Noralashinols D-F, New Norlignans from Syringa pinnatifolia and its Anti-inflammation in BV2 Cells.

Four new norlignans, noralashinols D-F (1a/b-3), and two known analogues (4 and 5) were isolated from the peeled stems of Syringa pinnatifolia Hemsl. The structures were elucidated by analysis of spectroscopic data, such as IR, HR-ESI-MS, 1D and 2D NMR, and ECD. All compounds were evaluated for anti-inflammatory activities against NO production induced by LPS in BV2 microglia cells. Compounds 1b and 2 exhibited moderate activities with IC50 values of 32.39 ± 9.1 and 47.83 ± 10.44 µM, respectively, compared with positive control indomethacin (IC50 = 21.62 µM). It is worth to note that 1, 3, and 4 have a distinctive woody fragrance.

Bacillus velezensis HN-2: a potent antiviral agent against pepper veinal mottle virus.

Background: Pepper veinal mottle virus (PVMV) belongs to the genus Potyvirus within the family Potyviridae and is a major threat to pepper production, causing reduction in yield and fruit quality; however, efficient pesticides and chemical treatments for plant protection against viral infections are lacking. Hence, there is a critical need to discover highly active and environment-friendly antiviral agents derived from natural sources. Bacillus spp. are widely utilized as biocontrol agents to manage fungal, bacterial, and viral plant diseases. Particularly, Bacillus velezensis HN-2 exhibits a strong antibiotic activity against plant pathogens and can also induce plant resistance. Methods: The experimental subjects employed in this study were Bacillus velezensis HN-2, benzothiadiazole, and dufulin, aiming to evaluate their impact on antioxidant activity, levels of reactive oxygen species, activity of defense enzymes, and expression of defense-related genes in Nicotiana benthamiana. Furthermore, the colonization ability of Bacillus velezensis HN-2 in Capsicum chinense was investigated. Results: The results of bioassays revealed the robust colonization capability of Bacillus velezensis HN-2, particularly in intercellular spaces, leading to delayed infection and enhanced protection against PVMV through multiple plant defense mechanisms, thereby promoting plant growth. Furthermore, Bacillus velezensis HN-2 increased the activities of antioxidant enzymes, thereby mitigating the PVMV-induced ROS production in Nicotiana benthamiana. Moreover, the application of Bacillus velezensis HN-2 at 5 dpi significantly increased the expression of JA-responsive genes, whereas the expression of salicylic acid-responsive genes remained unchanged, implying the activation of the JA signaling pathway as a crucial mechanism underlying Bacillus velezensis HN-2-induced anti-PVMV activity. Immunoblot analysis revealed that HN-2 treatment delayed PVMV infection at 15 dpi, further highlighting its role in inducing plant resistance and promoting growth and development. Conclusions: These findings underscore the potential of Bacillus velezensis HN-2 for field application in managing viral plant diseases effectively.

Release of dissolved organic matter from wetland plants and its interaction with polycyclic aromatic hydrocarbons.

Dissolved organic matter (DOM) derived from wetland plants played a critical role in CWs pollutant migration. This study investigated the character and release pattern of DOM derived from two wetland plants, Phragmites australis and Cladophora sp., and the interaction between DOM with phenanthrene (PHE), benzo(a)pyrene (Bap), and benzo [k]fluoranthene (BkF) under different physical conditions were also studied using spectroscopic techniques. DOM release was related to plant species and withering stage. Humic acid (HA)-like fractions (C3 and C5) were dominated in P. australis (52%) and completely withered Cladophora sp. groups (55%), while protein-like fractions (C1 and C2) dominated in early withered Cladophora sp. groups (52%). Due to the cell and tissue structure difference among plants and their withering stage, DOM derived from early withered P. australis revealed a two-stage slow-fast phase, while other groups were linearly released (R2 0.87207-0.97091). A strong correlation existed between HA-like fractions and water quality index, reflecting the critical influence of plant decay in CWs operation performance. The analysis with Stern-Volmer equation indicated that plant-based DOM interacted with PAHs to form ground state complexes with possible involvement of π-π interaction, hydrogen bonding and cation bridging effect. Aromatic, molecular weight, and hydrophilicity of both DOM and PAHs affected their binding with the interaction capability in the order of BKF > Bap > PHE and C3 > C5 > C2 > C1 > C4. Besides, alkaline environment and high DO condition was highly unsuitable for the combination. Scientific management and appropriate operating condition were important in optimizing operation performance and controlling pollutant migration in CWs.

Identification of GRIN2D as a novel therapeutic target in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a dismal prognosis, and despite significant advances in our understanding of its genetic drivers, like KRAS, TP53, CDKN2A, and SMAD4, effective therapies remain limited. Here, we identified a new therapeutic target GRIN2D and then explored its functions and mechanisms in PDAC progression. METHODS: We performed a genome-wide RNAi screen in a PDAC xenograft model and identified GRIN2D, which encodes the GluN2D subunit of N-methyl-D-aspartate receptors (NMDARs), as a potential oncogene. Western blot, immunohistochemistry, and analysis on Gene Expression Omnibus were used for detecting the expression of GRIN2D in PDAC. Cellular experiments were conducted for exploring the functions of GRIN2D in vitro while subcutaneous and orthotopic injections were used in in vivo study. To clarify the mechanism, we used RNA sequencing and cellular experiments to identify the related signaling pathway. Cellular assays, RT-qPCR, and western blot helped identify the impacts of the NMDAR antagonist memantine. RESULTS: We demonstrated that GRIN2D was highly expressed in PDAC cells, and further promoted oncogenic functions. Mechanistically, transcriptome profiling identified GRIN2D-regulated genes in PDAC cells. We found that GRIN2D promoted PDAC progression by activating the p38 MAPK signaling pathway and transcription factor CREB, which in turn promoted the expression of HMGA2 and IL20RB. The upregulated GRIN2D could effectively promote tumor growth and liver metastasis in PDAC. We also investigated the therapeutic potential of NMDAR antagonism in PDAC and found that memantine reduced the expression of GRIN2D and inhibited PDAC progression. CONCLUSION: Our results suggested that NMDA receptor GRIN2D plays important oncogenic roles in PDAC and represents a novel therapeutic target.

Combined use of CA125, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for the diagnosis of borderline and malignant epithelial ovarian tumors.

BACKGROUND: The mortality rate of ovarian cancer ranks first among three common gynecological malignant tumors due to insidious onset and lack of effective early diagnosis methods. Borderline epithelial ovarian tumor (BEOT) is a type of low malignant potential tumor that is typically associated with better outcomes than ovarian cancer. However, BEOTs are easily confused with benign and malignant epithelial ovarian tumors (EOTs) due to similar clinical symptoms and lack of specific tumor biomarkers and imaging examinations. Notably, a small subset of BEOTs will transform into low-grade serous ovarian carcinoma with a poor prognosis. Therefore, searching for potential biomarkers that can be easily obtained and accurately identify malignant epithelial ovarian tumors (MEOTs) as well as BEOTs is essential for the clinician. Cancer antigen 125 (CA125) is a commonly used biomarker for the diagnosis of EOTs in the preoperative scenario but has low sensitivity and specificity. Nowadays, inflammatory biomarkers including inflammatory cell counts and derived ratios such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been proved to be associated with tumor progression and poor prognosis, and were considered to be the most economically potential surrogate biomarkers for various malignancies. The purpose of this study was to find appropriate combinations of inflammatory and tumor biomarkers to improve the diagnostic efficiency of EOTs, especially the BEOTs. RESULTS: CA125, NLR and PLR increased steadily among benign, borderline and malignant EOTs and tended to be higher in advanced (stage III-IV) and lymph node metastasis MEOT groups than in early stage (stage I-II) and non-lymph node metastasis MEOT groups. CA125, NLR and PLR could be used separately in the differentiation of EOTs but could not take into account both sensitivity and specificity. The combined use of CA125, NLR and PLR was evaluated to be more efficient, especially in the identification of BEOTs, with both high sensitivity and high specificity. CONCLUSIONS: The levels of CA125, NLR and PLR were closely related to the nature of EOTs and malignant progression of MEOTs. The combination of CA125, NLR and PLR was more accurate in identifying the nature of EOTs than either alone or double combination, especially for BEOTs.

Design and experiment of a 3-DoF master device with a 2-DoF parallel mechanism for flexible ureteroscopy.

BACKGROUND: Traditional commercial master devices and specialied serial master devices meet insufficient workspace, low intuitiveness, low stiffness, and poor accuracy during master-slave mapping for robot-assisted flexible ureteroscopy (FURS). METHODS: This paper presents a 3-DoF master device for FURS. A 2-DoF parallel mechanism was designed and utilised in the master device for higher stiffness based on requirements analysis. A Back Propagation Neural Network was built for the forward kinematics of the parallel mechanism during master-slave mapping. Analysis of mechanical characteristics was carried out for the usability of the master device. A contrast experiment on the phantom was conducted to evaluate the performance between the proposed master device and a previous one. RESULTS: The completion time for each trial of the proposed master devices is shorter than that of the previous master serial device. Meanwhile, the proposed device provides a more comfortable operating style than the previous one. CONCLUSIONS: The proposed 3-DoF configuration for the master device is with more intuitive performance. A better comfort level indicates its usability in clinical applications.

Overexpression of Myrothamnus flabellifolia MfWRKY41 confers drought and salinity tolerance by enhancing root system and antioxidation ability in Arabidopsis.

Myrothamnus flabellifolia is the only woody resurrection plant discovered so far and could recover from extreme desiccation condition. However, few genes related to its strong drought tolerance have been characterized, and the underlying molecular mechanisms remains mysterious. Members of WRKY transcription factor family are effective in regulating abiotic stress responses or tolerance in various plants. An early dehydration-induced gene encoding a WRKY transcription factor namely MfWRKY41 was isolated from M. flabellifolia, which is homologous to AtWRKY41 of Arabidopsis. It contains a typical WRKY domain and zinc finger motif, and is located in the nucleus. Comparing to wild type, the four transgenic lines overexpressing MfWRKY41 showed better growth performance under drought and salt treatments, and exhibited higher chlorophyll content, lower water loss rate and stomatal aperture and better osmotic adjustment capacity. These results indicated that MfWRKY41 of M. flabellifolia positively regulates drought as well as salinity responses. Interestingly, the root system architecture, including lateral root number and primary root length, of the transgenic lines was enhanced by MfWRKY41 under both normal and stressful conditions, and the antioxidation ability was also significantly improved. Therefore, MfWRKY41 may have potential application values in genetic improvement of plant tolerance to drought and salinity stresses. The molecular mechanism involving in the regulatory roles of MfWRKY41 is worthy being explored in the future.

Heterologous Expression of MfWRKY7 of Resurrection Plant Myrothamnus flabellifolia Enhances Salt and Drought Tolerance in Arabidopsis.

Drought and salinity have become major environmental problems that affect the production of agriculture, forestry and horticulture. The identification of stress-tolerant genes from plants adaptive to harsh environments might be a feasible strategy for plant genetic improvement to address the challenges brought by global climate changes. In this study, a dehydration-upregulated gene MfWRKY7 of resurrection Plant Myrothamnusflabellifolia, encoding a group IId WRKY transcription factor, was cloned and characterized. The overexpression of MfWRKY7 in Arabidopsis increased root length and tolerance to drought and NaCl at both seedling and adult stages. Further investigation indicated that MfWRKY7 transgenic plants had higher contents of chlorophyll, proline, soluble protein, and soluble sugar but a lower water loss rate and malondialdehyde content compared with wild-type plants under both drought and salinity stresses. Moreover, the higher activities of antioxidant enzymes and lower accumulation of O2- and H2O2 in MfWRKY7 transgenic plants were also found, indicating enhanced antioxidation capacity by MfWRKY7. These findings showed that MfWRKY7 may function in positive regulation of responses to drought and salinity stresses, and therefore, it has potential application value in genetic improvement of plant tolerance to abiotic stress.

A WRKY Protein, MfWRKY40, of Resurrection Plant Myrothamnus flabellifolia Plays a Positive Role in Regulating Tolerance to Drought and Salinity Stresses of Arabidopsis.

WRKY transcription factors (TFs), one of the largest transcription factor families in plants, play an important role in abiotic stress responses. The resurrection plant, Myrothamnus flabellifolia, has a strong tolerance to dehydration, but only a few WRKY proteins related to abiotic stress response have been identified and functionally characterized in M. flabellifolia. In this study, we identified an early dehydration-induced gene, MfWRKY40, of M. flabellifolia. The deduced MfWRKY40 protein has a conserved WRKY motif but lacks a typical zinc finger motif in the WRKY domain and is localized in the nucleus. To investigate its potential roles in abiotic stresses, we overexpressed MfWRKY40 in Arabidopsis and found that transgenic lines exhibited better tolerance to both drought and salt stresses. Further detailed analysis indicated that MfWRKY40 promoted primary root length elongation and reduced water loss rate and stomata aperture (width/length) under stress, which may provide Arabidopsis the better water uptake and retention abilities. MfWRKY40 also facilitated osmotic adjustment under drought and salt stresses by accumulating more osmolytes, such as proline, soluble sugar, and soluble protein. Additionally, the antioxidation ability of transgenic lines was also significantly enhanced, represented by higher chlorophyll content, less malondialdehyde and reactive oxygen species accumulations, as well as higher antioxidation enzyme activities. All these results indicated that MfWRKY40 might positively regulate tolerance to drought and salinity stresses. Further investigation on the relationship of the missing zinc finger motif of MfWRKY40 and its regulatory role is necessary to obtain a better understanding of the mechanism underlying the excellent drought tolerance of M. flabellifolia.

The establishment of CDK9/RNA PolII/H3K4me3/DNA methylation feedback promotes HOTAIR expression by RNA elongation enhancement in cancer.

Long non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles. Importantly, since HOTAIR heavily contributes to cancer progression by promoting tumor growth and metastasis, HOTAIR becomes a potential target for cancer therapy. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we performed a pan-cancer analysis using more than 4,200 samples and found that intragenic exon CpG island (Ex-CGI) was hypermethylated and was positively correlated to HOTAIR expression. Also, we revealed that Ex-CGI methylation promotes HOTAIR expression through enhancing the transcription elongation process. Furthermore, we linked up the aberrant intragenic tri-methylation on H3 at lysine 4 (H3K4me3) and Ex-CGI DNA methylation in promoting transcription elongation of HOTAIR. Targeting the oncogenic CDK7-CDK9-H3K4me3 axis downregulated HOTAIR expression and inhibited cell growth in many cancers. To our knowledge, this is the first time that a positive feedback loop that involved CDK9-mediated phosphorylation of RNA Polymerase II Serine 2 (RNA PolII Ser2), H3K4me3, and intragenic DNA methylation, which induced robust transcriptional elongation and heavily contributed to the upregulation of oncogenic lncRNA in cancer has been demonstrated. Targeting the oncogenic CDK7-CDK9-H3K4me3 axis could be a novel therapy in many cancers through inhibiting the HOTAIR expression.

Insights into crucial odourants dominating the characteristic flavour of citrus-white teas prepared from citrus reticulata Blanco 'Chachiensis' and Camellia sinensis 'Fudingdabai'.

Citrus-white teas (CWs), which possess a balanced flavour of tea and citrus, are becoming more popular worldwide; however, their characteristic flavour and odourants received limited research. Volatile components of two types of CWs prepared from Citrus reticulata Blanco 'Chachiensis' and Camellia sinensis 'Fudingdabai' were comprehensively investigated using a combination of stir bar sorptive extraction and gas chromatography-mass spectrometry (GC-MS). Ninety-nine crucial odourants in the CWs were quantified by applying GC-olfactometry/MS, significant differences were compared, and their odour activity values (OAVs) were calculated. Twenty-two odourants (in total 2628.09 and 1131.18 mg/kg respectively) were further confirmed as traditional CW (CW-A) and innovated CW (CW-B) characteristic flavour crucial contributors which all possessed > 1 OAVs, particularly limonene (72919 in CW-A) and trans-ß-ionone (138953 in CW-B). The unravelling of CWs aroma composition will greatly expanding our understanding of tea aroma chemistry and the potential aroma interactions will offer insights into tea blending technologies.

Hypolipidaemic and antioxidant effects of various Chinese dark tea extracts obtained from the same raw material and their main chemical components.

In order to investigate the hypolipidaemic and antioxidant effects of various dark teas produced from different post-fermentation using the same raw material, a hyperlipidaemia zebrafish model combined with binding bile salts assay and antioxidant assays were performed in this study. Results showed that the hypolipidaemic effect of dark tea extracts increased significantly (p < 0.05) while the antioxidant ability decreased sharply compared with raw material. Particularly, Liupao tea (50%) and Pu-erh tea (48%) showed promising hypolipidaemic potential; however, the antioxidant capacity of Pu-erh tea decreased (31-49%) most dramatically. Besides, the levels of total polyphenols and catechins decreased sharply, but theabrownin, gallic acid, and caffeine increased significantly after post-fermentation. Moreover, the potential mechanisms of regulating hyperlipidaemia by dark tea extracts were discussed. These results suggest that microbial fermentation significantly affects the bioactivity of dark teas, and provide theoretical basis for processing and improving of dark tea products for hyperlipidaemia therapy.

Assessment of the contribution of chiral odorants to aroma property of baked green teas using an efficient sequential stir bar sorptive extraction approach.

Chiral volatile compounds are known to be distributed in teas at various enantiomeric ratios. However, the performance of each enantiomer, including aroma characteristics, aroma intensities, and contribution to the overall flavor of tea, is still unclear. In this study, aroma characteristics and intensities of 38 volatile enantiomers in standards and baked green teas with chestnut-like aroma and clean aroma were evaluated by an efficient sequential headspace-stir bar sorptive extraction (seq-HS-SBSE) approach combined with the enantioselective gas chromatography-olfactometry/mass spectrometry (Es-GC-O/MS) technique. Moreover, aroma recombination results for the two types of baked green teas using 14 chiral odorants and four achiral odorants indicated that the combinations of the detected odorants mainly contributed to the "floral", "sweet", and "chestnut-like" aromas. R-Linalool simultaneously enhanced the "floral", "sweet", and "chestnut-like" aromas; R-limonene mainly contributed to the "sweet" and "clean" aromas; and S-α-terpineol promoted the "sweet" and "floral" aromas of baked green tea.

Integrated proteomic and metabolomic analyses reveal the importance of aroma precursor accumulation and storage in methyl jasmonate-primed tea leaves.

In response to preharvest priming with exogenous methyl jasmonate (MeJA), tea plants adjust their physiological behavior at the molecular level. The whole-organism reconfiguration of aroma formation from the precursor to storage is poorly understood. In this study, we performed iTRAQ proteomic analysis and identified 337, 246, and 413 differentially expressed proteins in tea leaves primed with MeJA for 12 h, 24 h, and 48 h, respectively. Furthermore, a total of 266 nonvolatile and 100 volatile differential metabolites were identified by utilizing MS-based metabolomics. A novel approach that incorporated the integration of extended self-organizing map-based dimensionality was applied. The vivid time-scale changes tracing physiological responses in MeJA-primed tea leaves are marked in these maps. Jasmonates responded quickly to the activation of the jasmonic acid pathway in tea leaves, while hydroxyl and glycosyl jasmonates were biosynthesized simultaneously on a massive scale to compensate for the exhausted defense. The levels of α-linolenic acid, geranyl diphosphate, farnesyl diphosphate, geranylgeranyl diphosphate, and phenylalanine, which are crucial aroma precursors, were found to be significantly changed in MeJA-primed tea leaves. Green leaf volatiles, volatile terpenoids, and volatile phenylpropanoids/benzenoids were spontaneously biosynthesized from responding precursors and subsequently converted to their corresponding glycosidic forms, which can be stably stored in tea leaves. This study elucidated the physiological response of tea leaves primed with exogenous methyl jasmonate and revealed the molecular basis of source and sink changes on tea aroma biosynthesis and catabolism in response to exogenous stimuli. The results significantly enhance our comprehensive understanding of tea plant responses to exogenous treatment and will lead to the development of promising biotechnologies to improve fresh tea leaf quality.

Promoting Rural Tourism in Inner Mongolia: Attributes, Satisfaction, and Behaviors among Sustainable Tourists.

With the growth of rural tourism in China, this study aims to determine the destination attributes, tourism satisfaction, and intention of revisiting Inner Mongolia. This study also investigated the mean comparison of tourist satisfaction and revisit intention across domestic tourists' demographic characteristics. Structural analysis revealed that destination attributes have a positive influence on satisfaction and revisit intention. In addition, the result of the mean difference test showed that satisfaction is significantly different between male and female tourists, and revisit intention significantly varies across the season. Our findings have an excellent directive significance to bring forward rural tourism in Inner Mongolia.

Impact of Various Microbial-Fermented Methods on the Chemical Profile of Dark Tea Using a Single Raw Tea Material.

In the present study, we produced Pu-erh, Liubao, Qingzhuan, and Fuzhuan teas using a single raw tea material and applied widely targeted metabolomics to study the impact of various microbial-fermented methods on the chemical profile of dark tea. The contents of catechins and free amino acids decreased drastically, whereas the contents of gallic acid and theabrownins increased significantly during microbial fermentation. Pu-erh tea had the highest content of theabrownins (11.82 ± 0.49%). Moreover, MS-based metabolomics analysis revealed that the different types of dark teas were significantly different from their raw material. A total of 85 differential metabolites were screened among 569 metabolites identified referring to self-compiled database. Glycosylated, hydroxylated, methylated, and condensed and oxidated products originating from microbial bioconversion of their corresponding primitive forms were significantly increased in dark teas. These results suggest that various microbial-fermented methods greatly affect the metabolic profile of dark tea, which can provide useful information for dark tea biochemistry research.

Dehydration-Induced WRKY Transcriptional Factor MfWRKY70 of Myrothamnus flabellifolia Enhanced Drought and Salinity Tolerance in Arabidopsis.

The resurrection plants Myrothamnus flabellifolia can survive long term severe drought and desiccation conditions and soon recover after rewatering. However, few genes related to such excellent drought tolerance and underlying molecular mechanism have been excavated. WRKY transcription factors play critical roles in biotic and abiotic stress signaling, in which WRKY70 functions as a positive regulator in biotic stress response but a negative regulator in abiotic stress signaling in Arabidopsis and some other plant species. In the present study, the functions of a dehydration-induced MfWRKY70 of M. flabellifolia participating was investigated in the model plant Arabidopsis. Our results indicated that MfWRKY70 was localized in the nucleus and could significantly increase tolerance to drought, osmotic, and salinity stresses by promoting root growth and water retention, as well as enhancing the antioxidant enzyme system and maintaining reactive oxygen species (ROS) homeostasis and membrane-lipid stability under stressful conditions. Moreover, the expression of stress-associated genes (P5CS, NCED3 and RD29A) was positively regulated in the overexpression of MfWRKY70 Arabidopsis. We proposed that MfWRKY70 may function as a positive regulator for abiotic stress responses and can be considered as a potential gene for improvement of drought and salinity tolerance in plants.

Insight into the volatile profiles of four types of dark teas obtained from the same dark raw tea material.

Various dark teas are quite different in their volatile profiles, mainly due to the huge differences in the phytochemical profiles of dark raw tea and the diverse post-fermentation processing technologies. In this study, gas chromatography-mass spectrometry (GC-MS), qualitative GC-olfactometry (GC-O), and enantioselective GC-MS coupled with multivariate analysis were applied to characterise the volatile profiles of various dark teas obtained from the same dark raw tea material. A total of 159 volatile compounds were identified by stir bar sorptive extraction (SBSE) combined with GC-MS, and 49 odour-active compounds were identified. Moreover, microbial fermentation could greatly influence the distribution of volatile enantiomers in tea, and six pairs of enantiomers showed great diversity of enantiomeric ratios among various dark teas. These results suggest that post-fermentation processing technologies significantly affect the volatile profiles of various dark teas and provide a theoretical basis for the processing and quality control of dark tea products.

The efficacy of gabapentin combined with opioids for neuropathic cancer pain: a meta-analysis.

BACKGROUND: More than 30% of cancer patients experience neuropathic pain. Opioids, as standard pain-relief agents, cannot achieve satisfactory outcomes to treat neuropathic cancer pain due to drug resistance and side effects. Meanwhile, gabapentin, a third-generation anticonvulsant drug, has great potential in providing relief for neuropathic cancer pain. However, there is currently no sufficient evidence to support the efficacy of a combination of gabapentin and opioids in ameliorating neuropathic cancer pain. Hence, the aim of the present study was to explore the analgesic efficacy of gabapentin combined with opioids in treating neuropathic cancer pain. METHODS: PubMed, EMBASE, and Web of Science (Web of Knowledge) were searched for randomized controlled trials and prospective studies via the following keywords: "gabapentin", "opioid", "cancer", and "neuropathic pain". We used a scale of 0-10 (0 denoting no pain and 10 denoting the worst pain imaginable) to estimate pain intensity and utilized Review Manager 5.3 and Stata12 to analyze data. RESULTS: Seven studies meeting our criterion were selected from 110 records that were primarily searched. The mean difference of pooled pain intensity and the 95% confidence interval (CI) was -1.75 (-2.44, -1.07) (P value <0.00001; treatment group versus control group or time to outcome assessment versus baseline). The pain intensity of cancer patients after a combined treatment of gabapentin and opioids was significantly lower than that of patients receiving opioids alone. CONCLUSIONS: Our meta-analysis showed that gabapentin combined with opioids effectively alleviated neuropathic cancer pain compared with that of opioids alone.

MfbHLH38, a Myrothamnus flabellifolia bHLH transcription factor, confers tolerance to drought and salinity stresses in Arabidopsis.

BACKGROUND: The basic helix-loop-helix (bHLH) proteins, a large transcription factors family, are involved in plant growth and development, and defensive response to various environmental stresses. The resurrection plant Myrothamnus flabellifolia is known for its extremely strong drought tolerance, but few bHLHs taking part in abiotic stress response have been unveiled in M. flabellifolia. RESULTS: In the present research, we cloned and characterized a dehydration-inducible gene, MfbHLH38, from M. flabellifolia. The MfbHLH38 protein is localized in the nucleus, where it may act as a transcription factor. Heterologous expression of MfbHLH38 in Arabidopsis improved the tolerance to drought and salinity stresses, as determined by the studies on physiological indexes, such as contents of chlorophyll, malondialdehyde (MDA), proline (Pro), soluble protein, and soluble sugar, water loss rate of detached leaves, reactive oxygen species (ROS) accumulation, as well as antioxidant enzyme activities. Besides, MfbHLH38 overexpression increased the sensitivity of stomatal closure to mannitol and abscisic acid (ABA), improved ABA level under drought stress, and elevated the expression of genes associated with ABA biosynthesis and ABA responding, sucha as NCED3, P5CS, and RD29A. CONCLUSIONS: Our results presented evidence that MfbHLH38 enhanced tolerance to drought and salinity stresses in Arabidopsis through increasing water retention ability, regulating osmotic balance, decreasing stress-induced oxidation damage, and possibly participated in ABA-dependent stress-responding pathway.