Novel Carbon Quantum Dots Precisely Trigger Ferroptosis in Cancer Cells through Antioxidant Inhibition Synergistic Nanocatalytic Activity.

High levels of glutathione (GSH) are an important characteristic of malignant tumors and a significant cause of ineffective treatment and multidrug resistance. Although reactive oxygen species (ROS) therapy has been shown to induce tumor cell death, the strong clearance effect of GSH on ROS significantly reduces its therapeutic efficacy. Therefore, there is a need to develop new strategies for targeting GSH. In this study, novel carbon quantum dots derived from gentamycin (GM-CQDs) were designed and synthesized. On the basis of the results obtained, GM-CQDs contain sp2 and sp3 carbon atoms as well as nitrogen oxygen groups, which decrease the intracellular levels of GSH by downregulating SLC7A11, thereby disrupting redox balance, mediating lipid peroxidation, and inducing ferroptosis. Transcriptome analysis demonstrated that GM-CQDs downregulated the expression of molecules related to GSH metabolism while significantly increasing the expression of molecules related to ferroptosis. The in vivo results showed that the GM-CQDs exhibited excellent antitumor activity and immune activation ability. Furthermore, because of their ideal biological safety, GM-CQDs are highly promising for application as drugs targeting GSH in the treatment of malignant tumors.

Meeting medical emergency response criteria for hypertension is not associated with an increased likelihood of in-hospital mortality in a tertiary referral center.

Backgrounds: Rapid response team or medical emergency team (MET) calls are typically activated by significant alterations of vital signs in inpatients. However, the clinical significance of a specific criterion, blood pressure elevations, is uncertain. Objectives: The aim of this study was to evaluate the likelihood ratios associated with MET-activating vital signs, particularly in-patient hypertension, for predicting in-hospital mortality among general medicine inpatients who met MET criteria at any point during admission in a South Australian metropolitan teaching hospital. Results: Among the 15,734 admissions over a two-year period, 4282 (27.2%) met any MET criteria, with a positive likelihood ratio of 3.05 (95% CI 2.93 to 3.18) for in-hospital mortality. Individual MET criteria were significantly associated with in-hospital mortality, with the highest positive likelihood ratio for respiratory rate ≤ 7 breaths per minute (9.83, 95% CI 6.90 to 13.62), barring systolic pressure ≥ 200 mmHg (LR + 1.26, 95% CI 0.86 to 1.69). Conclusions: Our results show that meeting the MET criteria for hypertension, unlike other criteria, was not significant associated with in-hospital mortality. This observation warrants further research in other patient cohorts to determine whether blood pressure elevations should be routinely included in MET criteria.

Promoting Diabetic Wound Healing through a Hydrogel-Based Cascade Regulation Strategy of Fibroblast-Macrophage.

The management of diabetic wounds (DWs) continues to pose a significant challenge in the field of medicine. DWs are primarily prevented from healing due to damage to macrophage efferocytosis and fibroblast dysfunction. Consequently, a treatment strategy that involves both immunoregulation and the promotion of extracellular matrix (ECM) formation holds promise for healing DWs. Nevertheless, existing treatment methods necessitate complex interventions and are associated with increased costs, for example, the use of cytokines and cell therapy, both of which have limited effectiveness. In this study, a new type of ruthenium (IV) oxide nanoparticles (RNPs)-laden hybrid hydrogel dressing with a double network of Pluronic F127 and F68 has been developed. Notably, the hybrid hydrogel demonstrates remarkable thermosensitivity, injectability, immunoregulatory characteristics, and healing capability. RNPs in hydrogel effectively regulate both fibroblasts and macrophages in a cascade manner, stimulating fibroblast differentiation while synergistically enhancing the efferocytosis of macrophage. The immunoregulatory character of the hydrogel aids in restoring the intrinsic stability of the immune microenvironment in the wound and facilitates essential remodeling of the ECM. This hydrogel therefore offers a novel approach for treating DWs through intercellular communication.

Stereoselective cardiotoxic effects of metconazole on zebrafish (Danio rerio) based on AGE-RAGE signalling pathway.

Metconazole (MEZ) is a novel chiral triazole fungicide that is widely used to prevent and control soil-borne fungal pathogens and other fungal diseases. However, it has a long half-life in aquatic environments and thus poses potential environmental risks. This study evaluates the acute and stereoselective cardiotoxicity of MEZ in zebrafish (Danio rerio) embryos. In addition, transcriptomics, real-time quantitative PCR, enzyme activity determination, and molecular docking are performed to evaluate the molecular mechanisms underlying the cardiotoxicity of MEZ in zebrafish. MEZ decreases the heart rate while increasing the pericardial oedema rate; additionally, it induces stereoselective cardiotoxicity. 1S,5S-MEZ exhibits stronger cardiotoxicity than 1R,5R-MEZ. Furthermore, MEZ increases the expression of Ahr-associated genes and the transcription factors il6st, il1b, and AP-1. Heart development-related genes, including fbn2b, rbm24b, and tbx20 are differentially expressed. MEZ administration alters the activities of catalase, peroxidase, and glutathione-S-transferase in zebrafish larvae. Molecular docking indicates that 1R,5R-MEZ binds more strongly to the inhibitor-binding sites of p38 in the AGE-RAGE signalling pathway than to other MEZ enantiomers. Studies conducted in vivo and in silico have established the enantioselective cardiotoxicity of MEZ and its underlying mechanisms, highlighting the need to evaluate the environmental risk of chiral MEZ in aquatic organisms at the enantiomeric level.

Four-Chlorophenoxyacetic Acid Treatment Induces the Defense Resistance of Rice to White-Backed Planthopper Sogatella furcifera.

Chemical elicitors can increase plant defense against herbivorous insects and pathogens. The use of synthetic chemical elicitors is likely to be an alternative to traditional pesticides for crop pest control. However, only a few synthetic chemicals are reported to protect plants by regulating signaling pathways, increasing the levels of defense metabolites and interfering with insect feeding. Here, we found that the exogenous application of a phenoxycarboxylic compound, 4-chlorophenoxyacetic acid (4-CPA), can induce chemical defenses to protect rice plants from white-backed planthoppers (WBPH, Sogatella furcifera). Four-CPA was rapidly taken up by plant roots and degraded to 4-chlorophenol (4-CP). Four-CPA treatment modulated the activity of peroxidase (POD) and directly induced the deposition of lignin-like polymers using hydrogen peroxide (H2O2) as the electron acceptor. The polymers, which are thought to prevent the planthopper's stylet from reaching the phloem, were broken down by WBPH nymphs. Meanwhile, 4-CPA increased the levels of flavonoids and phenolamines (PAs). The increased flavonoids and PAs, together with the degradation product of the polymers, avoided nymphal feeding and prolonged the nymphal period for 1 day. These results indicate that 4-CPA has the potential to be used as a chemical elicitor to protect rice from planthoppers. Moreover, these findings also open a pathway for molecule structure design of phenoxycarboxylic compounds as chemical elicitors.

Knocking Out OsRLK7-1 Impairs Rice Growth and Development but Enhances Its Resistance to Planthoppers.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) are an important subfamily of receptor-like kinases (RLKs) in plants that play key roles in sensing different biotic and abiotic stress. However, the role of LRR-RLKs in herbivore-induced plant defense remains largely elusive. Here, we found that the expression of a rice gene, OsRLK7-1, was induced by mechanical wounding, but was slightly suppressed by the infestation of gravid females of brown planthopper (BPH, Nilaparvata lugens) or white-backed planthopper (WBPH, Sogatella furcifera). Through targeted disruption of OsRLK7-1 (resulting in the ko-rlk lines), we observed an augmentation in transcript levels of BPH-induced OsMPK3, OsWRKY30, OsWRKY33, and OsWRKY45, alongside heightened levels of planthopper-induced jasmonic acid, JA-isoleucine, and abscisic acid in plant tissues. These dynamic changes further facilitated the biosynthesis of multiple phenolamides within the rice plants, culminating in an enhanced resistance to planthopper infestations under both lab and field conditions. In addition, knocking out OsRLK7-1 impaired plant growth and reproduction. These results suggest that OsRLK7-1 plays an important role in regulating rice growth, development, and rice-planthopper interactions.

Systolic blood pressure levels and mortality in Australian medical inpatients.

The epidemiology of elevations in blood pressure is incompletely characterized, particularly in Australia. Given the lack of evidence regarding the frequency and the optimal management of in-hospital hypertension, the authors performed a multicenter retrospective cohort study of consecutive medical admissions in South Australia over a 2-year period to investigate systolic blood pressure levels and their association with in-hospital mortality. Among 16 896 inpatients, 76% had at least one systolic blood pressure reading of ≥140 mmHg and 11.7% of ≥180 mmHg during hospitalization. A statistically significant negative relationship was observed between having at least one reading ≥140 mmHg and a likelihood of in-hospital mortality (odds ratio 0.41, 95% CI: 0.35 to 0.49, P < .001). Our results suggest that elevations in systolic blood pressure are common in Australian medical inpatients. However, the inverse association observed between systolic blood pressure values ≥140 mmHg and in-hospital mortality warrants further research to determine the clinical significance and optimal management of blood pressure elevations in this group.

Antimicrobial activity and comparative metabolomic analysis of Priestia megaterium strains derived from potato and dendrobium.

The growth of endophytic bacteria is influenced by the host plants and their secondary metabolites and activities. In this study, P. megaterium P-NA14 and P. megaterium D-HT207 were isolated from potato tuber and dendrobium stem respectively. They were both identified as Priestia megaterium. The antimicrobial activities and metabolites of both strains were explored. For antimicrobial activities, results showed that P. megaterium P-NA14 exhibited a stronger inhibition effect on the pathogen of dendrobium, while P. megaterium D-HT207 exhibited a stronger inhibition effect on the pathogen of potato. The supernatant of P. megaterium P-NA14 showed an inhibition effect only on Staphylococcus aureus, while the sediment of P. megaterium D-HT207 showed an inhibition effect only on Escherichia coli. For metabolomic analysis, the content of L-phenylalanine in P. megaterium P-NA14 was higher than that of P. megaterium D-HT207, and several key downstream metabolites of L-phenylalanine were associated with inhibition of S. aureus including tyrosine, capsaicin, etc. Therefore, we speculated that the different antimicrobial activities between P. megaterium P-NA14 and P. megaterium D-HT207 were possibly related to the content of L-phenylalanine and its metabolites. This study preliminarily explored why the same strains isolated from different hosts exhibit different activities from the perspective of metabolomics.

Enantioselective activity and toxicity of chiral acaricide cyflumetofen toward target and non-target organisms.

Cyflumetofen (CYF), a novel chiral acaricide, exert enantiomer-specific effects on target organisms by binding to glutathione S-transferase. However, there is limited knowledge regarding the response of non-target organisms to CYF, including enantioselective toxicity. In this study, we investigated the effects of racemic CYF (rac-CYF) and its two enantiomers (+)-CYF and (-)-CYF on MCF-7 cells and non-target (honeybees) and target (bee mites and red spider mites) organisms. The results showed that similar to estradiol, 1 µM (+)-CYF promoted the proliferation and disturbed the redox homeostasis of MCF-7 cells, whereas at high concentrations (≥100 µM) it exerted a negative effect on cell viability that was substantially stronger than that of (-)-CYF or rac-CYF. (-)-CYF and rac-CYF at 1 µM concentration did not significantly affect cell proliferation, but caused cell damage at high concentrations (≥100 µM). Analysis of acute CYF toxicity against non-target and target organisms revealed that for honeybees, all CYF samples had high lethal dose (LD50) values, indicating low toxicity. In contrast, for bee mites and red spider mites, LD50 values were low, whereas those of (+)-CYF were the lowest, suggesting higher toxicity of (+)-CYF than that of the other CYF samples. Proteomics profiling revealed potential CYF-targeted proteins in honeybees related to energy metabolism, stress responses, and protein synthesis. Upregulation of estrogen-induced FAM102A protein analog indicated that CYF might exert estrogenic effects by dysregulating estradiol production and altering estrogen-dependent protein expression in bees. Our findings suggest that CYF functions as an endocrine disruptor in non-target organisms in an enantiomer-specific manner, indicating the necessity for general ecological risk assessment for chiral pesticides.

Research Progress on Hypoglycemic Mechanisms of Resistant Starch: A Review.

In recent years, the prevalence of diabetes is on the rise, globally. Resistant starch (RS) has been known as a kind of promising dietary fiber for the prevention or treatment of diabetes. Therefore, it has become a hot topic to explore the hypoglycemic mechanisms of RS. In this review, the mechanisms have been summarized, according to the relevant studies in the recent 15 years. In general, the blood glucose could be regulated by RS by regulating the intestinal microbiota disorder, resisting digestion, reducing inflammation, regulating the hypoglycemic related enzymes and some other mechanisms. Although the exact mechanisms of the beneficial effects of RS have not been fully verified, it is indicated that RS can be used as a daily dietary intervention to reduce the risk of diabetes in different ways. In addition, further research on hypoglycemic mechanisms of RS impacted by the RS categories, the different experimental animals and various dietary habits of human subjects, have also been discussed in this review.

The effect of a loading dose of meropenem on outcomes of patients with sepsis treated by continuous renal replacement: study protocol for a randomized controlled trial.

BACKGROUND: Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT. METHODS: This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety. DISCUSSION: This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .

Analysis of Endophytic Bacterial Diversity From Different Dendrobium Stems and Discovery of an Endophyte Produced Dendrobine-Type Sesquiterpenoid Alkaloids.

As the unique component of Dendrobium, dendrobine-type sesquiterpenoid alkaloids (DSAs) possess a variety of medicinal properties. It has been well documented that plant endophytes can in vitro synthesize secondary metabolites identical or similar to metabolites produced by their host plants. This study aimed to investigate the composition and distribution of endophytic bacteria of Dendrobium stems by Illumina MiSeq platform sequencing and cultivation-dependent methods and then to assess the potential for endophytic bacteria to produce DSAs. Results indicated that it was necessary to combine both cultivation-dependent and cultivation-independent methods to analyze the community structure of endophytic bacterial in plants comprehensively. The length of the Dendrobium stems influenced the endophytic bacterial community. The diversity and richness of endophytic bacteria in group J10_15cm of stems were the highest, which showed a significant difference from the other stem groups. However, there was no certain connection between the diversity and richness of endophytic bacteria and the content of dendrobine. It was most likely due to the influence of several specific endophytic bacteria genera, such as Sphingomonas and Rhodococcus. Athelia rolfsii, Myrothecium roridum, as pathogenic fungi, and Pectobacterium carotovorum subsp. actinidiae, as pathogenic bacteria of Dendrobium, were used to determine the antimicrobial activities. In these assays, six strains belonging to five genera showed antimicrobial activity against at least two phytopathogens. The strain BL-YJ10_15-29 (Paracoccus pueri THG-N2.35, 98.98%) showed the best antimicrobial activity against the three phytopathogens. In addition, 2 DSAs (6-hydroxydendrobine and nobilonine) were identified in the fermentation supernatant of the strain CM-YJ10_15-44 (Pseudomonas protegens CHA0, 99.24%), whereas the whole-genome analysis results further demonstrated that the precursors of the two DSAs [geranyl-PP and (E, E)-famesyl-PP] were synthesized mainly through the methyl-D-erythritol 4-phosphate pathway in this strain. This study provides new insight into the studies on the biosynthesis of DSAs and provides potential biocontrol bacteria.

Antimicrobial Activity Against Phytopathogens and Inhibitory Activity on Solanine in Potatoes of the Endophytic Bacteria Isolated From Potato Tubers.

As an important global crop, the potato (Solanum tuberosum L.) contains the endotoxin solanine that leads to human poisoning and major economic losses. Poisoning symptoms and even acute poisoning may occur when the content of solanine in potatoes exceeds 200 mg/kg. In addition, potatoes are susceptible to some pathogenic bacteria, including Streptomyces scabies and Erwinia carotovora subsp. atroseptica (Van Hall) dye, which can cause potato scab and potato blackleg disease, respectively. In this study, 37 culturable endophytic bacteria strains were obtained from potato tubers based on the culture-dependent method. Results indicated that nine strains showed antimicrobial activity against at least one pathogen by antimicrobial activity screening and 23 strains showed inhibitory activity on solanine in potato tubers. Among them, strain P-NA2-14 (Bacillus megaterium NBRC 15308T, 99.31%) showed not only better antimicrobial activity against both the two indicator pathogens, but also the best inhibitory activity on solanine, which was proved to be a potential biocontrol bacterium. Meanwhile, the relationship between the distribution of the endophytic bacterial community and the content of solanine in potato tubers was studied by Illumina-based analysis, indicating that the distribution of the endophytic bacterial community was obviously influenced by the content of solanine. The results showed a new insight into the relationship between plant secondary metabolites and endophytic bacteria in potato tubers and provided potential new technical support for the biological control of potato storage.

Induction of defense in cereals by 4-fluorophenoxyacetic acid suppresses insect pest populations and increases crop yields in the field.

Synthetic chemical elicitors, so called plant strengtheners, can protect plants from pests and pathogens. Most plant strengtheners act by modifying defense signaling pathways, and little is known about other mechanisms by which they may increase plant resistance. Moreover, whether plant strengtheners that enhance insect resistance actually enhance crop yields is often unclear. Here, we uncover how a mechanism by which 4-fluorophenoxyacetic acid (4-FPA) protects cereals from piercing-sucking insects and thereby increases rice yield in the field. Four-FPA does not stimulate hormonal signaling, but modulates the production of peroxidases, H2O2, and flavonoids and directly triggers the formation of flavonoid polymers. The increased deposition of phenolic polymers in rice parenchyma cells of 4-FPA-treated plants is associated with a decreased capacity of the white-backed planthopper (WBPH) Sogatella furcifera to reach the plant phloem. We demonstrate that application of 4-PFA in the field enhances rice yield by reducing the abundance of, and damage caused by, insect pests. We demonstrate that 4-FPA also increases the resistance of other major cereals such as wheat and barley to piercing-sucking insect pests. This study unravels a mode of action by which plant strengtheners can suppress herbivores and increase crop yield. We postulate that this represents a conserved defense mechanism of plants against piercing-sucking insect pests, at least in cereals.

Residues and enantioselective behavior of cyflumetofen from apple production.

The effect of food processing on the level and fate of chiral pesticide residues in apple products has rarely been investigated. In this study, we used ultra-performance convergence chromatography coupled with triple quadrupole mass spectrometry to determine the content of the novel chiral acaricide cyflumetofen. The matrix-matched calibration lines were constructed for apple slices, juice, wine and vinegar, and the determination coefficients (r2) exceeded 0.9954. Acceptable average recoveries were within 81.1% to 119.9%, and the relative standard deviations (RSDs) ranged from 0.8% to 11.0%. Processing effectiveness is represented by the processing factor (PF). The results indicated that the PFs of different procedures (washing, peeling, enzymolysis, fermentation, among others.) were generally less than 1. The reduction of cyflumetofen enantiomers during fermentation was in accordance with first-order kinetics, and stereoselective behavior was observed. This study provides reliable references for the risk assessment of cyflumetofen in the processing of apple products.

Osteopromotive carbon dots promote bone regeneration through the PERK-eIF2α-ATF4 pathway.

Bone defects are still an unsolved clinical issue that must be overcome. Carbon dots have shown very promising effects in biological therapy. In the current study, we explored their effects on osteogenesis. Furthermore, we revealed the mechanisms in order to develop novel therapeutic approaches to manage the bone defect. For this study, ascorbic acid carbon dots (CDs) were created by a one-step microwave-assisted method. Results showed that the CDs effectively enhanced matrix mineralization, promoted osteogenic differentiation in vitro, and promoted new bone regeneration in the skull defect model in vivo. Furthermore, our data demonstrated that the ER stress and PERK-eIF2α-ATF4 pathway were activated by the CD-induced increase in intracellular calcium. Taken together, our findings suggest that the PERK pathway plays a critical role in CD-induced osteogenic differentiation, and the CDs created herein have the potential to be used to repair bone defects in clinical practice.

Comparative efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B: A systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE, Clinical Trials and China National Knowledge Infrastructure(CNKI) databases were electronically searched to collect randomized controlled trials (RCTs) regarding the comparison between tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used for the meta-analysis. RESULTS: Early on, tenofovir had a greater ability to inhibit the hepatitis B virus, I2 = 0% [RR = 1.08, 95% CI (1.03, 1.13), P<0.01] (96 weeks). Entecavir can normalize the ALT levels earlier, I2 = 0% [RR = 0.87, 95% CI (0.77, 0.98), P = 0.02] (48 weeks). However, there was no statistically significant difference between TDF and ETV at 144 weeks. Tenofovir was as effective as entecavir in terms of HBeAg clearance and HBeAg seroconversion, I2 = 0% [RR = 1.05, 95% CI (0.68, 1.62), P = 0.82]; I2 = 69% [RR = 0.93, 95% CI (0.54, 1.61), P = 0.80]. The difference in the incidence of elevated creatine kinase levels was not statistically significant I2 = 0% [RR = 0.66, 95% CI (0.27, 1.60), P = 0.35]. CONCLUSIONS: Tenofovir and entecavir were equally effective in the treatment of patients with nucleos(t)ide analogue-naive chronic hepatitis B. In addition, TDF has an advantage in the incidence of hepatocellular carcinoma. Additional RCTs and a large-sample prospective cohort study should be performed.

Effectiveness of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic hepatitis b (CHB) is a serious problem worldwide. Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) both are first-line drugs for CHB, but there is debate about which is more appropriate in nucleos(t)ide analogue-naive CHB. OBJECTIVE: To systematically evaluate the effectiveness and safety of tenofovir and ETV in nucleos(t)ide analogue-naive CHB. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE, Clinical Trials, and China National Knowledge Infrastructure databases will be electronically searched to collect randomized controlled trials regarding the comparison between tenofovir and ETV in nucleos(t)ide analogue-naive CHB since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software will be used for the meta-analysis. RESULT: We will provide practical and targeted results assessing the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients, try to compare the advantages of TDF and ETV. CONCLUSION: The stronger evidence about the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients will be provided for clinicians. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42019134194.

Citrus sinensis MYB Transcription Factor CsMYB85 Induce Fruit Juice Sac Lignification Through Interaction With Other CsMYB Transcription Factors.

Varieties of Citrus are commercially important fruits that are cultivated worldwide and are valued for being highly nutritious and having an appealing flavor. Lignification of citrus fruit juice sacs is a serious physiological disorder that occurs during postharvest storage, for which the underlying transcriptional regulatory mechanisms remain unclear. In this study, we identified and isolated a candidate MYB transcription factor, CsMYB85, that is involved in the regulation of lignin biosynthesis in Citrus sinensis, which has homologs in Arabidopsis and other plants. We found that during juice sac lignification, CsMYB85 expression levels increase significantly, and therefore, suspected that this gene may control lignin biosynthesis during the lignification process. Our results indicated that CsMYB85 binds the CsMYB330 promoter, regulates its expression, and interacts with CsMYB308 in transgenic yeast and tobacco. A transient expression assay indicated that Cs4CL1 expression levels and lignin content significantly increased in fruit juice sacs overexpressing CsMYB85. At4CL1 expression levels and lignin content were also significantly increased in Arabidopsis overexpressing CsMYB85. We accordingly present convincing evidence for the participation of the CsMYB85 transcription factor in fruit juice sac lignification, and thereby provide new insights into the transcriptional regulation of this process in citrus fruits.