Submission of Evidence on Online Violence Against Women to the UN Special Rapporteur on Violence Against Women, its Causes and Consequences, Dr Dubravka Šimonović

Figure S1. B3GALNT2 levels determined by W.B. and ROC curve. a–c Relative mRNA expression of B3GALNT2 in HCC tumor tissues and normal liver tissues obtained from GSE76427, GSE36376, and TCGA-LIHC datasets. d Western blot analysis of B3GALNT2 levels in 24 pairs of HCC tissues. T HCC tumor tissue, N adjacent non-tumor tissue. e ROC curve analysis of the sensitivity and specificity for the predictive value of TNM model, B3GALNT2 expression, and the combination model. (TIFF 546 kb

Regression of the random coefficient model.

Regression of the random coefficient model.</p

Impact of water technologies on economic growth in Northwest China.

Impact of water technologies on economic growth in Northwest China.</p

Scope of the study region: Northwestern China and water resources per capital in the world, China and each province of Northwestern China.

Scope of the study region: Northwestern China and water resources per capital in the world, China and each province of Northwestern China.</p

Stochastic production frontier regression results.

Stochastic production frontier regression results.</p

Data-driven point adjusted Jouyban-Acree-Artificial neural network hybrid model for predicting solubility of active pharmaceutical ingredients in binary solvent mixtures

Solubility data of active pharmaceutical ingredients (APIs) in binary solvent mixtures are crucial for optimizing solid-liquid separation processes, conducting early solvent screening, and ensuring safety. This study presents data-driven models integrating Monte Carlo optimization algorithms, the Jouyban-Acree (JA) model, and artificial neural networks (ANN) to comprehensively predict API solubility in binary solvent mixtures. A comprehensive database comprising 71,888 data points was constructed, encompassing quantitative descriptors of the three-dimensional structures of solutes and binary solvent molecules, as well as the molecular interaction energies between these solvents. A hybrid model, Jouyban-Acree-ANN (JAANN), was developed to predict solubility across various temperatures and solvent compositions. This model demonstrated robust predictive performance, with prediction errors generally below 10%. Additionally, we introduced a Point Adjusted JAANN (PA-JAANN) model that integrates Monte Carlo simulations to refine solubility predictions by calibrating a single experimental data point. This calibration significantly enhances the model’s accuracy, achieving an average error reduction of over 20% compared to the standard JAANN model. A comparative Direct Prediction-ANN (DP-ANN) model was also constructed, providing rapid solubility predictions without experimental data, though it had limitations in robustness. The predictive abilities of these three models were thoroughly validated based on experiments involving the mefenamic acid-2-butanol-heptane system. These models can be used for different predictive needs, offering flexible and reliable solubility predictions essential for optimizing crystallization processes in pharmaceutical manufacturing.</p

Multivariate Analysis of a Highly Effective Drug Combination Tablet Containing the Antiepileptic Drug Gabapentin to Enhance Pharmaceutical Properties with a Multicomponent Crystal Strategy

A thorough grasp of the relationship between the crystal structure and properties is necessary for the design of crystals with specific properties using crystal engineering. Gabapentin (GBP), an analogue of the neurotransmitter gamma-aminobutyric acid, is used to treat partial seizures. GBP exhibits a fast dissolution rate. However, because of being plastically and elastically deforming, which increases the possibility of capping or laminating during compression, GBP exhibits poor compaction behavior. The aim of the study was to address the aforementioned issues, involving preparing and characterizing gabapentin monohydrate (GBP·H2O) and cocrystals (GBP-PABA) with p-aminobenzoic acid (PABA). Both the tablets of GBP·H2O and GBP-PABA can successfully slow down the dissolution rate of the original drug and reduce the intrinsic dissolution rate. Additionally, the multicomponent crystals of GBP have slip planes, demonstrating very excellent compaction properties, according to a thorough study on the mechanical properties of crystals. In terms of single-crystal structure and intermolecular interaction, the compressibility assessment of multicomponent crystals by analysis of relationships between mechanical properties and bulk powder compaction behavior further proved its plastic behavior and appropriateness for direct compression. Therefore, the development of multicomponent crystals will effectively solve the determination of the parent drug itself and become an efficient oral combined formulation

Theoretical and Structural Understanding of the Different Factors Influencing the Formation of Multicomponent Crystals of 2,4-Dichlorophenoxyacetic Acid with N‑heterocyclic Compounds

The formation of multicomponent crystals depends on many factors; therefore it is extremely challenging to predict and select the appropriate coformers (CCFs) to prepare functional multicomponent crystals. In this study, we selected the 2,4-dichlorophenoxyacetic acid (2,4-D) molecule and 10 N-heterocyclic compounds with similar structures to investigate the main factors affecting the synthesis of multicomponent crystals. On screening of multicomponent crystals by solution crystallization, we obtained nine kinds of multicomponent crystals of 2,4-D with different colors, including a hydrate of the 2,4-D-PYE cocrystal. However, 1,3-bis­(4-pyridyl)­propane (BPP) failed to form multicomponent crystals with 2,4-D using the solution crystallization methods. The influence of CCF on the formation of multicomponent crystals was discussed from three aspects: hydrogen bond donor and acceptor capacity (molecular electrostatic potential (MEP) surface, hydrogen bond acceptor ability h_ema calculated by Molecular Operating Environment software, and interaction site-pairing energy differences (ΔEsite‑pair)), thermodynamic enthalpy (the excess enthalpy ΔHex), and structural factors (molecular complementarity (MC) and molecular flexibility (Kier flex)). Molecular flexibility is the main reason no multicomponent crystals are formed between BPP and 2,4-D. A logistic regression calculation indicates that the formation of multicomponent crystals of 2,4-D is mainly affected by ΔEsite‑pair and MEP values. The cases considered in this study not only expand the crystal structure landscape of the 2,4-D but also provide a reference for the effective prediction and design of multicomponent crystals, in general

Multiple Mechanical Behaviors in One Crystal of 2,4-Dichlorophenoxyacetic Acid Form II: Thermomechanical Effect and Elastic Deformation

Mono-component crystals showing multiple stimuli-responsiveness have attracted tremendous interest and remain a big challenge. Herein, we report the discovery of the second polymorph of the famous herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (Form II), which exhibits multiple mechanical behaviors, including thermomechanical effect and elastic deformation. The relationship between mechanical behaviors and crystal structure was illustrated. The 2,4-D Form II crystals exhibit thermomechanical behavior due to the molecular rearrangement, generating strain within these crystals. The strain energy is developed and accumulated, followed by its rapid release. The elastic behavior requires multiple weak interactions and interlocked molecular packing that prevents sliding between layers. This work can contribute to a better understanding of the design of multifunctional crystal materials

Multiple Mechanical Behaviors in One Crystal of 2,4-Dichlorophenoxyacetic Acid Form II: Thermomechanical Effect and Elastic Deformation

Mono-component crystals showing multiple stimuli-responsiveness have attracted tremendous interest and remain a big challenge. Herein, we report the discovery of the second polymorph of the famous herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (Form II), which exhibits multiple mechanical behaviors, including thermomechanical effect and elastic deformation. The relationship between mechanical behaviors and crystal structure was illustrated. The 2,4-D Form II crystals exhibit thermomechanical behavior due to the molecular rearrangement, generating strain within these crystals. The strain energy is developed and accumulated, followed by its rapid release. The elastic behavior requires multiple weak interactions and interlocked molecular packing that prevents sliding between layers. This work can contribute to a better understanding of the design of multifunctional crystal materials