Computing equilibrium free energies through a nonequilibrium quench

Many methods to accelerate sampling of molecular configurations are based on the idea that temperature can be used to accelerate rare transitions. These methods typically compute equilibrium properties at a target temperature using reweighting or through Monte Carlo exchanges between replicas at higher temperatures. A recent paper demonstrated that accurate equilibrium densities of states can also be computed through a nonequilibrium ``quench'' process, where sampling is performed at a higher temperature to encourage rapid mixing and then quenched to lower energy states with dissipative dynamics. Here we provide an implementation of the quench dynamics in LAMMPS and evaluate a new formulation of nonequilibrium estimators for the computation of partition functions or free energy surfaces (FESs) of molecular systems. We show that the method is exact for a minimal model of $N$-independent harmonic springs, and use these analytical results to develop heuristics for the amount of quenching required to obtain accurate sampling.= We then test the quench approach on alanine dipeptide, where we show that it gives an FES that is accurate near the most stable configurations using the quench approach, but disagrees with a reference umbrella sampling calculation in high FE regions. We then show that combining quenching with umbrella sampling allows the efficient calculation of the free energy in all regions. Moreover, by using this combined scheme, we obtain the FES across a range of temperatures at no additional cost, making it much more efficient than standard umbrella sampling if this information is required. Finally, we discuss how this approach can be extended to solute tempering and demonstrate that it is highly accurate for the case of solvated alanine dipeptide without any additional modifications.Comment: 18 pages, with 8 figures, 1 table, and 9 supplemental figure

Zanubrutinib in the Maintenance Treatment of Elderly People with Primary Central Nervous System Lymphoma: A Report of 2 Cases

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma. The predominant subtype is diffuse large B-cell lymphoma (DLBCL), and no systematic lesion is identified at diagnosis. BTKi (Bruton’s tyrosine kinase inhibitor) has demonstrated significant clinical activity in DLBCL. We retrospectively reported on 2 patients who began with memory deterioration or right limb movement disabilities. A cranial magnetic resonance imaging (MRI) scan and a brain biopsy were used to diagnose PCNSLs. Middle-dose methotrexate (MD-MTX) regimens were initiated for induction treatment. Zanubrutinib was chosen as the maintenance regimen due to the patients' inability to tolerate continuous MTX regimens. For 1 patient, he achieved sustained complete remission (CR) demonstrated by MRI. Another patient achieved partial remission (PR). The two patients are both alive until now. We successfully extended the PFS and OS in elderly PCNSL patients treated with zanubrutinib

Efficacy of laser therapy for temporomandibular disorders: A systematic review and meta-analysis

Objective: The aim of this systematic review was to evaluate the efficacy of laser therapy in temporomandibular disorders (TMD). Methods: Randomized controlled trials (RCTs) in regard to this issue were searched in electronic databases. Three investigators independently screened the eligible studies, and the quality of the included studies was assessed according to the risk of bias tool recommended by the Cochrane handbook. The primary outcome measure was the degree of pain, reported on a visual analog scale (VAS), and the secondary outcome measures were TMJ function, including maximum active vertical opening (MAVO), maximum passive vertical opening (MPVO), left and right lateral movement (LLE, RLE). Pooled effect sizes were calculated using random effects models and 95% confidence interval (95% CI). Results: A total of 28 randomized controlled trials were included. Laser therapy had a more significant effect in terms of VAS (SMD=﹣1.88; 95% CI=﹣2.46 to﹣1.30; P < 0.00001; I2 =93%), MAVO (MD = 4.90; 95% CI= 3.29–6.50; P < 0.00001; I2 =72%), MPVO (MD=5.82; 95% CI= 4.62–7.01; P < 0.00001; I2 =40%) and RLE (MD = 0.73; 95% CI= 0.23–1.22; P = 0.004; I2 = 0%) as compared to placebo group. However, there was no significant difference in LLE between two groups (MD= 0.35; 95% CI=﹣0.31–1.01; P = 0.30; I2 =0%). Conclusions: Laser therapy can effectively reduce pain but have small effect on improving mandibular movement of TMD patients. More well-designed RCTs with large sample sizes are needed for further validation. And these studies should report detailed laser parameters and provide complete outcome measure data

Diversity of Reproductive Phenology Among Subtropical Grasses Is Constrained by Evolution and Climatic Niche

Reproductive phenology is sensitive to climatic changes and is associated with species functional types, distribution ranges, and their corresponding climatic niches. Phylogenetic niche conservatism in reproductive phenology also constrains its diversity and the distribution of species. Therefore, we assessed the effects of photosynthetic pathway, life history, phylogeny, and climatic niche on reproductive phenology. For 190 Poaceae species in subtropical China, we compiled data on flowering onset and reproductive period, functional type (photosynthetic pathway and life history), and 18 climatic variables across the species' global distributions and used phylogenetic models to determine associations. We found strong phylogenetic signals in flowering onset but not in reproductive period. Photosynthetic pathway and life history have significant interactive effects on both flowering onset and reproductive period, such that C(3)annual grasses flowered the earliest and had the longest reproductive period. We found that species with wider climatic niches would flower earlier and have longer reproductive periods. Specifically, species that experience wider ranges of mean annual precipitation and coldest-month temperatures would flower earlier, and species with higher mean annual temperature and wider ranges of wettest-quarter precipitation have a longer reproductive period. This study finds that the diversity of reproductive phenology among subtropical grasses is constrained by evolution and climatic niche and that photosynthetic pathway and life history have an interactive effect on the timing and the duration of reproduction.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Comprehensive reutilization of herbal waste: Coproduction of magnolol, honokiol, and β-amyrin from Magnolia officinalis residue

Herbal extraction residues (HERs) cause serious environmental pollution and resource waste. In this study, a novel green route was designed for the comprehensive reutilization of all components in HERs, taking Magnolia officinalis residues (MOR) as an example. The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients (magnolol and honokiol) originally remaining in MOR and to make MOR more accessible for hydrolysis. A metal–organic frame material MIL-101(Cr) with a maximum absorption capacity of 255.64 mg g−1 was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions, and 40 g L−1 reducing sugars were obtained with 81.8% enzymatic hydrolysis rate at 10% MOR solid loading. Finally, 382 mg L−1 β-amyrin was produced from MOR hydrolysates by an engineered yeast strain. In total, 1 kg honokiol, 8 kg magnolol, and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB

Assessment of chemistry knowledge in large language models that generate code

In this work, we investigate the question: do code-generating large language models know chemistry? Our results indicate, mostly yes. To evaluate this, we produce a benchmark set of problems, and evaluate these models based on correctness of code by automated testing and evaluation by experts. We find recent LLMs are able to write correct code across a variety of topics in chemistry and their accuracy can be increased by 30 percentage points via prompt engineering strategies, like putting copyright notices at the top of files. These dataset and evaluation tools are open source which can be contributed to or built upon by future researchers, and will serve as a community resource for evaluating the performance of new models as they emerge. We also describe some good practices for employing LLMs in chemistry. The general success of these models demonstrates that their impact on chemistry teaching and research is poised to be enormous