Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Automated classification of group B Streptococcus into different clonal complexes using MALDI-TOF mass spectrometry.

Objectives: To evaluate the performance of Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectra (MALDI-TOF MS) for automated classification of GBS (Group B Streptococcus) into five major CCs (clonal complexes) during routine GBS identification. Methods: MALDI-TOF MS of 167 GBS strains belonging to five major CCs (CC10, CC12, CC17, CC19, CC23) were grouped into a reference set (n = 67) and a validation set (n = 100) for the creation and evaluation with GBS CCs subtyping main spectrum (MSP) and MSP-M using MALDI BioTyper and ClinProTools. GBS CCs subtyping MSPs-M was generated by resetting the discriminative peaks of GBS CCs subtyping MSP according to the informative peaks from the optimal classification model of five major CCs and the contribution of each peak to the model created by ClinProTools. Results: The PPV for the GBS CCs subtyping MSP-M was greater than the subtyping MSP for CC10 (99.21% vs. 93.65%), but similar for CC12 (79.55% vs. 81.06%), CC17 (93.55% vs. 94.09%), and CC19 (92.59% vs. 95.37%), and lower for CC23 (66.67% vs. 83.33%). Conclusion: MALDI-TOF MS could be a promising tool for the automated categorization of GBS into 5 CCs by both CCs subtyping MSP and MSP-M, GBS CCs subtyping MSP-M is preferred for the accurate prediction of CCs with highly discriminative peaks.

Effectiveness and safety of GnRH antagonist originator and generic in real-world clinical practice: a retrospective cohort study.

Objective: This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide® and generic Ferpront®, in gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS). Methods: This retrospective cohort study investigates COS cycles utilizing GnRH antagonist protocols. The research was conducted at a specialized reproductive medicine center within a tertiary care hospital, spanning the period from October 2019 to October 2021. Within this timeframe, a total of 924 cycles were administered utilizing the GnRH antagonist originator, Cetrotide® (Group A), whereas 1984 cycles were undertaken using the generic, Ferpront® (Group B). Results: Ovarian reserve markers, including anti-Mullerian hormone, antral follicle number, and basal follicular stimulating hormone, were lower in Group A compared to Group B. Propensity score matching (PSM) was performed to balance these markers between the groups. After PSM, baseline clinical features were similar, except for a slightly longer infertile duration in Group A versus Group B (4.43 ± 2.92 years vs. 4.14 ± 2.84 years, P = 0.029). The duration of GnRH antagonist usage was slightly longer in Group B than in Group A (6.02 ± 1.41 vs. 5.71 ± 1.48 days, P < 0.001). Group B had a slightly lower number of retrieved oocytes compared to Group A (14.17 ± 7.30 vs. 14.96 ± 7.75, P = 0.024). However, comparable numbers of usable embryos on day 3 and good-quality embryos were found between the groups. Reproductive outcomes, including biochemical pregnancy loss, clinical pregnancy, miscarriage, and live birth rate, did not differ significantly between the groups. Multivariate logistic regression analyses suggested that the type of GnRH antagonist did not independently impact the number of oocytes retrieved, usable embryos, good-quality embryos, moderate to severe OHSS rate, clinical pregnancy, miscarriage, or live birth rate. Conclusion: The retrospective analysis revealed no clinically significant differences in reproductive outcomes between Cetrotide® and Ferpront® when used in women undergoing their first and second COS cycles utilizing the GnRH antagonist protocol.

Syntheses and Applications of Coumarin-Derived Fluorescent Probes for Real-Time Monitoring of NAD(P)H Dynamics in Living Cells across Diverse Chemical Environments.

Fluorescent probes play a crucial role in elucidating cellular processes, with NAD(P)H sensing being pivotal in understanding cellular metabolism and redox biology. Here, the development and characterization of three fluorescent probes, A, B, and C, based on the coumarin platform for monitoring of NAD(P)H levels in living cells are described. Probes A and B incorporate a coumarin-cyanine hybrid structure with vinyl and thiophene connection bridges to 3-quinolinium acceptors, respectively, while probe C introduces a dicyano moiety for replacement of the lactone carbonyl group of probe A which increases the reaction rate of the probe with NAD(P)H. Initially, all probes exhibit subdued fluorescence due to intramolecular charge transfer (ICT) quenching. However, upon hydride transfer by NAD(P)H, fluorescence activation is triggered through enhanced ICT. Theoretical calculations confirm that the electronic absorption changes upon the addition of hydride to originate from the quinoline moiety instead of the coumarin section and end up in the middle section, illustrating how the addition of hydride affects the nature of this absorption. Control and dose-response experiments provide conclusive evidence of probe C's specificity and reliability in identifying intracellular NAD(P)H levels within HeLa cells. Furthermore, colocalization studies indicate probe C's selective targeting of mitochondria. Investigation into metabolic substrates reveals the influence of glucose, maltose, pyruvate, lactate, acesulfame potassium, and aspartame on NAD(P)H levels, shedding light on cellular responses to nutrient availability and artificial sweeteners. Additionally, we explore the consequence of oxaliplatin on cellular NAD(P)H levels, revealing complex interplays between DNA damage repair, metabolic reprogramming, and enzyme activities. In vivo studies utilizing starved fruit fly larvae underscore probe C's efficacy in monitoring NAD(P)H dynamics in response to external compounds. These findings highlight probe C's utility as a versatile tool for investigating NAD(P)H signaling pathways in biomedical research contexts, offering insights into cellular metabolism, stress responses, and disease mechanisms.

Distribution of scoliosis in 2.22 million adolescents in mainland China: A population-wide analysis.

Background: The characteristics of scoliosis afflicting school children and adolescents in mainland China are still unclear. Therefore, we conducted a systematic review to estimate scoliosis's prevalence and characterise its distribution in China. Methods: We screened PubMed, Scopus, WanFang, China National Knowledge Infrastructure, National Science and Technology Library, and WeiPu databases for mainland China articles published between 1 January 1980 and 31 October 2022. Among them, we identified population-wide scoliosis studies in school children and adolescents. The main outcomes were the positive rate of primary screening and the prevalence of final screening. Primary screening mainly included general examination with/without the forward bending test in school. The final screening entailed clinical diagnosis by Röntgen radiation in a hospital (based on primary screening). A meta-analysis of scoliosis distribution by gender was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Further, we analysed the distributions of scoliosis by age, region, aetiological type, and severity of curvature, in addition to the correlation between its prevalence and altitude or latitude. Results: 77 studies with 2 224 320 participants were included. The positive rate through primary screening was 3.97%, whereas the prevalence of scoliosis at final screening was 1.20%. Analysing the data revealed a higher prevalence of scoliosis in girls (OR = 1.57; 95% CI = 1.38-1.81). The age-wise peak rate of scoliosis was 15-16 years (1.07%) in boys and 13-14 years (1.42%) in girls. The mean prevalence of scoliosis was 1.07% in the western region, 1.54% in the central, and 1.35% in the eastern. Scoliosis prevalence was not correlated with either altitude or latitude. The prevalence of idiopathic and congenital scoliosis was 1.18 and 0.03%. Among all subjects with scoliosis, 79.10 and 16.80% had mild and medium disease severity. Conclusions: According to this comprehensive study using data sets of scoliosis in adolescents across mainland China, the mean prevalence of scoliosis is 1.20%, yet 1.57 times higher in girls than boys, and is most prevalent in the middle region. Overall, scoliosis in adolescents could pose a burden to public health in mainland China. Registration: PROSPERO CRD42021231987.

An activated near-infrared mitochondrion-targetable fluorescent probe for rapid detection of NADH.

A novel NIR fluorescent probe based on quinoline-conjugated benzo[cd]indol dual-salt for NADH was developed. This probe swiftly detects and responds sensitively to both endogenous and exogenous NADH alterations, enabling imaging of NADH fluctuations in type II diabetic and AD model cells.

Decoding enterprise digital transformation: External oversight and carbon emission reduction performance.

Enterprise digital transformation (EDT) is a strategic initiative that provides robust support for optimising resource allocation, fosters business innovation, and significantly impacts ecological environment to increase financial performance. This study re-examines the substantial contributions of EDT to climate change mitigation. Drawing on data from Chinese A-share listed companies from 2010 to 2021, we investigated the changes and mechanisms influencing carbon emissions reduction performance (CERP) of enterprises undergoing digital transformation. The empirical results indicate that EDT actively contributes to enhancing the CERP of enterprises, with a more pronounced effect observed in non-polluting industries, state-owned enterprises, and manufacturing companies. Furthermore, empirical findings from mechanism tests reveal that EDT effectively improves the CERP by driving green technological innovation, strengthening industry chain connections, and enhancing capacity utilisation. Finally, within external oversight groups, particularly in government and investor supervision, the enhancement of enterprise CERP is more significant, highlighting the crucial role of external oversight in the EDT process.

Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a persistent infectious disease threatening human health. The existing diagnostic methods still have significant shortcomings, including a low positivity rate in pathogen-based diagnoses and the inability of immunological diagnostics to detect active TB. Hence, it is urgent to develop new techniques to detect TB more accurate and earlier. This research aims to scrutinize and authenticate DNA methylation markers suitable for tuberculosis diagnosis. Concurrently, Providing a new approach for tuberculosis diagnosis. Methods: Blood samples from patients with newly diagnosed tuberculosis and healthy controls (HC) were utilized in this study. Examining methylation microarray data from 40 whole blood samples (22TB + 18HC), we employed two procedures: signature gene methylated position analysis and signature region methylated position analysis to pinpoint distinctive methylated positions. Based on the screening results, diagnostic classifiers are constructed through machine learning, and validation was conducted through pyrosequencing in a separate queue (22TB + 18HC). Culminating in the development of a new tuberculosis diagnostic method via quantitative real-time methylation specific PCR (qMSP). Results: The combination of the two procedures revealed a total of 10 methylated positions, all of which were located in the promoter region. These 10 signature methylated positions facilitated the construction of a diagnostic classifier, exhibiting robust diagnostic accuracy in both cross-validation and external test sets. The LDA model demonstrated the best classification performance, achieving an AUC of 0.83, specificity of 0.8, and sensitivity of 0.86 on the external test set. Furthermore, the validation of signature methylated positions through pyrosequencing demonstrated high agreement with screening outcomes. Additionally, qMSP detection of 2 potential hypomethylated positions (cg04552852 and cg12464638) exhibited promising results, yielding an AUC of 0.794, specificity of 0.720, and sensitivity of 0.816. Conclusion: Our study demonstrates that the validated signature methylated positions through pyrosequencing emerge as plausible biomarkers for tuberculosis diagnosis. The specific methylation markers in the TSPAN4 gene, identified in whole blood samples, hold promise for improving tuberculosis diagnosis. This approach could significantly enhance diagnostic accuracy and speed, offering a new avenue for early detection and treatment.

Near-infrared Absorption and Emission Probes with Optimal Connection Bridges for Live Monitoring of NAD(P)H Dynamics in Living Systems.

Two NAD(P)H-biosensing probes consisting of 1,3,3-trimethyl-3H-indolium and 3-quinolinium acceptors, linked by thiophene, A, and 3,4-ethylenedioxythiophene, B, bridges are detailed. We synthesized probes C and D, replacing the thiophene connection in probe A with phenyl and 2,1,3-benzothiadiazole units, respectively. Probe E was prepared by substituting probe A's 3-quinolinium unit with a 1-methylquinoxalin-1-ium unit. Solutions are non-fluorescent but in the presence of NADH, exhibit near-infrared fluorescence at 742.1 nm and 727.2 nm for probes A and B, respectively, and generate absorbance signals at 690.6 nm and 685.9 nm. In contrast, probes C and D displayed pronounced interference from NADH fluorescence at 450 nm, whereas probe E exhibited minimal fluorescence alterations in response to NAD(P)H. Pre-treatment of A549 cells with glucose in the presence of probe A led to a significant increase in fluorescence intensity. Additionally, subjecting probe A to lactate and pyruvate molecules resulted in opposite changes in NAD(P)H levels, with lactate causing a substantial increase in fluorescence intensity, conversely, pyruvate resulted in a sharp decrease. Treatment of A549 cells with varying concentrations of the drugs cisplatin, gemcitabine, and camptothecin (5, 10, and 20 µM) led to a concentration-dependent increase in intracellular fluorescence intensity, signifying a rise in NAD(P)H levels. Finally, fruit fly larvae were treated with different concentrations of NADH and cisplatin illustrating applicability to live organisms. The results demonstrated a direct correlation between fluorescence intensity and the concentration of NADH and cisplatin, respectively, further confirming the efficacy of probe A in sensing changes in NAD(P)H levels within a whole organism.

Burden of neck pain in general population of China, 1990-2019: An analysis for the Global Burden of Disease Study 2019.

Background: Neck pain has become very common in China and has greatly affected individuals, families, and society in general. In this study, we aimed to report on the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) caused by neck pain in the general population of China from 1990 to 2019. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) study to estimate the number and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and YLDs in 33 provinces/municipalities/autonomous regions of China, stratified by age, sex, and sociodemographic index (SDI) from 1990 to 2019. We then compared these estimates with other G20 countries. Results: There were 6.80 × 107 patients with neck pain in 2019, presenting an increase from 3.79 × 107 in 1990. Likewise, the national age-standardised point prevalence increased slightly from 3.53% in 1990 to 3.57% in 2019. The YLDs increased by 78.08%, from 3814 × 103 in 1990 to 6792 × 103 in 2019. The age-standardised YLDs rate increased 1.50% from 352.84 in 1990 to 358.10 in 2019. The point prevalence of neck pain in 2019 was higher in females compared with males. These estimates were all above the global average level and increased more rapidly among G20 countries from 1990 to 2019. We generally observed a positive association between age-standardised YLD rates for neck pain and SDI, suggesting the burden is higher at higher sociodemographic indices. Conclusions: Neck pain is a serious public health problem in the general population in China, especially in its central and western regions, with an overall increasing trend in the last three decades. This is possibly related to changes of people's lifestyles and work patterns due to improvements in societal well-being and technology. Raising awareness of risk factors for neck pain in the general population and establishing effective preventive and treatment strategies could help reduce the future burden of neck disorders.

Incidence, prevalence, and causes of spinal injuries in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Spinal injuries are an urgent public health priority; nevertheless, no China-wide studies of these injuries exist. This study measured the incidence, prevalence, causes, regional distribution, and annual trends of spinal injuries in China from 1990 to 2019. METHODS: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in China. The data of 33 provincial-level administrative regions (excluding Taiwan, China) provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (CDC) were use to systematically analyze the provincial etiology, geographical distribution, and annual trends of spinal injuries. The Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence, prevalence, and mortality rates in each case. RESULTS: From 1990 to 2019, the number of living patients with spinal injuries in China increased by 138.32%, from 2.14 million to 5.10 million, while the corresponding age-standardized prevalence increased from 0.20% (95% uncertainty interval [UI]: 0.18-0.21%) to 0.27% (95% UI: 0.26-0.29%). The incidence of spinal injuries in China increased by 89.91% (95% UI: 72.39-107.66%), and the prevalence increased by 98.20% (95% UI: 89.56-106.82%), both the most significant increases among the G20 countries; 71.00% of the increase could be explained by age-specific prevalence. In 2019, the incidence was 16.47 (95% UI: 12.08-22.00, per 100,000 population), and the prevalence was 358.30 (95% UI: 333.96-386.62, per 100,000 population). Based on the data of 33 provincial-level administrative regions provided by CDC, age-standardized incidence and prevalence were both highest in developed provinces in Eastern China. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces. CONCLUSIONS: In China, the overall disease burden of spinal injuries increased significantly during the past three decades but varied considerably according to geographical location. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.

Evaluation of three decades of the burden of low back pain in China before COVID-19: Estimates from the Global Burden of Disease Database 2019.

Background: Low back pain (LBP) is reported as an urgent public-health concern globally because it occurs in all age groups and is now the leading cause of disability, with health systems unable to cope with this burden. We present China's burden of LBP by estimating its prevalence and years lived with disability (YLDs) from 1990 to 2019. Methods: We obtained the data relating to LBP from the Global Burden of Disease Database (GBD) 2019. Then we calculated years lived with disability caused by LBP by multiplying the prevalence of LBP sequelae by their corresponding disability weights. We performed an analysis of the age-, sex-, and province-specific prevalence and YLDs of 33 provinces/regions in China, as well as their relationship with the sociodemographic index (SDI). Results: China has the largest numbers of people with LBP (91.3 million) and YLDs (8.6 million) globally, and LBP is the leading cause of YLDs. The age-standardised prevalence was 7.25% in 1990, and this decreased to 5.13% in 2019. The age-standardised YLD rate was 579/100 000 in 2019, having decreased by 28.97%. Both measurements increased with age, being higher in women and varying across the 33 provinces/regions. For the 5-to-14-year age group, the prevalence (4.50%) and YLD rate (4.51%) increased in 2019 from 1990 (3.21% and 3.21%, respectively) when compared to the elderly group. Age-standardised YLD rates experienced decreases with increasing SDI, while there was an increasing tendency as SDI increased further; the changes for women were more obvious. Conclusions: Over the three decades considered, China has continued to have the largest number of people with LBP in the world, even though the age-standardised prevalence has decreased. YLDs were found to decrease as SDI increased, but they subsequently increased again. LBP still presents a burden, particularly for children and postmenopausal women.

Electromagnetically induced transparency enabled by quasi-bound states in the continuum modulated by epsilon-near-zero materials.

Highly tunable electromagnetically induced transparency (EIT) with high-quality-factor (Q-factor) excited by combining with the quasi-bound states in the continuum (quasi-BIC) resonances is crucial for many applications. This paper describes all-dielectric metasurface composed of silicon cuboid etched with two rectangular holes into a unit cell and periodically arranged on a SiO2 substrate. By breaking the C2 rotational symmetry of the unit cell, a high-Q factor EIT and double quasi-BIC resonant modes are excited at 1224.3, 1251.9 and 1299.6 nm with quality factors of 7604, 10064 and 15503, respectively. We show that the EIT resonance is caused by destructive interference between magnetic dipole resonances and quasi-BIC dominated by electric quadrupole. Toroidal dipole (TD) and electric quadrupole (EQ) dominate the other two quasi-BICs. The EIT window can be successfully modulated with transmission intensity from 90% to 5% and modulation depths ranging from -17 to 24 dB at 1200-1250 nm by integrating the metasurface with an epsilon-near-zero (ENZ) material indium tin oxide (ITO) film. Our findings pave the way for the development of applications such as optical switches and modulators with many potential applications in nonlinear optics, filters, and multichannel biosensors.

Impact of dietary digestible aromatic amino acid levels and stachyose on growth, nutrient utilization, and cecal odorous compounds in broiler chickens.

This study evaluated the impact of dietary digestible aromatic amino acid (DAAA) levels and stachyose on growth, nutrient utilization and cecal odorous compounds in broiler chickens. A 3×2 two-factor factorial design: Three dietary DAAA levels (1.40, 1.54, 1.68%) supplemented with either 5 g/kg of stachyose or without any stachyose were used to create 6 experimental diets. Each diet was fed to 6 replicates of 10 birds from d 22 to 42. Findings revealed that broilers receiving a diet with 1.54% DAAA levels supplemented with 5 g/kg stachyose exhibited a significant boost in average daily gain and improved utilization of crude protein, ether extract, tryptophan, and methionine compared to other diet treatments (P < 0.05). As the dietary DAAA levels increased, there was a significant rise in the concentrations of indole, skatole, p-methylphenol, and butyric acid in the cecum of broilers (P < 0.05). The addition of stachyose to diets reduced concentrations of indole, skatole, phenol, p-methylphenol, acetic acid and propionic acid in the cecum (P < 0.05). The lowest concentrations of indole, phenol, p-methylphenol, volatile fatty acids and pH in cecum of broilers were observed in the treatment which diet DAAA level was 1.40% with stachyose (P < 0.05). In conclusion, dietary DAAA levels and stachyose had significant interactions on the growth, main nutrient utilization and cecal odorous compounds in broilers. The dietary DAAA level was 1.54% with 5 g/kg of stachyose can improve the growth performance, nutrient utilization. However, the dietary DAAA level was 1.40% with stachyose was more beneficial to decrease the cecal odor compound composition in broilers.

Effect of phenylephrine rescue injection on hypotension after spinal anaesthesia for caesarean delivery when guided by both heart rate and SBP during an early warning window: A randomised controlled trial.

BACKGROUND: Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension. OBJECTIVE: To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability. SETTING: A teaching hospital. DESIGN: A randomised controlled trial. PATIENTS: One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study. INTERVENTIONS: All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion. MAIN OUTCOME MEASURES: The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events. RESULTS: The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P  = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ±â€Š9.49 vs. 86.7 ±â€Š11.16 mmHg, P   =  0.004). There was no significant difference in the incidence of hypertension between groups. CONCLUSION: After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension. TRIAL REGISTRATION: Chictr.org.cn; Identifier: ChiCTR 2100041812.

YTHDC1 delays cellular senescence and pulmonary fibrosis by activating ATR in an m6A-independent manner.

Accumulation of DNA damage in the lung induces cellular senescence and promotes age-related diseases such as idiopathic pulmonary fibrosis (IPF). Hence, understanding the mechanistic regulation of DNA damage repair is important for anti-aging therapies and disease control. Here, we identified an m6A-independent role of the RNA-binding protein YTHDC1 in counteracting stress-induced pulmonary senescence and fibrosis. YTHDC1 is primarily expressed in pulmonary alveolar epithelial type 2 (AECII) cells and its AECII expression is significantly decreased in AECIIs during fibrosis. Exogenous overexpression of YTHDC1 alleviates pulmonary senescence and fibrosis independent of its m6A-binding ability, while YTHDC1 deletion enhances disease progression in mice. Mechanistically, YTHDC1 promotes the interaction between TopBP1 and MRE11, thereby activating ATR and facilitating DNA damage repair. These findings reveal a noncanonical function of YTHDC1 in delaying cellular senescence, and suggest that enhancing YTHDC1 expression in the lung could be an effective treatment strategy for pulmonary fibrosis.

Characterization of complexes of PF4 and heparins by size-exclusion chromatography coupled with multi-angle light scattering detector.

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy. Antibodies binding to complexes of platelet factor 4 (PF4) and heparin is the trigger of HIT. A method using size exclusion chromatography with multi-angle laser light scattering detector (SEC-MALS) was developed in this work. The soluble ultra-large complex (ULC) was separated from the small complex (SC) and their molecular weights (MWs) were firstly measured. The complexes of PF4 and three heparins with different MW, including unfractionated heparin (UFH), dalteparin (Daltep) and enoxaparin (Eno) were characterized using this method. The contents and the sizes of ULC increased gradually when heparins were added to PF4 to certain amounts. While, they reduced after more heparins were added. It is the first time to measure the MWs of the biggest ULC of PF4-heparins as millions of Dalton. at the proper ratios of PF4 to heparin (PHR). Meanwhile, those mixtures at those certain PHRs induced the higher expression of CD83 and CD14 markers on dendritic cells (DCs) suggesting that they had stronger immunogenicity and is critical for HIT.

Preparation of PEG/P(U-AM-ChCl) composite hydrogels using ternary DES light polymerization and their properties.

Deep eutectic solvents (DES) were prepared using urea (U) and acrylamide (AM) as hydrogen bond donors (HBD) and choline chloride (ChCl) as hydrogen bond acceptor (HBA), and polyethylene glycol (PEG) was selected as a filler and uniformly dispersed in DES to prepare PEG/P(U-AM-ChCl) composite hydrogels by light polymerization. The composite hydrogels were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The effects of the content of PEG on the swelling properties, mechanical properties and fatigue resistance of the composite hydrogels were investigated. The results showed that the compressive strength and fatigue strength of the composite hydrogels were gradually enhanced with the increase of the PEG content in the composite hydrogels, in which the maximum compressive strength of the hydrogels with 1 wt% PEG added was increased by 1.86 times. The composite hydrogel had excellent swelling properties, and the equilibrium swelling degree of the hydrogel with 1 wt% PEG added reached 10.15. Meanwhile, the PEG/P(U-AM-ChCl) composite hydrogel had excellent self-healing properties, and the self-healing rate of the composite hydrogel with a PFG content of 1 wt% could reach 91.93% after 48 hours of healing. This study provides a convenient and efficient method to prepare composite hydrogels with superior swelling properties and self-healing properties.