Evaluating vonoprazan and tegoprazan for gastroesophageal reflux disease treatment in Chinese Healthcare: an EVIDEM framework analysis.

BACKGROUND: In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework. METHODS: The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ. RESULTS: The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'. CONCLUSION: Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.

Long-term outcomes of left atrial appendage closure with or without concomitant pulmonary vein isolation:a propensity score matching analysis based on CLACBAC study.

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.

Dexmedetomidine Infusion Versus Placebo During Light or Deep Anesthesia on Postoperative Delirium in Older Patients Undergoing Major Noncardiac Surgery: A Pilot Randomized Factorial Trial.

BACKGROUND: Postoperative delirium (POD) is common among older surgical patients and may be affected by dexmedetomidine and depth of anesthesia. We designed this pilot study to assess the feasibility of comparing dexmedetomidine with normal saline during light versus deep anesthesia on POD in older patients undergoing major noncardiac surgery. METHODS: In this pilot randomized factorial study, 80 patients aged 60 years or older undergoing major noncardiac surgery were randomized (1:1:1:1) to receive dexmedetomidine infusion 0.5 µg/kg/h or normal saline placebo during light (bispectral index [BIS] target 55) or deep (BIS target 40) anesthesia. Feasibility end points included consent rate and dropout rate, timely enrollment, blinded study drug administration throughout surgery, no inadvertent unmasking, achieving BIS target throughout >70% of surgery duration, and the process of twice-daily POD screening. In addition, we estimated the POD incidences in the 2 control groups (placebo and deep anesthesia) and treatment effects of dexmedetomidine and light anesthesia. RESULTS: Between November 1, 2021, and June 30, 2022, 78 patients completed the trial (mean [standard deviation, SD] age, 69.6 [4.6] years; 48 male patients [62%]; dexmedetomidine-deep, n = 19; dexmedetomidine-light, n = 20; placebo-deep, n = 19; placebo-light, n = 20). This study had a high consent rate (86%) and a low dropout rate (2.5%). Average recruitment was 5 patients at each center per month. Dexmedetomidine and normal saline were administered in a blinded fashion in all patients. Unmasking did not occur in either group. Approximately 99% of patients received the scheduled study drug infusion throughout the surgery. Approximately 81% of patients achieved the BIS targets throughout >70% of the surgery duration. The scheduled twice-daily POD screening was completed without exception. Overall, 10 of the 78 patients (13%; 95% confidence interval [CI], 7%-22%) developed POD. For the 2 reference groups, POD was observed in 7 of the 39 patients (17.9%; 95% CI, 9%-32.7%) in the placebo group and 7 of the 38 patients (18.4%; 95% CI, 9.2%-33.4%) in the deep anesthesia group. Regarding the treatment effects on POD, the estimated between-group difference was -10% (95% CI, -28% to 7%) for dexmedetomidine versus placebo, and -11% (95% CI, -28% to 6%) for light versus deep anesthesia. CONCLUSIONS: The findings of this pilot study demonstrate the feasibility of assessing dexmedetomidine versus placebo during light versus deep anesthesia on POD among older patients undergoing major noncardiac surgery, and justify a multicenter randomized factorial trial.

Nanobody peptide conjugate: a novel CD163 based broad neutralizing strategy against porcine reproductive and respiratory syndrome virus.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins. RESULTS: Four NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-ß activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12-24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV. CONCLUSION: The aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases.

Synergistic activity and mechanism of cytarabine and MCL-1 inhibitor AZD5991 against acute myeloid leukemia.

The 5-year overall survival rate of acute myeloid leukemia (AML) is less than 30%. Improving clinical outcomes is still a clinical challenge for AML treatment. Simultaneous use of chemotherapeutic drugs and targeting of apoptosis pathways has become a first-line clinical treatment for AML. Myeloid cell leukemia 1 (MCL-1) is a candidate target for AML treatment. In this study, we demonstrated that inhibition of the anti-apoptotic protein MCL-1 by AZD5991 synergistically increased chemotherapeutic agent cytarabine (Ara-C)-induced apoptosis in AML cell lines and primary patient samples. Apoptosis induced by a combination of Ara-C and AZD5991 was partially dependent on caspase activity and Bak/Bax. The downregulation of MCL-1 by Ara-C and the enhancement of Ara-C-induced DNA damage through inhibition of MCL-1 are potential mechanisms underlying the synergistic anti-AML activity between Ara-C and AZD5991. Our data support the application of MCL-1 inhibitor in combination with the conventional chemotherapeutic agent for the clinical treatment of AML.

Microplastic transport during desertification in drylands: Abundance and characterization of soil microplastics in the Amu Darya-Aral Sea basin, Central Asia.

Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.

Influence of ABO blood group on susceptibility to different pathological types of lung cancer: a retrospective study.

PURPOSE: Current research has shown a link between ABO blood group and many diseases. The purpose of this study aimed to investigate the influence of the ABO blood group on the risk of developing different pathological types of lung cancer. MATERIALS AND METHODS: This retrospective study was composed of 7681 patients with lung cancer and 12, 671 non-lung cancer patients who were admitted to the First Affiliated Hospital of Nanchang University from January 2016 to January 2021. The subjects with lung cancer were grouped into small cell lung cancer group (n = 725), lung adenocarcinoma group (n = 4520), and lung squamous cell carcinoma group (n = 2286) according to pathological types. The ABO blood group distribution of each lung cancer type group was compared with that of the control group. Statistical analysis was determined with chi-square and logistic regression. RESULTS: Univariate analysis showed that the ABO blood group distribution of lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer was different from that of the control group (P < 0.01). After adjusting for age, sex, smoking history, and drinking history, logistic regression analysis showed that the risk of lung adenocarcinoma in blood type O was higher than that in blood type A (P < 0.01). There was no significant difference in ABO blood group composition between small cell lung cancer group, lung squamous cell carcinoma group, and control group (P > 0.05). In addition, gender and age have an influence on all three types of lung cancer (P < 0.01). Smoking was a risk factor in lung squamous cell carcinoma and small cell carcinoma (P < 0.01). Alcohol consumption was a risk factor in lung adenocarcinoma (P < 0.01). CONCLUSION: ABO blood group may be correlated with the occurrence of lung adenocarcinoma in Jiangxi province, but not with lung squamous cell carcinoma and small cell carcinoma.

A Hybrid Scheme of MCS Selection and Spectrum Allocation for URLLC Traffic under Delay and Reliability Constraints.

The Ultra-Reliable Low-Latency Communication (URLLC) is expected to be an important feature of 5G and beyond networks. Supporting URLLC in a resource-efficient manner demands optimal Modulation and Coding Scheme (MCS) selection and spectrum allocation. This paper presents a study on MCS selection and spectrum allocation to support URLLC. The essential idea is to establish an analytical connection between the delay and reliability requirements of URLLC data transmission and the underlying MCS selection and spectrum allocation. In particular, the connection factors in fundamental aspects of wireless data communication include channel quality, coding and modulation, spectrum allocation and data traffic characteristics. With this connection, MCS selection and spectrum allocation can be efficiently performed based on the delay and reliability requirements of URLLC. Theoretical results in the scenario of a 5G New Radio system are presented, where the Signal-to-Noise Ratio (SNR) thresholds for adaptive MCS selection, data-transmission rate and delay, as well as spectrum allocation under different configurations, including data duplication, are discussed. Simulation results are also obtained and compared with the theoretical results, which validate the analysis and its efficiency.

Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease.

BACKGROUND: Accumulated evidence has indicated that a high-normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown. METHODS: This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long-term rate of AF recurrence after ablation were assessed. RESULTS: After a mean follow-up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093-1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014-1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF). CONCLUSION: Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.

Comparative pharmacokinetics of seven bioactive components in normal, sham-operated, and myocardial ischemia-reperfusion injury rats after oral administration of the Salvia Miltiorrhiza-Moutan Cortex herb pair.

Recently the Salvia Miltiorrhiza-Moutan Cortex (SM-MC) herb pair is considered as a promising Chinese medicinal mixture exhibiting a range of pharmacological activities, including treating cardiovascular disease due to its unique composition. In this study, we conducted the comparative pharmacokinetic analysis of seven main bioactive components of SM-MC in a different model rat. A straightforward ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) strategy that could simultaneously evaluate the levels of seven compounds was used to ensure the reliability of these pharmacokinetic analyses in rat plasma. The rat plasma samples were collected from normal, sham-operated, and myocardial ischemia-reperfusion injury (MIRI) groups at predetermined time points after the administration of SM-MC. The main pharmacokinetic parameters were detected and calculated. We successfully assessed the maximum concentration (Cmax ), time to Cmax (Tmax ), the elimination rate constant (λz ), total half-life (t1/2 ), total body clearance (CL), and the area under the concentration-time curve from 0 to last sampling time (AUC0-t ) and extrapolated to infinity (AUC0-∞ ). To sum up, an optimized UPLC-MS/MS approach that could be used to rapidly, simultaneously, and sensitively detect seven bioactive compounds derived from SM-MC extract preparations was successfully developed, which may offer a pharmacokinetic basis for preclinical and clinical studies of SM-MC herb pair for treating MIRI.

Acute left atrial ridge lesion after cryoballoon ablation: How does this affect left atrial appendage closure combined procedure?

BACKGROUND: Acute left atrial ridge (LAR) lesions have been observed following atrial fibrillation (AF) ablation. However, LAR lesions had not yet been quantitatively evaluated and their influence on procedure combining cryoballoon (CB) ablation with left atrial appendage closure (LAAC) remained to be explored. METHODS: The profile of LAR lesions was measured by transesophageal echocardiography (TEE) in 117 consecutive nonvalvular AF patients, who underwent the combined procedure of CB ablation and LAAC. We thoroughly investigated how LAR lesions correlated with baseline variables and clinical outcomes. RESULTS: A total of 95 out of 96 available TEE images presented prominent acute LAR lesions. In terms of dimensions, there was a greater change in width (Δwidth = 3.6 ± 2.3 mm) than the thickness (Δthickness = 2.6 ± 3.5 mm), and the outer ostium was narrowed (Δouter ostium diameter = -3.4 ± 4.0 mm), while the inner ostium remained unchanged. A higher nadir temperature when freezing the left superior pulmonary vein (LSPV) led to an LAR lesion with a two times greater width (adjusted odds ratio = 1.16; 95% confidence interval, 1.02-1.31). In the evaluation of LAAC outcomes, four patients implanted with Watchman devices had minimal residual flow at the inferior border, while two implanted with LAmbre devices developed residual flow at the LAR side. Clinical outcomes were similar between groups divided by lesion size. CONCLUSION: Acute LAR lesions frequently occurred following the CB ablation combined procedure, and lesion width positively correlates with LSPV nadir temperature. The presence of these lesions affects the measurement of pacifier devices but has little impact on that of occluder devices.

A Consortium Blockchain-Based Agricultural Machinery Scheduling System.

The introduction of a consortium blockchain-based agricultural machinery scheduling system will help improve the transparency and efficiency of the data flow within the sector. Currently, the traditional agricultural machinery centralized scheduling systems suffer when there is a failure of the single point control system, and it also comes with high cost managing with little transparency, not leaving out the wastage of resources. This paper proposes a consortium blockchain-based agricultural machinery scheduling system for solving the problems of single point of failure, high-cost, low transparency, and waste of resources. The consortium blockchain-based system eliminates the central server in the traditional way, optimizes the matching function and scheduling algorithm in the smart contract, and improves the scheduling efficiency. The data in the system can be traced, which increases transparency and improves the efficiency of decision-making in the process of scheduling. In addition, this system adopts a crowdsourcing scheduling mode, making full use of idle agricultural machinery in the society, which can effectively solve the problem of resource waste. Then, the proposed system implements authentication access mechanisms, and allows only authorized users into the system. It includes transactions based on digital currency and eliminates third-party platform to charge service fees. Moreover, participating organizations have the opportunity to obtain benefits and reduce transaction costs. Finally, the upper layers supervision improves the efficiency and security of consensus algorithm, allows supervisors to block users with malicious motives, and always ensures system security.

Exploration and Research of Human Identification Scheme Based on Inertial Data.

The identification work based on inertial data is not limited by space, and has high flexibility and concealment. Previous research has shown that inertial data contains information related to behavior categories. This article discusses whether inertial data contains information related to human identity. The classification experiment, based on the neural network feature fitting function, achieves 98.17% accuracy on the test set, confirming that the inertial data can be used for human identification. The accuracy of the classification method without feature extraction on the test set is only 63.84%, which further indicates the need for extracting features related to human identity from the changes in inertial data. In addition, the research on classification accuracy based on statistical features discusses the effect of different feature extraction functions on the results. The article also discusses the dimensionality reduction processing and visualization results of the collected data and the extracted features, which helps to intuitively assess the existence of features and the quality of different feature extraction effects.

Defects-Induced In-Plane Heterophase in Cobalt Oxide Nanosheets for Oxygen Evolution Reaction.

Cobalt oxides as efficient oxygen evolution reaction (OER) electrocatalysts have received much attention because of their rich reserves and cheap cost. There are two common cobalt oxides, Co3 O4 (spinel phase, stable but poor intrinsic activity) and CoO (rocksalt phase, active but easily be oxidatized). Constructing Co3 O4 /CoO heterophase can inherit both characteristic features of each component and form a heterophase interface facilitating charge transfer, which is believed to be an effective strategy in designing excellent electrocatalysts. Herein, an atomic arrangement engineering strategy is applied to improve electrocatalytic activity of Co3 O4 for the OER. With the presence of oxygen vacancies, cobalt atoms at tetrahedral sites in Co3 O4 can more easily diffuse into interstitial octahedral sites to form CoO phase structure as revealed by periodic density functional theory computations. The Co3 O4 /CoO spinel/rocksalt heterophase can be in situ fabricated at the atomic scale in plane. The overpotential to reach 10 mA cm-2 of Co3 O4 /CoO is 1.532 V, which is 92 mV smaller than that of Co3 O4 . Theoretical calculations confirm that the excellent electrochemical activity is corresponding to a decline in average p-state energy of adsorbed-O on the Co3 O4 /CoO heterophase interface. The reaction Gibbs energy barrier has been significantly decreased with the construction of the heterophase interface.

Efficacy and safety of cryoballoon ablation for Chinese patients over 75 years old: A comparison with a younger cohort.

INTRODUCTION: Cryoballoon ablation (CBA) results in satisfactory outcomes for drug-resistant atrial fibrillation (AF) patients. However, the efficacy and safety of CBA have not yet been tested in the Chinese elderly population. Therefore, this study compared the recurrence of AF and complications of CBA in patients ≥75 years and <75 years. METHODS: A total of 677 patients (<75 years, n = 550; ≥ 75 years, n = 127) with paroxysmal (n = 603) or persistent (n = 74) non-valvular drug-resistant AF were included. The efficacy was assessed by the recurrence of AF, and the safety was evaluated by peri- and post-procedural complications. RESULTS: The CHA2DS2-VASc (2.6 ± 1.7 vs 4.8 ± 1.6, P < .01) and HAS-BLED (1.8 ± 0.8 vs 2.0 ± 0.8, P = .01) scores were significantly higher in the elderly group. The instant pulmonary vein isolation success rate was comparable (99.11% younger vs 98.98% older, P = .99). After a mean follow-up time of 12.8 ± 9.6 months, the 1-year freedom from AF rate was 80.6% vs 85.8% in the older and younger groups, respectively, while the survival analysis showed a nonsignificant difference in the rate of freedom from AF (log-rank P = .46). Cox regression showed that age was not a predictive factor for AF recurrence and was not dichotomized (hazard ratio [HR] = 0.868, 95% confidence interval [CI] 0.509-1.481; P = .6046) or continuous (HR = 0.990, 95% CI, 0.968-1.012, P = .3642). Similar complications rates were observed, including stroke (1.0% younger vs 0.93% older, P = .95) and major hemorrhagic events (1.2% younger vs 0% elder, P = .25). CONCLUSIONS: The efficacy and safety profiles of CBA in patients older than 75 years are comparable with those in younger patients.

Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS/NO signaling pathway in rats.

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 µg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α2-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α2-ARs instead of IRs.

Rs4968309 in Myosin Light Chain 4 (MYL4) Associated With Atrial Fibrillation Onset and Predicts Clinical Outcomes After Catheter Ablation in Atrial Fibrillation Patients Without Structural Heart Disease.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia with serious complications and a high rate of recurrence after catheter ablation. Recently, mutation ofMYL4was reported as responsible for familial atrial cardiomyopathy and AF. This study aimed to determine the association between polymorphism inMYL4with the onset and recurrence of AF.Methods and Results:A total of 7 single-nucleotide polymorphisms were selected by linkage disequilibrium and genotyped in 510 consecutive AF patients and 192 controls without structural heart disease. A total of 246 AF patients who underwent cryoballoon ablation had a 1-year scheduled follow-up study for AF recurrence. C allele and CC genotype of rs4968309 and A allele of rs1515751were associated with AF onset both before and after adjustment of covariation (age, sex, hypertension, and diabetes). AF type and left atrial size were different among the genotypes of rs4968309. Moreover, CC genotype of rs4968309 increased susceptibly of AF recurrence after cryoballoon ablation. The prevalence of hypertension was associated with rs1515752, and left atrial size was associated with the genotype of rs2071438. CONCLUSIONS: C allele and CC genotype of rs4968309 inMYL4were associated with AF onset and recurrence. Moreover, the A allele of rs1515751 had a significant association with AF onset. The polymorphisms ofMYL4can predict AF onset and prognosis after ablation in AF patients without structural heart disease.

UPLC-Q-TOF-MS and UPLC-MS/MS methods for metabolism profiles and pharmacokinetics of major compounds in Xuanmai Ganjie Granules.

Xuanmai Ganjie Granules (XMGJ), a widely used Chinese herbal formula in the clinic, is used for treatment of sore throats and coughs. Despite the chemical constituents having been clarifying by our previous studies, both of the metabolism and pharmacokinetic studies of XMGJ are unclear. This study aimed to explore the disposition process of XMGJ in vivo. A sensitive and selective ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was developed to analyze the absorbed components and metabolites in rat plasma and urine after oral administration of XMGJ. A total of 42 absorbed components, including 16 prototype compounds and 26 metabolites, were identified or tentatively characterized in rat plasma and urine after oral administration of XMGJ. Moreover, the pharmacokinetic studies of five compounds of XMGJ were investigated using ultra-high liquid chromatography with tandem mass spectrometry method. The results indicated that liquiritin, harpagoside, glycyrrhetic acid, liquiritigenin, formononetin and their metabolites might be the major components involved in the pharmacokinetic and metabolism process of XMGJ. This research showed a comprehensive investigation of XMGJ in vivo, which could provide a meaningful basis for further material basis and pharmacological as well as toxicological research.

Highly Sensitive Hill-Type Small-Molecule pH Probe That Recognizes the Reversed pH Gradient of Cancer Cells.

A hallmark of cancer cells is a reversed transmembrane pH gradient, which could be exploited for robust and convenient intraoperative histopathological analysis. However, pathologically relevant pH changes are not significant enough for sensitive detection by conventional Henderson-Hasselbalch-type pH probes, exhibiting an acid-base transition width of 2 pH units. This challenge could potentially be addressed by a pH probe with a reduced acid-base transition width (i.e., Hill-type probe), appropriate p Ka, and membrane permeability. Yet, a guideline to allow rational design of such small-molecule Hill-type pH probes is still lacking. We have devised a novel molecular mechanism, enabled sequential protonation with high positive homotropic cooperativity, and synthesized small-molecule pH probes (PHX1-3) with acid-base transition ranges of ca. 1 pH unit. Notably, PHX2 has a p Ka of 6.9, matching the extracellular pH of cancer cells. Also, PHX2 is readily permeable to cell membrane and allowed direct mapping of both intra- and extracellular pH, hence the transmembrane pH gradient. PHX2 was successfully used for rapid and high-contrast distinction of fresh unprocessed biopsies of cancer cells from normal cells and therefore has broad potentials for intraoperative analysis of cancer surgery.

A Novel Tri-Axial MEMS Gyroscope Calibration Method over a Full Temperature Range.

The micro-electro-mechanical inertial measurement unit (MEMS-IMU) has gradually become a research hotspot in the field of mid-low navigation, because of its advantages of low cost, small size, light weight, and low power consumption (CSWap). However, the performance of MEMS-IMUs can be severely degraded when subjected to temperature changes, especially gyroscopes. In order to make full use of the navigation accuracy, this paper proposes an optimized error calibration method for a tri-axial MEMS gyroscope across a full temperature range. First of all, a calibration error model is established which includes package misalignment error, sensor-to-sensor non-orthogonality error, scale factor, and bias. Then, a simple three-position positive/reversed test is undertaken by carrying out a single-axis temperature-controlled turntable at different reference temperature points. Lastly, the error compensation vector is obtained using the least squares method to establish an error matrix. It is worth mentioning that the error compensation vector at a known temperature point can be calculated through Lagrange interpolation; then, the outputs of the tri-axial MEMS gyroscope can be well compensated, eliminating the need for a recalibration step. The experimental results confirm the effectiveness of the proposed method, which is feasible and operational in engineering applications, and has a certain reference value.