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Ferroptosis provides an innovative theoretical basis and method for tumor therapy but is limited by the low efficiency of conventional iron delivery systems. Herein, an efficient supramolecular iron delivery system (SIDS) is demonstrated upon the hydrolysis of FeCl

Phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), refers to the therapeutic strategy using a visible or near-infrared (NIR) laser to generate free radicals or heat for noninvasive and localized tumor treatment. However, limited by the low photoconversion efficiency of therapeutic agents, a single treatment method can hardly lead to complete tumor ablation, even when enhancing the power density of the laser and/or prolonging the irradiation duration. In this work, copper ion and ruthenium complex codoped polydopamine nanoparticles (Cu(II)/LRu/PDA NPs) are designed for PDT/PTT dual-mode therapy. The doped LRu in the NPs can generate reactive oxygen species under visible laser irradiation and enable PDT. Because of the strong absorption in the NIR region, PDA can not only generate heat for PTT under irradiation but also be used for photoacoustic tomography (PAT) imaging. Meanwhile, the doping of Cu(II) in the NPs through the coordination with PDA facilitates T

Although many semiconductor heterojunctions have been prepared to promote radiation-generated exciton separation for radiocatalysis therapy (RCT), most of them inevitably sacrifice the redox ability of radiation-generated electrons and holes. Herein, we design and construct BiOI/Bi

Porcine reproductive and respiratory syndrome (PRRS) is a globally important disease threatening the pork industry, and modified live-virus (MLV) vaccines are widely used for its prevention. However, PRRS MLV shows high potential for reversion to virulence, leading to a major concern about its safety. Yet the revertant mechanism is still poorly understood. Here, attenuated virus JXwn06-P80, derived from the highly pathogenic PRRS virus (PRRSV) strain JXwn06 by serial passaging in MARC-145 cells, was reversely passaged in pigs through intranasal inoculation to mimic natural infection for 13 rounds, and the pathogenicity of viruses at the 3rd, 5th, 9th, 10th, and 11th passages was evaluated in pigs. From the 9th passage, the viruses caused mortality, which was related to their increased adaptability and replication efficiency (100 times higher than those of JXwn06-P80) in porcine alveolar macrophage (PAM) target cells. Similarly, JXwn06-P80 could also regain fatal virulence through reverse passage in PAMs for 25 or more passages, indicating that the increased adaptability in PAMs directly contributes to its regained fatal virulence. Next, the full-genome sequences were analyzed to explore the genetic evolutionary processes during adaptation both

The influence of microbiota composition and metabolisms on the safety and quality of fermented fish products is attracting increasing attention. In this study, the total viable count (TVC), pH, total volatile base nitrogen (TVB-N) as well as biogenic amines (BAs) of traditional fermented

Objective This study aimed to investigate the factors influencing placenta accreta in pregnant women who previously underwent hysteroscopic adhesiolysis (HA). Methods This retrospective study enrolled 265 women with Intrauterine adhesions (IUAs) at the Sir Run Run Shaw Hospital from January 2014 to December 2018. We followed up their pregnancy outcomes and maternal complications. Results The menstrual pattern and gestational history before operation were significantly different between the live birth and pregnancy loss groups. The age, extent of cavity involved, type of adhesions, times of adhesiolysis performed, and time interval from surgery to pregnancy were not significantly different between these 2 groups. In the third trimester, 48 of 140 patients had 53 perinatal complications, including placenta accreta (27), gestational diabetes mellitus (10), pregnancy-induced hypertension (6), postpartum hemorrhage (4), intrahepatic cholestasis of pregnancy (2), placenta previa (1), oligohydramnios (1), and intrauterine growth restriction (1). Logistic regression analysis showed that extent of cavity involved and times of adhesiolysis performed were associated with placenta accreta. Conclusion The extent of cavity involved and times of adhesive separation surgeries were risk factors for placenta accreta in patients. The menstrual model and gestational history may provide the main predictive factors for pregnancy loss.

The exploration of two-leg spin-ladder materials is a great challenge to the chemical community since it is one of the most ideal models for the study of low-dimensional magnetism and high-Tc superconductivity. Herein, we report on a successful synthesis of a new Cu2+-based two-leg ladder compound constructed by CuO4Cl2 octahedra along the [101] direction. The magnetic results exhibit a broad peak at Tmax ∼ 265 K, and suggest that CdCu2(SeO3)2Cl2 has a spin singlet ground state. The fitting of the isolated two-leg spin-ladder model shows J⊥/kB = 429 K and J‖/kB = 21 K, leading to a large spin gap of ∼409 K.

A new selenite compound CaNi2(SeO3)3·2H2O (1) was obtained by a conventional hydrothermal method, featuring a distorted zemannite-type structure with a unique honeycomb-like hexagonal framework. The crystal-to-crystal transformation from 1 to a partially dehydrated form of CaNi2(SeO3)3·1.5H2O (2) with slightly shrunk hexagonal framework and further to an anhydrous CaNi2(SeO3)3 (3) with a square framework can be achieved by step-by-step dehydration under heating. The UV-vis-NIR absorption spectra indicate that all 1–3 to possess a wide band gap due to spin allowed d–d transition at Ni2+ ion centers. Further, magnetic measurements show a similar magnetic behavior with an antiferromagnetic transition in 1 and 2, while a different magnetic behavior with two magnetic transitions is observed in 3.

Two new selenite compounds Ca2Ni(HSeO3)2(SeO3)2 (CaNi) and Na2Cu(SeO3)2·2H2O (NaCu) were obtained by a hydrothermal method. Both compounds crystallize in the triclinic system of space group P1, featuring a selenite-bridged one-dimensional (1D) spin-chain structure running along the a-axis. Magnetic measurements indicate that CaNi undergoes a long-range antiferromagnetic order (LRO) at TN = ∼3.8 K, while NaCu does not exhibit a LRO down to 2 K but the onset of a short-range correlation at TM = ∼30 K. The intrachain exchange coupling J/kB = -2.59 K for CaNi and J/kB = -47.13 K for NaCu can be estimated by a fit using the 1D spin-chain model. The thermogravimetric analyses show that both compounds are stable below 130 °C. The UV-vis diffuse reflectance spectra indicate that the band gaps of CaNi and NaCu are 4.38 eV and 3.18 eV, respectively.

Cyclic ethers are important scaffolds employed in the synthesis of various natural products and pharmaceutical ingredients. A novel free radical-initiated reaction between cyclic ethers and maleimide iodides through C-H activation is developed, avoiding the use of transition metallic catalysts. This method provides a simple approach to derive cyclic ethers, which were further applied in various cross coupling reactions.

We have successfully synthesized a new transition metal tellurate compound K2Cu2(Te2O5)(TeO3)2·2H2O. The compound crystallizes in the monoclinic crystal system with space group P21/c; the Te coordi...

A new selenite-sulfate compound Co3(SeO3)(SO4)(OH)2 was prepared using a typical hydrothermal reaction. This compound is found to crystallize in an orthorhombic space group of Pnma, featuring a 2D ...

A novel transition metal tellurate single-crystal BaNi

Clinically, the surgical treatment of bladder cancer often faces the problem of tumor recurrence, and the surgical treatment combined with postoperative chemotherapy to inhibit tumor recurrence also faces high toxicity and side effects. Therefore, the need for innovative bladder cancer treatments is urgent. For the past few years, with the development of nano science and technology, imaging-guided therapy using nanomaterials with both imaging and therapy functions has shown great advantages and can not only identify the locations of the tumors but also exhibit biodistributions of nanomaterials in the tumors, significantly improving the accuracy and efficacy of treatment. In this work, we synthesized Fe(III)-doped polyaminopyrrole nanoparticles (FePPy-NH

Bladder cancer is a common urinary tract tumor in clinic, and its morbidity and mortality are always high. Surgical treatment is operator dependent, residual tumor cells often lead to tumor recurrence, and chemotherapy after surgery causes high side effects. So, it is urgent to develop new methods for the theranostics of bladder cancer. Among them, functional nanomaterials have shown good application in tumor theranostics, but they are rarely used in bladder cancer. In our work, we demonstrate the fabrication of folate-modified vincristine-loaded polydopamine-coated Fe3O4 superparticles (Fe3O4@PDA-VCR-FA SPs), and applied them in the theranostics of bladder cancer. The PDA shell not only improves the colloidal stability and biocompatibility, but also enhances the photothermal effect and prolongs the blood circulation half-life. The half-life of Fe3O4@PDA-VCR-FA SPs in blood is calculated as 2.83 h, and the tumor retention rate is 5.96 %ID g-1, these data are significantly higher than those before folic acid modification. The superparamagnetism of Fe3O4 and loading of vincristine endow Fe3O4@PDA-VCR-FA SPs with magnetic resonance imaging and chemotherapy capabilities. Further by employing NIR laser-triggered photothermal therapy, bladder tumors were ablated completely, and no recurrence was observed. Blood and histological tests of the major organs confirm that Fe3O4@PDA-VCR-FA SPs show good biosafety.

Enyne-allene compounds undergo Myers-Saito cyclization at physiological temperature to generate diradical intermediates that are capable of inducing DNA damage and cell death. The high reactivity of enyne-allene however limits their promising prospect as anticancer agents due to the spontaneous cyclization during storage and delivery. Regulating the cyclization process by taking advantage of the characteristics of a tumor cellular microenvironment, such as employing a low pH value to activate the cyclization process, is thus of essential importance. In this work, a novel enediyne (EDY) system with locked carbonyl groups was specifically designed and synthesized. Unlocking the protected carbonyl groups in the presence of acid would facilitate the rearrangement of propargyl moieties into an allene group, enabling the formation of an enyne-allene structure and occurrence of Myers-Saito cyclization. The pH-dependent diradical generation and DNA-cleavage ability of the designed EDY system were confirmed by electron paramagnetic resonance analysis and DNA gel electrophoresis. A promising cytotoxicity against HeLa cells with half inhibition concentrations (IC50) as low as 1.40 μM was obtained, which was comparable to those of many commercially applied anticancer drugs. Further in vitro experiments revealed that this EDY system induced intracellular DNA damage and subsequently resulted in S-phase arrest and cytotoxicity through programmed apoptosis.

The Cu2+-based breathing kagome material Pb(OF)Cu3(SeO3)2(NO3) with both corner-sharing and edge-sharing has been synthesized. Magnetic measurements suggest ferromagnetic interactions inside the layers and antiferromagnetic interactions between the neighboring layers, leading to an antiferromagnetic ground state with a field-induced spin-flip transition at low temperature.

The issue of robust dissipativity for delayed memristor-based inertial neural networks is studied in this article. By employing some famous inequalities, the results on global dissipativity and global robust dissipativity of the delayed memristor-based inertial neural networks are obtained via generalized Lyapunov functional method. Moreover, the positive invariant sets and globally attractive sets of the discussed system are also given. Without making the variable transformation, the second order functional differential system is investigated directly, which is different from the previous works. Finally, some examples and their numerical simulations are shown to corroborate the effectiveness of obtained results.

Enhancement of permeability and the retention effect is one of the main pathways for the accumulation of nanomaterials in tumor sites, but poor cellular internalization and rapid clearance of nanomaterials always hamper the efficacy of imaging diagnosis and treatment. With the consideration of both high tumor accumulation and cellular internalization, positively charged nanomaterials can adhere to the tumor cell membrane by an electrostatic force, which is conducive to cellular internalization, but they are easily recognized and cleared during blood circulation. However, negatively charged nanomaterials show an enhanced stealth-like effect and possess a long blood circulation time, which is conducive to tumor accumulation. Therefore, in this work, on the basis of the shielding effect of citrate ions to positive charge and the protonation under an acidic tumor microenvironment, pH-sensitive sodium citrate-modified polyaniline nanoshuttles (NSs) with negative charge during blood circulation but positive charge in tumor sites are designed. With this hierarchical targeting strategy, the blood circulation half-life increases from 4.35 to 7.33 h, and the retention rate of NSs in tumors increases from 5.29 to 8.57% ID/g. Because the retention rate of NSs is increased, the magnetic resonance imaging resolution and signal intensity are significantly improved. A synergistic treatment of tumors is further achieved by means of photothermal therapy with laser irradiation and chemotherapy via heat-stimulated drug release.

An approach for photonic generation of multi-function microwave/pulse signals has been proposed and verified, which is capable of achieving Nyquist/triangular pulse signals and frequency quadrupling/12-tupling microwave signals. Based on optical carrier suppressed modulation in a dual-parallel Mach–Zehnder modulator, a four-line optical frequency comb and a Nyquist pulse are generated. Subsequently, polarization controlling using an optical interleaver and a linear polarizer is conducted to manipulate spectra, after which a pulse signal with triangular shape and a microwave signal with high-frequency multiplication factor are generated. By applying a 10-GHz RF driving signal, a Nyquist pulse and a full-duty-cycle triangular pulse with repetition frequency of 40 GHz, and 40-/120-GHz millimeter-wave signals can be obtained. This proposal provides the potential of higher-frequency multi-waveform and millimeter-wave signals generator for an all-optical network.

The exploration of two-leg spin-ladder materials is a great challenge to the chemical community since it is one of the most ideal models for the study of low-dimensional magnetism and high-Tc superconductivity. Herein, we report on a successful synthesis of a new Cu2+-based two-leg ladder compound constructed by CuO4Cl2 octahedra along the [101] direction. The magnetic results exhibit a broad peak at Tmax ∼ 265 K, and suggest that CdCu2(SeO3)2Cl2 has a spin singlet ground state. The fitting of the isolated two-leg spin-ladder model shows J⊥/kB = 429 K and J‖/kB = 21 K, leading to a large spin gap of ∼409 K.

Myers-Saito cycloaromatization (MSC) is the working mechanism of many natural enediyne antibiotics with high antitumor potency. However, the presence of the equilibrium between diradical and zwitterionic intermediates in MSC severely hinders further improvement in cytotoxicity toward tumor cells. To this end, a series of maleimide-based enediynes with cyclopropane moieties were synthesized for enhanced cytotoxicity toward tumor cells. By taking advantage of radical clock reactions, the diradical intermediates generated from MSC would rearrange to new diradicals with much longer separation and weaker interactions between two radical centers. The computational study suggested a low energy barrier (4.4 kcal mol−1) for the radical rearrangement through the cyclopropane ring-opening process. Thermolysis experiments confirmed that this radical rearrangement results in the formation of a new diradical intermediate, followed by abstracting hydrogen atoms from 1,4-cyclohexadiene. Interestingly, the DNA cleavage ability and cytotoxicity of enediynes were significantly enhanced after the introduction of cyclopropane moieties. In addition, these maleimide-based enediynes exhibited a similar cytotoxicity under hypoxic conditions to that under normoxic conditions, which is beneficial for treating solid tumors where hypoxic environments frequently lead to deteriorated efficiency of many antitumor drugs. Docking studies indicated that the diradical intermediate was located between the minor groove of DNA with a binding energy of −7.40 kcal mol−1, which is in favor of intracellular DNA damage, and thereby inducing cell death via an apoptosis pathway as suggested by immunofluorescence analysis.

Cyclic ethers are important scaffolds employed in the synthesis of various natural products and pharmaceutical ingredients. A novel free radical-initiated reaction between cyclic ethers and maleimide iodides through C-H activation is developed, avoiding the use of transition metallic catalysts. This method provides a simple approach to derive cyclic ethers, which were further applied in various cross coupling reactions.

Combined photothermal therapy/chemotherapy by co-delivery of a photosensitizer (PS) and a chemotherapeutic drug has demonstrated great potential for cancer treatment. The intrinsic drawbacks of traditional drug delivery systems (DDSs), such as tedious synthetic procedures, side effects originated from the carrier materials, low loading efficiency, and uncontrolled drug release, however, have impaired their further advancement. On the other hand, enediyne antibiotics are highly cytotoxic toward cancer cells through the generation of lethal carbon radicals via thermal-induced cyclization, endowing them with great potential to achieve enhanced synergistic anticancer performance by incorporation with the photothermal effect of PS. To this end, a carrier-free and NIR/acid dual-responsive DDS was constructed for combined photothermal therapy/chemotherapy. The facile co-assembly of maleimide-based enediyne and PS IR820 was achieved in aqueous solution to give nanoparticles (EICN) with a hydrodynamic diameter of 90 nm and high stability. In vitro study confirmed the acid/NIR dual-responsive degradation and drug release, free radical generation and DNA-cleaving ability of EICN, which was accomplished by the corporation of enediyne and IR820 moieties. Further tests on HeLa cells verified the excellent synergistic anticancer performance of EICN including the improved cellular uptake, NIR-enhanced drug release, DNA damage and histone deacetylase inhibitor capacity. Overall, this carrier-free DDS with dual acid/NIR-responsivity would potentially provide new insights for the development of combined photothermal/chemotherapy.

Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options. The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity. In the present study, we demonstrate that Kir2.1, an inwardly-rectifying potassium channel, is highly expressed in non-WNT/SHH MBs, which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway. Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice. Moreover, Kir2.1high/nuclear N2ICDhigh MBs are associated with the significantly shorter lifespan of the patients. Thus, Kir2.1high/nuclear N2ICDhigh can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs. Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.

The follow-up reaction pathways of the diradical species formed from cycloaromatization of enediynes or enyne-allenes determine their ability of H-abstraction from DNA, significantly affecting their biological activity performance. To gain a deeper understanding of subsequent reaction pathways of the diradical intermediates formed from acyclic enediynes based on maleimide-assisted rearrangement and cycloaromatization (MARACA), a maleimide-based enediyne featuring methylene groups adjacent to the propargyl sites of the terminal alkynes was synthesized through the Sonogashira coupling reaction. Three thermal cyclization products after intramolecular hydrogen atom transfer (HAT) were obtained from the thermolysis experiment and their structures were confirmed by 1D and 2D nuclear magnetic resonance spectroscopic analysis. Density functional theory was employed to analyze the important elementary steps including rearrangement, cycloaromatization, and intramolecular HAT processes toward the formation of the cyclized products, where the low-energy barriers of HAT pathways relative to the formation of diradicals from cycloaromatization were successfully identified. Overall, the HAT processes to consume diradicals intramolecularly have become competitive with that of intermolecular H-abstraction, implying that the DNA-cleavage ability of enediynes can be further boosted once the HAT processes are halted. This study offers a promising direction for designing novel and potent acyclic enediynes for antitumor applications.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor progrnosis and a high recurrence rate after surgery. To this end, we examined the role of Nanog that is highly expressed in this tumor. NANOG is a transcription factor involved in the pluripotency of embryonic stem cells (ESCs) and the induction of malignancy in cancer stem-like cells (CSCs). Bioinformatic analysis revealed that NANOG may be associated with the development of stem-like traits in GBM. Forced expression of NANOG markedly increased the expression of cancer stem cell markers and promoted the sphere formation and migration of GBM cells. Nanog enhanced the expression of SHH which is required for the maintenance of the positive feedback loop of Hedgehog signaling pathway. Treatment of GBM cells with SANT-1 and GANT61 significantly reduced the tumor progression. These data support a view that reduction of Nanog might have therapeutic benefits in GBM.

The Cu

Acyclic enediynes are generally inactive under physiological conditions to be used as antitumor agents like their natural enediyne counterparts. A new mechanism named as maleimide-assisted rearrangement and cycloaromatization (MARACA) is uncovered to trigger the reactivity of acyclic enediynes. Through this mechanism, cascade 1,3-proton transfer processes are accelerated with the maleimide moiety at the ene position to enable the acyclic enediynes to undergo cycloaromatization and generate reactive radicals under physiological conditions. Computational studies suggest that the highest energy barrier for MARACA is 26.0 kcal/mol, much lower than that of Bergman cyclization pathway (39.6 kcal/mol). Experimental results show that maleimide-based enediynes exhibit low onset temperature, fast generation of radical species at 37 °C, and much faster reaction in aqueous solution than in nonpolar solvent, which is beneficial to achieve both high reactivity in physiological environment and high stability for storage and delivery in nonpolar media. The generated radical species are capable of causing high percentage of double-strand (ds) DNA cleavage, leading to significant cytotoxicity toward a panel of cancer cell lines with half inhibition concentration down to submicromolar level. Overall, the discovery of the MARACA mechanism provides a platform for designing novel acyclic enediynes with high potency for antitumor applications.

Light-cross-linked small-molecule micelles with enediyne units are designed for developing efficient drug-delivery systems. Gemcitabine (GEM) is chosen as a model hydrophilic drug and tethered with a maleimide-based enediyne (EDY) as a hydrophobic tail in the preparation of amphiphilic EDY-GEM. The stable micellar particles are obtained by cross-linking the enediyne moieties via photoinduced Bergman cyclization polymerization in aqueous media. The light-cross-linked spherical micelles with a size of 80 nm are characterized with dynamic light scattering and electron microscopy, showing robust micellar stability, bright fluorescent emission due to their intrinsic conjugated structure, and potential passive tumor-targeting ability through the enhanced permeability and retention effect. The drug-loaded micelles, as an example of light-cross-linked small-molecule micelle-based drug-delivery system, exhibit high drug-loading contents (50%) and greatly improved cytotoxicity toward A549 cells (decreasing the IC50 value of Gemcitabine by 10 times), thanks to the greatly increased cellular uptake of the drug-loaded micelles as confirmed by confocal laser scanning microscopy. The light-cross-linked enediyne-based small-molecule micelles system therefore provides a simple yet efficient drug-delivery platform for cancer chemotherapy.

A new selenite-sulfate compound Co

Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells. The IC50 value of the enediyne compound is comparable to many clinical used anti-tumor agents.

Single crystals of Fe2(TeO3)2(SO4)·3H2O with an alternating spin-chain structure are successfully grown by a hydrothermal method. Magnetic and heat capacity measurements show that this compound possesses a short-range antiferromagetic order at ~55 K and a long-range antiferromagetic order at 32.5 K. A large magnetic anisotropy with magnetization easy c-axis is observed, in which a weak ferromagnetic component is observed along the a- and b-axes, while a spin flop transition is observed at applied field along the c-axis. Also, the magnetic anisotropy energy at 2 K is estimated to be 4.78(3) × 108 ergs/cm3. Such magnetic anisotropy may be due to a strong nonsymmetric distortion in the FeO6 octahedra.

Three dodecanuclear 3d–4f coordination clusters, [CrIII6LnIII6(μ3-OH)8(tbdea)6(C6H5COO)16]·2H2O (Ln = Dy (1), Y (2)) and [CoIII6DyIII6(μ3-OH)8(nbdea)6(m-CH3C6H4COO)16]·2H2O·2CH3CN (3), have been synthesized under solvothermal conditions and characterized. Single-crystal X-ray diffraction analysis revealed that all three compounds possess an analogous {MIII6LnIII6} core (M = Cr, Co; Ln = Dy, Y) and dc magnetic susceptibility studies indicated that the magnetic exchange couplings between DyIII ions are dominant antiferromagnetic, while the CrIII–DyIII interactions are weakly ferromagnetic. Furthermore, the ac magnetic susceptibility measurements showed that both CrIII6DyIII6 compound 1 and CoIIi6DyIII6 compound 3 containing highly anisotropic DyIII ions displayed single-molecule magnetic (SMM) behavior with the energy barrier Ueff increasing from 12.8 K (for 1) to 20.8 K (for 3), indicating that weak 3d–4f exchange couplings enhance the QTM and reduce the energy barrier.