An Element-wise RSAV Algorithm for Unconstrained Optimization Problems

We present a novel optimization algorithm, element-wise relaxed scalar auxiliary variable (E-RSAV), that satisfies an unconditional energy dissipation law and exhibits improved alignment between the modified and the original energy. Our algorithm features rigorous proofs of linear convergence in the convex setting. Furthermore, we present a simple accelerated algorithm that improves the linear convergence rate to super-linear in the univariate case. We also propose an adaptive version of E-RSAV with Steffensen step size. We validate the robustness and fast convergence of our algorithm through ample numerical experiments.Comment: 25 pages, 7 figure

Application and potential value of curcumin in prostate cancer: a meta-analysis based on animal models

IntroductionCurcumin is gaining recognition as an agent for cancer chemoprevention and is presently administered to humans. However, the limited number of clinical trials conducted for the treatment of prostate cancer is noteworthy. Animal models serve as valuable tools for enhancing our understanding of disease mechanisms and etiology in humans. The objective of this study was to examine the anti-prostate cancer effects of curcumin in vivo for comprehending its current research status and potential clinical applicability.MethodsOur methodology involved a systematic exploration of animal studies pertaining to curcumin and prostate cancer, as documented in PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang database, Vip database, and SinoMed, up to 03 September 2023. Risk of bias was assessed using the SYRCLE Animal Study Risk of Bias tool. The results were combined using the RevMan 5.3.ResultsA comprehensive analysis was conducted on 17 studies encompassing 263 mouse transplantation tumor models. The findings of this meta-analysis demonstrated that curcumin exhibited a superior inhibitory effect on the volume of prostate cancer tumors in mice compared to the control group (standardized mean difference [SMD]: 1.16, 95% confidence interval [CI]: 0.52, 1.80, p < 0.001). Additionally, curcumin displayed a more effective inhibition of mice prostate cancer tumor weight (SMD: −3.27, 95% CI: −4.70, −1.83, p < 0.001). Furthermore, in terms of tumor inhibition rate, curcumin exhibited greater efficacy (SMD: 0.25, 95% CI: 0.23, 0.27, p < 0.001). Moreover, curcumin more effectively inhibited PCNA mRNA (SMD: −3.11, 95% CI: −4.60, −1.63, p < 0.001) and MMP2 mRNA (SMD: −3.19, 95% CI: 5.85, −0.53, p < 0.001).ConclusionCurcumin exhibited inhibitory properties towards prostate tumor growth and demonstrated a beneficial effect on prostate cancer treatment, thereby offering substantiation for further clinical investigations. It is important to acknowledge that the included animal studies exhibited considerable heterogeneity, primarily because of the limited number of studies included. Consequently, additional randomized controlled trials are required to comprehensively assess the efficacy of curcumin in humans.Systematic Review Registration(https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023464661), identifier (CRD42023464661)

Patterns of nucleotides that flank substitutions in human orthologous genes

<p>Abstract</p> <p>Background</p> <p>Sequence context is an important aspect of base mutagenesis, and three-base periodicity is an intrinsic property of coding sequences. However, how three-base periodicity is influenced in the vicinity of substitutions is still unclear. The effect of context on mutagenesis should be revealed in the usage of nucleotides that flank substitutions. Relative entropy (also known as Kullback-Leibler divergence) is useful for finding unusual patterns in biological sequences.</p> <p>Results</p> <p>Using relative entropy, we visualized the periodic patterns in the context of substitutions in human orthologous genes. Neighbouring patterns differed both among substitution categories and within a category that occurred at three codon positions. Transition tended to occur in periodic sequences relative to transversion. Periodic signals were stronger in a set of flanking sequences of substitutions that occurred at the third-codon positions than in those that occurred at the first- or second-codon positions. To determine how the three-base periodicity was affected near the substitution sites, we fitted a sine model to the values of the relative entropy. A sine of period equal to 3 is a good approximation for the three-base periodicity at sites not in close vicinity to some substitutions. These periods were interrupted near the substitution site and then reappeared away from substitutions. A comparative analysis between the native and codon-shuffled datasets suggested that the codon usage frequency was not the sole origin of the three-base periodicity, implying that the native order of codons also played an important role in this periodicity. Synonymous codon shuffling revealed that synonymous codon usage bias was one of the factors responsible for the observed three-base periodicity.</p> <p>Conclusions</p> <p>Our results offer an efficient way to illustrate unusual periodic patterns in the context of substitutions and provide further insight into the origin of three-base periodicity. This periodicity is a result of the native codon order in the reading frame. The length of the period equal to 3 is caused by the usage bias of nucleotides in synonymous codons. The periodic features in nucleotides surrounding substitutions aid in further understanding genetic variation and nucleotide mutagenesis.</p

Impacts of mutation effects and population size on mutation rate in asexual populations: a simulation study

<p>Abstract</p> <p>Background</p> <p>In any natural population, mutation is the primary source of genetic variation required for evolutionary novelty and adaptation. Nevertheless, most mutations, especially those with phenotypic effects, are harmful and are consequently removed by natural selection. For this reason, under natural selection, an organism will evolve to a lower mutation rate. Overall, the action of natural selection on mutation rate is related to population size and mutation effects. Although theoretical work has intensively investigated the relationship between natural selection and mutation rate, most of these studies have focused on individual competition within a population, rather than on competition among populations. The aim of the present study was to use computer simulations to investigate how natural selection adjusts mutation rate among asexually reproducing subpopulations with different mutation rates.</p> <p>Results</p> <p>The competition results for the different subpopulations showed that a population could evolve to an "optimum" mutation rate during long-term evolution, and that this rate was modulated by both population size and mutation effects. A larger population could evolve to a higher optimum mutation rate than could a smaller population. The optimum mutation rate depended on both the fraction and the effects of beneficial mutations, rather than on the effects of deleterious ones. The optimum mutation rate increased with either the fraction or the effects of beneficial mutations. When strongly favored mutations appeared, the optimum mutation rate was elevated to a much higher level. The competition time among the subpopulations also substantially shortened.</p> <p>Conclusions</p> <p>Competition at the population level revealed that the evolution of the mutation rate in asexual populations was determined by both population size and mutation effects. The most striking finding was that beneficial mutations, rather than deleterious mutations, were the leading force that modulated the optimum mutation rate. The initial configuration of the population appeared to have no effect on these conclusions, confirming the robustness of the simulation method developed in the present study. These findings might further explain the lower mutation rates observed in most asexual organisms, as well as the higher mutation rates in some viruses.</p

Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry

A unified mechanism for intron and exon definition and back-splicing.

The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes

Author Correction: CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing.

The originally published version of this Article contained several errors in Figure 2, panel a: the basepair register in SL3-4 of yeast U1 snRNA was depicted incorrectly; the basepair for A287-U295 in yeast U1 snRNA was erroneously present; basepairs for U84-G119, G309-U532, A288-U295 and U289-A294 in yeast U1 snRNA were missing; the bulging nucleotide in SL3 of human U1 snRNA was depicted as G instead of C; and the dashed boxes defining the 5' ss binding site and Sm site in both human and yeast snRNAs were not drawn accurately. These have now been corrected in both the PDF and HTML versions of the Article