The rate and mechanism of protein sequence evolution have been central questions in evolutionary biology since the 1960s. Although the rate of protein sequence evolution depends primarily on the ...level of functional constraint, exactly what determines functional constraint has remained unclear. The increasing availability of genomic data has enabled much needed empirical examinations on the nature of functional constraint. These studies found that the evolutionary rate of a protein is predominantly influenced by its expression level rather than functional importance. A combination of theoretical and empirical analyses has identified multiple mechanisms behind these observations and demonstrated a prominent role in protein evolution of selection against errors in molecular and cellular processes.
Achieving complex shape change of liquid‐crystal polymer networks (LCNs) under stimulation generally requires spatial configuration of the orientation direction, that is, patterned directors, of ...liquid crystal monomers prior to polymerization by means of treated surfaces. A strategy is demonstrated that needs only the simple uniaxial orientation of mesogens (monodomain) induced by mechanical stretching of LCNs. Using a rationally designed liquid crystal polymer, photocrosslinking is utilized to pattern or spatially organize the actuating monodomains in order to generate a differential contractile and/or extensional force field required for targeted shape change. Moreover, the approach enables versatile actuation modes and allows multiple shape changes to be programmed on a single piece of the polymer. This important feature is demonstrated with a specimen cut to have eight strips that, upon thermal stimulation, simultaneously display eight types of shape morphing.
Roll with the changes: An easily processable liquid crystal polymer with only uniaxial orientation of mesogens can be programmed to display multiple, complex shape morphing on a single piece of the material (eight changes are shown in the picture). The approach consists of using photocrosslinking to spatially configure and organize the actuation domains in a mechanically stretched specimen.
The assembly of spherical fullerenes, or buckyballs, into single crystals for crystallographic identification often suffers from disordered arrangement. Here we show a chiral configuration of ...decapyrrylcorannulene that has a concave 'palm' of corannulene and ten flexible electron-rich pyrryl group 'fingers' to mimic the smart molecular 'hands' for self-adaptably cradling various buckyballs in a (+)hand-ball-hand(-) mode. As exemplified by crystallographic identification of 15 buckyball structures representing pristine, exohedral, endohedral, dimeric and hetero-derivatization, the pyrryl groups twist with varying dihedral angles to adjust the interaction between decapyrrylcorannulene and fullerene. The self-adaptable electron-rich pyrryl groups, susceptible to methylation, are theoretically revealed to contribute more than the bowl-shaped palm of the corannulene in holding buckyball structures. The generality of the present decapyrrylcorannulene host with flexible pyrryl groups facilitates the visualization of numerous unknown/unsolved fullerenes by crystallography and the assembly of the otherwise close-packed spherical fullerenes into two-dimensional layered structures by intercalation.
Olfactory systems in eusocial insects play a vital role in the discrimination of various chemical cues. Odorant receptors (ORs) are critical for odorant detection, and this family has undergone ...extensive expansion in ants. In this study, we re-annotated the
genes from the most destructive invasive ant species
and 2 other Formicidae species,
and
, with the aim of systematically comparing and analyzing the evolution and the functions of the
in ant species, identifying 356, 298, and 306 potential functional
, respectively. The evolutionary analysis of these
showed that ants had undergone chromosomal rearrangements and that tandem duplication may be the main contributor to the expansion of the
gene family in
. Our further analysis revealed that 9-exon
had biased chromosome localization patterns in all three ant species and that a 9-exon
cluster (
) in
was under strong positive selection (Ka/Ks = 1.32). Moreover, we identified 5
genes, namely
,
,
,
, and
, with high sequence similarity (>70%) to the orthologs in
and
. An RT-PCR analysis was used to verify the antennal expression levels of these
, which showed caste-specific expression. The subsequent analysis of the antennal expression profiles of the
of the
workers from the polygyne and monogyne social forms indicated that
and
were expressed at much higher levels in the monogyne workers than in the polygyne workers and that
was expressed at higher levels in polygyne workers. Our study has contributed to the identification and analysis of the
gene family in ants and expanded the understanding of the evolution and functions of the ORs in Formicidae species.
Encapsulating photoluminescent lanthanide ions like erbium (Er) into fullerene cages affords photoluminescent endohedral metallofullerenes (EMFs). Few reported photoluminescent Er‐EMFs are all based ...on encapsulation of multiple (two to three) metal atoms, whereas mono‐Er‐EMFs exemplified by Er@C82 are not photoluminescent due to its narrow optical bandgap. Herein, by entrapping an Er‐cyanide cluster into various C82 cages to form novel Er‐monometallic cyanide clusterfullerenes (CYCFs), ErCN@C82 (C2(5), Cs(6), and C2v(9)), the photoluminescent properties of CYCFs are investigated, and obvious near‐infrared (NIR) photoluminescence only is observed for ErCN@C2(5)‐C82. Combined with a comparative photoluminescence study of three medium‐bandgap di‐Er‐EMFs, including Er2@Cs(6)‐C82, Er2O@Cs(6)‐C82, and Er2C2@Cs(6)‐C82, this study proposes that the optical bandgap can be used as a simple criterion for switching the photoluminescence of Er‐EMFs, and the bandgap threshold is determined to be between 0.83 and 0.74 eV. Furthermore, the photoluminescent patterns of these three di‐Er‐EMFs differ dramatically. It is found that the location of the Er atom within the same Cs(6)‐C82 cage is almost fixed and independent on the endo‐unit; thus the previous statement on the key role of metal position in photoluminescence of di‐Er‐EMFs seems erroneous, and the geometric configuration of the endo‐unit, especially the bridging mode of two Er ions, is decisive instead.
The photoluminescent property of monometallic cyanide clusterfullerenes is investigated. By encapsulating a triangular erbium (Er)‐cyanide cluster into a C2(5)‐C82 cage, photoluminescence of mono‐Er‐metallofullerene is switched on. Combined with three medium‐bandgap di‐erbium‐metallofullerenes, the bandgap threshold for judging whether an Er‐metallofullerenes is photoluminescent is determined to be between 0.83 and 0.74 eV.
The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). Sorafenib has been the mainstay of treatment for a decade and newer ...modalities were ineffective and did not confer any increased therapeutic benefit until the introduction of lenvatinib which was approved based on its non-inferiority to sorafenib. The subsequent success of regorafenib in HCC patients who progress on sorafenib treatment heralded a new era of second-line treatment and was quickly followed by ramucirumab, cabozantinib, and the most influential, immune checkpoint inhibitors (ICIs). Over the same period combination therapies, including anti-angiogenesis agents with ICIs, dual ICIs and targeted agents in conjunction with surgery or other loco-regional therapies, have been extensively investigated and have shown promise and provided the basis for exciting clinical trials. Work continues to develop additional novel therapeutic agents which could potentially augment the presently available options and understand the underlying mechanisms responsible for drug resistance, with the goal of improving the survival of patients with HCC.
Tumor‐associated neutrophils (TANs) play a crucial role in tumor development and progression in the cancer microenvironment. Despite increased understanding of TAN contributions to hepatocellular ...carcinoma (HCC) progression and prognosis, the direct interaction between TANs and HCC cells is not fully understood. In this study, we tested the effect of TANs on HCC cells in vitro and in vivo and investigated the mechanism of interaction between them. Our results showed that TANs secreted bone morphogenetic protein 2 and transforming growth factor beta 2 and triggered microRNA 301b‐3p (miR‐301‐3p) expression in HCC cells, subsequently suppressed gene expression of limbic system–associated membrane protein (LSAMP) and CYLD lysine 63 deubiquitinase (CYLD), and increased stem cell characteristics in HCC cells. These TAN‐induced HCC stem‐like cells were hyperactive in nuclear factor kappa B signaling, secreted higher levels of chemokine (C‐X‐C motif) ligand 5 (CXCL5), and recruited more TAN infiltration, suggesting a positive feedback loop. In clinical HCC samples, increased TANs correlated with elevated miR‐301b‐3p, decreased LSAMP and CYLD expression, and increased nuclear p65 accumulation and CXCL5 expression, all of which predicted patient outcome. Conclusion: Our work identified a positive feedback loop governing cancer stem‐like cells and TANs in HCC that controls tumor progression and patient outcome.
Although previous studies have found that melatonin can promote seed germination, the mechanisms involved in perceiving and signaling melatonin remain poorly understood. In this study, it was found ...that melatonin was synthesized during cucumber seed germination with a peak in melatonin levels occurring 14 hr into germination. This is indicative of a correlation between melatonin synthesis and seed germination. Meanwhile, seeds pretreated with exogenous melatonin (1 μm) showed enhanced germination rates under 150 mm NaCl stress compared to water‐pretreated seeds under salinity stress. There are two apparent mechanisms by which melatonin alleviated salinity‐induced inhibition of seed germination. Exogenous melatonin decreased oxidative damage induced by NaCl stress by enhancing gene expression of antioxidants. Under NaCl stress, compared to untreated control, the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were significantly increased by approximately 1.3–5.0‐fold, with a concomitant 1.4–2.0‐fold increase of CsCu‐ZnSOD, CsFe‐ZnSOD, CsCAT, and CsPOD in melatonin‐pretreated seeds. Melatonin also alleviated salinity stress by affecting abscisic acid (ABA) and gibberellin acid (GA) biosynthesis and catabolism during seed germination. Compared to NaCl treatment, melatonin significantly up‐regulated ABA catabolism genes (e.g., CsCYP707A1 and CsCYP707A2, 3.5 and 105‐fold higher than NaCl treatment at 16 hr, respectively) and down‐regulated ABA biosynthesis genes (e.g., CsNECD2, 0.29‐fold of CK2 at 16 hr), resulting in a rapid decrease of ABA content during the early stage of germination. At the same time, melatonin positively up‐regulated GA biosynthesis genes (e.g., GA20ox and GA3ox, 2.3 and 3.9‐fold higher than NaCl treatment at 0 and 12 hr, respectively), contributing to a significant increase of GA (especially GA4) content. In this study, we provide new evidence suggesting that melatonin alleviates the inhibitory effects of NaCl stress on germination mainly by regulating the biosynthesis and catabolism of ABA and GA4.
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