Active role of amino acid metabolism in early diagnosis and treatment of diabetic kidney disease.

Diabetic Kidney Disease (DKD) is one of the significant microvascular consequences of type 2 diabetes mellitus with a complex etiology and protracted course. In the early stages of DKD, the majority of patients experience an insidious onset and few overt clinical symptoms and indicators, but they are prone to develop end-stage renal disease in the later stage, which is life-threatening. The abnormal amino acid metabolism is tightly associated with the development of DKD, which involves several pathological processes such as oxidative stress, inflammatory response, and immune response and is also closely related to autophagy, mitochondrial dysfunction, and iron death. With a focus on taurine, branched-chain amino acids (BCAAs) and glutamine, we explored the biological effects of various amino acid mechanisms linked to DKD, the impact of amino acid metabolism in the early diagnosis of DKD, and the role of amino acid metabolism in treating DKD, to offer fresh objectives and guidelines for later early detection and DKD therapy.

Inducing the "re-development state" of periodontal ligament cells via tuning macrophage mediated immune microenvironment.

INTRODUCTION: Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of regenerative dentistry. In light of periodontal development, harnessing the multi-tissue developmental capabilities of periodontal ligament cells (PDLCs) and reinitiating the periodontal developmental process hold great promise as an effective strategy to foster the regeneration of the periodontal complex. OBJECTIVES: This study aims to delve into the potential effects of the macrophage-mediated immune microenvironment on the "developmental engineering" regeneration strategy and its underlying molecular mechanisms. METHODS: In this study, we conducted a comprehensive examination of the periodontium developmental process in the rat mandibular first molar using histological staining. Through the induction of diverse immune microenvironments in macrophages, we evaluated their potential effects on periodontal re-development events using a cytokine array. Additionally, we investigated PDLC-mediated periodontal re-development events under these distinct immune microenvironments through transcriptome sequencing and relevant functional assays. Furthermore, the underlying molecular mechanism was also performed. RESULTS: The activation of development-related functions in PDLCs proved challenging due to their declined activity. However, our findings suggest that modulating the macrophage immune response can effectively regulate PDLCs-mediated periodontium development-related events. The M1 type macrophage immune microenvironment was found to promote PDLC activities associated with epithelial-mesenchymal transition, fiber degradation, osteoclastogenesis, and inflammation through the Wnt, IL-17, and TNF signaling pathways. Conversely, the M2 type macrophage immune microenvironment demonstrated superiority in inducing epithelium induction, fibers formation, and mineralization performance of PDLCs by upregulating the TGFß and PI3K-Akt signaling pathway. CONCLUSION: The results of this study could provide some favorable theoretical bases for applying periodontal development engineering strategy in resolving the difficulties in periodontal multi-tissue regeneration.

Evaluation and clinical implications of interactions between compound Danshen dropping pill and warfarin associated with the epoxide hydrolase gene.

Introduction: In clinical practice, warfarin is often combined with Compound Danshen dripping pill (CDDP) for the treatment of cardiovascular diseases. However, warfarin has a narrow therapeutic index, wide interindividual variability (genetic and non-genetic factors), and is susceptible to drug-drug interactions. Our previous study indicated that CDDP might interact with warfarin in individuals with the epoxide hydrolase gene (EPHX1; single-nucleotide polymorphism: rs2292566) A/A subtype. We sought to clarify the interaction between CDDP and warfarin associated with EPHX1 in a comprehensive and accurate manner. Methods: Here, EPHX1 A and EPHX1 G cell lines were established. Expression of microsomal epoxide hydrolase (mEH), vitamin K epoxide reductase (VKOR), and vitamin K-dependent clotting factors (FII, FVII, FIX, FX) was measured by western blotting upon incubation with CDDP and warfarin. mEH activity was evaluated by measuring the transformation of epoxyeicosatrienoic acids into dihydroxyeicosatrienoic acids. Then, healthy volunteers (HVs) with the EPHX1 A/A genotype were recruited and administered warfarin and CDDP to investigate the pharmacokinetics and pharmacodynamics of warfarin. Results: CDDP combined with warfarin could decrease expression of mEH and VKOR, and increase protein expression of FII, FVII, FIX, and FX, in EPHX1 A cells. CDDP could slightly influence the pharmacokinetics/pharmacodynamics of warfarin in HVs with the EPHX1 A/A genotype. Discussion: Rational combination of CDDP and warfarin was safe with no risk of bleeding, but the therapeutic management is also needed. The clinical study is posted in the China Clinical Trial Registry (ChiCTR190002434).

Efficacy and safety of Zicuiyin decoction on diabetic kidney disease: A multicenter, randomized controlled trial.

BACKGROUD: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted. METHODS: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles. RESULTS: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group. CONCLUSIONS: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017.

Rapid Assessment of Meat Freshness by the Differential Sensing of Organic Sulfides Emitted during Spoilage.

In this work, we report the fabrication of a two-member fluorescence sensor array that enables the assessment of three stages (fresh, slightly spoiled, and moderately or severely spoiled) of meat spoilage. The first member of the array, which has strong chalcogen bonding and sulfur-π interactions with organic sulfides, exhibits very high sensitivity, while the second member of the array, which has weak chalcogen bonding and sulfur-π interactions with organic sulfides, exhibits lower sensitivity. On the basis of the combined fluorescence responses of the two members, three stages of meat spoilage, including fresh, slightly spoiled, and moderately or severely spoiled, can be monitored. Notably, using the volatiles collected from 5 g of meat products over a short period of time (1 min), this two-member sensor array achieves sensitive responses to the organic sulfides emitted from the meats. The capacity of this method to rapidly assess meat freshness facilitates its practical application, as illustrated by the monitoring of the freshness of chicken and pork products in the real world.

Therapeutic Effects of Traditional Chinese Medicine for Patients With Coronary Heart Disease After Treatment of Revascularization: A Prospective Cohort Study in the Northern of China.

Aim: To investigate the compliance and the outcome of Traditional Chinese Medicine (TCM) in patients with coronary heart disease (CHD) after treatment of revascularization. Methods: In this prospective cohort study, the non-exposure group (NEG), low-exposure group (LEG), and high-exposure group (HEG) were divided after 2 years follow-up. The primary outcome was a composite of death from cardiovascular causes, non-lethal myocardial infarction, heart transplantation, or stroke. Time-to-event data were evaluated by using the Cox regression analysis with hazard ratios (HRs) and 95% CIs. Then, the two-sided p-values were calculated by using the Cox models. In order to indicate the therapeutic effects of TCM on the CHD after revascularization, the survival analysis and the nested case-control study were conducted separately. Results: There were 1,003 patients with CHD enrolled, 356 patients (35.49%) did not choose the TCM, 379 patients (37.79%) used the TCM seldom, and only 268 patients (26.72%) used TCM regularly. A total of 653 patients with revascularization participated in the prospective cohort study. Over the duration of the trial, the primary endpoints occurred in 12 (4.35%), 11 (4.80%), and 2 (1.35%) patients in the NEG, LEG, and HEG, while the secondary endpoints occurred in 84 (30.43%), 57 (24.89%), and 15 (10.14%) patients in the NEG, LEG, and HEG, respectively. The occurrence time of secondary endpoint events in HEG was significantly postponed (p < 0.001) compared with the other cohorts. The Cox regression analysis indicated that the HRs in the primary endpoints, the secondary endpoint events, the major adverse cardiac and cerebrovascular events (MACCE), and the composite endpoint events for HEG were all around 0.3 (p < 0.05) and HRs for LEG were all around 0.8. The results of the nested case-control study showed that the TCM exposure was significantly different between the cases and controls in the secondary endpoints (p < 0.05), while no significant difference in the primary endpoints (p > 0.05), but the percentage of HEG in the cases was extremely lower than the controls. Conclusion: The HEG-TCM may improve the outcomes of the patients with CHD after treatment of revascularization. Registration: http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-17012995.

Development of a Fluorophore with Enhanced Unorthodox Chalcogen Bonding for Highly Sensitive Detection of Trimethyl Arsine Vapor.

In this work, we report the design of novel fluorophores that bear three benzothiadiazole and benzoselenadiazole groups, respectively, for sensitive detection of trimethyl arsine vapor. In particular, the fluorophore with the benzoselenadiazole groups can form stronger chalcogen bonding with trimethyl arsine than the fluorophore with the benzothiadiazole groups, which in turn triggers much faster and more sensitive fluorescence responses. On the basis of this novel mechanism, fluorescence detection of trimethyl arsine vapor with rapid response (∼3 s), high sensitivity (the theoretical LOD is 0.44 ppb), and high selectivity is achieved on bundled nanofibers from the fluorophore with the benzoselenadiazole groups. Here, the new fluorescence sensor may find wide applications in health and environmental monitoring, arsenic distribution recognition in soil, and arsenic mines exploration.

Alteration of gut microbial profile in patients with diabetic nephropathy.

AIMS: Investigations show that 30-40% of patients with diabetes develop diabetic nephropathy (DN). The gut microbiome has become lively field research in diabetes mellitus and chronic kidney disease. The gut microbial profile in DN (stage-3 or 4) patients and healthy controls were systematically analyzed, the discrepancies on microbial profiles in different disease stages, gender, and BMI in DN were also described. METHODS: Fecal samples from 37 healthy volunteers (HG) and 43 DN patients (PG) were recruited to gut microbiota 16S rDNA V3-V4 regions analysis. In consideration of disease stage, gender, and BMI, PG, and HG were further divided into three subgroups. To predict the DN stage, a random forest model was carried out, using the most discrepant genera selected from the PG and HG samples. RESULTS: Gut bacterial richness and diversity in PG were far less than HG. The gut microbiota composition in PG-III was at the middle level between HG and PG-IV. The gender and BMI had some impact on the gut microbiota profile but the major difference still came from the disease. The random forest model was constructed from 25 most discrepant microbe genera. The area under curve (AUC) of receiving operational curve (ROC) was 0.972, indicated a high discriminatory power to predict DN. CONCLUSIONS: DN patients showed dysbiosis and a decrease in gut bacterial richness and diversity compared with HG. Several characterized genera like Megasphaera, Veillonella, Escherichia-Shigella, Anaerostipes, and Haemophilus might be the new potential microbial biomarkers of DN.

Intermittent parathyroid hormone promotes cementogenesis via ephrinB2-EPHB4 forward signaling.

Intermittent parathyroid hormone (PTH) promotes periodontal repair, but the underlying mechanisms remained unclear. Recent studies found that ephrinB2-EPHB4 forward signaling mediated the anabolic effect of PTH in bone homeostasis. Considering the similarities between cementum and bone, we aimed to examine the therapeutic effect of PTH on resorbed roots and explore the role of forward signaling in this process. In vivo experiments showed that intermittent PTH significantly accelerated the regeneration of root resorption and promoted expression of EPHB4 and ephrinB2. When the signaling was blocked, the resorption repair was also delayed. In vitro studies showed that intermittent PTH promoted the expression of EPHB4 and ephrinB2 in OCCM-30 cells. The effects of PTH on the mineralization capacity of OCCM-30 cells was mediated through the ephrinB2-EPHB4 forward signaling. These results support the premise that the anabolic effects of intermittent PTH on the regeneration of root resorption is via the ephrinB2-EPHB4 forward signaling pathway.

Thirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies.

RELEVANCE: Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained. MATERIALS AND METHODS: We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters. RESULTS: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism. CONCLUSION: Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.

Downregulation of Interferon-γ Receptor Expression Endows Resistance to Anti-Programmed Death Protein 1 Therapy in Colorectal Cancer.

Immune checkpoint inhibitors have emerged as a frontline treatment of a variety of malignancies. However, only a subset of patients respond to these therapies, and many initial responders eventually develop resistance, leading to tumor relapse. Programmed death protein 1 is one of the checkpoint inhibitors that is expressed on activated T cells and suppresses the antitumor immune response when binding to its ligand, programmed death ligand 1, on tumor cells. Previous studies indicated that loss-of-function mutations in the IFN-γ pathway could result in acquired resistance to immune checkpoint inhibitors in human patients with cancer. Here, we investigated the effects of the IFN-γ receptor downexpression on the response to an anti-PD-1 antibody (αPD1) in a murine colorectal cancer model and the underlying mechanisms of resistance. IFN-γ receptor (IFNGR) 1 was knocked down in MC38 cells, a murine colon adenocarcinoma cell line using IFNGR1 short hairpin RNA (shRNA) lentiviral particles. Then, MC38 IFNGR1 knockdown (KD) cells and negative control (SC) cells were used in this study. In the C57BL/6 xenograft model, the KD tumor demonstrated resistance to αPD1 in comparison with SC cells. The observed treatment resistance might be associated with reduced tumor-infiltrating immune cells (TILs). When mixed, the resistant (KD) and control cells (SC) grew in spatially separated tumor areas, and αPD1 did not impact this pattern of spatial distribution. Our findings have proved that downregulation of the IFNGR1 endowed resistance to αPD1 and provided the potential mechanisms involving the TILs. SIGNIFICANCE STATEMENT: Immunological checkpoint blockades have achieved substantial efficacy in a variety of tumors. However, only a subset of patients respond to these therapies, and innate and acquired resistance is widely present. Our study found that the downregulation of the IFN-γ receptor caused resistance to an anti-PD-1 antibody in a murine colorectal cancer model associated with the reduced tumor-infiltrating lymphocytes. Our findings have substantial implications for improving the efficacy of checkpoint blockades.

Risk factors for maxillary impacted canine-linked severe lateral incisor root resorption: A cone-beam computed tomography study.

INTRODUCTION: Impacted maxillary canine-linked severe lateral incisor root resorption (SIRRc) is rare, but it greatly influences the survival of the affected teeth. Our study was designed to investigate the risk factors for SIRRc. METHODS: Eighty-two patients with SIRRc and 81 patients with impacted maxillary canines but without SIRRc were included and evaluated by cone-beam computed tomography in software programs by 1 examiner (H.W.). Age, sex, positions, and dental follicles and angular inclinations of impacted canines were measured in this study. Binary logistic regression was used to analyze the risk factors for SIRRc. RESULTS: SIRRc was highly related to sex, vertical and mesiodistal position, dental follicles sizes of canines, and intersection angles in 3 dimensions. The regression analysis showed female sex, dental follicles between 1 mm and 3 mm, mesial third and apical third position, vertical angle smaller than 30°, and the relative angle between 30° and 60° were significant risk factors for SIRRc. CONCLUSIONS: Early diagnosis and treatment for SIRRc are imperative, especially in Asian patients that are female with apically and mesially positioned canines as well as wider dental follicles. Vertical angles and relative angles of impacted canines should also be noticed.

Palatal expansion and relapse in rats: A histologic and immunohistochemical study.

INTRODUCTION: Rapid palatal expansion is an effective intervention for correcting transverse maxillary deficiency in growing patients. However, relapse after treatment is often observed, and the mechanisms of tissue remodeling during expansion and relapse remain unclear. This study aimed to gain insight into such a mechanism. METHODS: A total of 24 5-week-old male Wistar rats were randomly divided into either the expansion or sham device (control) group. Each rat underwent 7 days of expansion and 7 days of relapse. The width of the dental arch, palatal bone, and suture, as well as the angle of the teeth, were measured. Tissue remodeling in the midpalatal suture was examined using microcomputed tomography and histologic and immunohistochemical analyses. RESULTS: The mechanical expansion force caused an increase in arch width, which relapsed after the removal of force. Bilateral tilting of the teeth and midpalatal suture expansion contributed to the widening of the maxillary arch, and only the relapse of the palatal bone width was observed. Histochemical staining showed that suture tissue remodeling was activated by mechanical force in the expansion group and reverted to the level of the control group after relapse. Immunohistochemistry staining revealed that the expression of cathepsin K, osteocalcin, and collagen type I was higher in the expansion group than that in the control group on day 7; however, the difference dissipated by day 14. CONCLUSIONS: The expansion force stimulated osteogenic activity in the midpalatal suture area. After removal of the expansion force, tissue remodeling went back to the normal level.

Effects of estrogen on root repair after orthodontically induced root resorption in ovariectomized rats.

INTRODUCTION: This study aimed to investigate the effects of estrogen on root repair after orthodontically induced root resorption. METHODS: Seventy-two 6-week-old female Wistar rats were randomly divided into 3 groups: ovariectomy only (OVX), ovariectomy plus estradiol injection (OVX + E2), and sham operation (control). E2 was administrated to all the experimental animals after the establishment of the root repair model. One-way analysis of variance with the Tukey post-hoc test was used to analyze the experimental results. RESULTS: Micro-computed tomography and hematoxylin and eosin staining showed that the total volumes of resorption lacunae were significantly smaller in the control and OVX + E2 groups than those in the OVX group. Alkaline phosphatase and tartrate-resistant acid phosphatase stainings suggested that the cementoblastic activities and the amount of new cementum formation were inhibited while the activities of osteoclasts were obvious in the OVX group. The immunohistochemistry stainings revealed that the osteoprotegerin to receptor activator of nuclear factor-кB ligand ratio and the phosphorylated extracellular signal-regulated kinases to extracellular signal-regulated kinases ratio of the control and OVX + E2 groups were significantly greater than those of the OVX group. CONCLUSIONS: These findings demonstrated that estrogen administration might be a solution to reduce orthodontically induced root resorption through the activation of extracellular signal-regulated kinase-1/2 pathway and enhancement of cementogenesis.

A [001]-Oriented Hittorf's Phosphorus Nanorods/Polymeric Carbon Nitride Heterostructure for Boosting Wide-Spectrum-Responsive Photocatalytic Hydrogen Evolution from Pure Water.

Red phosphorus is a promising photocatalyst with wide visible-light absorption up to 700 nm, but the fast charge recombination limits its photocatalytic hydrogen evolution reaction (HER) activity. Now, [001]-oriented Hittorf's phosphorus (HP) nanorods were successfully grown on polymeric carbon nitride (PCN) by a chemical vapor deposition strategy. Compared with the bare PCN and HP, the optimized PCN@HP hybrid exhibited a significantly enhanced photocatalytic activity, with HER rates reaching 33.2 and 17.5 µmol h-1 from pure water under simulated solar light and visible light irradiation, respectively. It was theoretically and experimentally indicated that the strong electronic coupling between PCN and [001]-oriented HP nanorods gave rise to the enhanced visible light absorption and the greatly accelerated photoinduced electron-hole separation and transfer, which benefited the photocatalytic HER performance.

The Effect of Compound Danshen Dripping Pills on the Dose and Concentration of Warfarin in Patients with Various Genetic Polymorphisms.

PURPOSE: The combination of warfarin and compound Danshen dripping pill (CDDP) is helpful for patients with both coronary heart disease (CHD) and atrial fibrillation (AF). The main adverse drug reaction of warfarin is bleeding because of its narrow therapeutic index. The safety of a combination therapy with warfarin and CDDP is always a concern. Our previous research showed that the combination of warfarin and CDDP improved the quality of life for patients with both CHD and AF. This study describes the changes in dose and concentration of warfarin necessary and evaluates bleeding risk when warfarin is given concomitantly with CDDP. METHODS: An ultra-performance liquid chromatography-MS/MS method with a chiral column was developed to assay the concentration of S-warfarin and R-warfarin in human plasma simultaneously. The method was applied to compare the concentration of warfarin in patients taking warfarin combined with CDDP and without CDDP. International normalized ratio (INR) values were monitored to evaluate bleeding risk. Paired t tests were then used to compare the dose and the concentration in 2 periods. Moreover, patients with VKORC1, CYP2C9*3, CYP4F2, EPHX1, and PROC gene polymorphisms were evaluated to determine interactions. FINDINGS: The results indicate that the dose of warfarin had no significant change with or without CDDP. Also, the peak concentrations of S-warfarin and total warfarin were significantly different in CYP4F2 C/C patients, but there was no significant difference identified in other genetic groups. No bleeding occurred in the study. IMPLICATIONS: The dose of warfarin would be sustainable when combined with CDDP, because CDDP did not affect concentration of warfarin significantly in most patients and the change of INR was not significant. CHINA CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-ONRC-13003523.

3D Sulfur and Nitrogen Codoped Carbon Nanofiber Aerogels with Optimized Electronic Structure and Enlarged Interlayer Spacing Boost Potassium-Ion Storage.

Carbonaceous materials are promising anodes for potassium-ion batteries (PIBs). However, it is hard for large K ions (1.38 Å) to achieve long-distance diffusion in pristine carbonaceous materials. In this work, the following are synthesized: S/N codoped carbon nanofiber aerogels (S/N-CNFAs) with optimized electronic structure by S/N codoping, enhanced interlayer spacing by S doping, and a 3D interconnected porous structure of aerogel, through a pyrolysis sustainable seaweed (Fe-alginate) aerogel strategy. Specifically, the S/N-CNFAs electrode delivers high reversible capacities of 356 and 112 mA h g-1 at 100 and 5000 mA g-1 , respectively. The capacity reaches 168 mA h g-1 at 2000 mA g-1 after 1000 cycles. A full cell with a S/N-CNFAs anode and potassium prussian blue cathode displays a specific capacity of 198 mA h g-1 at 200 mA g-1 . Density functional theory calculations indicate that S/N codoping is beneficial to synergistically improve K ions storage of S/N-CNFAs by enhancing the adsorption of K ions and reducing the diffusion barrier of K ions. This work offers a facile heteroatom doping paradigm for designing new carbonaceous anodes for high-performance PIBs.

Intermittent parathyroid hormone promotes cementogenesis in a PKA- and ERK1/2-dependent manner.

BACKGROUND: Intermittent parathyroid hormone (PTH) promotes cementogenesis and provides a promising biotherapeutic to rehabilitate resorbed roots. However, the underlying mechanisms remain inconclusive. Cyclic aenosine monophosphate (AMP)-dependent protein kinases A (PKA) and extracellular signal-regulated MAP kinases 1/2 (ERK1/2) are key regulators of bone remodeling. The present study aims to investigate whether PKA and ERK1/2 are involved in the process of intermittent PTH-promoted cementogenesis. METHODS: Sprague-Dawley rats in experimental group (n = 30) received a daily subcutaneous injection of PTH and the control (n = 30) received placebo vehicle for 1, 2, 3, 4, and 5 weeks. Results were evaluated by hematoxylin and eosin and immunohistochemistry staining. In vitro, OCCM-30 cells were incubated with intermittent PTH. H89 and U0126 were used to determine the role of PKA and ERK1/2, respectively. The cementogenic results were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, alkaline phosphatase activity assay and Alizarin Red S staining. The interaction of PKA and p-ERK1/2 was determined by co-immunoprecipitation (Co-IP). RESULTS: Intermittent PTH exerted anabolic effect on cellular cementum in developing teeth with elevated expression of osteocalcin, osteopontin, and PKA (catalytic subunit) in PTH injection group. The promoting effects of intermittent PTH on cementogenesis and osteogenic differentiation were abrogated by H89 and U0126 in vitro, respectively. Blocking of PKA pathway downregulated intermittent PTH-induced ERK1/2 phosphorylation. CONCLUSIONS: Intermittent PTH promotes cementogenesis in a PKA- and ERK1/2-dependent manner. In this process, PKA and p-ERK1/2 interact with each other. These results support the future biotherapeutic applications of PTH in cementum resorption.

Simultaneous determination of seven effective components of Tripterygium glycosides in human biological matrices by ultra performance liquid chromatography-triple quadrupole mass spectrometry.

This paper developed a novel, sensitive, and selective ultra-performance liquid chromatography-triple quad mass spectrometry method to simultaneously determine seven effective constituents (triptolide, triptophenolide, celastrol, wilforgine, wilforine, wilfordine and wilfortrine) of Tripterygium glycosides (GTW) in human serum and urine. The chromatographic separation was performed on the C18 column using an ammonium acetate buffer solution-acetonitrile (both containing 0.1% formic acid) in a gradient program with a flow rate of 0.3 mL/min. Monitoring reaction mode was applied to target compounds quantitative analysis in the positive electrospray ionization (ESI) mode. The analysis process took 11 min in total. This method was fully validated with a linear range of 1-200 ng/mL for triptolide, 0.4-80 ng/mL for celastrol, 0.1-20 ng/mL for triptophenolide, wilforgine, wilforine, wilfordine, and wilfortrine. The intra-day and inter-day accuracy and precision of the target compounds all met the 15% criterion in both serum and urine. Extraction recovery, matrix effect, and dilution integrity were also validated. The short-term and long-term stability results indicated that all the constituents were stable in human serum and urine under the investigated storage conditions. 10 patients' specimens were collected and analyzed. Most of the compounds exhibited the tendency of higher concentration in urine than that in serum. The concentration that was detected in the serum and in the urine of alkaloids showed a positive-correlation property. This is the first time that triptophenolide was quantified in human bio-matrices. The method is feasible for multi-components therapeutic monitoring or pharmacokinetics study in clinical pharmaceutical research of Tripterygium glycosides.