Melatonin ameliorates simulated-microgravity-induced mitochondrial dysfunction and lipid metabolism dysregulation in hepatocytes.

The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.

KNIndex: a comprehensive database of physicochemical properties for k-tuple nucleotides.

With the development of high-throughput sequencing technology, the genomic sequences increased exponentially over the last decade. In order to decode these new genomic data, machine learning methods were introduced for genome annotation and analysis. Due to the requirement of most machines learning methods, the biological sequences must be represented as fixed-length digital vectors. In this representation procedure, the physicochemical properties of k-tuple nucleotides are important information. However, the values of the physicochemical properties of k-tuple nucleotides are scattered in different resources. To facilitate the studies on genomic sequences, we developed the first comprehensive database, namely KNIndex (https://knindex.pufengdu.org), for depositing and visualizing physicochemical properties of k-tuple nucleotides. Currently, the KNIndex database contains 182 properties including one for mononucleotide (DNA), 169 for dinucleotide (147 for DNA and 22 for RNA) and 12 for trinucleotide (DNA). KNIndex database also provides a user-friendly web-based interface for the users to browse, query, visualize and download the physicochemical properties of k-tuple nucleotides. With the built-in conversion and visualization functions, users are allowed to display DNA/RNA sequences as curves of multiple physicochemical properties. We wish that the KNIndex will facilitate the related studies in computational biology.

Nickel-Based Bifunctional Cocatalyst to Enhance CdS Photocatalytic Hydrogen Production.

The design of nanocomposites as a light-capturing system applied in photocatalytic water splitting is an emerging area of research. In our study, a simple in situ photodeposition method was proposed for the synthesis of CdS nanoflowers modified by nickel-based bifunctional, i.e., Ni/Ni(OH)2, cocatalysts. The introduction of cocatalysts has demonstrated a notable enhancement in the photocatalytic hydrogen evolution efficiency of CdS. The quantity of cocatalysts supported on CdS played an important role in governing the light absorption capability and photocatalytic efficacy. Ni-CdS-10 showed the best photocatalytic activity of 30.51 mmol g-1 h-1, which was 1.8 times and 2.6 times higher activity than Pt-CdS-1 wt % and pure CdS, respectively. Mechanism studies with UV-vis DRS, photoluminescence, and Mott-Schottky plots revealed the intrinsic electric field created at the p-n Ni(OH)2/CdS junctions, which can effectively implement the transport and separation of photoinduced carriers. From linear sweep voltammetry, electrochemical impedance spectroscopy, and DFT calculation, both Ni(OH)2 and Ni can effectively decrease the Gibbs free energies of hydrogen adsorption and reduce the overpotential of hydrogen evolution. As a result, the efficiency of generating H2 through photocatalysis experienced significant improvement, and the participation of bifunctional cocatalysts further reduced the photocorrosion of CdS, enhanced stability, improved low price, and efficient photocatalyst production.

To validate the integral conceptual model of frailty among community-dwelling older adults in China: a cross-sectional study.

PURPOSE: The integral conceptual model of frailty (ICFM) integrates physical, psychological, social aspects of individuals and stresses that frailty is a dynamic state evolving over time. This study aimed to validate the ICMF among community-dwelling older adults in China. METHODS: The study recruited 341 older community-dwelling adults by convenient sampling method between June 1 and August 30, 2019 in Hubei province, China. The data was collected by questionnaire-based survey. Frailty was assessed by the Chinese version of the Tilburg Frailty Index. Participants were assessed for life-course determinants, disease and adverse health outcomes. Hierarchical regression analyses, Bootstrap method and the structural equation model were conducted in data analysis. RESULTS: Both linear and logistic hierarchical regression models were statistically significant. Life-course determinants, disease, and three domains of frailty together explained 35.6% to 50.6% of the variance of disability and all domains of quality of life. The mediation effect of frailty between disease and all adverse outcomes was significant, excluding hospitalization. The structural equation model guided by the ICMF fits the data well. CONCLUSIONS: The ICMF is valid among community-dwelling older adults in China. Therefore, the multidimensional concept of frailty should be widely used in Chinese communities.

Progress in Intradermal and Transdermal Gene Therapy with Microneedles.

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.

Fat rather than health - Ecotoxic responses of Bufo raddei to environmental heavy metal stress during the non-breeding season.

The non-breeding season is a critical period for iteroparous animals to repair damage and store energy, which is crucial for future survival and reproductive success. However, it is unknown how animals allocate energy efficiently among reproduction, self-maintenance, and repair of oxidative damage caused by breeding during the non-breeding period, particularly under pollution. In the present study, the self-maintenance response and reproductive strategy of Bufo raddei to long-term environmental heavy metal stress was explored during the non-breeding season. Heavy metal enrichment level, organ coefficients, nutritional status, gonadal developmental level, oxidation level, and the immune status of B. raddei during the non-breeding season were tested, energy allocation preferences and energy consumption costs were analyzed. The results revealed significant heavy metal accumulation through biomagnification in the organs of B. raddei from the polluted area. Under long-term environmental heavy metal pollution, the energy investment by B. raddei for growth and energy storage was higher than that for health-maintenance during the early life cycle stage. The energy inputted for immune and antioxidant functions was significantly lower, and the energy inputted for self-maintenance during the early life stage was significantly higher than that during the late stage. B. raddei from a heavy metal polluted area spent more energy consumption cost on immunity and oxidative stress, but suffered higher oxidative stress and lower immune status. Moreover, the reproductive input of individuals in a heavy metal polluted area was generally low during the non-breeding season, and the energy input for reproduction limited the energy input for self-maintenance in females.

The prevalence and influencing factors for compassion fatigue among nurses in Fangcang shelter hospitals: A cross-sectional study.

AIM: We aim to investigate the prevalence and associated factors for compassion fatigue among nurses in Fangcang Shelter Hospitals in Wuhan. Studies have shown that compassion fatigue was more common among nurses than other health-care providers, and its predictors were also different. In recent years, most studies have investigated compassion fatigue in emergency and oncology nurses, whereas there is little information on compassion fatigue among nurses from the frontline of Fangcang Shelter Hospitals during the COVID-19 pandemic. METHODS: A descriptive, cross-sectional design was used in this study. An online survey was conducted among nurses (n = 972) of five Fangcang Shelter Hospitals in Wuhan, Hubei province, China, from 6 March to 10 March 2020. A self-administered questionnaire including demographic information, work-related information, General Health Questionnaire, Perceived Stress Scale and Compassion Fatigue Scale was used. RESULTS: The prevalence of compassion fatigue among nurses in Fangcang Shelter Hospitals was moderate, and most cases were mild. There was a significant relationship between compassion fatigue and work-related factors, mental health and perceived stress among nurses working in Fangcang Shelter Hospitals. CONCLUSIONS: Various factors contribute to compassion fatigue, including lower job satisfaction and job adaptability, less praise from patients, more fear of infection and more perceived stress. A good working atmosphere, organizational support and psychological consultation are essential to alleviate nurses' compassion fatigue during the anti-epidemic period.

Apathy co-occurs with subjective cognitive decline among community-dwelling older adults.

OBJECTIVE: To investigate the relationship between apathy and subjective cognitive decline (SCD) in community-dwelling older adults. METHODS: A total of 211 participants without objective cognitive impairment were included in this study. Their SCD, apathy, sleep quality, depression, and anxiety were assessed by face-to-face interviews. Multivariate logistic regression was constructed to examine the independent relationship between apathy and SCD with adjustment for confounders. RESULTS: The participants' average SCD-questionnaire and apathy evaluation scale-self scores were 7.13 and 30.65, respectively. Nearly half of the participants were categorized as having SCD. A quarter of participants were identified as apathetic. The apathy score was significantly associated with an increased risk of SCD (odds ratio 1.05, 95% confidence interval 1.01-1.10) after controlling for covariates. CONCLUSION: Apathy was independently and significantly associated with SCD in community-dwelling older adults without objective cognitive impairment. Thus early intervention on apathy is important to protect elderly cognitive functioning.

Cognition and practice on transitional care during the transfer from intensive care unit to a general ward among health care professionals: A qualitative study.

AIM: The aim of this study is to explore the cognition and practice on transitional care during the transfer from intensive care unit to a general ward among health care professionals in China. BACKGROUND: Due to the significant differences in the medical and humanistic environment at home and abroad, the safety of patients during the transmission from intensive care unit to the general ward is often ignored when their conditions become stable. There are few qualitative studies on the cognition and practice on transitional care during the transfer from intensive care unit to the ward among health care professionals in China. METHODS: With a qualitative research design, 20 medical and nursing staff in the neurosurgery intensive care unit and ward were interviewed from May 2021 to August 2021. NVivo 11.0 software was utilized for Colaizzi's (1978) method of data analysis. RESULTS: Based on data analysis, perceptions of transitional care, the influencing factors for transitional care and the recommendations for improving transitional care were obtained. CONCLUSION: To ensure the continuity of care and improve patient safety during the period from intensive care unit to a general ward in China, we should clarify the expectation for the content of intensive care unit transitional care services, establish the transitional nursing team, guide nursing work, standardize the handover mode and process from intensive care unit to the general ward, promote the communication and coordination of health care professionals and improve the transitional nursing security system from the perspective of institutional level. IMPLICATIONS FOR NURSING MANAGEMENT: This study can be used as a guide to help health care professionals provide a reference for the comprehensive development of transitional care services and the formulation of targeted intervention measures during the transfer from intensive care unit to a general ward in China.

The retrosplenial cortex as a possible "sensory integration" area: A neural network modeling approach of the differential outcomes effect in negative patterning.

We explored the hypothesis that learning a Pavlovian negative patterning task would be facilitated when training with differential, as opposed to non-differential, reinforcing outcomes. Two groups of rats received pairings of one visual and one auditory stimulus with food reward when these stimuli were presented on separate training trials, but without reward when both stimuli were presented on simultaneous stimulus compound trials (V+, A+, AV-; similar to an XOR problem). For Group Differential, each stimulus was separately paired with distinctively tasting food rewards, whereas for Group Non-Differential each stimulus was randomly paired with both food reward types across different stimulus element trials. We observed that rats learned the negative patterning task more rapidly and effectively when trained with differential outcomes. These data support a multi-layered connectionist model introduced by Delamater (2012) in which a multi-modal processing structure plays the role of a "sensory integration" area like that hypothesized for the retrosplenial cortex by Dave Bucci and his colleagues (e.g., Todd, Fournier, & Bucci, 2019). We discuss how such a region may develop different "negative occasion setting" and "configural inhibition" mechanisms in solving negative patterning and related tasks.

Grape seed proanthocyanidin extract ameliorates hepatic lipid accumulation and inflammation in grass carp (Ctenopharyngodon idella).

Hepatic lipid metabolism disorder due to excessive fat accumulation in fish is a significant problem in aquaculture. Studies have shown that grape seed procyanidin extract (GSPE) can regulate fish lipid metabolism and improve fish immunity. However, the mechanism is unclear. In this study, we used grass carp that stores excess fat in the liver as a model. In vitro, GSPE treatment of hepatocytes for 3 h significantly decreased TG content, accompanied with decreased expression of SREBP-1c, FAS, and ACC and increased expression of PPARα, ATGL, and LPL. GSPE treatment for 1 h significantly decreased expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1ß, and NF-κB) and increased the expression of anti-inflammatory cytokines (IL-10 and TGF-ß1). In vivo, the administration of GSPE significantly reduced high-fat diet-induced increase of serum CHOL, TG, and HDL, but increased LDL content. GSPE treatment for 3 h increased expression of ATGL and LPL, and significantly decreased the expression of HFD-fed-induced SREBP-1c, ACC, FAS, PPARγ, PPARα, and H-FABP. GSPE treatment for 3 h also significantly decreased the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1ß) and increased the expression of the anti-inflammatory cytokine IL-10. The expression levels of the lipogenic miRNAs, miR-33, and miR-122, were suppressed both in vivo and in vitro by GSPE. In summary, GSPE had hypolipidemic and potential anti-inflammatory effects in the liver, potentially mediated by miR-33 and miR-122.

Effects of Heavy Metal Pollution on Fitness and Swimming Performance of Bufo raddei Tadpole.

Systematic studies on the impact of environmental pollution on the survival adaptability of amphibians are relatively few. In this study, Bufo raddei tadpoles from two places with totally different backgrounds of heavy metal pollution were chosen to explore the effects of heavy metal pollution on fitness and swimming performance of tadpoles, the physiological effects were investigated as well. The tadpoles at GS 25, GS 30 and GS 35 were collected randomly from the two study sites and were exposed to different environmental temperatures. The results showed that heavy metal enrichment and antioxidant levels were significantly higher in the tadpoles under long-term heavy metal stress. Meanwhile, heavy metal pollution affected the adaptability of tadpoles to environmental change and decreased the swimming performance of the tadpoles. Unexpected, the tadpoles from heavy metal-polluted area also showed some adaptive changes, mainly reflected in the increase in swimming endurance.

Involvement of G6PD5 in ABA response during seed germination and root growth in Arabidopsis.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PDH or G6PD) functions in supply of NADPH, which is required for plant defense responses to stresses. However, whether G6PD functions in the abscisic acid (ABA) signaling pathway remains to be elucidated. In this study, we investigated the involvement of the cytosolic G6PD5 in the ABA signaling pathway in Arabidopsis. RESULTS: We characterized the Arabidopsis single null mutant g6pd5. Phenotypic analysis showed that the mutant is more sensitive to ABA during seed germination and root growth, whereas G6PD5-overexpressing plants are less sensitive to ABA compared to wild type (WT). Furthermore, ABA induces excessive accumulation of reactive oxygen species (ROS) in mutant seeds and seedlings. G6PD5 participates in the reduction of H2O2 to H2O in the ascorbate-glutathione cycle. In addition, we found that G6PD5 suppressed the expression of Abscisic Acid Insensitive 5 (ABI5), the major ABA signaling component in dormancy control. When G6PD5 was overexpressed, the ABA signaling pathway was inactivated. Consistently, G6PD5 negatively modulates ABA-blocked primary root growth in the meristem and elongation zones. Of note, the suppression of root elongation by ABA is triggered by the cell cycle B-type cyclin CYCB1. CONCLUSIONS: This study showed that G6PD5 is involved in the ABA-mediated seed germination and root growth by suppressing ABI5.

Exploration of CeO2-CuO Quantum Dots in Situ Grown on Graphene under Hypha Assistance for Highly Efficient Solar-Driven Hydrogen Production.

The development of an artificial model of photoinduced hydrogen production system requires efficient, long-term stability and cost-competitive photocatalysts to store solar energy in chemical bonds. However, the existing photocatalysts still suffer from the high cost, high recombination rate of photoexcited electron-hole pairs, and poor photostability. Herein, we demonstrate the synthesis of a p-type CuO/n-type CeO2 heterojunction in situ grown on graphene via a hypha assistance process. Amazingly, optical and photoelectrochemical measurements show the superiority of this hierarchically biomorphic structure. The observed H2 evolution rate of the CeO2-CuO quantum dots/graphene has reached 2481 µmol·h-1·g-1 and remains unchanged in four hydrogen production cycles. Considering the convenience of microbial culture, this heterostructure system has great potential as a photocatalyst for solar-fuel conversion.

Variation of fitness and reproductive strategy in male Bufo raddei under environmental heavy metal pollution.

Environmental pollution is known to adversely affect amphibian reproduction and survival, however, the knowledge of environmental heavy metal pollution on fitness of male amphibian is largely unknown. The present study aimed to explore the variation in fitness of male Bufo raddei, a widespread anuran in northwest China, subjected to long-term heavy metal stress in Baiyin (BY) city. BY is heavily polluted by heavy metals mainly copper, zinc, lead and cadmium; meanwhile, Liujiaxia (LJX), a relatively unpolluted area, was chosen as control. Differences in advertisement call, larynx size, breeding glands size, as well as forearm force during courtship and amplexus in male B. raddei between the two populations were analyzed. The results revealed a competitive advantage in advertisement call in BY population, together with larger breeding glands size and forearm force, which demonstrated a relatively higher fitness. Using skeletochronological analysis, we found that more than 40% of males from BY began to breed at 2 years old, which was only 6.93% for males from LJX. Correspondingly, the average age for all males participate in breeding was younger from BY than from LJX. Not surprisingly, males from BY showed a relatively lower body condition. All these results illustrated males from BY invested more in reproduction to increase fitness at the cost of health and survival. This reproductive trade-off might ultimately influence stability of B. raddei population because of the environmental heavy metal pollution.

Long-term heavy metal pollution varied female reproduction investment in free-living anura, Bufo raddei.

Environment contamination is known to affect the growth, reproduction, and even mortality of anuran species, and hence modulate their life history traits. Although knowledge of the ability of amphibians to cope with harsh environments has gained ongoing research, the reproductive strategy of free-living amphibians subjected to long-term heavy metal pollution is largely unknown. This study aimed to explore the variation in the life history traits, including age structure, maturation age, reproductive investment, and reproduction trade-off, in female Bufo raddei, a widespread anuran in Baiyin (BY) in northwest of China, subjected to sublethal heavy metal pollution. B. raddei collected from Liujiaxia (LJX), a relatively unpolluted area, were used as control. Skeletochronological analysis revealed variation in the average breeding age of females: more than 70% of females from BY began to breed 1 year before the toads collected from LJX. Females from BY tended to prioritize reproduction over survival and invested more in their first reproductive event. Further, females in BY with a high fluctuating asymmetry index showed a relatively lower reproductive investment. For trade-off in offspring number and size, BY population optimize larger clutch sizes with smaller egg size compared with population in LJX. Changes in female reproductive investment caused by heavy metal pollution might ultimately alter the structural stability of amphibian population.

Sperm Morphology and Motility of Bufo raddei Under Long-Term Environmental Heavy Metal Stress.

The present study aimed to investigate the effects of environmental heavy metals on sperm morphology and motility of Bufo raddei. We collected B. raddei from Baiyin (BY) and Liujiaxia (LJX); BY is an area heavily polluted by heavy metals, while LJX is a relatively unpolluted area. Significant accumulations of copper, zinc, lead and cadmium were observed in B. raddei from BY, together with relatively smaller sperm size and higher sperm abnormality rate. Unexpectedly, sperm velocity, percentages of sperm motility and viability of B. raddei from BY were significantly higher than those from LJX. Similarly, when sperm was suspended in heavy metal solutions, sperm velocity, percentages of sperm motility and viability significantly increased compared with those suspended in distilled water. These results indicate that environmental heavy metal stress may decrease sperm size, meanwhile enhance sperm motility through increasing the ratio of head length to total sperm length of B. raddei.

Fluctuating asymmetry rather than oxidative stress in Bufo raddei can be an accurate indicator of environmental pollution induced by heavy metals.

Oxidative stress (OS) and fluctuating asymmetry (FA) as risk markers for environmental stress are widely used to predict changes in the health and fitness of many animals exposed to pollutants. However, from the perspective of protecting declining amphibians, it remains to be verified which one would be a reliable indicator for amphibians exposed to long-term heavy metal pollution under natural conditions. In this study, the OS and FA of Bufo raddei exposed to natural heavy metal pollution were analyzed to determine which marker is more accurate for indicating heavy metal-induced stress. Three years of data were collected during the breeding season of B. raddei from Baiyin (BY), which has been mainly contaminated with Cu, Zn, Pb, and Cd compounds for a long period, and from Liujiaxia (LJX), which is a relatively unpolluted area. Unexpectedly, although significant accumulation of the four heavy metals was found in the kidney and liver of B. raddei from BY, the levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde in these two organs were found to be irregular, with low repeatability in both BY and LJX. However, significant differences in the levels of FA were observed in B. raddei populations from these two areas over the past 3 years (P < 0.01). The degrees of FA in B. raddei populations from BY and LJX were assessed as degree 4 and 1, respectively. In short, this study suggested that FA was a more reliable and effective indicator than OS to monitor and predict long-term environmental stress on anuran amphibians.

Clinical efficacy of Yingliu mixture combined with metimazole for treating diffuse goitre with hyperthyroidism and its impact on related cytokines.

CONTEXT: Yingliu mixture was developed in 1990s by Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, for treating diffuse goitre with hyperthyroidism (Graves' disease, GD). Former studies have shown Yingliu mixture combined with methimazole (Y-M) can effectively improve thyroid function and decrease thyrotropin-receptor antibody level. Furthermore, we researched its impact on related cytokines to prove that Y-M improve patients' immunity status. OBJECTIVE: To observe the clinical efficacy of Y-M for treating GD. METHODS: A total of 120 GD patients were randomly divided into two groups, the treatment and the control groups (n = 60). The treatment group's patients were treated with Y-M. The control group's patients were treated with methimazole alone. Yingliu mixture was orally administered, 25 mL three times daily. Methimazole was administered at 5-25 mg/day. After 12 weeks of the treatment, the cytokines, antibodies related to thyroid function, and Chinese medical syndromes were evaluated. RESULTS: After the treatment, the free triiodothyronine and thyroxine levels in both groups decreased. The thyroid-stimulating hormone level increased in the treatment group. The thyrotropin-receptor antibody levels and TNF-α levels decreased in both groups. In the control group, IL-6 and IFN-γ levels were lower than that before the treatment. In the treatment group, CD4+ and CD25+ levels were higher than pretreatment levels, but IL-10 levels were reduced. CLINICAL SYMPTOMS: the total CMS scores for both groups decreased. CONCLUSIONS: The Y-M combination can improve thyroid function, and decrease autoantibodies, cytokines, and clinical symptoms, so its efficacy may surpass that of methimazole alone.

[Preparation and release mechanism of tectorigenin intragastric floating sustained-release tablets].

To investigate the preparation technology and release mechanism of tectorigenin intragastric floating sustained-release tablets. The tablet was produced by wet granulation compression method, with hydroxypropyl methyl cellulose (HPMCK15M), cross-linked polyvinyl pyrrolidone (PVPP), octadecanol and sodium bicarbonate as excipient. The prescriptions were screened and optimized by orthogonal experimental design with in vitro floating capacity and drug release characteristics as the evaluation indexes. The optimization results were as follows: tectorigenin 33.3%, HPMCK15M 16.7%, PVPP 20.0%, octadecanol 13.3%, sodium bicarbonate 5%, and starch gel 10.7%. The prepared tablet can be floated within 10 s in the artificial gastric juice, lasting for 12 h in vitro, with a cumulative release rate of 70% in 10 h. The analysis of Rritger-Peppas equation showed that the sustained-release tablet had two advantages of both drug diffusion and skeleton dissolution. The tablet had good appearance and compressibility, as well as favorable floating capacity and drug release characteristics.