In vitro antibacterial activity of danofloxacin against Escherichia coli in Gushi chickens and its residue depletion following multiple oral administration.

This study aimed to investigate the in vitro antibacterial activity of danofloxacin against Escherichia coli isolated from Gushi chickens, as well as the tissue distribution and residue depletion of danofloxacin in Gushi chickens following multiple oral administration. A total of 42 clinical E. coli strains were isolated from the cloaca of locally farmed Gushi chickens between August and October 2023. Then the minimum inhibitory concentration (MIC) of danofloxacin against these isolates was determined by broth microdilution method. Additionally, 42 healthy Gushi chickens were randomly divided into 6 groups, and danofloxacin was orally administered at a dose of 5 mg/kg body weight (BW) for 3 consecutive days. Plasma, intestinal content, and tissue samples, including muscle, skin + fat, liver, kidney, lung, and intestine, were collected at 4, 12, 24, 48, 72, and 120 h after the last administration. Danofloxacin concentrations in all samples were determined using a high-performance liquid chromatography (HPLC) method. The average concentration vs. time data were then subjected to noncompartmental analysis using Phoenix software, and withdrawal periods for danofloxacin in Gushi chickens were further determined with WT1.4 software, setting a 95% confidence interval. Results indicated a notable inhibitory effect of danofloxacin on E. coli, with an MIC50 of 0.5 µg/mL. Additionally, danofloxacin exhibited widespread distribution in Gushi chickens, detectable in all collected samples. Among all tissues, the liver exhibited the highest concentration, followed by the intestine. Even on the fifth day postadministration, danofloxacin persisted in skin + fat, liver, and lung. The elimination half-lives (t1/2λzs) of danofloxacin varied across samples: skin + fat (47.87 h), lung (30.61 h), liver (22.07 h), plasma (16.05 h), muscle (12.53 h), intestine (9.83 h), and kidney (6.34 h). Considering residue depletion and the maximum residue limit (MRL) of danofloxacin in poultry set by Chinese regulatory authorities, withdrawal periods for the kidney, muscle, liver, and skin + fat were determined as 1.03, 1.38, 3.34, and 5.85 d, respectively, rounded to a final withdrawal time of 6 d.

Liberal surgical laparoscopy reduction for acute intussusception: experience from a tertiary pediatric institute.

The optimal treatment for acute intussusception has not yet been defined. In this study, we explored whether employing a liberal laparoscopic intervention for intussusception could lead to favorable outcomes. We performed a historical control analysis to evaluate the outcomes associated with this liberal surgical management protocol. This liberal surgical management protocol were revised to incorporate a new protocol centered around the laparoscopic approach. In some cases of acute intussusception, liberal laparoscopic exploration and intervention were undertaken without initial hydrostatic or pneumatic reduction. During the study interval, a retrospective review was conducted on a total of 3086 patients. These were categorized into two groups: 1338 cases before May 2019 (pre-protocol group) and 1748 cases after May 2019 (post-protocol group). Surgical intervention rates in the pre-protoco and post-protocol period were 10.2% and 27.4% respectively (odds ratio [OR] = 0.30 [95% CI 0.25-0.37]; p < 0.001). No significant differences were observed in baseline clinical characteristics or demographic features between the two groups. The duration from admission to operation was longer for the pre-protocol group (p = 0.008) than for the post-protocol group. The post-protocol group demonstrated decreases in both intestinal resection (OR = 1.50 [95% CI 0.96-2.35]; p = 0.048) and total recurrent events (OR = 1.27 [95% CI 1.04-1.55]; p = 0.012) compared to the pre-protocol group. Liberal laparoscopic intervention for intussusception may effectively reduce the risk of intestinal resection and total recurrent events, thereby exhibiting promising outcomes for patients with intussusception.

Potential and Limitations of ChatGPT 3.5 and 4.0 as a Source of COVID-19 Information: Comprehensive Comparative Analysis of Generative and Authoritative Information.

BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has necessitated reliable and authoritative information for public guidance. The World Health Organization (WHO) has been a primary source of such information, disseminating it through a question and answer format on its official website. Concurrently, ChatGPT 3.5 and 4.0, a deep learning-based natural language generation system, has shown potential in generating diverse text types based on user input. OBJECTIVE: This study evaluates the accuracy of COVID-19 information generated by ChatGPT 3.5 and 4.0, assessing its potential as a supplementary public information source during the pandemic. METHODS: We extracted 487 COVID-19-related questions from the WHO's official website and used ChatGPT 3.5 and 4.0 to generate corresponding answers. These generated answers were then compared against the official WHO responses for evaluation. Two clinical experts scored the generated answers on a scale of 0-5 across 4 dimensions-accuracy, comprehensiveness, relevance, and clarity-with higher scores indicating better performance in each dimension. The WHO responses served as the reference for this assessment. Additionally, we used the BERT (Bidirectional Encoder Representations from Transformers) model to generate similarity scores (0-1) between the generated and official answers, providing a dual validation mechanism. RESULTS: The mean (SD) scores for ChatGPT 3.5-generated answers were 3.47 (0.725) for accuracy, 3.89 (0.719) for comprehensiveness, 4.09 (0.787) for relevance, and 3.49 (0.809) for clarity. For ChatGPT 4.0, the mean (SD) scores were 4.15 (0.780), 4.47 (0.641), 4.56 (0.600), and 4.09 (0.698), respectively. All differences were statistically significant (P<.001), with ChatGPT 4.0 outperforming ChatGPT 3.5. The BERT model verification showed mean (SD) similarity scores of 0.83 (0.07) for ChatGPT 3.5 and 0.85 (0.07) for ChatGPT 4.0 compared with the official WHO answers. CONCLUSIONS: ChatGPT 3.5 and 4.0 can generate accurate and relevant COVID-19 information to a certain extent. However, compared with official WHO responses, gaps and deficiencies exist. Thus, users of ChatGPT 3.5 and 4.0 should also reference other reliable information sources to mitigate potential misinformation risks. Notably, ChatGPT 4.0 outperformed ChatGPT 3.5 across all evaluated dimensions, a finding corroborated by BERT model validation.

Combining CD4 count, CD8 count and CD4/CD8 ratio to predict risk of mortality among HIV-positive adults after therapy: a group-based multi-trajectory analysis.

Introduction: Previous studies have indicated different immunological recovery trajectories based on CD4 count or CD4/CD8 ratio. However, these immune indicators are interconnected, and relying solely on one indicator may lead to inaccurate estimates. Therefore, it is essential to develop a comprehensive trajectory model that integrates CD4 count, CD8 count and CD4/CD8 ratio. Methods: We utilized a group-based multi-trajectory model to characterize the latent cluster of recovery based on measurements of CD4 count, CD8 count and CD4/CD8 ratio over a period of up to 96 months following ART initiation. Subsequently, we investigated the characteristics associated with trajectory groups, especially sex and age. Cox model and Kaplan-Meier survival curve were employed to assess differences in all-cause, AIDS-related and non-AIDS related mortality between trajectory groups. Results: A total of 14,718 eligible individuals were followed for a median of 55 months. Longitudinal model identified four subgroups: group 1 (32.5%, low CD4 and CD4/CD8 inversion), group 2 (25.9%, high CD8 and CD4/CD8 inversion), group 3 (27.2%, slow recovery of CD4 and CD4/CD8 inversion) and group 4 (14.4%, rapid increase of CD4 and normal CD4/CD8). Immune recovery was slower in male than in female, and in elders than in youngers. Compared to group 2, group 1 (adjusted hazard ratio [aHR]=3.28; 95% CI 2.33-4.60) and group 3 (aHR=1.56; 95% CI 1.09-2.24) had increased risk of all-cause mortality after adjusting for other factors. Besides, group 1 (aHR=2.17) and group 3 (aHR=1.58) had higher risk of non-AIDS related mortality, and group 1 (aHR=5.92) had significantly increased risk of AIDS related mortality. Conclusion: Longitudinal trajectory analysis of multiple immune indicators can be employed to guide targeted interventions among vulnerable populations in clinical practice.

Regular use of low-dose of opioids after gastrointestinal surgery may lead to postoperative gastrointestinal tract dysfunction in children: a Chinese national regional health center experience sharing.

BACKGROUND: The need for pain management is increasing in pediatrics, but the side effects of overuse or abuse of analgesics can be harmful to children's health and even life-threatening in severe cases. METHODS: Patients who underwent resection of Meckel's diverticulum at the Children's Hospital of Chongqing Medical University from July 1, 2019, to July 1, 2022, were included in this study. Opioids were administered through patient-controlled analgesia (PCA). Based on the preoperative choices made by the legal guardians, patients were stratified into two groups: PCA Group (PCAG) and Non-PCA Group (NPCAG). Data pertaining to the clinical characteristics and prognoses of these patients were subsequently collected and analyzed to assess the impact of opioid administration. RESULTS: In the study, a total of 126 patients were enrolled, with 72 allocated to the Patient-Controlled Analgesia Group (PCAG) and 54 to the Non-Patient-Controlled Analgesia Group (NPCAG). When compared to the NPCAG, the PCAG exhibited a longer duration of postoperative fasting (median 72 vs. 62 h, p = 0.044) and increased utilization of laxatives (12[16.7%] vs. 2[3.7%], p = 0.022). However, the PCAG also experienced higher incidences of intestinal stasis and abnormal intestinal dilation (13[18.1%] vs. 3[5.6%], p = 0.037). No statistically significant differences were observed in pain assessments at the conclusion of the surgical procedure (0 vs. 1[1.9%], p = 0.429) or within the first 24 h postoperatively (16[22.2%] vs. 18[33.3%], p = 0.164). Additionally, NPCAG patients did not necessitate increased administration of rescue analgesics (2[2.8%] vs. 4[7.4%], p = 0.432). CONCLUSIONS: The administration of opioids did not demonstrably ameliorate postoperative pain but was associated with a heightened incidence of postoperative gastrointestinal tract dysfunction. The retrospective nature of the current research should be considered and should be clarified further.

Surface Activity, Wetting, and Aggregation of a Perfluoropolyether Quaternary Ammonium Salt Surfactant with a Hydroxyethyl Group.

This paper reports the synthesis of a novel quaternary surfactant containing a hydroxyethyl group (PFPE-C) and the surface properties of its aqueous solution (investigated by comparisons with two structurally similar chemicals, dodecyl-(2-hydroxyethyl)-dimethylammonium chloride (DHDAC) and PFPE-A). The minimum surface tension (γCMC) and critical micelle concentration (CMC) of the PFPE-C aqueous solution were 17.35 mN/m and 0.024 mmol/L, respectively. This study confirms that surfactants containing hydroxyethyl groups efficiently reduce the surface tension of aqueous solutions, and fluorocarbon surfactants exhibit better surface activity than ordinary hydrocarbon surfactants with similar structures. The micellization, aggregation, air-water interfacial adsorption, and wettability of PFPE-C aqueous solutions have been systematically investigated. Highly concentrated PFPE-C aqueous solutions exhibit good wettability on PTFE and paraffin films. Moreover, the aggregates of PFPE-C in the aqueous solution were clearly seen as vesicles on Cryo-TEM micrographs. Primary biodegradation results indicate that 19% of PFPC-C can be degraded within one week.

Impact of vaccination with different types of rotavirus vaccines on the incidence of intussusception: a randomized controlled meta-analysis.

Background: Intussusception is a prevalent pediatric issue causing acute abdominal pain, with potential links to rotavirus vaccines. The variety of these vaccines has grown in recent years. This meta-analysis study aims to evaluate the impact of various rotavirus vaccines on intussusception incidence. Methods: We executed a thorough search across databases like PubMed, Cochrane Library, Embase, and Web of Science, leading to the selection of 15 credible randomized controlled trials (RCTs) that encompass various types of rotavirus vaccines. From each study, we extracted essential details such as vaccine types and intussusception occurrences. We assessed the risk of bias using the Cochrane Collaboration's tool, conducted statistical analysis with R (version 4.2.3), determined relative risk (RR) using a random effects model, and performed a subgroup analysis for vaccines of differing brands and types. Results: We included 15 randomized controlled studies from various countries. While intussusception incidence differed between vaccinated and control groups, this difference was not statistically significant. The overall risk ratio (RR), calculated using a random effects model, was 0.81, with a 95% confidence interval of [0.53, 1.23]. This crossing 1 shows that vaccination didn't notably change disease risk. Additionally, the 0% group heterogeneity suggests consistency across studies, strengthening our conclusions. Subgroup analysis for different vaccine brands and types (RV1 (Rotarix, Rotavac, RV3-BB), RV3 (LLR3), RV5 (RotasiiL, RotaTeq), and RV6) showed no significant variation in intussusception incidence. Despite variations in RR among subgroups, these differences were not statistically significant (P > 0.05). Conclusions: Our study indicates that rotavirus vaccination does not significantly increase the incidence of intussusception. Despite varying impacts across different vaccine brands and types, these variations are insignificant. Given the substantial benefits outweighing the risks, promoting the use of newly developed rotavirus vaccines remains highly valuable. Systematic Review Registration: www.crd.york.ac.uk/prospero/, Identifier CRD42023425279.

Analysis on epidemiological characters and HIV care continuum of HIV-infected students: a retrospective cohort study in Shandong province, China.

BACKGROUD: The proportion of HIV-infected students in China showed an increasing trend. This study aimed to identify the epidemiological characteristics and the HIV care continuum for HIV-infected students in Shandong Province, China. METHODS: Case report and follow-up data of HIV-infected students were obtained from the National HIV/AIDS comprehensive response information management system. Logistic regression analyses were used to analyze the associating factors of HIV-infected students accepting CD4 + T cells (CD4) test and antiviral therapy (ART) in 30 days, and ArcGIS software was used for the spatial anlysis. RESULTS: From 2017 to 2019, 403 HIV-infected students were reported in Shandong Province. The majority of them were male (99.5%) and transmitted through homosexual sexual activity(92.1%). Most of them lived in Jinan city and Qingdao city. 68.5% (276 cases) accepted CD4 test in 30 days, and 48.6% (196 cases) started ART in 30 days. The heterosexual transmitted cases (AOR = 0.458, 95%CI: 0.210-0.998), patients accepting HIV care in western area (AOR = 0.266,95%CI: 0.147-0.481) were less likely to test CD4 within 30 days; patients aged 23-25 (AOR = 2.316, 95%CI: 1.009-5.316) and patients who had tested CD4 within 30 days (AOR = 4.377; 95%CI: 2.572-7.447) prefered to receive ART within 30 days; patients accepted HIV care in central area (AOR = 0.407; 95%CI: 0.251-0.657) and western area (AOR = 0.508; 95%CI: 0.261-0.989) and patients diagnosed by voluntary blood donation (AOR = 0.352; 95%CI: 0.144-0.864) were less willing to receive ART in 30 days. CONCLUSIONS: The HIV care continuum of HIV-infected students in Shandong Province still needed strenghthing. More health education and case management should be done for cases transmitted through heterosexual behavior, accepted HIV care in central and western area, and diagnosed by voluntary blood donation.

The care status and factors affecting antiretroviral therapy timing for people living with HIV: a retrospective cohort study in Shandong Province, China.

This study described the care status of People Living with HIV (PLWH) including antiretroviral therapy (ART) and viral suppression from 2018 to 2020. We recognized that immediate ART was associated with improved viral suppression. Therefore, we also aimed to explore the factors affecting the early initiation of ART. We initiated a retrospective cohort study to evaluate the care status of people living with HIV in Shandong Province. From 2018 to 2020, patients infected by homosexual transmission in particular had a higher ART rate (78.82%, 79.69%, and 87.72%, respectively). Of PLWH who received ART, 79.57%, 77.63%, and 67.71% achieved viral suppression, respectively. However, COVID-19 may affect the rate of ART and viral suppression, which we need to explore in our research. From 2018 to 2020, the proportion of immediate antiretroviral therapy within 30 days of diagnosis increased from 48.12% to 65.42%. Multivariate logistic regression demonstrated that patients with junior college degree or above (OR, 1.39 [95%CI, 1.12-1.73]) and key population or medical institutions (OR, 3.62 [95%CI, 2.18-6.16]; OR, 3.88 [95%CI, 2.33-6.59]) were substantially likely to receive ART immediately, while patients outside the province (OR, 0.60 [95%CI, 0.50-0.73]) were less likely to receive ART immediately.

Underwater Oleophobic Electrospun Membrane with Spindle-Knotted Structured Fibers for Oil-in-Water Emulsion Separation.

The potential of spider silk as an intriguing biological prototype for collecting water from a humid environment has attracted wide attention, and various materials with suitable structures have been engineered. Here, inspired by this phenomenon, a kind of superwetting poly(vinylidene fluoride) (PVDF) membrane with spindle-knotted structured fibers was prepared by the electrospinning method followed by oxygen plasma etching treatment. The prepared membrane presented a satisfactory separation efficiency for various oil-in-water emulsions. The cooperative effect of the special wettability property and the spindle-knot structure stimulated the emulsified oil droplets to accumulate quickly on the membrane surface. A model that explains the accumulation of emulsified oil droplets has also been developed. Furthermore, an artificial fiber comprising a micron-sized spindle-knot structure was prepared by the dip-coating method to clearly illustrate the aggregation process of the emulsified oil droplets and to verify the theoretical explanation. We hope that this study will provide new inspiration for oil/water emulsion separation techniques.

Simple Scoring System that Predicts the Need for Surgical Intervention in Infants with Necrotizing Enterocolitis.

BACKGROUND AND AIMS: It is difficult to identify those preterm infants who require surgical intervention. This study examined the predictive factors for bowel resection in infants with definitive and advanced necrotizing enterocolitis (NEC). We then developed a scoring system to better predict the need for surgical intervention. METHODS: A total of 203 infants with modified Bell's stage 2 or higher NEC from January 2018-December 2020 were identified for this study. A retrospective study evaluated the association between several comprehensive variables and surgical intervention using a multiple logistic regression analysis, and then a scoring system was developed based on the sum of coefficients (ß). RESULTS: Of the 135 patients who met the inclusion criteria, 57 infants underwent a surgical intervention. The multivariable logistic regression analysis showed that birth weight (regression coefficient, ß = 1.30), PCT (ß = 2.33), not having received enteral nutrition before the diagnosis of NEC (ß = 2.13), acidosis (ß = 1.57), respiratory alkalosis (ß = 2.42), hypokalemia (ß = 2.14), peritonitis (ß = 2.87) and coagulation disorders (ß = 1.78) were associated with the occurrence of bowel resection. A scoring system ranging from 0-17 was developed based on the total coefficient obtained. It was found that a cut-off score of 5 may distinguish those infants needing surgical intervention from other infants with NEC. CONCLUSION: We successfully developed a clinical decision-making tool associated with the need for surgical intervention among infants with advanced NEC. The risk scoring system could accurately identify infants who would benefit from surgical intervention.

A Novel Satellite PRN Code Assignment Method Based on Improved RLF Algorithm.

Low Earth Orbit (LEO) satellites have stronger received signals and more rapid geometry changes than Global Navigation Satellite System (GNSS) satellites, making them attractive for positioning, navigation, and timing (PNT) applications. Due to the low altitude, the LEO constellation requires more satellites to cover the entire globe and more Pseudo Random Noise (PRN) codes to realize Code Division Multiple Access (CDMA), which means greater receiver storage resources and receiver acquisition time. In this paper, different from the traditional methods that assign a unique PRN code to each satellite, we propose a novel method in which several satellites share the same PRN code, and simply demonstrate the feasibility and benefits of this method. To determine the minimum number of PRN codes needed for a constellation, we build a mathematical model. After the algorithm comparison, we improve the recursive largest first (RLF) algorithm so that it has a higher running speed and a smaller approximate optimal solution within a certain time period. By studying polar-orbiting and walker constellations, we find that if other satellite parameters remain the same, the higher the orbital altitude is, the more PRN codes are needed, and no matter what the orbital inclination is, the minimum number of PRN codes remains the same. Overall, it is feasible and meaningful for several satellites sharing the same PRN code to save storage resources and reduce the satellite acquisition time of the receiver. If this new technology is applied, the storage resources and the average satellite acquisition time of the receiver will be, at most, one-third of previous ones.

Estimating Costs of the HIV Comprehensive Intervention Using the Spectrum Model - China, 2015-2019.

Introduction: In order to facilitate human immunodeficiency virus (HIV) treatment and prevention, the resource needs for HIV national strategic planning in developing regions were estimated based on Spectrum, the universal HIV cost-effectiveness analysis software. Methods: Based on the theoretical framework of Spectrum, the study developed a cost measurement tool for HIV, and calculated the cost of HIV prevention and control in 6 sampled cities in China during 2015-2019 using the Spectrum model. Results: From 2015 to 2019, the average annual costs for HIV prevention and control for Shijiazhuang, Yantai, Ningbo, Zhenjiang, Foshan, and Wuxi cities were 46.78, 47.55, 137.49, 24.73, 74.37, and 58.30 million Chinese yuan (CNY), respectively. The per capita costs were 4.37, 6.73, 17.33, 7.77, 17.56, and 8.91 CNY, respectively. In terms of the cost structure, the ratio of preventive intervention funds to therapeutic intervention funds (antiviral treatment) varied in sampled cities. Discussion: Developing comprehensive and systematic HIV fund calculation methods can provide a research basis for rational resource allocation in the field of HIV.

Primary Broiler Hepatocytes for Establishment of a Steatosis Model.

Fatty liver hemorrhage syndrome (FLHS) in chickens is characterized by steatosis and bleeding in the liver, which has caused huge losses to the poultry industry. This study aimed to use primary cultured broiler hepatocytes to establish a steatosis model to explore the optimal conditions for inducing steatosis by incubating the cells with a fat emulsion. Primary hepatocytes were isolated from an AA broiler by a modified two-step in situ perfusion method. Hepatocytes were divided into an untreated control group and a fat emulsion group that was incubated with 2.5, 5, 10, or 20% fat emulsion for different times to determine the optimal conditions for inducing steatosis of primary hepatocytes. Incubation of the cells with 10% fat emulsion resulted in cell viability at 48 h of 67%, which was higher than the control group and met the requirements of the model. In the second experiment, steatosis was induced by incubating hepatocytes with 10% fat emulsion for 48 h. In consequence, the apoptosis rate decreased (p > 0.05) and the concentration of ALT (p < 0.001), AST (p < 0.01), and TG (p < 0.05) increased significantly; the expression level of SREBP-1c (p < 0.05) increased, and the expression levels of PPARα (p < 0.001), CPT1 (p < 0.001), and CPT2 (p < 0.05) were lower in the fat emulsion group than in the control group. In conclusion, the induction condition was selected as 10% fat emulsion incubation for 48 h, and we successfully established a fatty liver degeneration model for broilers.

Silver-decorated black phosphorus: a synergistic antibacterial strategy.

Black phosphorus (BP) exhibits great potential as antibacterial materials due to its unique photocatalytic activity. However, the unsatisfactory optical absorption and quick recombination of photoinduced electron-hole pairs restrain its photocatalytic antibacterial performance. In this work, silver nanoparticles (AgNPs) were decorated on BP to construct BP@AgNPs nanohybrids and then introduced into poly-l-lactic acid scaffold. Combining the tunable bandgap of BP and the LSPR effect of AgNPs, BP@AgNPs nanohybrids displayed the broaden visible light absorption. Furthermore, AgNPs acted as electron acceptors could accelerate charge transfer and suppress electron-hole recombination. Therefore, BP@AgNPs nanohybrids achieved synergistically enhanced photocatalytic antibacterial activity under visible light irradiation. Fluorescence probe experiment verified that BP@AgNPs promoted the generation of reactive oxygen species, which could disrupt bacteria membrane, damage DNA and oxide proteins, and finally lead to bacteria apoptosis. As a result, the scaffold possessed strong antibacterial efficiency with a bactericidal rate of 97% under light irradiation. Moreover, the scaffold also exhibited good cytocompatibility. This work highlighted a new strategy to develop photocatalytic antibacterial scaffold for bone implant application.

Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry.

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

Interface Engineering of CoP3/Ni2P for Boosting the Wide pH Range Water-Splitting Activity.

Developing electrocatalysts with low price, high energy efficiency, and universal pH value for hydrogen/oxygen evolution reaction (HER and OER) is very important for the wide application of electrochemical water splitting in hydrogen production. The results of density functional theory show that the interface region of CoP3/Ni2P heterostructures can significantly boost all of the catalytic performances. High-resolution transmission electron microscopy and X-ray photoelectron spectroscopy were used to confirm the abundant structural defects and the corresponding adjustment of the electronic state, thus ameliorating the activation energy, conductivity, and active area of the catalyst. Benefiting from these, CoP3/Ni2P heterostructures exhibit superior performance of both HER and OER in a wide pH range. CoP3/Ni2P can also be used for water splitting (1.557 V at 10 mA cm-2) more than 40 h, superior to benchmark pairs of Pt/C and RuO2 on Ni foam.

Polydopamine-decorated black phosphorous to enhance stability in polymer scaffold.

Black phosphorous (BP) is recognized as an effective reinforcement for polymer scaffold because of its excellent mechanical property and biocompatibility. Nevertheless, its poor stability in physiological environment limits its application in bone repair. In this work, BP was modified with dopamine by self-polymerization approach (donated as BP@PDA) to improve its stability, and then was introduced into poly-L-lactic acid (PLLA) scaffold fabricated by selective laser sintering technology. Results showed the compressive and tensile strength of PLLA/BP@PDA scaffold were improved by 105% and 50%, respectively. The enhanced strength was ascribed to the increased stability of BP and the improved compatibility of BP@PDA with PLLA matrix after modifying with polydopamine. Simultaneously, the bioactivity of PLLA scaffold was significantly improved. It was attributed to that BP@PDA provided the sustained source ofPO43-ions which could capture Ca2+ions from physiological medium to facilitatein situbiomineralization, thereby promoting cell adhesion, proliferation and differentiation. This study demonstrated the great potential of BP@PDA in bone repair.

Quantitative HPLC-MS/MS determination of Nuc, the active metabolite of remdesivir, and its pharmacokinetics in rat.

Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 µm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg-1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract.

3D Printed Zn-doped Mesoporous Silica-incorporated Poly-L-lactic Acid Scaffolds for Bone Repair.

Poly-L-lactic acid (PLLA) lacks osteogenic activity, which limits its application in bone repair. Zinc (Zn) is widely applied to strengthen the biological properties of polymers due to its excellent osteogenic activity. In the present study, Zn-doped mesoporous silica (Zn-MS) particles were synthesized by one-pot hydrothermal method. Then, the particles were induced into PLLA scaffolds prepared by selective laser sintering technique, aiming to improve their osteogenic activity. Our results showed that the synthesized particles possessed rosette-like morphology and uniform mesoporous structure, and the composite scaffold displayed the sustained release of Zn ion in a low concentration range, which was attributed to the shield effect of the PLLA matrix and the strong bonding interaction of Si-O-Zn. The scaffold could evidently promote osteogenesis differentiation of mouse bone marrow mesenchymal stem cells by upregulating their osteogenesis-related gene expression. Besides, Zn-MS particles could significantly increase the compressive strength of the PLLA scaffold because of their rosette-like morphology and mesoporous structure, which can form micromechanical interlocking with the PLLA matrix. The Zn-MS particles possess great potential to improve various polymer scaffold properties due to their advantageous morphology and physicochemical properties.