Comprehensive Characterization of a Subfamily of Ca2+-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution.

Ca2+-binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca2+ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions.

Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Analyzing venous thromboembolism risk in malignant tumors: thromboelastogram and coagulation factors study.

Aim: This retrospective clinical study was designed to examine the predictive value of thromboelastography (TEG) combined with coagulation function for venous thromboembolism (VTE) in hospitalized patients with cancer. Materials & methods: Among 215 patients admitted between May 2020 and January 2022, 39 (18.14%) were diagnosed with VTE during hospitalization. Results: Significant differences were found in D-dimer, ATIII and TEG parameters (maximum amplitude and coagulation index) between VTE-positive and VTE-negative patients (p < 0.05). Multivariate analysis revealed tumor node metastasis stage, concomitant infection, smoking history and D-dimer as independently associated with VTE. The constructed model and D-dimer areas under the curve were 0.809 and 0.764, respectively. Conclusion: TEG parameters were not significantly predictive indicators for VTE, with D-dimer remaining a key predictor.

[Box: see text].

An extracellular vesicle microRNA-initiated 3D DNAzyme motor for colorectal cancer diagnosis.

MicroRNA is regarded as a significant biomarker for cancer diagnosis, disease process evaluation and therapeutic guidance, and dual-parameter measurement may contribute to a more accurate and realistic assessment. To meet the urgent need for simultaneous detection of multiple biomarkers, we combined three-dimensional DNAzyme motors with single molecule imaging technique to construct a convenient, intuitive, and sensitive approach for the simultaneous detection of dual miRNAs in the free state or in extracellular vesicles. Quantification of target miRNAs can be realized through the detection of amplified fluorescence signals generated by the target miRNA-initiated cleavage of fluorescent substrate strands by the DNAzyme motors. The practicability was systematically validated with microRNA-21-5p and microRNA-10b-5p as targets, acquiring a satisfactory sensitivity sufficient to detect low abundance targets at 0.5 or 1 pM to 100 pM. Besides, the extracellular vesicular miRNAs can be conveniently detected without extraction. The clinical applicability was verified with a series of extracellular vesicles from clinical samples, which exhibited good distinguishability between colorectal cancer patients and healthy donors. In addition to the advantages of good specificity and high sensitivity, the system has potential to be easily adapted by minor alteration of the DNA sequences and fluorophore sets for detection of multiple miRNAs and even other types of biomarkers such as proteins. Therefore, it shows promise to be widely applied in various fields such as early diagnosis of cancer and its prognostic assessment.

Role of umbilical cord mesenchymal stromal cells in skin rejuvenation.

Aging is the main cause of many degenerative diseases. The skin is the largest and the most intuitive organ that reflects the aging of the body. Under the interaction of endogenous and exogenous factors, there are cumulative changes in the structure, function, and appearance of the skin, which are characterized by decreased synthesis of collagen and elastin, increased wrinkles, relaxation, pigmentation, and other aging characteristics. skin aging is inevitable, but it can be delayed. The successful isolation of mesenchymal stromal cells (MSC) in 1991 has greatly promoted the progress of cell therapy in human diseases. The International Society for Cellular Therapy (ISCT) points out that the MSC is a kind of pluripotent progenitor cells that have self-renewal ability (limited) in vitro and the potential for mesenchymal cell differentiation. This review mainly introduces the role of perinatal umbilical cord-derived MSC(UC-MSC) in the field of skin rejuvenation. An in-depth and systematic understanding of the mechanism of UC-MSCs against skin aging is of great significance for the early realization of the clinical transformation of UC-MSCs. This paper summarized the characteristics of skin aging and summarized the mechanism of UC-MSCs in skin rejuvenation reported in recent years. In order to provide a reference for further research of UC-MSCs to delay skin aging.

A novel robust evaluation approach to improve systematic behavior of failure safety in water supply system under various ellipsoid uncertainties.

This study proposes a novel robust optimization approach for an integrated water supply system, wherein the decision-makers attempt to improve failure safety of system under various uncertainty strategies. To cope with uncertainty, the ellipsoid uncertainty set is assumed to evaluate the best feasible solution in the direction of water supply under various strategies. We assessed the case of Hamoun watershed, a water-stressed watershed in southeastern of Iran, to evaluate the developed robust optimization model. In the following, the comparative feasibility under uncertainty levels is conducted to analyze the impacts of simulation strategies on the status of robust model. Based on the final results, the reliability of the model's objective functions experienced an increasing trend ( 58.3 % ), and the objective function values under the uncertainty strategies is greatly improved. The findings of the analysis show that the robust strategies in response to the failure safety achieve outstanding optimal objectives under uncertainty.

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Exo-Selective Diels-Alder Reactions.

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions.

The value of sequential application of hydrogen peroxide, povidone-iodine and physiological saline in reducing postoperative infections after total knee arthroplasty: A prospective, randomized, controlled study.

BACKGROUND: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA. METHODS: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study. RESULTS: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121). CONCLUSION: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis.

Highly Bright and Stable Lead-Free Double Perovskite White Light-Emitting Diodes.

Lead-free double perovskites (DPs) are emerging highly stable emitters with efficient broadband self-trapped exciton (STE) photoluminescence (PL), but their low electroluminescent (EL) efficiency is a critical shortcoming. This work promotes the external quantum efficiency (EQE) and luminance of DP-based white light-emitting diode (wLED) with a normal device structure to 0.76% and 2793 cd m-2 via two modifications: This work prevents the formation of adverse metallic silver, spatially confined STE, and lowers local site symmetry in Cs2 Na0.4 Ag0.6 In0.97 Bi0.03 Cl6 DP by terbium doping; and this work develops a guest-host strategy to improve film morphology, reduce defect density, and increase carrier mobility. These alterations cause substantial increase in STE radiative recombination and charge injection efficiency of perovskite layer. Finally, pure white EL with ideal color coordinates of (0.328, 0.329) and a record-breaking optoelectronic performance is achieved by introducing additional green carbon dots in LED to fill the deficient green component.

Application and challenges of stem cells in cardiovascular aging.

With the rapid development of society and the economy, population aging has become a common challenge faced by many countries in the world today. Structural and functional changes in the cardiovascular system can occur with age, increasing the incidence and severity of cardiovascular diseases in older adults. Due to the limited regenerative capacity of myocardial cells, myocardial infarction and its resulting heart failure and congenital heart disease have become the number one killer of human health. At present, the treatment of cardiovascular diseases includes drug therapy and nondrug therapy. Nondrug therapy mainly includes minimally invasive interventional therapy, surgical diagnosis and treatment, and cell therapy. Long-term drug treatment may cause headache due to vasodilation, lower blood pressure, digestive system dysfunction and other side effects. Surgical treatment is traumatic, difficult to treat, and expensive. In recent years, stem cell therapy has exhibited broad application prospects in basic and clinical research on cardiovascular disease because of its plasticity, self-renewal and multidirectional differentiation potential. Therefore, this paper looks at stem cell therapy for diseases, reviews recent advances in the mechanism and clinical transformation of cardiovascular aging and related diseases in China, and briefly discusses the development trend and future prospects of cardiovascular aging research.

Chromosome genome assembly and whole genome sequencing of 110 individuals of Conogethes punctiferalis (Guenée).

The yellow peach moth, Conogethes punctiferalis, is a highly polyphagous pest widespread in eastern and southern Asia. It demonstrates a unique ability to adapt to rotten host fruits and displays resistance to pathogenic microorganisms, including fungi. However, the lack of available genomic resources presents a challenge in comprehensively understanding the evolution of its innate immune genes. Here, we report a high-quality chromosome-level reference genome for C. punctiferalis utilizing PacBio HiFi sequencing and Hi-C technology. The genome assembly was 494 Mb in length with a contig N50 of 3.25 Mb. We successfully anchored 1,226 contigs to 31 pseudochromosomes. Our BUSCO analysis further demonstrated a gene coverage completeness of 96.3% in the genome assembly. Approximately 43% repeat sequences and 21,663 protein-coding genes were identified. In addition, we resequenced 110 C. punctiferalis individuals from east China, achieving an average coverage of 18.4 × and identifying 5.8 million high-quality SNPs. This work provides a crucial resource for understanding the evolutionary mechanism of C. punctiferalis' innate immune system and will help in developing new antibacterial drugs.

A novel objective for improving the sustainability of water supply system regarding hydrological response.

In general, the sustainability of the water supply system is indicative of an adaptive operational approach, wherein the decision-maker adjusts the system's performance based on the availability of water resources in a given time frame. In light of this, a novel framework is proposed in this study to evaluate sustainability, including three key indicators: resilience, reliability, and vulnerability. To address stressors that may lead to system failure, a multisectoral water allocation optimization is undertaken. In order to account for the future implications of climate change on the hydrological cycle, a simulation step, is incorporated, utilizing the Soil and Water Assessment Tool (SWAT) under various emission scenarios (RCP4.5 and RCP8.5), prior to integrating the streamflow data into our proposed optimal framework. To calibrate and validate historical data (2014-2019) and simulate future streamflow patterns (2025-2085), the Sistan Basin, located in an arid region of Iran, is analyzed as a case study. In light of the anticipated adverse impacts on the water supply system, certain adaptation measures, such as demand shrinkage scenarios, are considered to further appraise the proposed framework. Based on the final output, it is evident that the agricultural and industrial sectors, being the primary water consumers, are more susceptible to negative impacts resulting from the reduction in system sustainability. This susceptibility is primarily attributed to their highest vulnerability and comparatively lower reliability.

Adsorption Mechanism of Benzene Derivatives by Pagoda[n]arenes.

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment. The control of these substances has become an important subject of scientific research. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing pagoda[n]arene based supramolecular materials. Density functional theory calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes (Pa[4]As and Pa[5]As). Results indicate that Pa[4]As and Pa[5]As can effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]As possess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivatives to desorb from the adsorbing aggregates, and thus the material can be reutilized.

Synthesis towards Phainanoid F: Photo-induced 6π-Electrocyclization for Constructing Contiguous All-Carbon Quaternary Centers.

In this paper, we report an efficient strategy for synthesizing the DEFGH rings of phainanoid F. The key to the construction of the 13,30-cyclodammarane skeleton of the molecule was a photo-induced 6π-electrocyclization and a homoallylic elimination. Notably, this is a rare example of using electrocyclization reaction to simultaneously construct two vicinal quaternary carbons in total synthesis. The strategy outlined here forms the basis of our total synthesis of Phainanoid F, and it could also serve as a generally applicable approach for synthesizing other natural products containing similar 13,30-cyclodammarane skeletons.

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Improving robustness of water supply system using a multi-objective robust optimization framework.

Due to the uncertainty of rainfall and water demand, the water supply of various participants has been challenged in such a way that this challenge has accelerated the failure of water supply system. Thus, this study proposes a multi-stage Adjustable Robust Optimization integrated to the multi-objective programming framework to drive water supply system to the failure safety zone and thereby improve robustness of system under different scenarios. Indeed, Adjustable Robust Optimization framework is applied to investigate the two uncertain factors of rainfall and water demand. A real arid area of Sistan basin in southeastern Iran is considered to analyze the proposed multi-objective programming model. Next, various comparative feasibilities under different levels of uncertainty are carried out to examine the robustness status in more detail. In the following, due to the deterioration of climatic patterns in the coming years, some managerial insights are highlighted. According to the final outputs, the domestic sector has reached more optimal value compared to that of the agricultural and industrial participants in all objectives due to less water intake, and as a result, it has a significant impact on the robustness of water supply system.

Genome of the hoverfly Eupeodes corollae provides insights into the evolution of predation and pollination in insects.

BACKGROUND: Hoverflies (Diptera: Syrphidae) including Eupeodes corollae are important insects worldwide that provide dual ecosystem services including pest control and pollination. The larvae are dominant predators of aphids and can be used as biological control agents, and the adults are efficient pollinators. The different feeding habits of larvae and adults make hoverflies a valuable genetic resource for understanding the mechanisms underlying the evolution and adaptation to predation and pollination in insects. RESULTS: Here, we present a 595-Mb high-quality reference genome of the hoverfly E. corollae, which is typical of an aphid predator and a pollinator. Comparative genomic analyses of E. corollae and Coccinellidae (ladybugs, aphid predators) shed light on takeout genes (3), which are involved in circadian rhythms and feeding behavior and might regulate the feeding behavior of E. corollae in a circadian manner. Genes for sugar symporter (12) and lipid transport (7) related to energy production in E. corollae had homologs in pollinator honeybees and were absent in predatory ladybugs. A number of classical cytochrome P450 detoxification genes, mainly CYP6 subfamily members, were greatly expanded in E. corollae. Notably, comparative genomic analyses of E. corollae and other aphidophagous hoverflies highlighted three homologous trypsins (Ecor12299, Ecor12301, Ecor2966). Transcriptome analysis showed that nine trypsins, including Ecor12299, Ecor12301, and Ecor2966, are strongly expressed at the larval stage, and 10 opsin genes, which are involved in visual perception, are significantly upregulated at the adult stage of E. corollae. CONCLUSIONS: The high-quality genome assembly provided new insights into the genetic basis of predation and pollination by E. corollae and is a valuable resource for advancing studies on genetic adaptations and evolution of hoverflies and other natural enemies.

Computed Tomography Angiography and Three-Dimensional Reconstruction of Renal Arteries in Diagnosing the Bleedings After Mini-Percutaneous Nephrolithotomy: A Single-center Experience of 7 Years.

OBJECTIVE: This study aimed to investigate the role of computed tomography angiography (CTA) and three-dimensional (3D) reconstruction of renal arteries in the evaluation of bleeding after mini- percutaneous nephrolithotomy (PCNL). METHODS: Thirty-one consecutive patients with continuous renal hemorrhage after mini-PCNL were enrolled from January 2015 to January 2022. Demographic and clinical data were retrospectively recorded and analyzed. All patients had received CTA evaluation and subsequently digital subtraction angiography (DSA) embolization to manage renal bleeding. CTA and 3D reconstruction of renal arteries were performed using the 320 multi-detector computed tomography technique and the images were evaluated by experienced radiologists. DSA embolization were performed by an interventional radiologist with more than 10 years of experiences. RESULTS: CTA and 3D construction of renal arteries showed 28 cases of vascular lesions (28/31, 90.3%), including 15 cases of pseudoaneurysm (15/28, 53.6%), 9 cases of arteriovenous fistula (9/28, 32.1%), and 4 cases of suspicious bleeding spot (4/28, 14.3%). While DSA revealed 31 cases of vascular lesions (100%), including 15 cases of pseudoaneurysm (15/31, 48.4%), 10 cases of arteriovenous fistula (10/31, 32.3%), 6 cases of bleeding spot and (6/31, 19.4%). The serum creatinine level was elevated slightly before mini-PCNL and after DSA embolization (73.1±18.1 vs 92.1±33.6, P <.01). 15 patients (15/31, 48.4%) required blood transfusion, with mean blood transfusion volume of 700 ml ±660 ml (range, 400 ml-1800 ml). The bleeding was controlled without any further severe complications. CONCLUSION: CTA and 3D reconstruction of renal arteries were safe and effective in diagnosing renal arterial bleedings after mini-PCNL, with a sensitivity of 90.3% and a specificity of 100%.