Structural analysis of potassium borate solutions.

In this work, H/D isotopic substitution neutron diffraction was combined with empirical potential structure refinement (EPSR) and DFT-based quantum calculations to study the interactions between B(OH)3 boric acid molecules, B(OH)4- metaborate ions, water molecules, and potassium cations in borate solutions. The results show that the solute ions and molecules have a marked effect on the second coordination shell of the water molecules, causing a greater deviation from a tetrahedral structure than is observed for pure water. Potassium ions and trans-B(OH)3 tend to form a monodentate contact ion pair (MCIP) with a K-B distance ∼3.8 Å, which remains constant upon changing the solution concentration. Potassium ions and cis-B(OH)3 form both a MCIP at K-B ∼3.8 Å and a bidentate contact ion pair (BCIP) at K-B ∼3.4 Å. As the solution concentration increases, there is a BCIP to MCIP transformation. Boric acid molecules can undergo hydration in one of three ways: direct hydration, interstitial hydration, and axial hydration. The energetic hydration preference is direct hydration → interstitial hydration → axial hydration. Nine water molecules are required when all water molecules directly interact with the -OH groups of B(OH)4-, and a tenth water molecule is located at an interstitial position. The hydrogen bonding between boric acid molecule/metaborate ion and water molecules is stronger than that between water molecules in the hydration layer.

Cuproptosis-associated genes and immune microenvironment characterization in breast cancer.

Excess Cu can cause cell death as a cofactor for essential enzymes. The relationship between cuproptosis-associated genes (CAGs) and breast cancer (BR) is not completely investigated. Here, the transcriptome expression and mutation profile data of BR samples from the Cancer Genome Atlas database were retrieved to identify CAGs. Patients with BR were clustered using consensus clustering. A least absolute shrinkage and selection operator analysis was then performed to construct a CAGs risk signature. As a result, all 13 cuproptosis regulators were significantly differentially expressed between BR and normal samples; among them, 9 cuproptosis genes were correlated with prognoses. Patients with BR were separated into 2 clusters that were associated with patient survival, clinical phenotypes, and immune infiltration, Based on the components of cuproptosis. Subsequently, genes differentially expressed between clusters were obtained, and 11 CAGs were ultimately incorporated into the risk signature. Functional analyses revealed that the risk signature correlated with patient outcomes, ER, PR, HER2 expression, and BR IHC subtypes. Additionally, immune microenvironment analyses showed that CAGs-high-risk patients exhibited lower immune cell infiltration and immune functions. Furthermore, high-risk BR patients had higher TMB, lower immune checkpoint expression, higher m6A gene expression, and higher tumor stemness. Finally, the immunophenoscore analysis revealed that the risk signature could potentially predict the immune response in BR and help guide the application of various immunotherapeutic drugs. Overall, the newly constructed CAGs risk signature presented a predictive value for the prognosis and tumor microenvironment of BR patients and can be further used in the guidance of immunotherapy for BR.

Dihydrogen Bonds in Aqueous NaBD4 Solution by Neutron and X-ray Diffraction.

Neutron diffraction, X-ray diffraction, and empirical potential structure refinement modeling were employed to study the structure of alkaline aqueous NaBD4 solutions at different NaBD4 concentrations and temperatures. In 1.0 mol·dm-3 NaBD4 aqueous solutions, about 5.6 ± 1.6 water molecules bond to BD4- via tetrahedral edges or tetrahedral corners without a very specific hydration geometry; that is, each hydrogen atom of BD4- bonds to 2.2 ± 1.0 water molecules through dihydrogen bonds with the D(B)···D(W) distance of 1.95 Å. The number of dihydrogen bonds decreases with increasing concentration and increases with temperature. Dihydrogen bonding is a predominantly electrostatic interaction which shows relatively lower directionality and saturability in comparison with the regular hydrogen bonds between water molecules. The water orientation around BD4- shows that the proportion of tetrahedral-edge dihydrogen bonds increases with temperature and decreases with concentration.

Ion hydration and association in aqueous potassium tetrahydroxyborate solutions.

Potassium tetrahydroxyborate solution is a significant material in the borate solution family, but there is limited knowledge about hydration structures and interactions of K+, [B(OH)4-], and water. In this study, the X-ray diffraction measurements of potassium tetrahydroxyborate solutions have been made. The experimental structure factors are subjected to Empirical Potential Structure Refinement (EPSR) modeling to reveal the details of ion hydration and association in the aqueous solutions. This study shows that the O(W)-O(W) distance of water in the studied solutions ranges from 2.82 to 2.76 Å with a coordination number that ranges from 4.7 ± 1.4 to 3.1 ± 1.3 when the value of the water-salt molar ratio (WSR) is decreased from 30 to 6. The addition of ions slightly affects the tetrahedral structure of water even when the concentration of ions is high. The first hydration distance of K+ remained at ∼2.67 Å, whereas the value of the coordination number (CN) decreased from 5.4 ± 1.3 to 3.9 ± 1.5 when the concentration of the borate solution was increased. The hydration ability of K+ was weak and almost did not have a fixed local hydration structure. The pair distribution function (PDF) of gB-O(W)(r) shows that [B(OH)4-] has a broad hydration distance from 2.9 to 5.4 Å because of the complex interactive relationship between K+, [B(OH)4-] and water. There is a competitive hydration between K+ and [B(OH)4-]. Both the X-ray diffraction and DFT-based calculations confirm that the main species is monodentate contact ion pairs when WSR = 30, bidentate contact ion pairs when WSR = 14, and triple contact ion pairs when WSR = 6. These results will provide a new understanding about potassium tetrahydroxyborate solution.

Raman and ab initio analyses of ion pairs in concentrated K[B(OH)4] droplets.

In this study, microscopic Raman spectroscopy and Ab initio quantum chemical calculation were used to determine the structural details of ion pairs and their transformation in concentrated K[B(OH)4] droplets. The Raman experiment shows that the vsym-B(OH)4- undergoes a downward shift with the decrease of WSR. The contact ion pairs (CIPs) change to solvent shared ion pairs when the molar water-to-solute ratio (WSR) is bigger than 6; CIPs are the dominant species when 1.33 < WSR < 6, where K+ bonds to [B(OH)4-] in bidentate form (CIP-II); the CIPs quickly dehydrate and associate to triple ion pairs (TIPs) when WSR < 5. Raman experiment and ab initio quantum chemical calculation show that TIPs are mainly present in "anionic" type such as {[B(OH)4-]K+[B(OH)4-](H2O)n}, where K+ bonds to two [B(OH)4-] in bidentate or/and tridentate form (TIP-a-II or/and TIP-a-III). When WSR <1.33, most TIPs convert to complex clusters such as chain-like structure. The remaining TIPs associate to six-membered ring structure [B3O3(OH)4-] and the relative content increases from 0 to 20% when the WSR ranges from 1.33 to 0.55.

Micro-Raman and density functional theory analyses of ion pairs in concentrated sodium tetrahydroxyborate droplets.

In this study, ion pairs in a single sodium tetrahydroxyborate [Na [B(OH)4] droplet were analyzed using an "in-situ strategy" in which a sample-droplet of nanogram mass was deposited on a hydrophobic substrate and droplet was forced to enter into a supersaturated state by decreasing the relative humidity (RH) of the environment. The structure of the solvated [B(OH)4-] ionic moiety with various molar water-to-solute ratios (WSR) was analyzed using Raman spectroscopy. To confirm the structural changes in the droplet, electronic structure calculations were carried out using density functional theory (DFT). The frequencies calculated for the totally symmetric BO stretching vibration (vsym(BO)) of the [B(OH)4-] moiety were compared with those of the fundamental bands observed in the Raman spectra recorded of the droplets. The following results have been obtained: (i) when WSR is reduced from 9 to 0.1, the frequency of the band that corresponds to vsym(BO) shifts from 745 to 746 cm-1, and its full-width at half-maximum value increases from 19.7 to 20.5 cm-1; (ii) when WSR ≥7, the solvent-shared ion pair (SIP) is predominantly present in the solution, whereas in the case of WSR < 7, SIP transforms into a contact ion pair (CIP) formed by Na+ and [B(OH)4-] in bidentate coordination; (iii) when WSR = 3, most of the CIPs transform into a cationic type of triple ion pair (TIP) composed of two Na+ and one [B(OH)4-] in bidentate coordination; (iv) when WSR is further reduced, most TIP continually associate to form a more complex structure and with a small amount of six-membered ring complex also formed. These results will help us understand the ion association mechanism during dehydration process of Na[B(OH)4] droplets.

Ab-initio investigation on ion-associated species and association process in Li[B(OH)4] solution.

In this paper, the factors determining the spectroscopic characteristics of vsym-B(OH)4- band including coupling effect, hydrogen bonding effect, and direct contact effect in Li[B(OH)4] solutions are investigated by using ab initio calculation. The coupling effect between the liberations of water and [B(OH)4-] has a larger effect on vsym-B(OH)4- in solvent-shared ion pair (SIP) and monodentate contact ion pair (MCIP), but the smaller effect in bidentate contact ion pair (BCIP). Water molecule tends to hydrate to the middle position between the first sphere of B(OH)4- and outer-sphere of [Li(H2O)4+] and has a different effect on vsym-B(OH)4- in ion pairs. The direct contact effect and polarization effect lead to 19.7 cm-1 red shift of vsym-B(OH)4- in MCIP, and 0.4 cm-1 blue shift in BCIP. The association process in Li[B(OH)4] solution was also introduced by using Raman spectral evolution of vsym -B(OH)4- in the dehydration process.

Synthesis, characterization and thermal decomposition kinetics of a bio-based transparent nylon 10I/10T.

Herein, we report a novel transparent engineering plastic nylon 10I/10T based on bio-based poly(decamethylene isophthalamide) (nylon10I). We have demonstrated the one-step melt polycondensation synthesis of transparent nylon and carried out Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR) to confirm the chemical structure. Furthermore, the dynamic mechanical analysis (DMA) and thermogravimetric analysis (TGA) were used to analyze the thermal properties. Glass transition temperature (Tg ) and thermal decomposition onset temperature (T1 ) of nylon 10I/10T (15 wt. % 10T) were 118.9 and 438.0 °C, respectively. The intrinsic viscosity, water absorption, light transmittance, mechanical properties, solvent resistance and the decomposition mechanism of nylon 10I/10T have also been investigated. The results show that the nylon 10I/10T has lower water absorption and enhanced solvent resistance compared to nylon 6-3-T, which indicates that nylon 10I/10T is a promising transparent plastic.

Microhydration of BH4-: Dihydrogen Bonds, Structure, Stability, and Raman Spectra.

Hydridic-to-protonic interactions in unconventional dihydrogen bonding influence the structure, reactivity, and selectivity in solution and in the solid state. In this study, the structure, stability, and Raman spectra of BH4- hydrated clusters, [BH4(H2O)n]- (n = 1-8, 10, 12, 14, 16) are systematically investigated using density functional theory (DFT) at the wB97XD/6-311++g(3df,3pd) basis set level. The successive microhydration process is described to illustrate in detail the changes in dihydrogen bonding with increasing hydration cluster size. The results of DFT calculations indicate that seven or eight water molecules hydrate BH4- with a total of 12 dihydrogen bonds in the tetrahedral edge or tetrahedral corner forms, and a maximum of six water molecules in the tetrahedral-edge form. Raman spectra of [BH4(H2O)n]- show a blue shift in the B-H stretching band due to hydration. Car-Parrinello molecular dynamics simulations verify strong BH4- water interactions. The hydration number of BH4- is 6.7, with a hydration B-O(W) distance of 3.40 Å, and each hydrogen in BH4- bonds with 2.66 hydrogen atoms from water.

B(OH)4- hydration and association in sodium metaborate solutions by X-ray diffraction and empirical potential structure refinement.

X-ray diffraction is used to study the structure of aqueous sodium metaborate solutions at salt concentrations of 1, 3, and 5 (oversaturated) mol dm-3. The X-ray structure factors are subjected to empirical potential structure refinement (EPSR) modelling to extract the individual site-site pair correlation functions, the coordination numbers, and the spatial density functions (three-dimensional structure) of ion hydration and association as well as solvent water in the borate solutions. The sodium ion is surrounded on average by (5.4 ± 0.7), (4.6 ± 1.0), and (3.7 ± 1.2) water molecules at 1, 3, and 5 mol dm-3, respectively, with the Na-O (H2O) distance of 2.34 Å. The decrease in hydration number of the sodium ion is compensated by direct binding of the oxygen atom of the borate ion, B(OH)4-, with the average coordination number of (0.2 ± 0.5), (1.0 ± 0.8), and (2.1 ± 1.3) at the Na-O(B) distance of 2.34 Å to keep the octahedral hydration shell of the sodium ion. The average number of water molecules around the borate ion is (13.9 ± 1.8), (14.2 ± 1.8), and (16.1 ± 2.4) per borate ion with increasing salt concentration with the B-O(H2O) distance of 3.72 Å. The number of nearest-neighbour water molecules around a central water molecule in a solvent decreases as (4.8 ± 1.2), (3.8 ± 1.1), and (2.8 ± 1.1) with an increase in salt concentration with the O(H2O)-O(H2O) distance of 2.79 Å. The Na+-B(OH)4- ion association is characterized by the Na-O(B) and Na-B pair correlation functions. The Na-B interactions are observed at 3.00 Å as a shoulder and 3.57 Å as a main peak in the site-site pair correlation function, suggesting two occupancy sites of Na+ with one for the edge-shared bidentate bonding and the other for the corner-shared monodentate bonding. The total number of Na-B interactions at 3.00 and 3.57 Å is consistent with that of the Na-O(B) interactions. The detailed three-dimensional structure of the ion hydration and association is visualized as a function of salt concentration. The structure and stability of [NaB(OH)4(H2O)6]0 clusters are further investigated by DFT calculations, and the most likely structure is proposed and cross-checked.

New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy.

Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

Direct contact versus solvent-shared ion pairs in saturated NiCl2 aqueous solution: a DFT, CPMD, and EXAFS investigation.

In this work, a systematic investigation of the competition coordination of H2O and Cl(-) with Ni(2+) in saturated NiCl2 aqueous solution at room temperature was conducted using density functional theory (DFT), Car-Parrinello molecular dynamics (CPMD) simulations, and extended X-ray absorption fine structure (EXAFS) spectra. The calculated results reveal that the six-coordinated structure is favorable for [NiCl(x)(H2O)(n)](2-x) (x = 0-2; n = 1-12) clusters in the aqueous phase. The hydration energy calculation shows that the six-coordinated solvent-shared ion pair (SSIP) ([Ni(H2O)6(H2O)(n-6)Cl](+)) is more stable than its contact ion pair (CIP) ([NiCl(H2O)5(H2O)(n-5)](+)) isomer as n ≥ 9 in the aqueous phase, and the six-coordinated solvent-shared ion pair with a dissociated double Cl(-) (SSIP/d) ([Ni(H2O)6(H2O)(n-6)Cl2](0)) is more preferable than its CIP ([NiCl2(H2O)4(H2O)(n-4)](0)) and solvent-shared ion pair with single dissociated Cl(-) (SSIP/s) ([NiCl(H2O)5(H2O)(n-5)Cl](0)) isomers as n ≥ 11. The six-coordinated SSIP/d ([Ni(H2O)6(H2O)(n-6)Cl2](0)) conformers are the dominant structures in a saturated NiCl2(aq) solution (NiCl2 concentration: ~5.05 mol·kg(-1), corresponding to n ≈ 11). The CPMD simulations exhibited that there are six water molecules with Ni-O distance at ~205.0 pm on average around each Ni(2+) in the first hydration sphere, even in the saturated NiCl2 aqueous solution (~5.05 mol·kg(-1)) at room temperature, and no obvious Ni-Cl interaction was found. The EXAFS spectra revealed that the first solvation shell of Ni(2+) is an octahedral structure with six water molecules tightly bound in the NiCl2(aq) solution with a concentration ranging from 1.00 to 5.05 mol·kg(-1), and there is no obvious evidence of Ni-Cl contact ion pairs. A comprehensive conclusion from the DFT, CPMD, and EXAFS studies is that there is no obvious direct contact between Ni(2+) and Cl(-), even in saturated NiCl2 aqueous solution at room temperature.

Solution structure of energy stored system I: aqua-B(OH)4(-): a DFT, Car-Parrinello molecular dynamics, and Raman study.

A systematic study on the structure, stability, and Raman spectra of the metaborate anion hydrated clusters, B(OH)4(-)(H2O)n, (n = 1-15) was carried out by DFT in both gaseous and aqueous phase at the B3LYP/aug-cc-pVDZ level; all of these stable configurations were described, and the most stable hydrated clusters were chosen. The hydrogen bonds in those hydrated clusters were described in three different items: symmetrical double hydrogen bonding (DHB), single hydrogen bonding (SHB), and interwater hydrogen bonding (WHB). The distance of SHB is shorter than that of DHB, and multiple SHBs are more stable than a single DHB. In small size clusters (n ≤ 5), a structure with more DHBs is more stable than other arrangements. With continued increase in size, more SHBs were found in the first hydration sphere: when n ≥ 9, only SHBs can be found, and when n ≥ 12, a full hydration structure is formed with 12 SHBs and a hydration number of 10-12. The Car-Parrinello molecular dynamics simulation shows that only the first hydration sphere can be found, and the hydration number of B(OH)4(-) is 9.2 and the hydration distance is 3.68. The total symmetrical stretching vibration of B(OH)4(-) in hydrated B(OH)4(-)(H2O)n is blue shifted with increasing cluster size. After consideration of hydration, the calculated characteristic frequencies are in accord with the experiment characteristic frequency of B(OH)4(-).

Race, ABO blood group, and venous thromboembolism risk: not black and white.

BACKGROUND: The rate of venous thromboembolism (VTE) has been reported to be higher in blacks compared to whites. Non-O blood groups have also been associated with a significantly higher VTE risk. Given that a higher proportion of blacks have O blood group, one might have expected that black individuals would have fewer VTEs. STUDY DESIGN AND METHODS: In this study, we analyzed race, sex, age, ABO or Rh blood group, and VTE risk in 60,982 black and white patients admitted over a span of 10 years. RESULTS: The overall occurrence of VTEs was 7.6%, higher in males (8.7% males vs. 7.2% females), higher in non-O blood groups (8.5% non-O vs. 6.9% O blood group), and increased with age (5.8% <65 years, 11.3% ≥65 years). No difference in VTE rate was noted with Rh antigen positivity. When stratified by age, VTE rate was consistently higher in blacks and non-O blood groups. No difference was detected among the various non-O blood groups. To assess the potential confounder of comorbidities, we stratified patients according to Charlson comorbidity score. In a subgroup of healthy patients with age-independent Charlson comorbidity scores of 0 (n = 28,387), blacks still had an increased VTE risk and this risk was still higher with increasing age and in those with non-O blood groups. CONCLUSION: We conclude that black race and non-O blood groups have increased VTE risk when stratified for age and that associated comorbidities do not explain these differences.

PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans.

Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non-sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

Polyborates in aqueous borate solution: a Raman and DFT theory investigation.

The geometries, energies and vibrational frequencies of various polyborates in both gaseous and aqueous phase were calculated at the B3LYP/aug-cc-pVDZ level. The calculated total symmetrical stretching Raman shifts of B(OH)(3), B(OH)(4)(-), B(2)O(OH)(4), B(2)O(OH)(5)(-), B(2)O(OH)(6)(2-), B(3)O(3)(OH)(3), B(3)O(3)(OH)(4)(-), B(3)O(3)(OH)(5)(2-), B(3)O(3)(OH)(6)(3-), B(4)O(5)(OH)(4)(2-) and B(5)O(6)(OH)(4)(-) were assigned to 877.40, 735.33, 785.22, 792.90, 696.79, 587.72, 599.06, 740.16, 705.01, 551.67 and 521.04cm(-1), respectively. The results can be used as the characteristic frequency for polyborates in aqueous phase at room temperature. At least six types of polyborates B(OH)(3), B(OH)(4)(-), B(3)O(3)(OH)(4)(-), B(3)O(3)(OH)(5)(2-), B(4)O(5)(OH)(4)(2-) and B(5)O(6)(OH)(4)(-), occur in aqueous solutions at ambient temperature. The chemical species distribution and the relevant interaction mechanisms among polyborates in the solutions were also suggested.