Poly[μ-aqua-diaqua(μ3-1H-benzimid­azole-5-carboxylato-κ3 N 3:O,O′)(μ2-1H-benzimidazole-5-carboxylato-κ3 N 3:O:O′)-μ5-sulfato-μ4-sulfato-tri­cadmium]

The asymmetric unit of the title compound, [Cd3(C8H5N2O2)2(SO4)2(H2O)3]n, contains three CdII ions, two sulfate anions, two 1H-benzimidazole-5-carboxyl­ate (H2bic) ligands and three coordinated water mol­ecules. One CdII ion is six-coordinated and exhibits a distorted octa­hedral geometry, while the other two CdII ions are seven-coordinated, displaying a distorted penta­gonal–bipyramidal geometry. The CdII ions are bridged by two types of sulfate anions, producing inorganic chains along [100]. These chains are further connected by the H2bic ligands, leading to a three-dimensional framework. N—H⋯O and O—H⋯O hydrogen bonds and π–π inter­actions between the imidazole and benzene rings [centroid–centroid distances = 3.953 (2), 3.507 (2), 3.407 (2) and 3.561 (2) Å] further stabilize the crystal structure

Towards Personalized Healthcare in Cardiac Population: The Development of a Wearable ECG Monitoring System, an ECG Lossy Compression Schema, and a ResNet-Based AF Detector

Cardiovascular diseases (CVDs) are the number one cause of death worldwide. While there is growing evidence that the atrial fibrillation (AF) has strong associations with various CVDs, this heart arrhythmia is usually diagnosed using electrocardiography (ECG) which is a risk-free, non-intrusive, and cost-efficient tool. Continuously and remotely monitoring the subjects' ECG information unlocks the potentials of prompt pre-diagnosis and timely pre-treatment of AF before the development of any life-threatening conditions/diseases. Ultimately, the CVDs associated mortality could be reduced. In this manuscript, the design and implementation of a personalized healthcare system embodying a wearable ECG device, a mobile application, and a back-end server are presented. This system continuously monitors the users' ECG information to provide personalized health warnings/feedbacks. The users are able to communicate with their paired health advisors through this system for remote diagnoses, interventions, etc. The implemented wearable ECG devices have been evaluated and showed excellent intra-consistency (CVRMS=5.5%), acceptable inter-consistency (CVRMS=12.1%), and negligible RR-interval errors (ARE<1.4%). To boost the battery life of the wearable devices, a lossy compression schema utilizing the quasi-periodic feature of ECG signals to achieve compression was proposed. Compared to the recognized schemata, it outperformed the others in terms of compression efficiency and distortion, and achieved at least 2x of CR at a certain PRD or RMSE for ECG signals from the MIT-BIH database. To enable automated AF diagnosis/screening in the proposed system, a ResNet-based AF detector was developed. For the ECG records from the 2017 PhysioNet CinC challenge, this AF detector obtained an average testing F1=85.10% and a best testing F1=87.31%, outperforming the state-of-the-art

Overexpression of GATA2 Enhances Development and Maintenance of Human Embryonic Stem Cell-Derived Hematopoietic Stem Cell-like Progenitors

GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34⁺CD45⁺CD90⁺CD38⁻ HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs

Overexpression of GATA2 Enhances Development and Maintenance of Human Embryonic Stem Cell-Derived Hematopoietic Stem Cell-like Progenitors

GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38– HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs

Comparative outcomes of SARS-CoV-2 primary and reinfection in older adult patients

BackgroundThe outcomes of older adult people acquiring SARS-CoV-2 reinfection was unclear. This study aimed to compare the outcomes of older adult patients with COVID-19 reinfection and those with primary infection.MethodsThis retrospective cohort study used electronic medical records from the TriNetX Research Network. Older adult patients (aged ≥65 years) with COVID-19 between January 1, 2022, and December 31, 2022, were included in the study. The patients were subsequently categorized into reinfection or primary infection groups, according to whether they manifested two distinct COVID-19 episodes with an intervening period of more than 90 days. Propensity score matching was performed for covariate adjustment between the reinfection and primary infection groups. The primary outcome was a composite outcome, including emergency department visits, hospitalization, intensive care unit admission, mechanical ventilation use, and mortality, following primary infection and reinfection.ResultsAfter matching, 31,899 patients were identified in both the reinfection and primary infection groups. The risk of primary composite outcomes was 7.15% (n = 2,281) in the reinfection group and 7.53% (n = 2,403) in the primary infection group. No significant difference in the primary outcome was observed between groups (HR, 0.96; 95% CI, 0.91 to 1.02, p = 0.17). In addition, there was no significant differences between the reinfection and primary infection groups in terms of emergency department visit (HR, 1.03; 95% CI, 0.95 to 1.11, p = 0.49), all-cause hospitalization (HR, 0.94; 95% CI, 0.86 to 1.02, p = 0.14), intensive care unit admission (HR, 0.92; 95% CI, 0.67 to 1.28, p = 0.62), mechanical ventilation use (HR,1.35 95% CI, 0.69 to 2.64 p = 0.38), and all-cause mortality (HR, 0.94; 95% CI, 0.74 to 1.20, p = 0.62).ConclusionThere were no significant differences in clinical outcomes between older adult patients with COVID-19 reinfection and those with primary infection

eIF4E binding protein 1 expression is associated with clinical survival outcomes in colorectal cancer

eIF4E binding protein 1 (4E-BP1), is critical for cap-dependent and cap-independent translation. This study is the first to demonstrate that 4E-BP1 expression correlates with colorectal cancer (CRC) progression. Compared to its expression in normal colon epithelial cells, 4E-BP1 was upregulated in CRC cell lines and was detected in patient tumor tissues. Furthermore, high 4E-BP1 expression was statistically associated with poor prognosis. Hypoxia has been considered as an obstacle for cancer therapeutics. Our previous data showed that YXM110, a cryptopleurine derivative, exhibited anticancer activity via 4E-BP1 depletion. Here, we investigated whether YXM110 could inhibit protein synthesis under hypoxia. 4E-BP1 expression was notably decreased by YXM110 under hypoxic conditions, implying that cap-independent translation could be suppressed by YXM110. Moreover, YXM110 repressed hypoxia-inducible factor 1α (HIF-1α) expression, which resulted in decreased downstream vascular endothelial growth factor (VEGF) expression. These observations highlight 4E-BP1 as a useful biomarker and therapeutic target, indicating that YXM110 could be a potent CRC therapeutic drug

Humanization and Characterization of an Anti-Human TNF-α Murine Monoclonal Antibody

A murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions were identified via a molecular modeling of m357 built by computer-assisted homology modeling. By replacing these critical surface residues with the human counterparts, a humanized version, h357, was generated. The humanized h357 IgG1 was then stably expressed in a mammalian cell line and the purified antibody maintained the high antigen binding affinity as compared with the parental m357 based on a soluble TNF-α neutralization bioassay. Furthermore, h357 IgG1 possesses the ability to mediate antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity upon binding to cells bearing the transmembrane form of TNF-α. In a mouse model of collagen antibody-induced arthritis, h357 IgG significantly inhibited disease progression by intra-peritoneal injection of 50 µg/mouse once-daily for 9 consecutive days. These results provided a basis for the development of h357 IgG as therapeutic use