Transplanted MSCs promote alveolar bone repair via hypoxia-induced extracellular vesicle secretion.

OBJECT: Mesenchymal stem cell (MSC) therapy is a potential strategy for promoting alveolar bone regeneration. This study evaluated the effects and mechanisms of transplanted MSCs on alveolar bone repair. METHODS: Mouse alveolar bone defect model was treated using mouse bone marrow mesenchymal stem cell (BMSC) transplantation. The bone repair was evaluated by micro-CT and Masson staining. The conditioned medium of hypoxia-treated BMSCs was co-cultured with normal BMSCs in vitro to detect the regulatory effect of transplanted MSCs on the chemotactic and migratory functions of host cells. The mechanisms were investigated using Becn siRNA transfection and western blotting. RESULTS: BMSC transplantation promoted bone defect regeneration. The hypoxic microenvironment induces BMSCs to release multiple extracellular vesicle (EV)-mediated regulatory proteins that promote the migration of host stem cells. Protein array analysis, western blotting, GFP-LC3 detection, and Becn siRNA transfection confirmed that autophagy activation in BMSCs plays a key role during this process. CONCLUSION: The local hypoxic microenvironment induces transplanted MSCs to secrete a large number of EV-mediated regulatory proteins, thereby upregulating the migration function of the host stem cells and promoting alveolar bone defect regeneration. This process depends on the autophagy-related mechanism of the transplanted MSCs.

Prediction of physicochemical and pharmacokinetic properties of botanical constituents by computational models.

Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. This study sought to use computational (i.e., in silico) models, including quantitative structure-activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were investigated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half of these constituents fell into BCS classes I and II at dose levels no greater than 100 mg per day, indicating high permeability and absorption (%Fa > 75%) in the gastrointestinal tract. However, some constituents such as glycosides in ashwagandha and Asian ginseng showed low bioavailability after oral administration due to poor absorption (BCS classes III and IV, %Fa < 40%). These in silico results fill data gaps for botanical constituents and could guide future safety studies. For example, the predicted human plasma concentrations may help select concentrations for in vitro toxicity testing. Additionally, the in silico data could be used in tiered or batteries of assays to assess the safety of botanical products. For example, highly absorbed botanical constituents indicate potential high exposure in the body, which could lead to toxic effects.

Old people's preference for nursing homes in East China: a discrete choice experiment.

BACKGROUND: The aged people who live in nursing home are predicted to keep growing in the following decades. There are both quantitative imbalance and structural imbalance in the utilization of nursing homes in China. This study aimed to analyze old people's preference for nursing homes and help the government optimize resource allocation. METHODS: A discrete choice experiment (DCE) was conducted and six attributes of nursing homes including monthly fee, distance from home, geographical location, medical facilities, environment of nursing homes and nursing staff were determined. Respondents were recruited from Nantong and Yangzhou city, China. In each city, two communities or villages were randomly selected. In each community/village, about 65 old people were randomly selected. Analysis was conducted using mixed logit regression models to determine preferences for potential attributes. RESULTS: A total of 233 old people were included in the analysis. The findings indicated that all six attributes were statistically significant factors for participants. "Professional nursing staff" was the most important characteristic to participants, followed by "Medical facilities". Compared with female, the males preferred professional nursing staff (ß = 2.939 vs. ß = 2.643, P < 0.001), medical facilities (ß = 1.890 vs. ß = 1.498, P < 0.001), and the environment (ß = 0.752, P < 0.01). For different age groups, participants aged 60-69 didn't pay attention to distance and location, while those aged 80 and above only paid attention to professional nursing staff and medical facilities. CONCLUSIONS: The present study provides important insights into the characteristics of nursing home that are most preferred by old people. Authorities should take into account old people's preference in the planning, design and evaluation of nursing homes.

Enabling robust blue circularly polarized organic afterglow through self-confining isolated chiral chromophore.

Creating circularly polarized organic afterglow system with elevated triplet energy levels, suppressed non-radiative transitions, and effective chirality, which are three critical prerequisites for achieving blue circularly polarized afterglow, has posed a formidable challenge. Herein, a straightforward approach is unveiled to attain blue circularly polarized afterglow materials by covalently self-confining isolated chiral chromophore within polymer matrix. The formation of robust hydrogen bonds within the polymer matrix confers a distinctly isolated and stabilized molecular state of chiral chromophores, endowing a blue emission band at 414 nm, lifetime of 3.0 s, and luminescent dissymmetry factor of ~ 10-2. Utilizing the synergistic afterglow and chirality energy transfer, full-color circularly polarized afterglow systems are endowed by doping colorful fluorescent molecules into designed blue polymers, empowering versatile applications. This work paves the way for the streamlined design of blue circularly polarized afterglow materials, expanding the horizons of circularly polarized afterglow materials into various domains.

Integrative physiological, metabolomic, and transcriptomic analysis reveals the drought responses of two apple rootstock cultivars.

BACKGROUND: Drought is considered the main environmental factor restricting apple production and thus the development of the apple industry. Rootstocks play an important role in enhancing the drought tolerance of apple plants. Studies of the physiology have demonstrated that 'ZC9-3' is a strong drought-resistant rootstock, whereas 'Jizhen-2' is a weak drought-resistant rootstock. However, the metabolites in these two apple rootstock varieties that respond to drought stress have not yet been characterized, and the molecular mechanisms underlying their responses to drought stress remain unclear. RESULTS: In this study, the physiological and molecular mechanisms underlying differences in the drought resistance of 'Jizhen-2' (drought-sensitive) and 'ZC9-3' (drought-resistant) apple rootstocks were explored. Under drought stress, the relative water content of the leaves was maintained at higher levels in 'ZC9-3' than in 'Jizhen-2', and the photosynthetic, antioxidant, and osmoregulatory capacities of 'ZC9-3' were stronger than those of 'Jizhen-2'. Metabolome analysis revealed a total of 95 and 156 differentially accumulated metabolites in 'Jizhen-2' and 'ZC9-3' under drought stress, respectively. The up-regulated metabolites in the two cultivars were mainly amino acids and derivatives. Transcriptome analysis revealed that there were more differentially expressed genes and transcription factors in 'ZC9-3' than in 'Jizhen-2' throughout the drought treatment. Metabolomic and transcriptomic analysis revealed that amino acid biosynthesis pathways play key roles in mediating drought resistance in apple rootstocks. A total of 13 metabolites, including L-α-aminoadipate, L-homoserine, L-threonine, L-isoleucine, L-valine, L-leucine, (2S)-2-isopropylmalate, anthranilate, L-tryptophan, L-phenylalanine, L-tyrosine, L-glutamate, and L-proline, play an important role in the difference in drought resistance between 'ZC9-3' and 'Jizhen-2'. In addition, 13 genes encoding O-acetylserine-(thiol)-lyase, S-adenosylmethionine synthetase, ketol-acid isomeroreductase, dihydroxyacid dehydratase, isopropylmalate isomerase, branched-chain aminotransferase, pyruvate kinase, 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase, N-acetylglutamate-5-P-reductase, and pyrroline-5-carboxylate synthetase positively regulate the response of 'ZC9-3' to drought stress. CONCLUSIONS: This study enhances our understanding of the response of apple rootstocks to drought stress at the physiological, metabolic, and transcriptional levels and provides key insights that will aid the cultivation of drought-resistant apple rootstock cultivars. Especially, it identifies key metabolites and genes underlying the drought resistance of apple rootstocks.

Advances in the Study of Extracellular Vesicles for Bone Regeneration.

Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications.

Phototriggered Fluoroalkylation/Cyclization of Unactivated 1-Acryloyl-2-cyanoindoles: Synthesis of RCOCF2-Substituted Pyrrolo[1,2-a]indolediones.

A photochemical approach toward RCOCF2-substituted pyrrolo[1,2-a]indolediones was developed by the radical cascade difluoroalkylation/cyclization reaction of unactivated 1-acryloyl-2-cyanoindoles with ethyl iododifluoroacetate or iododifluoramides under visible-light irradiation. This transition-metal- and photosensitizer-free protocol afforded diverse difluoroalkylated pyrrolo[1,2-a]indolediones in moderate to good yields under mild reaction conditions. Most appealingly, the reaction can proceed smoothly under sunlight irradiation, which opens a new avenue toward difluoroalkylated pyrrolo[1,2-a]indolediones.

Dynamic Changes in Neuroglial Reaction and Tissue Repair after Photothrombotic Stroke in Neonatal Mouse.

Perinatal and neonatal ischemic stroke is a significant cause of cognitive and behavioral impairments. Further research is needed to support models of neonatal ischemic stroke and advance our understanding of the mechanisms of infarction formation following such strokes. We used two different levels of photothrombotic stroke (PTS) models to assess stroke outcomes in neonatal mice. We measured brain damage, dynamic changes in glial cells, and neuronal expression at various time points within two weeks following ischemic injury. Our results from 2,3,5-Triphenyltetrazolium chloride (TTC) staining and immunofluorescence staining showed that in the severe group, a dense border of astrocytes and microglia was observed within 3 days post infarct. This ultimately resulted in the formation of a permanent cortical cavity, accompanied by neuronal loss in the surrounding tissues. In the mild group, a relatively sparse arrangement of glial borders was observed 7 days post infarct. This was accompanied by intact cortical tissue and the restoration of viability in the brain tissue beyond the glial boundary. Additionally, neonatal ischemic injury leads to the altered expression of key molecules such as Aldh1L1 and Olig2 in immature astrocytes. In conclusion, we demonstrated the dynamic changes in glial cells and neuronal expression following different degrees of ischemic injury in a mouse model of PTS. These findings provide new insights for studying the cellular and molecular mechanisms underlying neuroprotection and neural regeneration after neonatal ischemic injury.

Reuterin isolated from the probiotic Lactobacillus reuteri promotes periodontal tissue regeneration by inhibiting Cx43-mediated the intercellular transmission of endoplasmic reticulum stress.

OBJECTIVE: The present study aimed to evaluate the effects of reuterin, a bioactive isolated from the probiotic Lactobacillus reuteri (L. reuteri) on periodontal tissue regeneration, and provide a new strategy for periodontitis treatment in the future. BACKGROUND: Data discussing the present state of the field: Probiotics are essential for maintaining oral microecological balance. Our previous study confirmed that probiotic L. reuteri extracts could rescue the function of mesenchymal stem cells (MSCs) and promote soft tissue wound healing by neutralizing inflammatory Porphyromonas gingivalis-LPS. Periodontitis is a chronic inflammatory disease caused by bacteria seriously leading to tooth loss. In this study, we isolated and purified reuterin from an extract of L. reuteri to characterize from the extracts of L. reuteri to characterize its role in promoting periodontal tissue regeneration and controlling inflammation in periodontitis. METHODS: Chromatographic analysis was used to isolate and purify reuterin from an extract of L. reuteri, and HNMR was used to characterize its structure. The inflammatory cytokine TNFα was used to simulate the inflammatory environment. Periodontal ligament stem cells (PDLSCs) were treated with TNFα and reuterin after which their effects were characterized using scratch wound cell migration assays to determine the concentration of reuterin, an experimental periodontitis model in rats was used to investigate the function of reuterin in periodontal regeneration and inflammation control in vivo. Real-time PCR, dye transfer experiments, image analysis, alkaline phosphatase activity, Alizarin red staining, cell proliferation, RNA-sequencing and Western Blot assays were used to detect the function of PDLSCs. RESULTS: In vivo, local injection of reuterin promoted periodontal tissue regeneration of experimental periodontitis in rats and reduced local inflammatory response. Moreover, we found that TNFα stimulation caused endoplasmic reticulum (ER) stress in PDLSCs, which resulted in decreased osteogenic differentiation. Treatment with reuterin inhibited the ER stress state of PDLSCs caused by the inflammatory environment and restored the osteogenic differentiation and cell proliferation functions of inflammatory PDLSCs. Mechanistically, we found that reuterin restored the functions of inflammatory PDLSCs by inhibiting the intercellular transmission of ER stress mediated by Cx43 in inflammatory PDLSCs and regulated osteogenic differentiation capacity. CONCLUSION: Our findings identified reuterin isolated from extracts of the probiotic L. reuteri, which improves tissue regeneration and controls inflammation, thus providing a new therapeutic method for treating periodontitis.

Temporal-spatial Generation of Astrocytes in the Developing Diencephalon.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.

A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase.

Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barré syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection. The non-structural protein NS5 of ZIKV has been recognized as a valuable target of antivirals because of its RNA-dependent RNA polymerase (RdRp) and methyltransferase (MTase) activities essential for viral RNA synthesis. Here, we report a cell-based assay for discovering inhibitors of ZIKV NS5 and found that 5-Azacytidine potently inhibits ZIKV NS5, with EC50 of 4.9 µM. Furthermore, 5-Azacytidine suppresses ZIKV replication by inhibiting NS5-mediated viral RNA transcription. Therefore, we have developed a cell-based ZIKV NS5 assay which can be deployed to discover ZIKV NS5 inhibitors and demonstrated the potential of 5-Azacytidine for further development as a ZIKV NS5 inhibitor.

Purpurolide C-based microneedle promotes macrophage-mediated diabetic wound healing via inhibiting TLR4-MD2 dimerization and MYD88 phosphorylation.

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement.

BACKGROUND: MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms. METHODS: In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155. RESULTS: During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155. CONCLUSIONS: Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.

Customizable High-Contrast Optical Responses: Dual Photosensitive Colors for Smart Textiles.

Smart textiles demonstrating optical responses to external light stimuli hold great promise as functional materials with a wide range of applications in personalized decoration and information visualization. The incorporation of high-contrast, vivid, and real-time optical signals, such as color change or fluorescence emission, to indicate light on/off states is both crucial and challenging. In this study, we have developed a dual output photosensitive dye system possessing photochromic and photofluorescent properties, which was successfully applied to the dyeing and finishing processes of cotton fabrics. The design and fabrication of this dye system were based on the unique photoinduced proton transfer (PPT) principle exhibited by the water-soluble spiropyran (trans-MCH) molecule. The dual output response relies on the open-/closed-loop mechanism, wherein light regulates the trans-MCH molecule. Upon excitation by UV or visible light, the dye system and dyed fabrics display significant color changes and fluorescence switching in a real-time and highly reversible manner. Moreover, diverse photosensitive color systems can be tailored by direct blending with commercially available water-soluble dyes. By integrating high-contrast dual optical outputs into this scalable, versatile, and reversible dye system, we envisage the development and design of smart textiles capable of producing high-end products.

The bidirectional effect of neutrophils on periodontitis model in mice: A systematic review.

OBJECTIVE: To evaluate the regulatory role of neutrophils as the first line of host immune defense in the periodontal microenvironment of mice. METHODS: A systematic search was performed using PubMed, Web of Science, and ScienceDirect databases for articles published between 2012 and 2023. In this review, articles investigating the effect of neutrophils on alveolar bone resorption in a mouse model of periodontitis were selected and evaluated according to eligibility criteria. Important variables that may influence outcomes were analyzed. RESULTS: Eleven articles were included in this systematic review. The results showed that because of their immune defense functions, the functional homeostasis of local neutrophils is critical for periodontal health. Neutrophil deficiency aggravates alveolar bone loss. However, several studies have shown that excessive neutrophil infiltration is positively correlated with alveolar bone resorption caused by periodontitis in mice. Therefore, the homeostasis of neutrophil function needs to be considered in the treatment of periodontitis. CONCLUSIONS: Pooled analysis suggests that neutrophils play a bidirectional role in periodontal tissue remodeling in mouse periodontitis models. Therefore, targeted regulation of local neutrophil function provides a novel strategy for the treatment of periodontitis.

Molecular properties, structure, neurotrophic and anti-inflammatory activities of cultured secondary metabolites from the cultures of the mushroom Cyathus striatus CBPFE A06.

Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3-5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1-5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1-5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC50 values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 µM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases.

Near-infrared molecular sensor for visualizing and tracking ONOO- during the process of anti-tuberculosis drug-induced liver damage.

Isoniazid (INH) and pyrazinamide (PZA) are both the first-line anti-tuberculosis drugs in clinical treatment. It is notable that there are serious side effects of the drugs along with upregulation of reactive nitrogen species, mainly including peripheral neuritis, gastrointestinal reactions, and acute drug-induced liver injury (DILI). Among them, DILI is the most common clinical symptom as well as the basic reason of treatment interruption, protocol change, and drug resistance. As vital reactive nitrogen species (RNS), peroxynitrite (ONOO-) has been demonstrated as a biomarker for evaluation and pre-diagnosis of drug-induced liver injury (DILI). In this work, we developed a red-emitting D-π-A type fluorescence probe DIC-NP which was based on 4'-hydroxy-4-biphenylcarbonitrile modified with dicyanoisophorone as a fluorescent reporter and diphenyl phosphinic chloride group as the reaction site for highly selective and sensitive sensing ONOO-. Probe DIC-NP displayed a low detection limit (14.9 nM) and 60-fold fluorescent enhancement at 669 nm in the sensing of ONOO-. Probe DIC-NP was successfully applied to monitor exogenous and endogenous ONOO- in living HeLa cells and zebrafish. Furthermore, we verified the toxicity of isoniazid (INH) and pyrazinamide (PZA) by taking the oxidative stress induced by APAP as a reference, and successfully imaged anti-tuberculosis drug-induced endogenous ONOO- in HepG2 cells. More importantly, we developed a series of mice models of liver injury and investigated the hepatotoxicity caused by the treatment of anti-tuberculosis drugs. At the same time, H&E of mice organs (heart, liver, spleen, lung, kidney) further confirmed the competence of probe DIC-NP for estimating the degree of drug-induced liver injury, which laid a solid foundation for medical research.

Synthesis and Evaluation of 99mTc-Labelled 2-Nitroimidazole Derivatives with Different Linkers for Tumour Hypoxia Imaging.

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel 99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable 99mTc-complexes ([99mTc]Tc-L1, [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5). Corresponding rhenium analogues of [99mTc]Tc-L1 were synthesised and suggested the structures of these 99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel 99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five 99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging.