Transcriptome and small RNA analysis unveils novel insights into the C4 gene regulation in sugarcane.

MAIN CONCLUSION: This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.

The Effect of Nitrogen Functional Groups on Pb0, PbO, and PbCl2 Adsorption over a Carbonaceous Surface.

Lead (Pb) pollution, especially from the incineration of municipal solid waste (MSW), poses a significant threat to the environment. Among all the effective methods, activated carbon (AC) injection serves as an effective approach for lead removal from flue gas, while the modification of ACs emerges as a crucial pathway for enhancing Pb adsorption capacities. Density functional theory (DFT) is employed in this study to investigate the mechanisms underlying the enhanced adsorption of Pb species (Pb0, PbO, and PbCl2) on nitrogen-functionalized carbonaceous surfaces. The results show that nitrogen-containing groups substantially enhance lead adsorption capacity, with adsorption energies ranging from -526.18 to -288.31 kJ/mol on nitrogen-decorated carbonaceous surfaces, much higher than those on unmodified surfaces (-310.35 to -260.96 kJ/mol). Additionally, electrostatic potential and density-of-states analyses evidence that pyridinic nitrogen atoms remarkably expand charge distribution and strengthen orbital hybridization, thereby augmenting lead capture. This research elucidates the role of nitrogen-containing functional groups in lead adsorption, offering valuable insights for the development of highly efficient biomass-derived activated carbon sorbents for lead removal.

Near-Infrared Thermally Activated Delayed Fluorescence Nanoparticle: A Metal-Free Photosensitizer for Two-Photon-Activated Photodynamic Therapy at the Cell and Small Animal Levels.

Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy.

LncRNA FGD5-AS1 potentiates autophagy-associated doxorubicin resistance by regulating the miR-154-5p/WNT5A axis in osteosarcoma.

Osteosarcoma is prevalent in children and adolescent. The oncogenic function of long-chain noncoding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) has been reported. However, the function of FGD5-AS1 in doxorubicin-resistance in osteosarcoma remains to be illucidated. Quantitative real-time PCR (qRT-PCR) and western blot analysis (WB) were used to measure the expression of FGD5-AS1, miR-154-5p, WNT5A and autophagy proteins. MTT assay was used to assess cell viability and transwell assay was performed to evaluate migration. A nude mouse xenograft model was developed to verify the function of FGD5-AS1 in vivo. FGD5-AS1 was upregulated in doxorubicin-resistant (DXR) osteosarcoma cells. Knockdown of FGD5-AS1 suppressed osteosarcoma cell proliferation, migration, and autophagy. FGD5-AS1 upregulated WNT5A expression via sponging miR-154-5p. Furthermore, FGD5-AS1 enhanced osteosarcoma cell chemotherapy resistance through upregulation of WNT5A by inhibiting miR-154-5p. Suppression of FGD5-AS1 significantly suppressed tumor growth in nude mice. FGD5-AS1 may promote chemoresistance through WNT5A-induced autophagy by sponging miR-154-5p in osteosarcoma cells.

A Novel Combination of Keratinocyte and Autologous Microskin Grafting to Repair Full-Thickness Skin Loss.

INTRODUCTION: The high mortality of patients with extensive deep burns is mainly attributed to the extensive burn wound and the scarce autologous skin left for wound repair. The purpose of this study was to explore how to effectively use the limited remaining autologous skin to repair the extensive deep wound. METHODS: Human keratinocytes harvested from the foreskin were cultured and transfected with epidermal growth factors (EGFs) by an adenovirus vector (Ad-EGF). The expression and the biological activity of EGF in both the normal human keratinocytes and the EGF gene-modified human keratinocytes were quantified by ELISA assay and CCK-8 assay, respectively. The differentiated phenotype of epidermal cells was detected by immunofluorescence staining via CK10, CK14, and CK19 expressions. Rats were subjected to a full-thickness skin loss (3.3 cm × 3.0 cm) on the dorsum, which was repaired with the EGF gene-modified human keratinocyte suspension and autologous microskin and covered with the allogeneic skin. The wound healing was quantified, and the expression of EGF mRNA was measured by RT-PCR. RESULTS: The EGF gene-modified human keratinocytes highly expressed EGF. CK10, CK14, and CK19 as keratinocyte differentiation markers were increased in the EGF gene-modified human keratinocytes. Wound healing was accelerated remarkably by the combination of autologous microskin grafting and EGF gene-modified human keratinocytes in vivo, and a very high EGF mRNA expression was observed in EGF gene-modified human keratinocytes groups on days 7 and 14 compared with other groups. DISCUSSION/CONCLUSION: The EGF gene-modified human keratinocyte suspension may serve as promising seed cells which can effectively secrete EGF to accelerate wound repair in combination with autologous microskin grafting and reduce the autologous skin requirement for wound repair.

Light regulation and long-lived stability of RGB colors in cholesteric liquid crystal physical gels via a mixing strategy.

Photo-responsive cholesteric liquid crystals (CLCs) have attracted much attention due to the dynamic tunability of their unique helical superstructure. However, it is still a challenge to endow the mechanical properties and to regulate the reflection colors at the same time. In this work, a simple strategy is developed for the construction of thermo-responsive CLC physical gels via the direct mixing of photo-responsive dopants and a gelator with nematic LCs. The reflection colors of CLCs and the mechanical properties of gels can be independently regulated due to the separation of the photo-responsive chiral group from the gelator. In addition, the CLC reflection colors can be regulated via visible light in the range of RGB with long-lived thermal stability. Finally, the information storage properties of this kind of CLC gel have been investigated.

A ratiometric nanoprobe based on carboxylated graphitic carbon nitride nanosheets and Eu3+ for the detection of tetracyclines.

A ratiometric fluorescence method based on carboxylated graphitic carbon nitride nanosheets (C-g-C3N4) and Eu3+ (C-g-C3N4-Eu3+) is described for the detection of tetracyclines (TCs), a broad-spectrum antibiotic. C-g-C3N4, which was used as a fluorescence enhancer of Eu3+, was prepared by direct pyrolysis of melamine and post-functionalization. In the presence of TCs, the fluorescence intensity of Eu3+ at 616 nm increased, accompanied by a decrease of fluorescence intensity of C-g-C3N4 at 435 nm. Under the optimal conditions, the ratio of fluorescence intensity at 616 nm to the one at 435 nm (I616/I415) increases linearly in the 10 nM to 40 µM TC concentration range with a detection limit of 7.7 nM (S/N = 3). It has been successfully applied in the detection of TCs in spiked tap water and soil samples with satisfactory recovery (96.6-107.2%) and high precision. Furthermore, a test paper and smartphone can assist in rapidly detecting TCs due to the emission color change from blue to red with the addition of TCs. This shows that the proposed method has great potential for the rapid detection TCs in real samples.

The Deformation Behavior and Bending Emissions of ZnO Microwire Affected by Deformation-Induced Defects and Thermal Tunneling Effect.

The realization of electrically pumped emitters at micro and nanoscale, especially with flexibility or special shapes is still a goal for prospective fundamental research and application. Herein, zinc oxide (ZnO) microwires were produced to investigate the luminescent properties affected by stress. To exploit the initial stress, room temperature in situ elastic bending stress was applied on the microwires by squeezing between the two approaching electrodes. A novel unrecoverable deformation phenomenon was observed by applying a large enough voltage, resulting in the formation of additional defects at bent regions. The electrical characteristics of the microwire changed with the applied bending deformation due to the introduction of defects by stress. When the injection current exceeded certain values, bright emission was observed at bent regions, ZnO microwires showed illumination at the bent region priority to straight region. The bent emission can be attributed to the effect of thermal tunneling electroluminescence appeared primarily at bent regions. The physical mechanism of the observed thermoluminescence phenomena was analyzed using theoretical simulations. The realization of electrically induced deformation and the related bending emissions in single microwires shows the possibility to fabricate special-shaped light sources and offer a method to develop photoelectronic devices.

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells.

Molecular imaging is essential for diagnosis and treatment planning for glioblastoma patients. Positron emission tomography (PET) with tracers for the detection of the solute carrier family 7 member 5 (SLC7A5; also known as the amino acid transporter light chain L system, LAT1) and for the mitochondrial translocator protein (TSPO) is successfully used to provide additional information on tumor volume and prognosis. The current approaches for TSPO-PET and the visualization of tracer ([18F] Fluoroethyltyrosine, FET) uptake by LAT1 (FET-PET) do not yet exploit the full diagnostic potential of these molecular imaging techniques. Therefore, we investigated the expression of TSPO and LAT1 in patient glioblastoma (GBM) samples, as well as in various GBM mouse models representing patient GBMs of different genetic subtypes. By immunohistochemistry, we found that TSPO and LAT1 are upregulated in human GBM samples compared to normal brain tissue. Next, we orthotopically implanted patient-derived GBM cells, as well as genetically engineered murine GBM cells, representing different genetic subtypes of the disease. To determine TSPO and LAT1 expression, we performed immunofluorescence staining. We found that both TSPO and LAT1 expression was increased in tumor regions of the implanted human or murine GBM cells when compared to the neighboring mouse brain tissue. While LAT1 was largely restricted to tumor cells, we found that TSPO was also expressed by microglia, tumor-associated macrophages, endothelial cells, and pericytes. The Cancer Genome Atlas (TCGA)-data analysis corroborates the upregulation of TSPO in a bigger cohort of GBM patient samples compared to tumor-free brain tissue. In addition, AIF1 (the gene encoding for the myeloid cell marker Iba1) was also upregulated in GBM compared to the control. Interestingly, TSPO, as well as AIF1, showed significantly different expression levels depending on the GBM genetic subtype, with the highest expression being exhibited in the mesenchymal subtype. High TSPO and AIF1 expression also correlated with a significant decrease in patient survival compared to low expression. In line with this finding, the expression levels for TSPO and AIF1 were also significantly higher in (isocitrate-dehydrogenase wild-type) IDHWT compared to IDH mutant (IDHMUT) GBM. LAT1 expression, on the other hand, was not different among the individual GBM subtypes. Therefore, we could conclude that FET- and TSPO-PET confer different information on pathological features based on different genetic GBM subtypes and may thus help in planning individualized strategies for brain tumor therapy in the future. A combination of TSPO-PET and FET-PET could be a promising way to visualize tumor-associated myeloid cells and select patients for treatment strategies targeting the myeloid compartment.

Visible Light Rewritable and Long-Lived Colors in Cholesteric Liquid Crystals: A Facile Co-Doping Strategy.

Photoresponsive cholesteric liquid crystals (CLCs) are able to selectively reflect colors upon light exposure. Yet, it still remains a formidable challenge to realize simultaneous rewriting and long-life color in CLCs using visible light. Herein, guided by time dependent density functional theory (TD-DFT) computation, an octafluorinated binaphthyl azobenzene is synthesized to achieve the fast response and long-life color upon visible light exposure. Subsequently, based on the solubility parameter, uniform CLCs are formulated through a facile co-doping strategy. Interestingly, the CLCs change reflection colors from blue to green, red, and then into the near infrared region in seconds upon 550 nm light illumination. The completely reversible process is readily accessable upon 450 nm irradiation. More importantly, each color is independently stable for ≈24 h in the dark.

Photomodulated Morphologies in Halogen Bond-Driven Assembly during Gel-Sol Transition.

Photoresponsive supramolecular gels with various applications are being constantly pursued; however, achieving well-defined morphology changes of gels via light irradiation remains a formidable challenge. In this study, a gel is prepared through halogen bond between azopyridine-containing Azopy-C10 and 1,4-tetrafluorodiiodobenzene. The gel exhibits gel-sol transition due to trans-cis isomerization of the azopyridine moiety upon UV irradiation. During this transition, the morphologies vary from flake to fluffy bobble-like and finally to peony-like with increasing exposure time, which is difficult to achieve in traditional assembly systems. The microstructure change is attributed to the variations of cis-isomer content and halogen-bonding strength. The supramolecular gel provides a novel method to achieve photomodulated morphologies and broadens the applications of such kind of materials, ranging from information storage to high-tech anticounterfeit.

Labeling and Single-Particle-Tracking-Based Entry Mechanism Study of Vaccinia Virus from the Tiantan Strain.

Entry is the first and critical step of viral infection, while the entry mechanisms of many viruses are still unclear due to the lack of efficient technology. In this report, by taking advantage of the single-virion fluorescence tracking technique and simultaneous dual-labeling methods for viruses we developed, the entry pathway of vaccinia virus from tiantan strain (VACV-TT) was studied in real-time. By combining with the technologies of virology and cell biology, we found that VACV-TT moved toward the Vero cell body along the filopodia induced by the virions interaction, and then, they were internalized through macropinocytosis, which was an actin-, ATP-dependent but clathrin-, caveolin-independent endocytosis. These results are of significant importance for VACV-TT-based vaccine vectors and oncolytic virus study.

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma.

BACKGROUND/AIMS: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. METHODS: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. RESULTS: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. CONCLUSION: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

Photomodulated Electro-optical Response in Self-Supporting Liquid Crystalline Physical Gels.

Photoresponsive liquid crystal (LC) physical gels have attracted more and more attention because of the nature of strong response via light stimulus. Although many efforts on the breaking and recovering of physical gels through photoisomerization have been focused, fast electro-optical response and high mechanical properties even upon light irradiations are difficult to achieve at the same time. In this work, two kinds of azobenzene-containing gelators (AG1 and AG2) with different terminal groups were designed and synthesized. Both gelators could induce the nematic LC P0616A self-assemble into anisotropic phase-separated LC physical gels at low contents. Their phase-transition behavior, thermal stability, microstructure, and mechanical strength were systematically studied. Compared with AG2 in P0616A, the P0616A/AG1 gels showed better mechanical property. When the gelator content was above 3 wt %, the P0616A/AG1 gels possessed good self-supporting ability with a storage modulus more than 104 Pa. Thus, the photoresponsive electro-optical properties and structures of P0616A/AG1 gels were focused in detail. It was surprising that the electro-optical response speed of the P0616A/AG1 gels could be promoted upon UV irradiation. In particular, the decay time (τoff) was only about half when compared with the initial state, whereas the gels still exhibited good self-supporting ability; also the network of the LC physical gels had no change at macro- and microstructural levels. These exciting results would open a door for the application of this material in electro-optical devices.

Precisely Tuning Helical Twisting Power via Photoisomerization Kinetics of Dopants in Chiral Nematic Liquid Crystals.

It has been paid much attention to improve the helical twisting power (ß) of dopants in chiral nematic liquid crystals (CLCs); however, the correlations between the ß value and the molecular structures as well as the interaction with nematic LCs are far from clear. In this work, a series of reversibly photo-switchable axially chiral dopants with different lengths of alkyl or alkoxyl substituent groups have been successfully synthesized through nucleophilic substitution and the thiol-ene click reaction. Then, the effect of miscibility between these dopants and nematic LCs on the ß values, as well as the time-dependent decay/growth of the ß values upon irradiations, has been investigated. The theoretical Teas solubility parameter shows that the miscibility between dopants and nematic LCs decreases with increasing of the length of substituent groups from dopant 1 to dopant 4. The ß value of chiral dopants in nematic LCs decreases from dopant 1 to dopant 4 both at the visible light photostationary state (PSS) and at the UV PSS after UV irradiation. With increasing of the length of substituent groups, the photoisomerization rate constant of dopants increases for trans-cis transformation upon UV irradiation and decreases for the reverse process upon visible light irradiation either in isotropic ethyl acetate or in anisotropic LCs, although the constant in ethyl acetate is several times larger than the corresponding value in LCs. Also, the color of the CLCs could be tuned upon light irradiations. These results enable the precise tuning of the pitch and selective reflection wavelength/color of CLCs, which paves the way to the applications in electro-optic devices, information storage, high-tech anticounterfeit, and so forth.

Robust multi-responsive supramolecular hydrogel based on a mono-component host-guest gelator.

Supramolecular hydrogels have been widely investigated, but the construction of stimuli-responsive mono-component host-guest hydrogels remains a challenge in that it is still hard to balance the solubility and gelation ability of the gelator. In this work, three azobenzene-modified ß-cyclodextrin derivatives with different alkyl lengths (ß-CD-Azo-Cn) have been synthesized. The length of the alkyl chain dramatically influences the solubility and gelation ability of ß-CD derivatives in water. Among these derivatives, ß-CD-Azo-C8 possesses the lowest minimum gelation concentration (MGC). Based on the host-guest interaction between ß-CD and azobenzene units in aqueous solution, which is confirmed by UV-visible and ROESY NMR spectra, the gelators self-assemble and further interwine into networks through the hydrogen bonds on the surface of ß-CD cavities. Hydrogels formed by mono-component gelators can collapse under external stimuli such as heating, competition guests and hosts, and UV irradiation. When the concentration of the gelator is more than 8 wt%, the hydrogel exhibits good self-supporting ability with a storage modulus higher than 104 Pa. The gel-sol transition temperature of the hydrogel is near body temperature, indicating its potential applications in biological materials.

Ginsenoside Rb1 protects against spinal cord ischemia-reperfusion injury in rats by downregulating the Bax/Bcl-2 ratio and caspase-3 and p-Ask-1 levels.

The aim of this study was to confirm the effects of ginsenoside Rb1 on neural cell apoptosis in the spinal cord of rats with spinal cord ischemia-reperfusion injury (SCII) and to explore its potential mechanisms. A total of 100 healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (n = 10), sham-operated (n = 10), SCII model (n = 40), and ginsenoside Rb1-treated groups (n = 40). Basso, Beattie, Bresnahan (BBB) scale was used to examine rat hindlimb locomotor function. Nissl and Tunnel staining were used to observe neural cell injury and apoptosis, respectively, in the spinal cord of rats with SCII. Immunofluorescence staining was performed to detect the expression of Bax and Bcl-2. The levels of caspase-3 and phosphorylated Ask-1 (p-Ask-1) were detected by western blotting. Ginsenoside Rb1 prevented neural cell apoptosis in the spinal cord and improved hindlimb locomotor dysfunction of rats (P < .05). Moreover, SCII-induced upregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio were significantly decreased by ginsenoside Rb1 (P < .05). The protective effects of ginsenoside Rb1 on neural cells in the spinal cord of rats with SCII were mediated by the ginsenoside Rb1-induced downregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio.

Integrating Two Efficient and Specific Bioorthogonal Ligation Reactions with Natural Metabolic Incorporation in One Cell for Virus Dual Labeling.

Though techniques in bioorthogonal chemistry and metabolic incorporation have been developed over the past decade, it remains difficult to integrate different bioorthogonal reactions or metabolic incorporations into one system. In this report, the protein and DNA metabolic incorporations were combined with two bioorthogonal reactions in one cell to develop a facile and universal method for virus dual labeling. Azide and vinyl groups were introduced into the proteins or genomes of viruses, respectively, through the intrinsic biosynthesis of biomolecules, which were subsequently fluorescently labeled via copper-free click chemistry or alkene-tetrazine ligation reactions during natural propagation process in host cells. Both the envelope viruses and the capsid viruses could be labeled, and the dual labeling efficiency was more than 80%. The labeled progeny virions were structurally intact and fully infectious, and their fluorescence was strong enough to track single virions.

Ru(ii) polypyridyl complex-incorporated and folate-conjugated vehicle for cancer cell imaging and photoinduced inactivation.

Ru(ii) polypyridyl complexes have been expected as promising therapeutic agents against cancer owing to its DNA photocleavage activity. However, the lack of cell selectivity poses a significant obstacle to their practical application. Herein, the strategy combining cell-specific imaging with photoinduced cell death based on [Ru(phen)2(dppz)](2+) has been developed by incorporating [Ru(phen)2(dppz)](2+) into folate-conjugated liposomes. The cells overexpressing folate receptors could specifically recognize this vehicle and be imaged through the luminescence of [Ru(phen)2(dppz)](2+). Thereafter, the delivered [Ru(phen)2(dppz)](2+) interacted with DNA in cells and led to photoinduced cell death. This work provided a possible alternative for cancer diagnosis and therapy.

Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis.