Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Background: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management. Objectives: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety. Materials and methods: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes. Results: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22). Conclusion: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

Cloning and Expression Analysis of Key Enzyme Gene CoGPPS Involved in Iridoid Glycoside Synthesis in Cornus officinalis.

Cornus iridoid glycosides (CIGs), including loganin and morroniside, are the main active components of Cornus officinalis. As one of the key enzymes in the biosynthesis of CIGs, geranyl pyrophosphate synthase (GPPS) catalyzes the formation of geranyl pyrophosphate, which is the direct precursor of CIGs. In this study, the C. officinalis geranyl pyrophosphate synthase (CoGPPS) sequence was cloned from C. officinalis and analyzed. The cDNA sequence of the CoGPPS gene was 915 bp (GenBank No. OR725699). Phylogenetic analysis showed that CoGPPS was closely related to the GPPS sequence of Actinidia chinensis and Camellia sinensis, but relatively distantly related to Paeonia lactiflora and Tripterygium wilfordii. Results from the quantitative real-time PCR showed the spatiotemporal expression pattern of CoGPPS; that is, CoGPPS was specifically expressed in the fruits. Subcellular localization assay proved that CoGPPS was specifically found in chloroplasts. Loganin and morroniside contents in the tissues were detected by high-performance liquid chromatography, and both compounds were found to be at higher levels in the fruits than in leaves. Thus, this study laid the foundation for further studies on the synthetic pathway of CIGs.

Molecular mechanism of somatic embryogenesis in paeonia ostii 'Fengdan' based on transcriptome analysis combined histomorphological observation and metabolite determination.

BACKGROUND: Tree peony (Paeonia sect. Moutan DC.) is a famous flower native to China with high ornamental, medicinal, and oil value. However, the low regeneration rate of callus is one of the main constraints for the establishment of a genetic transformation system in tree peony. By histomorphological observation, transcriptomic analysis and metabolite determination, we investigated the molecular mechanism of somatic embryogenesis after the establishment of a culture system and the induction of somatic embryo(SE) formation. RESULTS: We found that SE formation was successfully induced when cotyledons were used as explants. A total of 3185 differentially expressed genes were screened by comparative transcriptomic analysis of embryogenic callus (EC), SE, and non-embryogenic callus (NEC). Compared to NEC, the auxin synthesis-related genes GH3.6 and PCO2 were up-regulated, whereas cytokinin dehydrogenase (CKX6) and CYP450 family genes were down-regulated in somatic embryogenesis. In SE, the auxin content was significantly higher than the cytokinin content. The methyltransferase-related gene S-adenosylmethionine synthase (SAMS) and the flavonoid biosynthesis-related gene (ANS and F3'5'H) were down-regulated in somatic embryogenesis. The determination of flavonoids showed that rhoifolin and hyperoside had the highest content in SE. The results of transcriptome analysis were consistent with the relative expression of 8 candidate genes by quantitative polymerase chain reaction analysis. CONCLUSION: The results revealed that auxin and cytokinin may play a key role in 'Fengdan' somatic embryogenesis. The genes related to somatic embryogenesis were revealed, which has partly elucidated the molecular mechanism of somatic embryogenesis in 'Fengdan'.

Gene Expression and Interaction Analysis of FsWRKY4 and FsMAPK3 in Forsythia suspensa.

Forsythia suspensa is a deciduous shrub that belongs to the family Myrtaceae, and its dried fruits are used as medicine. F. suspensa contains several secondary metabolites, which exert pharmacological effects. One of the main active components is forsythin, which exhibits free radical scavenging, antioxidant, anti-inflammatory, and anti-cancer effects. Mitogen-activated protein kinase (MAPKs) can increase the activity of WRKY family transcription factors in a phosphorylated manner, thereby increasing the content of secondary metabolites. However, the mechanism of interaction between MAPKs and WRKYs in F. suspensa remains unclear. In this study, we cloned the genes of FsWRKY4 and FsMAPK3, and performed a bioinformatics analysis. The expression patterns of FsWRKY4 and FsMAPK3 were analyzed in the different developmental stages of leaf and fruit from F. suspensa using real-time fluorescence quantitative PCR (qRT-PCR). Subcellular localization analysis of FsWRKY4 and FsMAPK3 proteins was performed using a laser scanning confocal microscope. The existence of interactions between FsWRKY4 and FsMPAK3 in vitro was verified by yeast two-hybridization. Results showed that the cDNA of FsWRKY4 (GenBank number: OR566682) and FsMAPK3 (GenBank number: OR566683) were 1587 and 522 bp, respectively. The expression of FsWRKY4 was higher in the leaves than in fruits, and the expression of FsMAPK3 was higher in fruits but lower in leaves. The subcellular localization results indicated that FsWRKY4 was localized in the nucleus and FsMAPK3 in the cytoplasm and nucleus. The prey vector pGADT7-FsWRKY4 and bait vector pGBKT7-FsMAPK3 were constructed and co-transferred into Y2H Glod yeast receptor cells. The results indicated that FsWRKY4 and FsMAPK3 proteins interact with each other in vitro. The preliminary study may provide a basis for more precise elucidation of the synthesis of secondary metabolites in F. suspensa.

Response and Tolerance of Macleaya cordata to Excess Zinc Based on Transcriptome and Proteome Patterns.

Macleaya cordata is a dominant plant of mine tailings and a zinc (Zn) accumulator with high Zn tolerance. In this study, M. cordata seedlings cultured in Hoagland solution were treated with 200 µmol·L-1 of Zn for 1 day or 7 days, and then, their leaves were taken for a comparative analysis of the transcriptomes and proteomes between the leaves of the control and Zn treatments. Differentially expressed genes included those that were iron (Fe)-deficiency-induced, such as vacuolar iron transporter VIT, ABC transporter ABCI17 and ferric reduction oxidase FRO. Those genes were significantly upregulated by Zn and could be responsible for Zn transport in the leaves of M. cordata. Differentially expressed proteins, such as chlorophyll a/b-binding proteins, ATP-dependent protease, and vacuolar-type ATPase located on the tonoplast, were significantly upregulated by Zn and, thus, could be important in chlorophyll biosynthesis and cytoplasm pH stabilization. Moreover, the changes in Zn accumulation, the production of hydrogen peroxide, and the numbers of mesophyll cells in the leaves of M. cordata were consistent with the expression of the genes and proteins. Thus, the proteins involved in the homeostasis of Zn and Fe are hypothesized to be the keys to the tolerance and accumulation of Zn in M. cordata. Such mechanisms in M. cordata can suggest novel approaches to genetically engineering and biofortifying crops.

Radiomics of Spinal Metastases Originating From Primary Nonsmall Cell Lung Cancer or Breast Cancer and Ability to Predict Epidermal Growth Factor Receptor Mutation/Ki-67 Levels.

OBJECTIVES: The aims of the study are to explore spinal magnetic resonance imaging (MRI)-based radiomics to differentiate spinal metastases from primary nonsmall cell lung cancer (NSCLC) or breast cancer (BC) and to further predict the epidermal growth factor receptor (EGFR) mutation and Ki-67 expression level. METHODS: In total, 268 patients with spinal metastases from primary NSCLC (n = 148) and BC (n = 120) were enrolled between January 2016 and December 2021. All patients underwent spinal contrast-enhanced T1-weighted MRI before treatment. Two- and 3-dimensional radiomics features were extracted from the spinal MRI images of each patient. The least absolute shrinkage and selection operator regression were applied to identify the most important features related to the origin of the metastasis and the EGFR mutation and Ki-67 level. Radiomics signatures (RSs) were established using the selected features and evaluated using receiver operating characteristic curve analysis. RESULTS: We identified 6, 5, and 4 features from spinal MRI to develop Ori-RS, EGFR-RS, and Ki-67-RS for predicting the metastatic origin, EGFR mutation, and Ki-67 level, respectively. The 3 RSs performed well in the training (area under the receiver operating characteristic curves: Ori-RS vs EGFR-RS vs Ki-67-RS, 0.890 vs 0.793 vs 0.798) and validation (area under the receiver operating characteristic curves: Ori-RS vs EGFR-RS vs Ki-67-RS, 0.881 vs 0.744 vs 0.738) cohorts. CONCLUSIONS: Our study demonstrated the value of spinal MRI-based radiomics for identifying the metastatic origin and evaluating the EGFR mutation status and Ki-67 level in patients with NSCLC and BC, respectively, which may have the potential to guide subsequent individual treatment planning.

Physiological and molecular response and tolerance of Macleaya cordata to lead toxicity.

BACKGROUND: Macleaya cordata is a traditional medicinal herb, and it has high tolerance and accumulation ability to heavy metals, which make it a good candidate species for studying phytoremediation. The objectives of this study were to investigate response and tolerance of M. cordata to lead (Pb) toxicity based on comparative analysis of transcriptome and proteome. RESULTS: In this study, the seedlings of M. cordata cultured in Hoagland solution were treated with 100 µmol·L- 1 Pb for 1 day (Pb 1d) or 7 days (Pb 7d), subsequently leaves of M. cordata were taken for the determination of Pb accumulation and hydrogen peroxide production (H2O2), meanwhile a total number of 223 significantly differentially expressed genes (DEGs) and 296 differentially expressed proteins (DEPs) were screened between control and Pb treatments. The results showed leaves of M. cordata had a special mechanism to maintain Pb at an appropriate level. Firstly, some DEGs were iron (Fe) deficiency-induced transporters, for example, genes of vacuolar iron transporter and three ABC transporter I family numbers were upregulated by Pb, which can maintain Fe homeostasis in cytoplasm or chloroplast. In addition, five genes of calcium (Ca2+) binding proteins were downregulated in Pb 1d, which may regulate cytoplasmic Ca2+ concentration and H2O2 signaling pathway. On the other hand, the cysteine synthase upregulated, glutathione S-transferase downregulated and glutathione reductase downregulated in Pb 7d can cause reduced glutathione accumulation and decrease Pb detoxification in leaves. Furthermore, DEPs of eight chlorophyll a/b binding proteins, five ATPases and eight ribosomal proteins can play a pivotal role on chloroplast turnover and ATP metabolism. CONCLUSIONS: Our results suggest that the proteins involved in Fe homeostasis and chloroplast turnover in mesophyll cells may play key roles in tolerance of M. cordata to Pb. This study offers some novel insights into Pb tolerance mechanism of plants, and the potential valuable for environmental remediation of this important medicinal plant.

Food security and overuse of agrochemicals: evidence from China's major grain-producing areas policy.

China's major grain-producing areas (MGPA) policy is the core policy to ensure national food security. While achieving long-term stable growth of grain production, assessing the impact of MGPA policy on agrochemical application has important practical significance in sustainable agricultural development and environmental protection. Based on panel data of 31 provinces in China from 1997 to 2020 and taking the MGPA policy introduced in 2004 as a quasi-natural experiment, we construct a difference-in-difference (DID) model to evaluate the overall impact and dynamic effect of MGPA policy. It is found that the MGPA policy do not exacerbate chemical overuse as a whole, but significantly reduce the fertilizer use by 11% and the pesticide use by 6%. Using the event study to decompose the policy effect year by year, we find that the MGPA policy significantly increased the fertilizer and pesticide use in a short period of time. Its influence on the application amount of two chemicals began to turn negative until the fourth and sixth years of the policy implementation and became more and more obvious. We conclude the intermediate paths of MGPA policy to change planting structure, deepen agricultural division of labor, and reduce the use of agrochemicals, which were verified by the intermediary effect model. From the perspective of provincial differences, MGPA policy reduced chemical use more in provinces with large output contribution and northern provinces. In addition, the MGPA policy has reduced the amount of fertilizer application in major rice-growing provinces, but not the amount of pesticide application. Our research can provide implications for other developing countries and emerging economies where agricultural production is highly dependent on chemicals and has green agricultural transition plans.

Expression Analysis of CoHMGS in Cornus officinalis and Subcellular Localization of the Enzyme It Encodes.

Cornus officinalis is a perennial deciduous tree or shrub. Its mature fruits are extracted and used in Traditional Chinese Medicine, called Shanzhuyu. The characteristic active components of C. officinalis include loganin and morroniside, which belong to iridoid glycosides. 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is a key enzyme in the cytoplasmic mevalonate pathway providing the precursor molecules isopentenyl pyrophosphate and dimethylallyl pyrophosphate for isoprenoid biosynthesis such as sterols, triterpenes, and their derivatives such as iridoid glycosides. Different concentrations of methyl jasmonate (MeJA) and ethephon (ETH) solutions were sprayed on C. officinalis seedlings, and the effect of hormones on CoHMGS gene expression was detected by real-time fluorescence quantitative PCR. The quantitative real-time PCR results showed that 750 mg/L ETH treatment had the most significant induction effect on CoHMGS gene expression. The HPLC analysis of extracts revealed that the treatment could also significantly increase the content of morroniside and loganin in the leaves of C. officinalis. By use of a CoHMGS-green fluorescent protein (GFP) fusion construct for heterologous expression in tobacco, laser scanning confocal microscopy revealed a cytoplasmic localization. This preliminary study of the CoHMGS gene could prepare the ground for more precisely elucidating the synthesis of secondary metabolite in C. officinalis.

Oxidative Stress Response and Metal Transport in Roots of Macleaya cordata Exposed to Lead and Zinc.

Heavy metal pollution possesses potential hazards to plant, animal and human health, which has become the focus of recent attention. Hence, phytoremediation has been regarded as one of the most important remediation technologies for heavy-metal-contaminated soils. In this research, a dominant mine tailing plant, Macleaya cordata, was used as the experimental material to compare the metal transport and oxidative stress response in its roots under lead (Pb) and zinc (Zn) treatments. The result showed that Pb was mainly accumulated in the roots of M. cordata under the Pb treatment; less than 1% Pb was transported to the parts above. An analysis of the Zn content demonstrated a 39% accumulation in the shoots. The production of reactive oxygen species was detected using the in situ histological staining of roots, which showed that hydrogen peroxide in the root tips was observed to increase with the increase in both Pb and Zn concentrations. No significant superoxide anion changes were noted in the root tips under the Pb treatment. An analysis of the root enzyme activity showed that increase in NADPH oxidase activity can be responsible for the production of superoxide anions, subsequent the inhibition of root growth and decrease in antioxidant enzyme activities in the roots of M. cordata exposed to excess Zn. In total, this research provides evidence that the root of M. cordata has a high antioxidant capacity for Pb stress, so it can accumulate more Pb without oxidative damage. On the other hand, the Zn accumulated in the roots of M. cordata causes oxidative damage to the root tips, which can stimulate more Zn transport to the shoots to reduce the damage to the roots. This result will provide a basis for the application of M. cordata in the phytoremediation of soil polluted by Pb-Zn compounds.

Environmental effects of rural e-commerce: A case study of chemical fertilizer reduction in China.

The economic effects of rural e-commerce have been fully discussed by scholars, but few studies focus on the environmental effects of rural e-commerce. This study takes the reduced application of chemical fertilizer in China as an example. On the basis of constructing the corresponding theoretical framework, we take the promotion of Rural E-Commerce Demonstration County (REDC) policy as a quasi-natural experiment, using the county panel data from 2000 to 2020 and the multi-period difference-in-difference method to excavate the influence of rural e-commerce on the fertilizer reduction. Our results show that REDC policy reduces the amount of chemical fertilizer applied in the county by 21%, which is unexpected. Our findings passed a series of robustness tests, including dealing with selective bias, eliminating other policy interference in the same period and placebo test. Based on the heterogeneity analysis of grain production and marketing regions and informatization level, it is found that the effect of fertilizer reduction by rural e-commerce is more impressive in the major grain production areas and counties with low informatization level. According to the theoretical framework, we use the mediating effect model to verify the transmission mechanism of marginal income improvement, mechanization and labor transfer. Therefore, we believe that policy designers can use e-commerce to promote farmers to adopt the production strategies of reducing fertilizer application. The findings and recommendations of this study may be relevant to other countries with free trading markets and e-commerce platforms.

Radiomics signatures for predicting the Ki-67 level and HER-2 status based on bone metastasis from primary breast cancer.

This study explores the potential of radiomics to predict the proliferation marker protein Ki-67 levels and human epidermal growth factor receptor 2 (HER-2) status based on MRI images of patients with spinal metastasis from primary breast cancer. A total of 110 patients with pathologically confirmed spinal metastases from primary breast cancer were enrolled between Dec. 2017 and Dec. 2021. All patients underwent T1-weighted contrast-enhanced MRI scans. The PyRadiomics package was used to extract features from the MRI images based on the intraclass correlation coefficient and least absolute shrinkage and selection operator. The most predictive features were used to develop the radiomics signature. The Chi-Square test, Fisher's exact test, Student's t-test, and Mann-Whitney U test were used to evaluate the clinical and pathological characteristics between the high- and low-level Ki-67 groups and the HER-2 positive/negative groups. The radiomics models were compared using receiver operating characteristic curve analysis. The area under the receiver operating characteristic curve (AUC), sensitivity (SEN), and specificity (SPE) were generated as comparison metrics. From the spinal MRI scans, five and two features were identified as the most predictive for the Ki-67 level and HER-2 status, respectively. The developed radiomics signatures generated good prediction performance for the Ki-67 level in the training (AUC = 0.812, 95% CI: 0.710-0.914, SEN = 0.667, SPE = 0.846) and validation (AUC = 0.799, 95% CI: 0.652-0.947, SEN = 0.722, SPE = 0.833) cohorts. Good prediction performance for the HER-2 status was also achieved in the training (AUC = 0.796, 95% CI: 0.686-0.906, SEN = 0.720, SPE = 0.776) and validation (AUC = 0.705, 95% CI: 0.506-0.904, SEN = 0.733, SPE = 0.762) cohorts. The results of this study provide a better understanding of the potential clinical implications of spinal MRI-based radiomics on the prediction of Ki-67 levels and HER-2 status in breast cancer.

Comparative Transcriptome Analysis of MeJA Responsive Enzymes Involved in Phillyrin Biosynthesis of Forsythia suspensa.

Forsythia suspensa (Thunb.) has been widely used in traditional medicines in Asia. According to the 2020 edition of Chinese Pharmacopoeia, phillyrin is the main active ingredient in F. suspensa, which is effective in clearing heat, reducing swelling, and dispersing nodules. F. suspensa leaf is a non-toxic substance and it can be used to make a health tea. Here, we combine elicitors and transcriptomics to investigate the inducible biosynthesis of the phillyrin from the F. suspensa. After the fruits and leaves of F. suspensa were treated with different concentrations of methyl jasmonate (MeJA), the content of phillyrin in the fruits reached a peak at 200 µM MeJA for 12 h, but which was decreased in leaves. To analyze the differences in key enzyme genes involved in the phillyrin biosynthesis, we sequenced the transcriptome of F. suspensa leaves and fruits treated with 200 µM MeJA for 12 h. We hypothesized that nine genes related to coniferin synthesis including: F. suspensa UDP-glycosyltransferase (FsUGT); F. suspensa 4-coumarate coenzyme CoA ligase (Fs4CL); and F. suspensa Caffeoyl-CoA O-methyltransferase (FsCCoAOMT) etc. The qRT-PCR analysis of genes related to phillyrin biosynthesis was consistent with RNA-seq analysis. We also investigated the dynamic changes of genes in F. suspensa leaves and fruits at different time points after 200 µM MeJA treatment, which laid the foundation for further study of the molecular mechanisms regulating the biosynthesis of phillyrin.

How Do Non-Agricultural Employment and Regional Selection Affect Farmers' Domestic Sewage Discharge Behavior? Empirical Evidence from Rural China.

In many countries, along with rising rural labor transfer, the problem of rural domestic sewage discharge is becoming increasingly serious due to labor shortages in the villages. It is urgent to solve the environment pollution and health problems of residents which is caused by the massive discharge of domestic sewage in rural areas. Based on the survey data collected from Nanjing Agricultural University in 2020, this paper employs the ordered probit model and the CMP method, to empirically test the impact of non-agricultural employment and regional choice on farmers' domestic sewage discharge behavior and the moderating effect of environmental cognition and the social network. The results show that: (1) There is a significantly positive correlation between non-agricultural employment and farmers' sewage treatment behavior. (2) Environmental cognition significantly improves the participation of urban non-agricultural employment farmers in sewage treatment, and the social network has a significant role in promoting the adoption of sewage treatment behavior of local non-agricultural employment farmers. (3) Further heterogeneity analysis results show that the inhibitory effect of urban non-agricultural employment on random sewage discharge is more pronounced than that of local non-agricultural employment. Therefore, in order to effectively solve the problem of rural domestic sewage discharge, it is necessary to actively guide the sewage discharge behavior of non-agricultural employment households, strengthen the social network interaction within the village, and increase the publicity for sewage discharge knowledge.

Anthocyanins accumulation analysis of correlated genes by metabolome and transcriptome in green and purple peppers (Capsicum annuum).

BACKGROUND: In order to clarify the the molecular mechanism of anthocyanin accumulation in green and purple fruits of pepper using metabolomics and transcriptomics,to identify different anthocyanin metabolites,and to analyze the differentially expressed genes involved in anthocyanin biosynthesis.. RESULTS: We analyzed the anthocyanin metabolome and transcriptome data of the fruits of 2 purple pepper and 1 green pepper. A total of 5 anthocyanin metabolites and 2224 differentially expressed genes were identified between the green and purple fruits of pepper. Among the 5 anthocyanin metabolites,delphin chloride was unique to purple pepper fruits,which is the mainly responsible for the purple fruit color of pepper. A total of 59 unigenes encoding 7 enzymes were identified as candidate genes involved in anthocyanin biosynthesis in pepper fruit. The six enzymes (PAL,C4H,CHI,DFR,ANS,UFGT) had higher expression levels except the F3H gene in purple compared with green fruits. In addition,seven transcription factors were also found in this study. These transcription factors may contribute to anthocyanin metabolite biosynthesis in the fruits of pepper. One of differentially expressed gene novel.2098 was founded. It was not annotated in NCBI. Though blast analysis we preliminarily considered that this gene related to MYB transcription factor and was involved in anthocyanin biosynthesis in pepper fruit. CONCLUSIONS: Overall, the results of this study provide useful information for understanding anthocyanin accumulation and the molecular mechanism of anthocyanin biosynthesis in peppers.

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

Context: Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending. Objective: We studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children. Design Setting and Patients: This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children. Intervention: Subjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks. Main Outcome Measure: The primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes. Results: At week 26, the median HtSDSCA changed from -2.75, -2.82, and -2.78 to -2.31, -2.43, and -2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%-90.34% and 76.08%-90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups. Conclusions: Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02976675.

Corrigendum: Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

[This corrects the article DOI: 10.3389/fendo.2021.779365.].

Efficient Ni/Au Mesh Transparent Electrodes for ITO-Free Planar Perovskite Solar Cells.

Indium thin oxide (ITO)-free planar perovskite solar cells (PSCs) were fabricated at a low temperature (150 °C) in this work based on the transparent electrode of photolithography processed nickel/gold (Ni/Au) mesh and the high conductivity polymer, PH1000. Ultrathin Au was introduced to increase the conductivity of metal mesh, and the optimal hexagonal Ni (30 nm)/Au (10 nm) mesh (line width of 5 µm) shows a transmittance close to 80% in the visible light region and a sheet resistance lower than 16.9 Ω/sq. The conductive polymer PH1000 not only smooths the raised surface of the metal mesh but also enhances the charge collection ability of metal mesh. The fabricated PSCs have the typical planar structure (glass/Ni-Au mesh/PH1000/PEDOT:PSS/MAyFA1-yPbIxCl3-x/PCBM/BCP/Ag) and the champion PSC (0.09 cm2) obtains a power conversion efficiency (PCE) of 13.88%, negligible current hysteresis, steady current density and PCE outputs, and good process repeatability. Its photovoltaic performance and stability are comparable to the reference PSC based on the ITO electrodes (PCE = 15.70%), which demonstrates that the Ni/Au mesh transparent electrodes are a promising ITO alternative to fabricate efficient PSCs. The relatively lower performance of Ni/Au based PSC results from the relatively slower charge extraction and stronger charge recombination than the ITO based PSC. Further, we tried to fabricate the large area (1 cm2) device and achieve a PCE over 6% with negligible hysteresis and steady current density and PCE outputs. The improvements of perovskite film quality and interface modification should be an effective approach to further enhance the device performance of Ni/Au based PSCs, and the Ni/Au mesh electrode may find wider applications in PSCs and flexible devices.

Computational Insight Into Vitamin K1 ω-Hydroxylation by Cytochrome P450 4F2.

Vitamin K1 (VK1) plays an important role in the modulation of bleeding disorders. It has been reported that ω-hydroxylation on the VK1 aliphatic chain is catalyzed by cytochrome P450 4F2 (CYP4F2), an enzyme responsible for the metabolism of eicosanoids. However, the mechanism of VK1 ω-hydroxylation by CYP4F2 has not been disclosed. In this study, we employed a combination of quantum mechanism (QM) calculations, homology modeling, molecular docking, molecular dynamics (MD) simulations, and combined quantum mechanism/molecular mechanism (QM/MM) calculations to investigate the metabolism profile of VK1 ω-hydroxylation. QM calculations based on the truncated VK1 model show that the energy barrier for ω-hydroxylation is about 6-25 kJ/mol higher than those at other potential sites of metabolism. However, results from the MD simulations indicate that hydroxylation at the ω-site is more favorable than at the other potential sites, which is in accordance with the experimental observation. The evaluation of MD simulations was further endorsed by the QM/MM calculation results. Our studies thus suggest that the active site residues of CYP4F2 play a determinant role in the ω-hydroxylation. Our results provide structural insights into the mechanism of VK1 ω-hydroxylation by CYP4F2 at the atomistic level and are helpful not only for characterizing the CYP4F2 functions but also for looking into the ω-hydroxylation mediated by other CYP4 enzymes.

Several newly discovered Mo-enriched plants with a focus on Macleaya cordata.

Phytoremediation as an alternative strategy has been a widespread attention. The screening of enriched plants and hyperaccumulators is the key of the strategy. So this study examined the status of heavy metal pollution in molybdenum (Mo) mine soils, metal accumulation in plants growing on mine, and their tolerance strategies. The analysis of 14 soils and 27 plant samples in mining area showed that Mo, zinc (Zn), and cadmium (Cd) concentrations exceeded soil safety standards and their levels varied in 27 plant samples. Mo was the heavy pollution with an average total content of 256.1 mg/kg in soils. As Mo-enriched plants, Mo concentrations of Macleaya cordata (Willd.) R. Br. and Morus australis Poir. were 704.4 and 772.4 mg/kg, respectively. M. cordata was selected as the research material, due to its high biomass. Molybdenum significantly decreased the biomass and photosynthesis of M. cordata at high concentration (> 200 µmol/L), but its biomass and photosynthesis reached the maximum after 50 µmol/L Mo treatment, respectively. Analysis of the subcellular distribution and chemical speciation showed that Mo was distributed a certain way in the extracts and that this suggested that it may be present in cell wall and soluble fraction of roots (51.9-63.9%; 26.1-44.7%) or shoots (30.0-44.4%; 47.3-56.0%) and complexed to organic acid, pectate, oxalate, and protein. This might be responsible for the adaptation of M. cordata to Mo stress. Therefore, M. cordata could serve as a potential plant to utilize for the phytoremediation of Mo-contaminated soil.