Standing waves for two-component elliptic system with critical growth in R4\mathbb{R}^{4}: the attractive case

In this paper, we consider the following two-component elliptic system with critical growth \begin{equation*} \begin{cases} -\Delta u+(V_1(x)+\lambda)u=\mu_1u^{3}+\beta uv^{2}, \ \ x\in \mathbb{R}^4, -\Delta v+(V_2(x)+\lambda)v=\mu_2v^{3}+\beta vu^{2}, \ \ x\in \mathbb{R}^4 , % u\geq 0, \ \ v\geq 0 \ \text{in} \ \R^4. \end{cases} \end{equation*} where $V_j(x) \in L^{2}(\mathbb{R}^4)$ are nonnegative potentials and the nonlinear coefficients $\beta ,\mu_j$, $j=1,2$, are positive. Here we also assume $\lambda>0$. By variational methods combined with degree theory, we prove some results about the existence and multiplicity of positive solutions under the hypothesis $\beta>\max\{\mu_1,\mu_2\}$. These results generalize the results for semilinear Schr\"{o}dinger equation on half space by Cerami and Passaseo (SIAM J. Math. Anal., 28, 867-885, (1997)) to the above elliptic system, while extending the existence result from Liu and Liu (Calc. Var. Partial Differential Equations, 59:145, (2020))

The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson’s Disease

Background: Posture instability gait difficulty-dominant (PIGD) and tremor-dominant (TD) are two subtypes of Parkinson’s disease (PD). The thalamus is involved in the neural circuits of both subtypes. However, which subregion of the thalamus has an influence on the PD subtypes remains unclear.Objective: To explore the core subregion of the thalamus showing a significant influence on the PD subtypes and its directional interaction between the PD subtypes.Methods: A total of 79 PD patients (43 TD and 36 PIGD) and 31 normal controls (NC) were enrolled, and the gray matter volume and perfusion characteristics in the thalamus were compared between the three groups. The subregion of the thalamus with significantly different perfusion and volume among three groups was used as the seed of a Granger causality analysis (GCA) to compare the causal connectivity between different subtypes.Results: Perfusion with an increased gradient among the three groups (TD > PIGD > NC) in the bilateral ventral intermediate nucleus (Vim) was observed, which was positively correlated with the clinical tremor scores. The GCA revealed that TD patients had enhanced causal connectivity from the bilateral Vim to the bilateral paracentral gyrus, M1 and the cerebellum compared with the NC group, while the PIGD subtype revealed an increased causal connectivity from the bilateral Vim to the bilateral premotor cortex (preM) and putamen. Additionally, there were positive correlations between the tremor scores and a causal connectivity from the Vim to the cerebellum. The connectivity from the right Vim to the right preM and the right putamen was positively correlated with the PIGD scores.Conclusion: This multilevel analysis showed that the Vim had a significant influence on the PD subtypes and that it differentially mediated the TD and PIGD-related causal connectivity pattern in PD

Acupuncture for menstruation-related migraine prophylaxis:A multicenter randomized controlled trial

OBJECTIVE: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). PATIENTS AND METHODS: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1−3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1−3 and 4−6. RESULTS: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17–0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82–1.07) in the acupuncture group and 0.61 (95% CI, 0.50–0.71) in the medication group over cycles 1−3. CONCLUSION: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. CLINICAL TRIAL REGISTRATION: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606]

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs

A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes

BACKGROUND: Bread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines. RESULTS: A sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies. CONCLUSIONS: Evidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets