Class B G protein–coupled receptors, an important class of therapeutic targets, signal mainly through the Gs class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo–electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, Gs or Gi1. These two structures adopt a similar open binding cavity to accommodate Gs and Gi1. The Gs binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect Gi more than Gs binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.

CTCF, a conserved 3D genome architecture protein, determines proper genome-wide chromatin looping interactions through directional binding to specific sequence elements of four modules within numerous CTCF-binding sites (CBSs) by its 11 zinc fingers (ZFs). Here, we report four crystal structures of human CTCF in complex with CBSs of the protocadherin (Pcdh) clusters. We show that directional CTCF binding to cognate CBSs of the Pcdh enhancers and promoters is achieved through inserting its ZF3, ZFs 4-7, and ZFs 9-11 into the major groove along CBSs, resulting in a sequence-specific recognition of module 4, modules 3 and 2, and module 1, respectively; and ZF8 serves as a spacer element for variable distances between modules 1 and 2. In addition, the base contact with the asymmetric "A" in the central position of modules 2-3, is essential for directional recognition of the CBSs with symmetric core sequences but lacking module 1. Furthermore, CTCF tolerates base changes at specific positions within the degenerated CBS sequences, permitting genome-wide CTCF binding to a diverse range of CBSs. Together, these complex structures provide important insights into the molecular mechanisms for the directionality, diversity, flexibility, dynamics, and conservation of multivalent CTCF binding to its cognate sites across the entire human genome.

Nuclear factor, erythroid 2 like 2 (NFE2L2, NRF2) is a transcription factor that regulates various antioxidant enzymes. It plays a vital physiological role in regulating oxidative stress and inflammatory response. However, the roles of NFE2L2 in human cancers are still unclear. Our study is aimed at analyzing the prognostic value of NFE2L2 in pan-cancer and at revealing the relationship between NFE2L2 expression and tumor immunity. The present study revealed that NFE2L2 was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels and DNA methyltransferase expression in human pan-cancer. In particular, pan-cancer survival analysis indicated that NFE2L2 expression was associated with adverse outcomes—overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI)—in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), and pancreatic adenocarcinoma (PAAD) patients. A positive relationship was also found between NFE2L2 expression and immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), LGG, liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Additionally, NFE2L2 expression was positively correlated with the immune score and the expression of immune checkpoint markers in LGG. In conclusion, these results indicate that transcription factor NFE2L2 is a potential prognostic biomarker and is correlated with immune infiltration in LGG.

We have investigated the electronic structure and carrier mobility of armchair and zigzag single-walled MoS2 nanotubes using density functional theory combined with Boltzmann transport method with relaxation time approximation. It is shown that armchair nanotubes are indirect bandgap semiconductors, while zigzag nanotubes are direct ones. The band gaps of single-walled MoS2 nanotubes are along with the augment of their diameters. For armchair nanotubes (5 ≤ Na ≤ 14), the hole mobility raise from 98.62 ~ 740.93 cm2V−1s−1 at room temperature, which is about six times of the electron mobility. For zigzag nanotubes (9 ≤ Na ≤ 15), the hole mobility is 56.61 ~ 91.32 cm2V−1s−1 at room temperature, which is about half of the electron mobility.

Several recent reports implicate an important role played by c-Jun N-terminal kinases (JNKs) in long-term potentiation (LTP). However, little is known about how the isoforms of JNKs participate in synaptic plasticity. Here we showed that short-term synaptic plasticity was impaired in the hippocampal area CA1 of JNK1-deficient (JNK1-/-) mice; these mice showed normal LTP in response to a strong tetanus and no alteration of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) in the hippocampus. However, LTD induced either by group I metabotropic glutamate receptors (mGluRs) agonist dihydroxyphenylglycine or by paired-pulse low-frequency stimulation was absent in both the JNK1-/- slices and in JNK inhibitor anthrax [1, 9-cd] pyrazol-6(2H)-1 (SP600125)-pretreated slices. Induction of mGluR-dependent LTD resulted in an increase in phosphorylation of JNK1 substrates, including p-c-Jun and p-ATF2 in wild-type (WT) mice, and these increases failed to occur in the JNK1-/- or SP600125-pretreated mice. These results demonstrated that JNK1 played a crucial role in the short-term synaptic plasticity and mGluR-dependent LTD, whereas hippocampus LTP was not affected by JNK1 deficiency.

The modification of the electronic structure of bilayer MoS2 by an external electric field can have potential applications in optoelectronics and valleytronics. Nevertheless, the underlying physical mechanism is not clearly understood, especially the effects of the van der Waals interaction. In this study, the spin orbit-coupled electronic structure of bilayer MoS2 has been investigated using the first-principle density functional theory. We find that the van der Waals interaction as well as the interlayer distance has significant effects on the band structure. When the interlayer distance of bilayer MoS2 increases from 0.614 nm to 0.71 nm, the indirect gap between the Γ and Λ points increases from 1.25 eV to 1.70 eV. Meanwhile, the energy gap of bilayer MoS2 transforms from an indirect one to a direct one. An external electric field can shift down (up) the energy bands of the bottom (top) MoS2 layer and also breaks the inversion symmetry of bilayer MoS2. As a result, the electric field can affect the band gaps, the spin-orbit interaction and splits the valance bands into two groups. The present study can help us understand more about the electronic structures of MoS2 materials for potential applications in electronics and optoelectronics.

The linguistic intuitionistic fuzzy sets (LIFSs) and linguistic Pythagorean fuzzy sets (LPFSs) are two linguistic orthopair fuzzy sets whose membership grades are pairs of linguistic terms from the predefined linguistic term sets (LTSs). One linguistic term indicates the membership degree (MD), while the other one gives the nonmembership degree (NMD). In each LIFS, the sum of the subscripts of MD and NMD is less than the cardinality of LTS. In the LPFSs, the sum of the squares of the subscripts of MD and NMD is less than the square of the cardinality of LTS. In this paper, we propose a general form of these two linguistic orthopair fuzzy sets, which can be named linguistic q-rung orthopair fuzzy sets. We devise the operational laws, based on which, the linguistic q-rung orthopair fuzzy weighted averaging (LqROFWA) operator and linguistic q-rung orthopair fuzzy weighted geometric (LqROFWG) operator are developed to aggregate the linguistic q-rung orthopair fuzzy numbers (LqROFNs). Then, the novel interactional operational laws that consider the interactions between the MD and NMD from different LqROFNs are given. The partitioned geometric Heronian mean (PGHM) operator can effectively solve the decisionmaking problems in which the attributes grouped into the same clusters have interrelationships and the attributes belonging to different clusters have no The rest of this paper is arranged as follows: The concepts of LIFSs and LPFSs as well as PGHM are briefly introduced in Section 2. The notion of LqROFSs, their NIOLs, as well as averaging and geometric operators are given in Section 3. Section 4 analyzes the drawback of NIOLs and devises some novel IOLs. Based on the IOLs, the LqROFIPGHM and LqROFIWPGHM operators are presented in Section 5. A novel MAGDM model with the LqROFIWPGHM operator is shown in Section 6. Some illustrative examples are given to demonstrate the proposed MAGDM model and validate the superiorities of our proposed IOLs and LqROFIWPGHM operator in Section 7. Finally, the conclusions of this study are drawn in Section 8.

COVID‐19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in global social and economic disruption, putting the world economy to the largest global recession since the Great Depression. To control the spread of COVID‐19, cutting off the transmission route is a critical step. In this work, the efficient inactivation of human coronavirus with photodynamic therapy (PDT) by employing photosensitizers with aggregation‐induced emission characteristics (DTTPB) is reported. DTTPB is designed to bear a hydrophilic head and two hydrophobic tails, mimicking the structure of phospholipids on biological membranes. DTTPB demonstrates a broad absorption band covering the whole visible light range and high molar absorptivity, as well as excellent reactive oxygen species sensitizing ability, making it an excellent candidate for PDT. Besides, DTTPB can target membrane structure, and bind to the envelope of human coronaviruses. Upon light irradiation, DTTPB demonstrates highly effective antiviral behavior: human coronavirus treated with DTTPB and white‐light irradiation can be efficiently inactivated with complete loss of infectivity, as revealed by the significant decrease of virus RNA and proteins in host cells. Thus, DTTPB sensitized PDT can efficiently prevent the infection and the spread of human coronavirus, which provides a new avenue for photodynamic combating of COVID‐19.