DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.

Maintaining stability of the genome requires dedicated DNA repair and signalling processes that are essential for the faithful duplication and propagation of chromosomes. These DNA damage response (DDR) mechanisms counteract the potentially mutagenic impact of daily genotoxic stresses from both exogenous and endogenous sources. Inherent to these DNA repair pathways is the activity of protein factors that instigate repair processes in response to DNA lesions. The regulation, coordination, and orchestration of these DDR factors is carried out, in a large part, by post-translational modifications, such as phosphorylation, ubiquitylation, and modification with ubiquitin-like proteins (UBLs). The importance of ubiquitylation and UBLylation with SUMO in DNA repair is well established, with the modified targets and downstream signalling consequences relatively well characterised. However, the role of dedicated erasers for ubiquitin and UBLs, known as deubiquitylases (DUBs) and ubiquitin-like proteases (ULPs) respectively, in genome stability is less well established, particularly for emerging UBLs such as ISG15 and UFM1. In this review, we provide an overview of the known regulatory roles and mechanisms of DUBs and ULPs involved in genome stability pathways. Expanding our understanding of the molecular agents and mechanisms underlying the removal of ubiquitin and UBL modifications will be fundamental for progressing our knowledge of the DDR and likely provide new therapeutic avenues for relevant human diseases, such as cancer.

Environmental effects and their impact on yield in adjacent experimental plots of high-stem and short-stem wheat varieties.

BACKGROUND: In regional wheat trials, when short-stem wheat varieties and high-stem wheat varieties are planted adjacent to each other in small plots, changes in their marginal plot environment can lead to bias in yield evaluation. Currently, there is no relevant research revealing the degree of their mutual influence. RESULTS: In a regional wheat experiment, when high-stem wheat varieties and short-stem wheat varieties were planted adjacent to one another, there was no significant change in soil temperature or humidity in the high-stem wheat variety experimental plot from November to May compared to the control plot, while the soil humidity in the short-stem wheat variety experimental plot was greater than that in the control plot. In May, the soil temperature of the short-stem wheat varieties in the experimental plot was lower than that in the control plot. Illumination of the wheat canopy in the high-stem wheat variety experimental plot had a significant positive effect in April and May, while illumination of the wheat canopy in the short-stem wheat variety experimental plot had a negative effect. The chlorophyll fluorescence parameters of flag leaves in the high-stem wheat variety experimental plots showed an overall increasing trend, while the chlorophyll fluorescence parameters of flag leaves in the experimental plots of short-stem wheat varieties showed a decreasing trend. The analysis of the economic yield, biological yield, and yield factors in each experimental plot revealed that the marginal effects of the economic yield and 1000-grain weight were particularly significant and manifested as positive effects in the high-stem wheat variety experimental plot and as negative effects in the short-stem wheat variety experimental plot. The economic yield of the high-stem wheat variety experimental plot was significantly greater than that of the control plot, the economic yield of the short-stem wheat variety experimental plot was significantly lower than that of the control plot, and the economic yield of the high-stem experimental plot was significantly greater than that of the short-stem experimental plot. When the yield of the control plot of the high-stem wheat varieties was compared to that of the control plot of the short-stem wheat varieties, the yield of the control plot of the short-stem wheat varieties was significantly greater than that of the control plot of the high-stem wheat varieties. CONCLUSIONS: Based on these findings, it is concluded that plots with high-stem and short-stem wheat varieties are adjacent in regional wheat trials, the plots of high-stem wheat varieties are subject to marginal positive effects, resulting in a significant increase in economic yield; the plots of short-stem wheat varieties are subject to marginal negative effects, resulting in a decrease in economic yield. This study reveals the mutual influence mechanism of environment and yield with adjacent planting of high-stem and short-stem wheat varieties in regional wheat trials, providing a useful reference and guidance for optimizing the layout of regional wheat trials.

A Qualitative Study of the Care Experience of Mothers of Asthmatic Children from Low-Income Families.

Objectives: This study aimed to explore the experiences and caregiving perspectives of mothers from low-income families who have children with asthma,and to establish a foundation for the development of tailored nursing strategies specifically designed for families facing similar circumstances. Method: A descriptive qualitative research method was employed. Fifteen mothers of asthmatic children from low-income families receiving treatment at the Respiratory Centre of Chongqing Children's Hospital were purposefully sampled from June to December 2021. Semi-structured interviews were conducted to gather data on their caregiving experiences, and thematic analysis was utilized to analyze the interview data. Results: The interviewees were 27-42 years old (SD=32.3 years), 33.3% were full-time mothers(A woman who quit work, in order to focus on taking care of the child and the family ), 53.3% had one child, 46.6% had a college degree or higher, and 100% had health insurance. Through in-depth interviews, four main themes and eight sub-themes were identified, including (a) insufficient knowledge about the disease, (b) anxiety and uncertainty, (c) insufficient social support system, and (d) insufficient resources for medical services. The first theme describes a weak willingness to learn and medication discontinuation at will. The second theme describes financial burden and psychological stress, the third theme describes lack of family support and low social participation, and the fourth theme describes insufficient health insurance support and unequal distribution of healthcare resources. Conclusion: Mothers from low-income families with asthmatic children face substantial psychological burdens and familial pressures. It is crucial for healthcare professionals to actively engage with and deepen their understanding of these mothers' caregiving experiences and psychological well-being. By doing so, positive coping strategies can be developed, promoting the physical and mental health of these mothers and improving asthma control in their children.

A Strategy of On-Demand Immune Activation for Antifungal Treatment Using Near-Infrared Responsive Conjugated Polymer Nanoparticles.

Pathogenic fungal infection is a major clinical threat because pathogenic fungi have developed resistant mechanisms to evade the innate immune response, especially interactions with macrophages. Herein, a strategy to activate immune responses of macrophages to fungi based on near-infrared (NIR) responsive conjugated polymer nanoparticles (CPNs-M) is reported for antifungal immunotherapy. Under NIR light irradiation, CPNs-M exposes ß-glucan on the surface of fungal conidia by photothermal damage and drug released from CPNs-M. The exposed ß-glucan elicits macrophage recognition and subsequently activates calcium-calmodulin (Ca2+-CaM) signaling followed by the LC3-associated phagocytosis (LAP) pathway to kill fungal conidia. Consequently, a remarkable elimination of intracellular fugal conidia and successful treatment of fungal pneumonia are achieved. This remote regulation strategy to restore pathogen-immune cell interaction on demand provides a new insight into combatting intractable intracellular infections.

Quality of Life Among Older Adults With Frailty: A Structural Equation Modeling.

PURPOSE: Frailty is a complex age-related clinical condition among older adults. Quality of life (QOL) among older adults with frailty is an important topic of interest. The current cross-sectional study aimed to develop a structural equation model to identify factors affecting QOL. METHOD: A total of 180 older adults with frailty were recruited from general units in two hospitals in Fuzhou, China. Data were collected using the World Health Organization Quality of Life Brief Version, Pittsburgh Sleep Quality Index, Geriatric Depression Scale-15, and Simplified Coping Style Questionnaire. Structural equation modeling was used to analyze data. RESULTS: The final model exhibited a good fit. Poor sleep quality was associated with depression, passive coping style, and poor QOL. Depression was also associated with poor QOL. Passive coping style was associated with better QOL. CONCLUSION: This study demonstrated that sleep quality has direct and indirect effects on QOL of older adults with frailty through depression and passive coping style. Recommendations are that care providers pay attention to biological and physiological variables, symptom status, and functional status of older adults with frailty. This study also provides a theoretical basis for developing interventions that may lead to improvements in QOL among older adults with frailty. [Journal of Psychosocial Nursing and Mental Health Services, 62(5), 49-55.].

Challenges towards management of CARD9-deficient patients with phaeohyphomycosis: A case report and case series study.

BACKGROUND: A number of recalcitrant phaeohyphomycosis cases with a life-threatening prognosis have been observed in CARD9-deficient patients, but little is known about the long-term management strategies that are effective for such intractable individuals. OBJECTIVES: To study the genetic and immunological mechanisms underlying recalcitrant phaeohyphomycosis and to share our clinical experiences regarding its treatment. PATIENTS/METHODS: Ten CARD9-deficient patients with recalcitrant phaeohyphomycosis admitted to our centre in the past two decades were followed-up, and their clinical presentations, laboratory findings, treatment and prognoses were analysed; one of them was a novel case of recalcitrant phaeohyphomycosis harbouring CARD9 mutations. Innate and adaptive immunological responses of patient-derived peripheral blood mononuclear cells were evaluated using ELISA and flow cytometry. RESULTS: We identified a total of seven CARD9 mutations in the ten analysed patients. Moreover, patient-derived cells exhibited a significant impairment of innate and adaptive immune responses upon fungus-specific stimulation. All the patients experienced recurrence and exacerbation; four of them died, two exhibited continued disease progress with unsatisfactory therapeutic efficacy, three showed obvious improvement under maintenance therapy, and only one achieved a clinical cure. CONCLUSIONS: Our study highlighted that otherwise healthy patients diagnosed with early-onset, unexplained and recalcitrant phaeohyphomycosis should be analysed for CARD9 mutations and immune deficiency. Thereafter, the length and choice of management remain challengeable and must be adjusted based on the clinical presentations and responses of patients over their lifetimes. Although continued posaconazole treatment may be the promising first-line therapy at present, novel strategies are worth exploring.

Spatial and Temporal Distribution of Phenolic and Flavonoid Compounds in Sour Jujube (Ziziphus. Acidojujuba Cheng et Liu) and Their Antioxidant Activities.

In order to comprehensively analyze the antioxidant substances in sour jujube, total phenolic content (TPC) and total flavonoids contents (TFC) in different organs, including stem, leaf, flower, fruit pulp, and seed were analyzed for their contents and antioxidant activities. The results showed that leaves possessed significantly higher TPC and TFC (20.4 and 20.5 mg/g, respectively) than the other organs and have the highest antioxidant activity, which were also higher than the wild blueberry (A well-known for its high TPC). Subsequently, the variations in the antioxidant content and antioxidant activity of leaves were analyzed during leaf development. TPC in leaves sampled in may and august were significantly higher than that in other months, while the highest one was found in may. The n-hexane, ethyl acetate, n-butanol, and water fractions obtained from the main methanol extract of sour jujube leaves were evaluated for TPC and TFC and their antioxidant activity and it was found that ethyl acetate fraction displayed the highest TPC and TFC (184.5 and 193.3 mg/g, respectively), as well as the best antioxidant activity. In addition, using LC-MS and HPLC, ethyl acetate fraction was analyzed from qualitative and quantitative aspects; 31-one phenolic compounds, including catechin (33.0 mg/g), epigallocatechin (15.3 mg/g), quercetin 3-O-glucoside (11.4 mg/g), naringenin (6.7 mg/g), esculetin (4.8 mg/g), and chlorogenic acid (4.6 mg/g) were identified. Catechin, esculetin, epigallocatechin, chlorogenic acid, quercetin 3-O-glucoside, and naringenin exhibited high antioxidant activity. These results provide a theoretical basis for further study and utilization of flavonoid and polyphenols in sour jujube.

Transcriptomic and anatomic profiling reveal the germination process of different wheat varieties in response to waterlogging stress.

BACKGROUND: Waterlogging is one of the most serious abiotic stresses affecting wheat-growing regions in China. Considerable differences in waterlogging tolerance have been found among different wheat varieties, and the mechanisms governing the waterlogging tolerance of wheat seeds during germination have not been elucidated. RESULTS: The results showed no significant difference between the germination rate of 'Bainong 207' (BN207) (after 72 h of waterlogging treatment) and that of the control seeds. However, the degree of emulsification and the degradation rate of endosperm cells under waterlogging stress were higher than those obtained with the control treatment, and the number of amyloplasts in the endosperm was significantly reduced by waterlogging. Transcriptomic data were obtained from seed samples (a total of 18 samples) of three wheat varieties, 'Zhoumai 22' (ZM22), BN207 and 'Bainong 607' (BN607), subjected to the waterlogging and control treatments. A comprehensive analysis identified a total of 2775 differentially expressed genes (DEGs). In addition, an analysis of the correlations among the expression difference levels of DEGs and the seed germination rates of the three wheat varieties under waterlogging stress revealed that the relative expression levels of 563 and 398 genes were positively and negatively correlated with the germination rate of the wheat seeds, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the difference in the waterlogging tolerance among the three wheat varieties was related to the abundance of key genes involved in the glycolysis pathway, the starch and sucrose metabolism pathway, and the lactose metabolism pathway. The alcohol dehydrogenase (ADH) gene in the endosperm of BN607 was induced immediately after short-term waterlogging, and the energy provided by the glycolysis pathway enabled the BN607 seeds to germinate as early as possible; in addition, the expression of the AP2/ERF transcription factor was upregulated to further enhance the waterlogging tolerance of this cultivar. CONCLUSIONS: Taken together, the results of this study help elucidate the mechanisms through which different wheat varieties respond to waterlogging stress during germination.

Influence of patient and hospital characteristics on inpatient satisfaction in China's tertiary hospitals: A cross-sectional study.

BACKGROUND: Patient satisfaction has been seen as a key criterion when evaluating hospitals and is one of the main focuses of the current health-care reform in China. This paper aimed to explore patient- and hospital-level factors associated with inpatient satisfaction, which can provide policy implications for the evaluation and development of a patient-oriented health-care system. METHODS: The paper analyses data from the 2017 China National Patient Survey which includes 20 300 inpatients from 131 tertiary hospitals across 31 provinces. Descriptive analysis and multivariable logistic regressions are conducted to identify key factors related to satisfaction. RESULTS: Patient sociodemographic characteristics, including gender, age, income and insurance type, are found to be strongly associated with their satisfaction of inpatient experience. In terms of institutional characteristics, hospital type, size, staffing and financial performance are also significantly correlated with inpatient satisfaction. Patients are more satisfied with specialist hospitals and large hospitals measured by the number of beds and surgeries. Hospitals with higher nurse-to-bed ratio also receive more satisfaction. The financial performance of hospitals, however, is negatively associated with satisfaction. CONCLUSION: Patient satisfaction contains unique information on service quality and thus should be incorporated into the matrix of hospital evaluation. Meanwhile, differences in patient composition must be adjusted to make fair comparisons across hospitals. Moreover, future reform needs to put greater efforts in the design of comprehensive public insurance scheme, efficient hospital structure and an overall well-functioning health-care delivery system in order to better serve patients in China.

Malignant transformation of craniofacial fibrous dysplasia: a systematic review of overall survival.

The incidence of malignant transformation of fibrous dysplasia (FD) is very rare. Thus, the available knowledge of its characteristics, management, and survival is scarce. Here, we present a systemic review of fibrous dysplasia that had undergone malignant transformation. A comprehensive search was performed on PubMed electronic database. The survival rates and hazard ratios of age, gender, past history of previous radiotherapy, type of FD, and treatment were collected from the published articles and analyzed. Forty-eight cases were eligible for inclusion in the study. Patient's age, gender, past history radiotherapy, and type of FD did not influence the overall survival (OS). The Kaplan Meier analysis showed that the patients who had not received any treatment had poor prognosis with a median survival of 4 months. The patients that received surgery had significantly longer OS than that in the biopsy group. The prognosis of malignant transformation of FD is relatively poor, and surgery is the optimal treatment of choice. Nevertheless, the efficacy of postoperative adjuvant therapy to patient OS is still undefined.

Frailty as a predictor of future falls in hospitalized patients: A systematic review and meta-analysis.

The aims of this review were to identify prospective studies examining associations between frailty and falls and to combine the risk measures to synthesize pooled evidence on frailty as a predictor of falls. A systematic literature search was conducted through Embase, Scopus, PubMed, CINAHL Plus, and the Cochrane Library for studies published from inception through May 2018. Odds ratios (OR) and hazard ratios (HR) extracted from the studies were combined to synthesize pooled effect measures using random-effects or fixed-effects models. Six studies involving 3881 hospitalized patients were included in this study. Frailty was found to be significantly associated with future falls among three studies with OR (pooled OR = 1.323, 95%confidence interval = 1.137-1.538, P < 0.000) and three studies with HR (pooled OR = 1.890, 95%confidence interval = 1.456-2.453, P < 0.000). Frailty was a significant predictor of future falls in hospitalized patients. Paying more attention to frailty may lead to lowering fall risks.

Effects of anti-Helicobacter pylori concomitant therapy and probiotic supplementation on the throat and gut microbiota in humans.

The microbiota within humans maintains homeostasis and plays important roles in human health. However, some situations such as the use of antibiotics may disrupt the microbiota balance and result in a series of adverse effects. This study aimed to investigate the effects of a commonly used anti-Helicobacter pylori concomitant therapy on the composition of the gut and throat microbiota and any antibiotic resistance that may develop. In addition to the standard regimen, two different supplementary probiotic regimens that both used Saccharomyces boulardii were included. Microbiological culture-based techniques were used to analyse the microbiota composition and antibiotic resistance. Our results showed marked quantitative and qualitative alterations in both the gut and throat microbiota after treatment with not only the standard concomitant therapy but also with either supplementary probiotic regimen. Nevertheless, most of the changes in the gut microbiota (except for yeast and Bacteroides spp. counts) reverted by Day 71, whereas the alterations in the throat microbiota appeared to persist. Patients treated with the eradication therapy in the absence of probiotic supplementation experienced the most pronounced disturbances in the throat microbiota, whereas changes in the throat microbiota appeared to stabilize in the groups that received probiotic supplementation. We also detected higher antibiotic resistance rates for Enterobacteriaceae, Enterococcus spp. and Bacteroides spp. after treatment with the eradication therapy. Co-administration of probiotics is likely to be more effective than post-antibiotic supplementation, and although some beneficial effects were observed, the probiotic combination did not exert significant effects on the unbalanced commensal gut and throat microbiota composition.

A study of baseline data from SPRINT: Exploring lipid profile changes in middle-aged and elderly patients.

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.

Prevalence of Frailty and Associated Factors Among Hospitalized Older Adults: A Cross-Sectional Study.

This study aimed to estimate the prevalence of frailty and associated factors among hospitalized older adults. It consisted of 184 hospitalized older adults recruited between October 2019 to January 2020. We used the FRAIL scale, Geriatric Depression Scale-15, and the Pittsburg Sleep Quality Index to collect data. Descriptive statistics, independent group t-test, Chi-square (χ2) tests, and logistic regression were applied to statistical analysis. It found that the prevalence of frailty among hospitalized older adults was 39.7%. Depression (Mild: OR = 5.312, 95% CI [2.384-11.833]; Moderate: OR = 6.630, 95% CI [2.077-21.160]) and low activities of daily living (ADL) (Slight dependence: OR = 5.667, 95% CI [1.308-24.557]; Moderate dependence: OR = 15.188, 95% CI [3.342-69.016]; Severe dependence: OR = 5.872, 95% CI [2.645-13.038]) were independent predictors of frailty. Future studies on the interventions to reduce depression, improve ADL and delay the progression of frailty are encouraged. We should focus more on ADL, emotional and psychological state of hospitalized older adults to prevent frailty.

Occurrence, vertical distribution and transport of organic amine pesticides in the seawater from the East China Sea and the South China Sea.

Organic amine pesticides (OAPs) are widely used as insecticides, fungicides and herbicides in agricultural production. China is a large agricultural country, and the sprayed pesticides may impact the fragile marine environment through surface runoff. This study revealed the pollution characteristics of thirty-three OAPs in the East China Sea (ECS) and the South China Sea (SCS) and investigated their vertical variations in water columns. The ∑OAPs ranged from below method detection limits to 3.4 ng/ L, with an average value of 0.93 ng/ L. Diphenylamine and beflubutamid were the two most abundant compounds, contributing 64 % and 14 % of the ∑OAPs, respectively. The ∑OAPs in the ECS were significantly (M-W U test, p < 0.01) higher than that in the SCS, and OAPs exhibited different composition profiles. Diphenylamine was the most abundant compound in the ECS, while beflubutamid was dominant in the SCS, which may be related to industrial production (such as rubber synthesis) and agricultural activities. In the water columns, OAPs concentrations were higher in deep layers compared to that in surface seawater, which may be due to weak light and low temperature reducing the degradation of pesticides, indicating the deep ocean is a sink for OAPs. Under the dilution of seawater, the concentrations of OAPs decreased from the Pearl River Estuary to the open sea, and the South China Sea Warm Current also caused the decrease of OAPs from south to north. A preliminary risk assessment indicated that OAPs in the water pose no significant risk to aquatic organisms.

Optimization of Mopan Persimmon Wine Fermentation with Pectinase and Analysis of Its Mechanism of Action.

Due to the high sugar content of Mopan persimmon, which has an annual output of more than 0.5 million tons in China, it can be processed to make fruit wine. In this study, a strain of yeast screened from different persimmon samples was used for persimmon wine fermentation. The optimal conditions of persimmon wine fermentation were determined through single-factor experiments as follows: Yeast addition of 0.08 g/kg; a fermentation temperature of 28 °C; sucrose addition of 18%; and pectinase addition of 0.01%. Under these conditions, the alcohol content of persimmon wine reached 12.9%. The addition of pectinase during persimmon wine fermentation was found to decompose pectin at high speed, reduce the viscosity of the fermentation liquid, increase the dissolved oxygen content in the fermentation liquid, promote the growth and reproduction of yeast, and effectively convert the sugars into alcohol. After fermentation, alcohol, residual sugars, and total phenolic content with or without pectinase treatment were 12.9 and 4.4%, 2.2 and 13.4 g/L, and 738.7 and 302 µg/mL, respectively. Scanning electron microscopy (SEM) results showed that compared with the mash without pectinase treatment, the mash with pectinase had a larger network structure and more pores and yeasts.

To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology.

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology. The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language. In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The "component-target" network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer. Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.