Exploiting relationship directionality to enhance statistical modeling of peer-influence across social networks.

Risky-prescribing is the excessive or inappropriate prescription of drugs that singly or in combination pose significant risks of adverse health outcomes. In the United States, prescribing of opioids and other "risky" drugs is a national public health concern. We use a novel data framework-a directed network connecting physicians who encounter the same patients in a sequence of visits-to investigate if risky-prescribing diffuses across physicians through a process of peer-influence. Using a shared-patient network of 10 661 Ohio-based physicians constructed from Medicare claims data over 2014-2015, we extract information on the order in which patients encountered physicians to derive a directed patient-sharing network. This enables the novel decomposition of peer-effects of a medical practice such as risky-prescribing into directional (outbound and inbound) and bidirectional (mutual) relationship components. Using this framework, we develop models of peer-effects for contagion in risky-prescribing behavior as well as spillover effects. The latter is measured in terms of adverse health events suspected to be related to risky-prescribing in patients of peer-physicians. Estimated peer-effects were strongest when the patient-sharing relationship was mutual as opposed to directional. Using simulations we confirmed that our modeling and estimation strategies allows simultaneous estimation of each type of peer-effect (mutual and directional) with accuracy and precision. We also show that failing to account for these distinct mechanisms (a form of model mis-specification) produces misleading results, demonstrating the importance of retaining directional information in the construction of physician shared-patient networks. These findings suggest network-based interventions for reducing risky-prescribing.

Functional characterization of MdERF113 in apple.

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.

Theoretical characterization of two-photon fluorescent probes for nitric oxide detection: sensing mechanism, photophysical properties and protonation effects.

Nitric oxide (NO) is an important signal molecule in biological systems and is correlated with many physiological processes and pathological diseases. To date, numerous fluorescent probes based on o-diamino aromatics have been designed and synthesized for NO detection utilizing the principle of photoinduced electron transfer (PET). However, the underlying PET mechanism has rarely been validated, and a systematic computational study on the photophysical properties is urgently desired. In this study, we used a theoretical protocol to comparatively investigate the sensing mechanism, photophysical properties and protonation effects of two emblematic probes NINO and PYSNO in aqueous solution, which combines a polarizable continuum model (PCM), time-dependent density functional theory (TD-DFT) and thermal vibration correlation function formalism (TVCF). Our findings reveal that the weak emission of NINO is due to activated PET with negative driving energy and blocked fluorescence with significant charge separation. In contrast, the poor luminescence of PYSNO is caused by the facilitated non-radiative dissipation, even though the fluorescence emission remains unobstructed. Although NINO has been successfully used in two-photon microscopy for detecting NO, we suggest that PYSNO possesses a superior two-photon absorption (TPA) cross section in the near-infrared region. The protonation effects suggest that both probes can function effectively in practical acidic lysosomal environments. Our study opens a new avenue for understanding the mechanism and predicting the properties of two-photon fluorescent probes for NO detection, thus aiding the rational design of efficient fluorescent sensors.

Effects of ultrasound-guided erector spinae plane block on postoperative acute pain and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy: a prospective randomized, controlled trial.

OBJECTIVE: To investigate the effects of ultrasound-guided erector spinae plane block (ESPB) on acute and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy. METHODS: A total of 94 patients, who underwent elective unilateral video-assisted thoracoscopic lobotomy from August 2021 to December 2021 were randomly divided into general anesthesia group (group A, n = 46) and ESPB combined with general anesthesia group (group B, n = 48) by computer. Patient controlled intravenous analgesia(PCIA) was performed in both groups after operation. The numerical rating scale(NRS) of rest and cough pain at post anesthesia care unit(PACU), 2 h, 6 h, 12 h, 24 and 48 h after operation, frequency of PCIA in 24 h after operation, frequency of rescue analgesia, patient satisfaction, adverse reactions and complications were recorded in the two groups. Incidence of chronic pain at 3 months and 6 months after operation, the effect of daily life and rating of chronic pain management measures were recorded in the two groups. RESULTS: Compared with group A, rest and cough NRS score at 2 h, 6 h, 12 h, 24 and 48 h after surgery, frequency of PCIA use at 24 h after surgery, frequency of rescue analgesia were significantly decreased in group B (P < 0.05). There was no significant difference in NRS scores of rest and cough at PACU after operation between 2 groups after surgery at post anesthesia care unit (P > 0.05). There were no significant differences in the incidence of postoperative chronic pain between the 2 groups(P > 0.05);The effect of postoperative chronic pain on daily life and pain management measures in group B were significantly lower than those in group A(P < 0.05). Compared with group A, patients in group B had higher satisfaction degree, lower incidence of postoperative nausea and vomiting(PONV), and lower incidence of agitation during anesthesia recovery (P < 0.05). There were no pneumothorax, hematoma and toxicity of local anesthetic in the 2 groups. CONCLUSION: Ultrasound-guided erector spinae plane block can significantly reduce acute post-surgical pain, can not reduce the incidence of chronic post-surgical pain, but can significantly reduce the severity of chronic pain in patients underwent video-assisted thoracoscopic lobectomy. TRIAL REGISTRATION: ChiCTR2100050313,date of registration:26/08/2021.

Palladium-Catalyzed Preparation of N-Substituted Benz[c,d]indol-2-imines and N-Substituted Amino-1-naphthylamides.

Here, we report a novel and facile protocol for the synthesis of benz[c,d]indol-2-imines via palladium-catalyzed C-C and C-N coupling of 8-halo-1-naphthylamines with isocyanides in a single step. The reaction features broad substrate scopes and mild conditions, providing an efficient alternative for the construction of antiproliferative agents and BET bromodomain inhibitors. If 0.1 mL of H2O was added to this reaction, the N-substituted amino-1-naphthylamides could be obtained easily.

Optimization of programmed intermittent epidural bolus volume for different concentrations of ropivacaine in labor analgesia: a biased coin up-and-down sequential allocation trial.

BACKGROUND AND OBJECTIVES: To date, programmed intermittent epidural bolus (PIEB) has been widely used in obstetric analgesia, while no optimal PIEB regimen has been proposed. This study aimed to assess effective analgesia in 90% of women (EV90) with different concentrations of ropivacaine (0.075% and 0.1%) combined with 0.5 µg/mL sufentanil, at an interval of 40 min using the biased coin design-up-and-down method (BCD-UDM), and to explore whether there is a difference in EV90 with the increase of ropivacaine concentration. METHODS: In total, 103 primiparous women were assigned to two groups, including group A (n = 52) and group B (n = 51). Parturients in group A were treated with 0.075% ropivacaine and 0.5 µg/mL sufentanil, while those in group B were treated with 0.1% ropivacaine and 0.5 µg/mL sufentanil. Used the biased coin up-and-down sequential allocation method to determine the EV90. The secondary outcomes were sensory block level, motor block, and adverse events (hypotension, urinary retention, and pruritus). RESULTS: The results revealed that EV90 was 10 mL (95% confidence interval (CI):8.03-11.54) in group A, and EV90 was 9 mL (95% CI:7.49-10.51) in group B by the isotonic regression method. The highest level of the sensory block was T8, and the lowest was T12. No case of hypotension was recorded,and only 4 parturients complained of motor block. CONCLUSION: With an interval of 40 min, the optimal PIEB bolus volume of 0.075% ropivacaine and 0.5 µg/mL sufentanil was 10 mL, 0.1% ropivacaine and 0.5 µg/mL sufentanil was 9 mL. Moreover, the PIEB volume decreased along with the higher concentration of ropivacaine. TRIAL REGISTRATION: ChiCTR registration number: ChiCTR2000040917 . Registration date: December 15, 2020.

Nocardia huaxiensis sp. nov., an actinomycete isolated from human skin.

A novel actinomycete, designated as strain WCH-YHL-001T, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001T were C16 : 0, C18 : 1 ω9c, C18 : 0 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4ω-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001T belonged to the genus Nocardia. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain WCH-YHL-001T and type strains of Nocardia species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for isDDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001T represented a novel species of the genus Nocardia, for which the name Nocardia huaxiensis sp. nov. is proposed, with the type strain WCH-YHL-001T (=GDMCC 4.181T=JCM 34475 T=NBRC 114973T).

Skin Microbiota in Non-inflammatory and Inflammatory Lesions of Acne Vulgaris: The Underlying Changes within the Pilosebaceous Unit.

Acne vulgaris is a common chronic inflammatory skin disease of the pilosebaceous unit. Clinical manifestations include seborrhea, non-inflammatory lesions, inflammatory lesions, or scar formation. Fourteen eligible participants of either sex, aged 18-28 years old, with mild to moderate acne lesions, were recruited in this observational study. The contents of 10 pilosebaceous units of non-inflammatory (comedones) and inflammatory lesions (papules and pustules) were collected from each participant's face and examined by amplicon metagenomics sequencing and real-time Polymerase Chain Reaction (PCR). Male participants, participants with a higher body mass index (BMI) than normal, and participants younger than 20 years old, were revealed to have a higher proportion of Malassezia in their non-inflammatory lesions than that in inflammatory lesions. There was an increased abundance of Malassezia restricta (M. restricta) and Cutibacterium acnes (C. acnes) in the non-inflammatory group. Correlation analysis indicated that Staphylococcus epidermidis (S. epidermidis) and M. restricta have similar proliferation trends with C. acnes during the transformation from non-inflammatory to inflammatory lesions. M. restricta probably involve in the microecological balance within the pilosebaceous unit.

Synthesis of Hydroxylatopillar[6]arene-Controlled Gold Nanoparticles-Cellulose Nanocrystals and Their Applications.

In this work, two macrocyclic hosts, named hydroxylatopillar[6]arene and dihydroxylatopillar[6]arene (HP6, 2HP6), are proposed. We found that the reduction of Au3+ to Au0 can success by using HP6 or 2HP6 as a reductant and stabilizing agent. At the end of HP6/2HP6, hydroxyl (-OH) groups were used as a reductant to reduce Au3+ to Au0. At the same time, -OH on HP6/2HP6 was oxidized to -COOH, and then the formed -COOH can be used as the stabilizer to prevent the infinite growth of AuNPs. The cellulose nanocrystals (CNCs) prepared by a clean and nonpolluting method were used as carriers to load AuNPs on them. The CNCs were applied for the adsorption of methylene blue (MB), and then the MB was catalytically degraded by HP6/2HP6-AuNPs-CNC. Besides, the HP6/2HP6-AuNPs-CNC showed remarkable catalytic performance for reducing nitro to the amino group in 4-nitrophenol. The advantages of clean and green synthesis make the HP6/2HP6-AuNPs-CNC a hybrid material and its application sustainable.

Novel technologies applied for recovery and value addition of high value compounds from plant byproducts: A review.

Plant byproducts of food processing industry line are undervalued yet important resource. These byproducts contain large percentage of high value functional substances such as antioxidants, pectin, polyphenols and so on. Recently, many research studies concentrated on innovative technologies that promise to overcome such issues as time consuming, inefficiency, and low yield, among others, which exist in most conventional techniques. Consequently, to achieve the recovery of nutraceuticals from high added-value by-products, it is necessary to have more knowledge of these novel technologies and more importantly explore the possibility of application of these latest technologies to the recovery downstream processing. The present work will summarize state-of-the-art technological approaches concerning extraction, superfine and drying applied to plant food processing residues. Simultaneously, the application of the bioactive components originated from byproducts in food industry will also be reviewed.

Vacuum radio frequency drying: a novel method to improve the main qualities of chicken powders.

Vacuum radio frequency drying (VRFD) combining the advantages of RF heating with vacuum drying (VD) was applied to produce chicken powders. Drying time and some properties of VRFD the powders were compared with VD and microwave vacuum drying (MVD) (915 MHz and 2450 MHz). Results showed that the total drying time of VRFD chicken powders was the shortest (100 min) while that for VD powders was the longest (180 min). VRFD chicken powders exhibited the lowest hygroscopicity (2.17%), the highest water holding capacity (254.80%), and better color and taste. Besides, VRFD powders had maximum umami flavor among the obtained powders. Contrarily, the color and flavor of VD powders were the most undesirable. Additionally, VRFD had less effect on protein secondary structures compared with MVD. It was concluded that, VRFD possesses the necessary potential for use at industrial level in the production of chicken powders with high qualities.

Ultrasensitive Electrochemical Detection of Clostridium perfringens DNA Based Morphology-Dependent DNA Adsorption Properties of CeO2 Nanorods in Dairy Products.

Foodborne pathogens such as Clostridium perfringens can cause diverse illnesses and seriously threaten to human health, yet far less attention has been given to detecting these pathogenic bacteria. Herein, two morphologies of nanoceria were synthesized via adjusting the concentration of NaOH, and CeO2 nanorod has been utilized as sensing material to achieve sensitive and selective detection of C. perfringens DNA sequence due to its strong adsorption ability towards DNA compared to nanoparticle. The DNA probe was tightly immobilized on CeO2/chitosan modified electrode surface via metal coordination, and the DNA surface density was 2.51 × 10−10 mol/cm². Under optimal experimental conditions, the electrochemical impedance biosensor displays favorable selectivity toward target DNA in comparison with base-mismatched and non-complementary DNA. The dynamic linear range of the proposed biosensor for detecting oligonucleotide sequence of Clostridium perfringens was from 1.0 × 10−14 to 1.0 × 10−7 mol/L. The detection limit was 7.06 × 10−15 mol/L. In comparison, differential pulse voltammetry (DPV) method quantified the target DNA with a detection limit of 1.95 × 10−15 mol/L. Moreover, the DNA biosensor could detect C. perfringens extracted DNA in dairy products and provided a potential application in food quality control.

Farrerol Ameliorates TNBS-Induced Colonic Inflammation by Inhibiting ERK1/2, JNK1/2, and NF-κB Signaling Pathway.

Farrerol, a type of 2, 3-dihydro-flavonoid, is obtained from Rhododendron. Previous studies have shown that Farrerol performs multiple biological activities, such as anti-inflammatory, antibacterial, and antioxidant activity. In this study, we aim to investigate the effect of Farrerol on colonic inflammation and explore its potential mechanisms. We found that the effect of Farrerol was evaluated via the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in mice and found that Farrerol has a protective effect on TNBS-induced colitis. Farrerol administration significantly improved the weight change, clinical scores, colon length, and intestinal epithelium barrier damage and markedly decreased the inflammatory cytokines production in TNBS-induced mice. The protective effect of Farrerol was also observed in LPS-induced RAW264.7 cells. We found that Farrerol observably reduced the production of inflammatory mediators including IL-1ß, IL-6, TNF-α, COX-2, and iNOS in LPS-induced RAW264.7 cells via suppressing AKT, ERK1/2, JNK1/2, and NF-κB p65 phosphorylation. In conclusion, the study found that Farrerol has a beneficial effect on TNBS-induced colitis and might be a natural therapeutic agent for IBD treatment.

Tubeimoside I Protects Dopaminergic Neurons Against Inflammation-Mediated Damage in Lipopolysaccharide (LPS)-Evoked Model of Parkinson's Disease in Rats.

Parkinson's disease (PD), a frequent degenerative disease in the elderly, is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc). Neuroinflammation caused by over-activated microglia plays a crucial role in the pathogenesis of PD. Tubeimoside I (TBMS1) has a broad anti-inflammatory effect in peripheral tissues, but the effect on neuroinflammation has not been reported. Therefore, we explored whether TBMS1 could protect dopaminergic neurons by inhibiting the activation of microglia in lipopolysaccharide (LPS)-induced PD rat model. In addition, then, the effect and mechanism of TBMS1 on neuroinflammation were assessed in LPS-exposed murine microglial BV-2 cells. The results in vivo showed that TBMS1 suppressed microglial activation and dopaminergic neurons' reduction in LPS-injected PD rat model. In vitro study found that TBMS1 could inhibit LPS-induced inflammatory responses in BV-2 cells, and this effect was mediated by suppressing the phosphorylation of protein kinase B (AKT), nuclear factor-kappa B (NF-κB p65), p38 and extracellular regulated protein kinases (ERK1/2). Taken together, these results demonstrated for the first time that TBMS1 played a role in protecting dopaminergic neurons by inhibiting neuroinflammation mediated by microglia.

Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways.

Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation. We evaluated the effects of peiminine on behavioural dysfunction, microglial activation and the loss of dopaminergic neurons in a rat model of lipopolysaccharide (LPS)-induced PD. BV-2 cells were pretreated with peiminine for 1 h and then stimulated with LPS for different times. Then, inflammatory responses and the related signalling pathways were analysed. Peiminine markedly attenuated behavioural dysfunction and inhibited the loss of dopaminergic neurons and microglial activation in the LPS-induced PD rat model. In BV-2 cells, peiminine significantly decreased LPS-induced expression of the pro-inflammatory mediators TNF-α, IL-6 and IL-1ß, COX-2 and iNOS by inhibiting the phosphorylation of ERK1/2, AKT and NF-κB p65. Based on these results demonstrated that peiminine has a role in protecting dopaminergic neurons in the LPS-induced PD rat model by inhibiting neuroinflammation.

Overexpression of a New Chitinase Gene EuCHIT2 Enhances Resistance to Erysiphe cichoracearum DC in Tobacco Plants.

In this study, we cloned a new chitinase gene, EuCHIT2, from Eucommia ulmoides Oliver (E. ulmoides) using rapid amplification of cDNA ends (RACE) technology and constructed an overexpression vector, pSH-35S-EuCHIT2, to introduce it into tobacco (Nicotiana tabacum cv. Xanthi). Resistance to Erysiphe cichoracearum de Candolle (E.cichoracearum DC) and molecular mechanisms in the transgenic tobacco were determined by drop inoculation, spore counting, determination of physicochemical indicators, and analysis of gene expression. The chitinase activity and resistance to E. cichoracearum DC were significantly higher in the transgenic tobacco than in wild-type tobacco (p < 0.05). The activities of peroxidase (POD) and catalase (CAT), after inoculation with E. cichoracearum DC, were higher in the transgenic tobacco than in the wild-type. Conversely, the malondialdehyde (MDA) content was significantly lower in the transgenic tobacco than the wild-type before and after inoculation. In addition, our study also indicated that the resistance to E. cichoracearum DC might involve the salicylic acid (SA) and jasmonic acid (JA) pathways, because the expression levels of pathogenesis-related gene 1 (PR-1a) and coronatine-insensitive 1 (COI1) were significantly increased and decreased, respectively, after inoculation with E. cichoracearum DC. The present study supports the notion that PR-1a and POD participate in resistance to E. cichoracearum DC in the transgenic tobacco plants.