CwJAZ4/9 negatively regulates jasmonate-mediated biosynthesis of terpenoids through interacting with CwMYC2 and confers salt tolerance in Curcuma wenyujin.

Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Spin Crossover in [Fe(qsal-5-Brq)2]+ Complexes with a Quinoline-Substituted Qsal Ligand.

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

[Deficiency of cathepsin K improves ischemic angiogenesis in high-fat diet fed mice].

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.

Hysteretic Spin Crossover with High Transition Temperatures in Two Cobalt(II) Complexes.

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

Syntheses, Structures, and Magnetic Properties of Three Cyano-Bridged FeII-MoIII Single-Molecule Magnets.

Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.

A novel aptamer beacon for rapid screening of recombinant cells and in vivo monitoring of recombinant proteins.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

A novel clinical diagnostic marker predicting the relationship between visceral adiposity and renal function evaluated by estimated glomerular filtration rate (eGFR) in the Chinese physical examination population.

BACKGROUND AND AIMS: The effect of body fat deposition on the kidney has received increasing attention. The Chinese visceral adiposity index (CVAI) is an important indicator of recent research. The purpose of this study was to explore the predictive value of CVAI and other organ obesity indicators in predicting CKD in Chinese residents. METHODS: A retrospective cross-sectional study of 5355 subjects was performed. First, the study utilized locally estimated scatterplot smoothing to describe the dose-response relationship between the estimated glomerular filtration rate (eGFR) and CVAI. The L1-penalized least absolute shrinkage and selection operator (LASSO) regression algorithm was used for covariation screening, and the correlation between CVAI and eGFR was quantified using multiple logistic regression. At the same time, the diagnostic efficiency of CVAI and other obesity indicators was evaluated by ROC curve analysis. RESULTS: CVAI and eGFR were negatively correlated. Using group one as the control, an odds ratio (OR) was calculated to quantify CVAI quartiles (ORs of Q2, Q3, and Q4 were 2.21, 2.99, and 4.42, respectively; P for trend < 0.001). CVAI had the maximum area under the ROC curve compared with other obesity indicators, especially in the female population (AUC: 0.74, 95% CI: 0.71-0.76). CONCLUSIONS: CVAI is closely linked to renal function decline and has certain reference value for the screening of CKD patients, particularly in women.

A Coordination-Driven Self-Assembly and NIR Photothermal Conversion Study of Organometallic Handcuffs.

Due to their fascinating topological structures and application prospects, coordination supramolecular complexes have continuously been studied by scientists. However, the controlled construction and property study of organometallic handcuffs remains a significant and challenging research subject in the area of supramolecular chemistry. Hence, a series of tetranuclear organometallic and heterometallic handcuffs bearing different size and metal types were rationally designed and successfully synthesized by utilizing a quadridentate pyridyl ligand (tetra-(3-pyridylphenyl)ethylene) based on three Cp*Rh (Cp* = η5-C5Me5) fragments bearing specific longitudinal dimensions and conjugated planes. These results were determined with single-crystal X-ray diffraction analysis technology, ESI-MS NMR spectroscopy, etc. Importantly, the photoquenching effect of Cp* groups and the discrepancy of intermolecular π-π stacking interactions between building block and half-sandwich fragments promote markedly different photothermal conversion results. These results will further push the synthesis of topological structures and the development of photothermal conversion materials.

Manipulating Electron-Transfer Events in [Fe4 Co4 ] Cubes via a Mixed-Ligand Approach: The Impact of Elastic Frustration.

The engineering of intermolecular interaction is challenging but critical for magnetically switchable molecules. Here, we prepared two cyanide-bridged [Fe4 Co4 ] cube complexes via the alkynyl- and alcohol-functionalized trispyrazoyl capping ligands. The alkynyl-functionalized complex 1 exhibited a thermally-induced incomplete metal-to-metal electron transfer (MMET) behaviour at around 220 K, while the mixed alkynyl/alcohol-functionalized cube of 2 showed a complete and abrupt MMET behaviour at 232 K. Remarkably, both compounds showed a long-lived photo-induced metastable state up to 200 K. The crystallographic study demonstrated that the incomplete transition of 1 was likely due to the possible elastic frustration originating from the competition between the anion-propagated elastic interactions and inter-cluster alkynyl-alkynyl & CH-alkynyl interactions, whereas the latter are eliminated in 2 as a result of the partial substitution by the alcohol-functionalized ligand. Additionally, the introduction of chemically distinguishable cobalt centers within the cube unit of 2 did not lead to a two-step but a one-step transition, possibly because of the strong ferroelastic intramolecular interaction through the cyanide bridges.

Enantioselective Synthesis of Quaternary Oxindoles: Desymmetrizing Staudinger-Aza-Wittig Reaction Enabled by a Bespoke HypPhos Oxide Catalyst.

This paper describes a catalytic asymmetric Staudinger-aza-Wittig reaction of (o-azidoaryl)malonates, allowing access to chiral quaternary oxindoles through phosphine oxide catalysis. We designed a novel HypPhos oxide catalyst to enable the desymmetrizing Staudinger-aza-Wittig reaction through the PIII/PV═O redox cycle in the presence of a silane reductant and an IrI-based Lewis acid. The reaction occurs under mild conditions, with good functional group tolerance, a wide substrate scope, and excellent enantioselectivity. Density functional theory revealed that the enantioselectivity in the desymmetrizing reaction arose from the cooperative effects of the IrI species and the HypPhos catalyst. The utility of this methodology is demonstrated by the (formal) syntheses of seven alkaloid targets: (-)-gliocladin C, (-)-coerulescine, (-)-horsfiline, (+)-deoxyeseroline, (+)-esermethole, (+)-physostigmine, and (+)-physovenine.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Solvent Modification of the Structures and Magnetic Properties of a Series of Dysprosium(III) Single-Molecule Magnets.

Solvent effects on the structures and magnetic properties of single-molecule magnets (SMMs) have been of great interest for modification of the SMMs using chemical modulation. By systematically varying the reaction solvents (MeOH, ethanol, n-propanol, and n-butanol), we have successfully synthesized a series of DyIII-H4daps complexes (H4daps = N',N‴-[(1E,1'E)-pyridine-2,6-diylbis(ethan-1-yl-1-ylidene)]bis(2-hydroxybenzohydrazide), including two binuclear compounds, [Dy2(H2daps)2(MeOH)4(H2O)2](CF3SO3)2·0.5MeOH (1MeOH) and [Dy2(H2daps)3(EtOH)2]·2EtOH·Et2O (2EtOH), and two mononuclear compounds, [Dy(H4daps)2](CF3SO3)3·n-PrOH (3PrOH) and [Dy(H4daps)(CF3SO3)3(n-BuOH)]·0.5Et2O (4BuOH). Using different solvents, the ligand-to-metal ratios can be adjusted from 1:1 in 1MeOH and 4BuOH to 3:2 in 2EtOH and 2:1 in 3PrOH. Through the solvent crossover experiments, the role of the solvents and the conditions to form these complexes were carefully studied. The size of the different alcohols, their coordination ability to the DyIII center, and the solubility of the complexes in these alcohols might affect the assembly process and lead to modification of the structures and magnetic properties of these DyIII-H4daps complexes. Magnetic studies revealed that these four complexes all exhibit slow magnetic relaxation under a zero or an applied direct-current field, with an energy barrier of about 100 K for the binuclear compound 1MeOH. In combination with theoretical calculations, the magnetic-structure relationship of these four compounds has been analyzed. This work demonstrates the crucial role of different solvent molecules in the fine-tuning of the structures and magnetic performances of different lanthanide complexes.

Modulating the Structures and Magnetic Properties of Dy(III) Single-Molecule Magnets through Acid-Base Regulation.

Chemical modulation on the structures and physical properties of the coordination complexes is of great interest for the preparation of new functional materials. By changing the acidity or basicity of the reaction medium, the deprotonation degree of a multidentate ligand with multiple active protons, H4daps (H4daps = N',N'″-((1E,1'E)-pyridine-2,6-diylbis(ethan-1-yl-1-ylidene))bis(2-hydroxybenzohydrazide)), can be regulated on purpose. With this ligand of different deprotonation and charges, three new DyIII complexes ([Dy(H3daps)(CH3COO)2(EtOH)]·CH3COOH (1Dy), [Dy2(H2daps)2(EtOH)2(H2O)2(MeOH)2](CF3SO3)2·(H2O)2 (2Dy), and [Dy3(H1daps)2(H2daps)(µ3-OH)(EtOH)(H2O)] (3Dy)) of different nuclearities (mono-, di-, and trinuclear for 1Dy to 3Dy, respectively) have been synthesized and characterized structurally and magnetically. Analyses on the related bond lengths and resulting hydrogen bond modes in the complexes provide the details of the deprotonation position and the charge of the ligands, which can be in the form of H3daps-, H2daps2-, and H1daps3-. Interestingly, the more deprotonated ligand can act as a bridging ligand between the DyIII centers using the phenol and/or carbonyl oxygen atoms, which leads to the multinuclear structures. Magnetic studies on these complexes revealed that complex 1Dy is a field-induced single-molecule magnet (SMM), while complexes 2Dy and 3Dy show SMM behavior under a zero dc field.

Anion Modified Spin Crossover in [Fe(qsal-4-F)]+ Complexes with a 4-Position Substituted Qsal Ligand.

Four iron(III) complexes, [Fe(qsal-4-F)2]Y·sol (Hqsal-4-F = 4-fluoro-N-(8-quinolyl)salicylaldimine; Y = NO3-, sol = 0.91MeOH·0.57H2O (1NO3); Y = PF6- (2PF6); Y = BF4- (3BF4); Y = OTf-, sol =1.5MeOH (4OTf)), with a new 4-position substituted qsal type ligand Hqsal-4-F have been synthesized and structurally and magnetically characterized. Complexes 1NO3-3BF4 consist of 1D chains formed by the [Fe(qsal-4-F)2]+ cations connected by π-π and C-H···O interactions, which are further linked by more weak interactions to form 2D layers and 3D networks. On the other hand, complex 4OTf has a structure of nearly isolated 1D column where the [Fe(qsal-4-F)2]+ cations are connected by π-π, C-H···π, and C-F···π interactions. Magnetic studies revealed the occurrence of two-step symmetry-breaking SCO in 1NO3 and two-step gradual SCO in 2PF6. Complex 3BF4 undergoes a gradual SCO, whereas 4OTf remains almost high-spin. The smaller anions tend to stabilize the low-spin state, while larger anions tend to stabilize the high-spin state. In addition, the intermediate spin state of 1NO3 could be thermally trapped by quenching from the high temperature, thereby kinetically suppressing the spin transition to the full low-spin state. This work represents a good example that the position of the substituent and the anions plays critical roles in the preparation of SCO materials with tunable properties.

Controlling Solution-State Aggregation and Solid-State Microstructures of Conjugated Polymers by Tuning Backbone Conformation.

Molecular ordering of conjugated polymers both in solution-state aggregates and in solid-state microstructures is a determining factor of the charge transport properties in optoelectronic devices. However, the effect of backbone conformation in conjugated polymers on assembly structures is still unclear. Herein, to understand such backbone conformation effect, three novel chlorinated benzodifurandionge-based oligo(p-phenylene vinylene) (BDOPV) polymers are systematically developed. These BDOPV-based polymers exhibit significantly twisted backbone conformation (near 90° interunit torsion angle) between conjugated units, which can prevent polymer chains from forming ordered assembly structures by increasing conformational energy penalty in closely packed chains. A higher rotational barrier of the torsion angle would further prevent polymer chains from assembling, finally resulting in nonaggregated chains in solution and highly disordered solid-state packing structures. This work will deepen the understanding of the relationship between polymer backbone conformation and assembly structures, contributing to the exploration of the structure-property relationship of polymers.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

[Preparation of microemulsion gel loading enriched ingredients of Epimedii Folium and its pharmacodynamics evaluation].

On the basis of previous studies, this study prepared and evaluated microemulsion gel loading enriched ingredients of Epimedii Folium and investigated its protective effect against peripheral nervous system damage caused by chemotherapeutics. The preparation method and the type and dosage of the matrix were investigated from rheology, preparation difficulty, and drug loading. Then the optimal prescription was determined and the microemulsion gel loading enriched ingredients of Epimedii Folium was prepared. The in vitro release and transdermal behaviors of the gel were investigated in the Franz diffusion cell with epimedin A1,A,B,C, and icariin as evaluation indicators. The oxaliplatin-induced peripheral neuropathy(OIPN) model was established in Wistar rats. The protective effect of the microemulsion gel loading enriched ingredients of Epimedii Folium against peripheral nervous system damage caused by chemotherapeutics was evaluated by behavioral measurement after drug administration and histopathological examination of dorsal root ganglia and sciatic nerve. The preparation process of the microemulsion gel loading enriched ingredients of Epimedii Folium was stable, and the release of the five components was consistent with the Hixson-Crowell cube root law. Behavioral indicators intuitively showed that the drug could effectively relieve mechanical allodynia caused by oxaliplatin. The histopathological examination showed that the drug can improve neuron damage in the dorsal root ganglia, axon degeneration, and demyelination caused by oxaliplatin. Therefore, the preparation process of the microemulsion gel loading enriched ingredients of Epimedii Folium is feasible, which can achieve stable drug release. It has a certain therapeutic effect on chemotherapy-induced peripheral neuropathy(CIPN).

Regulation of High Miscibility for Efficient Charge-Transport in n-Doped Conjugated Polymers.

Strong interchain interactions of conjugated polymers usually result in poor miscibility with molecular dopants, limiting the doping efficiency because of uncontrolled phase separation. We have developed a strategy to achieve efficient charge-transport and high doping miscibility in n-doped conjugated polymers. We solve the miscibility issue through disorder side-chains containing dopants better. Systemic structural characterization reveals a farther side-chain branching point will lead to higher disorders, which provides appropriate sites to accommodate extrinsic molecular dopants without harming original chain packings and charge-transport channels. Therefore, better sustainability of solid-state microstructure is obtained, yielding a stable conductivity even when overloading massive dopants. This work highlights the importance of realizing high host-dopant miscibility in molecular doping of conjugated polymers.