Testing influences of openness, conscientiousness, nationalism, media diversity, social class, and informational echo chambers on support for official responses to COVID-19 in Wuhan in November, 2020.

Introduction: As the COVID-19 pandemic raged, controversies about governmental responses to the epidemic also emerged in China. Previous studies mainly described the phenomenon of individual differences on support for governmental responses to COVID-19 with less attention to the underlying causal mechanisms. Thus, this study tries to verify the factors influencing public support for official behaviors in COVID-19. Method: A questionnaire survey was drew on in Wuhan city during the COVID-19 outbreak. The quota sampling method was adopted according to the gender and age structure of the population in Wuhan as well as the educational structure of the urban population in China. Results: Through structural equation analysis, this study confirms that personal factors (namely conscientiousness and nationalistic ideology), behavioral factors (namely media diversity and echo chamber acts) exert significantly positive impacts on support for governmental responses. The echo chamber acts play important mediating roles in the relationship between each independent variable and support for governmental responses. Discussion: The originality of this study is that it constructs a comprehensive model of influencing factors of support for governmental responses with the personal, behavioral, and environmental factors. While contributing insight to political attitude in China, the research results also have significance for promoting public trust and constructing healthy public opinion in China.

Genetic model of selective COX2 inhibition improve learning and memory ability and brain pathological changes in 5xFAD mouse.

Alzheimer's disease (AD) is the most common neurodegenerative disease that leads to dementia. Its pathogenesis is very complex, and inflammation is one of the main pathophysiological mechanisms of AD. Non-steroidal anti-inflammatory drugs (NSAIDs), which mainly target cyclooxygenase (COX) activity, are used to reduce the risk of AD, but several side effects limit their application. Here we assess the effect of Cyclooxygenase-2 (COX2) catalytic activity on learning ability and AD pathology using 5x Familial Alzheimer's Disease (FAD) mice with COX2 inhibition (5xFAD/COX2 KO), 5xFAD mice with cyclooxygenase inactivation of COX2 (5xFAD/COX2 Y385F), and 5xFAD mice with peroxidase (POX) inactivation of COX2 (5xFAD/COX2) H374Y), respectively. Our results indicate that learning ability of COX2 KO and mutants is improved compared to 5xFAD mice, further investigations show that Aß depositions are reduced, microglia and astrocytes homeostasis are changed in COX2 KO and mutants. Especially, there is more responsive microglia in the brain of 5xFAD/COX2 Y385F mice, and Aß depositions are more effectively cleaned at old age. Taken together, these results identify a role of COX2 Y385F in regulating microglia function and may have important implications for future treatment of AD.

PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which is associated with high malignancy, high rate of recurrence and distant metastasis, and poor prognosis among all types of breast cancer. However, there are currently no effective therapies for BLBC. Furthermore, chemoresistance limits the therapeutic options for BLBC treatment. In this study, we screen out protein activator of the interferon-induced protein kinase (PACT) as an essential gene in BLBC metastasis. We find that high PACT expression level was associated with poor prognosis among BLBC patients. In vivo and in vitro investigations indicated that PACT could regulate BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9 to stimulate the SUMOylation and thus consequently the activation of Rac1. BLBC patients receiving chemotherapy presents poorer prognosis with PACT high expression, and PACT disruption sensitizes experimental mammary tumor metastases to chemotherapy, thus providing insights to consider PACT as a potential therapeutic target to overcome acquired chemoresistance in BLBC.

Shaoyao-Gancao Decoction Promoted Microglia M2 Polarization via the IL-13-Mediated JAK2/STAT6 Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury.

Microglia in the penumbra shifted from M2 to M1 phenotype between 3 and 5 days after cerebral ischemia-reperfusion, which promoted local inflammation and injury. Shaoyao-Gancao Decoction (SGD) has been found to result in a significant upregulation of IL-13 in the penumbra, which has been shown to induce polarization of M2 microglia. There was thus a hypothesis that SGD could exert an anti-inflammatory and neuroprotective effect by activating IL-13 to induce microglia polarization towards M2 phenotype, and the purpose of this study was to explore the influence of SGD on microglia phenotype switching and its possible mechanism. Rats who received middle cerebral artery occlusion surgery (MCAO) were treated with SGD for 3 or 6 days, to investigate the therapeutic effect and the underlying mechanism of SGD for cerebral ischemia-reperfusion injury (CI/RP). The results indicated that SGD improved neurobehavioral scores and reduced apoptosis. Furthermore, SGD significantly decreased M1 microglia and M1-like markers, but increased M2 microglia and M2 markers. Moreover, higher levels of IL-13 and ratios of p-JAK2/JAK2 and p-STAT6/STAT6 were found in the SGD group compared to the MCAO. In conclusion, it was verified that SGD prevented injury by driving microglia phenotypic switching from M1 to M2, probably via IL-13 and its downstream JAK2-STAT6 pathway. Given that no further validation tests were included in this study, it is necessary to conduct more experiments to confirm the reliability of the above results.

Spraying alginate oligosaccharide improves photosynthetic performance and sugar accumulation in citrus by regulating antioxidant system and related gene expression.

Alginate oligosaccharides (AOS) are functional substances in seaweed extracts that regulate crop quality and stress tolerance. In this paper, the effects of AOS spray application on the antioxidant system, photosynthesis and fruit sugar accumulation in citrus was investigated through a two-year field experiment. The results showed that 8-10 spray cycles of 300-500 mg L-1 AOS (once per 15 days) increased soluble sugar and soluble solid contents by 7.74-15.79% and 9.98-15.35%, respectively, from citrus fruit expansion to harvesting. Compared with the control, the antioxidant enzyme activity and the expression of some related genes in citrus leaves started to increase significantly after the 1st AOS spray application, while the net photosynthetic rate of leaves increased obviously only after the 3rd AOS spray cycle, and the soluble sugar content of AOS-treated leaves increased by 8.43-12.96% at harvest. This suggests that AOS may enhance photosynthesis and sugar accumulation in leaves by antioxidant system regulation. Moreover, analysis of fruit sugar metabolism showed that during the 3rd to 8th AOS spray cycles, AOS treatment increased the activity of enzymes related to sucrose synthesis (SPS, SSs), upregulated the expression of sucrose metabolism (CitSPS1, CitSPS2, SUS) and transport (SUC3, SUC4) genes, and promoted the accumulation of sucrose, glucose and fructose in fruits. Notably, the concentration of soluble sugars in citrus fruits was significantly reduced at all treatments with 40% reduction in leaves of the same branch, but the loss of soluble sugars in AOS-treated fruits (18.18%) was higher than that in the control treatment (14.10%). It showed that there was a positive effect of AOS application on leaf assimilation product transport and fruit sugar accumulation. In summary, AOS application may improve fruit sugar accumulation and quality by regulating the leaf antioxidant system, increasing the photosynthetic rate and assimilate product accumulation, and promoting sugar transfer from leaves to fruits. This study shows the potential application of AOS in the production of citrus fruits for sugar enhancement.

Treadmill Exercise Attenuates Cerebral Ischemia-Reperfusion Injury by Promoting Activation of M2 Microglia via Upregulation of Interleukin-4.

Background: Exercise has been proven to be an effective therapy for stroke by reducing the microglia-initiated proinflammatory response. Few studies, however, have focused on the phenotypic changes in microglia cells caused by exercise training. The present study was designed to evaluate the influence of treadmill exercise on microglia polarization and the molecular mechanisms involved. Methods: Male Sprague-Dawley rats were randomly assigned into 3 groups: sham, MCAO and exercise. The middle cerebral artery occlusion (MCAO) and exercise groups received MCAO surgery and the sham group a sham operation. The exercise group also underwent treadmill exercise after the surgery. These groups were studied after 4 and 7 days to evaluate behavioral performance using a modified neurological severity score (mNSS), and infarct conditions using 2,3,5-triphenyl tetrazolium chloride. Quantitative real-time polymerase chain reaction (qRT-PCR) and Luminex was employed to determine the expressions of markers of microglia phenotypes. Western blotting was employed to identify the phosphorylation levels of Janus kinase1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Immunofluorescence was conducted to identify microglia phenotypes. Results: Treadmill exercise was found to improve neurobehavioral outcomes, mainly motor and balance functions, reduce infarct volumes and significantly increase interleukin-4 (IL-4) expression. In addition, treadmill exercise inhibited M1 microglia and promoted M2 microglia activation as evidenced by decreased M1 and increased M2 markers. Furthermore, an obvious increase in p-JAK1 and p-STAT6 was observed in the exercise group. Conclusions: Treadmill exercise ameliorates cerebral ischemia-reperfusion injury by enhancing IL-4 expression to promote M2 microglia polarization, possibly via the JAK1-STAT6 pathway.

Development of a Portable Method for Serum Lithium Measurement Based on Low-Cost Miniaturized Ultrasonic Nebulization Coupled with Atmospheric-Pressure Air-Sustained Discharge.

An accurate, rapid but cheap, and portable method for monitoring of serum lithium (Li) is highly desirable for mental patients who take Li medicine for treatment. Conventional techniques are usually bulky, costly, and cannot provide on-site real-time measurements. Herein, a miniaturized, reliable, cost-effective, and portable optical emission method for rapid and sensitive determination of serum Li was developed based on a combination of miniaturized ultrasonic nebulization (MUN) and a low-power (≈22 W) atmospheric-pressure air-sustained discharge (APAD) excitation source. The proposed method eliminates the use of any compressed gas or pump and can achieve serum Li detection within 40 s with low sample consumption (less than 20 µL serum). Except for dilution with water, no extra treatment is needed for serum Li analysis by MUN-APAD-OES. In addition, it offers a significant advantage of good tolerance to the coexisting high concentration of Na, K, Ca, and Mg, which is in contrast with the obvious matrix effect encountered in conventional inductively coupled plasma optical emission spectrometry (ICP-OES). Different operating parameters affecting the performance of MUN-APAD-OES were evaluated. Under optimized conditions, the detection limit of Li (670.8 nm) was calculated to be 0.6 µg L-1 (6 µg L-1 in serum). Finally, the accuracy of the proposed method was validated by the analysis of two certified reference materials (Seronorm serum L-1 and L-2 RUO), six real human serum samples, and eight real animal serum samples. All of the results indicate that the low-cost and low-power MUN-APAD-OES provides a promising reliable method for on-site serum Li measurement and may also be extended to other elements.

Binge Alcohol Exposure Causes Neurobehavioral Deficits and GSK3ß Activation in the Hippocampus of Adolescent Rats.

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris water maze. However, alcohol did not alter the spontaneous locomotor activity which was determined by the open field test. GSK3ß is a multi-function serine/threonine protein kinase regulating both neuronal survival and neurogenesis and plays an important role in various neurodegenerative disorders. We have previously shown that GSK3ß is a key mediator of alcohol-induced neuron apoptosis in the developing brain. We showed here binge alcohol exposure caused GSK3ß activation by inducing dephosphorylation at Ser9 without affecting the phosphorylation of Tyr216 in the hippocampus. Thus, GSK3ß may be involved in binge alcohol exposure-induced neuronal damage to the adolescent hippocampus.

PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum.

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration.

Autophagy alleviates neurodegeneration caused by mild impairment of oxidative metabolism.

Thiamine deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the brain, which may be mediated by neuronal oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation. TD-induced brain damage is used to model neurodegenerative disorders, and the mechanism for the neuronal death is still unclear. We hypothesized that autophagy might be activated in the TD brain and play a protective role in TD-induced neuronal death. Our results demonstrated that TD induced the accumulation of autophagosomes in thalamic neurons measured by transmission electron microscopy, and the up-regulation of autophagic markers LC3-II, Atg5, and Beclin1 as measured with western blotting. TD also increased the expression of autophagic markers and induced LC3 puncta in SH-SY5Y neuroblastoma cells. TD-induced expression of autophagic markers was reversed once thiamine was re-administered. Both inhibition of autophagy by wortmannin and Beclin1 siRNA potentiated TD-induced death of SH-SY5Y cells. In contrast, activation of autophagy by rapamycin alleviated cell death induced by TD. Intraperitoneal injection of rapamycin stimulated neuronal autophagy and attenuated TD-induced neuronal death and microglia activation in the submedial thalamus nucleus (SmTN). TD inhibited the phosphorylation of p70S6 kinase, suggesting mTOR/p70S6 kinase pathway was involved in the TD-induced autophagy. These results suggest that autophagy is neuroprotective in response to TD-induced neuronal death in the central nervous system. This opens a potential therapeutic avenue for neurodegenerative diseases caused by mild impairment of oxidative metabolism. Autophagy is neuroprotective in response to thiamine deficiency (TD)-induced neuronal death. TD caused neuronal damage and induced the formation of autophagosome, and increased the expression of autophagy-related proteins. Autophagy sequestered damaged and dysfunctional organelles/protein, and transported them to lysosomes for degradation/recycling. This process provided nutrients for injured neurons. Wortmannin and knockdown of Beclin1 inhibited autophagy, and exacerbated TD-induced cell death, while activation of autophagy by rapamycin offered protection against TD neurotoxicity.

Thiamine nutritional status and depressive symptoms are inversely associated among older Chinese adults.

Thiamine has been hypothesized to play an important role in mental health; however, few studies have investigated the association between thiamine nutritional status and depression in the general population. Concentrations of free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men and women aged 50-70 y. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score of ≥16. The median erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and 169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower concentrations of all 3 erythrocyte thiamine biomarkers were monotonically associated with a higher prevalence of depressive symptoms: the multivariable adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI = 1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P-trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP. In conclusion, poorer thiamine nutritional status and higher odds of depressive symptoms were associated among older Chinese adults. This finding should be further investigated in prospective or interventional studies.

Lithium fails to protect dopaminergic neurons in the 6-OHDA model of Parkinson's disease.

Lithium has been used for the treatment of bipolar mood disorder and is shown to have neuroprotective properties. Since lithium inhibits the activity of glycogen synthase kinase 3 (GSK3) which is implicated in various human diseases, particularly neurodegenerative diseases, the therapeutic potential of lithium receives great attention. Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the pathological loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Intranigral injection of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) causes selective and progressive degeneration of dopaminergic neurons in SNpc, and is a commonly used animal model of PD. The current study was designated to determine whether lithium is effective in alleviating 6-OHDA-induced neurodegeneration in the SNpc of rats. We demonstrated that chronic subcutaneous administration of lithium inhibited GSK3 activity in the SNpc, which was evident by an increase in phosphorylation of GSK3ß at serine 9, cyclin D1 expression, and a decrease in tau phosphorylation. 6-OHDA did not affect GSK3 activity in the SNpc. Moreover, lithium was unable to alleviate 6-OHDA-induced degeneration of SNpc dopaminergic neurons. The results suggest that GSK3 is minimally involved in the neurodegeneration in the rat 6-OHDA model of PD.

Neuronal MCP-1 mediates microglia recruitment and neurodegeneration induced by the mild impairment of oxidative metabolism.

Chemokines are implicated in the neuroinflammation of several chronic neurodegenerative disorders. However, the precise role of chemokines in neurodegeneration is unknown. Thiamine deficiency (TD) causes abnormal oxidative metabolism in the brain as well as a well-defined microglia activation and neurodegeneration in the submedial thalamus nucleus (SmTN), which are common features of neurodegenerative diseases. We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. Among the chemokines examined, TD selectively induced neuronal expression of monocyte chemoattractant protein-1 (MCP-1) in the SmTN prior to microglia activation and neurodegeneration. The conditioned medium collected from TD-induced neurons caused microglia activation. With a neuron/microglia co-culture system, we showed that MCP-1-induced neurotoxicity required the presence of microglia, and exogenous MCP-1 was able to activate microglia and stimulated microglia to produce cytokines. A MCP-1 neutralizing antibody inhibited MCP-1-induced microglia activation and neuronal death in culture and in the thalamus. MCP-1 knockout mice were resistant to TD-induced neuronal death in SmTN. TD selectively induced the accumulation of reactive oxygen species in neurons, and antioxidants blocked TD-induced MCP-1 expression. Together, our results indicated an induction of neuronal MCP-1 during mild impairment of oxidative metabolism caused by microglia recruitment/activation, which exacerbated neurodegeneration.

Senescence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism.

Neuronal loss and impairment of oxidative metabolism are frequently observed in aging associated neurodegenerative diseases. Thiamine deficiency (TD) induces the region selective neuronal loss in the brain, which has been used to model neurodegeneration, accompanied by mild impairment of oxidative metabolism. C57BL/6 mice were commonly used animals for TD experiments; however, the individual variations among C57BL/6 mice in response to TD limited the consistence of brain pathology. The senescence accelerated prone 8 (SAMP8) mouse strain exhibits age-related morphological changes in the brain and deficits in learning and memory. In this study, we compared the effects of TD on SAMP8 mice, senescence accelerated resistant 1 (SAMR1) mice and C57BL/6 mice. TD-induced body weight loss in SAMP8 mice was much greater than in SAMR1 and C57BL/6 mice. In addition, earlier and more severe loss of neurons in the submedial thalamic nucleus (SmTN) of the thalamus was detected in the SAMP8 mice. After 8 days of TD (TD8), the loss of NeuN-positive neurons in the SmTN of SAMP8, SAMR1 and C57BL/6 mice was 65%, 50%, and 36%, respectively. TD also caused accumulation of amyloid precursor protein (APP) in the thalamus. After TD10, APP immunoreactivity in the thalamus of SAMP8 was much more intense than that of SAMR1 and C57BL/6 mice. These results suggest that SAMP8 mice are sensitive to TD and therefore offer a useful model for studying aging related neurodegeneration caused by the impairment of oxidative metabolism.