A meta-analysis-based adverse outcome pathway for the male reproductive toxicity induced by microplastics and nanoplastics in mammals.

The male reproductive toxicity of microplastics (MPs) and nanoplastics (NPs) has attracted great attention, but the latent mechanisms remain fragmented. This review performed the adverse outcome pathway (AOP) analysis and meta-analysis in 39 relevant studies, with the AOP analysis to reveal the cause-and-effect relationships of MPs/NPs-induced male reproductive toxicity and the meta-analysis to quantify the toxic effects. In the AOP framework, increased reactive oxygen species (ROS) is the molecular initiating event (MIE), which triggered several key events (KEs) at different levels. At the cellular level, the KEs included oxidative stress, mitochondrial dysfunction, sperm DNA damage, endoplasmic reticulum stress, apoptosis and autophagy of testicular cells, repressed expression of steroidogenic enzymes and steroidogenic acute regulatory protein, disrupted hypothalamic-pituitary-testicular (HPT) axis, and gut microbiota alteration. These KEs further induced the reduction of testosterone, impaired blood-testis barrier (BTB), testicular inflammation, and impaired spermatogenesis at tissue/organ levels. Ultimately, decreased sperm quality or quantity was noted and proved by meta-analysis, which demonstrated that MPs/NPs led to a decrease of 5.99 million/mL in sperm concentration, 14.62% in sperm motility, and 23.56% in sperm viability, while causing an increase of 10.65% in sperm abnormality rate. Overall, this is the first AOP for MPs/NPs-mediated male reproductive toxicity in mammals. The innovative integration of meta-analysis into the AOP analysis increases the rigorism of the results.

Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells.

There is a paucity of studies on the multigenerational reproductive toxicity of fine particle matter (PM2.5) exposure during pregnancy on male offspring and the underlying mechanisms. This study explored the effects of PM2.5 exposure during pregnancy on the spermatogenesis of three consecutive generations of male mouse offspring. We randomized pregnant C57BL/6 mice into the control group, the Quartz Fiber Membrane control group, and two experimental groups exposed to different concentrations of PM2.5 (4.8 and 43.2 mg/kg B.Wt.). Pregnant mice from experimental groups received intratracheal instillation of PM2.5 of different doses on a three-day basis until birth. F1 mature male offspring from PM2.5-exposed pregnant mice were mated with normal female C57BL/6 mice. Likewise, their F2 mature male followed the same to produce the F3 generation. The results showed that PM2.5 exposure during pregnancy led to decreased body and tail length, body weight, and survival rates, decreased sperm concentration and sperm motility, and increased sperm abnormality rates significantly in F1 male offspring. We barely observed significant impacts of PM2.5 on the birth number, survival rates, and index of testes in the F2 and F3 offspring. Further exploration showed that PM2.5 exposure during pregnancy caused the morphological abnormality of Sertoli cells, downregulated androgen receptor (AR) and connexin43, upregulated anti-Müllerian hormone (AMH), cytokeratin-18 (CK-18), caspase-3, and cleaved caspase-3, decreased thyroid-stimulating hormone (TSH) and testosterone (T), and increased triiodothyronine (T3) in F1 male mouse offspring. Overall, we hypothesize that PM2.5 exposure during pregnancy mainly negatively impacts spermatogenesis in the F1 offspring. The possible mechanism could be that PM2.5 exposure during pregnancy disrupts endocrine hormone release in the F1 generation, thereby influencing the maturation and proliferation of their Sertoli cells and hindering spermatogenesis. This study for the first time investigates the role of Sertoli cells in the reproductive toxicity of PM2.5 on offspring.

Change of gut microbiome structure in preterm infants with hypoxic ischemic encephalopathy induced by apnea.

BACKGROUND: Since a high incidence of mortality and morbidity is induced by preterm birth, it is important to understand how hypoxic ischemic encephalopathy (HIE) in preterm infants alters gut microbiota development. METHODS: We analyzed 89 stools from 30 term newborns (NNG), 30 preterm infants without apnea (PG) and 29 preterm infants with definite diagnosis of apnea (PAG) by 16S rRNA gene sequencing in this study. RESULTS: The data showed that species richness and diversity in PG and PAG were significantly lower compared with NNG. This study investigated the difference in bacteria and relative abundance between NNG, PG and PAG. The abundance of Klebsiella and Streptococcus strains were markedly increased, while Clostridium was significantly decreased in PAG compared with PG. The most notable exceptions included Klebsiella pneumoniae and Escherichia coli, which were markedly increased in PG and PAG, and these provide the main bacterial source of dopamine and serotonin production. This study also revealed that Lactobacillus and Bifidobacterium were markedly increased in PG and PAG, and these are the main source of GABA production for bacteria. CONCLUSION: The present study confirmed that apnea had a uniform effect on species richness and diversity. However, it cannot be established whether the abundance and difference of these bacterial genera and species directly affect the occurrence and development of preterm infants with HIE by secreting intestinal neurotransmitters.

Comparative efficacy of different eating patterns in the management of type 2 diabetes and prediabetes: An arm-based Bayesian network meta-analysis.

AIMS/INTRODUCTION: Diet therapy is a vital approach to manage type 2 diabetes and prediabetes. However, the comparative efficacy of different eating patterns is not clear enough. We aimed to compare the efficacy of various eating patterns for glycemic control, anthropometrics, and serum lipid profiles in the management of type 2 diabetes and prediabetes. MATERIALS AND METHODS: We conducted a network meta-analysis using arm-based Bayesian methods and random effect models, and drew the conclusions using the partially contextualized framework. We searched twelve databases and yielded 9,534 related references, where 107 studies were eligible, comprising 8,909 participants. RESULTS: Eleven diets were evaluated for 14 outcomes. Caloric restriction was ranked as the best pattern for weight loss (SUCRA 86.8%) and waist circumference (82.2%), low-carbohydrate diets for body mass index (81.6%), and high-density lipoprotein (84.0%), and low-glycemic-index diets for total cholesterol (87.5%) and low-density lipoprotein (86.6%). Other interventions showed some superiorities, but were imprecise due to insufficient participants and needed further investigation. The attrition rates of interventions were similar. Meta-regression suggested that macronutrients, energy intake, and weight may modify outcomes differently. The evidence was of moderate-to-low quality, and 38.2% of the evidence items met the minimal clinically important differences. CONCLUSIONS: The selection and development of dietary strategies for diabetic/prediabetic patients should depend on their holistic conditions, i.e., serum lipid profiles, glucometabolic patterns, weight, and blood pressure. It is recommended to identify the most critical and urgent metabolic indicator to control for one specific patient, and then choose the most appropriate eating pattern accordingly.

Administration approaches of nursing assistants in hospitals: a scoping review.

OBJECTIVES: The administration of nursing assistants (NAs) is closely associated with patient outcomes, but studies evaluating intrahospital administration of NAs are limited. This study aimed to identify existing literature on intrahospital NAs' administration approaches. DESIGN: Scoping review. DATA SOURCES: PubMed, Embase, CINAHL, Scopus, ProQuest, CNKI, APA PsycInfo, Wanfang Med, SinoMed, Ovid Emcare, NICE, AHRQ, CADTH, JBI EBP and Cochrane DSR were searched for articles published between January 2011 and March 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Qualitative, quantitative or mixed-method studies and evidence syntheses that evaluate administration approaches, models and appraisal tools of intrahospital NAs were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers conducted search, data selection and data extraction according to Joanna Briggs Institute guidance and methodology for scoping review. The quality of included studies was assessed using Mixed Methods Appraisal Tool or AMSTAR V.2. Data were synthesised using narrative methods and frequency effect size analysis. RESULTS: Thirty-six studies were eligible, with acceptable quality. We identified 1 administration model, 9 administration methods, 15 educational programmes and 7 appraisal tools from the included studies. The frequency effect size analysis yielded 15 topics of the main focus at four levels, suggesting that included articles were mainly (33%) focused on the competency of NAs, and the lectures were the most (80%) used strategy in quality improvement projects. Evidence from the studies was of low-to-moderate quality, indicating huge gaps between evidence-based research and management practice. CONCLUSIONS: Practical intrahospital administration approaches were revealed, and fifteen primarily focused topics were identified. We should explore this area more thoroughly using structured frameworks and standardised methodology. This scoping review will help managers find more effective ways to improve the quality of care. Researchers may focus more on evidence-based practice in NA administration using the 15 topics as a breakthrough.

Anxiety, depression and post-traumatic stress disorder and related factors among Chinese population during the COVID-19 pandemic: A cross-sectional study.

The sudden outbreak of coronavirus disease 2019 (COVID-19) has deep and wide negative mental impacts on the public, and studies on the impact of COVID-19 on social and mental well-being are necessary. This study aimed to evaluate mental distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), and its related risk factors in Chinese adults in the early stages of the COVID-19 pandemic. This study used a large-scale cross-sectional design. A total of 2067 adult participants completed the online survey via REDcap from 1st to 15th of March 2020 during the COVID-19 outbreak in China. Anxiety, depression, PTSD, and related risk factors, including self-efficacy, coping style, and social support, were measured using valid and reliable instruments. The data were analyzed using multiple linear regression. We found that 201 (9.7%) participants reported moderate-to-severe anxiety, 669 (33.8%) reported depression, and 368 (17.8%) reported symptoms of PTSD. Self-efficacy, coping style, and social support significantly affected anxiety, depression, and PTSD symptoms. Participants' sociodemographic characteristics, COVID-19 pandemic-related factors, low self-efficacy, low social support, and negative coping were predictors of mental distress during the COVID-19 pandemic. Our study will help healthcare professionals carry out early predictions and identification of high-risk groups and provide appropriate interventions to target groups during public health emergencies that plague the world.

Neuroprotective effect of ketamine against TNF-α-induced necroptosis in hippocampal neurons.

Tumour necrosis factor-α (TNF-α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF-α-induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT-22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF-α-induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF-α-induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre-treatment inhibiting reactive oxygen species production and mixed lineage kinase domain-like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF-α-induced necroptosis-associated diseases.

Effect of Information-Motivation-Behavioral Model Based on Protection Motivation Theory on the Psychological Resilience and Quality of Life of Patients with Type 2 DM.

Diabetes mellitus (DM) is one of the remarkable disease challenges in the twenty-first century and poses threat to patients' physical health. Given the difficulty of treatment and the high possibility of relapse, patients often have mental illness. A total of 117 patients with type 2 DM were randomly divided into two groups for a 2-month intervention. The intervention group underwent an Information-Motivation-Behavioral skills (IMB) intervention program based on protection motivation theory, and traditional intervention was applied to the control group. No significant difference is found between the intervention and control groups before the intervention (P > 0.05). However, after the intervention, the blood glucose level and depression score of the intervention group are lower than those of the control group (P < 0.05), and the psychological resilience and quality of life are significantly higher than those of the control group (P < 0.05). The blood glucose level and depression score of the intervention group decrease after the intervention (P < 0.05), and the psychological resilience and quality of life are significantly increase (P < 0.05). No significant difference is found in the blood glucose level, depression, psychological resilience, and quality of life of the control group before and after the intervention (P > 0.05). The combination of IMB intervention and protection motivation theory is important to improving the psychological resilience of patients with type 2 DM, raising their quality of life and reducing their blood glucose level.

Kidney-targeted baicalin-lysozyme conjugate ameliorates renal fibrosis in rats with diabetic nephropathy induced by streptozotocin.

BACKGROUND: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, and is the most important cause of death for diabetic patients. Baicalin (BAI) has anti-oxidative, anti-inflammatory and anti-apoptotic activities, which play a role in attenuating insulin resistance and protecting the kidney. Moreover, cell-specific targeting of renal tubular cells is an approach to enhance drug accumulation in the kidney. METHODS: Forty-five Sprague-Dawley rats were divided into four groups. A diabetes model was created using streptozotocin (STZ) intraperitoneally injection. The four groups included: Control group (n = 10), DN (n = 15), BAI treatment (BAI; n = 10) and BAI-LZM treatment (BAI-LZM; n = 10) groups. In the current study, the renoprotection and anti-fibrotic effects of BAI-lysozyme (LZM) conjugate were further investigated in rats with DN induced by STZ compared with BAI treatment alone. RESULTS: The results suggest that BAI-LZM better ameliorates renal impairment, metabolic disorder and renal fibrosis than BAI alone in rats with DN, and the potential regulatory mechanism likely involves inhibiting inflammation via the nuclear factor-κB signaling pathway, inhibiting extracellular matrix accumulation via the transforming growth factor-ß/Smad3 pathway and regulating cell proliferation via the insulin-like growth factor (IGF)-1/IGF-1 receptor/p38 Mitogen-activated protein kinase (MAPK) pathway. BAI and the kidney-targeted BAI-LZM can utilize the body's cytoprotective pathways to reactivate autophagy (as indicated by the autophagy markers mechanistic target of rapamycin and sirtuin 1 to ameliorate DN outcomes. CONCLUSIONS: Our data support the traditional use of S. baicalensis as an important anti-DN traditional chinese medicine (TCM), and BAI, above all BAI-LZM, is a promising source for the identification of molecules with anti-DN effects.

Plasmodium yoelii 17XL infection modified maturation and function of dendritic cells by skewing Tregs and amplificating Th17.

BACKGROUND: Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL). METHODS: DCs detection/analysis dynamically was performed by Tregs depletion or Th17 neutralization in P.y17XL infected BALB/c mice via flow cytometry. Then the levels of cytokines production were detected using enzyme-linked mmunosorbent assay (ELISA). RESULTS: Our results indicated that Tregs depletion or Th17 neutralization in BALB/c mice infected with P.y17XL significantly up-regulated the percentages of mDC and pDC, increased the expressions of major histocompatibility complex (MHC) class II, CD80, CD86 on DCs and the levels of IL-10/IL-12 secreted by DCs, indicating that abnormal amplification of Tregs or Th17 may damage the maturation and function of DCs during the early stage of malaria infection. Interestingly, we also found that the abnormal amplification of Th17, as well as Tregs, could inhibit the maturation of DCs. CONCLUSIONS: Tregs skewing or Th17 amplification during the early stage of malaria infection may inhibit the maturation and function of DCs by modifying the subsets of DCs, expressions of surface molecules on DCs and secretion mode of cytokines.

IL-8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells.

Interleukin-8 (IL-8) serves an important function in chronic inflammation and cancer development; however, the underlying molecular mechanism(s) of IL-8 in uterine cervical cancer remains unclear. The present study investigated whether IL-8 and its receptors [IL-8 receptor (IL-8R)A and IL-8RB] contributed to the proliferative and migratory abilities of HeLa cervical cancer cells, and also investigated the potential underlying molecular mechanisms. Results demonstrated that IL-8 and its receptors were detected in HeLa cells, and levels of IL-8RA were significantly increased compared with those of IL-8RB. Furthermore, the level of IL-8 in cervical cancer tissues was significantly increased compared with that in normal uterine cervical tissues, and migratory and proliferative efficiencies of HeLa cells treated with exogenous IL-8 were increased, compared with untreated HeLa cells. In addition, exogenous IL-8 was able to downregulate endocytic adaptor protein (NUMB), and upregulate IL-8RA, IL-8RB and extracellular signal-regulated protein kinases (ERKs) expression levels in HeLa cells. Results suggest that IL-8 and its receptors were associated with the tumorigenesis of uterine cervical cancer, and exogenous IL-8 promotes the carcinogenic potential of HeLa cells by increasing the expression levels of IL-8RA, IL-8RB and ERK, and decreasing the expression level of NUMB.

TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and Mitochondrial Apoptotic Pathways After Experimental Stroke.

Neurogenin-2 (Ngn2) is a basic helix-loop-helix (bHLH) transcription factor that contributes to the identification and specification of neuronal fate during neurogenesis. In our previous study, we found that Ngn2 plays an important role in alleviating neuronal apoptosis, which may be viewed as an attractive candidate target for the treatment of cerebral ischemia. However, novel strategies require an understanding of the function and mechanism of Ngn2 in mature hippocampal neurons after global cerebral ischemic injury. Here, we found that the expression of Ngn2 decreased in the hippocampus after global cerebral ischemic injury in mice and in primary hippocampal neurons after oxygen glucose deprivation (OGD) injury. Then, transactivator of transcription (TAT)-Ngn2, which was constructed by fusing a TAT domain to Ngn2, was effectively transported and incorporated into hippocampal neurons after intraperitoneal (i.p.) injection and enhanced cognitive functional recovery in the acute stage after reperfusion. Furthermore, TAT-Ngn2 alleviated hippocampal neuronal damage and apoptosis, and inhibited the cytochrome C (CytC) leak from the mitochondria to the cytoplasm through regulating the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylation tropomyosin-related kinase B (pTrkB), Bcl-2, Bax and cleaved caspase-3 after reperfusion injury in vivo and in vitro. These findings suggest that the downregulation of Ngn2 expression may have an important role in triggering brain injury after ischemic stroke and that the neuroprotection of TAT-Ngn2 against stroke might involve the modulation of BDNF-TrkB signaling that regulates caspase-dependent and mitochondrial apoptotic pathways, which may be an attractive therapeutic strategy for cerebral ischemic injury.

Local and global synchronization transitions induced by time delays in small-world neuronal networks with chemical synapses.

Effects of time delay on the local and global synchronization in small-world neuronal networks with chemical synapses are investigated in this paper. Numerical results show that, for both excitatory and inhibitory coupling types, the information transmission delay can always induce synchronization transitions of spiking neurons in small-world networks. In particular, regions of in-phase and out-of-phase synchronization of connected neurons emerge intermittently as the synaptic delay increases. For excitatory coupling, all transitions to spiking synchronization occur approximately at integer multiples of the firing period of individual neurons; while for inhibitory coupling, these transitions appear at the odd multiples of the half of the firing period of neurons. More importantly, the local synchronization transition is more profound than the global synchronization transition, depending on the type of coupling synapse. For excitatory synapses, the local in-phase synchronization observed for some values of the delay also occur at a global scale; while for inhibitory ones, this synchronization, observed at the local scale, disappears at a global scale. Furthermore, the small-world structure can also affect the phase synchronization of neuronal networks. It is demonstrated that increasing the rewiring probability can always improve the global synchronization of neuronal activity, but has little effect on the local synchronization of neighboring neurons.

Effects of time delay and random rewiring on the stochastic resonance in excitable small-world neuronal networks.

The effects of time delay and rewiring probability on stochastic resonance and spatiotemporal order in small-world neuronal networks are studied in this paper. Numerical results show that, irrespective of the pacemaker introduced to one single neuron or all neurons of the network, the phenomenon of stochastic resonance occurs. The time delay in the coupling process can either enhance or destroy stochastic resonance on small-world neuronal networks. In particular, appropriately tuned delays can induce multiple stochastic resonances, which appear intermittently at integer multiples of the oscillation period of the pacemaker. More importantly, it is found that the small-world topology can significantly affect the stochastic resonance on excitable neuronal networks. For small time delays, increasing the rewiring probability can largely enhance the efficiency of pacemaker-driven stochastic resonance. We argue that the time delay and the rewiring probability both play a key role in determining the ability of the small-world neuronal network to improve the noise-induced outreach of the localized subthreshold pacemaker.

Effects of time delay on the stochastic resonance in small-world neuronal networks.

The effects of time delay on stochastic resonance in small-world neuronal networks are investigated. Without delay, an intermediate intensity of additive noise is able to optimize the temporal response of the neural system to the subthreshold periodic signal imposed on all neurons constituting the network. The time delay in the coupling process can either enhance or destroy stochastic resonance of neuronal activity in the small-world network. In particular, appropriately tuned delays can induce multiple stochastic resonances, which appear intermittently at integer multiples of the oscillation period of weak external forcing. It is found that the delay-induced multiple stochastic resonances are most efficient when the forcing frequency is close to the global-resonance frequency of each individual neuron. Furthermore, the impact of time delay on stochastic resonance is largely independent of the small-world topology, except for resonance peaks. Considering that information transmission delays are inevitable in intra- and inter-neuronal communication, the presented results could have important implications for the weak signal detection and information propagation in neural systems.