Two-layer molecular rotors: A zinc dimer rotating over planar hypercoordinate motifs.

Multi-layer molecular rotors represent a class of unique combination of topology and bonding, featuring a barrier-free rotation of one layer with respect to other layers. This emerging fluxional behavior has been found in a few doped boron clusters. Herein, we strongly enrich this intriguing family followed by an effective design strategy, summarized as essential factors: i) considerable electrostatic interactions originated from a strong charge transfer between layers; ii) the absence of strong covalent bonds between layers; and iii) fully delocalized σ/π electrons from at least one layer. We found that planar hypercoordinate motifs consisting of monocyclic boron rings and metals with σ + π dual aromaticity can be regarded as one promising layer, which can support the suspended X2 (X = Zn, Cd, Hg) dimers. By detailed investigations of thermodynamic and kinetic stabilities of 60 species, eventually, MB7 X2 - and MB8 X2 (X = Zn, Cd; M = Be, Ru, Os; Be works only for Zn-based cases) clusters were verified to be the global-minimum two-layer molecular rotors. Especially, their electronic structure analyses vividly confirm the practicability of the electronic structure requirements mentioned above for designing multi-layer molecular rotors.

Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Mimicking the C2 molecule: M2B2 and M3B2+ clusters (M = Li, Na) and the reactivity of the N-heterocyclic carbene bound Li2B2 complex.

C2 has attracted considerable attention from the scientific community for its debatable bonding situation. Herein, we show that the global minima of M2B2 and M3B2+ (M = Li, Na) possess similar covalent bonding patterns to C2. Because of strong charge transfer from M2/M3 to B2 dimer, they can be better described as [M2]2+[B2]2- and [M3]3+[B2]2- salt complexes with the B22- core surrounded perpendicularly by two and three M+ atoms, respectively. The energy decomposition analyses in combination with the natural orbital for chemical valence theory give four bonding components in C2, M2B2, and M3B2+ clusters. However, the fourth component does not arise from a bonding interaction but from polarization/hybridization. Considering the effect of Pauli repulsion in σ-space, the attractive covalent interaction in these molecules mainly comes from the two π-bonds. We further presented stable N-heterocyclic carbene (NHC) and triphenylphosphine (PPh3) ligands bound Li2B2(NHC)2 and Li2B2(PPh3)2 complexes. A comparative study of reactivity towards L = CO2, CO, and N2 between Li2B2(NHC)2 and B2(NHC)2 is also performed. L-Li2B2(NHC)2 is highly stable against L dissociation at room temperature for L = CO2 and CO, and the stability is markedly higher than that in L-B2(NHC)2. The larger B2→L π-backdonation in L-Li2B2(NHC)2 also makes L more activated than in L-B2(NHC)2.

Stabilization of Cyclic C4 by Four Donor Ligands: A Theoretical Study of (L)4C4 (L = Carbene).

Quantum chemical studies using density functional theory were carried out for the (L)4C4 complexes with L = cAAC, DAC, NHC, SNHC, MIC1, and MIC2. The results show that the title complexes are highly stable with respect to dissociation, (L)4C4 → C4 + 4L. However, their stability with respect to (L)4C4 → 2(L)2C2 is crucial for the assessment of their experimental viability. The (L)4C4 complexes with L = cAAC and DAC dissociate exergonically at room temperature into two (L)2C2 units. In contrast, the other (L)4C4 complexes with L = NHC, SNHC, MIC1, and MIC2 are thermochemically stable with respect to dissociation, (L)4C4 → 2(L)2C2. The computed adiabatic ionization potentials of (L)4C4 complexes with L = NHC, MIC1, and MIC2 are lower than those for the cesium atom. Particularly, (MIC1)4C4 and (MIC2)4C4 will very easily lose electrons to form cationic complexes. The SNHC ligand is the best for the experimental realization of (L)4C4 complexes, followed by NHC. The bonding analysis using charge and energy decomposition methods suggests that the (L)3C4-CL bond can be best described as a typical electron-sharing double bond with a strong σ-bond and a weaker π-bond. Therefore, the core bonding pictures in the title complexes resemble a [4]radialene. Larger substituents at the carbene ligands enhance the stability of the complexes (L)4C4 against dissociation.

Clusters and bulky Lewis acid protected complexes with planar hexacoordinate beryllium and magnesium.

Planar hexacoordination (ph) is only rarely reported in the literature. So far, only a few neutral and cationic molecules possessing phE (E = C, Si, B, Al, Ga) in the most stable isomer are predicted theoretically. Present electronic structure calculations report hitherto unknown anionic planar hexcoordinate beryllium and magnesium, phBe/Mg, as the most stable isomer. Global minimum searches show that the lowest energy structure of BeC6M3- (M = Al, Ga) and MgC6M3- (M = Ga, In, Tl) is the D3h symmetric phBe/Mg clusters, where beryllium/magnesium is covalently bonded with six carbon centers and M is located in a bridging position between two carbon centers. These global minimum phBe/Mg clusters are highly kinetically stable against isomerization, facilitating the experimental confirmation by photoelectron spectroscopy. Noteworthy is the fact that the phBe/Mg center is linked with carbon centers through three 7c-2e delocalized σ bonds and three 7c-2e π bonds, making the cluster double aromatic (σ + π) in nature. The bonding between the Be/Mg and outer ring moiety can be best expressed as an electron-sharing σ-bond between the s orbital of Be+/Mg+ and C6M32- followed by three dative interactions involving empty pπ and two in-plane p orbitals of Be/Mg. Furthermore, Lewis basic M centers of the title clusters can be passivated through the complexation with bulky Lewis acid, 9-boratriptycene, lowering the overall reactivity of the cluster, which can eventually open up the possibility of their large-scale syntheses.

Simultaneous Spectral Tuning and Thermal Stability Adjustment in Ca8ZnGa(1-x)Lax(PO4)7:Eu2+ Phosphors.

The modifications of local structure in solid solution are a crucial step to regulate the photoluminescence properties of rare-earth ion-based phosphors. However, the structural diversity of host matrices and the uncertain occupation of activators make it challenging to obtain phosphors with both high stability and tailored emission. Herein, We synthesized a series of ß-Ca3(PO4)2-type Ca8ZnGa(1-x)Lax(PO4)7:Eu2+ solid solution phosphors by design. By modifying the Ga/La ratio, controllable regulation of the emission spectrum and thermal stability of the phosphors can be achieved at the same time. The introduction of La3+ can regulate the crystal field splitting strength of the Eu2+ activators, causing redshifts in the emission spectrum while increasing Ga3+ content will lead to enhanced energy transfer between the oxygen vacancy and Eu2+, as well as improved thermal stability. Through local structure modification, the spectrum and thermal stability of phosphors can be facilely tuned. The results indicate that this series of phosphors have versatile potentials in various applications.

Polydopamine Nanocluster Embedded Nanofibrous Membrane via Blow Spinning for Separation of Oil/Water Emulsions.

Developing a porous separation membrane that can efficiently separate oil-water emulsions still represents a challenge. In this study, nanofiber membranes with polydopamine clusters polymerized and embedded on the surface were successfully constructed using a solution blow-spinning process. The hierarchical surface structure enhanced the selective wettability, superhydrophilicity in air (≈0°), and underwater oleophobicity (≈160.2°) of the membrane. This membrane can effectively separate oil-water emulsions, achieving an excellent permeation flux (1552 Lm-2 h-1) and high separation efficiency (~99.86%) while operating only under the force of gravity. When the external driving pressure was increased to 20 kPa, the separation efficiency hardly changed (99.81%). However, the permeation flux significantly increased to 5894 Lm-2 h-1. These results show that the as-prepared polydopamine nanocluster-embedded nanofiber membrane has an excellent potential for oily wastewater treatment applications.

Yellow Emission Obtained by Combination of Broadband Emission and Multi-Peak Emission in Garnet Structure Na2YMg2V3O12: Dy3+ Phosphor.

The fabrication and luminescent performance of novel phosphors Na2YMg2V3O12:Dy3+ were investigated by a conventional solid-state reaction method. Under near-UV light, the Na2YMg2V3O12 host self-activated and released a broad emission band (400-700 nm, with a peak at 524 nm) ascribable to charge transfer in the (VO4)3- groups. Meanwhile, the Na2YMg2V3O12:Dy3+ phosphors emitted bright yellow light within both the broad emission band of the (VO4)3- groups and the sharp peaks of the Dy3+ ions at 490, 582, and 663 nm at a quenching concentration of 0.03 mol. The emission of the as-prepared Na2YMg2V3O12:Dy3+ phosphors remained stable at high temperatures. The obtained phosphors, commercial Y2O3:Eu3+ red phosphors, and BaMgAl10O17:Eu2+ blue phosphors were packed into a white light-emitting diode (WLED) device with a near-UV chip. The designed WLED emitted bright white light with good chromaticity coordinates (0.331, 0.361), satisfactory color rendering index (80.2), and proper correlation to a color temperature (7364 K). These results indicate the potential utility of Na2YMg2V3O12:Dy3+ phosphor as a yellow-emitting phosphor in solid-state illumination.

Synthesis and Luminescence Properties of a Novel Green-Yellow-Emitting Phosphor BiOCl:Pr3+ for Blue-Light-Based w-LEDs.

The development of white-light-emitting diodes (w-LEDs) makes it meaningful to develop novel high-performance phosphors excited by blue light. Herein, BiOCl:Pr3+ green-yellow phosphors were prepared via a high-temperature solid-state reaction method. The crystal structure, luminescent properties, lifetime, thermal quenching behavior, and quantum yield were studied in detail. The BiOCl:Pr3+ phosphors presented several emission peaks located in green and red regions, under excitation at 453 nm. The CIE coordinates could be tuned along with the changed doping concentration with fair luminescence efficiency. The results also indicated that the optimized doping concentration of Pr3+ ions was at x = 0.0075 because of the concentration quenching behavior resulting from an intense exchange effect. When the temperature reached 150 °C, the intensity of the emission peak at 495 nm could remain at 78% of that at room temperature. The activation energy of 0.20 eV also confirmed that the BiOCl:Pr3+ phosphor exhibited good thermal stability. All these results indicate that the prepared products have potential to be used as a high-performance green-yellow-light-emitting phosphor for blue-light-based w-LEDs.

"114"-Type Nitrides LnAl(Si4-x Alx )N7 Oδ with Unusual [AlN6 ] Octahedral Coordination.

Aluminum-nitrogen six-fold octahedral coordination, [AlN6 ], is unusual and has only been seen in the high-pressure rocksalt-type aluminum nitride or some complex compounds. Herein we report novel nitrides LnAl(Si4-x Alx )N7 Oδ (Ln=La, Sm), the first inorganic compounds with [AlN6 ] coordination prepared via non-high-pressure synthesis. Structure refinements of neutron powder diffraction and single-crystal X-ray diffraction data show that these compounds crystallize in the hexagonal Swedenborgite structure type with P63 mc symmetry where Ln and Al atoms locate in anticuboctahedral and octahedral interstitials, respectively, between the triangular and Kagomé layers of [SiN4 ] tetrahedra. Solid-state NMR data of high-purity La-114 powders confirm the unusual [AlN6 ] coordination. These compounds are the first examples of the "33-114" sub-type in the "114" family. The additional site for over-stoichiometric oxygen in the structure of 114-type compounds was also identified.

Cembranoids from the Gum Resin of Boswellia carterii as Potential Antiulcerative Colitis Agents.

Eight new cembranoids, boscartins A-H (1, 2, and 4-9), and the known incensole oxide were isolated from the gum resin of Boswellia carterii. The absolute configurations of 1, 2, 4, and incensole oxide were unequivocally resolved using single-crystal X-ray diffraction analysis with Cu Kα radiation, and the absolute configuration of 5 was resolved via electronic circular dichroism data. The antiulcerative colitis activities of the compounds were evaluated in an in vitro x-box-binding protein 1 (XBP 1) transcriptional activity assay using dual luciferase reporter detection. At 10 µM, compounds 1, 5, 6, and 7 significantly activated XBP 1 transcription with EC50 values of 0.34, 1.14, 0.88, and 0.42 µM, respectively, compared with the pGL3-basic vector control.

Hepatoprotective benzofurans and furanolignans from Gymnema tingens.

Two new benzofurans, gymnefuranols A (1) and B (2), together with six known furanolignans (3-8), were isolated from Gymnema tingens. The structures of the new compounds were elucidated by comprehensive analysis of the NMR and HR-MS data. Compounds 1, 2, 6, and 7 showed hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.

Regulation of CK2 by phosphorylation and O-GlcNAcylation revealed by semisynthesis.

Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O-linked ß-N-acetyl-glucosamine (O-GlcNAc) on Ser347, proximal to a cyclin-dependent kinase phosphorylation site (Thr344). We use protein semisynthesis to show that phosphorylation of Thr344 increases the cellular stability of CK2α by strengthening its interaction with Pin1, whereas glycosylation of Ser347 seems to be antagonistic to Thr344 phosphorylation and permissive to proteasomal degradation. By performing kinase assays with site-specifically phospho- and glyco-modified CK2α in combination with CK2ß and Pin1 binding partners on human protein microarrays, we show that the kinase substrate selectivity of CK2 is modulated by these specific post-translational modifications. This study suggests how a promiscuous protein kinase can be regulated at multiple levels to achieve particular biological outputs.

Energy transfer from Sm3+ to Eu3+ in red-emitting phosphor LaMgAl11O19:Sm3+, Eu3+ for solar cells and near-ultraviolet white light-emitting diodes.

The red-emitting phosphor LaMgAl11O19:Sm(3+), Eu(3+) was prepared by solid-state reaction at 1600 °C for 4 h. The phase formation, luminescence properties, and energy transfer from Sm(3+) to Eu(3+) were studied. With the addition of 5 mol % Sm(3+) as the sensitizer, the excitation wavelength of LaMgAl11O19:Eu(3+) phosphor was extended from 464 to 403 nm, and the emission intensity under the excitation at 403 nm was also enhanced. The host material LaMgAl11O19 could contain the high doping content of Eu(3+) (20 mol %) without concentration quenching. This energy transfer from Sm(3+) to Eu(3+) was confirmed by the decay times of energy donor Sm(3+). The mechanism of energy transfer (Sm(3+) → Eu(3+)) was proved to be quadrupole-quadrupole interaction. Under the 403 nm excitation at 150 °C, the emission intensities of the characteristic peaks of Sm(3+) and Eu(3+) in LaMgAl11O19:0.05Sm(3+), 0.2Eu(3+) phosphor were decreased to 65% and 56% of the initial intensities at room temperature, and the relatively high activation energy proved that this phosphor had a good thermal stability. The CIE coordinate was calculated to be (x = 0.601, y = 0.390). The LaMgAl11O19:0.05Sm(3+), 0.2Eu(3+) phosphor is a candidate for copper phthalocyanine-based solar cells and white light-emitting diodes.

Cadmium activation of wild-type and constitutively active estrogen receptor alpha.

The estrogen receptor alpha (ERα) plays a central role in the etiology, progression, and treatment of breast cancers. Constitutively activating somatic mutations Y537S and D538G, in the ligand binding domain (LBD) of ESR1, are associated with acquired resistance to endocrine therapies. We have previously shown that the metalloestrogen calcium activates ERα through an interaction with the LBD of the receptor. This study shows that cadmium activates ERα through a mechanism similar to calcium and contributes to, and further increases, the constitutive activity of the ERα mutants Y537S and D538G. Mutational analysis identified C381, N532A, H516A/N519A/E523A, and E542/D545A on the solvent accessible surface of the LBD as possible calcium/metal interaction sites. In contrast to estradiol, which did not increase the activity of the Y537S and D538G mutants, cadmium increased the activity of the constitutive mutants. Mutation of the calcium/metal interaction sites in Y537S and D538G mutants resulted in a significant decrease in constitutive activity and cadmium induced activity. Mutation of calcium/metal interaction sites in wtERα diminished binding of the receptor to the enhancer of estrogen responsive genes and the binding of nuclear receptor coactivator 1 and RNA polymerase II. In contrast to wtERα, mutation of the calcium/metal interaction sites in the Y537S and D538G mutants did not diminish binding to DNA but prevented a stable interaction with the coactivator and polymerase. Growth assays further revealed that calcium channel blockers and chelators significantly decreased the growth of MCF7 cells expressing these constitutively active mutants. Taken together, the results suggest that exposure to cadmium plays a role in the etiology, progression, and response to treatment of breast cancer due, in part, to its ability to activate ERα.

Hepatoprotective prenylaromadendrane-type diterpenes from the gum resin of Boswellia carterii.

Chemical examination of the exuded gum resin of Boswellia carterii resulted in the isolation of nine new prenylaromadendrane-type diterpenes, boscartols A-I (1-9). The structures of these compounds were established by extensive 1D and 2D NMR spectroscopic analyses, mass spectrometric data, and circular dichroism spectra. Compounds 1-3, 5, 6, 8, and 9 (10 µM) showed moderate hepatoprotective activity against d-galactosamine-induced HL-7702 cell damage.

Hepatoprotective phenolic glycosides from Gymnema tingens.

Six new phenolic diglycosides, named gymnetinosides A-F (1-6), were isolated from the ethanolic extract of Gymnema tingens, together with three known diglycosides, sequinoside K (7), khaephuoside B (8), and albibrissinoside A (9). The structures of the new compounds were determined by spectroscopic techniques including 1D-, 2D NMR, mass spectroscopy, and circular dichroism. Compounds 1, 5, and 6 showed hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.

Calcium Activation of the Androgen Receptor in Prostate Cells.

Background: Although prostate cancer patients initially respond to androgen deprivation therapy, most patients progress to a resistant phenotype. Castration resistance is due, in part, to intratumoral and/or adrenal synthesis of androgens, overexpression or mutation of the androgen receptor (AR), stabilization of AR by chaperones, and ligand-independent activation of AR. Increasing evidence also links disruption of calcium homeostasis to progression of prostate cancer. Our previous study shows that heavy metal cadmium activates the AR through a ligand-independent mechanism. Cadmium mimics calcium in biological systems due to their similar ionic charge and radius. This study determines whether calcium activates AR and whether first- and second-generation antiandrogens block the ability of calcium to activate the receptor. Methods: The expression of androgen-responsive genes and calcium channels was measured in prostate cells using a quantitative real-time polymerase chain reaction assay. Cell growth was measured. Results: To ask whether calcium activates AR, prostate cells were treated with calcium in the absence and presence of the first-generation antiandrogens hydroxyflutamide and bicalutamide and the second-generation antiandrogen enzalutamide, and the expression of androgen-responsive genes and cell growth was measured. In the normal PWR-1E cells and HEK293T cells transiently expressing AR, treatment with calcium increased the expression of androgen-responsive genes by approximately 3-fold. The increase was blocked by enzalutamide but was not consistently blocked by the first-generation antiandrogens. In LNCaP cells which contain a mutant AR, treatment with calcium also increased the expression of androgen-responsive genes by approximately 3-fold, and the increase was more effectively blocked by enzalutamide than by hydroxyflutamide or bicalutamide. Treatment with calcium also increased cell growth that was blocked by enzalutamide. To ask whether dysregulation of calcium channels is associated with castration resistance, calcium channels were measured in the normal PWR-1E prostate cells, the hormone-responsive LNCaP cells, and the castration-resistant VCaP and 22RV1 cells. Compared to normal prostate cells, the hormone-responsive and hormone-resistant cells overexpressed several calcium channels. Conclusions: The results of this study show that calcium activates AR and increases cell growth and that calcium channels are overexpressed in hormone-responsive and hormone-resistant prostate cancer cells. Taken together, the results suggest a novel role of calcium in the castration-resistant phenotype.

Planar pentacoordinate s-block metals.

The presence of a delocalized π-bond is often considered an essential criterion for achieving planar hypercoordination. Herein, we show that σ-delocalization could be sufficient to make the planar configuration the most stable isomer in a series of planar pentacoordinate s-block metals. High-level ab initio computations reveal that the global minimum of a series of interalkali and interalkali-alkaline earth clusters (LiNa5, Li5Mg+, Na5Mg+, K5Ca+, CaRb5+, Rb5Sr+, and SrCs5+) adopts a singlet D5h structure with a planar pentacoordinate lithium or alkaline earth metal (AE = Mg, Ca, Sr). These clusters are unusual combinations to stabilize a planar pentacoordinate atom, as all their constituents are electropositive. Despite the absence of π-electrons, Hückel's rule is fulfilled by the six σ-electrons. Furthermore, the systems exhibit a diatropic ring current in response to an external magnetic field and a strong magnetic shielding, so they might be classified as σ-aromatic. Therefore, multicenter σ-bonds and the resulting σ-delocalization stabilize these clusters, even though they lack π-aromaticity.

Soft tissue tuberculosis detected by next-generation sequencing: A case report and review of literature.

BACKGROUND: Soft tissue tuberculosis is rare and insidious, with most patients presenting with a localized enlarged mass or swelling, which may be factors associated with delayed diagnosis and treatment. In recent years, next-generation sequencing has rapidly evolved and has been successfully applied to numerous areas of basic and clinical research. A literature search revealed that the use of next-generation sequencing in the diagnosis of soft tissue tuberculosis has been rarely reported. CASE SUMMARY: A 44-year-old man presented with recurrent swelling and ulcers on the left thigh. Magnetic resonance imaging suggested a soft tissue abscess. The lesion was surgically removed and tissue biopsy and culture were performed; however, no organism growth was detected. Finally, Mycobacterium tuberculosis was confirmed as the pathogen responsible for infection through next-generation sequencing analysis of the surgical specimen. The patient received a standardized anti-tuberculosis treatment and showed clinical improvement. We also performed a literature review on soft tissue tuberculosis using studies published in the past 10 years. CONCLUSION: This case highlights the importance of next-generation sequencing for the early diagnosis of soft tissue tuberculosis, which can provide guidance for clinical treatment and improve prognosis.