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Severe heat exposure causes mitochondrial fragmentation and dysfunction, which contribute to the pathogenesis of heat-related illness. L-citrulline is a naturally occurring amino acid and has been suggested to influence heat shock responses. This study aimed to test whether L-citrulline supplementation would preserve mitochondrial integrity and attenuate heat-induced skeletal muscle injury, and elucidate the underlying mechanisms. At 37°C, L-citrulline (2 mM) increased mitochondrial elongation in mouse C2C12 myoblasts, a process associated with a reduction in mitochondrial fission protein Drp1 levels. Mechanistic studies revealed that L-citrulline increased cellular nitric oxide (NO) levels, but not S-nitrosylation of Drp1. L-citrulline caused a decrease in phosphorylation of Drp1 at Ser 616 and an increase in phosphorylation of Drp1 at Ser 637, which resulted in a reduced mitochondrial localization of Drp1. L-NAME, a non-selective NO synthase inhibitor, abolished the increase in L-citrulline-induced NO levels and inhibited Drp1 phosphorylation changes and mitochondrial elongation, which indicates involvement of a NO-dependent pathway. Under 43°C heat stress conditions, L-citrulline prevented translocation of Drp1 to mitochondria, mitochondrial fragmentation and decreased membrane potential. Finally, L-citrulline pretreatment inhibited heat-induced reactive oxygen species (ROS) overproduction, caspase 3/7 activation, apoptotic cell death, and improved cell viability. NO inhibitor L-NAME abolished all the above protective effects of L-citrulline under heat stress. Our results suggest that L-citrulline prevents heat-induced mitochondrial dysfunction and cell injury through NO-mediated Drp1 inhibition in C2C12 myoblasts. L-citrulline may be an effective treatment for heat-related illnesses and other mitochondrial diseases.
In this paper, we derive the optimal cyclical design of a target benefit (TB) pension plan that balances the sustainability and the benefit stability using the optimal control approach. The optimal design possesses a linear risk sharing structure with cyclical parameters. We observe that the optimal design should be pro-cyclical in the usual circumstances, but counter-cyclical when the pension plan is severely in deficit. We compare the TB plans with the defined benefit plans and conclude that a more aggressive investment strategy should be adopted for the TB plans. In the end, we provide a cautionary note on the optimal control approach in the study of the TB plans.
To address the shortcomings of existing methods for rotorcraft searching, positioning, tracking and landing on a ship at sea, a dual-channel LIDAR searching, positioning, tracking and landing system (DCLSPTLS) is proposed in this paper, which utilises the multi-pulse laser echoes accumulation method and the physical phenomenon that the laser reflectivity of the ship deck in the near-infrared band is four orders of magnitude higher than that of the sea surface. The DCLSPTLS searching and positioning model, tracking model and landing model are established, respectively. The searching and positioning model can provide estimates of the azimuth angle, the distance of the ship relative to the rotorcraft and the ship's course. With the above parameters as inputs, the total tracking time and the direction of the rotorcraft tracking speed can be obtained by using the tracking model. The landing model can calculate the pitch and the roll angles of the ship's deck relative to the rotorcraft by using the least squares method and the laser irradiation coordinates. The simulation shows that the DCLSPTLS can realise the functions of rotorcraft searching, positioning, tracking and landing by using the above parameters. To verify the effectiveness of the DCLSPTLS, a functional test is performed using a rotorcraft and a model ship on a lake. The test results are consistent with the results of the simulation.
COVID-19 is erupting globally and Wuhan successfully controlled it within a month. Infections arose from infectious persons outside hospitals. After data revision, data-based and model-based analyses are implemented and the conclusions are as follows. The incubation period of most infected people may be 6-7 days. The number of infectious persons outside hospitals in Wuhan on Jan.20 is about 10000 and reached more than 20000 on the day of Lockdown, it exceeded 72000 on Feb.4. Both data-based and model-based analyses gave out the evolution of the reproduction number, which is over 2.5 in early January, then go down to 1.62 in late January and 1.20 in early February, a sudden drop to less than 0.5 due to the strict Stay-at-home management after Feb.11. Strategies of Stay-at-home, Safe-protective measures and Ark hospitals are the main contributions to control COVID-19 in Wuhan. Two inflection points of COVID-19 in Wuhan exactly correspond to Feb.5 and Feb.15, the two days when Ark hospitals were introduced and the complete implementation of Stay-at-home. Based on the expression of the reproduction number, group immunity also is discussed. It shows that only when the group immunization rate is over 75 percent can COVID-19 be under control, group immunity actually would be full infection and the total deaths will be 220,000 for a city as big as Wuhan. Sensitivity analysis suggests that 30 percent of people staying at home in combination with better behavior changes, such as social-distancing and frequent hand-washing, can effectively contain COVID-19. But only when this proportion is over 60 percent can the control effect and efficiency like Wuhan be obtained.
The COVID-19 pandemic resulted in millions of deaths worldwide and is considered a significant mass-casualty disaster (MCD). The surge of patients and scarcity of resources negatively impacted hospitals, patients, and medical practice. We hypothesized ICUs during this MCD had a higher acuity of illness and subsequently had increased lengths of stay (LOS), complication rates, death rates, and costs of care. The purpose of this study was to investigate those outcomes.
This was a multicenter, retrospective study that compared intensive care admissions in 2020 to those in 2019 to evaluate patient outcomes and cost of care. Data were obtained from the Vizient Clinical Data Base/Resource Manager.
Data included the number of ICU admissions, patient outcomes, case mix index, and summary of cost reports. Quality outcomes were also collected. 1,304,981 patients from 333 hospitals were included. For all medical centers, there was a significant increase in LOS index, ICU LOS, complication rate, case mix index, total cost, and direct cost index.
The MCD caused by COVID-19 was associated with increased adverse outcomes and cost-of-care for ICU patients.
Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.
In this study, an active defence cooperative guidance (ADCG) law that enables cheap and low-speed airborne defence missiles with low manoeuverability to accurately intercept fast and expensive attack missiles with high manoeuverability was designed to enhance the capability of aircraft for active defence. This guidance law relies on the line-of-sight (LOS) guidance method, and it realises active defence by adjusting the geometric LOS relationship involving an attack missile, a defence missile and an aircraft. We use a nonlinear integral sliding surface and an improved second-order sliding mode reaching law to design the guidance law. This can not only reduce the chattering phenomenon in the guidance command, but it can also ensure that the system can reach the sliding surface from any initial position in a finite time. Simulations were carried out to verify the proposed law using four cases: different manoeuvering modes of the aircraft, different speed ratios of the attack and defence missiles, different reaching laws applied to the ADCG law and a robustness analysis. The results show that the proposed guidance law can enable a defence missile to intercept an attack missile by simultaneously using information about the relative motions of the attack missile and the aircraft. It is also highly robust in the presence of errors and noise.
Neuromedin U (NMU) has a critical function on the regulation of food intake in mammals, while the information is little in teleost. To investigate the function of NMU on appetite regulation of Siberian sturgeon (Acipenser baerii), this study firstly cloned nmu cDNA sequence that encoded 154 amino acids including NMU-25 peptide. Besides, the results showed that nmu mRNA was widely distributed in various tissues especially in the hypothalamus and telencephalon. The results of nutritional status (pre-feeding and post-feeding, fasting and re-feeding) experiments showed that nmu mRNA expression was significantly decreased at 1 and 3 h after feeding in different brain regions. Similarly, after feeding, the expression of nmu significantly decreased in peripheral tissues. Moreover, nmu expression in the hypothalamus was significantly increased after fasting 1 day, but decreased after fasting 17 days, which was significantly reversed after re-feeding. However, other brain regions like telencephalon and peripheral tissues like esophagus, intestinum valvula and liver have different change patterns. Further study showed that acute i.c.v. and i.p. injection of NMU and chronic i.p. injection of NMU significantly reduced the food intake in a dose dependent mode. In addition, the expressions of several critical appetite factors (nmu, aplein, cart, cck, ghrelin, npy, nucb2, pyy and ucn3) were significantly affected by acute NMU-25 administration in the hypothalamus, intestinum valvula and liver. These results indicate that NMU-25 has the anorexigenic function on food intake by affecting different appetite factors in Siberian sturgeon, which provides a foundation for further exploring the appetite regulation networks in fish.
The vortex dynamics in a stratified environment is of fundamental importance in various flow systems, however, the mechanism of successive vortex–interface interactions remains not fully understood. This study investigates synthetic jet vortex rings impinging on a water–oil interface by experiment and numerical simulation. Two cases in the laminar and transitional regimes are concerned with the Froude number (Fr) of 0.35 and 0.82, respectively. The vortex rings for the two cases follow a similar evolution with three distinct stages, including vortex free-travel, vortex–interface interaction and vortex stretching. As products of the vortex–interface interaction, the secondary vortex rings are baroclinically generated in both water and oil followed by the formation of hairpin vortices through azimuthal deformation. Distinguished from an isolated vortex–interface interaction, complex interactions occur between the primary vortex ring and hairpin vortices, which can enhance the vortex ring instability in existence of the stratification for the laminar case. However, the vortex ring instability for the transitional case can develop earlier due to nonlinear effects with increasing Reynolds number. The spatio-temporal properties of the interface deformation and interfacial waves are analysed. The maximum penetration height of vortex rings scales with Fr2 as that for the isolated situation. Particularly, the transitional case is found to produce destabilization of the interfacial waves at a further radial location. The mechanism is revealed by connecting the dynamics of the vortex and the interface, which can be attributed to the radial development of perturbances stemming from the vortex ring instability under strong vortex–interface interaction.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
A new system for preparing 14C samples was established for a compact accelerator mass spectrometer (GXNU-AMS) at Guangxi Normal University. This sample preparation system consists of three units: a vacuum maintenance unit, a CO2 purification unit, and a CO2 reduction unit, all of which were made of quartz glass. A series of radiocarbon (14C) preparation experiments were conducted to verify the reliability of the system. The recovery rate of graphite obtained was more than 80%. The carbon content in the commercial toner and wood sample was linearly fitted to the CO2 pressure in the measurement unit of the system. The results showed a good linear relationship, indicating that the reliability of the sample preparation system. AMS measurements were conducted on a batch of standard, wood, and dead graphite samples prepared using this system. The results showed that the beam current of 12C- for each sample was more than 40 μA, the carbon contamination introduced during the sample preparation process was ∼ 2 × 10–15, and that the new sample preparation system is compact, low-contamination, and efficient and meets the GXNU-AMS requirements for 14C samples.
Does the language we speak affect the way we think? This Element provides a synthesis of contemporary research on the interplay between language and cognition in speakers of two or more languages and examines variables deemed to impact bilingual acquisition and conceptualization of language-specific thinking patterns during L2 learning. An overview of different yet interrelated studies is offered across a variety of conceptual domains to illustrate different approaches and key variables. The comparison of monolingual and bilingual data demonstrates the highly integrative nature between L2 learning and the changing of one's entire cognitive outlook in L2 speakers. This Element makes relevant connections between language learning and bilingual cognition, aiming to shed new light on how learners acquire conceptual distinctions of the target language(s). It also raises theoretical and pedagogical issues that encourage teachers to reflect upon how to incorporate recent advances in language-and-cognition research with aspects of L2 teaching.
In the past 10–15 years, the government of China has made various efforts in tackling excessive antibiotics use. Yet, little is known about their effects at rural primary care settings. This study aimed to determine the impact of government policies and the COVID-19 pandemic on antibiotic prescribing practices at such settings utilizing data from separate studies carried out pre- and during the pandemic, in 2016 and 2021 in Anhui province, China, using identical sampling and survey approaches. Data on antibiotics prescribed, diagnosis, socio-demographic, etc., were obtained through non-participative observation and a structured exit survey. Data analysis comprised mainly descriptive comparisons of 1153 and 762 patients with respiratory infections recruited in 2016 and 2021, respectively. The overall antibiotics prescription rate decreased from 89.6% in 2016 to 69.1% in 2021, and the proportion of prescriptions for two or more classes of antibiotics was estimated as 35.9% in 2016 and 11.0% in 2021. There was a statistically significant decrease in the number of days from symptom onset to clinic visits between the year groups. In conclusion, measures to constrain excessive prescription of antibiotics have led to some improvements at the rural primary care level, and the COVID-19 pandemic has had varying effects on antibiotic use.
Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial.
In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets.
As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated).
These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.
Under global warming, many glaciers worldwide are receding. However, recent studies have suggested the extension of the Karakoram Anomaly, a region of anomalous glacier mass gain, into the western Kunlun and eastern Pamir mountains. However, the eastern limit of this anomaly in the Kunlun Mountains is unclear. This study, using changes in glacier area and surface elevation, estimates the eastern limit of the Kunlun-Pamir-Karakoram anomaly at ~85°E. Over the past 50 years, glaciers west of 85°E in the Kunlun Mountains decreased in area from 8401 to 7945 km2 at a rate of −0.12 ± 0.07% a−1, showed a reduction in the rate of retreat through time and have recently gained mass, with surface elevation changes of 0.15 ± 0.35 m a−1 over the period of 2000–2013. Glaciers east of 85°E have experienced greater rates of area change (−61 ± 12 km2 and −0.43 ± 0.13% a−1) over the past 50 years, accelerated area loss in recent years and elevation change rate of −0.51 ± 0.18 m a−1 between 2000 and 2013. These patterns of elevation and area change are consistent with regional increases in summer temperature in the eastern Kunlun Mountains and slight cooling in the western Kunlun Mountains.
To determine if limb lengths, as markers of early life environment, are associated with the risk of diabetes in China.
We performed a cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), and multivariable-adjusted Cox proportional hazard regression models were used to examine the associations between baseline limb lengths and subsequent risk of diabetes.
The CHARLS, 2011–2018.
The study confined the eligible subject to 10 711 adults aged over 45 years from the CHARLS.
During a mean follow-up period of 6·13 years, 1358 cases of incident diabetes were detected. When controlling for potential covariates, upper arm length was inversely related to diabetes (hazard ratio (HR) 0·95, 95 % CI (0·91, 0·99), P = 0·028), and for every 1-cm difference in knee height, the risk of diabetes decreased by about 4 % (HR 0·96, 95 % CI (0·93, 0·99), P = 0·023). The association between upper arm length and diabetes was only significant among females while the association between knee height and diabetes was only significant among males. In analyses stratified by BMI, significant associations between upper arm length/knee height and diabetes only existed among those who were underweight (HR 0·91, 95 % CI (0·83, 1·00), P = 0·049, HR 0·92, 95 % CI (0·86, 0·99), P = 0·031).
Inverse associations were observed between upper arm length, knee height and the risk for diabetes development in a large Asian population, suggesting early life environment, especially infant nutritional status, may play an important role in the determination of future diabetes risk.
This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.
The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.