Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

Trace Sample Proteome Quantification by Data-Dependent Acquisition without Dynamic Exclusion.

Despite continuous technological improvements in sample preparation, mass-spectrometry-based proteomics for trace samples faces the challenges of sensitivity, quantification accuracy, and reproducibility. Herein, we explored the applicability of turboDDA (a method that uses data-dependent acquisition without dynamic exclusion) for quantitative proteomics of trace samples. After systematic optimization of acquisition parameters, we compared the performance of turboDDA with that of data-dependent acquisition with dynamic exclusion (DEDDA). By benchmarking the analysis of trace unlabeled human cell digests, turboDDA showed substantially better sensitivity in comparison with DEDDA, whether for unfractionated or high pH fractionated samples. Furthermore, through designing an iTRAQ-labeled three-proteome model (i.e., tryptic digest of protein lysates from yeast, human, and E. coli) to document the interference effect, we evaluated the quantification interference, accuracy, reproducibility of iTRAQ labeled trace samples, and the impact of PIF (precursor intensity fraction) cutoff for different approaches (turboDDA and DEDDA). The results showed that improved quantification accuracy and reproducibility could be achieved by turboDDA, while a more stringent PIF cutoff resulted in more accurate quantification but less peptide identification for both approaches. Finally, the turboDDA strategy was applied to the differential analysis of limited amounts of human lung cancer cell samples, showing great promise in trace proteomics sample analysis.

Development of a Mixed Multinuclear Cluster Strategy in Metal-Organic Frameworks for Methane Purification and Storage.

Metal-organic frameworks (MOFs) have attracted extensive attention in methane (CH4) purification and storage. Specially, multinuclear cluster-based MOFs usually have prominent performance because of large cluster size and abundant open metal sites. However, compared to diverse combinations of organic linkers, one MOF with two or more multinuclear clusters is difficult to achieve. In this paper, we demonstrate a mixed multinuclear cluster strategy, which successfully led to three new heterometallic MOFs (SNNU-328-330) with the same common H3TATB [2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine] tritopic linker and six types of multinuclear clusters ([YCd(COO)4(µ2-H2O)], [YCd2(COO)8], [In3(COO)6(µ3-OH)], [In3Eu2(COO)9(µ3-OH)3(µ4-O)], [Y9(COO)12(µ3-OH)14] and [Y2Cd8(COO)16(µ2-H2O)4(µ3-OH)8]). Three MOF adsorbents all show great potentials to remove the impurities (CO2 and C2-hydrocarbons) in natural gas and show prominent high-pressure methane storage capacity. Among them, the ideal adsorbed solution theory separation ratios of equimolar C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 at 298 K for SNNU-328 reach to 29.7-16.0, 19.1-8.2, 33.2-10.3, and 74.3-8.5, which have surpassed many famous MOF adsorbents. Dynamic breakthrough experiments conducted at 273 and 298 K showed that SNNU-330 can separate CH4 from C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 mixtures with the breakthrough interval times of about 48.2, 17.9, 37.2, and 17.1 min g-1 (273 K, 1 bar, v/v = 50/50, 2 mL min-1), respectively. Remarkably, SNNU-329 exhibits extremely high methane storage performance at 298 K with the total uptake and working capacity of 192 cm3 cm-3 (95 bar) and 171 cm3 cm-3 (65 bar) due to the synergistic effects of high surface area, suitable pore sizes, and multiple open metal sites.

A Phase III Clinical Trial Evaluating the Efficacy of Yinghua Tablet in the Treatment of Sequelae of Pelvic Inflammatory Disease.

Objective: To evaluate the efficacy and safety of the Yinghua tablet in treating sequelae of pelvic inflammatory diseases (PID) that manifest as the syndrome of dampness-heat stasis. Methods: The experimental group enrolled 360 cases, while the control group enrolled 120 cases. The experimental group took Yinghua tablets three times a day, three tablets each time, and the control group took Fuyankang tablets three times a day, three tablets each time. The treatment course was six weeks. Before treatment, at three weeks and six weeks of treatment, the patients were scored for TCM syndrome, clinical symptoms and, signs, and adverse events during treatment were recorded. Results: The experimental group included 340 cases, and the control group finally included 114 cases. After six weeks of treatment, statistically significant differences were observed between the two groups in the treatment effect, recovery rate, markedly effective rate, and total effective rate (P < .05). The two groups had no significant difference in the effective rate of local signs (P > .05). However, the two groups had a significant difference in the total effective rate (P < .05). Before and after treatment, traditional Chinese medicine (TCM) symptoms score, symptom sign score, and local sign score were statistically significant (P < .05). The incidence of adverse events (AEs) after taking Yinghua Tablets was 3.61% (13 times), of which the incidence of adverse events related to study drugs was 0.28% (1 case). The AEs of Fuyankang Tablets were 1.67% (2 times), of which the incidence of adverse events related to study drugs was 1.67% (2 cases). There was no significant difference in the incidence of AEs between the two groups as compared to Fisher (P = .3767), indicating that no serious AEs occurred in either group. Conclusions: Yinghua tablet was effective and safe in treating sequelae of pelvic inflammatory diseases.

Synthesis, Crystal Structures, and Photochemical Properties of a Family of Heterometallic Titanium Oxo Clusters.

The incorporation of heterometallic atoms into the structure of titanium-oxygen nanomaterials is one of the known and effective strategies to develop new high-performance photovoltaic active materials. In this study, we have synthesized three benzoic acid-stabilized heterometallic titanium oxo clusters with the different transition metals Co, Cu, and Cd, formulated as [Ti4Co2(µ2-O)2(µ3-O)2(C6H5COO)12(CH3CN)2]·2CH3CN (1), [Ti5Cu4(µ3-O)6(C6H5COO)16] (2), and [Ti12Cd5(µ2-O)(µ3-O)15(µ4-O)2(C6H5COO)22(C6H5COOH)(CH3CN)]·CH3CN·C6H5COOH (3), and then we characterized their structures. UV-vis spectroscopy analysis revealed an enhanced UV-vis-light absorption of those heterometallic clusters. The density functional theory calculations indicated that charge transfer occurs from the p orbital of O atoms to the d orbital of Ti atoms in the TiO core (O → Ti) as well as from the metal to the core in 1 and 2. We also measured the photocurrent response and photocatalytic H2 evolution, which shows enhancement in the photocurrent intensity and good H2 evolution ability because of the cooperative effect of heterometal doping in titanium oxo clusters.

Designed Cluster Assembly of Multidimensional Titanium Coordination Polymers: Syntheses, Crystal Structure and Properties.

The exploitation of new titanium-based coordination polymers (Ti CPs) with high crystallinity is difficult but highly desirable for their potential applications in photocatalysis. Herein, a cluster-cooperative assemble strategy is developed to synthesize Ti CPs. By utilizing various bifunctional ligands containing carboxylate acids and N-donor groups, we successfully assembled the zero-dimensional (0D) [(Ti3 O)(iPrO)8 ]2+ or [(Ti4 O2 )(iPrO)6 ]6+ clusters into one-dimensional (1D) tube-, ribbon-, or helical chain-shape architectures, two-dimensional (2D) layered structures, and a rare parallel 2D→three-dimensional (3D) polycatenation framework with various copper iodide dopants, including rhombus- or wing-shaped Cu2 I2 and tetrahedron- or ladder-shaped Cu4 I4 . The as-synthesized compounds display strong absorption in the visible region with narrow band gaps ranging from 1.70 to 2.72 eV and exhibit good photocatalytic activities in the degradation of organic pollutants.

[Co2 @Ge16 ]4- : Localized versus Delocalized Bonding in Two Isomeric Intermetalloid Clusters.

We report the successful isolation and structural elucidation of two bimetallic doped [Co2 @Ge16 ]4- clusters (α and ß form), which were synthesized through the reaction of [{(ArN)2 CtBu}Co(η6 -toluene)] (Ar=2,6-diisopropylphenyl) and K4 Ge9 in ethylenediamine (en) solution and co-crystallized together in [K(2,2,2-crypt)]4 [Co2 @Ge16 ]⋅en. The α-[Co2 @Ge16 ]4- isomer prefers a distinct D2h 3-connected architecture, whereas the deltahedral isomeric ß-[Co2 @Ge16 ]4- isomer adopts a quasi-C2h geometry and can be seen as coupling of two distorted arachno-[Co@Ge10 ] units. Chemical bonding analyses indicate that the skeleton of the α isomer is mainly composed of localized bonds, whereas only multicenter bonding interactions govern the geometry of the ß isomer, which was further found to exhibit a fluxional behavior. The coexistence of both isomers within one unit cell links the 3-connected clusters with their deltahedral congeners, thus highlighting the structural and electronic flexibility of such discreet cluster systems.

Reactivity Studies of [Co@Sn9]4- with Transition Metal Reagents: Bottom-Up Synthesis of Ternary Functionalized Zintl Clusters.

The binary cluster [Co@Sn9]4- (1) was extracted directly from ethylenediamine (en) solutions of an intermetallic precursor with nominal composition "K5Co3Sn9", and its reactions with various organometallic reagents were explored. Reaction with Ni(PPh3)2(CO)2 gives [Co@Sn9Ni(CO)]3- (2), a Co-centered closo-Sn9Ni bicapped square antiprism. Analogous reactions with Ni(COD)2, Pt(PPh3)4, and Au(PPh3)Ph led to the isolation of [Co@Sn9Ni(C2H4)]3- (3), [Co@Sn9Pt(PPh3)]3- (4), and [Co@Sn9AuPh]3- (5), respectively. 3 is structurally similar to 2 but significantly distorted from a closo-cluster with one open square face. The coordination of [CoSn9]3- by PtPPh3 (4) or AuPh (5) induces a structural transformation in the CoSn9 core, from a monocapped square antiprism ( C4 v) to a tricapped trigonal prismatic structure ( pseudo- C3 v), with the transition metal fragment capping a triangular face. The four trimetallic anions presented here represent a new family of ternary functionalized Zintl clusters incorporating a d9 transition metal center. All clusters were characterized by single-crystal X-ray diffraction and electrospray ionization mass spectrometry (ESI-MS).

Construction of Uranyl Organic Hybrids by Phosphonate and in Situ Generated Carboxyphosphonate Ligands.

The hydrothermal reaction of uranyl ions with (5-methyl-1,3-phenylene)diphosphonic acid (H4MPDP) in the presence of additives such as nitric acid, N-bearing species, and heterometal ions yielded five new uranyl organic hybrids: (H3O)[(UO2)5(H2O)4(H3DPB)2(H2DPB)(HDPB)]·2H2O (1), (Hphen)(phen)[(UO2)3(H2DPB)(HDPB)] (2), (H2dipy)[(UO2)3(MPDP)2] (3), Zn(bipy)(UO2)(MPDP) (4), and Co(bipy)(UO2)(MPDP)·H2O (5) (H5DPB = 3,5-diphosphonobenzoic acid; phen = 1,10-phenanthroline; dipy = 4,4'-bipyridine; bipy = 2,2'-bipyridine). Single-crystal X-ray diffraction (XRD) demonstrates that 1 and 2 are 3D frameworks constructed of uranyl centers and carboxyphosphonate DPB ligands; the latter were formed via the in situ oxidation of H4MPDP. In the homometallic uranyl diphosphonate 3, less common UO6 square bipyramids connected by MPDP ligands were incorporated to form the 2D assembly. A further introduction of heterometal ions produced two heterobimetallic uranyl phosphonates 4 and 5. Both of them show layered structures, formed by UO6 square bipyramids linked by MPDP ligands with heterometal-centered polyhedra decorated on the sides of the layers. It is found that the pH and heterometal ions have significant effects on the structures of the complexes. In addition to the syntheses and XRD characterization, the spectroscopic properties of these uranyl complexes were also addressed. To complement the experimental results, density functional theory calculations were carried out on several model complexes that feature a homo- or heterobimetallic molecular skeleton. Geometrical/electronic structures, IR spectra, and electronic absorptions were discussed.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

A Multifunctional Mn(II) Phosphonate for Rapid Separation of Methyl Orange and Electron-Transfer Photochromism.

A Mn(II) phosphonate of the general formula [Mn(H2 L)2 (H2 O)2 (H2 bibp)] adopts a layered motif with protonated H2 bibp(2+) cations embedded in the channels (H4 L=thiophene-2-phosphonic acid; bibp=4,4'-bis(1-imidazolyl)biphenyl). The title compound exhibits excellent adsorptive removal of methyl orange (MO) dye from aqueous solution. Its advantageous features include fast adsorption, high uptake capacity, selective removal, and reusability, which are of great significance for practical application in wastewater treatment. Meanwhile, the compound displays rapid photochromism upon irradiation with visible light at room temperature. Extensive research has demonstrated that such behavior is based on a ligand-to-ligand charge-transfer (LLCT) mechanism. The irradiated sample possesses an ultra-long-lived charge-separated state. Moreover, not only is the compound the first Mn-based photochromic MOF, but it is also one of the very few examples showing LLCT with non-photochromic components.

Particular Handedness Excess through Symmetry-Breaking Crystallization of a 3D Cobalt Phosphonate.

A 3D chiral cobalt phosphonate has been obtained from achiral precursors in the absence of chiral inducers. Remarkably, the bulk sample is largely enantio-enriched with particular handedness through symmetry-breaking crystallization in spite of multiple repeated experiments. Moreover, protonation of this chiral material introduces Brønsted acid sites, the structure of which is unique to the heterogeneous phase for the ring opening of epoxies.

Regioisomer-specific electron affinities and electronic structures of C70para-adducts at polar and equatorial positions with (bromo)benzyl radicals: photoelectron spectroscopy and theoretical study.

Negative ion photoelectron spectroscopy shows interesting regioisomer-specific electron affinities (EAs) of 2,5- and 7,23-para-adducts of C70 [(ArCH2)2C70] (Ar = Ph, o-, m-, and p-BrC6H4). Their EA values are larger than that of C70 by 5-150 meV with the 2,5-polar adducts' EAs being higher than their corresponding 7,23-equatorial counterparts, exhibiting appreciable EA tunable ranges and regioisomeric specificity. Density functional theory (DFT) calculations reproduce both the experimental EA values and EA trends very well.

All-Metal Antiaromaticity in Sb4 -Type Lanthanocene Anions.

Antiaromaticity, as introduced in 1965, usually refers to monocyclic systems with 4n π electrons. This concept was extended to all-metal molecules after the observation of Li3 Al4 (-) in the gas phase. However, the solid-phase counterparts have not been documented to date. Herein, we describe a series of all-metal antiaromatic anions, [Ln(η(4) -Sb4 )3 ](3-) (Ln=La, Y, Ho, Er, Lu), which were isolated as the K([2.2.2]crypt) salts and identified by single-crystal X-ray diffraction. Based on the results obtained from the chemical bonding analysis, multicenter indices, and the electron-counting rule, we conclude that the core [Ln(η(4) -Sb4 )3 ](3-) fragment of the crystal has three locally π-antiaromatic Sb4 fragments. This complex represents the first locally π-antiaromatic all-metal system in the solid state, which is stabilized by interactions of the three π-antiaromatic units with the central metal atom.

Peculiar All-Metal σ-Aromaticity of the [Au2 Sb16 ]4- Anion in the Solid State.

Gas-phase clusters are deemed to be σ-aromatic when they satisfy the 4n+2 rule of aromaticity for delocalized σ electrons and fulfill other requirements known for aromatic systems. While the range of n values was shown to be quite broad when applied to short-lived clusters found in molecular-beam experiments, stability of all-metal cluster-like fragments isolated in condensed phase was previously shown to be mainly ascribed to two electrons (n=0). In this work, the applicability of this concept is extended towards solid-state compounds by demonstrating a unique example of a storable compound, which was isolated as a stable [K([2.2.2]crypt)]+ salt, featuring a [Au2 Sb16 ]4- cluster core possessing two all-metal aromatic AuSb4 fragments with six delocalized σ electrons each (n=1). This discovery pushes the boundaries of the original idea of Kekulé and firmly establishes the usefulness of the σ-aromaticity concept as a general idea for both small clusters and solid-state compounds.

An All-Metal Aromatic Sandwich Complex [Sb3Au3Sb3](3-).

A sandwich complex, as exemplified by ferrocene in the 1950s, usually refers to one metal center bound by two arene ligands. The subject has subsequently been extended to carbon-free aromatic ligands and multiple-metal-atom "monolayered" center, but not to an all-metal species. Here, we describe the synthesis of an unprecedented all-metal aromatic sandwich complex, [Sb3Au3Sb3](3-), which was isolated as K([2.2.2]crypt)(+) salt and identified by single-crystal X-ray diffraction. Quantum chemical calculations indicate that intramolecular electron transfers for the three metallic layers (Sb → Au donation and Sb ← Au back-donation) markedly redistribute the valence electrons from the cyclo-Sb3 ligands and Au3 interlayer to the Au-Sb bonds, which hold the complex together via σ bonding. Each cyclo-Sb3 possesses aromaticity with delocalized three-center three-electron (3c-3e) π bonds, which are essentially equivalent to a 3c-4e ππ* triplet system, following the reversed 4n Hückel rule for aromaticity in a triplet state.

METTL4-mediated N6-methyladenine DNA modification regulates thermotolerance in Arabidopsis thaliana.

DNA N6-methyladenine (6 mA) is an evolutionarily conserved DNA modification in procaryotes and eukaryotes. The DNA 6 mA methylation is tightly controlled by 6 mA regulatory proteins. DNA N6-adenine methyltransferase 1 (DAMT-1) has been identified as a DNA 6 mA methyltransferase in animals. In plants, DNA 6 mA methylation has been found, however, the DNA 6 mA methyltransferases and their function in plants are largely unknown. In our study, we find METTL4 is a DNA 6 mA methyltransferase in Arabidopsis thaliana. Both in vitro and in vivo evidences support the DNA 6 mA methyltransferase activity of METTL4. mettl4 mutant is hypersensitive to heat stress, suggesting DNA 6 mA methylation plays important role in heat stress adaption. RNA-seq and 6 mA IP-qPCR analysis show that METTL4 participates in heat stress tolerance by regulating expression of heat responsive genes. Our study find METTL4 is a plant DNA 6 mA methyltransferase and illustrates its function in regulating heat stress response.

Auricularia auricular Adsorbs Aflatoxin B1 and Ameliorates Aflatoxin B1-Induced Liver Damage in Sprague Dawley Rats.

Aflatoxin B1 (AFB1), as a class I carcinogen, poses a substantial health risk to individuals. Contamination of food sources, particularly grains and nuts, with Aspergillus flavus (A. flavus) contributes to the prevalence of AFB1. The impact of global warming has spurred research into the development of AFB1 prevention technologies. While edible fungi have shown potential in detoxifying AFB1, there is a scarcity of literature on the application of Auricularia auricular (A. auricular) in this context. This study aimed to investigate the ability and underlying mechanism of A. auricular mycelia to adsorb aflatoxin B1, as well as evaluate its protective effects on the AFB1-induced liver damage in SD rats. Additionally, the effects of temperature, time, pH, and reaction ratio on the adsorption rate were examined. Combining thermodynamic and kinetic data, the adsorption process was characterized as a complex mechanism primarily driven by chemical adsorption. In SD rats, the A. auricular mycelia exhibited alleviation of AFB1-induced liver damage. The protective effects on the liver attributed to A. auricular mycelia may involve a reduction in AFB1 adsorption in the intestine, mitigation of oxidative stress, and augmentation of second-phase detoxification enzyme activity. The adsorption method for AFB1 not only ensures safety and non-toxicity, but also represents a dietary regulation strategy for achieving effective defense against AFB1.

Effect of Structural Elements of Heparin-Mimicking Polymers on Vascular Cell Distribution and Functions: Chemically Homogeneous or Heterogeneous?

Heparin-mimicking polymers (HMPs) are artificially synthesized alternatives to heparin with comparable regulatory effects on protein adsorption and cell behavior. By introducing two major structural elements of HMPs (sulfonate- and glyco-containing units) to different areas of material surfaces, heterogeneous surfaces patterned with different HMPs and homogeneous surfaces patterned with the same HMPs can be obtained. In this work, heterogeneous HMP-patterned poly(dimethylsiloxane) (PDMS) surfaces with sulfonate-containing polySS (pS) and glyco-containing polyMAG (pM) distributed in circular patterns (with a diameter of 300 µm) were prepared (S-M and M-S). Specifically, pS and pM were distributed inside and outside the circles on S-M, respectively, and exchanged their distribution on M-S. Homogeneous HMP-patterned silicone surfaces (SM-SM) where sulfonate- and glyco-containing poly(SS-co-MAG) (pSM) were distributed uniformly were prepared. Vascular cells showed interestingly different behaviors between chemically homogeneous and heterogeneous surfaces. They tended to grow in the sulfonate-modified area on S-M and M-S and were distributed uniformly on SM-SM. Compared with M-S, S-M showed a better promoting effect on the growth of vascular cells. Among all the samples, SM-SM exhibited the highest proliferation density and an optimum spreading state of vascular cells, as well as the highest human umbilical vein endothelial cell (HUVEC) viability (∼99%) and relatively low human umbilical vein smooth muscle cell (HUVSMC) viability (∼72%). By heterogeneous or homogeneous patterning with different structural elements of HMPs, the modified silicone surfaces spatially guided vascular cell distribution and functions. This strategy provides a new surface engineering approach to the study of cell-HMP interactions.

PERK/ATF3-Reduced ER Stress on high potassium environment in the suppression of tumor ferroptosis.

Potassium (K+) is a vital intracellular cation. In the human body, it regulates membrane potential, electrical excitation, protein synthesis, and cell death. Recent studies revealed that dying cancer cells release potassium into the tumor microenvironment (TME), thereby influencing cell survival-related events. Several investigations reported that potassium channels and high potassium levels influence apoptosis. Increasing extracellular potassium and inhibiting K+ efflux channels significantly block the apoptotic machinery. However, it is unknown whether a high-potassium environment also affects other types of cell death such as ferroptosis. In the present study, cell counting kit (CCK-8), colony formation ability, and 5-ethynyl-2'-deoxyuridine (EdU) assays demonstrated that a high-potassium environment reverses erastin-induced ferroptosis. RNA sequencing (RNA-Seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses indicated that high potassium levels attenuated the unfolded protein response that is characteristic of endoplasmic reticulum (ER) stress. The ER transmembrane proteins PRKR-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6) are recognized as ER stress sensors. Here, the PERK blocker GSK2606414 significantly rescued ferroptosis. The present work also disclosed that the ER-related gene activating transcription factor 3 (ATF3) played a vital role in regulating ferroptosis in a high-potassium environment. The foregoing results revealed the roles of potassium and the TME in cancer cell ferroptosis and provided a potential clinical therapeutic strategy for cancer.