Lactoferrin alleviates chronic low­grade inflammation response in obese mice by regulating intestinal flora.

Chronic low­grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin (LF) has a biological function in regulating intestinal flora. The present study aimed to investigate the therapeutic and anti­-inflammatory effects of LF in obese mice based on intestinal flora. A total of 30 C57BL/6 mice were divided into three groups consisting of 10 mice each. Subsequently, one group was fed a normal diet (Group K), another group was fed a high­fat diet (Group M) and the remaining group switched from regular drinking to drinking 2% LF water (Group Z2) after 2 weeks of high­fat diet; all mice were fed for 12 weeks. After the experiment, the mouse blood lipid and lipopolysaccharide levels, levels of inflammatory factors and intestinal tight junction proteins were assessed. Mouse stool samples were analyzed using 16S ribosomal RNA sequencing. The results showed that LF reduced serum total cholesterol, triglycerides and low­density lipoprotein levels, elevated high­density lipoprotein levels, suppressed metabolic endotoxemia and attenuated chronic low­grade inflammatory responses in obese mice. In addition, LF upregulated zonula occludens­1 and occludin protein expression levels in the intestine, thereby improving intestinal barrier integrity. LF altered the intestinal microbial structure of obese mice, reduced the ratio of Firmicutes and an elevated ratio of Bacteroidota, modifying the bacterial population to the increased relative abundance of Alistipes, Acidobacteriota, Psychrobacter and Bryobacter.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Identification of key pathways and mRNAs in interstitial cystitis/bladder pain syndrome treatment with quercetin through bioinformatics analysis of mRNA-sequence data.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. METHODS: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. RESULTS: QCT treatment significantly decreased the level of MPO, IL-1ß, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1ß, IL-6 and TNF-α. CONCLUSION: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.

First detection of Candidatus Rickettsia tarasevichiae in Hyalomma marginatum ticks.

Ticks are important vectors of zoonotic diseases and play a major role in the circulation and transmission of many rickettsial species. The aim of this study was to investigate the carriage of Candidatus Rickettsia tarasevichiae (CRT) in a total of 1168 ticks collected in Inner Mongolia to elucidate the potential public health risk of this pathogen, provide a basis for infectious disease prevention, control and prediction and contribute diagnostic ideas for clinical diseases that present with fever in populations exposed to ticks. A total of four tick species, Haemaphysalis concinna (n = 21), Dermacentor nuttalli (n = 122), Hyalomma marginatum (n = 148), and Ixodes persulcatus (n = 877), were collected at nine sampling sites in Inner Mongolia, China, and identified by morphological and molecular biological methods. Reverse transcription PCR targeting the 16S ribosomal RNA (rrs), gltA, groEL, ompB and Sca4 genes was used to detect CRT DNA. Sequencing was used for pathogen species confirmation. The molecular epidemiological analysis showed that three species of ticks were infected with CRT, and the overall positive rate was as high as 42%. The positive rate of I. persulcatus collected in Hinggan League city was up to 96%, and that of I. persulcatus collected in Hulun Buir city was 50%. The pool positive rates of D. nuttalli and H. marginatum collected in Bayan Nur city and H. concinna collected in Hulun Buir city were 0%, 28% and 40%, respectively. This study revealed the high prevalence of CRT infection in ticks from Inner Mongolia and the first confirmation of CRT detected in H. marginatum in China. The wide host range and high infection rate in Inner Mongolia may dramatically increase the exposure of CRT to humans and other vertebrates. The role of H. marginatum in the transmission of rickettsiosis and its potential risk to public health should be further considered.

Microbial diversity of ticks and a novel typhus group Rickettsia species (Rickettsiales bacterium Ac37b) in Inner Mongolia, China.

Ticks can carry multiple pathogens, and Inner Mongolia's animal husbandry provides excellent environmental conditions for ticks. This study characterized the microbiome of ticks from different geographical locations in Inner Mongolia; 905 Dermacentor nuttalli and 36 Ixodes persulcatus were collected from sheep in three main pasture areas and from bushes within the forested area. Mixed DNA samples were prepared from three specimens from each region and tick species. Microbial diversity was analyzed by 16S rRNA sequencing, and α and ß diversity were determined. The predominant bacterial genera were Rickettsia (54.60%), including Rickettsiales bacterium Ac37b (19.33%) and other Rickettsia (35.27%), Arsenophonus (11.21%), Candidatus Lariskella (10.84%), and Acinetobacter (7.17%). Rickettsia bellii was identified in I. persulcatus, while Rickettsiales bacterium Ac37b was found in D. nuttalli from Ordos and Chifeng. Potential Rickettsia and Anaplasma coinfections were observed in the Ordos region. Tick microbial diversity analysis in Inner Mongolia suggests that sheep at the sampling sites were exposed to multiple pathogens.

Title: Diversité microbienne des tiques et nouvelle espèce de Rickettsia du groupe du typhus (bactérie Rickettsiales Ac37b) en Mongolie intérieure, Chine. Abstract: Les tiques peuvent être porteuses de plusieurs agents pathogènes et l'élevage en Mongolie intérieure offre d'excellentes conditions environnementales pour les tiques. Cette étude a caractérisé le microbiome des tiques de différentes zones géographiques de Mongolie intérieure; 905 Dermacentor nuttalli et 36 Ixodes persulcatus ont été collectés sur des moutons dans trois principales zones de pâturage et dans des buissons de la zone forestière. Des échantillons d'ADN mixtes ont été préparés à partir de trois spécimens de chaque région et espèce de tique. La diversité microbienne a été analysée par séquençage de l'ARNr 16S et la diversité α et ß a été déterminée. Les genres bactériens prédominants étaient les Rickettsia (54,60 %), dont la bactérie Rickettsiales Ac37b (19,33 %) et d'autres Rickettsia (35,27 %), Arsenophonus (11,21 %), Candidatus Lariskella (10,84 %) et Acinetobacter (7,17 %). Rickettsia bellii a été identifiée chez I. persulcatus, tandis que la bactérie Rickettsiales Ac37b a été trouvée chez D. nuttalli d'Ordos et Chifeng. Des co-infections potentielles à Rickettsia et Anaplasma ont été observées dans la région d'Ordos. L'analyse de la diversité microbienne des tiques en Mongolie intérieure montre que les moutons présents sur les sites d'échantillonnage sont exposés à plusieurs agents pathogènes.

Chronic Unpredictable Mild Stress in Rats based on the Mongolian medicine.

Depression is a prevalent affective disorder and constitutes a leading cause of global disability. The limitations of current pharmacological interventions contribute to the substantial health burden attributed to this condition. There is a pressing need for a deeper understanding of the underlying mechanisms of depression, making pre-clinical models with translational potential highly valuable. Mongolian medicine, a subset of traditional medicine, posits that disease occurrence is closely tied to the equilibrium of wind, bile, and Phlegm. In this study, we introduce a protocol for the chronic unpredictable mild stress (CUMS) method in rats. Within this framework, rats are subjected to a series of fluctuating, mild stressors to induce a depression-like phenotype, mimicking the pathogenesis of human depression. Behavioral assays employed in this protocol include the sucrose preference test (SPT), indicative of anhedonia-a core symptom of depression; the open field test (OFT), which measures anxiety levels; and the Morris water maze test (MWM), which evaluates spatial memory and learning abilities. The CUMS method demonstrates the capability to induce anhedonia and to cause long-term behavioral deficits. Furthermore, this protocol is more aligned with Mongolian medical theory than other animal models designed to elicit depression-like behavior. The development of this animal model and subsequent research provide a robust foundation for future innovative studies in the realm of Mongolian medicine.

Indication and adverse event profiles of denosumab and zoledronic acid: based on U.S. FDA adverse event reporting system (FAERS).

Objective: To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference. Methods: We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer. Results: 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%). Conclusion: Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It's also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label.

Association of Caffeine Consumption and Brain Amyloid Positivity in Cognitively Normal Older Adults.

BACKGROUND: Several epidemiological studies have reported the protective role of caffeine on health outcomes; however, it remained debatable on caffeine consumption and brain amyloid positivity. OBJECTIVE: We aimed to determine the relationship between caffeine consumption and brain amyloid pathology in cognitively normal older adults. METHODS: The dataset used for analysis in this cross-sectional study was selected from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study. Multivariable logistic regression analyses were performed to explore the association between caffeine consumption and amyloid positivity using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In total, 4,394 participants were included in the final analysis. No significant association between caffeine consumption and amyloid positivity was observed in the whole participants (OR, 0.95; 95% CI, 0.78-1.14; p = 0.558). Subgroup analysis showed that caffeine intake was significantly associated with decreased amyloid positivity in males (OR, 0.72; 95% CI, 0.54-0.97; p = 0.032) but not in females (OR, 1.14; 95% CI, 0.90-1.46; p = 0.280), and the association between caffeine and amyloid positivity was not affected by age or APOE genotypes. In addition, different levels of caffeine were not associated with amyloid positivity. CONCLUSION: The findings suggest that caffeine consumption was not significantly associated with amyloid positivity in the whole sample. However, caffeine consumption may be inversely associated with amyloid positivity among males but not females. More studies are needed to explore the mechanisms underlying caffeine consumption and brain amyloid positivity.

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression.

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic effects of Zadi-5 against depression have been indicated in previously reported clinical studies, the identity and impact of the active pharmaceutical compounds present in the drug have not been fully elucidated. This study used network pharmacology to predict the drug composition and identify the therapeutically active compounds in Zadi-5 pills. Here, we established a rat model of chronic unpredicted mild stress (CUMS) and conducted an open field test (OFT), Morris water maze (MWM) analysis, and sucrose consumption test (SCT) to investigate the potential therapeutic efficacy of Zadi-5 in depression. This study aimed to demonstrate Zadi-5's therapeutic effects for depression and predict the critical pathway of the action of Zadi-5 against the disorder. The vertical and horizontal scores (OFT), SCT, and zone crossing numbers of the fluoxetine (positive control) and Zadi-5 groups were significantly higher (P < 0.05) than those of the CUMS group rats without treatment. According to the results of network pharmacology analysis, the PI3K-AKT pathway was found to be essential for the antidepressant effect of Zadi-5.

[Challenges of and Responses to Mental Health Problems in the Post-COVID-19 Era].

Since the first outbreak of the coronavirus disease 2019 (COVID-19), prevention and control of the pandemic remains a grim issue because of the continuous emergence of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, and the constant emergence of new domestic outbreaks. During the COVID-19 pandemic, mental and psychological problems have increased significantly among different populations, including patients of COVID-19 and their families, health workers, college students, adolescents, children, and even the general population. At present, the COVID-19 epidemic situation in China is rather complicated. The general population is confronted with a variety of challenges, including the threat of infection or reinfection, lower efficiency in study and work, and reduced incomes, and is hence experiencing many mental health problems related to the epidemic situation. Therefore, the relevant governmental departments and health institutions in China have attached high importance to the mental health issue in the process of implementing pandemic control measures of COVID-19. Close collaboration to implement the required epidemic prevention and control measures, improvements in the mental health services for public health emergencies in China, and commitment to the protection of the mental health and well-being of the people in the post-pandemic era have become the top priorities for now. Based on a review of the mental health problems related to COVID-19 pandemic, we suggested strategies to deal with mental health problems in the post-COVID-19 era.

Neuronal C-Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain.

Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc-gamma-receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen-specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI-related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI-related signaling in the DRG, and conditional knockout (CKO) of the FcγRI-encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C-reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI-related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI-related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.

Linking knowledge with attitude: a cross-sectional study of public knowledge and attitude towards sleep disturbances and dementia.

OBJECTIVES: Sleep disturbances increase the risk of dementia; however, there is insufficient information regarding this. We aimed to investigate public knowledge on the relationship between sleep disturbances and dementia, as well as attitudes towards improving sleep quality and obtaining knowledge on dementia. DESIGN AND SETTING: A cross-sectional web-based questionnaire was administered between May and October 2019. PARTICIPANTS: All participants provided informed consent and were able to respond to the survey. PRIMARY OUTCOMES: Factors associated with the knowledge that sleep disturbances are risk factors for dementia and proportions of individuals with this knowledge; attitudes towards improving sleep quality and obtaining knowledge about dementia. RESULTS: Of the 3329 eligible samples, 72.57% correctly recognised that sleep disturbances increased the risk of dementia. In total, 92.97% of participants were willing to take at least one measure to improve sleep quality, and the percentages of those adopting these measures are as follows: 78.73% would lead a regular life, 67.88% would engage in strengthening exercise, 28.84% would undergo psychotherapy and 19.41% would take medication. The awareness regarding sleep disturbances increasing the risk of dementia was the only factor associated with the willingness to improve sleep quality in all four categories of measures. Almost all participants (95.25%) were willing to take at least one measure to acquire knowledge about dementia, with the following participants displaying higher willingness to obtain knowledge about dementia: female, had contact with dementia and considered sleep disturbances to increase the risk of dementia. CONCLUSIONS: Our findings indicate an association between people's knowledge and attitudes, suggesting the importance of disseminating knowledge about sleep disturbances and dementia to achieve dementia prevention in future.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

[Adaptability of Broussonetia papyrifera to sewage sludge and its characteristics of nutrient and heavy metal uptake and accumulation]. / æž„æ ‘çš„æ±¡æ³¥é€‚åº”æ€§åŠå »åˆ†å’Œé‡é‡‘å±žå¸æ”¶ç´¯ç§¯ç‰¹å¾.

Broussonetia papyrifera, an important fast-growing economic tree species in China, has the advantages of strong adaptability, high-biomass, and high bioconcentration of heavy metals. Sewage sludge contains a great deal of nutrients and heavy metals. Planting B. papyrifera with sewage sludge can achieve the goals of sewage sludge remediation as well as resources production of B. papyrifera. A pot experiment was conducted to investigate growth, uptake and accumulation of nutrient and heavy metal in different organs (root, stem, leaf) of B. papyrifera, with treatments of control (lateritic red soil), 50% sewage sludge (mixed substrates of 50% sewage sludge and 50% lateritic red soil based on weight) and 100% sewage sludge. The comprehensive evaluation of capacity of uptake and accumulation was also carried out by principal component analysis and membership function. The results showed that B. papyrifera could grow normally in both 50% and 100% sewage sludge substrates, with higher plant height and biomass than that in the control, especially in 100% sewage sludge substrate. The quality index in 100% sewage sludge substrate (1.02) was 4.3 times and 2.4 times as that of the control and 50% sewage sludge substrate, respectively. The content of N in different organs and P in stem increased significantly in both 50% and 100% sewage sludge substrates. The content of K in stem and leaf was significantly decreased in 100% sewage sludge substrate, which were significant lower than that of control. The uptake of heavy metals such as Cu, Zn, Pb, Cd, Ni for B. papyrifera were mainly through roots. There was positive correlation between the content of heavy metals in root and sewage sludge ratio. The content of Pb and Cd in leaves were lower than the limit value of Hygienic Standard For Feeds (GB 13078-2017). The capacity for absorption and accumulation of Cd was better than that of other heavy metals. Compared with the control, rootretention rates of Zn, Pb and Cd significantly increased in both 50% and 100% sewage sludge substrates (57.8%-85.8%), while Cu and Ni significantly increased in 100% sewage sludge substrate (67.5% and 74.8%). Nutrient and heavy metal accumulations in total plant in both 50% and 100% sewage sludge substrates were significantly higher than that in the control, with 100% sewage sludge substrate being significantly higher than that in 50% sewage sludge substrate. Compared with 50% sewage sludge substrate, the increment rates of nutrient and heavy metal accumulations in different organs as well as total plants in 100% sewage sludge substrates were greatly increased. The rank of comprehensive evaluation scores of adaptability, element uptake and accumulation was in an order: 100% sewage sludge substrate (0.848) > 50% sewage sludge substrate (0.344) > control (0.080). With good adaptability to sewage sludge, B. papyrifera could grow normally in sewage sludge andeffectively absorb and fix nutrients and heavy metals. It is feasible to plant B. papyrifera into the sewage sludge for remediation of sewage sludge and resource production.

Astrocytic phosphatase and tensin homolog deleted on chromosome 10 regulates neuropathic pain by facilitating 3-hydroxy-3-methylglutaryl-CoA reductase-dependent cholesterol biosynthesis.

ABSTRACT: Recent studies have noted the role of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in developing neuropathic pain, but the underlying mechanisms are obscure. We found that PTEN was mainly expressed in astrocytes in the rat spinal cord and dramatically downregulated after chronic constriction injury (CCI). Intrathecal injection of a PTEN inhibitor induced pain-related behaviors in naive rats. By contrast, administration of a PTEN protector effectively mitigated CCI-induced pain. Adeno-associated virus-mediated overexpression of astrocytic PTEN in the spinal cord reduced glial activation and neuroinflammation and subsequently alleviated pain-related behaviors. Importantly, astrocyte-specific PTEN knockout ( Pten conditional knockout , Pten CKO) mice showed nociceptive sensitization and glial activation. Proteomic analysis revealed that PTEN overexpression upregulated at least 7 enzymes in the cholesterol biosynthesis pathway and the total cholesterol level in the spinal cord of CCI rats. Furthermore, PTEN directly interacted with enzymes, including 3-hydroxy-3-methylglutaryl-CoA reductase, in the cholesterol biosynthesis pathway. Astrocytic 3-hydroxy-3-methylglutaryl-CoA reductase overexpression alleviated both CCI-induced pain and mechanical allodynia in Pten CKO mice. Finally, cholesterol replenishment attenuated CCI-induced pain and suppressed spinal glial activation. Taken together, these findings imply that spinal astrocytic PTEN plays a beneficial role in CCI-induced pain by regulating cholesterol biosynthesis, and an increased level of PTEN may accelerate cholesterol biosynthesis and reduce glial activation, thereby alleviating neuropathic pain. Recovery of PTEN or cholesterol might be an effective therapeutic strategy for neuropathic pain.

Efficacy and practice of facemask use in general population: a systematic review and meta-analysis.

In recent decades, respiratory infections, including SARS, HINI and the currently spreading COVID-19, caused by various viruses such as influenza and coronavirus have seriously threatened human health. It has generated inconsistent recommendations on the mandatory use of facemasks across countries on a population level due to insufficient evidence on the efficacy of facemask use among the general population. This meta-analysis aimed to explore (1) the efficacy of facemask use on preventing respiratory infections, and (2) the perceptions, intentions, and practice about facemask use among the general population worldwide. We searched PubMed, MEDLINE, Web of Science, Cochrane, bioRxiv, and medRxiv databases since inception to August 17, 2020. From 21,341 records identified, eight RCTs on facemask in preventing infections and 78 studies on perception, intention, and practice of facemask use among the general population were included in the analysis. The meta-analysis of RCTs found a significant protective effect of facemask intervention (OR = 0.84; 95% CI = 0.71-0.99; I2 = 0%). This protective effect was even more pronounced when the intervention duration was more than two weeks (OR = 0.76; 95% CI = 0.66-0.88; I2 = 0%). The meta-analysis of observational studies on perception, intention, and practice on facemask use showed that 71% of respondents perceived facemasks to be effective for infection prevention, 68% of respondents would wear facemasks, and 54% of respondents wore facemasks for preventing respiratory infections. Differences in perception, intention, and practice behavior of facemask use in different regions may be related to the impact of respiratory infections, regional culture, and policies. The governments and relevant organizations should make effort to reduce the barriers in the use of facemasks.

Sudan Black B treatment uncovers the distribution of angiotensin-converting enzyme2 in nociceptors.

Nervous system manifestations caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of great concern. Neurological symptoms and the neurological effects induced by SARS-CoV-2, such as the loss of various sensory perceptions, indicate direct viral invasion into sensory neurons. Therefore, it is very important to identify the distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in human nervous system. However, autofluorescence from lipofuscin obviously impacted immunofluorescence analysis in previous studies. We demonstrated that Sudan Black B (SBB) remarkably reduced the massive lipofuscin-like autofluorescence and the immunofluorescence signal would be sharpened following the exposure compensation. Additionally, we confirmed that ACE2 was expressed in IB4+, CGRP+, and NF200+ sensory subpopulations. The mapping of ACE2 distribution in hDRG would facilitate the understanding of sensory disorder induced by SARS-CoV-2.

Acute and subchronic toxicity studies of rhein in immature and d-galactose-induced aged mice and its potential hepatotoxicity mechanisms.

Rhein is a key ingredient in many herbal remedies and is widely used. However, herbs containing rhein are frequently associated with poisoning incidents, especially in elderly subjects. Acute and subchronic toxicity of rhein in Kunming mice (KM) was investigated in this experiment. Acute toxicity tests showed a 40% lethality at a given rhein dose of 4000 mg/kg, and the LD50 of rhein was calculated by the bliss method to be greater than 2185.6 mg/kg. In subchronic toxicity, d-gal-induced aged and immature animals were randomized into three groups that were exposed to rhein of 0, 175, and 375 mg/kg/d for 75 days, respectively. No mortality was observed in immature mice group, whereas 55.5% (5/9) subjects in aged mice groups died in the high dosage group. AST, ALT, IL-6, TNF-α levels and typical histopathological changes indicate that rhein causes liver injury. In addition, our investigation explored possible hepatotoxic mechanisms of rhein and experimental results showed increased ROS production, NRF-2 and MDA levels and decreased SOD levels, demonstrating that rhein causes oxidative stress. MMP and mitochondrial swelling levels were able to assess the impact of rhein on mitochondrial function. Furthermore, the effect of rhein on apoptosis can be detected by flow cytometry. Our studies suggested that rhein induces oxidative stress leading to mitochondria dysfunction and apoptotic activation. Multidrug resistance protein (MRP) is an efflux transporter protein and is capable of transporting cellular oxidative stress-related substances. To further clarify the role of MRP in rhein induced oxidative stress, we examined MRP expression in the liver. However, the expression of MRP has no statistical significance.

Perceived uncertainty stress and its predictors among residents in China during the COVID-19 pandemic.

The prevalence of and risk factors for uncertainty stress among residents during the COVID-19 pandemic remain unclear. An online cross-sectional survey was conducted to explore and identify the risk factors for high perceived uncertainty stress among the general public in China during the COVID-19 outbreak. Information about the respondents' socioeconomic characteristics, knowledge of and attitudes towards COVID-19, perceived uncertainty stress, social capital, anxiety, and depressive symptoms was collected and analysed. Among the 1205 respondents, 45.3% (546) reported a high level of uncertainty stress. Multiple linear regression analysis indicated that anxiety (ß=3.871,P<0.001) and depression symptoms (ß=2.458, P<0.001), family residence (in towns or rural areas) (ß=0.947, P<0.001), lack of support for local epidemic control strategies (ß=1.253, P<0.001), worry about the pandemic (ß=1.191, P<0.001), and symptoms of weakness among family members (ß=1.525, P=0.002) were positively associated with perceived uncertainty stress. Cognitive social capital (ß=-0.883, P<0.001) and social networks (ß=-0.726, P<0.001) were negatively, but social participation (ß=0.714, P<0.001) was positively associated with perceived uncertainty stress. Our findings identify factors associated with a higher level of uncertainty stress and should be helpful in the consideration of effective policies and interventions for uncertainty stress during the initial phases of public health emergencies.