Domain-Agnostic Molecular Generation with Self-feedback

The generation of molecules with desired properties has gained tremendous popularity, revolutionizing the way scientists design molecular structures and providing valuable support for chemical and drug design. However, despite the potential of language models in molecule generation, they face numerous challenges such as the generation of syntactically or chemically flawed molecules, narrow domain focus, and limitations in creating diverse and directionally feasible molecules due to a dearth of annotated data or external molecular databases. To this end, we introduce MolGen, a pre-trained molecular language model tailored specifically for molecule generation. MolGen acquires intrinsic structural and grammatical insights by reconstructing over 100 million molecular SELFIES, while facilitating knowledge transfer between different domains through domain-agnostic molecular prefix tuning. Moreover, we present a self-feedback paradigm that inspires the pre-trained model to align with the ultimate goal of producing molecules with desirable properties. Extensive experiments on well-known benchmarks confirm MolGen's optimization capabilities, encompassing penalized logP, QED, and molecular docking properties. Further analysis shows that MolGen can accurately capture molecule distributions, implicitly learn their structural characteristics, and efficiently explore chemical space. The pre-trained model, codes, and datasets are publicly available for future research at https://github.com/zjunlp/MolGen.Comment: Work in progress. Add results of binding affinit

Forward modeling of P- and S-waves response of fractures intersected with horizontal wells in tight reservoirs

Horizontal wells play an important role in expanding the drilling volume of reservoirs and oil production area, and are widely used in unconventional reservoirs. Fractures have a positive effect on reservoir permeability, but fractures can also cause accidents such as casing deformation and inter-well frac-hit. It is of great significance to identify and evaluate fractures intersected with horizontal wells in tight reservoirs. In this paper, a three-dimensional numerical model of horizontal wells and fractures in tight reservoirs is designed. The responses of monopole P-wave and dipole S-wave to fractures with different width, dip angle and filling medium are systematically studied, by using three-dimensional finite difference algorithm. The results show that when the fracture is filled with calcite, the amplitude attenuation of monopole P-wave and dipole S-wave has a monotonic exponential increase with the increase of fracture width and the decrease of fracture dip angle. In the real data processing, the amplitude attenuation of P- and S-waves can be used to jointly evaluate the fracture filled with calcite. When the fracture is filled with water, both P- and S-waves have prominent amplitude attenuation. P wave amplitude attenuation does not have a monotonic variation with the increase of fracture width but it has a monotonic increase with the decrease of fracture dip angle. S wave amplitude attenuation has a monotonic increase with the increase of fracture width and the decrease of fracture dip angle. The amplitude attenuation of P- and S- waves rises significantly when the fracture is filled with natural gas. This study is crucial for better understanding the response of P- and S-waves to fractures intersected with borehole in tight reservoirs, and it provides useful information for the inversion of fracture parameters by using P- and S-waves

Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Models

Large Language Models (LLMs), with their remarkable task-handling capabilities and innovative outputs, have catalyzed significant advancements across a spectrum of fields. However, their proficiency within specialized domains such as biomolecular studies remains limited. To address this challenge, we introduce Mol-Instructions, a meticulously curated, comprehensive instruction dataset expressly designed for the biomolecular realm. Mol-Instructions is composed of three pivotal components: molecule-oriented instructions, protein-oriented instructions, and biomolecular text instructions, each curated to enhance the understanding and prediction capabilities of LLMs concerning biomolecular features and behaviors. Through extensive instruction tuning experiments on the representative LLM, we underscore the potency of Mol-Instructions to enhance the adaptability and cognitive acuity of large models within the complex sphere of biomolecular studies, thereby promoting advancements in the biomolecular research community. Mol-Instructions is made publicly accessible for future research endeavors and will be subjected to continual updates for enhanced applicability.Comment: Project homepage: https://github.com/zjunlp/Mol-Instructions. Add quantitative evaluation

Impact of Zr substitution on the electronic structure of ferroelectric hafnia

$\mathrm{HfO_2}$-based dielectrics are promising for nanoscale ferroelectric applications, and the most favorable material within the family is Zr-substituted hafnia, i.e., $\mathrm{Hf_{1-x}Zr_xO_2}$ (HZO). The extent of Zr substitution can be great, and x is commonly set to 0.5. However, the band gap of $\mathrm{ZrO_2}$ is lower than $\mathrm{HfO_2}$, thus it is uncertain how the Zr content should influence the electronic band structure of HZO. A reduced band gap is detrimental to the cycling endurance as charge injection and dielectric breakdown would become easier. Another issue is regarding the comparison on the band gaps between $\mathrm{HfO_2}$/$\mathrm{ZrO_2}$ superlattices and HZO solid-state solutions. In this work we systematically investigated the electronic structures of $\mathrm{HfO_2}$, $\mathrm{ZrO_2}$ and HZO using self-energy corrected density functional theory. In particular, the conduction band minimum of $Pca2_1$-$\mathrm{HfO_2}$ is found to lie at an ordinary k-point on the Brillouin zone border, not related to any interlines between high-symmetry k-points. Moreover, the rule of HZO band gap variation with respect to x has been extracted. The physical mechanisms for the exponential reduction regime and linear decay regime have been revealed. The band gaps of $\mathrm{HfO_2}$/$\mathrm{ZrO_2}$ ferroelectric superlattices are investigated in a systematic manner, and the reason why the superlattice could possess a band gap lower than that of $\mathrm{ZrO_2}$ is revealed through comprehensive analysis.Comment: 23 pages, 9 figure

Simultaneous extraction and purification of alkaloids from Sophora flavescens Ait. by microwave-assisted aqueous two-phase extraction with ethanol/ammonia sulfate system

A rapid and effective method of integrating extraction and purification for alkaloids from Sophora flavescens Ait. was developed by microwave-assisted aqueous two-phase extraction (MAATPE) based on the high efficiency of microwave-assisted extraction (MAE) and the demixing effect of aqueous two-phase extraction (ATPE). The aqueous two-phase system (ATPS), ethanol/ammonia sulfate was chosen from seven combinations of ethanol/salt systems, and its extraction properties were investigated in detail. Key factors, namely, the compositions of ATPS, solvent-to-materials ratio, and the extraction temperature were selected for optimization of the experimental conditions using response surface methodology (RSM) on the basis of the results of the single-factor experiment. The final optimized conditions were, the compositions of ATPS: ethanol 28% (w/w) and (NH4)2SO4 18% (w/w), solvent-to-material ratio 60:1, temperature 90 C, extraction time 5 min, and microwave power 780 W. MAATPE was superior to MAE, the latter using a single solvent, not only in extraction yield but also in impurity content. Moreover, compared with the combination of MAE and ATPE in the two-step mode, MAATP demonstrated fewer impurities, a better yield (63.78 ± 0.45 mg/g) and a higher recovery (92.09 ± 0.14%) in the extraction and purification of alkaloids. A continuous multiphase-extraction model of MAATPE was proposed to explicate the extraction mechanism. MAATPE revealed that the interaction between microwave and ATPS cannot only cause plant cell rupture but also accelerate demixing, improving mass-transfer from solid–liquid extraction to liquid– liquid purification. MAATPE simplified procedures also contributed to the lower loss occurrence, better extraction efficiency, and reduced impurity to target constituents.The Science and Technology Project of Guangzhou (No. 2008Z1-E301) and Faculty Development fund Project of Guangdong Pharmaceutical University (No. 52104109

Preparation, characterization and application of a molecularly imprinted polymer for selective recognition of Sulpiride

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor α of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP–sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug releas

Functional soil organic matter fractions in response to long-term fertilization in upland and paddy systems in South China

Soil organic matter (SOM) and its fractions play key roles in optimizing crop yield and improving soil quality. However, how functional SOM fractions responded to long-term fertilization and their relative importance for C sequestration were less addressed. In this study, we determined the effects of long-term fertilization on six functional SOM fractions (unprotected, physically protected, physico-biochemically protected, physico-chemically protected, chemically protected, and biochemically protected) based on two long-term fertilization experiments carried out in South China. The unprotected coarse particulate organic matter (cPOM), the biochemically and chemically protected silt-sized fractions (NH-dSilt and H-dSilt) were the primary C storage fractions under long-term fertilization, accounting for 23.6–46.2%, 15.7–19.4%, and 14.4–17.4% of the total soil organic carbon (SOC) content in upland soil and 19.5–29.3%, 9.9–15.5%, and 14.2–17.2% of the total SOC content in paddy soil, respectively. Compared with the control treatment (CK) in upland soil, the application of manure combined with mineral NPK (NPKM) resulted in an increase in the SOC content in the cPOM, pure physically protected fraction (iPOM), the physico-chemically protected (H-μSilt), and the chemically protected (H-dSilt) fraction by 233%, 166%, 124%, and 58%, respectively. Besides, the SOC increase in upland soil expressed as SOC content per unit of total SOC for iPOM, H-μSilt, cPOM and H-dSilt were the highest and as large as 283%, 248%, 194%, and 105% respectively. In paddy soil, the highest increase per unit of total SOC was H-dSilt (190%), followed by H-dClay (156%) and H-μSilt (155%). These results suggested that the upland soil could stabilize more C through the pure physical, whereas the chemical protection mechanism played a more important role in paddy soil. Chemical protection mechanism within the microaggregates played important roles in sequestrating C in both upland and paddy soils. Overall, the different responses of functional SOM fractions to long-term fertilization indicate different mechanisms for SOM cycling in terms of C sequestration under upland and paddy systems

Structure, piezoelectric, and ferroelectric properties of BaZrO 3 substituted Bi(Mg 1/2Ti 1/2)O 3-PbTiO 3 perovskite

The structure and electric properties of (0.9-x)Bi(Mg1/2 Ti 1/2)O3-xPbTiO3-0.1BaZrO3(0.45 ≤x ≤0.53) ceramics were investigated. The morphotropic phase boundary between tetragonal ferroelectric and pseudo-cubic relaxor phases is ascertained at x=0.50. The BaZrO3 substitution can much reduce the coercive field of Bi(Mg1/2 Ti1/2)O3-PbTiO3. The studies on temperature dependence of both ferroelectric and dielectric constant indicate a direct evidence for the antiferroelectric relaxor phase, which was ever suggested in the binary system of Bi(Mg1/2 Ti1/2)O3-PbTiO3. The phase transition of ferroelectric to antiferroelectric relaxor produces the thermal depoling below the Curie temperature. The ceramic of BMT-0.47PT-0.1BZ exhibits a high strain 0.37% and a large-signal d33 (530 pm/V) in the antiferroelectric-relaxor phase. BaZrO3 substituted Bi(Mg1/2 Ti1/2)O3-PbTiO3 shows an analogous phase diagram to that of lead-free (Bi, Na)TiO 3-BaTiO 3