NOP14-mediated ribosome biogenesis is required for mTORC2 activation and predicts rapamycin sensitivity.

The mechanistic target of rapamycin (mTOR) forms two distinct complexes: rapamycin-sensitive mTOR complex 1 (mTORC1) and rapamycin-insensitive mTORC2. mTORC2 primarily regulates cell survival by phosphorylating Akt, though the upstream regulation of mTORC2 remains less well-defined than that of mTORC1. In this study, we show that NOP14, a 40S ribosome biogenesis factor and a target of the mTORC1-S6K axis, plays an essential role in mTORC2 signaling. Knockdown of NOP14 led to mTORC2 inactivation and Akt destabilization. Conversely, overexpression of NOP14 stimulated mTORC2-Akt activation and enhanced cell proliferation. Fractionation and coimmunoprecipitation assays demonstrated that the mTORC2 complex was recruited to the rough endoplasmic reticulum through association with endoplasmic reticulum-bound ribosomes. In vivo, high levels of NOP14 correlated with poor prognosis in multiple cancer types. Notably, cancer cells with NOP14 high expression exhibit increased sensitivity to mTOR inhibitors, because the feedback activation of the PI3K-PDK1-Akt axis by mTORC1 inhibition was compensated by mTORC2 inhibition partly through NOP14 downregulation. In conclusion, our findings reveal a spatial regulation of mTORC2-Akt signaling and identify ribosome biogenesis as a potential biomarker for assessing rapalog response in cancer therapy.

Gastrodin alleviates premature senescence of vascular endothelial cells by enhancing the Nrf2/HO-1 signalling pathway.

Endothelial dysfunction is an independent risk factor for stroke. The dysfunction of endothelial cells (EC) is closely concerned with EC senescence. Gastrodin (GAS) is an organic compound extracted from the dried root mass of the Orchidaceae plant Gastrodiae gastrodiae. It is used clinically to treat diseases such as vertebrobasilar insufficiency, vestibular neuronitis and vertigo. In the present study, we used hydrogen peroxide (H2 O2 )-induced human umbilical vein endothelial cells (HUVECs) to establish an in vitro EC senescence model and to investigate the role and mechanism of GAS in EC senescence. It's found that H2 O2 -treated HUVECs increased the proportion of senescence-associated ß-galactosidase (SA ß-gal) positive cells and the relative protein expression levels of senescence-associated cyclin p16 and p21. In addition, GAS reduced the proportion of SA ß-gal positive cells and the relative protein expression levels of p16 and p21, and increased the proliferation and migration ability of HUVECs. Meanwhile, GAS increased the expression of the anti-oxidative stress protein HO-1 and its nuclear expression level of Nrf2. The anti-senescence effect of GAS was blocked when HO-1 expression was inhibited by SnPPIX. Furthermore, absence of HO-1 abolished the effect of GAS on HUVEC proliferation and migration. In conclusion, GAS ameliorated H2 O2 -induced cellular senescence and enhanced cell proliferation and migration by enhancing Nrf2/HO-1 signalling in HUVECs. These findings of our study expanded the understanding of GAS pharmacology and suggested that GAS may offer a potential therapeutic agent for stroke.

Multiplex assays reveal anti-EBV antibody profile and its implication in detection and diagnosis of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV-based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti-BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b-IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913-0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced-stage than in early-stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1-IgA and BNLF2b-IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%-21.7%, p < .0001) compared with the two-antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression.

miR396b/GRF6 module contributes to salt tolerance in rice.

Salinity, as one of the most challenging environmental factors restraining crop growth and yield, poses a severe threat to global food security. To address the rising food demand, it is urgent to develop crop varieties with enhanced yield and greater salt tolerance by delving into genes associated with salt tolerance and high-yield traits. MiR396b/GRF6 module has previously been demonstrated to increase rice yield by shaping the inflorescence architecture. In this study, we revealed that miR396b/GRF6 module can significantly improve salt tolerance of rice. In comparison with the wild type, the survival rate of MIM396 and OE-GRF6 transgenic lines increased by 48.0% and 74.4%, respectively. Concurrent with the increased salt tolerance, the transgenic plants exhibited reduced H2 O2 accumulation and elevated activities of ROS-scavenging enzymes (CAT, SOD and POD). Furthermore, we identified ZNF9, a negative regulator of rice salt tolerance, as directly binding to the promoter of miR396b to modulate the expression of miR396b/GRF6. Combined transcriptome and ChIP-seq analysis showed that MYB3R serves as the downstream target of miR396b/GRF6 in response to salt tolerance, and overexpression of MYB3R significantly enhanced salt tolerance. In conclusion, this study elucidated the potential mechanism underlying the response of the miR396b/GRF6 network to salt stress in rice. These findings offer a valuable genetic resource for the molecular breeding of high-yield rice varieties endowed with stronger salt tolerance.

Aberrant accumulation of ceramides in mitochondria triggers cell death by inducing autophagy in Arabidopsis.

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.

Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

A fast and efficient liquid chromatography-tandem mass spectrometry method for measuring l- and d-amino acids in the urine of patients with immunoglobulin A nephropathy.

Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC-tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l- and d-amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d-amino acids and 20 l-amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l- and d-amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l-amino acids and lower concentrations of d-amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.

Clinical efficacy of sodium aescinate administration following endovenous laser ablation for varicose veins.

BACKGROUND: Endovenous interventions and minimally invasive procedures are effective in the management of varicose veins. However, they can cause postoperative discomfort. OBJECTIVE: To evaluate the clinical efficacy of sodium aescinate (SA) in improving edema, pain, vein-specific symptoms, and quality of life in patients following endovenous laser ablation (EVLA) for varicose veins. METHODS: In this single-center randomized controlled trial (RCT), patients were allocated into two groups: in Group A, 60 mg SA was administered twice daily for 20 days, and in Group B (control), no venoactive drug was prescribed. The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system for chronic venous disorders was used to assess the varicose veins. The circumferences of the calf and ankle were recorded for evaluating edema. The 10-point Visual Analog Scale (VAS), Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Veins Questionnaire (AVVQ) were used to measure the pain intensity, overall varicose vein severity, and patient's quality of life, respectively. RESULTS: The study included 87 patients (mean age, 59.9 ± 10.7 years; 54 men) with CEAP class C2-C5 varicose veins who underwent EVLA and phlebectomy or foam sclerotherapy. The calf circumference recovered quicker in Group A than in Group B by days 10, 21, and 30 (difference from baseline was 1.04 ± 0.35 vs 2.39 ± 1.15 [p < .001], 0.48 ± 0.42 vs1.73 ± 1.00 [p < .001], and 0.18 ± 0.64 vs 0.82 ± 0.96 [p < .001], respectively). The ankle circumference recovered quicker in Group A than in Group B by days 10 and 21 (the difference from baseline was 1.37 ± 0.52 vs 2.36 ± 0.93 [p < .001] and 0.58 ± 0.60 vs 1.14 ± 0.88 [p = .002], respectively). Pain relief was achieved quicker in Group A than in Group B (0.257 ± 1.097 [p = .0863] vs 0.506 ± 1.250 [p = .0168] by day 21). There were no significant differences in the VCSS and AVVQ scores between both groups. There were no drug-related adverse effects. CONCLUSIONS: SA, in combination with compression therapy, can relieve edema and alleviate pain in patients following EVLA for varicose veins.

Association between phthalates and sleep problems in the U.S. adult females from NHANES 2011-2014.

There is little research on the relationship between phthalates exposure and sleep problems in adult females, with existing studies only assessing the association between exposure to individual phthalates with sleep problems. We aimed to analyse the relationship between phthalates and sleep problems in 1366 US females aged 20 years and older from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) by age stratification. Multivariate logistic regression showed that the fourth quartile of MECPP increased the risk of sleep problems in females aged 20-39 compared with the reference quartile (OR: 1.87, 95% CI: 1.14, 3.08). The WQS index was significantly associated with the sleep problems in females aged 20-39. In the BKMR, a positive overall trend between the mixture and sleep problems in females aged 20-39. In this study, we concluded that phthalates might increase the risk of sleep problems in females aged 20-39.

Ceramides regulate defense response by binding to RbohD in Arabidopsis.

Sphingolipids, a class of bioactive lipids, play a critical role in signal transduction. Ceramides, which are central components of sphingolipid metabolism, are involved in plant development and defense. However, the mechanistic link between ceramides and downstream signaling remains unclear. Here, the mutation of alkaline ceramidase in a ceramide kinase mutant acd5 resulted in spontaneous programmed cell death early in development and was accompanied by ceramide accumulation, while other types of sphingolipids, such as long chain base, glucosylceramide, and glycosyl inositol phosphorylceramide, remained at the same level as the wild-type plants. Analysis of the transcriptome indicated that genes related to the salicylic acid (SA) pathway and oxidative stress pathway were induced dramatically in acer acd5 plants. Comparison of the level of reactive oxygen species (ROS), SA, and ceramides in the wild-type and acer acd5 plants at different developmental stages indicated that the acer acd5 mutant exhibited constitutive activation of SA and ROS signaling, which occurred simultaneously with the alteration of ceramides. Overexpressing NahG in the acer acd5 mutant could completely suppress its cell death and ceramide accumulation, while benzo-(1,2,3)-thiadiazole-7-carbothioc acid S-methyl ester treatment restored its phenotype again. Moreover, we found that the plasma membrane of acer acd5 mutant was the main site of ROS production. Ceramides accumulated in the plasma membrane of acer acd5, directly binding and activating the NADPH oxidase RbohD and promoting hydrogen peroxide generation and SA- or defense-related gene activation. Our data illustrated that ceramides play an essential role in plant defense.

Orosomucoid proteins limit endoplasmic reticulum stress in plants.

Sphingolipids are cell membrane components and signaling molecules that induce endoplasmic reticulum (ER) stress responses, but the underlying mechanism is unknown. Orosomucoid proteins (ORMs) negatively regulate serine palmitoyltransferase activity, thus helping maintain proper sphingolipid levels in humans, yeast, and plants. In this report, we explored the roles of ORMs in regulating ER stress in Arabidopsis thaliana. Loss of ORM1 and ORM2 function caused constitutive activation of the unfolded protein response (UPR), as did treatment with the ceramide synthase inhibitor Fumonisin B1 (FB1) or ceramides. FB1 treatment induced the transcription factor bZIP28 to relocate from the ER membrane to the nucleus. The transcription factor WRKY75 positively regulates the UPR and physically interacted with bZIP28. We also found that the orm mutants showed impaired ER-associated degradation (ERAD), blocking the degradation of misfolded MILDEW RESISTANCE LOCUS-O 12 (MLO-12). ORM1 and ORM2 bind to EMS-MUTAGENIZED BRI1 SUPPRESSOR 7 (EBS7), a plant-specific component of the Arabidopsis ERAD complex, and regulate its stability. These data strongly suggest that ORMs in the ER membrane play vital roles in the UPR and ERAD pathways to prevent ER stress in Arabidopsis. Our results reveal that ORMs coordinate sphingolipid homeostasis with ER quality control and play a role in stress responses.

SUMO and PIAS repress NF-κB activation in a basal chordate.

Small ubiquitin-like modifier (SUMO) regulates various biological processes, including the MyD88/TICAMs-IRAKs-TRAF6-NF-κB pathway, one of the core immune pathways. However, its functions are inconsistent between invertebrates and vertebrates and have rarely been investigated in lower chordates, including amphioxus and fishes. Here, we investigated the SUMOylation gene system in the amphioxus, a living basal chordate. We found that amphioxus has a SUMOylation system that has a complete set of genes and preserves several ancestral traits. We proceeded to study their molecular functions using the mammal cell lines. Both amphioxus SUMO1 and SUMO2 were shown to be able to attach to NF-κB Rel and to inhibit NF-κB activation by 50-75% in a dose-dependent fashion. The inhibition by SUMO2 could be further enhanced by the addition of the SUMO E2 ligase UBC9. In comparison, while human SUMO2 inhibited RelA, human SUMO1 slightly activated RelA. We also showed that, similar to human PIAS1-4, amphioxus PIAS could serve as a SUMO E3 ligase and promote its self-SUMOylation. This suggests that amphioxus PIAS is functionally compatible in human cells. Moreover, we showed that amphioxus PIAS is not only able to inhibit NF-κB activation induced by MyD88, TICAM-like, TRAF6 and IRAK4 but also able to suppress NF-κB Rel completely in the presence of SUMO1/2 in a dose-insensitive manner. This suggests that PIAS could effectively block Rel by promoting Rel SUMOylation. In comparison, in humans, only PIAS3, but not PIAS1/2/4, has been reported to promote NF-κB SUMOylation. Taken together, the findings from amphioxus, together with those from mammals and other species, not only offer insights into the functional volatility of the animal SUMO system, but also shed light on its evolutionary transitions from amphioxus to fish, and ultimately to humans.

Genome-wide identification and characterization of the bHLH gene family and analysis of their potential relevance to chlorophyll metabolism in Raphanus sativus L.

BACKGROUND: Green-fleshed radish (Raphanus sativus L.) is an economically important root vegetable of the Brassicaceae family, and chlorophyll accumulates in its root tissues. It was reported that the basic helix-loop-helix (bHLH) transcription factors play vital roles in the process of chlorophyll metabolism. Nevertheless, a comprehensive study on the bHLH gene family has not been performed in Raphanus sativus L. RESULTS: In this study, a total of 213 Raphanus sativus L. bHLH (RsbHLH) genes were screened in the radish genome, which were grouped into 22 subfamilies. 204 RsbHLH genes were unevenly distributed on nine chromosomes, and nine RsbHLH genes were located on the scaffolds. Gene structure analysis showed that 25 RsbHLH genes were intron-less. Collineation analysis revealed the syntenic orthologous bHLH gene pairs between radish and Arabidopsis thaliana/Brassica rapa/Brassica oleracea. 162 RsbHLH genes were duplicated and retained from the whole genome duplication event, indicating that the whole genome duplication contributed to the expansion of the RsbHLH gene family. RNA-seq results revealed that RsbHLH genes had a variety of expression patterns at five development stages of green-fleshed radish and white-fleshed radish. In addition, the weighted gene co-expression network analysis confirmed four RsbHLH genes closely related to chlorophyll content. CONCLUSIONS: A total of 213 RsbHLH genes were identified, and we systematically analyzed their gene structure, evolutionary and collineation relationships, conserved motifs, gene duplication, cis-regulatory elements and expression patterns. Finally, four bHLH genes closely involved in chlorophyll content were identified, which may be associated with the photosynthesis of the green-fleshed radish. The current study would provide valuable information for further functional exploration of RsbHLH genes, and facilitate clarifying the molecular mechanism underlying photosynthesis process in green-fleshed radish.

Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-ß axis.

Currently, the reported source of extracellular vesicles (EVs) for the treatment of ischemic stroke（IS）is limited to mammals. Moreover, these EVs are restricted to clinical translation by the high cost of cell culture. In this respect, Lactobacillus plantarum culture is advantaged by low cost and high yield. However, it is poorly understood whether Lactobacillus plantarum-derived EVs (LEVs) are applicable for the treatment of IS. Here, our results demonstrated that LEVs reduced apoptosis in ischemic neuron both in vivo and in vitro. As revealed by high-throughput sequencing, miR-101a-3p expression was significantly elevated by LEV treatment in OGD/R-induced neurons, as confirmed in the tMCAO mice treated with LEVs. Mechanistically, c-Fos was directly targeted by miR-101a-3p. In addition, c-Fos determined ischemia-induced neuron apoptosis in vivo and in vitro through the TGF-ß1 pathway, miR-101a-3p inhibition aggravated ischemia-induced neuron apoptosis in vitro and in vivo, and miR-101a-3p overexpression produced the opposite results. Hsa-miR-101-3p was downregulated in the plasma of patients with IS but upregulated in the patients with neurological recovery after rt-PA intravenous thrombolysis. In conclusion, Our results demonstrated for the first time that LEVs might inhibit neuron apoptosis via the miR-101a-3p/c-Fos/TGF-ß axis, and has-miR-101-3p is a potential marker of neurological recovery in IS patients.

Remaining Useful Life Prediction Based on Adaptive SHRINKAGE Processing and Temporal Convolutional Network.

The remaining useful life (RUL) prediction is important for improving the safety, supportability, maintainability, and reliability of modern industrial equipment. The traditional data-driven rolling bearing RUL prediction methods require a substantial amount of prior knowledge to extract degraded features. A large number of recurrent neural networks (RNNs) have been applied to RUL, but their shortcomings of long-term dependence and inability to remember long-term historical information can result in low RUL prediction accuracy. To address this limitation, this paper proposes an RUL prediction method based on adaptive shrinkage processing and a temporal convolutional network (TCN). In the proposed method, instead of performing the feature extraction to preprocess the original data, the multi-channel data are directly used as an input of a prediction network. In addition, an adaptive shrinkage processing sub-network is designed to allocate the parameters of the soft-thresholding function adaptively to reduce noise-related information amount while retaining useful features. Therefore, compared with the existing RUL prediction methods, the proposed method can more accurately describe RUL based on the original historical data. Through experiments on a PHM2012 rolling bearing data set, a XJTU-SY data set and comparison with different methods, the predicted mean absolute error (MAE) is reduced by 52% at most, and the root mean square error (RMSE) is reduced by 64% at most. The experimental results show that the proposed adaptive shrinkage processing method, combined with the TCN model, can predict the RUL accurately and has a high application value.

Quantitative Trait Locus Mapping of Salt Tolerance in Wild Rice Oryza longistaminata.

Salt stress is one of the most severe adverse environments in rice production; increasing salinization is seriously endangering rice production around the world. In this study, a rice backcross inbred line (BIL) population derived from the cross of 9311 and wild rice Oryza longistaminata was employed to identify the favorable genetic loci of O. longistaminata for salt tolerance. A total of 27 quantitative trait loci (QTLs) related to salt tolerance were identified in 140 rice BILs, and 17 QTLs formed seven QTL clusters on different chromosomes, of which 18 QTLs were derived from O. longistaminata, and a QTL for salt injury score (SIS), water content of seedlings (WCS) under salt treatment, and relative water content of seedlings (RWCS) was repeatedly detected and colocalized at the same site on chromosome 2, and a cytochrome P450 86B1 (MH02t0466900) was suggested as the potential candidate gene responsible for the salt tolerance based on sequence and expression analysis. These findings laid the foundation for further improving rice salt tolerance through molecular breeding in the future.

Genome-Wide Identification and Analysis of the Metallothionein Genes in Oryza Genus.

Metallothionein (MT) proteins are low molecular mass, cysteine-rich, and metal-binding proteins that play an important role in maintaining metal homeostasis and stress response. However, the evolutionary relationships and functional differentiation of MT in the Oryza genus remain unclear. Here we identified 53 MT genes from six Oryza genera, including O. sativa ssp. japonica, O. rufipogon, O. sativa ssp. indica, O. nivara, O. glumaepatula, and O. barthii. The MT genes were clustered into four groups based on phylogenetic analysis. MT genes are unevenly distributed on chromosomes; almost half of the MT genes were clustered on chromosome 12, which may result from a fragment duplication containing the MT genes on chromosome 12. Five pairs of segmental duplication events and ten pairs of tandem duplication events were found in the rice MT family. The Ka/Ks values of the fifteen duplicated MT genes indicated that the duplicated MT genes were under a strong negative selection during evolution. Next, combining the promoter activity assay with gene expression analysis revealed different expression patterns of MT genes. In addition, the expression of OsMT genes was induced under different stresses, including NaCl, CdCl2, ABA, and MeJ treatments. Additionally, we found that OsMT genes were mainly located in chloroplasts. These results imply that OsMT genes play different roles in response to these stresses. All results provide important insights into the evolution of the MT gene family in the Oryza genus, and will be helpful to further study the function of MT genes.

Highly Stable Passively Q-Switched Erbium-Doped All-Fiber Laser Based on Niobium Diselenide Saturable Absorber.

A saturable absorber (SA) based on niobium diselenide (NbSe2), which is a layered transition metal dichalcogenide (TMD) in the VB group, is fabricated by the optically driven deposition method, and the related nonlinear optical properties are characterized. The modulation depth, saturable intensity, and nonsaturable loss of the as-prepared NbSe2 nanosheet-based SA are measured to be 16.2%, 0.76 MW/cm2, and 14%, respectively. By using the as-fabricated NbSe2 SA, a highly stable, passively Q-switched, erbium-doped, all-fiber laser is realized. The obtained shortest pulse width is 1.49 µs, with a pulse energy of 48.33 nJ at a center wavelength of 1560.38 nm. As far as we know, this is the shortest pulse duration ever obtained by an NbSe2 SA in a Q-switched fiber laser.

Experimental and Theoretical Study of an Actively Q-Switched Tm:YLF Laser with an Acousto-Optic Modulator.

We report the characteristics of a diode-end-pumped, high-repetition-rate, acoustic-optic (AO) Q-switched Tm:YLF laser operating from 5 kHz to 10 kHz. In the continuous-wave (CW) regime, a maximum average output power of 8.5 W was obtained with a slope efficiency of 30.7%. Under the AO Q-switching regime, a maximum output power of 7.32 W was obtained at a repetition frequency of 5 kHz with a pulse width of 68 ns and a pulse energy of 1.4 mJ, corresponding to a peak power of 21.5 kW. A time-dependent rate equation model is introduced to theoretically analyze the results obtained in the experiment, in which the cross-relaxation phenomenon, upconversion losses and ground-state depletion are taken into account. Additionally, the evolution processes of population inversion density and intracavity photon number density with time are also presented. The theoretical results well predict the dependence of laser output characteristics of Tm:YLF crystal on the incident pump powers.

Pharmacokinetics of gallic acid and protocatechuic acid in humans after dosing with Relinqing (RLQ) and the potential for RLQ-perpetrated drug-drug interactions on organic anion transporter (OAT) 1/3.

CONTEXT: Relinqing granules (RLQ) are being used alone or in combination with antibacterial drugs to treat urological disorders. OBJECTIVE: This study investigates the pharmacokinetics of RLQ in humans and the potential for RLQ-perpetrated interactions on transporters. MATERIALS AND METHODS: Twelve healthy subjects (six women and six men) participated to compare single- and multiple-dose pharmacokinetics of RLQ. In the single-dose study, all 12 subjects received 8 g of RLQ orally. After a 7-d washout period, the subjects received 8 g of RLQ for seven consecutive days (t.i.d.) and then a single dose. Gallic acid (GA) and protocatechuic acid (PCA) in plasma and urine samples were analysed using LC-MS/MS. The transfected cells were used to study the inhibitory effect of GA (50-5000 µg/L) and PCA (10-1000 µg/L) on transporters OAT1, OAT3, OCT2, OATP1B1, P-gp and BCRP. RESULTS: GA and PCA were absorbed into the blood within 1 h after administration and rapidly eliminated with a half-life of less than 2 h. The mean peak concentrations of GA (102 and 176 µg/L) and PCA (4.54 and 7.58 µg/L) were lower in males than females, respectively. The 24 h urine recovery rates of GA and PCA were about 10% and 5%, respectively. The steady-state was reached in 7 d without accumulation. GA was a potent inhibitor of OAT1 (IC50 = 3.73 µM) and OAT3 (IC50 = 29.41 µM), but not OCT2, OATP1B1, P-gp or BCRP. DISCUSSION AND CONCLUSIONS: GA and PCA are recommended as PK-markers in RLQ-related pharmacokinetic and drug interaction studies. We should pay more attention to the potential for RLQ-perpetrated interactions on transporters.