SARS-CoV-2 Omicron Variants Show Attenuated Neurovirulence Compared with the Wild-Type Strain in Elderly Human Brain Spheroids.

Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-ß deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.

Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1.

Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain protein 2 (SUN2) linking cytoskeleton and nucleoskeleton in the flavivirus replication. CRISPR/Cas9-mediated knockout of SUN2, but not SUN1, significantly reduces the replication of Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV). In contrast, SUN2 does not affect the infection of non-flaviviridae RNA viruses. All three regions of SUN2 are required for its proviral effect. Mechanistically, SUN2 facilitates rearrangement of cytoskeleton and formation of replication organelles induced by viral infection, and hence promotes viral RNA synthesis. SUN2 is required for the interaction between cytoskeleton actin and ZIKV nonstructural protein 1 (NS1). Expression of dominant negative Nesprin-1 and Nesprin-2, which connect SUN2 to cytoskeleton proteins, alleviates the interaction between actin and NS1 and reduces viral replication levels. In a neonatal mouse infection model, SUN2 knockout dramatically alleviates the in vivo ZIKV replication and development of neuropathology. This work elucidates that recruitment of cytoskeleton proteins by flavivirus is coordinated by nuclear membrane proteins SUN2 and Nesprins, providing evidence for a link between nuclear membrane proteins and flavivirus infection.

VDAC1, as a downstream molecule of MLKL, participates in OGD/R-induced necroptosis by inducing mitochondrial damage.

Ischemia-reperfusion (I/R) injury constitutes a significant risk factor for a range of diseases, including ischemic stroke, myocardial infarction, and trauma. Following the restoration of blood flow post-tissue ischemia, oxidative stress can lead to various forms of cell death, including necrosis, apoptosis, autophagy, and necroptosis. Recent evidence has highlighted the crucial role of mitochondrial dysfunction in I/R injury. Nevertheless, there remains much to be explored regarding the molecular signaling network governing cell death under conditions of oxidative stress. Voltage-dependent anion channel 1 (VDAC1), a major component in the outer mitochondrial membrane, is closely involved in the regulation of cell death. In a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R), which effectively simulates I/R injury in vitro, our study reveals that OGD/R induces VDAC1 oligomerization, consequently exacerbating cell death. Furthermore, we have revealed the translocation of mixed lineage kinase domain-like protein (MLKL) to the mitochondria, where it interacts with VDAC1 following OGD/R injury, leading to an increased mitochondrial membrane permeability. Notably, the inhibition of MLKL by necrosulfonamide hinders the binding of MLKL to VDAC1, primarily by affecting the membrane translocation of MLKL, and reduces OGD/R-induced VDAC1 oligomerization. Collectively, our findings provide preliminary evidence of the functional association between MLKL and VDAC1 in the regulation of necroptosis.

Exploring the effect of photobiomodulation and gamma visual stimulation induced by 808 nm and visible LED in Alzheimer's disease mouse model.

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-ß (Aß) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aß plaques, showing that the amount of Aß plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD.

Accuracy of physician and nurse predictions for 28-day prognosis in ICU: a single center prospective study.

The proportion of correctly predicted prognoses and factors associated with prediction accuracy are unknown. The objective of this study was to explore the accuracy of physician and nurse predictions of 28-day mortality in the ICU. This was a prospective observational single-center study. All medical staff in the ICU have access to patient data, can communicate with patients or clients, and can independently predict the prognosis of patients within 24 h of patient admission. The only question of the questionnaire survey was: What is the patient's outcome on day 28 (alive or death)? There were 2155 questionnaires completed by 18 physicians and 1916 submitted by 15 nurses. In the 312 patients included, the 28-day mortality rates were predicted by physicians and nurses. The overall proportion of correct prognosis prediction was 90.1% for physicians and 64.4% for nurses (P = 0.000). There was no significant difference in the overall correct proportion and average correct proportion among physicians with different seniority levels. The overall correct proportion and average correct proportion increased among nurses with seniority. Physicians in the ICU can moderately predict 28-day mortality in critically ill patients. Nurses with a seniority of less than 10 years in ICU cannot accurately predict 28-day mortality in critically ill patients. However, the accuracy of nurses' prediction of patients' 28-day prognosis increased with their seniority in the ICU.

A screening identifies harmine as a novel antibacterial compound against Ralstonia solanacearum.

Ralstonia solanacearum, the causal agent of bacterial wilt, is a devastating plant pathogenic bacterium that infects more than 450 plant species. Until now, there has been no efficient control strategy against bacterial wilt. In this study, we screened a library of 100 plant-derived compounds for their antibacterial activity against R. solanacearum. Twelve compounds, including harmine, harmine hydrochloride, citral, vanillin, and vincamine, suppressed bacterial growth of R. solanacearum in liquid medium with an inhibition rate higher than 50%. Further focus on harmine revealed that the minimum inhibitory concentration of this compound is 120 mg/L. Treatment with 120 mg/L of harmine for 1 and 2 h killed more than 90% of bacteria. Harmine treatment suppressed the expression of the virulence-associated gene xpsR. Harmine also significantly inhibited biofilm formation by R. solanacearum at concentrations ranging from 20 mg/L to 60 mg/L. Furthermore, application of harmine effectively reduced bacterial wilt disease development in both tobacco and tomato plants. Collectively, our results demonstrate the great potential of plant-derived compounds as antibacterial agents against R. solanacearum, providing alternative ways for the efficient control of bacterial wilt.

[Myocardial injury caused by infection of coronavirus].

Coronaviruses are single-stranded RNA viruses that are common in animals. In the past 20 years, there have been three large-scale epidemics of coronaviruses, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease (COVID). Heart disease is an independent risk factor for severe COVID. At the same time, SARS-CoV-2 infection is often complicated with myocardial injury, which is closely related to poor prognosis. The receptors of SARS coronavirus are angiotensin-converting enzyme 2 (ACE2) and CD209L, among which ACE2 is the main receptor, and ACE2 is abundant in the heart. The receptor of MERS-coronavirus is dipeptide peptidase 4 (DPP4), which is not expressed in myocardial cells, but existed in vascular endothelial cells and blood. These receptors are important factors for the myocardial injury caused by coronavirus infection.

A New Paradigm in Spinal Cord Injury Therapy: from Cell-free Treatment to Engineering Modifications.

Spinal cord injury (SCI) is an intractable and poorly prognostic neurological disease, and current treatments are still unable to cure it completely and avoid sequelae. Extracellular vesicles (EVs), as important carriers of intercellular communication and pharmacological effects, are considered to be the most promising candidates for SCI therapy because of their low toxicity and immunogenicity, their ability to encapsulate endogenous bioactive molecules (e.g., proteins, lipids, and nucleic acids), and their ability to cross the blood-brain/cerebrospinal barriers. However, poor targeting, low retention rate, and limited therapeutic efficacy of natural EVs have bottlenecked EV-based SCI therapy. A new paradigm for SCI treatment will be provided by engineering modified EVs. Furthermore, our limited understanding of the role of EVs in SCI pathology hinders the rational design of novel EVbased therapeutic approaches. In this study, we review the pathophysiology after SCI, especially the multicellular EVs-mediated crosstalk; briefly describe the shift from cellular to cell-free therapies for SCI treatment; discuss and analyze the issues related to the route and dose of EVs administration; summarize and present the common strategies for EVs drug loading in the treatment of SCI and point out the shortcomings of these drug loading methods; finally, we analyze and highlight the feasibility and advantages of bio-scaffold-encapsulated EVs for SCI treatment, providing scalable insights into cell-free therapy for SCI.

Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss.

Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP. Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome sequencing, and Sanger sequencing, as well as co-segregation analysis were performed. Results: Three heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*), c.4745T>C (p.L1582P), and c.14740G>A (p.E4914K), were identified in the proband, which were inherited from parents and transmitted to the daughters. Bioinformatics analysis supported the pathogenicity of the c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P) variants. Conclusions: Novel compound heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P), were identified as the genetic causes of autosomal recessive RP. The findings may enhance the current knowledge of the pathogenesis of USH2A-associated phenotypes, expand the spectrum of the USH2A gene variants, and contribute to improved genetic counseling, prenatal diagnosis, and disease management.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases.

The discovery of the necroptosis, a form of regulated necrosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL), represents a major breakthrough that has dramatically altered the conception of necrosis - traditionally thought of as uncontrolled cell death - in various human diseases. Retinal cell death is a leading cause of blindness and has been identified in most retinal diseases, e.g., age-related macular degeneration, glaucoma, retinal detachment, retinitis pigmentosa, etc. Increasing evidence demonstrates that retinal degenerative diseases also share a common mechanism in necroptosis. Exacerbated necroptotic cell death hinders the treatment for retinal degenerative diseases. In this review, we highlight recent advances in identifying retinal necroptosis, summarize the underlying mechanisms of necroptosis in retinal degenerative diseases, and discuss potential anti-necroptosis strategies, such as selective inhibitors and chemical agents, for treating retinal degenerative diseases.

Inhibition of mitochondrial VDAC1 oligomerization alleviates apoptosis and necroptosis of retinal neurons following OGD/R injury.

Ischemia-reperfusion (I/R) injury is a common pathological mechanism in many retinal diseases, which can lead to cell death via mitochondrial dysfunction. Voltage-dependent anion channel 1 (VDAC1), which is mainly located in the outer mitochondrial membrane, is the gatekeeper of mitochondria. The permeability of mitochondrial membrane can be regulated by controlling the oligomerization of VDAC1. However, the functional mechanism of VDAC1 in retinal I/R injury was unclear. Our results demonstrate that oxygen-glucose deprivation and re-oxygenation (OGD/R) injury leads to apoptosis, necroptosis, and mitochondrial dysfunction of R28 cells. The OGD/R injury increases the levels of VDAC1 oligomerization. Inhibition of VDAC1 oligomerization by VBIT-12 rescued mitochondrial dysfunction by OGD/R and also reduced apoptosis/necroptosis of R28 cells. In vivo, the use of VBIT-12 significantly reduced aHIOP-induced neuronal death (apoptosis/necroptosis) in the rat retina. Our findings indicate that VDAC1 oligomers may open and enlarge mitochondrial membrane pores during OGD/R injury, leading to the release of death-related factors in mitochondria, resulting in apoptosis and necroptosis. This study provides a potential therapeutic strategy against ocular diseases caused by I/R injury.

Public awareness and attitudes toward biobank and sample donation: A regional Chinese survey.

Background: The biobank is an extraordinary aid to research and scientific progress. Public involvement in biobanks, necessary for their development, is limited due to inadequate knowledge of biobanking and concerns about sample donation. This study explores the effectiveness of different publicity methods in improving participants' willingness to donate, and assesses public motivations and concerns. It aims to identify an efficient method of improving participants' awareness of biobanking and promoting sample donation. Methods: A structured 20-item questionnaire was formulated to evaluate participants' knowledge of and attitudes toward biobanks and sample donation. In total, 1,500 questionnaires were disseminated to three groups of 500 participants who received, respectively, picture-based promotional material, text-based promotional material, or who attended a biobank-related lecture. Of these, 945 completed questionnaires were received. All the participants completed the questionnaires twice, before and after the corresponding publicity education. Results: After each of the three methods of publicity based on text, pictures and a lecture, respondents' willingness to donate samples was significantly increased (P < 0.001), the lecture being more effective than the other two methods (P = 0.001). Participants with a medical background were more willing to donate biospecimens after publicity than those without medical backgrounds (P < 0.005) but had common motivations for donation including altruism and aiding medical research. The main concern hindering respondents' willingness to donate was the security of personal information. Conclusion: Different types of biobank-related publicity based on text material, pictorial material and a lecture all improved respondents' willingness to donate and reduced concerns regarding sample donation. Medical background was a critical factor affecting attitudes toward sample donation after publicity. The results of this study suggest strategies that may popularize biobanks and enhance sample donation, further promoting the development of biobanks.

Valdecoxib Protects against Cell Apoptosis Induced by Endoplasmic Reticulum Stress via the Inhibition of PERK-ATF4-CHOP Pathway in Experimental Glaucoma.

The purpose of this study was to investigate the effects of valdecoxib on the retina in retinal ischemia-reperfusion injury (IRI) and R28 cells following oxygen-glucose deprivation/recovery (OGD/R) injury, as well as the underlying mechanisms. Immunofluorescence and Cell Counting Kit-8 (CCK-8) analyses were used to identify the proper timepoint and concentration of valdecoxib's protective effect on the R28 cells in the OGD/R model. Hematoxylin-eosin (HE) staining and immunofluorescence were used to explore valdecoxib's effect on the retina and retina ganglion cell (RGC) in IRI. Cell apoptosis was determined by a TUNEL Apoptosis Detection Kit and Annexin V-FITC/PI flow cytometry. The expression levels of p-PERK, transcription factor 4 (ATF4), GRP78, CHOP, cleaved caspase 3, bax and bcl-2 were measured by Western blot analyses. The valdecoxib protected the R28 cells from OGD/R injury by decreasing the cell apoptosis rate, and it exerted a protective effect on retinas in I/R injury by inhibiting RGC apoptosis. The valdecoxib pretreatment reversed the expression of p-PERK, ATF4, CHOP, GRP78, cleaved caspase 3 and bax induced by the glaucomatous model. Meanwhile, the CCT020312 reversed the valdecoxib's anti-apoptosis effect by activating PERK-ATF4-CHOP pathway-mediated endoplasmic reticulum (ER) stress. These findings suggest that valdecoxib protects against glaucomatous injury by inhibiting ER stress-induced apoptosis via the inhibition of the PERK-ATF4-CHOP pathway.

Facilitators and barriers of African postgraduate nursing students' adaptation to internship: A qualitative study.

BACKGROUND: Clinical internship is a focused and supervised practice where nursing students have opportunities to master clinical skills and better adapt to the real working environment, promoting the formation of professional practice quality. However, for African postgraduate nursing students who had an internship in China, the factors affecting their adaptation to the internship have not yet been sufficiently explored. OBJECTIVE: To explore the facilitators and barriers of African postgraduate nursing students' adaptation to an internship. DESIGN: Qualitative descriptive study. SETTINGS: A comprehensive university with three affiliated hospitals in southern China. PARTICIPANTS: Twelve African postgraduate nursing students who finished a three-month internship in the two-year postgraduate programme. METHODS: Participants were recruited using purposive sampling. Semi-structured interviews were conducted between April and December 2021. Data were thematically analysed using the Colaizzi seven-step method. RESULTS: Three facilitators and four barriers to their adaptation to the internship emerged in the study. Facilitators included the teacher-student interactions, harmonious working atmosphere and positive inner incentives of the students. Barriers to adaptation were language barriers, unsuitable internship arrangements, lack of opportunities to practice clinical skills and disparities in hospital routine works. CONCLUSIONS: The present findings could contribute to the improvement of a more effective clinical training programme. Nursing colleges and teaching hospitals should make more efforts to enhance the current clinical internship programmes. Further support is necessary for international nursing students according to their culturally and linguistically diverse backgrounds.

A novel IFNbeta-induced long non-coding RNA ZAP-IT1 interrupts Zika virus replication in A549 cells.

Zika virus (ZIKV) infection can cause severe neurological diseases including neonatal microcephaly and Guillain-Barre syndrome. Long noncoding RNAs (lncRNAs) are the by-products of the transcription process, which are considered to affect viral infection. However, it remains largely unexplored whether host lncRNAs play a role in ZIKV infection. Here, we identified a group of human lncRNAs that were up-regulated upon ZIKV infection and were dependent on the type I interferon (IFN) signaling. Overexpression of lncRNA ZAP-IT1 leads to an impairment of ZIKV infection. Correspondently, deficiency of ZAP-IT1 led to an enhancement of ZIKV infection. We further confirmed that ZAP-IT1, an intronic lncRNA with total 551 â€‹nt in length, is mainly located in the nuclear upon ZIKV infection. Knockout of ZAP-IT1 also led to the increase of dengue virus (DENV), Japanese encephalitis virus (JEV), or vesicular stomatitis virus (VSV) infection. Mechanically, we found that the antiviral effect of ZAP-IT1 was independent of the type I IFN signaling pathway. Therefore, our data unveiled that host lncRNA ZAP-IT1 induced by the type I IFN signaling, showed robust restriction on ZIKV infection, and even on DENV, JEV, and VSV infection, which may benefit the development of antiviral therapeutics.

Comparing the Effect of Dexmedetomidine and Midazolam in Patients with Brain Injury.

BACKGROUND: Studies have shown that dexmedetomidine improves neurological function. Whether dexmedetomidine reduces mortality or improves quantitative electroencephalography (qEEG) among patients post-craniotomy remains unclear. METHODS: This single-center randomized study was conducted prospectively from 1 January 2019 to 31 December 2020. Patients who were transferred to the ICU after craniotomy within 24 h were included. The analgesic was titrated to a Critical care Pain Observation Tool (CPOT) score ≤2, and the sedative was titrated to a Richmond Agitation-Sedation Scale (RASS) score ≤-3 for at least 24 h. The qEEG signals were collected by four electrodes (F3, T3, F4, and T4 according to the international 10/20 EEG electrode practice). The primary outcome was 28-day mortality and qEEG results on day 1 and day 3 after sedation. RESULTS: One hundred and fifty-one patients were enrolled in this study, of whom 77 were in the dexmedetomidine group and 74 in the midazolam group. No significant difference was found between the two groups in mortality at 28 days (14.3% vs. 24.3%; p = 0.117) as well as in the theta/beta ratio (TBR), the delta/alpha ratio (DAR), and the (delta + theta)/(alpha + beta) ratio (DTABR) between the two groups on day 1 or day 3. However, both the TBR and the DTABR were significantly increased in the dexmedetomidine group. The DTABR in the midazolam group was significantly increased. The DAR was significantly increased on the right side in the dexmedetomidine group (20.4 (11.6-43.3) vs. 35.1 (16.7-65.0), p = 0.006) as well as on both sides in the midazolam group (Left: 19.5 (10.1-35.8) vs. 37.3 (19.3-75.7), p = 0.006; Right: 18.9 (10.1-52.3) vs. 39.8 (17.5-99.9), p = 0.002). CONCLUSION: Compared with midazolam, dexmedetomidine did not lead to a lower 28-day mortality or better qEEG results in brain injury patients after a craniotomy.

Effect of NaCl addition on alcohol-alkali-treated waxy rice starch: Structural and physicochemical functionality.

The physicochemical and structural properties of waxy rice starch (WRS) and alcohol-alkali-treated waxy rice starch (AAT-WRS) were determined in the presence of different concentrations of NaCl (0, 2, 4, 6 and 8%). The results showed that NaCl decreased the transparency of WRS and AAT-WRS pastes, but enhanced both freeze-thaw stability and apparent viscosity (p < 0.05). The rheological measurement results showed that the addition of NaCl could improve the modulus values of both WRS and AAT-WRS, and the effect on WRS was more significant than that on AAT-WRS. The textural parameters of WRS pastes were evidently enhanced by NaCl, but the presence of NaCl had no significant effect on the firmness of AAT-WRS pastes. The results of SEM and FT-IR revealed that NaCl could protect the granular morphology and increase the degree of short-range order of WRS and AAT-WRS.

ROR2 Downregulation Activates the MSX2/NSUN2/p21 Regulatory Axis and Promotes Dental Pulp Stem Cell Senescence.

Cellular senescence severely limits the research and the application of dental pulp stem cells (DPSCs). A previous study conducted by our research group revealed a close implication of ROR2 in DPSC senescence, although the mechanism underlying the regulation of ROR2 in DPSCs remains poorly understood so far. In the present study, it was revealed that the expression of the ROR2-interacting transcription factor MSX2 was increased in aging DPSCs. It was demonstrated that the depletion of MSX2 inhibits the senescence of DPSCs and restores their self-renewal capacity, and the simultaneous overexpression of ROR2 enhanced this effect. Moreover, MSX2 knockdown suppressed the transcription of NOP2/Sun domain family member 2 (NSUN2), which regulates the expression of p21 by binding to and causing the 5-methylcytidine methylation of the 3'- untranslated region of p21 mRNA. Interestingly, ROR2 downregulation elevated the levels of MSX2 protein, and not the MSX2 mRNA expression, by reducing the phosphorylation level of MSX2 and inhibiting the RNF34-mediated MSX2 ubiquitination degradation. The results of the present study demonstrated the vital role of the ROR2/MSX2/NSUN2 axis in the regulation of DPSC senescence, thereby revealing a potential target for antagonizing DPSC aging.

Preparation, characterization and evaluation of capsaicin-loaded indica rice starch nanoparticles.

Capsaicin (CAP) is an alkaloid with multiple physiological effects, but its application is difficult. In this research, indica rice starch nanoparticles (IRSNPs) based nanocarrier was used to load CAP to obtain capsaicin-loaded indica rice starch nanoparticles (CAP-IRSNPs). The microstructure, characteristics and in vitro release behaviors of CAP-IRSNPs were analyzed. CAP-IRSNPs presented average particle sizes of 617.84 ± 6.38 nm, encapsulation efficiency of 70.05 ± 1.78% and loading capacity of 13.41 ± 0.18%. Fourier-transform infrared spectroscopy confirmed that CAP-IRSNPs might be formed by hydrogen-bonding action. Differential scanning calorimetry and X-ray diffraction showed that IRSNPs influenced the crystallization and melting temperatures of CAP. In in vitro release study, CAP-IRSNPs exhibited a sustained release. The CAP concentration, CAP diffusion from matrix and matrix erosion might be the potentially possible mechanisms for capsaicin release from CAP-IRSNPs. These new results concluded that IRSNPs may be a promising nanocarrier for CAP or other hydrophobic bioactive ingredients.