Material stock analysis of urban road from nighttime light data based on a bottom-up approach.

In recent years, there has been an increasing focus on the dynamics of material stock, that is, the basis of material flow in the entire ecosystem. With the gradual improvement of the global road network encryption project, the uncontrolled extraction, processing, and transportation of raw materials impose serious resource concerns and environmental pressure. Quantifying material stocks enable governments to formulate scientific policies because socio-economic metabolism, including resource allocation, use, and waste recovery, can be systematically assessed. In this study, OpenStreetMap road network data were used to extract the urban road skeleton, and nighttime light images were divided by watershed to construct regression equations based on geographical location attributes. Resultantly, a generic road material stock estimation model was developed and applied to Kunming. We concluded that (1) the top three stocks are stone chips, macadam, and grit (total weight is 380 million tons), (2) the proportion of asphalt, mineral powder, lime, and fly ash is correspondingly similar, and (3) the unit area stock decreases as the road grade declines; therefore, the branch road has the lowest unit stock.

Sulourea-coordinated Pd nanocubes for NIR-responsive photothermal/H2S therapy of cancer.

BACKGROUND: Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H2S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H2S gas therapy is expected to achieve synergistic tumor treatment. METHODS: Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H2S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H2S release, realizing the effective combination of photothermal therapy and H2S gas therapy. RESULTS: The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g-1), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H2S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H2S produces a strong synergetic effect by H2S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment. CONCLUSIONS: The proposed NIR-responsive heat/H2S release strategy provides a new approach for effective cancer therapy.

Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy.

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.

Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk.

Inflammatory bowel disease (IBD) results from aberrant immune stimulation against a dysbiotic mucosal but relatively preserved luminal microbiota and preferentially affects males in early onset disease. However, factors contributing to sex-specific risk and the pattern of dysbiosis are largely unexplored. Core 1 ß3GalT-specific molecular chaperone (Cosmc), which encodes an X-linked chaperone important for glycocalyx formation, was recently identified as an IBD risk factor by genome-wide association study. We deleted Cosmc in mouse intestinal epithelial cells (IECs) and found marked reduction of microbiota diversity in progression from the proximal to the distal gut mucosa, but not in the overlying lumen, as seen in IBD. This loss of diversity coincided with local emergence of a proinflammatory pathobiont and distal gut restricted pathology. Mechanistically, we found that Cosmc regulates host genes, bacterial ligands, and nutrient availability to control microbiota biogeography. Loss of one Cosmc allele in males (IEC-Cosmc-/y) resulted in a compromised mucus layer, spontaneous microbe-dependent inflammation, and enhanced experimental colitis; however, females with loss of one allele and mosaic deletion of Cosmc in 50% of crypts (IEC-Cosmc+/-) were protected from spontaneous inflammation and partially protected from experimental colitis, likely due to lateral migration of normal mucin glycocalyx from WT cells over KO crypts. These studies functionally validate Cosmc as an IBD risk factor and implicate it in regulating the spatial pattern of dysbiosis and sex bias in IBD.

Coexpression of octopine and succinamopine Agrobacterium virulence genes to generate high quality transgenic events in maize by reducing vector backbone integration.

Agrobacterium-mediated transformation is a complex process that is widely utilized for generating transgenic plants. However, one of the major concerns of this process is the frequent presence of undesirable T-DNA vector backbone sequences in the transgenic plants. To mitigate this deficiency, a ternary strain of A. tumefaciens was modified to increase the precision of T-DNA border nicking such that the backbone transfer is minimized. This particular strain supplemented the native succinamopine VirD1/VirD2 of EHA105 with VirD1/VirD2 derived from an octopine source (pTi15955), the same source as the binary T-DNA borders tested here, residing on a ternary helper plasmid containing an extra copy of the succinamopine VirB/C/G operons and VirD1. Transformation of maize immature embryos was carried out with two different test constructs, pDAB101556 and pDAB111437, bearing the reporter YFP gene and insecticidal toxin Cry1Fa gene, respectively, contained in the VirD-supplemented and regular control ternary strains. Molecular analyses of ~ 700 transgenic events revealed a significant 2.6-fold decrease in events containing vector backbone sequences, from 35.7% with the control to 13.9% with the VirD-supplemented strain for pDAB101556 and from 24.9% with the control to 9.3% with the VirD-supplemented strain for pDAB111437, without compromising transformation efficiency. In addition, while the number of single copy events recovered was similar, there was a 24-26% increase in backbone-free events with the VirD-supplemented strain compared to the control strain. Thus, supplementing existing VirD1/VirD2 genes in Agrobacterium, to recognize diverse T-DNA borders, proved to be a useful tool to increase the number of high quality events in maize.

Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species.

The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic-eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)-dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox-mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential.

Comparison of the impact of viral and plant-derived promoters regulating selectable marker gene on maize transformation and transgene expression.

KEY MESSAGE: The choice of promoter regulating the selectable marker gene impacts transformation efficiency, copy number and the expression of selectable marker and flanking genes in maize. Viral or plant-derived constitutive promoters are often used to regulate selectable marker genes. We compared two viral promoters, cauliflower mosaic virus (CaMV 35T) and sugarcane bacilliform virus (SCBV) with two plant promoters, rice actin1 (OsAct1) and maize ubiquitin 1 (ZmUbi1) to drive aryloxyalkanoate dioxygenase (aad-1) selectable marker gene in maize inbred line B104. ZmUbi1- and OsAct1-containing constructs demonstrated higher transformation frequencies (43.8 and 41.4%, respectively) than the two viral promoter constructs, CaMV 35T (25%) and SCBV (8%). Interestingly, a higher percentage of single copy events were recovered for SCBV (82.1%) and CaMV 35T (59.3%) promoter constructs, compared to the two plant-derived promoters, OsAct1 (40.0%), and ZmUbi1 (27.6%). Analysis of protein expression suggested that the viral promoter CaMV 35T expressed significantly higher AAD-1 protein (174.6 ng/cm2) than the OsAct1 promoter (12.6 ng/cm2) in T0 leaf tissue. When measured in T2 callus tissue, the two viral promoters both had higher expression and more variability than the two plant-derived promoters. A potential explanation for why viral promoters produce lower transformation efficiencies but higher percentages of low copy number events is discussed. In addition, viral promoters regulating aad-1 were found to influence the expression of upstream flanking genes in both T0 leaf and T2 callus tissue.

Wild-type and mutant AvrA- Salmonella induce broadly similar immune pathways in the chicken ceca with key differences in signaling intermediates and inflammation.

Salmonella enterica serovar Typhimurium (ST) is a serious infectious disease throughout the world, and a major reservoir for Salmonella is chicken. Chicken infected with Salmonella do not develop clinical disease, this may be the result of important host interactions with key virulence proteins. To study this, we inoculated chicken with mutant Salmonella Typhimurium that lacked the virulence protein AvrA (AvrA(-)). AvrA is referred to as an avirulence factor, as it moderates the host immune response. The lack of the AvrA virulence gene in ST resulted in reduced weight gain, enhanced persistence and greater extraintestinal organ invasion in chickens, as compared to wild-type (WT) ST. Kinome analysis was performed on inoculated cecal tissue. The majority of the signal transduction pathways induced by AvrA(-) and WT ST were similar; however, we observed alterations in innate immune system signaling. In addition, a leukocyte migration pathway was altered by AvrA(-) ST that may allow greater gut barrier permeability and invasion by the mutant. Cytokine expression did not appear significantly altered at 7 d post-inoculation; at 14 d post-inoculation, there was an observed increase in the expression of anti-inflammatory IL-10 in the WT inoculated ceca. This study is the first to describe mutant AvrA(-) ST infection of chicken and provides further insight into the Salmonella responses observed in chicken relative to other species such as humans and cattle.

Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis.

BACKGROUND: There are a number of studies regarding to the susceptibility of A20 SNPs in rheumatoid arthritis (RA); however, a few of these studies have shown an association between polymorphisms in the A20 gene and RA risk in the Chinese population. The aim of this study was to investigate the characteristics of A20 gene polymorphisms, the association between polymorphisms and clinical significance in Chinese RA patients. METHODS: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) (50 cases), synovial fluid (11 cases) from RA patients and PBMCs from 30 healthy individuals. Quantitative Real-time PCR (qRT-PCR) was used to analyze the A20 mRNA expression in 38 RA patients and 40 healthy individuals. Pearson's Chi square test and two independent-samples Wilcoxon tests were used for statistical analysis. RESULTS: Eight single nucleotide polymorphisms (SNPs) (rs5029937, rs3799491, rs598493, rs2307859, rs146534657, rs2230926, rs661561, and rs582757) were identified in PBMCs of RA patients. One new mutation (14284 T > A) was identified in synovial fluid mononuclear cells from one RA case. rs146534657 was identified for the first time in two RA cases. Patients with rs146534657 (12411 A > G, Asn102Ser) AG genotype or rs2230926 (12486 T > G, Phe127Cys) TG genotype had poor outcome. Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001). There was a higher A20 mRNA expression in RA patients with rs2230926 TG genotype and rs146534657 AG genotype (11.56 ± 7.39) than patients with rs2230926 TT genotype and rs146534657 AA genotype (5.63 ± 4.37) (p = 0.031). CONCLUSION: Significantly lower A20 expression was found in RA patients. The polymorphisms of A20 were characterized in RA patients. We detected rs146534657 for the first time and identified a new A20 mutation (14284 T > A). A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients.

General protocol for the synthesis of functionalized magnetic nanoparticles for magnetic resonance imaging from protected metal-organic precursors.

The development of magnetic nanoparticles (MNPs) with functional groups has been intensively pursued in recent years. Herein, a simple, versatile, and cost-effective strategy to synthesize water-soluble and amino-functionalized MNPs, based on the thermal decomposition of phthalimide-protected metal-organic precursors followed by deprotection, was developed. The resulting amino-functionalized Fe3O4, MnFe2O4, and Mn3O4 MNPs with particle sizes of about 14.3, 7.5, and 6.6 nm, respectively, had narrow size distributions and good dispersibility in water. These MNPs also exhibited high magnetism and relaxivities of r2 = 107.25 mM(-1) s(-1) for Fe3O4, r2 = 245.75 mM(-1) s(-1) for MnFe2O4, and r1 = 2.74 mM(-1) s(-1) for Mn3O4. The amino-functionalized MNPs were further conjugated with a fluorescent dye (rhodamine B) and a targeting ligand (folic acid: FA) and used as multifunctional probes. Magnetic resonance imaging and flow-cytometric studies showed that these probes could specifically target cancer cells overexpressing FA receptors. This new protocol opens a new way for the synthesis and design of water-soluble and amino-functionalized MNPs by an easy and versatile route.

[Role and mechanism of NKp44+NK cells in the proliferation and inflammation of synovium of rheumatoid arthritis patients].

OBJECTIVE: To explore the effects of NKp44+NK cells from rheumatoid arthritis (RA) patients on the proliferation and monocyte chemotactic protein 1 production of fibroblast-like synoviocytes (FLS). METHODS: The proportions of natural killer (NK) p44 NK cells in peripheral blood (PB) of 50 RA patients and 50 healthy individuals were detected by flow cytometry. Synovial fluid (SF) samples from 30 RA patients were also detected. NKp44+NK cells in RA SF were sorted by flow cytometry for 5 times. The supernatant level of interleukin (IL)-22 was measured by enzyme-linked immunosorbent assay (ELISA). The proliferation of FLS after an addition of culture supernatant of NKp44+NK cells was detected by methyl thiazolyl tetrazolium (MTT) at 24, 48 and 72 h. Monocyte chemotactic protein (MCP)-1 production of RA FLS after an addition of rhIL-22 was detected by ELISA. RESULTS: The proportion of NKp44+NK cells in PB of RA patients was significantly higher than that of normal controls while the proportion of NKp44+NK cells in SF of RA patients was higher than that in PB of matched RA patients (1.270% vs 0, 15.190% vs 2.425%, P < 0.01). The supernatant level of IL-22 in NKp44+NK cell culture was (1 603 ± 332) ng/L. Rapid proliferation of RA FLS was observed at 24, 48, 72 h after an addition of culture supernatant (P < 0.01). IL-22 antibody obviously inhibited the proliferation of RA FLS induced by NKp44+NK cells. MCP-1 production of RA FLS was detected at 72 h after an addition of rhIL-22 (P < 0.01). CONCLUSION: NKp44+NK cells can promote the proliferation and MCP-1 production of RA FLS through the production of IL-22 so as to play an important role in the synovial proliferation and inflammation of RA.

Glutathione-triggered release of SO2 gas to augment oxidative stress for enhanced chemodynamic and sonodynamic therapy.

Recently, gas therapy has emerged as a promising alternative treatment for deep-seated tumors. However, some challenges regarding insufficient or uncontrolled gas generation as well as unclear therapeutic mechanisms restrict its further clinical application. Herein, a well-designed nanoreactor based on intracellular glutathione (GSH)-triggered generation of sulfur dioxide (SO2) gas to augment oxidative stress has been developed for synergistic chemodynamic therapy (CDT)/sonodynamic therapy (SDT)/SO2 gas therapy. The nanoreactor (designed as CCM@FH-DNs) is constructed by employing iron-doped hollow mesoporous silica nanoparticles as carriers, the surface of which was modified with the SO2 prodrug 2,4-dinitrobenzenesulfonyl (DNs) and further coated with cancer cell membranes for homologous targeting. The CCM@FH-DNs can not only serve as a Fenton-like agent for CDT, but also as a sonosensitizer for SDT. Importantly, CCM@FH-DNs can release SO2 for SO2-mediated gas therapy. Both in vitro and in vivo evaluations demonstrate that the CCM@FH-DNs nanoreactor performs well in augmenting oxidative stress for SO2 gas therapy-enhanced CDT/SDT via GSH depletion and glutathione peroxidase-4 enzyme deactivation as well as superoxide dismutase inhibition. Moreover, the doped iron ions ensure that the CCM@FH-DNs nanoreactors enable magnetic resonance imaging-guided therapy. Such a GSH-triggered SO2 gas therapy-enhanced CDT/SDT strategy provides an intelligent paradigm for developing efficient tumor microenvironment-responsive treatments.

Nitrogen-doped carbon dots derived from ellagic acid and L-tyrosine for photothermal anticancer and anti-inflammation.

Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.

The Salmonella effector AvrA mediates bacterial intracellular survival during infection in vivo.

The enteric pathogen Salmonella typhimurium secretes the preformed AvrA effector protein into host cells. This acetyltransferase has been shown to modulate mammalian intestinal immune and survival responses by inhibition of JNK MAPK. To study the role of this effector in natural enteric infection, we used a mouse model to compare wild-type S. typhimurium to an isogenic AvrA null Salmonella mutant. Salmonella lacking AvrA induced increased intestinal inflammation, more intense systemic cytokine responses, and increased apoptosis in epithelial cells. Increased apoptosis was also observed in extra epithelial macrophages. AvrA null-infected mice consistently showed higher bacterial burden within mucosal lymphoid tissues, spleen and liver by 5 days post infection, which indicated a more severe clinical course. To study the molecular mechanisms involved, recombinant adenoviruses expressing AvrA or mutant AvrA proteins were constructed, which showed appropriate expression and mediated the expected inhibition of JNK signalling. Cultured epithelial cells and macrophages transduced with AvrA expressing adenovirus were protected from apoptosis induced by exogenous stimuli. In conclusion, the results demonstrated that Salmonella AvrA modulates survival of infected macrophages likely via JNK suppression, and prevents macrophage death and rapid bacterial dissemination. AvrA suppression of apoptosis in infected macrophages may allow for establishment of a stable intracellular niche typical of intracellular pathogens.

Modulation of hypoxia and redox in the solid tumor microenvironment with a catalytic nanoplatform to enhance combinational chemodynamic/sonodynamic therapy.

The efficacy of reactive oxygen species-mediated therapy is generally limited by hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME). To address these issues, herein, a smart Mn3O4/OCN-PpIX@BSA nanoplatform is rationally developed to enhance the combinational therapeutic efficacy of chemodynamic therapy (CDT) and sonodynamic therapy (SDT) through TME modulation. For constructing the catalytic nanoplatform (Mn3O4/OCN-PpIX@BSA), Mn3O4 nanoparticles were grown in situ on oxidized g-C3N4 (OCN) nanosheets, and the as-prepared Mn3O4/OCN nano-hybrids were then successively loaded with protoporphyrin (PpIX) and coated with bovine serum albumin (BSA). The catalase-like Mn3O4 nanoparticles are able to effectively catalyze the overexpressed endogenous H2O2 to produce O2, which could relieve hypoxia and improve the therapeutic effect of combinational CDT/SDT. The decomposition of Mn3O4 by GSH enables the release of Mn2+ ions, which not only facilitates good T1/T2 dual-modal magnetic resonance imaging for tumor localization but also results in the depletion of GSH and the Mn2+-driven Fenton-like reaction, thus further amplifying the oxidative stress and achieving improved therapeutic efficacy. It is worth noting that the Mn3O4/OCN-PpIX@BSA nanocomposites exhibit minimal toxicity to normal tissues at therapeutic doses. These positive findings provide a new strategy for the convenient construction of TME-regulating smart theranostic nanoagents to improve the therapeutic outcomes towards malignant tumors effectively.

An Ultrasound-Triggered Nanoplatform for Synergistic Sonodynamic-Nitric Oxide Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) has aroused intensive interest as a powerful alternative for cancer treatment in recent years due to its non-invasiveness and deep tissue penetration. However, the therapeutic effect of SDT alone is still limited by intrinsic hypoxia in solid tumors. Combined synergistic therapy strategies are highly desired for improving therapeutic efficiency. Herein, a rationally designed intelligent theranostic nanoplatform is developed for the enhancement of cancer treatment through synergistic SDT and nitric oxide (NO) therapy. This US-triggered nanoplatform is fabricated by integrating a sonosensitizer Rose Bengal (RB) and a NO donor (SNO) into manganese-doped hollow mesoporous silica nanoparticles (MH-SNO@RB). Impressively, the acidic and reducing tumor microenvironment accelerates the sustainable release of Mn ions from the framework, which facilitates the MH-SNO@RB to be used as a contrast agent for magnetic resonance imaging. More importantly, the reactive oxygen species (ROS) generated by RB and NO molecules released from SNO, which are simultaneously triggered by US, can react with each other to yield highly reactive peroxynitrite (ONOO-) ions for effective tumor inhibition both in vitro and in vivo. Furthermore, the nanoplatform demonstrates good hemocompatibility and histocompatibility. This study opens a new strategy for the full utilization of US and intelligent design avenues for high-performance cancer treatment.

Novel biallelic ASTL variants are associated with polyspermy and female infertility: A successful live birth following ICSI treatment.

Fertilization of the egg by the sperm is the first vital stage of embryogenesis. In mammals, only one sperm is incorporated into the oocyte. Polyspermy is a key anomaly of fertilization that is generally lethal to the embryo. To date, only a few causative genes for polyspermy have been reported. In a recent study, a homozygous variant in astacin-like metalloendopeptidase (ASTL), which encodes the ovastacin enzyme that cleaves ZP2 to prevent polyspermy, was found to be associated with female infertility characterized by polyspermy in vitro. Herein, we identified two ASTL variants in a Chinese woman likely responsible for her primary infertility and polyspermy in in vitro fertilization. Both variants were located within the key catalytic domain and predicted to alter hydrogen bonds, potentially impairing protein stability. Moreover, expression and immunoblot analyses in CHO-K1 cells indicated abnormal ovastacin zymogen activation or decreased enzyme stability. Intracytoplasmic sperm injection treatment successfully bypassed the defect in polyspermy blocking and resulted in a live birth. Our study associates ASTL variants with human infertility and further supports the contribution of this gene to blocking polyspermy in humans. Our findings expand the spectrum of ASTL mutations and should facilitate the diagnosis of oocyte-borne polyspermy.

Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy.

The ingenious combination of nano-enzymes with multi-enzyme activities and therapeutic drugs that can promote reactive oxygen species (ROS) production in cancer cells will enhance the therapeutic efficacy of nanomedicines on malignant tumors by amplifying oxidative stress. Herein, PEGylated Ce-doped hollow mesoporous silica nanoparticles (Ce-HMSN-PEG) loaded with saikosaponin A (SSA) are elaborately constructed as a smart nanoplatform for improving the efficiency of tumor therapy. The carrier Ce-HMSN-PEG showed multi-enzyme activities due to the presence of mixed Ce3+/Ce4+ ions. In the tumor microenvironment, peroxidase-like Ce3+ ions convert endogenous H2O2 into highly toxic ˙OH for chemodynamic therapy, while Ce4+ ions not only show catalase-like activity to reduce tumor hypoxia but also exhibit glutathione (GSH) peroxidase-mimicking properties to effectively deplete GSH in tumor cells. Moreover, the loaded SSA can cause the enrichment of superoxide anions (˙O2-) and H2O2 within tumor cells by disrupting mitochondrial functions. By integrating the respective advantages of Ce-HMSN-PEG and SSA, the as-prepared SSA@Ce-HMSN-PEG nanoplatform can efficiently trigger cancer cell death and inhibit tumor growth via significantly enhanced ROS production. Therefore, this positive combination therapy strategy has a good application prospect for enhancing antitumor efficacy.

Supplementing a specific synbiotic suppressed the incidence of AOM/DSS-induced colorectal cancer in mice.

In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/ß-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.

A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis.

Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter. Our previous study showed that this 1-kb promoter was active enough to dictate reporter expression faithfully reflecting endogenous CDCA8 expression. Two founder mice carrying the transgene were identified. In vivo imaging and luciferase assays in tissue lysates revealed that CDCA8 promoter was highly activated and drove robust luciferase expression in testes. Subsequently, immunohistochemical and immunofluorescent staining showed that in adult transgenic testes, the expression of luciferase was restricted to a subset of spermatogonia that were located along the basement membrane and positive for the expression of GFRA1, a consensus marker for early undifferentiated spermatogonia. These findings for the first time indicate that the CDCA8 was transcriptionally activated in testis and thus may play a role in adult spermatogenesis. Moreover, the 1-kb CDCA8 promoter could be used for spermatogonia-specific gene expression in vivo and the transgenic lines constructed here could also be used for recovery of spermatogonia from adult testes.