Dose and formulation of azithromycin in mass drug administration studies: a systematic review protocol

Introduction: Azithromycin has been given for tropical infectious diseases such as trachoma and yaws by mass drug administration (MDA). As well as controlling the infectious disease in question, MDA may have a beneficial effect in reducing mortality in young children. However, the dose, formulation, frequency and duration of azithromycin used in certain infectious diseases may vary in different studies, and these differences may have impacts on the effectiveness of azithromycin MDA. Furthermore, whether the dose, formulation, frequency and duration are associated with the effectiveness of azithromycin for reducing child mortality—if indeed this effect can be confirmed—remain unknown. In this study, we will investigate whether different strategies such as different dose, formulation, frequency and duration affect the effectiveness of azithromycin MDA on the prevalence of certain infectious diseases or child mortality.Methods and analysis: A narrative systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform will be searched. No language restrictions will be applied. All randomised/quasi-controlled trials, observational studies (cross-sectional studies, cohort studies and case–control studies), case series and registered protocols will be considered. Dose, duration, frequency, rounds and formulations of azithromycin used in MDA will be collected and reviewed. The outcomes will be disease prevalence/control in children and child mortality. Data from the individual studies will not be pooled

Synthetic lethality between TP53 and ENDOD1

The atypical nuclease ENDOD1 functions with cGAS-STING in innate immunity. Here we identify a previously uncharacterized ENDOD1 function in DNA repair. ENDOD1 is enriched in the nucleus following H2O2 treatment and ENDOD1−/− cells show increased PARP chromatin-association. Loss of ENDOD1 function is synthetic lethal with homologous recombination defects, with affected cells accumulating DNA double strand breaks. Remarkably, we also uncover an additional synthetic lethality between ENDOD1 and p53. ENDOD1 depletion in TP53 mutated tumour cells, or p53 depletion in ENDOD1−/− cells, results in rapid single stranded DNA accumulation and cell death. Because TP53 is mutated in ~50% of tumours, ENDOD1 has potential as a wide-spectrum target for synthetic lethal treatments. To support this we demonstrate that systemic knockdown of mouse EndoD1 is well tolerated and whole-animal siRNA against human ENDOD1 restrains TP53 mutated tumour progression in xenograft models. These data identify ENDOD1 as a potential cancer-specific target for SL drug discovery

Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows

IntroductionPeripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows.MethodsIn this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal.ResultsIn comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography–mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines.DiscussionIn summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation

Near-Optimal Active Learning for Multilingual Grapheme-to-Phoneme Conversion

The construction of pronunciation dictionaries relies on high-quality and extensive training data in data-driven way. However, the manual annotation of corpus for this purpose is both costly and time consuming, especially for low-resource languages that lack sufficient data and resources. A multilingual pronunciation dictionary includes some common phonemes or phonetic units, which means that these phonemes or units have similarities in the pronunciation of different languages and can be used in the construction process of pronunciation dictionaries for low-resource languages. By using a multilingual pronunciation dictionary, knowledge can be shared among different languages, thus improving the quality and accuracy of pronunciation dictionaries for low-resource languages. In this paper, we propose using shared articulatory features among multiple languages to construct a universal phoneme set, which is then used to label words for multiple languages. To achieve this, we first developed a grapheme−phoneme (G2P) model based on an encoder−decoder deep neural network. We then adopted a near-optimal active learning method in the process of building the pronunciation dictionary to select informative samples from a large, unlabeled corpus and had them labeled by experts. Our experiments demonstrate that this method selected about 1/5 of the unlabeled data and achieved an even higher conversion accuracy than the results of the large data training method. By selectively labeling samples with a high uncertainty in the model, while avoiding labeling samples that were accurately predicted by the current model, our method greatly enhances the efficiency of pronunciation dictionary construction

The Effect of Artificial Mowing on the Competition of Phragmites australis and Spartina alterniflora in the Yangtze Estuary

Spartina alterniflora Loisel. is one of the most invasive species in the world. However, little is known about the role of artificial mowing in its invasiveness and competiveness. In this work, we studied the effect of mowing on its interspecific interactions with native species Phragmites australis (Cav.) Trin ex Steud of the Yangtze Estuary, China. We calculated their relative neighbor effect (RNE) index, effect of relative crowding (Dr) index, and interaction strength (I) index. The results showed that the RNE of Phragmites australis and Spartina alterniflora was 0.354 and 0.619, respectively, and they have competitive interactions. The mowing treatments can significantly influence the RNE of Phragmites australis and Spartina alterniflora on each other. Concretely, the RNE of Spartina alterniflora in the removal treatments was significantly higher than the value in the controls. But the RNE of Phragmites australis in the removal treatments was significantly lower than the value in the controls. Meanwhile, Dr of the two species on the targets was higher in the removal treatments than that in the controls, and the opposite was for I. We concluded that artificial mowing could promote the invasion of Spartina alterniflora by increasing its competitive performance compared with native species

Coordinated optimization method for IGBT peak voltage suppression of mine-used inverter

At present, the methods of optimizing busbar structure parameters, changing gate drive resistance and designing absorption circuit are commonly used to suppress the peak voltage of insulated gate bipolar transistor (IGBT) in mine-used inverter caused by stray inductance. But the existing research has not revealed the coordination and unification relationship between the methods and their coordination and optimization criteria. In order to solve this problem, taking BPJ5-630-1140 type mine-used four-quadrant inverter as the research object, based on the analysis of the influence of stray inductance on the electric-thermal performance of IGBT, a coordinated optimization method of IGBT peak voltage suppression is proposed. ① The method analyzes the influence of busbar structure parameters and grid drive resistance on IGBT peak voltage and power loss. The results show that the peak voltage and power loss of IGBT increase with the AC busbar length increase and the AC busbar width decrease. With the increase of gate drive resistance, IGBT peak voltage decreases and power loss increases. ② The diode clamped absorption circuit is designed, which is verified by experiments to reduce the peak voltage and power loss of IGBT. ③ Considering that the AC busbar width has no effect on the layout and heat dissipation performance of IGBT, the gate drive resistance and the AC busbar length are selected as decision variables. The BP neural network and elitist non-dominated sorting genetic algorithm (BP-NSGAⅡ) are used to achieve multi-objective optimization of IGBT peak voltage, the maximum IGBT temperature and the maximum temperature of radiator surface. The experimented results show that when the maximum temperature of radiator surface is 55-65 ℃ and the maximum IGBT temperature is 74-80 ℃, the minimum IGBT peak voltage is 1861 V. The corresponding grid drive resistance is 5 Ω, the AC busbar length is 300 mm, and the AC busbar width is 200 mm. The optimized IGBT peak voltage of BPJ5-630-1140 type inventer is 1 856 V, which is 35% lower than 2 856 V before optimization. The IGBT peak voltage is effectively suppressed, and the operation reliability of the mine-used inverter is improved

Adaptive Pressure Control of the Clutch Hydraulic Actuator in Wet Dual Clutch Transmission Based on T-S Fuzzy Model and Extended State Observer

The wet dual-clutch transmission (DCT) controls clutch engagement via a hydraulic actuator to facilitate smooth starting and gearshifts. The quality of these operations is directly influenced by the hydraulic actuator’s precision in pressure control. However, existing research has overlooked that uncertainties, such as variations in the dynamic model parameters of the hydraulic actuator and modeling errors, can impact the effectiveness of pressure control. Furthermore, the intricate nonlinear characteristics of the hydraulic actuator pose significant challenges in designing an appropriate hydraulic controller. In response to these challenges, we propose an adaptive pressure control method for the hydraulic actuator, leveraging a T-S fuzzy model and an extended state observer. Firstly, a dynamic model is established for the clutch hydraulic actuator that comprehensively accounts for its nonlinear attributes. An extended state observer is then designed to estimate variables that are arduous to measure directly, including parameter fluctuations, modeling inaccuracies, and the state variables. Building upon this foundation, the T-S fuzzy modeling technique is employed to approximate the nonlinear components embedded within the dynamic model, and the backstepping method is employed to design an adaptive pressure controller for the hydraulic actuator. Simulation verification results demonstrate the efficacy and robustness of the adaptive pressure control method in addressing parameter fluctuations and other pertinent factors

Analysis of heat dissipation performance of mine inverter based on the integrated model

The space of the mine inverter is closed. The internal power device itself will produce a lot of heat in the operation process, which is easy to produce thermal degradation and thermal failure. In the existing research, a certain power device or a radiator of the mine inverter is analyzed independently. The heat exchange effect among the power device or the radiator is not considered. The combination with the running state of the mine inverter is not close enough. Therefore, the deviation between the heat generation and heat transfer processes and the actual situation is large. This reduces the accuracy and comprehensiveness of the heat dissipation performance analysis. In order to the above problems, taking the 630 kW/1 140 V four-quadrant mine inverter as the research object, the heat dissipation performance of the mine inverter is analyzed based on integrated model . A topological model of the main circuit of the mine inverter considering equivalent resistance is established. The electrical characteristics of the bus bar and the cable, the charge/discharge resistance, the absorption resistance, the IGBT module and the output reactor are analyzed, and the power loss is calculated. The cooling system of the inverter is optimized by forced water cooling + air cooling + natural cooling. The IGBT module and the absorption resistor are arranged on the substrate of the water-cooling radiator. The fan is configured to accelerate the heat exchange efficiency of the output reactor, and other power devices dissipate heat naturally. Based on the integrated model, the temperature field characteristics and heat transfer characteristics of the mine inverter are numerically simulated and analyzed. The correctness of the temperature field simulation based on the integrated model and the effectiveness of the heat dissipation design are verified by building the loading test platform of mineing inverter . The results show the following points. ① Under the heat transfer of conduction, convection and radiation of the internal power devices, the temperature of the flameproof enclosure is higher than the ambient temperature. The lowest temperature is 36 ℃. The temperature of the rear substrate is higher than that of the other flameproof surfaces, and the highest temperature can reach 70 ℃. The temperature of the internal components of the mine inverter is not higher than 80 ℃, which is far lower than the specified value of relevant standards. The mine inverter has good heat dissipation performance. The temperature of IGBT module is the highest, the temperature of the bus bar assembly is the second, and the temperature of the DC filter capacitor assembly is the lowest. ② The power device in the process of charging has a larger loss. But because of the short charging time, the loss will not cause severe changes in temperature. The instantaneous temperature of the power device is not more than 59 ℃. The maximum instantaneous temperature of the discharge resistance can reach 267 ℃, and the action time above 100 ℃ is 200 seconds. The high-temperature impact resistance of the trapezoidal aluminum shell resistor can meet the application scenario. It does not form a thermal stress cycle, and will not produce thermal breakdown and thermal failure. ③ The temperature of each power device tends to be stable gradually after 2-3 h. The experimental and simulation results of each calibration temperature measurement point keep good consistency in the overall trend

Surface-Engineered Graphene Navigate Divergent Biological Outcomes toward Macrophages

The &quot;nano-bio&quot; interface profoundly shapes the interaction between cells and nanomaterials and can even decide a cell&#39;s fate. As a nascent two-dimensional material, graphene has many unique attributes and is proposed to be a promising candidate for biomedical applications. Thus, for graphene-based applications, it is necessary to clarify how the graphene surface navigates biological outcomes when encountering &quot;janitorial&quot; cells (macrophages). For this purpose, we synthesized nanographene oxide (nGO) and engineered the surface with polyethylene glycol (PEG), bovine serum albumin (BSA), and poly(ether imide) (PEI). In contrast to pristine nGO, decoration with PEG and BSA hindered endocytosis and improved their benignancy toward macrophages. Contrarily, nGO-PEI commenced with favorable endocytosis but then suffered stagnation due to compromised macrophage viability. To unravel the underlying mechanisms regulating these diverse macrophage fates, we built a stepwise analysis. Compared to the others, nGO-PEI tended to interact electrostatically with mitochondria after their cellular internalization. Such an unexpected encounter disrupted the normal potential and integrity of mitochondria and then elicited an alteration in reactive oxygen species and cytochrome c. These responses further initiated the activation of the caspase family and ultimately dictated cells to undergo apoptosis. The advances described above will complement our knowledge of graphene functionality and serve to guide its application in biotechnological applications.</p

Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro

Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%− 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, β-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA