Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization.

BACKGROUND: Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis. AIM: To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis. Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis. METHODS: Cell culture and various experiments, including protein analysis, immunohistochemistry, and animal model experiments, were conducted. We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features. Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers. Finally, we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms. RESULTS: Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to adverse tumor features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to increased anti-inflammatory factor release. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B prevented tumor cell invasion and metastasis. CONCLUSION: FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to the development of new strategies for treating PDAC. For example, interfering with the FAM53B signaling pathway may prevent cancer spread. Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

[Characteristics of Epiphytic Bacterial Community on Submerged Macrophytes in Water Environment Supplemented with Reclaimed Water].

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas, Aeromonas, Pseudomonas, and Acinetobacter, accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD5, TN, NH4+-N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals.

Emerging viral pathogens cause substantial morbidity and pose a severe threat to health worldwide. However, a universal antiviral strategy for producing safe and immunogenic inactivated vaccines is lacking. Here, we report an antiviral strategy using the novel singlet oxygen (1O2)-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated 1O2 in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The 1O2 produced by LJ002 oxidized lipids in the viral envelope and consequently destroyed the viral membrane structure, thus inhibiting the viral and cell membrane fusion necessary for infection. Moreover, the 1O2-based inactivated pseudorabies virus (PRV) vaccine had no effect on the content of the viral surface proteins. Immunization of mice with LJ002-inactiviated PRV vaccine harboring comparable antigen induced more neutralizing antibody responses and efficient protection against PRV infection than conventional formalin-inactivated vaccine. Additionally, LJ002 inactivated a broad spectrum of enveloped viruses. Together, our results may provide a new paradigm of using broad-spectrum, highly effective inactivants functioning through 1O2-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.

BRD4 inhibition exerts anti-viral activity through DNA damage-dependent innate immune responses.

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.

Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

Crystal structure of (5'S,8'S)-3-(2,5-di-methyl-phen-yl)-8-meth-oxy-3-nitro-1-aza-spiro-[4.5]decane-2,4-dione.

The title compound, C18H22N2O5, was synthesized by nitrification of its enol precursor. The pyrrolidine ring plane adopts a twisted conformation about the C-C bond linking the spiro centre and the C=O group remote from the N atom. It makes dihedral angles of 71.69 (9) and 88.92 (9)°, respectively, with the benzene ring plane and the plane defined by the four C atoms that form the seat of the of the cyclo-hexane chair. At the spiro centre, the NH group is axial and the C=O group is equatorial with respect to the cyclo-hexane ring. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R 2 (2)(8) loops. The dimers are linked by C-H⋯O inter-actions, generating a three-dimensional network.

[Effects of neurally adjusted ventilatory assist on prevention of ventilator-induced diaphragmatic dysfunction in acute respiratory distress syndrome rabbits].

OBJECTIVE: To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits. METHODS: Twenty New Zealand white rabbits were randomly divided into 4 groups: (1) control group (n = 5); (2) Volume control (VC) group (n = 5); (3) Pressure support (PSV) group (n = 5); (4) NAVA group (n = 5). In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation. Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing. In all rabbits, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) of diaphragm were measured. Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber. RESULTS: (1) MDA: Compared with the control [(0.15 ± 0.06) nmol/mg], PSV group [(0.30 ± 0.11) nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [(0.28 ± 0.19) nmol/mg] (F = 2.730, P > 0.05). MDA in VC group [(0.40 ± 0.16) nmol/mg] was significantly higher than the control group (P < 0.05). (2) SOD: Compared with control [(111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [(94 ± 9) U/mg] (F = 4.422, P > 0.05). SOD in VC group [(80 ± 21) U/mg] was significantly lower than the control group (P < 0.05). (3) GSH: Compared with control [(5.3 ± 1.0) mg/g] and PSV group [(4.5 ± 1.2) mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g] (F = 3.001, P > 0.05). GSH in VC group [(3.3 ± 1.7) mg/g] is significantly lower than control and NAVA groups (P < 0.05). (4) Light microscope: In VC group, many changes were observed in the muscle, such as myelofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups. (5) Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal. Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria. (6) CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group (P > 0.05); The CSA of type II fibers in VC group was markedly lower than control group (P < 0.05). CONCLUSIONS: Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.

Synthesis of Janus type nucleoside analogues and their preliminary bioactivity.

Novel Janus type nucleoside analogues 1a and 1b were synthesized in seven steps from 2-amino-4,6-dihydroxypyrimidine and 4,6-dihydroxypyrimidine. The base moiety of 1a has one face with a Watson-Crick donor-donor-acceptor (DDA) H-bond array of guanine and the other face with an acceptor-acceptor-donor (AAD) array of cytosine, which might lead to its base pairing with either cytosine or guanine due to the rotating of the glycosyl bond. This property may enable Janus type nucleoside analogues to act as an antiviral compound in a similar way to ribavirin. Both 1a and 1b were screened by a vitro HBV DNA replication inhibition test and indeed 1a showed a great potential with IC(50) = 10 µM and SI = 78.9 for antiviral drug development.