METTL16 deficiency attenuates apoptosis through translational control of extrinsic death receptor during nutrient deprivation.

METTL16 is a well-characterized m6A methyltransferase that has been reported to contribute to tumorigenesis in various types of cancer. However, the effect of METTL16 on tumor progression under restricted nutrient conditions, which commonly occur in tumor microenvironment, has yet to be elucidated. Herein, our study initially reported the inhibitory effect of METTL16 depletion on apoptosis under amino acid starvation conditions. Mechanistically, we determined that the METTL16 knockdown represses the expression of extrinsic death receptors at both transcription and translation levels. Depletion of METTL16 prevented protein synthesis of GCN2, resulting in diminished ATF4 expression in a GCN2-eIF2α-dependent manner. Reduction of ATF4 further declined the expression of apoptotic receptor protein DR5. Meanwhile, METTL16 deficiency directly hampered protein synthesis of FADD and DR5, thereby impairing apoptosis and promoting cancer cell survival. Taken together, our study provides novel evidence for the involvement of METTL16 in regulating cancer progression, suggesting that METTL16 as a potential therapeutic target for cancer treatment.

Comparison of pulmonary function during interscalene block vs. supraclavicular block: a single-center, double-blind, randomized trial.

BACKROUND: The supraclavicular plexus block (SCB) and interscalene plexus block (ISB) have the potential to pulmonary function, the duration of the potential remains uncertain. So, we compared the effect of SCB and ISB on pulmonary function, especially the duration time. METHODS: Ninety-six patients were finally allocated to group I and group S. The ISB and the SCB procedures were performed with ultrasound guidance before anesthesia induction. An investigator recorded the diaphragm mobility and respiratory function test indicators before the block (T0) and at 30 min (T30 min), 4 h (T4), 8 h (T8), and 12 h (T12) after the block. The diaphragmatic paralysis rate was calculated for above timepoint. The VAS, the recovery time for the sensory and motor block, and adverse reactions within 24 h of administering the block were also recorded. RESULTS: The recovery times of diaphragm mobility in group I were longer than those in group S. Compared with group I, group S had a significantly lower diaphragmatic paralysis rate during eupnea breathing at T30 min and T8 after the block. Similarly, group S had a significantly lower diaphragmatic paralysis rate at deep breathing at T30 min, T8, and T12 after the block. The recovery times of FEV1 and FVC in group I were longer than those in group S. The other results were not statistically significant. CONCLUSIONS: Ultrasound-guided ISB resulted in a longer periods with a suppressive effect on pulmonary function than SCB. TRIALS REGISTRATION: 17/12/2019, ChiCTR1900028286.

Plastome comparison and phylogenomics of Fagopyrum (Polygonaceae): insights into sequence differences between Fagopyrum and its related taxa.

BACKGROUND: Fagopyrum (Polygonaceae) is a small plant lineage comprised of more than fifteen economically and medicinally important species. However, the phylogenetic relationships of the genus are not well explored, and the characteristics of Fagopyrum chloroplast genomes (plastomes) remain poorly understood so far. It restricts the comprehension of species diversity in Fagopyrum. Therefore, a comparative plastome analysis and comprehensive phylogenomic analyses are required to reveal the taxonomic relationship among species of Fagopyrum. RESULTS: In the current study, 12 plastomes were sequenced and assembled from eight species and two varieties of Fagopyrum. In the comparative analysis and phylogenetic analysis, eight previously published plastomes of Fagopyrum were also included. A total of 49 plastomes of other genera in Polygonaceae were retrieved from GenBank and used for comparative analysis with Fagopyrum. The variation of the Fagopyrum plastomes is mainly reflected in the size and boundaries of inverted repeat/single copy (IR/SC) regions. Fagopyrum is a relatively basal taxon in the phylogenomic framework of Polygonaceae comprising a relatively smaller plastome size (158,768-159,985 bp) than another genus of Polygonaceae (158,851-170,232 bp). A few genera of Polygonaceae have nested distribution of the IR/SC boundary variations. Although most species of Fagopyrum show the same IRb/SC boundary with species of Polygonaceae, only a few species show different IRa/SC boundaries. The phylogenomic analyses of Fagopyrum supported the cymosum and urophyllum groups and resolved the systematic position of subclades within the urophyllum group. Moreover, the repeat sequence types and numbers were found different between groups of Fagopyrum. The plastome sequence identity showed significant differences between intra-group and inter-group. CONCLUSIONS: The deletions of intergenic regions cause a short length of Fagopyrum plastomes, which may be the main reason for plastome size diversity in Polygonaceae species. The phylogenomic reconstruction combined with the characteristics comparison of plastomes supports grouping within Fagopyrum. The outcome of these genome resources may facilitate the taxonomy, germplasm resources identification as well as plant breeding of Fagopyrum.

Surface-mediated construction of diverse coordination-dominated nanostructures with 4-azidobenzoic acid molecule.

The coordination reactions of 4-Azidobenzoic Acid (ABA) molecules on different active surfaces are studied by scanning tunneling microscopy and density functional theory calculations. ABA molecules deposited on Ag(111)/Ag(100)/Cu(100) held at room temperature lead to the decomposition of azide groups and the release of a N2 molecule per ABA molecule. Two residual segments of ABA molecules can interact with one Ag/Cu adatom to form a coordination dimer through the N-Ag/Cu-N coordination bond on different substrates. Different orientations with different symmetries can result in different nanostructures based on the dimers. Interestingly, the residual segments of ABA molecules can generate four Cu adatoms as the coordination center on Cu(100) to form a novel coordination complex after annealing, which is the first report for trapping four adatoms as a coordination center. The number and the species of adatoms captured can be changed to alter coordination structures. It expounds that various regulatory effects of different substrates lead to the diversity of nanostructures dominated by coordination bonds.

Bilateral thoracic paravertebral block combined with general anesthesia vs. general anesthesia for patients undergoing off-pump coronary artery bypass grafting: a feasibility study.

BACKGROUND: Whether thoracic paravertebral block (PVB) is useful in patients undergoing off-pump coronary artery bypass grafting (OPCABG) remains unknown. This study aimed to investigate the feasibility of bilateral PVB combined with general anesthesia (GA) in patients undergoing OPCABG. METHODS: This feasibility study assessed 60 patients scheduled for OPCABG at the Qingdao Municipal Hospital in 2016-2017. Patients were randomly assigned to receive nerve stimulator-guided bilateral PVB combined with GA (PVB + GA) or GA alone (n = 30/group). Patients were asked to rate rest and cough pain hourly after the surgery. The primary endpoint was the visual analogue scale (VAS) pain score within 48 h postoperatively. Secondary endpoints were rescue analgesia and morphine consumption, fentanyl dose within 48 h postoperatively, as well as operative time, time to extubation, intensive care unit (ICU) stay, hospital stay and other postoperative adverse events. RESULTS: Both rest and cough pains were lower in the PVB + GA group at 12, 24, 36, and 48 h after surgery compared with the GA group. There were fewer patients who needed rescue analgesia in the PVB + GA group at 12 and 24 h than in the GA group. Morphine consumptions at 24 and 48 h were lower in the PVB + GA group compared with the GA group. Time to extubation (P = 0.035) and ICU stay (P = 0.028) were shorter in the PVB + GA group compared with the GA group. AEs showed no differences between the two groups. CONCLUSIONS: Nerve stimulator-guided bilateral thoracic PVB combined with GA in OPCABG is associated with a reduced rescue analgesia and morphine consumption, compared to GA.

Floral morphology and morphogenesis in Camptotheca (Nyssaceae), and its systematic significance.

Background and Aims: Camptotheca is endemic to China and there are limited data about the breeding system and morphogenesis of the flowers. Camptotheca is thought to be related to Nyssa and Davidia in Nyssaceae, which has sometimes been included in Cornaceae. However, molecular phylogenetic studies confirmed the inclusion of Camptotheca in Nyssaceae and its exclusion from Cornaceae. The aim of this study was to reveal developmental features of the inflorescence and flowers in Camptotheca to compare with related taxa in Cornales. Methods: Inflorescences and flowers of Camptotheca acuminata at all developmental stages were collected and studied with a scanning electron microscope and stereo microscope. Key Results: Camptotheca has botryoids which are composed of several capitate floral units (FUs) that are initiated acropetally. On each FU, flowers are grouped in dyads that are initiated acropetally. All floral organs are initiated centripetally. Calyx lobes are restricted to five teeth. The hypanthium, with five toothed calyx lobes, is adnate to the ovary. The five petals are free and valvate. Ten stamens are inserted in two whorls around the central depression, in which the style is immersed. Three carpels are initiated independently but the ovary is syncarpous and unilocular. The ovule is unitegmic and heterotropous. Inflorescences are functionally andromonoecious varying with the position of the FUs on the inflorescence system. Flowers on the upper FU often have robust styles and fully developed ovules. Flowers on the lower FU have undeveloped styles and aborted ovules, and the flowers on the middle FU are transitional. Conclusions: Camptotheca possesses several traits that unify it with Nyssa, Mastixia and Diplopanax. Inflorescence and floral characters support a close relationship with Nyssaceae and Mastixiaceae but a distant relationship with Cornus. Our results corroborate molecular inferences and support a separate family Nyssaceae.

The reasons for Chinese nursing staff to report adverse events: a questionnaire survey.

AIMS: To investigate the impact of nurses' perception of patient safety culture and adverse event reporting, and demographic factors on adverse event reporting in Chinese hospitals. BACKGROUND: Accurate and timely adverse event reporting is integral in promoting patient safety and professional learning around the incident. METHODS: In a cross-sectional survey, a sample of 919 nurses completed a structured questionnaire composed of two validated instruments measuring nurses' perception of patient safety culture and adverse event reporting. Associations between the variables were examined using multiple linear regression analysis. RESULTS: The positive response rates of five dimensions of the Patient Safety Culture Assessment Scale varied from 47.55% to 80.62%. The accuracy rate of Adverse Event Reporting Perception Scale was 63.16%. Five hundred and thirty-one (58.03%) nurses did not report adverse event in past 12 months. Six variables were found to be associated with nurses' adverse event reporting: total work experience (P = 0.003), overall patient safety culture score (P < 0.001), safety climate (P < 0.001), teamwork climate (P < 0.001), overall the adverse event reporting perception scale score (P = 0.003) and importance or reporting (P = 0.002). CONCLUSIONS: The results confirmed that improvements in the patient safety culture and nurses' perception of adverse event reporting were related to an increase in voluntary adverse event reporting. IMPLICATIONS FOR NURSING MANAGEMENT: The knowledge of adverse event reporting should be integrated into the patient safety curriculum. Interventions that target a specific domain are necessary to improve the safety culture.

Construction of a new model of job engagement, psychological empowerment and perceived work environment among Chinese registered nurses at four large university hospitals: implications for nurse managers seeking to enhance nursing retention and quality of care.

AIM: To explore the relationships among perceived work environment, psychological empowerment and job engagement of clinical nurses in Harbin, China. BACKGROUND: Previous studies have focused on organisational factors or nurses' personal characteristics contributing to job engagement. Limited studies have examined the effects of perceived work environment and psychological empowerment on job engagement among Chinese nurses. METHOD: A cross-sectional quantitative survey with 923 registered nurses at four large university hospitals in China was carried out. Research instruments included the Chinese versions of the perceived nurse work environment scale, the psychological empowerment scale and the job engagement scale. The relationships of the variables were tested using structural equation modelling. RESULTS: Structural equation modelling revealed a good fit of the model, χ(2) /df = 4.46, GFI = 0.936, CFI = 0.957. Perceived work environment was a significant positive direct predictor of psychological empowerment and job engagement. Psychological empowerment was a significant positive direct contributor to job engagement and had a mediating effect on the relationship between perceived work environment and job engagement. CONCLUSIONS: Perceived work environment may result in increased job engagement by facilitating the development of psychological empowerment. IMPLICATIONS FOR NURSING MANAGEMENT: For nurse managers wishing to increase nurse engagement and to achieve effective management, both perceived work environment and psychological empowerment are factors that need to be well controlled in the process of nurse administration.

Restrictive Fluid Resuscitation Leads to Better Oxygenation than Non-Restrictive Fluid Resuscitation in Piglets with Pulmonary or Extrapulmonary Acute Respiratory Distress Syndrome.

BACKGROUND: Early goal-directed therapy (EGDT) is used to reduce mortality from septic shock and could be used in early fluid resuscitation of acute respiratory distress syndrome (ARDS). The aim of the present study was to assess the effects of restrictive (RFR) and nonrestrictive fluid resuscitation (NRFR) on hemodynamics, oxygenation, pulmonary function, tissue perfusion, and inflammation in piglets with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp). MATERIAL AND METHODS: Chinese miniature piglets (6-8 weeks; 15 ± 1 kg) were randomly divided into 2 groups (n=12/group) for establishing ARDSp and ARDSexp models, and were further divided into 2 subgroups (n=6/subgroup) for performing RFR and NRFR. Piglets were anesthetized and hemodynamic, pulmonary, and oxygenation indicators were collected at different time points for 6 hours. The goal of EGDT was set for PiCCO parameters (mean arterial pressure (MAP), urine output and cardiac index (CI), and central venous oxygen saturation (ScvO2). RESULTS: Piglets under RFR had lower urine output compared with NRFR, as well as lower total fluid volume (P<0.05). EVLW was decreased in ARDSp+RFR and NRFR, as well as in ARDSexp+RFR, but EVLW increased in ARDSexp+NRFR (P<0.05). PaO2/FiO2 decreased in ARDSp using both methods, but was higher with RFR (P<0.05), and was increased in ARDSexp+RFR. Other pulmonary indicators were comparable. The anti-inflammatory cytokines IL-10 and LXA4 were increased in ARDSexp after RFR (P<0.05), but not in the other groups. CONCLUSIONS: RFR led to better oxygenation in ARDSp and ARDSexp compared with NRFR, but fluid restriction improved oxygenation in ARDSexp only.

Occupational stress and coping strategies among emergency department nurses of China.

Emergency department(ED) nurses work in a rapidly changing environment with patients that have wide variety of conditions. Occupational stress in emergency department nurses is a common problem. The purpose of this study was to describe the relationship between coping strategies and occupational stress among ED nurses in China. A correlational, cross-sectional design was adopted. Two questionnaires were given to a random sample of 127 ED nurses registered at the Heilongjiang Nurses' Association. Data were collected from the nurses that worked in the ED of five general hospitals in Harbin China. Occupational stress and coping strategies were measured by two questionnaires. A multiple regression model was applied to analyze the relationship between stress and coping strategies. The stressors of ED nurses mainly come from the ED specialty of nursing (2.97±0.55), workload and time distribution (2.97±0.58). The mean score of positive coping strategies was 2.19±0.35, higher than the norm (1.78±0.52). The mean score of negative coping strategies was 1.20±0.61, lower than the norm (1.59±0.66), both had significant statistical difference (P<0.001). Too much documents work, criticism, instrument equipment shortage, night shift, rank of professional were the influence factors about occupational stress to positive coping styles. Too much documents work, and medical insurance for ED nurses were the influential factors on occupational stress to negative coping styles. This study identified several factors associated with occupational stress in ED nurses. These results could be used to guide nurse managers of ED nurses to reduce work stress. The managers could pay more attention to the ED nurse's coping strategies which can further influence their health state and quality of nursing care. Reducing occupational stress and enhancing coping strategies are vital not only for encouraging nurses but also for the future of nursing development.

Effect of high frequency oscillatory ventilation on EVLW and lung capillary permeability of piglets with acute respiratory distress syndrome caused by pulmonary and extrapulmonary insults.

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group (P<0.05). The EVLWI in ARDSp group was increased at T1 (P=0.008), and sustained continuously within 2 h (P=0.679, P=0.216), but decreased at T4 (P=0.007) and T5 (P=0.037). The EVLWI in ARDSexp group was also increased at T1 (P=0.003), but significantly decreased at T3 (P=0.002) and T4 (P=0.019). PVPI was increased after modeling in both two groups (P=0.004, P=0.012), but there was no significant change within 4 h (T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI (P=0.13), ΔPVPI (P=0.28) and ΔEVLW/ITBV between the two groups (P=0.63). The significant decreases in both CC16 and sICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.

Developing tools for identifying employer and employee satisfaction of nursing new graduates in China.

PURPOSE: Researchers developed evaluation tools measuring employment relevant satisfaction for nursing new graduates. The evaluation tools were designed to be relevant to nursing managers who make employment decisions and nursing new graduates who were just employed. METHODS: In-depth interviews and an expert panel were established to review the activities that evaluate the employee and employer satisfaction of nursing new graduates. Based on individual interviews and literature review, evaluation items were selected. A two-round Delphi study was then conducted from September 2008 to May 2009 with a panel of experts from a range of nursing colleges in China. RESULTS: The response rate was 100% and Kendall's W was 0.73 in the second round of Delphi study. After two rounds of Delphi surveys, a list of 5 employee satisfaction items and 4 employer satisfaction items was identified for nursing new graduates. CONCLUSIONS: The findings of this study identified a different but multidimensional set of factors for employment relevant satisfaction, which confirmed the importance of certain fundamental aspects of practice. We developed the evaluation tools to assess the employer and employee satisfaction of nursing new graduates, which provided a database for further study.

A survey on 465 patients with post-stroke depression in China.

The incidence of PSD patients is very high. To analyze the related factors and incidence of post-stroke depression (PSD). A total of 465 stroke patients were evaluated by a self-designed questionnaire, Self-Rating Depression Scale (SDS) and Hamilton Depression Rating Scale (HAMD). The neurologic deficit score was tested using the National Institute of Health stroke scale (NIHSS). A multiple factor analysis with the logistic regression method was carried out to analyze related factors of PSD. A total of 146 cases (31.4%) were identified as suffering from PSD. In addition the stepwise regression analysis showed that important risk factors of PSD included of sex, lesion location, the course of post-stroke and degree of neurological deficit score (all P<0.05). Above mentioned factors about the patients of PSD are very significant and may provide reference for further treating.

The psychometric properties of the Chinese version of the Conditions of Work Effectiveness Questionnaire-II.

AIMS: The present study was conducted to evaluate the psychometric properties of a newly adapted Chinese version of an instrument designed to measure structural empowerment among staff nurses. BACKGROUND: Structural empowerment has been shown to be important to nurses in Western cultures, but its importance in China is unknown. METHODS: A convenience sample of 650 staff nurses was selected from six hospitals in Harbin, China. After linguistic adaptation using the forward-backward translation method, the 19-item Conditions of Work Effectiveness Questionnaire-II (CWEQ-II-CV) was answered by participants. Content validity, Cronbach's alpha, item-to-total correlation and exploratory factor analysis were used to assess the reliability and validity of the translated instrument. RESULTS: In the factor analysis, a six-factor solution was found to be reasonable with the sub-dimensions of structural empowerment that included support (three items), resources (three items), information (three items), opportunity (three items), formal power (three items) and informal power (four items). Cronbach's alpha coefficient for the total instrument was 0.92 and ranged from 0.68 to 0.86 in the six subscales. The item-to-total correlation coefficients ranged from 0.48 to 0.80. The findings also gave support for content validity. CONCLUSIONS: Evidence was found to support the reliability and validity of the CWEQ-II-CV scale that measures the quality of the work environment for nurses from a structural empowerment perspective. IMPLICATIONS FOR NURSING MANAGEMENT: The translated version of CWEQ-II-CV can provide an effective evaluation tool for structural empowerment in the Chinese nursing workplace.

The impact of whole-body vibration training and proprioceptive neuromuscular facilitation on biomechanical characteristics of lower extremity during cutting movement in individuals with functional ankle instability: A parallel-group study.

BACKGROUND: We compared the effects of whole-body vibration training and proprioceptive neuromuscular facilitation on the biomechanical characteristics of the lower limbs in functional ankle instability patients during cutting movement to ascertain the superior rehabilitation method. METHODS: Twenty-two male College students with unilateral functional ankle instability volunteered for this study and were randomly divided into whole-body vibration training group and proprioceptive neuromuscular facilitation group. Kinematics data and ground reaction forces were collected using infrared motion capture system and 3-D force plates synchronously during cutting. Repeated measures two-way ANOVA was performed to analyze the data. FINDINGS: Both training methods reduced the maximum hip abduction angle (p = 0.010, effect size: proprioceptive neuromuscular facilitation = 0.69; whole-body vibration training = 0.20), maximum knee flexion angle (p = 0.008, effect size: proprioceptive neuromuscular facilitation = 0.39, whole-body vibration training = 1.26) and angular velocity (p = 0.014, effect size: proprioceptive neuromuscular facilitation = 0.62, whole-body vibration training = 0.55), maximum ankle inversion angular velocity (p = 0.020, effect size: proprioceptive neuromuscular facilitation = 0.52, whole-body vibration training = 0.81), and knee flexion angle at the time of maximum vertical ground reaction forces (p = 0.018, effect size: proprioceptive neuromuscular facilitation = 0.27, whole-body vibration training = 0.76), and increased the maximum ankle dorsiflexion moment (p = 0.049, effect size: proprioceptive neuromuscular facilitation = -0.52, whole-body vibration training = -0.22). Whole-body vibration training reduced the maximum ground reaction forces value in the mediolateral directions (p = 0.010, effect size = 0.82) during cutting movement. INTERPRETATION: These findings suggested that the two types of training might increase neuromuscular conduction function around the ankle. After these two types of training, functional ankle instability patients showed a similar risk of injury to the lateral ankle ligaments during cutting.

Tetramerization of pyruvate kinase M2 attenuates graft-versus-host disease by inhibition of Th1 and Th17 differentiation.

Lethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the activation of NF-κB pathway and decreased the inflammation level of GVHD mice. PKM2 tetramerization blocked Th1 and Th17 cell differentiation and secretion of pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-17). Meanwhile, differentiation of Treg cells and IL-10 secretion were promoted by tetramerized PKM2. These findings demonstrated that PKM2 enhanced the augment of Th1 and Th17 cells to accelerate the progression of GVHD, and allosteric activation of PKM2 targeted Th1 and Th17 cells attenuated GVHD. Furthermore, we also confirmed that TEPP-46 administration did not compromise GVL activity and resulted in slightly improvement of leukemia-free survive. Thus, targeting Th1 and Th17 cell response with PKM2 allosteric activator may be a promising therapeutic strategy for GVHD prevention while preserving the GVL activity in patients receiving Allo-HSCT.

Epidemiology and Azole Resistance of Clinical Isolates of Aspergillus fumigatus from a Large Tertiary Hospital in Ningxia, China.

Purpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023. Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms. Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region. Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.

Acute effects of Kinesio Taping on lower-limb coordination of gait in hemiplegic patients.

BACKGROUND: Kinesio taping can effectively strengthen weakened muscles, increase walking speed, and improve dynamic balance in hemiplegic patients, but its effect on lower-limb coordination is not clear. Improving lower-limb coordination in hemiplegic patients can decrease risk of fall during walking. RESEARCH QUESTION: This study utilized continuous relative phase to depict the pattern and variability of lower-limb coordination in hemiplegic patients and healthy subjects during walking, and investigate whether it has the acute effect of Kinesio Taping on lower-limb coordination in hemiplegic patients during walking. METHODS: Gait was measured by a three-dimensional motion capture system for 29 hemiplegic patients (KT group) and 15 healthy subjects (control group). Mean continuous relative phase (MCRP) and mean continuous relative phase variability (MCRPV) were calculated to describe and evaluate lower-limb coordination. RESULTS: KT intervention only changed the coordination between the bilateral ankle joints in hemiplegic patients. Before the intervention, the MCRP of the two ankles (AA-MCRP) in the stance period of the control group was greater than the KT group (P < 0.001), the MCRPV of the two ankles (AA-MCRPV) in the swing period was lower than that in KT group (P < 0.001). After the intervention, the AA-MCRP in the stance period of the KT group increased (P < 0.001), the AA-MRPV in the swing period of KT group significantly decreased (P = 0.001). SIGNIFICANCE: Immediate ankle KT intervention can result in the in-phase or anti-phase coordination between the two ankles developing to out-of-phase coordination during the stance period of the affected limb during walking, and increase the stability of the out-of-phase coordination between the two ankles during the swing period of the affected limb. KT can be used in rehabilitation treatment for hemiplegic patients to improve acute coordination between the patients' ankles.

Sodium butyrate (SB) ameliorated inflammation of COPD induced by cigarette smoke through activating the GPR43 to inhibit NF-κB/MAPKs signaling pathways.

Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1ß, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.

METTL16 promotes translation and lung tumorigenesis by sequestering cytoplasmic eIF4E2.

N6-methyladenosine (m6A) plays crucial roles in regulating RNA metabolisms. METTL16 identified as a single-component methyltransferase catalyzes m6A formation in the nucleus; whether it regulates cytoplasmic RNA fate remains unknown. Here, we detected the dual localization of METTL16 in the nucleus and cytoplasm. METTL16 depletion attenuates protein synthesis, but the methyltransferase activity is not required for its translation-promoting function. Mechanistically, we identified an interactor of METTL16, eIF4E2, which represses translation by acting as a competitor of eIF4E. The METTL16-eIF4E2 interaction impedes the recruitment of eIF4E2 to 5' cap structure, promoting the cap recognition by eIF4E and selective protein synthesis. Depletion of METTL16 suppresses lung tumorigenesis by downregulating the translation of key oncogenes. Collectively, our study reports a role of METTL16 in modulating translation and provides a therapeutic target for lung cancer treatment.