Multifaceted Intensive Blood Pressure Control Model in Older and Younger Individuals With Hypertension: A Randomized Clinical Trial.

Importance: The sustainable effectiveness and safety of a nonphysician community health care practitioner-led intensive blood pressure intervention on cardiovascular disease have not, to the authors' knowledge, been studied, especially in the older adult population. Objective: To evaluate such a multifaceted model with a more stringent blood pressure treatment goal (<130/80 mm Hg) among patients aged 60 years and older with hypertension. Design, Setting, and Participants: This was a 48-month follow-up study of the China Rural Hypertension Control Project (CRHCP), an open-cluster randomized clinical trial, conducted from 2018 to 2023. Participants 60 years and older and younger than 60 years with a diagnosis of hypertension from the CRHCP trial were included for analysis. Individuals were recruited from 326 villages in rural China. Interventions: The well-trained, nonphysician, community health care practitioner implemented a multifaceted intervention program (eg, initiation or titration of antihypertensive medications) to achieve a blood pressure level of less than 130/80 mm Hg, supervised by primary care physicians. Main Outcomes and Measures: Cardiovascular disease (a composite of myocardial infarction, stroke, heart failure requiring hospitalization, and cardiovascular disease death). Results: A total of 22 386 individuals 60 years and older with hypertension and 11 609 individuals younger than 60 years with hypertension were included in the analysis. The mean (SD) age of the participants was 63.0 (9.0) years and included 20 825 females (61.3%). Among the older individuals with hypertension, a total of 11 289 patients were randomly assigned to the intervention group and 11 097 to the usual-care group. During a median (IQR) of 4.0 (4.0-4.1) years, there was a significantly lower rate of total cardiovascular disease (1133 [2.7%] vs 1433 [3.5%] per year; hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and all-cause mortality (1111 [2.5%] vs 1210 [2.8%] per year; HR, 0.90; 95% CI, 0.83-0.98; P = .01) in the intervention group than in the usual-care group. For patients younger than 60 years, the risk reductions were also significant for total cardiovascular disease (HR, 0.64; 95% CI, 0.56-0.75; P < .001), stroke (HR, 0.64; 95% CI, 0.55-0.76; P < .001), heart failure (HR, 0.39; 95% CI, 0.18-0.87; P = .02), and cardiovascular death (HR, 0.54; 95% CI, 0.37-0.77; P < .001), with all interaction P values for age groups greater than .05. In both age categories, the incidences of injurious falls, symptomatic hypotension, syncope, and the results for kidney outcomes did not differ significantly between groups. Conclusions and Relevance: In both the aging and younger general population with hypertension, the nonphysician health care practitioner-led, multifaceted, intensive blood pressure intervention model could effectively and safely reduce the risk of cardiovascular disease and all-cause death. Trial Registration: ClinicalTrials.gov Identifier: NCT03527719.

Impact of baseline cardiovascular risk on the outcomes of intensive blood pressure intervention: a post hoc analysis of the China rural hypertension control project.

BACKGROUND: The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). METHODS: This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.

Pushing the Limits of Capacitively Coupled Contactless Conductivity Detection for Capillary Electrophoresis.

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has proven to be an efficient technique for the separation and detection of charged inorganic, organic, and biochemical analytes. It offers several advantages, including cost-effectiveness, nanoliter injection volume, short analysis time, good separation efficiency, suitability for miniaturization, and portability. However, the routine determination of common inorganic cations (NH4+, K+, Na+, Ca2+, Mg2+, and Li+) and inorganic anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-) in water quality monitoring typically exhibits limits of detection of about 0.3-1 µM without preconcentration. This sensitivity often proves insufficient for the applications of CE-C4D in trace analysis situations. Here, we explore methods to push the detection limits of CE-C4D through a comprehensive consideration of signal and noise sources. In particular, we (i) studied the model of C4D and its guiding roles in C4D and CE-C4D, (ii) optimized the bandwidth and noise performance of the current-to-voltage (I-V) converter, and (iii) reduced the noise level due to the strong background signal of the background electrolyte by adaptive differential detection. We characterized the system with Li+; the 3-fold signal-to-noise (S/N) detection limit for Li+ was determined at 20 nM, with a linear range spanning from 60 nM to 1.6 mM. Moreover, the optimized CE-C4D method was applied to the analysis of common mixed inorganic cations (K+, Na+, Ca2+, Mg2+, and Li+), anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-), toxic halides (BrO3-) and heavy metal ions (Pb2+, Cd2+, Cr3+, Co2+, Ni2+, Zn2+, and Cu2+) at trace concentrations of 200 nM. All electropherograms showed good S/N ratios, thus proving its applicability and accuracy. Our results have shown that the developed CE-C4D method is feasible for trace ion analysis in water quality control.

Annual dynamics of global remote industrial heat sources dataset from 2012 to 2021.

The spatiotemporal distribution of industrial heat sources (IHS) is an important indicator for assessing levels of energy consumption and air pollution. Continuous, comprehensive, dynamic monitoring and publicly available datasets of global IHS (GIHS) are lacking and urgently needed. In this study, we built the first long-term (2012-2021) GIHS dataset based on the density-based spatiotemporal clustering method using multi-sources remote sensing data. A total of 25,544 IHS objects with 19 characteristics are identified and validated individually using high-resolution remote sensing images and point of interest (POI) data. The results show that the user's accuracy of the GIHS dataset ranges from 90.95% to 93.46%, surpassing other global IHS products in terms of accuracy, omission rates, and granularity. This long-term GIHS dataset serves as a valuable resource for understanding global environmental changes and making informed policy decisions. Its availability contributes to filling the gap in GIHS data and enhances our knowledge of global-scale industrial heat sources.

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

Regulatory mechanisms used by ZmMYB39 to enhance drought tolerance in maize (Zea mays) seedlings.

Drought is a significant abiotic stressor that limits maize (Zea mays L.) growth and development. Thus, enhancing drought tolerance is critical for promoting maize production. Our findings demonstrated that ZmMYB39 is an MYB transcription factor with transcriptional activation activity. Drought stress experiments involving ZmMYB39 overexpression and knockout lines indicated that ZmMYB39 positively regulated drought stress tolerance in maize. DAP-Seq, EMSA, dual-LUC, and RT-qPCR provided initial insights into the molecular regulatory mechanisms by which ZmMYB39 enhances drought tolerance in maize. ZmMYB39 directly promoted the expression of ZmP5CS1, ZmPOX1, ZmSOD2, ZmRD22, ZmNAC49, and ZmDREB2A, which are involved in stress resistance. ZmMYB39 enhanced drought tolerance by interacting with and promoting the expression of ZmFNR1, ZmHSP20, and ZmDOF6. Our study offers a theoretical basis for understanding the molecular regulatory networks involved in maize drought stress response. Furthermore, ZmMYB39 serves as a valuable genetic resource for breeding drought-resistant maize.

Transcriptome Analysis of Sesame (Sesamum indicum L.) Reveals the LncRNA and mRNA Regulatory Network Responding to Low Nitrogen Stress.

Nitrogen is one of the important factors restricting the development of sesame planting and industry in China. Cultivating sesame varieties tolerant to low nitrogen is an effective way to solve the problem of crop nitrogen deficiency. To date, the mechanism of low nitrogen tolerance in sesame has not been elucidated at the transcriptional level. In this study, two sesame varieties Zhengzhi HL05 (ZZ, nitrogen efficient) and Burmese prolific (MD, nitrogen inefficient) in low nitrogen were used for RNA-sequencing. A total of 3964 DEGs (differentially expressed genes) and 221 DELs (differentially expressed lncRNAs) were identified in two sesame varieties at 3d and 9d after low nitrogen stress. Among them, 1227 genes related to low nitrogen tolerance are mainly located in amino acid metabolism, starch and sucrose metabolism and secondary metabolism, and participate in the process of transporter activity and antioxidant activity. In addition, a total of 209 pairs of lncRNA-mRNA were detected, including 21 pairs of trans and 188 cis. WGCNA (weighted gene co-expression network analysis) analysis divided the obtained genes into 29 modules; phenotypic association analysis identified three low-nitrogen response modules; through lncRNA-mRNA co-expression network, a number of hub genes and cis/trans-regulatory factors were identified in response to low-nitrogen stress including GS1-2 (glutamine synthetase 1-2), PAL (phenylalanine ammonia-lyase), CHS (chalcone synthase, CHS), CAB21 (chlorophyll a-b binding protein 21) and transcription factors MYB54, MYB88 and NAC75 and so on. As a trans regulator, lncRNA MSTRG.13854.1 affects the expression of some genes related to low nitrogen response by regulating the expression of MYB54, thus responding to low nitrogen stress. Our research is the first to provide a more comprehensive understanding of DEGs involved in the low nitrogen stress of sesame at the transcriptome level. These results may reveal insights into the molecular mechanisms of low nitrogen tolerance in sesame and provide diverse genetic resources involved in low nitrogen tolerance research.

Enhanced Path Planning and Obstacle Avoidance Based on High-Precision Mapping and Positioning.

High-precision positioning and multi-target detection have been proposed as key technologies for robotic path planning and obstacle avoidance. First, the Cartographer algorithm was used to generate high-quality maps. Then, the iterative nearest point (ICP) and the occupation probability algorithms were combined to scan and match the local point cloud, and the positions and attitudes of the robot were obtained. Furthermore, Sparse Matrix Pose Optimization was carried out to improve the positioning accuracy. The positioning accuracy of the robot in x and y directions was kept within 5 cm, the angle error was controlled within 2°, and the positioning time was reduced by 40%. An improved timing elastic band (TEB) algorithm was proposed to guide the robot to move safely and smoothly. A critical factor was introduced to adjust the distance between the waypoints and the obstacle, generating a safer trajectory, and increasing the constraint of acceleration and end speed; thus, smooth navigation of the robot to the target point was achieved. The experimental results showed that, in the case of multiple obstacles being present, the robot could choose the path with fewer obstacles, and the robot moved smoothly when facing turns and approaching the target point by reducing its overshoot. The proposed mapping, positioning, and improved TEB algorithms were effective for high-precision positioning and efficient multi-target detection.

CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies.

Surgery, chemotherapy, and endocrine therapy have improved the overall survival and postoperative recurrence rates of Luminal A, Luminal B, and HER2-positive breast cancers but treatment modalities for triple-negative breast cancer (TNBC) with poor prognosis remain limited. The effective application of the rapidly developing chimeric antigen receptor (CAR)-T cell therapy in hematological tumors provides new ideas for the treatment of breast cancer. Choosing suitable and specific targets is crucial for applying CAR-T therapy for breast cancer treatment. In this paper, we summarize CAR-T therapy's effective targets and potential targets in different subtypes based on the existing research progress, especially for TNBC. CAR-based immunotherapy has resulted in advancements in the treatment of breast cancer. CAR-macrophages, CAR-NK cells, and CAR-mesenchymal stem cells (MSCs) may be more effective and safer for treating solid tumors, such as breast cancer. However, the tumor microenvironment (TME) of breast tumors and the side effects of CAR-T therapy pose challenges to CAR-based immunotherapy. CAR-T cells and CAR-NK cells-derived exosomes are advantageous in tumor therapy. Exosomes carrying CAR for breast cancer immunotherapy are of immense research value and may provide a treatment modality with good treatment effects. In this review, we provide an overview of the development and challenges of CAR-based immunotherapy in treating different subtypes of breast cancer and discuss the progress of CAR-expressing exosomes for breast cancer treatment. We elaborate on the development of CAR-T cells in TNBC therapy and the prospects of using CAR-macrophages, CAR-NK cells, and CAR-MSCs for treating breast cancer.

Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbß3 Integrin Activation and Degranulation.

BACKGROUND: Platelet glycoprotein VI (GPVI) stimulation activates the tyrosine kinases Syk and Btk, and the effector proteins phospholipase Cγ 2 (PLCγ2) and protein kinase C (PKC). Here, the activation sequence, crosstalk, and downstream effects of this Syk-Btk-PKC signalosome in human platelets were analyzed. METHODS AND RESULTS: Using immunoblotting, we quantified 14 regulated phospho-sites in platelets stimulated by convulxin with and without inhibition of Syk, Btk, or PKC. Convulxin induced fast, reversible tyrosine phosphorylation (pY) of Syk, Btk, LAT, and PLCγ2, followed by reversible serine/threonine phosphorylation (pS/T) of Syk, Btk, and downstream kinases MEK1/2, Erk1/2, p38, and Akt. Syk inhibition by PRT-060318 abolished all phosphorylations, except Syk pY352. Btk inhibition by acalabrutinib strongly decreased Btk pY223/pS180, Syk pS297, PLCγ2 pY759/Y1217, MEK1/2 pS217/221, Erk1/2 pT202/Y204, p38 pT180/Y182, and Akt pT308/S473. PKC inhibition by GF109203X abolished most pS/T phosphorylations except p38 pT180/Y182 and Akt pT308, but enhanced most Y-phosphorylations. Acalabrutinib, but not GF109203X, suppressed convulxin-induced intracellular Ca2+ mobilization, whereas all three protein kinase inhibitors abolished degranulation and αIIbß3 integrin activation assessed by flow cytometry. Inhibition of autocrine ADP effects by AR-C669931 partly diminished convulxin-triggered degranulation. CONCLUSION: Kinetic analysis of GPVI-initiated multisite protein phosphorylation in human platelets demonstrates multiple phases and interactions of tyrosine and serine/threonine kinases with activation-altering feedforward and feedback loops partly involving PKC. The protein kinase inhibitor effects on multisite protein phosphorylation and functional readouts reveal that the signaling network of Syk, Btk, and PKC controls platelet granule exocytosis and αIIbß3 integrin activation.

Small-Scale High-Pressure Hydrogen Storage Vessels: A Review.

Nowadays, high-pressure hydrogen storage is the most commercially used technology owing to its high hydrogen purity, rapid charging/discharging of hydrogen, and low-cost manufacturing. Despite numerous reviews on hydrogen storage technologies, there is a relative scarcity of comprehensive examinations specifically focused on high-pressure gaseous hydrogen storage and its associated materials. This article systematically presents the manufacturing processes and materials used for a variety of high-pressure hydrogen storage containers, including metal cylinders, carbon fiber composite cylinders, and emerging glass material-based hydrogen storage containers. Furthermore, it introduces the relevant principles and theoretical studies, showcasing their advantages and disadvantages compared to conventional high-pressure hydrogen storage containers. Finally, this article provides an outlook on the future development of high-pressure hydrogen storage containers.

Enhancer-MDLF: a novel deep learning framework for identifying cell-specific enhancers.

Enhancers, noncoding DNA fragments, play a pivotal role in gene regulation, facilitating gene transcription. Identifying enhancers is crucial for understanding genomic regulatory mechanisms, pinpointing key elements and investigating networks governing gene expression and disease-related mechanisms. Existing enhancer identification methods exhibit limitations, prompting the development of our novel multi-input deep learning framework, termed Enhancer-MDLF. Experimental results illustrate that Enhancer-MDLF outperforms the previous method, Enhancer-IF, across eight distinct human cell lines and exhibits superior performance on generic enhancer datasets and enhancer-promoter datasets, affirming the robustness of Enhancer-MDLF. Additionally, we introduce transfer learning to provide an effective and potential solution to address the prediction challenges posed by enhancer specificity. Furthermore, we utilize model interpretation to identify transcription factor binding site motifs that may be associated with enhancer regions, with important implications for facilitating the study of enhancer regulatory mechanisms. The source code is openly accessible at https://github.com/HaoWuLab-Bioinformatics/Enhancer-MDLF.

Separable amygdala activation patterns in the evaluations of robots.

Given the increasing presence of robots in everyday environments and the significant challenge posed by social interactions with robots, it is crucial to gain a deeper understanding into the social evaluations of robots. One potentially effective approach to comprehend the fundamental processes underlying controlled and automatic evaluations of robots is to probe brain response to different perception levels of robot-related stimuli. Here, we investigate controlled and automatic evaluations of robots based on brain responses during viewing of suprathreshold (duration: 200 ms) and subthreshold (duration: 17 ms) humanoid robot stimuli. Our behavioral analysis revealed that despite participants' self-reported positive attitudes, they held negative implicit attitudes toward humanoid robots. Neuroimaging analysis indicated that subthreshold presentation of humanoid robot stimuli elicited significant activation in the left amygdala, which was associated with negative implicit attitudes. Conversely, no significant left amygdala activation was observed during suprathreshold presentation. Following successful attenuation of negative attitudes, the left amygdala response to subthreshold presentation of humanoid robot stimuli decreased, and this decrease correlated positively with the reduction in negative attitudes. These findings provide evidence for separable patterns of amygdala activation between controlled and automatic processing of robots, suggesting that controlled evaluations may influence automatic evaluations of robots.

Construction and validation of a nomogram to predict left ventricular hypertrophy in low-risk patients with hypertension.

Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false-negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG-LVH based on Cornell product criteria (low-risk hypertensive population). A cross-sectional dataset was used for model construction and divided into development (n = 2906) and verification (n = 1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low-risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo-LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist-hip ratio, education level, tea consumption, hypochloremia, and other ECG-LVH diagnostic criteria (including Sokolow-Lyon, Sokolow-Lyon products, and Peguero-Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity = 0.606) and 0.700 (sensitivity = 0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity = 0.734) and 0.716 (sensitivity = 0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo-LVH risk in patients with hypertension and without ECG-LVH based on Cornell product criteria.

Exploration on the occurrence state of fluorine in cement hydration products mixed with high fluorine alkali free liquid accelerator.

If there was abundant fluorine in shotcrete, it might leach out and pollute the soil or migrate to corrode the reinforcement.Therefore, this research mainly investigated the basic properties of high-fluorine alkali free liquid accelerator (HF-AFA) and its occurrence forms in cement hydration products.The macro-test results showed that with the increase of HF-AFA dosage, it appeared excellent coagulation promoting property. However, when the HF-AFA dosage exceeded 7.0%, the 1d compressive strength of mortar was lower than 7.0 MPa. In addition, by measuring the early hydration heat of cement, C3A, C3S, C2S and C4AF pastes with and without HF-AFA, and combining XRD and SEM micro-analysis, the occurrence forms of fluorine in different clinker minerals were obtained.The final analysis results indicated that fluorine mainly existed in the form of CaF2, CaAlF5 and Ca2AlF7 crystals in C3A and C3S minerals, while only little CaF2 crystals appeared in C2S and C4AF minerals.

Elevated plasma levels of specific antiplatelet glycoprotein autoantibodies in patients with primary Sjögren syndrome with thrombocytopenia.

INTRODUCTION: Thrombocytopenia is one of the primary Sjögren's syndrome (pSS) hematological manifestations. The objective of this study was to evaluate the possible roles of antiplatelet glycoprotein autoantibodies in the pathogenesis of thrombocytopenia in primary Sjögren's syndrome (pSS). METHODS: The level of plasma anti-glycoprotein Ib, IIIa and IIb/IIIa autoantibodies in 36 pSS patients without thrombocytopenia and 35 pSS patients with thrombocytopenia, 36 Idiopathic thrombocytopenic purpura (ITP) patients and 39 normal control were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (0.813 ± 0.161 vs 0.688 ± 0.133; 0.917 ± 0.094 vs 0.802 ± 0.070; 0.911 ± 0.125 vs 0.782 ± 0.109). Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (25.7% vs 0%; 65.7% vs 11.1%; 31.4% vs 0%). In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients ((25.67 ± 5.5) × 10^9/L vs (116.8 ± 84.52) × 10^9/L; 29.04 ± 11.33 × 10^9/L vs (152.0 ± 75.47) × 10^9/L; (31.55 ± 14.0) × 10^9/L vs (118.8 ± 85.24) × 10^9/L). CONCLUSION: Elevated plasma levels of anti-platelet glycoprotein autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS. Key Points • The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was increased. • Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was increased. • In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients.

Association between normalized lactate load and in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Lactate was a prognostic indicator for acute myocardial infarction (AMI) patients. However, the association between normalized lactate load, representing hypoxic burden over time, and in-hospital mortality remained uncertain. METHODS: The data for this study was obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. The normalized lactate load, describing the average intensity of hyperlactatemia, was calculated as the area under the curve (AUC) of lactate divided by time. 5882 AMI patients enrolled in this study were divided into survivor (n = 5015), and non-survivor group (n = 867). The primary endpoint was in-hospital mortality. Receiver operating characteristic (ROC) curves were generated to assess the predictive efficacy of normalized lactate load for in-hospital mortality, and areas under the curves of different parameters were compared using DeLong test. Multivariate binary logistic regression analysis was employed to explore the association between normalized lactate load and in-hospital mortality. The adjusting variables included age, gender, ethnicity, heart rate, systolic blood pressure, congestive heart failure, shock, dyslipidemia, cardiac arrest, cerebrovascular disease, neutrophil, lymphocyte, creatinine, blood nitrogen urea, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), statins, dialysis, extracorporeal membrane oxygenation (ECMO), the Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score II (SAPS II). Restricted cubic spline (RCS) was conducted to evaluate nonlinear associations of normalized lactate load with in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 14.7%. After adjusting for confounding variables, normalized lactate load was independently associated with increased risk of in-hospital mortality (Normalized lactate load≥2.6 vs Normalized lactate load<2.6: OR, 95% CI: 1.56, 1.27-1.93). The RCS demonstrated a positive linear relationship between normalized lactate load and in-hospital mortality (non-linear p = 0.725). ROC curves showed that normalized lactate load was better than first lactate, maximum lactate, and mean lactate in predicting in-hospital mortality, but lower than SOFA and SAPS II. Among participants with at least nine lactate measures, normalized lactate load showed predictive performance comparable to SOFA and SAPS II. CONCLUSION: Normalized lactate load can be used to predict the prognosis of in-hospital mortality in AMI patients, and its prediction performance increases with the increase of lactate measurement.

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy

ABSTRACT Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

Molecular mechanism analysis of ZmRL6 positively regulating drought stress tolerance in maize.

MYB-related genes, a subclass of MYB transcription factor family, have been documented to play important roles in biological processes such as secondary metabolism and stress responses that affect plant growth and development. However, the regulatory roles of MYB-related genes in drought stress response remain unclear in maize. In this study, we discovered that a 1R-MYB gene, ZmRL6, encodes a 96-amino acid protein and is highly drought-inducible. We also found that it is conserved in both barley (Hordeum vulgare L.) and Aegilops tauschii. Furthermore, we observed that overexpression of ZmRL6 can enhance drought tolerance while knock-out of ZmRL6 by CRISPR-Cas9 results in drought hypersensitivity. DAP-seq analyses additionally revealed the ZmRL6 target genes mainly contain ACCGTT, TTACCAAAC and AGCCCGAG motifs in their promoters. By combining RNA-seq and DAP-seq results together, we subsequently identified eight novel target genes of ZmRL6 that are involved in maize's hormone signal transduction, sugar metabolism, lignin synthesis, and redox signaling/oxidative stress. Collectively, our data provided insights into the roles of ZmRL6 in maize's drought response.

The mechanisms of tanshinone in the treatment of tumors.

Tanshinone is a lipophilic compound that is present in traditional Chinese medicine and is derived from the roots of Salvia miltiorrhiza (Danshen). It has been proven to be highly effective in combating tumors in various parts of the body, including liver carcinoma, gastric cancer, ovarian cancer, cervix carcinoma, breast cancer, colon cancer, and prostate cancer. Tanshinone can efficiently prevent the reproduction of cancerous cells, induce cell death, and inhibit the spread of cancerous cells, which are mainly involved in the PI3K/Akt signaling pathway, NF-κB pathway, Bcl-2 family, Caspase cascades, MicroRNA, MAPK signaling pathway, p21, STAT3 pathway, miR30b-P53-PTPN11/SHP2 axis, ß-catenin, and Skp2. However, the properties and mechanisms of tanshinone's anti-tumor effects remain unclear currently. Thus, this study aims to review the research progress on tumor prevention and mechanisms of tanshinone to gain new perspectives for further development and clinical application of tanshinone.