ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.

An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia.

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.

Tailoring the Wettability and Substrate Adherence of Thin Polymer Films with Surface-Segregating Bottlebrush Copolymer Additives.

We developed "reactive" bottlebrush polymers based on styrene (S) and t-butyl acrylate (tBA) as additives for polystyrene (PS) coatings. The bottlebrush polymers spontaneously bloom to both the air and substrate interfaces during solution casting. While neat PS films are hydrophobic and poorly adhere to the native oxide on clean silicon wafers, the hydrophilicity and substrate adherence of bottlebrush-incorporating PS films can be tailored through the thermally activated deprotection of tBA to produce acrylic acid (AA) and acrylic anhydride (AH). A critical design parameter is the manner by which tBA is incorporated into the bottlebrush: When the bottlebrush side chains are copolymers of S and tBA, the extent of deprotection is extremely low, even after prolonged thermal annealing at elevated temperature. However, when the bottlebrush contains a mixture of poly(t-butyl acrylate) (PtBA) and PS side chains, nearly all tBA is converted to AA and AH. Consequently, using the "mixed-chain" bottlebrush design with thermal processing and appropriate conditioning, the water contact angle is reduced from over 90° on unmodified PS down to 75° on bottlebrush-incorporating PS films, and the substrate adherence is improved in proportion to the extent of tBA deprotection.

Human disease clinical treatment network for the elderly: analysis of the medicare inpatient length of stay and readmission data.

Clinical treatment outcomes are the quality and cost targets that health-care providers aim to improve. Most existing outcome analysis focuses on a single disease or all diseases combined. Motivated by the success of molecular and phenotypic human disease networks (HDNs), this article develops a clinical treatment network that describes the interconnections among diseases in terms of inpatient length of stay (LOS) and readmission. Here one node represents one disease, and two nodes are linked with an edge if their LOS and number of readmissions are conditionally dependent. This is the very first HDN that jointly analyzes multiple clinical treatment outcomes at the pan-disease level. To accommodate the unique data characteristics, we propose a modeling approach based on two-part generalized linear models and estimation based on penalized integrative analysis. Analysis is conducted on the Medicare inpatient data of 100,000 randomly selected subjects for the period of January 2010 to December 2018. The resulted network has 1008 edges for 106 nodes. We analyze key network properties including connectivity, module/hub, and temporal variation. The findings are biomedically sensible. For example, high connectivity and hub conditions, such as disorders of lipid metabolism and essential hypertension, are identified. There are also findings that are less/not investigated in the literature. Overall, this study can provide additional insight into diseases' properties and their interconnections and assist more efficient disease management and health-care resources allocation.

Network and covariate adjusted response-adaptive design for binary response.

Randomization is a distinguishing feature of clinical trials for unbiased assessment of treatment efficacy. With a growing demand for more flexible and efficient randomization schemes and motivated by the idea of adaptive design, in this article we propose the network and covariate adjusted response-adaptive (NCARA) design that can concurrently manage three challenges: (1) maximizing benefits of a trial by assigning more patients to the superior treatment group randomly; (2) balancing social network ties across treatment arms to eliminate potential network interference; and (3) ensuring balance of important covariates, such as age, gender, and other potential confounders. We conduct simulation with different network structures and a variety of parameter settings. It is observed that the NCARA design outperforms four alternative randomization designs in solving the above-mentioned problems and has comparable power and type I error for detecting true difference between treatment groups. In addition, we conduct real data analysis to implement the new design in two clinical trials. Compared to equal randomization (the original design utilized in the trials), the NCARA design slightly increases power, largely increases the percentage of patients assigned to the better-performing group, and significantly improves network and covariate balances. It is also noted that the advantages of the NCARA design are augmented when the sample size is small and the level of network interference is high. In summary, the proposed NCARA design assists researchers in conducting clinical trials with high-quality and high-efficiency.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

Constructing BiOBr1-xIx-y with Abundant Surface Br Vacancies for Excellent Visible-Light Photodegradation Capability of High-Concentration Refractory Contaminants.

Bismuth oxybromide (BiOBr) is a promising photocatalytic semiconductor material due to its unique hierarchical structure and band structure. However, its photocatalytic applications are restricted due to its narrow visible-light absorption range and poor photooxidation capability. In this study, BiOBr1-xIx-y with rich surface Br vacancies (BrVs-rich BiOBr1-xIx-y) was created via a facile indirect substitution strategy. Benefiting from the broadened visible-light response range and reduced recombination rate of photogenerated carriers, BiOBr1-xIx-y shows excellent visible-light photodegradation ability for high-concentration refractory contaminants, such as phenol, tetracycline, bisphenol A, rhodamine B, methyl orange, and even real wastewater. At the same time, the Br vacancies can regulate the band structure of BiOBr1-xIx-y and serve as trap states to promote charge separation, thus facilitating surface photoredox reactions. An in-depth investigation of the Br vacancy effect and photodegradation mechanism was conducted. This novel study revealed the significance of Br vacancies in enhancing the photocatalytic performance of BiOBr under visible light, providing a promising strategy for improving the utilization efficiency of sunlight in wastewater treatment.

In Situ Construction of BiO(ClBr)(1-x)/2Ix-n Solid Solution with Appropriate Surface Iodine Vacancies for Synergistically Boosting Visible-Light Photo-Oxidation Capability.

A proposed BiO(ClBr)(1-x)/2Ix-n solid solution containing abundant iodine vacancies has been constructed through a facile solvothermal treatment strategy. Fascinatingly, the iodine-vacancy BiO(ClBr)(1-x)/2Ix-n solid solution exhibits an outstanding visible-light photocatalytic degradation property for the environmentally hazardous pollutants of methyl orange, tetracycline, and phenol solutions, which is credited to the synergistic effect of iodine vacancies and the solid solution. By manipulating the molar ratios of Cl, Br, and I, the band structure of the solid solution attained is controlled, enabling the samples to maximize the harvest of visible light and to possess strong oxidation features. More importantly, the construction of iodine vacancies is bound to modulate the local surface atomic structure and promotes the efficiency of the separation of photogenerated carriers. Given these, the microstructure and physicochemical and photoelectrochemical properties of the photocatalysts are fully characterized in a series. In addition, the iodine-vacancy BiO(ClBr)(1-x)/2Ix-n solid solution has a stable crystal structure that permits favorable recyclability even after multiple cycles of degradation. This study sheds light on the significance of the simultaneous existence of vacancy and the solid solution for the enhanced performance of photocatalysts and opens up new insights for sustainable solar-chemical energy conversion.

Efficacy of dual enkephalinase inhibition in a preclinical migraine model is mediated by activation of peripheral delta opioid receptors.

OBJECTIVE: The aim of this study was to evaluate whether elevating levels of enkephalin by inhibiting their degradation can attenuate stress-induced migraine-like behaviors in mice. BACKGROUND: Previous studies in animals have suggested the delta opioid receptor (DOR) as a novel migraine target. The primary endogenous ligands for DOR are enkephalins and their levels can be increased by pharmacological inhibition of enkephalinases; however, it is not clear whether enkephalinase inhibition can be efficacious in preclinical migraine models through activation of DOR or whether other opioid receptors might be involved. Further, it is not clear whether opioid receptors in the central nervous system are necessary for these effects. METHODS: This study used a model of repetitive restraint stress in mice that induces periorbital hypersensitivity and priming to the nitric oxide donor sodium nitroprusside (SNP; 0.1 mg/kg). Von Frey filaments were used to measure periorbital mechanical thresholds and grimace scores were evaluated by observing mouse facial features. Animals were treated with the dual enkephalinase inhibitor (DENKI) PL37. RESULTS: On day two post-stress, PL37 given to mice via either intravenous injection (10 mg/kg) or oral gavage (20 mg/kg) significantly attenuated stress-induced periorbital hypersensitivity and facial grimace responses. Additionally, both intravenous (10 mg/kg) and oral gavage (20 mg/kg) of PL37 prior to SNP (0.1 mg/kg) administration on day 14 post-stress significantly reduced SNP-induced facial hypersensitivity. Injection of the DOR antagonist naltrindole (0.1 mg/kg) but not the mu-opioid receptor antagonist CTAP (1 mg/kg) prior to PL37 treatment blocked the effects. Finally, pretreatment of mice with the peripherally restricted opioid receptor antagonist naloxone methiodide (5 mg/kg) blocked the effects of PL37. CONCLUSIONS: These data demonstrate that inhibiting enkephalinases, and thus protecting enkephalins from degradation, attenuates stress-induced migraine-like behavior via activation of peripheral DOR. Peripheral targeting of endogenous opioid signaling may be an effective therapeutic strategy for migraine.

Ratiometric fluorescence determination of alkaline phosphatase activity based on carbon dots and Ce3+-crosslinked copper nanoclusters.

A new ratiometric fluorescent probe for efficient determination of ALP was developed. The probe was constructed by combining Ce3+-crosslinked copper nanoclusters (Ce3+-CuNCs) which exhibit the aggregation-induced emission (AIE) feature with carbon dots (CDs). The introduction of phosphate (Pi) induced the generation of CePO4 precipitation, resulting in significant decrease of fluorescence emission of CuNCs at 634 nm. At the same time, the fluorescence of CDs at 455 nm was obviously enhanced, thus generating ratiometric fluorescence response. Based on the fact that the hydrolysis of pyrophosphate (PPi) by ALP can produce Pi, the CD/Ce3+-CuNCs ratiometric probe was successfully used to determine ALP. A good linear relationship between the ratiometric value of F455/F634 and ALP concentrations ranging from 0.2 to 80 U·L- 1 was obtained, with a low detection limit of 0.1 U·L- 1. The ratiometric responses of the probe resulted in the visible fluorescence color change from orange red to blue with the increase of ALP concentration. The smartphone-based RGB recognition of the fluorescent sample images was used for ALP quantitative determination. A novel ratiometric fluorescent system based on Ce3+-CuNCs with AIE feature and CDs were constructed for efficient detection of ALP.

Assessment of breast lesions by the Kaiser score for differential diagnosis on MRI: the added value of ADC and machine learning modeling.

OBJECTIVES: To evaluate the diagnostic performance of Kaiser score (KS) adjusted with the apparent diffusion coefficient (ADC) (KS+) and machine learning (ML) modeling. METHODS: A dataset of 402 malignant and 257 benign lesions was identified. Two radiologists assigned the KS. If a lesion with KS > 4 had ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 to become KS+. In order to consider the full spectrum of ADC as a continuous variable, the KS and ADC values were used to train diagnostic models using 5 ML algorithms. The performance was evaluated using the ROC analysis, compared by the DeLong test. The sensitivity, specificity, and accuracy achieved using the threshold of KS > 4, KS+ > 4, and ADC ≤ 1.4 × 10-3 mm2/s were obtained and compared by the McNemar test. RESULTS: The ROC curves of KS, KS+, and all ML models had comparable AUC in the range of 0.883-0.921, significantly higher than that of ADC (0.837, p < 0.0001). The KS had sensitivity = 97.3% and specificity = 59.1%; and the KS+ had sensitivity = 95.5% with significantly improved specificity to 68.5% (p < 0.0001). However, when setting at the same sensitivity of 97.3%, KS+ could not improve specificity. In ML analysis, the logistic regression model had the best performance. At sensitivity = 97.3% and specificity = 65.3%, i.e., compared to KS, 16 false-positives may be avoided without affecting true cancer diagnosis (p = 0.0015). CONCLUSION: Using dichotomized ADC to modify KS to KS+ can improve specificity, but at the price of lowered sensitivity. Machine learning algorithms may be applied to consider the ADC as a continuous variable to build more accurate diagnostic models. KEY POINTS: • When using ADC to modify the Kaiser score to KS+, the diagnostic specificity according to the results of two independent readers was improved by 9.4-9.7%, at the price of slightly degraded sensitivity by 1.5-1.8%, and overall had improved accuracy by 2.6-2.9%. • When the KS and the continuous ADC values were combined to train models by machine learning algorithms, the diagnostic specificity achieved by the logistic regression model could be significantly improved from 59.1 to 65.3% (p = 0.0015), while maintaining at the high sensitivity of KS = 97.3%, and thus, the results demonstrated the potential of ML modeling to further evaluate the contribution of ADC. • When setting the sensitivity at the same levels, the modified KS+ and the original KS have comparable specificity; therefore, KS+ with consideration of ADC may not offer much practical help, and the original KS without ADC remains as an excellent robust diagnostic method.

The importance of CYP2C19 genotype in tacrolimus dose optimization when concomitant with voriconazole in heart transplant recipients.

AIMS: Voriconazole remains the mainstay for the treatment of invasive fungal infections in heart transplant patients and can significantly increase tacrolimus exposure because of drug-drug interaction (DDI). However, the magnitude of this DDI is highly variable and difficult to predict. The purpose of this study was to present the characteristics of the DDI between tacrolimus and voriconazole, and further identify the various predictors of tacrolimus dose modification. METHODS: We retrospectively enrolled 69 heart transplant recipients who did not use voriconazole as the control and 68 patients received voriconazole treatment in voriconazole group. CYP3A4*1G, CYP3A5*3 and CYP2C19*2 or *3 were thereafter genotyped by Sanger sequencing. The dose of tacrolimus required to achieve the therapeutic concentrations and tacrolimus dose-corrected trough concentration (C0 /D) before and after VRC administration was evaluated. RESULTS: The DDI between tacrolimus and voriconazole displayed a large interindividual variability with more than 10-fold changes in tacrolimus dose (range 1.28-13.00) and C0 /D (range 1.43-13.75). In addition, the fold changes for the tacrolimus dose were associated with CYP2C19 genotype, which was found to be significantly lower in CYP2C19 extensive metabolizers than in CYP2C19 intermediate metabolizers or poor metabolizers (4.06 ± 1.85 vs 5.49 ± 2.47, P = .0031). However, no significant difference was found in both CYP3A4 and CYP3A5 genotypes. Moreover, CYP2C19 genotype and hematocrit acted as independent predicting factors for tacrolimus dose modification after voriconazole co-therapy. CONCLUSIONS: The findings of this study have identified the various important factors to adjust tacrolimus dosage when co-administrated with voriconazole in individual patients. CYP2C19 genotype and haematocrit should be considered when tailoring tacrolimus dose.

Indirect Substitution Constructing Halogen-Vacancy BiOCl1-xIn Solid Solution with a Suitable Surface Structure for Enhanced Photoredox Performance.

Photocatalytic technology has made a series of breakthroughs in environmental remediation, but the degradation performance of persistent heavy metal ions and organic pollutants is not particularly excellent. In addition, the layered structure of bismuth oxyhalides (BiOX, X = I, Br, and Cl) has been a popular material for photodegradation and photoelectrochemistry. Accordingly, with a view to construct a suitable band structure and control the surface structure, it is necessary to develop a strategy to synthesize a BiOCl1-xIn solid solution with halogen vacancies. In this study, halogen vacancies are in situ introduced into the BiOCl1-xIn solid solution through constructing chemical bonds between the hydroxyl groups in glycerol and the I ions during the growth process. The band of the halogen-vacancy BiOCl1-xIn solid solution is widened and active sites centered at halogen vacancies are formed in the direction favorable for the photocatalytic reaction, resulting in enhanced performance in the reduction of Cr(VI) and the oxidation of phenol. The results obtained can provide a new idea for the design of efficient photocatalysts by controlling the formation of halogen vacancies.

Self-Assembly of Metal-Organic Frameworks on Graphene Oxide Nanosheets and In Situ Conversion into a Nickel Hydroxide/Graphene Oxide Battery-Type Electrode.

Graphene oxide (GO) has been widely reported as a supercapacitor electrode. Especially, GO is usually utilized to composite with electrochemical active materials, such as transition-metal oxide/hydroxide/sulfide, due to its considerable conductivity and mechanical strength. However, the ideal design and treatment for compositing GO with active materials are still challenging. Herein, an Ni-metal-organic framework (MOF) was self-assembled on GO nanosheets via the solvothermal method and was subsequently etched into the Ni(OH)2-GO composite electrode material through a gentle hydrolysis strategy. The GO support enables fast electron transport within the composite material, and the nickel hydroxide growth on GO nanosheets can prevent their aggregation, guaranteeing rapid ion migration. The improved Ni(OH)2-GO battery-type electrode features outstanding stability (capacity retention of 108% at 8000 cycles) and a considerable specific capacity (SC) of 1007.5 C g-1 at a current density of 0.5 A g-1. Compared with MOF-derived Ni(OH)2 obtained through hydrolysis, Ni(OH)2-GO only contains 7.41% wt GO, while its SC is almost 50% higher. An asymmetric supercapacitor has an energy density of 65.22 W h kg-1 and a power density of 395.27 W kg-1 utilizing p-phenylenediamine-functional reduced GO as the negative electrode, and it can maintain 73.08% capacity during 8000 cycles at a current density of 5 A g-1.

Sulphur ylide-mediated cyclopropanation and subsequent spirocyclopropane rearrangement reactions.

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation via sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-c]quinoline framework through a novel rearrangement process.

Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing.

BACKGROUND: In the last decade, genomic studies have identified and replicated thousands of genetic associations with measures of health and disease and contributed to the understanding of the etiology of a variety of health conditions. Proteins are key biomarkers in clinical medicine and often drug-therapy targets. Like genomics, proteomics can advance our understanding of biology. METHODS AND RESULTS: In the setting of the Cardiovascular Health Study (CHS), a cohort study of older adults, an aptamer-based method that has high sensitivity for low-abundance proteins was used to assay 4979 proteins in frozen, stored plasma from 3188 participants (61% women, mean age 74 years). CHS provides active support, including central analysis, for seven phenotype-specific working groups (WGs). Each CHS WG is led by one or two senior investigators and includes 10 to 20 early or mid-career scientists. In this setting of mentored access, the proteomic data and analytic methods are widely shared with the WGs and investigators so that they may evaluate associations between baseline levels of circulating proteins and the incidence of a variety of health outcomes in prospective cohort analyses. We describe the design of CHS, the CHS Proteomics Study, characteristics of participants, quality control measures, and structural characteristics of the data provided to CHS WGs. We additionally highlight plans for validation and replication of novel proteomic associations. CONCLUSION: The CHS Proteomics Study offers an opportunity for collaborative data sharing to improve our understanding of the etiology of a variety of health conditions in older adults.

Effects of childhood obesity and related genetic factors on precocious puberty: protocol for a multi-center prospective cohort study.

BACKGROUND: Childhood obesity has important effects on the onset and development of puberty. Although a number of studies have confirmed the relationship between obesity and precocious puberty, little is known about the pleiotropic genes of obesity and precocious puberty and the interaction between genes and environment. There are four objectives: (1) to analyze the incidence of precocious puberty in the general population in China; (2) to verify the direct effect of obesity on children's precocious puberty using a variety of methods; (3) to verify the effect of obesity and its risk gene polymorphism on precocious puberty in a prospective cohort study; and (4) to analyze the interaction effect of genes and environment on pubertal development. METHODS: We will conduct a multi-center prospective cohort study in three cities, which are selected in southern, central, and northern China, respectively. Primary schools in these cities will be selected by a stratified cluster random sampling method. Primary school students from grade 1 to grade 3 (6 to 10 years old) will be selected for the cohort with extensive baseline data collection, including assessment of pubertal development, family demographic information, early development, sleep pattern, dietary pattern, and physical activity. Participants will be followed up for at least three years, and long-term follow-up will depend on future funding. DISCUSSION: The findings of this multicenter prospective population-based cohort study may expand previous related puberty development research as well as provide important information on the mechanism of early puberty. Targeted interventions can also be developed to improve adolescent health problems related to puberty development based on the available evidence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04113070 , prospectively registered on October 2, 2019.