Comparative Transcriptomic Analyses Propose the Molecular Regulatory Mechanisms Underlying 1,8-Cineole from Cinnamomum kanehirae Hay and Promote the Asexual Sporulation of Antrodia cinnamomea in Submerged Fermentation.

Antrodia cinnamomea is a valuable edible and medicinal mushroom with antitumor, hepatoprotective, and antiviral effects that play a role in intestinal flora regulation. Spore-inoculation submerged fermentation has become the most efficient and well-known artificial culture process for A. cinnamomea. In this study, a specific low-molecular compound named 1,8-cineole (cineole) from Cinnamomum kanehirae Hay was first reported to have remarkably promoted the asexual sporulation of A. cinnamomea in submerged fermentation (AcSmF). Then, RNA sequencing, real-time quantitative PCR, and a literature review were performed to predict the molecular regulatory mechanisms underlying the cineole-promoted sporulation of AcSmF. The available evidence supports the hypothesis that after receiving the signal of cineole through cell receptors Wsc1 and Mid2, Pkc1 promoted the expression levels of rlm1 and wetA and facilitated their transfer to the cell wall integrity (CWI) signal pathway, and wetA in turn promoted the sporulation of AcSmF. Moreover, cineole changed the membrane functional state of the A. cinnamomea cell and thus activated the heat stress response by the CWI pathway. Then, heat shock protein 90 and its chaperone Cdc37 promoted the expression of stuA and brlA, thus promoting sporulation of AcSmF. In addition, cineole promoted the expression of areA, flbA, and flbD through the transcription factor NCP1 and inhibited the expression of pkaA through the ammonium permease of MEP, finally promoting the sporulation of AcSmF. This study may improve the efficiency of the inoculum (spores) preparation of AcSmF and thereby enhance the production benefits of A. cinnamomea.

Molecular Regulatory Mechanism of the Iron-Ion-Promoted Asexual Sporulation of Antrodia cinnamomea in Submerged Fermentation Revealed by Comparative Transcriptomics.

Antrodia cinnamomea is a precious edible and medicinal fungus with activities of antitumor, antivirus, and immunoregulation. Fe2+ was found to promote the asexual sporulation of A. cinnamomea markedly, but the molecular regulatory mechanism of the effect is unclear. In the present study, comparative transcriptomics analysis using RNA sequencing (RNA-seq) and real time quantitative PCR (RT-qPCR) were conducted on A. cinnamomea mycelia cultured in the presence or absence of Fe2+ to reveal the molecular regulatory mechanisms underlying iron-ion-promoted asexual sporulation. The obtained mechanism is as follows: A. cinnamomea acquires iron ions through reductive iron assimilation (RIA) and siderophore-mediated iron assimilation (SIA). In RIA, ferrous iron ions are directly transported into cells by the high-affinity protein complex formed by a ferroxidase (FetC) and an Fe transporter permease (FtrA). In SIA, siderophores are secreted externally to chelate the iron in the extracellular environment. Then, the chelates are transported into cells through the siderophore channels (Sit1/MirB) on the cell membrane and hydrolyzed by a hydrolase (EstB) in the cell to release iron ions. The O-methyltransferase TpcA and the regulatory protein URBS1 promote the synthesis of siderophores. HapX and SreA respond to and maintain the balance of the intercellular concentration of iron ions. Furthermore, HapX and SreA promote the expression of flbD and abaA, respectively. In addition, iron ions promote the expression of relevant genes in the cell wall integrity signaling pathway, thereby accelerating the cell wall synthesis and maturation of spores. This study contributes to the rational adjustment and control of the sporulation of A. cinnamomea and thereby improves the efficiency of the preparation of inoculum for submerged fermentation.

Activating NO-sGC crosstalk in the mouse vascular niche promotes vascular integrity and mitigates acute lung injury.

Disruption of endothelial cell (ECs) and pericytes interactions results in vascular leakage in acute lung injury (ALI). However, molecular signals mediating EC-pericyte crosstalk have not been systemically investigated, and whether targeting such crosstalk could be adopted to combat ALI remains elusive. Using comparative genome-wide EC-pericyte crosstalk analysis of healthy and LPS-challenged lungs, we discovered that crosstalk between endothelial nitric oxide and pericyte soluble guanylate cyclase (NO-sGC) is impaired in ALI. Indeed, stimulating the NO-sGC pathway promotes vascular integrity and reduces lung edema and inflammation-induced lung injury, while pericyte-specific sGC knockout abolishes this protective effect. Mechanistically, sGC activation suppresses cytoskeleton rearrangement in pericytes through inhibiting VASP-dependent F-actin formation and MRTFA/SRF-dependent de novo synthesis of genes associated with cytoskeleton rearrangement, thereby leading to the stabilization of EC-pericyte interactions. Collectively, our data demonstrate that impaired NO-sGC crosstalk in the vascular niche results in elevated vascular permeability, and pharmacological activation of this crosstalk represents a promising translational therapy for ALI.

A WeChat-based self-compassion training to improve the treatment adherence of patients with schizophrenia in China: Protocol for a randomized controlled trial.

Background: At present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated that increasing a patient's level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia. Methods: The protocol for the randomized controlled trial (RCT) is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline (T0), immediately after the intervention (T1), and 3 weeks after the intervention (T2). Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention (T1). Expected results: The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients' desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries.

Association between self-care disability and depressive symptoms among middle-aged and elderly Chinese people.

OBJECTIVE: In the context of an increased focus on geriatric depression in recent years, this study examined the associations between different types of self-care disability, the number of self-care disabilities, and depressive symptoms among middle-aged and elderly Chinese people. METHOD: The data for this study were extracted from the follow-up survey (conducted in 2018) of the China Health and Retirement Longitudinal Study (CHARLS). The sample comprised 10808 participants aged 45 years and older. The Activities of Daily Living (ADL) scale and the Center for Epidemiological Studies Depression (CESD-10) Scale were used to assess self-care disability and depressive symptoms, respectively. RESULT: The prevalence of depressive symptoms and self-care disability among the surveyed residents was 45.1% and 23.4%, respectively. Overall, there was a significant positive association between self-care disability and depressive symptoms. Participants who reported having a self-care disability in relation dressing, bathing, transferring in and out of bed, using the toilet, and controlling urination and defecation were found to have a significantly higher risk of depressive symptoms. In addition, participants with a greater cumulative quantity of self-care disabilities had a higher risk of depressive symptoms, and higher CESD-10 scores. CONCLUSION: Self-care disability is a risk factor for depressive symptoms among middle-aged and elderly Chinese people. A positive correlation between the number of self-care disabilities and the risk of depressive symptoms was found.

KANK4 Promotes Arteriogenesis by Potentiating VEGFR2 Signaling in a TALIN-1-Dependent Manner.

BACKGROUND: Arteriogenesis plays a critical role in maintaining adequate tissue blood supply and is related to a favorable prognosis in arterial occlusive diseases. Strategies aimed at promoting arteriogenesis have thus far not been successful because the factors involved in arteriogenesis remain incompletely understood. Previous studies suggest that evolutionarily conserved KANK4 (KN motif and ankyrin repeat domain-containing proteins 4) might involve in vertebrate vessel development. However, how the KANK4 regulates vessel function remains unknown. We aim to determine the role of endothelial cell-specifically expressed KANK4 in arteriogenesis. METHODS: The role of KANK4 in regulating arteriogenesis was evaluated using Kank4-/- and KANK4iECOE mice. Molecular mechanisms underlying KANK4-potentiated arteriogenesis were investigated by employing RNA transcriptomic profiling and mass spectrometry analysis. RESULTS: By analyzing Kank4-EGFP reporter mice, we showed that KANK4 was specifically expressed in endothelial cells. In particular, KANK4 displayed a dynamic expression pattern from being ubiquitously expressed in all endothelial cells of the developing vasculature to being explicitly expressed in the endothelial cells of arterioles and arteries in matured vessels. In vitro microfluidic chip-based vascular morphology analysis and in vivo hindlimb ischemia assays using Kank4-/- and KANK4iECOE mice demonstrated that deletion of KANK4 impaired collateral artery growth and the recovery of blood perfusion, whereas KANK4 overexpression leads to increased vessel caliber and blood perfusion. Bulk RNA sequencing and Co-immunoprecipitation/mass spectrometry (Co-IP/MS) analysis identified that KANK4 promoted EC proliferation and collateral artery remodeling through coupling VEGFR2 (vascular endothelial growth factor receptor 2) to TALIN-1, which augmented the activation of the VEGFR2 signaling cascade. CONCLUSIONS: This study reveals a novel role for KANK4 in arteriogenesis in response to ischemia. KANK4 links VEGFR2 to TALIN-1, resulting in enhanced VEGFR2 activation and increased EC proliferation, highlighting that KANK4 is a potential therapeutic target for promoting arteriogenesis for arterial occlusive diseases.

Photodissociation of particulate nitrate as a source of daytime tropospheric Cl2.

Chlorine atoms (Cl) are highly reactive and can strongly influence the abundances of climate and air quality-relevant trace gases. Despite extensive research on molecular chlorine (Cl2), a Cl precursor, in the polar atmosphere, its sources in other regions are still poorly understood. Here we report the daytime Cl2 concentrations of up to 1 ppbv observed in a coastal area of Hong Kong, revealing a large daytime source of Cl2 (2.7 pptv s-1 at noon). Field and laboratory experiments indicate that photodissociation of particulate nitrate by sunlight under acidic conditions (pH < 3.0) can activate chloride and account for the observed daytime Cl2 production. The high Cl2 concentrations significantly increased atmospheric oxidation. Given the ubiquitous existence of chloride, nitrate, and acidic aerosols, we propose that nitrate photolysis is a significant daytime chlorine source globally. This so far unaccounted for source of chlorine can have substantial impacts on atmospheric chemistry.

Dignity and its related factors among older adults in long-term care facilities: A cross-sectional study.

OBJECTIVES: This study aimed to explore the dignity and related factors among older adults in long-term care facilities. METHODS: Cross-sectional data were obtained from a sample of 253 Chinese older adults dwelling in long-term care facilities. Dignity among older adults was measured using the Dignity Scale, and its potential correlates were explored using multiple linear regressions. RESULTS: Results showed that the total score of the Dignity Scale is 151.95 ± 11.75. From high to low, the different factors of dignity among older adults in long-term care facilities were as follows: caring factors (4.83 ± 0.33), social factors (4.73 ± 0.41), psychological factors (4.66 ± 0.71), value factors (4.56 ± 0.53), autonomous factors (4.50 ± 0.57), and physical factors (4.38 ± 0.55). A higher score of the Dignity Scale was associated with higher economic status, fewer chronic diseases, less medication, better daily living ability and long-time lived in cities. CONCLUSION: Older adults with low economic status, more chronic diseases, and poor daily living ability, taking more medications, or the previous residence in rural areas seem to be most at low-level dignity in long-term care facilities and thus require more attention than their peers.

Sodium Danshensu promotes the healing of stage 2 pressure injury wounds in ischemia/reperfusion injury rat models: possible regulation of apoptosis and inflammatory response.

OBJECTIVE: To investigate the protective effect and possible mechanism of sodium Danshensu (SDSS) against pressure injury caused by ischemia/reperfusion (I/R) injury. METHODS: Sprague-Dawley rats were randomly divided into five groups of eight rats each: control group, model group, 10 mg/kg SDSS-treated group, 20 mg/kg SDSS-treated group, and 40 mg/kg SDSS-treated group. We used two round ferrite magnetic plates of 15 mm diameter and 3 mm thickness to establish stage 2 pressure injury model rats. Each rat was subjected to five cycles of ischemia and reperfusion to induce pressure injury. One cycle consisted of 2 h of ischemia and 0.5 h of reperfusion, which meant that each cycle included 2 h of pressure and 0.5 h of pressure relief. The outline of the wound was delineated by butter paper and marker pen, and histopathological changes were observed by hematoxylin and eosin staining. In addition, the number of apoptotic cells and the activity of caspase-3 were assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling and caspase-3 assay kits, respectively. The expression of apoptosis-regulatory proteins and inflammatory mediators was investigated by enzyme-linked immunosorbent assay. RESULTS: Results showed that treatment with SDSS for 7 d after establishing the pressure injury model remarkably improved the healing rate of the wound. SDSS also inhibited the levels of tumor ne- crosis factor-α, myeloperoxidase, and intercellular cell adhesion molecule-1; decreased the number of apoptotic cells; increased the ratio of B-cell lymphoma-2 (Bcl-2) / Bcl-2-associated X (Bax); and regulated the expression and activity of caspase-3. CONCLUSION: Our results suggest that SDSS exhibits a treatment efficacy for pressure injury caused by I/R injury possibly by inhibiting apoptosis and inflammatory response.

Fast heterogeneous loss of N2O5 leads to significant nighttime NOx removal and nitrate aerosol formation at a coastal background environment of southern China.

Nitrate radical (NO3) and dinitrogen pentoxide (N2O5) play crucial roles in the nocturnal atmosphere. To quantify their impacts, we deployed a thermal-dissociation chemical ionization mass spectrometry (TD-CIMS), to measure their concentration, as well as ClNO2 at a coastal background site in the southern of China during the late autumn of 2012. Moderate levels of NO3, N2O5 and high concentration of ClNO2 were observed during the study period, indicating active NOx-O3 chemistry in the region. Distinct features of NO3, N2O5 and ClNO2 mixing ratios were observed in different airmasses. Further analysis revealed that the N2O5 heterogeneous reaction was the dominant loss of N2O5 and NO3, which showed higher loss rate compared to that in other coastal sites. Especially, the N2O5 loss rates could reach up to 0.0139 s-1 when airmasses went across the sea. The fast heterogeneous loss of N2O5 led to rapid NOx loss which could be comparable to the daytime process through NO2 oxidization by OH, and on the other hand, to rapid nitrate aerosol formation. In summary, our results revealed that the N2O5 hydrolysis could play significant roles in regulating the air quality by reducing NOx but forming nitrate aerosols.

Endothelial cell fitness dictates the source of regenerating liver vasculature.

Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis in livers with intact endothelium was solely mediated by proliferation of resident ECs. However, following irradiation-induced EC damage, bone marrow-derived mononuclear cells were recruited and incorporated into the vasculature. Further experiments with direct bone marrow infusion or granulocyte colony-stimulating factor (G-CSF)-mediated progenitor cell mobilization, which resembles clinically relevant stem cell therapy, demonstrated that bone marrow-derived cells did not contribute to the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx). Taken together, the data reconcile many of the discrepancies in the literature and highlight that the cellular source of regenerating endothelium depends on the fitness of the residual vasculature.