JASMONATE ZIM-domain protein 3 regulates photomorphogenesis and thermomorphogenesis through inhibiting PIF4 in Arabidopsis.

Light and temperature are 2 major environmental factors that affect the growth and development of plants during their life cycle. Plants have evolved complex mechanisms to adapt to varying external environments. Here, we show that JASMONATE ZIM-domain protein 3 (JAZ3), a jasmonic acid signaling component, acts as a factor to integrate light and temperature in regulating seedling morphogenesis. JAZ3 overexpression transgenic lines display short hypocotyls under red, far-red, and blue light and warm temperature (28 °C) conditions compared to the wild type in Arabidopsis (Arabidopsis thaliana). We show that JAZ3 interacts with the transcription factor PHYTOCHROME-INTERACTING FACTOR4 (PIF4). Interestingly, JAZ3 spontaneously undergoes liquid-liquid phase separation (LLPS) in vitro and in vivo and promotes LLPS formation of PIF4. Moreover, transcriptomic analyses indicate that JAZ3 regulates the expression of genes involved in many biological processes, such as response to auxin, auxin-activated signaling pathway, regulation of growth, and response to red light. Finally, JAZ3 inhibits the transcriptional activation activity and binding ability of PIF4. Collectively, our study reveals a function and molecular mechanism of JAZ3 in regulating plant growth in response to environmental factors such as light and temperature.

The RNA helicase UAP56 and the E3 ubiquitin ligase COP1 coordinately regulate alternative splicing to repress photomorphogenesis in Arabidopsis.

Light is a key environmental signal that regulates plant growth and development. While posttranscriptional regulatory mechanisms of gene expression include alternative splicing (AS) of pre-messenger RNA (mRNA) in both plants and animals, how light signaling affects AS in plants is largely unknown. Here, we identify DExD/H RNA helicase U2AF65-associated protein (UAP56) as a negative regulator of photomorphogenesis in Arabidopsis thaliana. UAP56 is encoded by the homologs UAP56a and UAP56b. Knockdown of UAP56 led to enhanced photomorphogenic responses and diverse developmental defects during vegetative and reproductive growth. UAP56 physically interacts with the central light signaling repressor constitutive photomorphogenic 1 (COP1) and U2AF65. Global transcriptome analysis revealed that UAP56 and COP1 co-regulate the transcription of a subset of genes. Furthermore, deep RNA-sequencing analysis showed that UAP56 and COP1 control pre-mRNA AS in both overlapping and distinct manners. Ribonucleic acid immunoprecipitation assays showed that UAP56 and COP1 bind to common small nuclear RNAs and mRNAs of downstream targets. Our study reveals that both UAP56 and COP1 function as splicing factors that coordinately regulate AS during light-regulated plant growth and development.

PHYTOCHROME-INTERACTING FACTOR-LIKE14 and SLENDER RICE1 Interaction Controls Seedling Growth under Salt Stress.

Early seedling development and emergence from the soil, which are critical for plant growth and important for crop production, are controlled by internal factors, such as phytohormones, and external factors, such as light and salt. However, little is known about how light and salt signals are integrated with endogenous cues in controlling plant physiological processes. Here, we show that overexpression of rice (Oryza sativa) PHYTOCHROME-INTERACTING FACTOR-LIKE14 (OsPIL14) or loss of function of the DELLA protein SLENDER RICE1 (SLR1) promotes mesocotyl and root growth, specifically in the dark and under salt stress. Furthermore, salt induces OsPIL14 turnover but enhances SLR1 accumulation. OsPIL14 directly binds to the promoter of cell elongation-related genes and regulates their expression. SLR1 physically interacts with OsPIL14 and negatively regulates its function. Our study reveals a mechanism by which the OsPIL14-SLR1 transcriptional module integrates light and gibberellin signals to fine-tune seedling growth under salt stress, enhancing understanding about how crops adapt to saline environments.

A pentatricopeptide repeat protein DUA1 interacts with sigma factor 1 to regulate chloroplast gene expression in Rice.

Chloroplast gene expression is controlled by both plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA polymerase and is crucial for chloroplast development and photosynthesis. Environmental factors such as light and temperature can influence transcription in chloroplasts. In this study, we showed that mutation in DUA1, which encodes a pentatricopeptide repeat (PPR) protein in rice (Oryza sativa), led to deficiency in chloroplast development and chlorophyll biosynthesis, impaired photosystems, and reduced expression of PEP-dependent transcripts at low temperature especially under low-light conditions. Furthermore, we demonstrated that sigma factor OsSIG1 interacted with DUA1 in vitro and in vivo. Moreover, the levels of chlorophyll and PEP-dependent gene expression were significantly decreased in the Ossig1 mutants at low-temperature and low-light conditions. Our study reveals that the PPR protein DUA1 plays an important role in regulating PEP-mediated chloroplast gene expression through interacting with OsSIG1, thus modulates chloroplast development in response to environmental signals.

Electromagnetic navigation-assisted percutaneous endoscopic foraminoplasty and discectomy for lumbar disc herniation: technical note and preliminary results.

BACKGROUND: The aim of the present study was to report a new technique for electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy and to evaluate the efficacy of this technology in the treatment of lumbar disc herniation (LDH). METHODS: This is a retrospective study. Seventeen patients who underwent electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy in our department from September to November 2018 were included in the study. Patients' hospital charts, magnetic resonance imaging results, surgical data and follow-up records were reviewed. Outcomes were assessed by visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and postoperative complications. RESULTS: The median follow-up time was 20.64 months (range, 19-21 months). The average operating time was 52.94±12.88 min (range, 35-78 min), including the working tube introduction time (13.59±2.89 min), decompression time (39.35±13.61 min), and the fluoroscopic time (3.65±2.52 min). Postoperative back VAS, leg VAS, and ODI were significantly improved compared with pre-operation, respectively (P<0.01). The overall excellent and good rate of these seventeen patients was 94%. There were no significant complications related to the operation. CONCLUSIONS: Electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy is a safe and effective method for treating LDH and this method has the advantage of short operative time and fluoroscopic times.

Percutaneous Full-Endoscopic Lumbar Foraminoplasty and Decompression by Using a Visualization Reamer for Lumbar Lateral Recess and Foraminal Stenosis in Elderly Patients.

BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.

Systematic acute and subchronic toxicity evaluation of polysaccharide-protein complex-functionalized selenium nanoparticles with anticancer potency.

Functionalized selenium nanoparticles (SeNPs) have demonstrated potential for applications in cancer chemotherapy, radio-sensitization, nephroprotection and drug delivery. However, their clinical application requires further systemic safety evaluation. Therefore, in this study, we examine the systematic acute and subchronic toxicity of polysaccharide-protein complex coated SeNPs (PTR-SeNPs). These particles exhibited a low oral acute toxicity (higher LD50) in SPF grade ICR mice and SD rats, and the evaluation of subchronic toxicity demonstrated that the no observed effect level (NOAEL) of the PTR-SeNPs was less than 200 µg Se per kg BW per day, which is about 30 times the tolerable upper intake levels of Se in the human body. In addition, we also found that, under a safe dose (0.75-7.5 mg kg-1), the oral administration of PTR-SeNPs dramatically inhibited the growth of cancer in a tumor-bearing nude mouse model, and the results of the histological analysis indicated that PTR-SeNPs did not significantly damage the major organs, including the liver, spleen, heart, kidneys and lungs. Moreover, the induction of caspase activation and mitochondrial dysfunction was the major anticancer action mechanism of PTR-SeNPs. Taken together, the results of this study provide a simple approach for the facile and large-scale manufacturing of SeNPs with reduced toxicity and enhanced anticancer activity through the regulation of the surface properties of SeNPs. Furthermore, this study generates evidence for the future exploration and translational application of these materials through oral administration in nanomedicine and nutritional sciences.

Designing multifunctionalized selenium nanoparticles to reverse oxidative stress-induced spinal cord injury by attenuating ROS overproduction and mitochondria dysfunction.

Spinal cord injury (SCI) remains a challenging clinical problem worldwide, due to the lack of effective drugs for precise treatment. Among the complex pathophysiological events following SCI, reactive oxygen species (ROS) overproduction plays a particularly significant role. As therapeutic agents for neurological diseases, tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) have been widely used in the clinical treatment of SCI. Our previous studies have reported that functionalized selenium nanoparticles (SeNPs) exhibit excellent antioxidant activity against oxidative stress-related diseases. Therefore, in this study, novel multifunctionalized SeNPs decorated with polysaccharide-protein complex (PTW)/PG-6 peptide and loaded with TMP/GM1 were rationally designed and synthesized, which exhibited a satisfactory size distribution and superior stability. Furthermore, the protective effects of SeNPs@GM1/TMP on PC12 cells against tert-butyl hydroperoxide (t-BOOH)-induced cytotoxicity and the underlying mechanisms were also explored. Flow cytometric analysis indicated that SeNPs@GM1/TMP showed strongly protective effects against t-BOOH-induced G2/M phase arrest and apoptosis. Moreover, we found that SeNPs@GM1/TMP could attenuate ROS overproduction to prevent mitochondria dysfunction via inhibiting the activation of p53 and MAPK pathways. Effects of SeNPs@GM1/TMP on functional recovery after SCI were evaluated by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. The results of hematoxylin-eosin staining and Nissl staining also showed that SeNPs@GM1/TMP provided a neuroprotective effect in SCI rats. This finding suggests that SeNPs@GM1/TMP could be further developed as a promising nanomedicine for efficient SCI treatment.

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

Effects of ginsenoside Rg1-loaded alginate-chitosan microspheres on human bone marrow stromal cells.

The ginsenoside Rg1 is the most abundant compound in ginseng. Recent studies showed that Rg1 had neuroprotective effects on neuronal cells. The present study was to prepare Rg1-loaded alginate-chitosan microspheres and research the effects of microspheres on human bone marrow (BM) stromal cells (hBMSC). The alginate-chitosan microspheres were prepared by mechanical emulsification technique in combination with ion (Ca2+) and chitosan solidification. Subsequently, the microspheres were employed to load Rg1 ginseng extracts. The microspheres had a smooth surface and were spherical in shape. The average diameter of the microspheres was 3.95 µm. The loading efficiency was approximately 2.12%. The purity of isolated hBMSC was over 98.8%. Rg1-loaded microspheres could promote hBMSC proliferation and differentiation. Meanwhile, Rg1-loaded microspheres could also suppress hBMSC apoptosis induced by hypoxia-reoxygenation. In conclusion, these loaded microspheres may be used in the research of neuroprotective effects of Rg1.

X-ray-responsive selenium nanoparticles for enhanced cancer chemo-radiotherapy.

Resistance of cancer to radiotherapy and/or chemotherapy is one of the important reasons of clinical treatment failure and recurrence. Chemoradiation is an optional method to over-coming of radioresistance and chemoresistance. Selenium nanoparticles (SeNPs) with special chemical and physical properties, has been identified as a novel nanocarrier and therapy agent with broad-spectrum anticancer activities due to generate ROS in cells. Herein, X-ray responsive selenium nanoparticles were facilely fabricated by using PEG as surface decorator and template. This nanosystem (PEG-SeNPs) demonstrated X-ray responsive property that was attributed to its amorphous characteristic. Interestingly, the nanosystem demonstrated significant radiosensitization effects with X-ray. Specifically, co-treatment of cancer cells with PEG-SeNPs and X-ray significantly and synergistically enhanced the cells growth inhibition through induction of cell apoptosis, as evidenced by DNA fragmentation and activation of caspase-3. In the cell model, we found that internalized nanoparticles could degrade upon X-ray exposure, which further confirm the X-ray responsive property of the nanoparticles. Moreover, the nanosystem could significantly induced intracellular ROS generation in a time-dependent manner, which peaked at about 40min and gradually decreased thereafter. As a results, ROS overproduction led to mitochondria fragmentation and the cell apoptosis. Taken together, this study provides a novel strategy for rational design and facile synthesis of chemo-radio therapeutic radiosensitization nanomaterials.

Mitochondrial fragmentation is an important cellular event induced by ruthenium(II) polypyridyl complexes in osteosarcoma cells.

A series of ruthenium(II) polypyridyl complexes were synthesized and evaluated for their in vitro anticancer activities. The results showed that ruthenium polypyridyl complexes, especially [Ru(bpy)2 (p-tFPIP)](2+) (2 a; bpy=bipyridine, tFPIP=2-(2-trifluoromethane phenyl)imidazole[4,5-f][1,10]phenanthroline), exhibited novel anticancer activity against human cancer cell lines, but with less toxicity to a human normal cell line. The results of flow cytometry and caspase activities analysis indicated that the 2 a-induced growth inhibition against MG-63 osteosarcoma cells was mainly caused by mitochondria-mediated apoptosis. DNA fragmentation and nuclear condensation as detected by TUNEL-DAPI co-staining further confirmed 2 a-induced apoptotic cell death. Further, fluorescence imaging revealed that ruthenium(II) polypyridyl complexes could target mitochondria to induce mitochondrial fragmentation, accompanied by depletion of mitochondrial membrane potential. Taken together, these findings suggest a potential application of theses ruthenium(II) complexes in the treatment of cancers.