilane, functioning as Cu(I)-stabilizing ligands, and the installation of this building block into the backbone of mesoporous organosilica nanoparticles (TTASi) by a sol-gel way. Upon coordinating with Cu(I), the mesoporous CuI-TTASi, with a restricted metal active center inside the pore, functions as a molecular-sieve-typed nanoreactor to efficiently perform Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions on small-molecule substrates but fails to work on macromolecules larger than the pore diameter. As a proof of concept, we witnessed the advantages of selective nanoreactors in screening protein substrates for small molecules. Also, the robust CuI-TTASi could be implanted into the body of animal models including zebrafish and mice as biorthogonal catalysts without apparent toxicity, extending its utilization in vivo ranging from fluorescent labeling to in situ drug synthesis.

Regulatory T Cell Therapy Following Liver Transplantation.

Liver transplantation (LT) is considered the gold standard of curative treatment for patients with end-stage liver disease or nonresectable hepatic malignant tumors. Rejection after LT is the main nontechnical factor affecting the prognosis of recipients. Medical and surgical advances, combined with improved immunosuppression with drugs such as calcineurin inhibitors (CNIs), have contributed to an increase in 1-year graft survival to around 80%. However, medium- and long-term improvements in LT outcomes have lagged behind. Importantly, CNIs and other classical immunosuppressive drugs are associated with significant adverse effects, including malignancies, cardiovascular disease, and severe renal dysfunction. Immunomodulation using regulatory T cells (Tregs) is emerging as a promising alternative to classical immunosuppression. Since their discovery, the immunomodulatory effects of Tregs have been demonstrated in a range of diseases. This has rejuvenated the interest in using Tregs as a therapeutic strategy to induce immune tolerance after LT. In this review, we first summarize the discovery and development of Tregs. We then review the preclinical data supporting their production, mechanism of action, and therapeutic efficacy followed by a summary of relevant clinical trials. Finally, we discuss the outstanding challenges of Treg therapy and its future prospects for routine use in LT.

Halogen-Substituted Spin-Crossover Fe(III) Compounds with Photoresponsive Properties.

Halogen-substituted Fe(III) compounds, [Fe(HphsalpmX)2]PTFB (HphsalpmX = 5-X-(R,S)-((phenyl(2-pyridyl)methylimino)methyl)phenol, PTFB = phenyltrifluoroborate; X = F for 1, Cl for 2, Br for 3) and [Fe(HphsalpmX)2]PTFB·MeOH (X = I for 4·MeOH), were synthesized. Compounds 1, 4·MeOH, and its desolvated form 4 exhibited an invariant high-spin state in the whole temperature range, while 2 and 3 underwent gradual, nonhysteretic, and incomplete spin crossover (SCO) with transition temperatures (TC) of 153 and 220 K, respectively. Interestingly, the SCO-active compounds 2 and 3 showed light-induced excited spin-state trapping (LIESST) effects at 10 K, and light-induced reversible ON/OFF switching behaviors were realized by alternately using 880 and 1064 nm light, while the thermally inert compound 4·MeOH unexpectedly showed a reverse-LIESST effect. These results may help to design and synthesize new photoresponsive SCO Fe(III) compounds for the development of switchable materials.

Design, synthesis and biological evaluation of cinnamamide-quinazoline derivatives as potential EGFR inhibitors to reverse T790M mutation.

Gatekeeper T790M mutation in EGFR is the most common factor for acquired resistance. Acrylamide-bearing 4-anilinoquinazoline scaffold are powerful irreversible inhibitors for overcoming resistance. In this work, three series of EGFR inhibitors derived from incorporation of cinnamamide into the quinazoline scaffold were designed and synthesized to reverse resistance resulting from insurgence of T790M mutation. SAR studies revealed that methoxy and acetoxy substitutions on the cinnamic phenyl ring were found to elevate the activity. In particular, compound 7g emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib (0.95 µM) towards H1975 cells with an IC50 value of 1.22 µM. Kinase inhibition studies indicated that 7g showed excellent inhibitory effect on EGFRT790M enzyme, which was 11 times more effective than gefitinib. Besides, selectivity index of 7g toward the EGFRT790M mutant over the EGFRWT is 2.72, hinting its effect of reducing off-target. Mechanism study indicated that 7g induced apoptosis of H1975 cells and arrest the cell cycle at G2/M phase in a dose-dependent manner. Moreover, 7g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of 7g inside EGFRWT and EGFRT790M binding sites.

Dual-target platinum(IV) complexes exhibit antiproliferative activity through DNA damage and induce ER-stress-mediated apoptosis in A549 cells.

Platinum(II)-based chemotherapeutics are commonly used to treat various types of solid tumors, such as lung cancers. However, these compounds can cause serious side effects, including nephrotoxicity and ototoxicity, which affect the quality of life of patients. In our work, four novel dual target platinum(IV) complexes were designed and synthesized. In vitro results indicated that the title platinum(IV) complexes exhibited effective antitumor activities against the tested cancer cells and had lower toxicity and resistance factors than oxaliplatin and cisplatin. Further mechanistic experiments demonstrated that complex 11 accumulated in mitochondria and induced an elevation in ROS and an ER stress response via mitochondrial dysfunction. Notably, complex 11 significantly modulated the expression levels of proapoptosis proteins including cleaved-Caspase-3, Bax, and p53, and decreased the level of the prosurvival protein Bcl-2. Together, these results suggested that complex 11 might be a potential lead compound for future cancer therapy due to its potency and selectivity.