Impact of Tolvaptan Combined with Low-Dose Dopamine in Heart Failure Patients with Acute Kidney Injury.

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 µg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

Self-regulation and conflict goals management capabilities of ecosystem entrepreneurs: a case study of Haier ecosystem.

The inherent dual roles of "follower" and "leader" among ecosystem entrepreneurs inevitably introduce challenges in managing conflicting dependent and independent goals. Ecosystem entrepreneurs' capabilities in conflict goals management directly influence new venture survival and development. This single-case qualitative study explores how ecosystem entrepreneurs develop conflict goals management capabilities through self-regulation, which is not only a unique practical challenge in ecosystem entrepreneurship, but also a cutting-edge topic in current theoretical research. Through research of entrepreneurs in Haier Entrepreneurship Ecosystem, the paper finds: (1) strategic corresponding and mechanism adapting emerge as the two trigger factors enabling ecosystem entrepreneurs to recognize the equilibrium or disequilibrium between conflicting goals; (2) by leveraging self-control, grit, and metacognition, ecosystem entrepreneurs construct decoupling mechanisms for antagonistic goal recognition and coupling mechanisms for synergistic goal recognition; (3) ecosystem entrepreneurs enhance their conflict goals management capabilities by developing both segregative and synergistic management capabilities. Furthermore, this research explores the self-regulation process underlying ecosystem entrepreneurs' conflict goals management behaviors, including environmental interaction perception, conflict goals analysis, and delineation of goal relationships. Findings provide insights for ecosystem entrepreneurs on improving their conflict goals management capabilities through self-assessment and skill development.

Identification of suitable habitats and priority conservation areas under climate change scenarios for the Chinese alligator (Alligator sinensis).

Amphibians and reptiles, especially the critically endangered Chinese alligators, are vulnerable to climate change. Historically, the decline in suitable habitats and fragmentation has restricted the distribution of Chinese alligators to a small area in southeast Anhui Province in China. However, the effects of climate change on range-restricted Chinese alligator habitats are largely unknown. We aimed to predict current and future (2050s and 2070s) Chinese alligator distribution and identify priority conservation areas under climate change. We employed species distribution models, barycenter migration analyses, and the Marxian model to assess current and future Chinese alligator distribution and identify priority conservation areas under climate change. The results showed that the lowest temperature and rainfall seasonality in the coldest month were the two most important factors affecting the distribution of Chinese alligators. Future predictions indicate a reduction (3.39%-98.41%) in suitable habitats and a westward shift in their distribution. Further, the study emphasizes that suitable habitats for Chinese alligators are threatened by climate change. Despite the impact of the Anhui Chinese Alligator National Nature Reserve, protection gaps persist, with 78.27% of the area lacking priority protected area. Our study provides crucial data for Chinese alligator adaptation to climate change and underscores the need for improved conservation strategies. Future research should refine conservation efforts, consider individual plasticity, and address identified limitations to enhance the resilience of Chinese alligator populations in the face of ongoing climate change.

Diagnosis and therapies for patients with cerebral palsy over the past 30 years: a bibliometric analysis.

Background: Currently, the incidence of cerebral palsy is high in newborns. However, the current methods for diagnosing and treating patients with cerebral palsy are complex and poorly targeted. Moreover, these studies lack the support of bibliometric analysis results. Objective: Our study focused on a bibliometric analysis of published papers on the diagnosis and treatment of patients with cerebral palsy. This study identified the primary authors, institutions, and countries involved in analyzing the status and trends of research on the diagnosis and treatment of patients with cerebral palsy. Additionally, the study also involved screening pathways related to cerebral palsy. Methods: The PubMed database was searched for publications on the diagnosis and treatment of patients with cerebral palsy between 1990 and 2023. R v4.2.2 and VOSviewer v1.6.18 software tools were utilized to perform bibliometric analysis and visualization. Results: There were 1,965 publications on cerebral palsy diagnosis and 5,418 articles on the qualified treatment strategies, and the annual number of publications also increased. The United States dominated in this field of research. Gregory Y.H. Lip and Patrizio Lancellotti published the most number of papers. The Cleveland Clinic published the most number of papers in the field. According to the analysis of the co-occurrence of keywords, we found that the main research directions were age, sex, disease diagnosis, and treatment. Newly emerging research has focused mainly on heart failure, which is related to valvular heart disease. Conclusion: The findings presented in this study offer valuable insights into ongoing research and potential future directions pertaining to cerebral palsy. These insights can assist researchers in identifying suitable collaborators and enhancing their investigations aimed at identifying the underlying molecular mechanisms associated with cerebral palsy, encompassing its etiology, preventive measures, and therapeutic interventions.

A de novo Mutation (p.Gln277X) of Cyclin D2 is Responsible for a Child with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke.

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Transcriptomic analysis provides insights into the molecular mechanism of melatonin-mediated cadmium tolerance in Medicago sativa L.

Cadmium (Cd), a toxic element, often makes a serious threat to plant growth and development. Previous studies found that melatonin (Mel) reduced Cd accumulation and reestablished the redox balance to alleviate Cd stress in Medicago sativa L., however, the complex molecular mechanisms are still elusive. Here, comparative transcriptome analysis and biochemical experiments were conducted to explore the molecular mechanisms of Mel in enhancing Cd tolerance. Results showed that 7237 differentially expressed genes (DEGs) were regulated by Mel pretreatment to Cd stress compared to the control condition in roots of Medicago sativa L. Besides, in comparison with Cd stress alone, Mel upregulated 1081 DEGs, and downregulated 1085 DEGs. These DEGs were mainly involved in the transcription and translation of genes and folding, sorting and degradation of proteins, carbohydrate metabolism, and hormone signal network. Application of Mel regulated the expression of several genes encoding ribosomal protein and E3 ubiquitin-protein ligase involved in folding, sorting and degradation of proteins. Moreover, transcriptomic analyse suggested that Mel might regulate the expression of genes encoding pectin lyase, UDP-glucose dehydrogenase, sucrose-phosphate synthase, hexokinase-1, and protein phosphorylation in the sugar metabolism. Therefore, these could promote sucrose accumulation and subsequently alleviate the Cd damage. In conclusion, above findings provided the mining of important genes and molecular basis of Mel in mitigating Cd tolerance and genetic cultivation of Medicago sativa L.

A review on synthesis and applications of gallium oxide materials.

Gallium oxide (Ga2O3), as a new kind of ultra-wide band gap semiconductor material, is widely studied in many fields, such as power electronics, UV - blind photodetectors, solar cells and so on. Owing to the advantages of its excellent performance and broad application prospects in semiconductor technology, Ga2O3 materials have attracted extensive academic and technological attention. This review mainly focuses on introducing the main liquid-phase synthesis methods of Ga2O3 nanoparticles, such as direct-precipitation, chemical bath deposition, hydrothermal, solvothermal, and sol-gel method, including the characteristics in process and advantages and disadvantages of these methods. Then, the effects of reaction conditions, such as pH, capping agent, aging and calcination conditions, on the morphologies and sizes of the precursor and the final products were elucidated. Moreover, the applications of Ga2O3 particles in the fields of catalysis, gas sensors, and other devices in current research on Ga2O3 nanomaterials are discussed with the description of the basic working principle and influence factors.

Directional Moisture-Wicking Triboelectric Materials Enabled by Laplace Pressure Differences.

Wearable sensors are experiencing vibrant growth in the fields of health monitoring systems and human motion detection, with comfort becoming a significant research direction for wearable sensing devices. However, the weak moisture-wicking capability of sensor materials leads to liquid retention, severely restricting the comfort of the wearable sensors. This study employs a pattern-guided alignment strategy to construct microhill arrays, endowing triboelectric materials with directional moisture-wicking capability. Within 2.25 s, triboelectric materials can quickly and directionally remove the droplets, driven by the Laplace pressure differences and the wettability gradient. The directional moisture-wicking triboelectric materials exhibit excellent pressure sensing performance, enabling rapid response/recovery (29.1/37.0 ms), thereby achieving real-time online monitoring of human respiration and movement states. This work addresses the long-standing challenge of insufficient moisture-wicking driving force in flexible electronic sensing materials, holding significant implications for enhancing the comfort and application potential of electronic skin and wearable electronic devices.

High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics.

The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.

Association of suPAR, ST2, and galectin-3 with eGFR decline and mortality in patients with advanced heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m2, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (ß coefficient = -0.36 √(ml/min/1.73 m2), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m2) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m2) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

The timing for embryo transfer after antibiotic therapy for chronic endometritis.

OBJECTIVE: To explore the optimal timing of embryo transfer after the first round treatment of chronic endometritis (CE) in vitro. MATERIALS AND METHODS: A total of 184 patients were recruited from a retrospective analysis of a large university-affiliated reproduction center in 2021. Some people chose to undergo embryo transfer in the same menstrual cycle with the first round of antibiotic treatment (Group 1, n = 29). Others received embryo transfer in the next cycle after the first round of treatment (Group 2, n = 69) or even one cycle later (Group 3，n = 96). RESULTS: Patients in Group 1 got significantly lower biochemical pregnancy rate and clinical pregnancy rate and live birth rate than Group 2 (p < 0.05) and also Group 3 (p < 0.05). Then after comparing the influence factors, we found embryo transfer in the next cycle after antibiotic treatment had a higher clinical pregnancy rate than group 1 (OR = 3.2 p < 0.05) and group 3(OR = 2.5, p < 0.05). The live birth rate in group 2 was higher than group 1(OR = 3.5, p < 0.05). CONCLUSION: These findings illustrate that embryo transfer in the next menstrual cycle is the optimal time. Embryo transfer in the same menstrual cycle with the first round of treatment reduces the pregnancy rate.

Copper/O2-Mediated Oxidative C-C Activation of Nitriles for Selective Acylation-Bromination of Anilines.

This study reports selective dual amino acylation and C-H bromination of aniline compounds enabled by Cu/O2 catalyst systems. This method involves crucial oxidation-induced C-CN bond cleavage of α-methylene nitriles to generate an acylcyanide intermediate that is facilely intercepted by anilines. After amino acylation, the Cu(II) precatalyst in combination with NBS generates Cu(III)-Br in situ that engages in selective electrophilic para- or ortho-C-H bromination. The substrate scope, mechanistic aspects, and late-stage functionalization of biologically active anilines are studied. This study shows the synthetic potential of oxidative C-CN bond activation of nitriles for the development of valuable reactions.

Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial.

Background: Postoperative sleep disturbance (PSD) is a common and serious postoperative complication and is associated with poor postoperative outcomes. Aims: This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on PSD in older patients undergoing lower limb major arthroplasty. Methods: In this prospective, double-blind, pilot, randomised, sham-controlled trial, patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS (a-tDCS) or sham tDCS (s-tDCS). The primary outcomes were the objective sleep measures on postoperative nights (N) 1 and N2. Results: 116 inpatients were assessed for eligibility, and a total of 92 patients were enrolled; 47 received a-tDCS and 45 received s-tDCS. tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups; the respective comparisons were as follows: the promotion of rapid eye movement (REM) sleep time on N1 (64.5 (33.5-105.5) vs 19.0 (0.0, 45.0) min, F=20.10, p<0.001) and N2 (75.0 (36.0-120.8) vs 30.0 (1.3-59.3) min, F=12.55, p<0.001); the total sleep time on N1 (506.0 (408.0-561.0) vs 392.0 (243.0-483.5) min, F=14.13, p<0.001) and N2 (488.5 (455.5-548.5) vs 346.0 (286.5-517.5) min, F=7.36, p=0.007); the deep sleep time on N1 (130.0 (103.3-177.0) vs 42.5 (9.8-100.8) min, F=24.4, p<0.001) and N2 (103.5 (46.0-154.8) vs 57.5 (23.3-106.5) min, F=8.4, p=0.004); and the percentages of light sleep and REM sleep on N1 and N2 (p<0.05 for each). The postoperative depression and anxiety scores did not differ significantly between the two groups. No significant adverse events were reported. Conclusion: In older patients undergoing lower limb major arthroplasty, a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures. However, this benefit was temporary and was not maintained over time.

Pixelwise calibration method for a telecentric structured light system.

This paper introduces a pixelwise calibration method designed for a structured light system utilizing a camera attached with a telecentric lens. In the calibration process, a white flat surface and a flat surface with circle dots serve as the calibration targets. After deriving the properties of the pinhole projector through a conventional camera calibration method using circle dots and determining the camera's attributes via 3D feature points estimation through iterative optimizations, the white surface calibration target was positioned at various poses and reconstructed with initial camera and projector calibration data. Each 3D reconstruction was fitted with a virtual ideal plane that was further used to create the pixelwise phase-to-coordinate mapping. To optimize the calibration accuracy, various angled poses of the calibration target are employed to refine the initial results. Experimental findings show that the proposed approach offers high calibration accuracy for a structured light system using a telecentric lens.

Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs.

BACKGROUND: Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. RESULTS: Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model. CONCLUSIONS: Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms.

Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O-GlcNAcylation of ß-catenin.

Ischemic stroke remains a major cause of disability and death. Kaempferol (Kae) is a neuroprotective flavonoid compound. Thus, this study aimed to explore the impact of Kae on cerebral infarction. We generated the middle cerebral artery occlusion (MCAO) mouse model to study the effects of Kae on infarction volume and neurological function. The oxygen and glucose deprivation (OGD)/reoxygenation (R) model of neural stem cells (NSCs) was established to study the effects of Kae on cell viability, migration, and apoptosis. Cell processes were assessed by cell counting kit-8, Transwell assay, flow cytometry, and TUNEL analysis. The molecular mechanism was assessed using the Western blot. The results indicated that Kae attenuated MCAO-induced cerebral infarction and neurological injury. Besides, Kae promoted cell viability and migration and inhibited apoptosis of OGD/R-treated NSCs. Moreover, OGD/R suppressed total O-GlcNAcylation level and O-GlcNAcylation of ß-catenin, thereby suppressing the Wnt/ß-catenin pathway, whereas Kae reversed the suppression. Inactivation of the Wnt/ß-catenin pathway abrogated the biological functions of NSCs mediated by Kae. In conclusion, Kae suppressed cerebral infarction by facilitating NSC viability, migration, and inhibiting apoptosis. Mechanically, Kae promoted O-GlcNAcylation of ß-catenin to activate the Wnt/ß-catenin pathway. Kae may have a lessening effect on ischemic stroke.