Bortezomib restrains M2 polarization and reduces CXCL16-associated CXCR6+CD4 T cell chemotaxis in bleomycin-induced pulmonary fibrosis.

BACKGROUND: The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. METHODS: A model of bleomycin-induced pulmonary fibrosis was established, followed by treatment with bortezomib. Tissue samples were collected for analysis of immune cell subsets and functional assessment by flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors, as well as the characteristics of cell populations. RESULTS: Here, we observed that the expression of CXCL16 and CXCR6 was elevated in the lung tissue of a pulmonary fibrosis model. In the context of pulmonary fibrosis or TGF-ß1 stimulation in vitro, macrophages exhibited an M2-polarized phenotype and secreted more CXCL16 than those of the control group. Moreover, flow cytometry revealed increased expression levels of CD69 and CXCR6 in pulmonary CD4 T cells during fibrosis progression. The administration of bortezomib alleviated bleomycin-induced pulmonary fibrosis, accompanied by reduced ratio of M2-polarized macrophages and decreased accumulation of CD4 T cells expressing CXCR6. CONCLUSIONS: Our findings provide insights into the key immune players involved in bleomycin-induced pulmonary fibrosis and offer preclinical evidence supporting the repurposing strategy and combination approaches to reduce lung fibrosis.

The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, the etiology of which involves the alterations in circulating cytokine levels. However, the cause-and-effect relationships and in-depth clinical relevance of them remain to be systematically investigated. We conducted a two-sample Mendelian randomization (MR) study to assess the causality of circulating cytokine levels and SLE and found that genetically determined elevated CTACK and IL-18 were associated with an increased risk of SLE, whereas a higher level of GRO-a was associated with decreased risk. Furthermore, we performed an observational study to further reveal the association between 27 cytokines and the severity measured by SLEDAI score, as well as lupus nephritis (LN), of SLE. We identified six cytokines (MCP1, MIP1ß, CTACK, IP10, HGF, IL18, IL13) that were identified as associated with the clinical severity of SLE, and five cytokines, especially IL18, were related with LN and may have good diagnostic value. Moreover, we also predicted four compounds that might have good binding activities with IL18. The evidence supported a potential causal role of circulating cytokines on the risk of SLE. Targeting IL18 might be a meaningful strategy for the prevention or treatment of SLE, especially in LN patients.

Discovery and Heterologous Expression of Trilenodin, an Antimicrobial Lasso Peptide with a Unique Tri-isoleucine Motif.

Lasso peptides are an increasingly relevant class of peptide natural products with diverse biological activities, intriguing physical properties, and unique chemical structures. Most characterized lasso peptides have been from Actinobacteria and Proteobacteria, despite bioinformatic analyses suggesting that other bacterial taxa, particularly those from Firmicutes, are rich in biosynthetic gene clusters (BGCs) encoding lasso peptides. Herein, we report the bioinformatic identification of a lasso peptide BGC from Paenibacillus taiwanensis DSM18679 which we termed pats. We used a bioinformatics-guided isolation approach and high-resolution tandem mass spectrometry (HRMS/MS) to isolate and subsequently characterize a new lasso peptide produced from the pats BGC, which we named trilenodin, after the tri-isoleucine motif present in its primary sequence. This tri-isoleucine motif is unique among currently characterized lasso peptides. We confirmed the connection between the pats BGC and trilenodin production by establishing the first Bacillus subtilis 168-based heterologous expression system for expressing Firmicutes lasso peptides. We finally determined that trilenodin exhibits potent antimicrobial activity against B. subtilis and Klebsiella pneumoniae, making trilenodin the first characterized biologically active lasso peptide from Firmicutes. Collectively, we demonstrate that bacteria from Firmicutes can serve as high-potential sources of chemically and biologically diverse lasso peptides.

Structure and Functions of Endophytic Bacterial Communities Associated with Sphagnum Mosses and Their Drivers in Two Different Nutrient Types of Peatlands.

Sphagnum mosses are keystone plant species in the peatland ecosystems that play a crucial role in the formation of peat, which shelters a broad diversity of endophytic bacteria with important ecological functions. In particular, methanotrophic and nitrogen-fixing endophytic bacteria benefit Sphagnum moss hosts by providing both carbon and nitrogen. However, the composition and abundance of endophytic bacteria from different species of Sphagnum moss in peatlands of different nutrient statuses and their drivers remain unclear. This study used 16S rRNA gene amplicon sequencing to examine endophytic bacterial communities in Sphagnum mosses and measured the activity of methanotrophic microbial by the 13C-CH4 oxidation rate. According to the results, the endophytic bacterial community structure varied among Sphagnum moss species and Sphagnum capillifolium had the highest endophytic bacterial alpha diversity. Moreover, chlorophyll, phenol oxidase, carbon contents, and water retention capacity strongly shaped the communities of endophytic bacteria. Finally, Sphagnum palustre in Hani (SP) had a higher methane oxidation rate than S. palustre in Taishanmiao. This result is associated with the higher average relative abundance of Methyloferula an obligate methanotroph in SP. In summary, this work highlights the effects of Sphagnum moss characteristics on the endophytic bacteriome. The endophytic bacteriome is important for Sphagnum moss productivity, as well as for carbon and nitrogen cycles in Sphagnum moss peatlands.

Ultrasonic Non-Destructive Testing and Evaluation of Stainless-Steel Resistance Spot Welding Based on Spiral C-Scan Technique.

In order to achieve the non-destructive testing and quality evaluation of stainless-steel resistance spot welding (RSW) joints, a portable ultrasonic spiral C-scan testing instrument was developed based on the principle of ultrasonic pulse reflection. A mathematical model for the quality evaluation of RSW joints was established, and the centroid of the ultrasonic C-scan image in the nugget zone of the RSW was determined based on the principle of static moment. The longest and shortest axes passing through the centroid in the image were extracted, and the ratio of the longest axis to the shortest axis (RLS) factor and the average of axis (AOA) factor were calculated, respectively, to evaluate the quality of the joint. To study the effectiveness of the detection results, tensile tests, and stereo analysis were conducted on the solder joints after sampling. The results indicate that this detection method can realize online detection and significantly improve the detection efficiency; the detection value of internal defect size is close to the true value with an error of 0.1 mm; the combination of RLS and AOA factors can be used to evaluate the mechanical properties of RSW joints. This technology can be used to solve the NDT, evaluate problems of RSW joints, and realize engineering applications.

Barriers and facilitators to offering post-intensive care follow-up services from the perspective of critical care professionals: A qualitative study.

BACKGROUND: Various programmes and models for post-intensive care unit (ICU) follow-up services have been developed worldwide. In China, post-ICU follow-up remains in the exploratory stage and little is known regarding the appropriate form and challenges of implementation, which need to be further explored. AIM: This study aimed to explore and describe the barriers to and facilitators of post-ICU follow-up services from the perspective of critical care professionals. DESIGN: This was a descriptive qualitative study. Semi-structured interviews were conducted with 21 health care workers whose units had offered ICU survivors different forms of follow-up services; the data were analysed by qualitative content analysis during August 2022 and December 2022. SETTING: The study was conducted at 14 ICUs in 11 tertiary hospitals in Shanghai, China. FINDINGS: Seventeen subthemes were extracted as barriers and facilitators in the follow-up of ICU survivors. In the initiating process, the barriers included the restriction of decision-making rights and scope of practice, indifferent attitude towards survivors and repeated work. The facilitators included admitted significance, the needs of ICU survivors, the conscientiousness of professionals and the pioneers and leadership support. In the implementation process, lack of confidence, lack of cooperation in medical consortium, distrusted relationships, restrictions of medical insurance, ageing problems and insufficient human resources acted as barriers, whereas lessons learned, positive feedback and digital support served as facilitators. Furthermore, recommendations and tips were identified for offering follow-up services. CONCLUSION: Medical personnel can better utilize available resources and develop strategies to overcome constraints by gaining insights into the abovementioned barriers and facilitators. The findings of this study can provide a useful reference for structured and systematic follow-ups to ameliorate post-intensive care syndrome in low- and middle-income countries. RELEVANCE TO CLINICAL PRACTICE: Publicity and educational measures play a crucial role in enhancing the awareness of survivors and the consensus of health care professionals from medical consortium regarding impairments after critical care. Leadership and policy support can address numerous obstacles to guiding follow-up services.

Investigation on the construction of teaching case base in medical genetics.

Medical genetics is a basic medical course that discusses the diagnosis, prevention and treatment of diseases in relation with genetic factors. This course requires students who have abilities of strong logical thinking, independent thinking, problem analyzing and solving. Single "cramming" teaching is difficult to mobilize students' autonomous learning, and hardly achieves teaching effect of medical genetics. Teaching of case-based discussion breaks passive teaching mode in traditional class. The teacher throws out typically clinical cases. The students prepare materials around relevant problems of cases, and carry out class discussion. Then, key and difficult points of the course are integrated in teaching and learning interaction, which reaches a remarkable effect of teaching. Since 2013, the teaching and research group has carried out teaching of case-based discussion in undergraduates majoring in clinical medicine. In this paper, we screen and sort clinical cases on the basis of course teaching plan and case-based discussion in the teaching of medical genetics. The cases are summarized into 8 chapters in teaching case base, which basically cover the teaching of disease genetics and clinical genetics.The construction of teaching case base in medical genetics has realized the deep integration of clinical cases and teaching. Students can understand and master important and difficult points of teaching in a more intuitive way, which is helpful to stimulate students' innovative thinking, improve students' learning interest and class participation.

Strophioblachins A-K, Structurally Intriguing Diterpenoids from Strophioblachia fimbricalyx with Potential Anticardiac Hypertrophic Inhibitory Activity.

Three new rearranged diterpenoids, strophioblachins A-C (1-3), eight new diterpenoids, strophioblachins D-K (4-11), and seven previously described diterpenoids (12-18) were purified from the aerial parts of Strophioblachia fimbricalyx. Compounds 1 and 2 contain a rare 6/6/5/6 ring system, while 3 has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1-11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11 and 9. The absolute configurations of compounds 1, 3, and 10 were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10 and 15 dose-dependently lowered the mRNA expression of Nppa and Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10 and 15 lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10 and 15 were only very weakly active in the range.

Improved equations to estimate GFR in Chinese children with chronic kidney disease.

BACKGROUND: There is currently no specific equation for estimating glomerular filtration rate (GFR) in Chinese children with chronic kidney disease (CKD). The commonly used equations are less robust than expected; we therefore sought to derive more appropriate equations for GFR estimation. METHODS: A total of 751 Chinese children with CKD were divided into 2 groups, training group (n = 501) and validation group (n = 250). In the training group, a univariate linear regression model was used to calculate predictability of variables associated with GFR. Residuals were compared to determine multivariate predictability of GFR in the equation. Standard regression techniques for Gaussian data were used to determine coefficients of GFR-estimating equations after logarithmic transformation of measured GFR (iGFR), height/serum creatinine (height/Scr), cystatin C, blood urea nitrogen (BUN), and height. These were compared with other well-known equations using the validation group. RESULTS: Median 99mTc-DTPA GFR was 90.1 (interquartile range: 67.3-108.6) mL/min/1.73 m2 in training dataset. Our CKD equation, eGFR (mL/min/1.73 m2) = 91.021 [height(m)/Scr(mg/dL)/2.7]0.443 [1.2/Cystatin C(mg/L)]0.335 [13.7/BUN (mg/dL)]-0.095 [ 0.991male] [height(m)/1.4]0.275, was derived. This was further tested in the validation group, with percentages of eGFR values within 30% and 15% of iGFR (P30 and P15) of 76.00% and 48.40%, respectively. For centres with no access to cystatin C, a creatinine-based equation, eGFR (mL/min/1.73 m2) = 89.674 [height(m)/Scr(mg/dL)/2.7]0.579 [ 1.007male] [height(m)/1.4]0.187, was derived, with P30 and P15 73.60% and 49.20%, respectively. These were significantly higher compared to other well-known equations (p < 0.05). CONCLUSION: We developed equations for GFR estimation in Chinese children with CKD based on Scr, BUN and cystatin C. These are more accurate than commonly used equations in this population.

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A.

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H2O2). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H2O2 or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline-Fe2+ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H2O2, superoxide anion (O2-·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H2O2 or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage.

Exploration of the Adsorption Kinetics of Surfactants at the Water-Oil Interface via Grand-Canonical Molecular Dynamics Simulations.

It is well-known that surfactants tend to aggregate into clusters or micelles in aqueous solutions due to their special structures, and it is difficult for the surfactant molecules involved in the aggregation to move spontaneously to the oil-water interface. In this article, we developed a new grand-canonical molecular dynamics (GCMD) model to predict the saturated adsorption amount of surfactant with constant concentration of surfactant molecules in the bulk phase, which can prevent surfactants aggregating in the bulk phase and get the atomic details of the interfacial structural change with increase of the adsorption amount through a single GCMD run. The adsorption of anionic surfactant sodium dodecyl sulfate (SDS) at the heptane-water interface was studied to validate the model. The saturated adsorption amount obtained from the GCMD simulation is consistent with the experimental results. The adsorption kinetics of SDS molecules during the simulation can be divided into three stages: linear adsorption stage, transition adsorption stage, and dynamic equilibrium stage. We also carried out equilibrium molecular dynamics (EMD) simulations to compare with GCMD simulation. This GCMD model can effectively reduce the simulation time with correct prediction of the interfacial saturation adsorption. We believe the GCMD method could be especially helpful for the computational study of surfactant adsorption under complex environments or emulsion systems with the adsorption of multiple types of surfactants.

Pseudo Polyampholytes with Sensitively Ion-Responsive Conformational Transition Based on Positively Charged Host-Guest Complexes.

Biological polyampholytes are ubiquitous in living organisms with primary functions including serving as transporters for moving chemical molecular species across the cell membranes. Synthetic amphoteric macromolecules that can change their phase states depending on the environment to simulate some properties of natural polyampholytes are of great interest. Here, the implementation of synthetic pseudo polymeric ampholytes is explored with ion-recognition-triggered conformational change. The phase transition behaviors of the ion-recognition-creative polyampholytes that contain deprotonated carboxylic acid groups as negative charges and 18-crown-6 units for forming positively charged host-guest complexes are systematically investigated. The ion-recognition-triggered phase transition behaviors of pseudo polyampholytes significantly depend on cation species and concentrations. Only those specific ions such as K+ , Ba2+ , Sr2+ and Pb2+ ions that can form 1:1 host-guest complexes with 18-crown-6 units in polymers enable control over conformational change like that of traditional pH-dependent polyampholytes. By regulating the content of carboxylic acid groups to match the content of ion-recognized positive charges provided by the host-guest complexes, the pseudo polyampholytes are more sensitive to the recognizable cations. Such ion-recognition-triggered amphoteric characteristics make the pseudo polyampholytes act like biological proteins, nucleic acids, and enzymes as molecular transporters, genetic code storage, and biocatalysts in artificial systems.

Influence of Nutritional Status on Prognosis of Stroke Patients With Dysphagia.

Context: Stroke is an acute cerebrovascular disease and a neurological disorder that occurs due to a cerebral arterial embolism and rupture. Acute stroke is often accompanied by dysphagia, which reduces patients' intake of food and nutrients, decreases their nutritional status, and affects their quality of life. Objective: The study intended to identify the demographic and clinical characteristics of stroke patients with dysphagia and to explore the relationship of those characteristics to nutritional status and prognosis. Methods: The research team retrospectively collected the clinical data of patients to compare the nutritional status and prognoses of patients with different demographic and clinical characteristics. Setting: The study took place in the Department of Neurology at the First People's Hospital of Shenyang in Shenyang, China. Participants: Participants were 789 stroke patients with dysphagia who had been admitted to the general ward of the neurology departments of hospitals of Grade 3 or higher in Northeast China between January 2019 and September 2020. Based on the results of the Nutrition Risk Screening (NRS-2002) and Subjective Global Assessment (SGA) scales at baseline, participants were enrolled in this study. Outcome Measures: The outcomes were the correlations between participants' demographic and clinical characteristics and their nutritional statuses and prognoses. The Modified Rankin Scale (mRS) was used to evaluate the prognosis of the patients at seven days and three months after participants' enrollment in the study. Using the SPSS 26.0, a t test, chi-square test, and F test were performed to analyze and verify the presence of fundamental differences in baseline characteristics between participants with good nutrition and those with poor nutrition. Also, a statistical correlation analysis was performed. Results: The study showed that participants with different nutritional levels had statistically significant differences in the presence or absence of infections and body temperature and scores on the Standardized Swallowing Assessment (SSA) and National Institutes of Health Stroke Scale (NIHSS), with all P < .001. At baseline seven days after enrollment, the prognoses of participants were significantly different for different previous histories of stroke (P < .001), family history of stroke (P = .005), presence or absence of infections (P < .001), body temperature (P < .001), and SSA (P < .001) and NIHSS (P < .001) scale scores. At three months after enrollment, the prognoses of participants were significantly different for previous history of stroke (P = .003), different body temperatures (P < .001), presence or absence of infections(P < .001), and SSA (P < .001) and NIHSS (P < .001) scale scores. Age, gender, family history of stroke, smoking, alcohol consumption, previous history of stroke, education level, SSA scale score, NIHSS scale score, body mass index (BMI), body temperature, and infection were adjusted in the model. Nutritional status as classified by NRS-2002 and SGA was significantly correlated with prognosis (P < .001). The prognosis of stroke patients with dysphagia was associated with nutritional status by unconditional logistic regression. Conclusion: The prognosis of stroke patients with dysphagia is related to their nutritional status. A better nutritional status indicates the better prognosis, and vice versa. In clinical treatment, attention should be paid to use of a nutritional intervention.

Grincamycins P-T: Rearranged Angucyclines from the Marine Sediment-Derived Streptomyces sp. CNZ-748 Inhibit Cell Lines of the Rare Cancer Pseudomyxoma Peritonei.

While marine natural products have been investigated for anticancer drug discovery, they are barely screened against rare cancers. Thus, in our effort to discover potential drug leads against the rare cancer pseudomyxoma peritonei (PMP), which currently lacks effective drug treatments, we screened extracts of marine actinomycete bacteria against the PMP cell line ABX023-1. This effort led to the isolation of nine rearranged angucyclines from Streptomyces sp. CNZ-748, including five new analogues, namely, grincamycins P-T (1-5). The chemical structures of these compounds were unambiguously established based on spectroscopic and chemical analyses. Particularly, grincamycin R (3) possesses an S-containing α-l-methylthio-aculose residue, which was discovered in nature for the first time. All of the isolated compounds were evaluated against four PMP cell lines and some exhibited low micromolar inhibitory activities. To identify a candidate biosynthetic gene cluster (BGC) encoding the grincamycins, we sequenced the genome of the producing strain, Streptomyces sp. CNZ-748, and compared the BGCs detected with those linked to the production of angucyclines with different aglycon structures.

Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. DATA SOURCES: PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. STUDY SELECTION: Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. DATA EXTRACTION: Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. CONCLUSIONS: BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.

Ferrous hemoglobin and hemoglobin-based oxygen carriers acting as a peroxidase can inhibit oxidative damage to endothelial cells caused by hydrogen peroxide.

Oxidative damage caused by the ferryl hemoglobin is one of the major clinical adverse reactions of hemoglobin-based oxygen carriers (HBOCs), while the production of reactive oxygen species in a pathological state can oxidize hemoglobin (HbFe2+ ) to ferryl Hb, which can then enter the pseudoperoxidase cycle, making hemoglobin highly toxic. In this study, we found that ferrous hemoglobin and polymerized porcine hemoglobin (one of the HBOCs) have the peroxidase activity different from the pseudoperoxidase activity of ferric hemoglobin. Ferrous hemoglobin can catalyze the reaction of tyrosine (Tyr) with hydrogen peroxide. In addition, the results also indicated that ferrous hemoglobin and pPolyHb have a strong inhibitory effect on the pseudoperoxidase activity of ferric hemoglobin. Therefore, hydrogen peroxide was consumed in a large amount, which greatly prevented hemoglobin from becoming oxidized and entering the pseudoperoxidase cycle, thus inhibiting ferryl Hb toxicity. We further cultured human umbilical vein endothelial cells and monitored cell morphology, viability, cell cycle, apoptosis, lactate dehydrogenase (LDH) release, and malondialdehydes (MDAs) formation when incubated with H2 O2 , Tyr, and HbFe2+ . HbFe2+ and pPolyHb reduced cell cycle arrest, apoptosis, LDH release, and MDA formation. These results showed that reducing oxidative damage induced by H2 O2 and converted hemoglobin from a molecule that is toxic to one that inhibits oxidative damage, suggesting a new strategy for development of a safer HBOCs.

Anxiety and depression and its correlates in patients with coronavirus disease 2019 in Wuhan.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) first broke-out in Wuhan China in December 2019, and spread throughout the entire country within a short time. This cross-sectional study investigated the prevalence of depression and anxiety and associated risk factors were analysed in patients with COVID-19. METHODS: This single-center cross-sectional study focussed on measuring depression and anxiety using self-report scales. Linear regression was used to determine independent predictors for depression and anxiety. RESULTS: A total of 78 patients who were confirmed to have COVID-19 were enrolled in the study. Prevalence of depression and anxiety symptoms were diagnosed in 35.9% and 38.5% of the patients, respectively. Multivariate linear regression analysis found female gender was an independent predictor for higher depression severity index. Having family members who were diagnosed with COVID-19 and family members who died from COVID-19 were independently associated with higher depression severity index and anxiety score. CONCLUSIONS: Patients with COVID-19 especially those who had family members diagnosed with COVID-19 or died from COVID-19 were more susceptible to depression and anxiety than were other patients. Effective strategies should be pursued to improve the mental health of this patient population.Key pointsPatients with COVID-19 showed a significantly high prevalence of depression and anxiety.Female patients were associated with higher risk of depression.Patients with family members diagnosed as COVID-19 or died from this disease were associated with higher risk of depression and anxiety.

Dynamics of NK, CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID-19.

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8+ T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3+ Tfh-like cell and CD226+ Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8+ T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4+ T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19.

Use of partitioned GMM marginal regression model with time-dependent covariates: analysis of Chinese Longitudinal Healthy Longevity Study.

BACKGROUND: Elderly population's health is a major concern for most industrial nations. National health surveys provide a measure of the state of elderly health. One such survey is the Chinese Longitudinal Healthy Longevity Survey. It collects data on risk factors and outcomes on the elderly. We examine these longitudinal survey data to determine the changes in health and to identify risk factors as they impact health outcomes including the elderly's ability to do a physical check. METHODS: We use a Partitioned GMM logistic regression model to identify risk factors. The model also accounts for the correlation between lagged time-dependent covariates and the outcomes. It addresses present and past measures of time-dependent covariates on simultaneous outcomes. The relation produces additional regression coefficients as byproduct of the Partitioned model, identifying the immediate, delayed effects (lag - 1), further delayed (lag-2), etc. Therefore, the model presents the opportunity for decision makers to monitor the covariate over time. This technique is particularly useful in healthcare and health related research. We use the Chinese Longitudinal Health Longevity Survey data to identify those risk factors and to display the utility of the model. RESULTS: We found that one's ability to make own decisions, frequently consuming vegetables, exercise frequently, one's ability to transfer without assistance, having visual difficulties and being able to pick book from floor while standing had varying effects of significance on one's health and ability to complete physical checks as they get older. CONCLUSIONS: The partitioning of the covariates as immediate effect, delayed effect or further delayed effect are important measures in a declining population.

Systemic Analysis of the Prognosis-Related RNA Alternative Splicing Signals in Melanoma.

BACKGROUND Alternative splicing (AS), the mechanism underlying the occurrence of protein diversity, may result in cancer genesis and development when it becomes out of control, as suggested by a growing number of studies. However, systemically analyze of AS events at the genome-wide level for skin cutaneous melanoma (SKCM) is still in a preliminary phase. This study aimed to systemically analyze the bioinformatics of the AS events at a genome-wide level using The Cancer Genome Atlas (TCGA) SKCM data. MATERIAL AND METHODS The SpliceSeq tool was used to analyze the AS profiles for SKCM clinical specimens from the TCGA database. The association between AS events and overall survival was analyzed by Cox regression analysis. AS event intersections and a gene interaction network were established by UpSet plot. A multivariate survival model was used to establish a feature genes prognosis model. RESULTS A total of 103 SKCM patients with full clinical parameters available were included in this study. We established an AS network that investigated the relationship between AS events and clinical prognosis information. Furthermore, 4 underlying feature genes of SKCM (MCF2L, HARS, TFR2, and RALGPS1) were found in the AS network. We performed function analysis as well as correlation analysis of AS events with gene expression. Using the multivariate survival model, we further confirmed the 4 genes that impacted the classifying SKCM prognosis at the level of AS events as well as gene expression, especially in wild-type SKCM. CONCLUSIONS AS events could be ideal indicators for SKCM prognosis. The key feature gene MCF2L played an important role in wild-type SKCM.