Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence.

Tripeptidyl peptidase II (TPPII or TPP2) degrades N-terminal tripeptides from proteins and peptides. Studies in both humans and mice have shown that TPPII deficiency is linked to cellular immune-senescence, lifespan regulation and the aging process. However, the mechanism of how TPPII participates in these processes is less clear. In this study, we established a chemical probe-based assay and found that although the mRNA and protein levels of TPPII were not altered during senescence, its enzymatic activity was reduced in senescent human fibroblasts. We also showed that elevation of the levels of the serine protease inhibitor serpinB2 reduced TPPII activity in senescent cells. Moreover, suppression of TPPII led to elevation in the amount of lysosomal contents as in well as TPPI (TPP1) and ß-galactosidase activities, suggesting that lysosome biogenesis is induced to compensate for the reduction of TPPII activity in senescent cells. Together, this study discloses a critical role of the serpinB2-TPPII signaling pathway in proteostasis during senescence. Since serpinB2 levels can be increased by a variety of cellular stresses, reduction of TPPII activity through activation of serpinB2 might represent a common pathway for cells to respond to different stress conditions. This article has an associated First Person interview with the first author of the paper.

Effects of chain-chain interaction on the configuration of short-chain alkanethiol self-assembled monolayers on a metal surface.

Surface-specific sum frequency generation vibrational spectroscopy is applied to study the molecular configuration of short-chain n-alkanethiol self-assembled monolayers (SAMs with n = 2-6) on the Au surface. For monolayers with n≥ 3, the alkanethiols are upright-oriented, with the CH3 tilt angle varying between ∼33° and ∼46° in clear even-odd dependency. The ethanethiol monolayer (n = 2) is, however, found to exhibit a distinct lying-down configuration with a larger methyl tilt angle (67°-79°) and a smaller CH2 tilt angle (56°-68°). Such a unique configurational transition from n = 2 to n≥ 3 discloses the steric effect owing to chain-chain interaction among neighboring molecules. Through density functional theory calculations, the transition is further confirmed to be energetically favorable for thiols on a defective reconstructed Au(111) surface but not on the pristine one. Our study highlights the roles of the chain-chain interaction and the substrate surface atomic structure when organizing SAMs, offering a strategic pathway for exploiting their applications.

Guiding Metal Organic Framework Morphology via Monolayer Artificial Defect-Induced Preferential Facet Selection.

Guiding metal organic framework (MOF) morphology, especially without the need for chemical additives, still remains a challenge. For the first time, we report a unique surface guiding approach in controlling the crystal morphology formation of zeolitic imidazole framework-8 (ZIF-8) and HKUST-1 MOFs on disrupted alkanethiol self-assembled monolayer (SAM)-covered Au substrates. Selective molecule removal is applied to generate diverse SAM matrices rich in artificial molecular defects in a monolayer to direct the dynamic crystal growth process. When a 11-mercaptoundecanol alkanethiol monolayer is ruptured, the hydroxyl tail groups of surface residue molecules act as nucleating sites by coordination with precursor metal ions. Meanwhile, the exposed alkane chain backbones stabilize a particular facet of MOF nuclei in the dynamic growth by slowing down their crystal growth rates along a specific direction. The competitive formation between the [110] and [100] planes of ZIF-8 ultimately regulates the crystal shapes from rhombic dodecahedron, truncated rhombic dodecahedron, and truncated cube to cube. Similarly, changeable morphologies of HKUST-1 crystals are also achieved from cube and tetrakaidekahedron to octahedron, originating from the competitive selection between the [100] and [111] planes. In addition to the artificial matrix preferred orientation of initial nucleation, parameters such as temperature also play a crucial role in the resulting crystal morphology. Standing on the additive-free MOF crystal morphology growth control, porous architectures prepared in this approach can act as templates for ligand-free metal (Au, Ag, and Cu) nanocluster synthesis. The nanocluster-embedded MOF structures represent distinct crystal morphology-dependent optical properties, and interestingly, their fluorescence emission can be highly enhanced by facet-induced nanocluster packing alignments. These findings not only provide a unique thought on MOF crystal morphology guidance but also pave a new route for the accompanied property investigation and further application.

Gap-directed chemical lift-off lithographic nanoarchitectonics for arbitrary sub-micrometer patterning.

We introduce a unique soft lithographic operation that exploits stamp roof collapse-induced gaps to selectively remove an alkanethiol self-assembled monolayer (SAM) on Au to generate surface patterns that are orders of magnitude smaller than structures on the original elastomer stamp. The smallest achieved feature dimension is 5 nm using a micrometer-scale structured stamp in a chemical lift-off lithography (CLL) process. Molecular patterns retained in the gaps between stamp features and their circumscribed or inscribed circles follow mathematical predictions, and their sizes can be tuned by altering the stamp structure dimensions, including height, pitch, and shape. These generated surface molecular patterns can function as biorecognition arrays or be transferred to the underneath Au layer for metallic structure creation. By combining CLL process with this gap phenomenon, soft material properties that are previously thought as demerits can be used to achieve sub-10 nm features in a straightforward sketch.

Antidepressant-like activities of live and heat-killed Lactobacillus paracasei PS23 in chronic corticosterone-treated mice and possible mechanisms.

Emerging evidence indicates that ingestion of specific probiotics, known as "psychobiotics", confer beneficial effects on mental health. This study investigated antidepressant-like effects and possible underlying mechanisms of Lactobacillus paracasei PS23 (PS23), live or heat-killed, in a mouse model of corticosterone-induced depression using fluoxetine as standard drug. PS23 were orally gavaged to mice from day 1 to 41 or fluoxetine from day 17 to 41 and injected with corticosterone from day 17 to 37. After the last corticosterone treatment, anxiety- and depression-like behaviors were tested within 4 days. On day 42, serum and brain tissue were collected 24 min after forced swim stress. Abnormal behavioral changes induced by corticosterone were ameliorated by treatment with live PS23 in open field and sucrose preference tests, with heat-killed PS23 in open field, forced swim and sucrose preference tests, and with fluoxetine in open field and forced swim tests. Furthermore, both live and heat-killed PS23 and fluoxetine reversed corticosterone-reduced protein levels of brain-derived neurotropic factor, mineralocorticoid, and glucocorticoid receptors in the hippocampus. In addition, live PS23 also reverses corticosterone-reduced serotonin levels in hippocampus, prefrontal cortex and striatum; whereas heat-killed PS23 reverses corticosterone-reduced dopamine levels in hippocampus and prefrontal cortex. And fluoxetine normalized reduced corticosterone level in serum. These studies showed that both live and heat-killed PS23 can reverse chronic corticosterone-induced anxiety- and depression-like behaviors and that may provide insights into the mechanism and a potential psychobiotic for depression management.