Hyaluronan and Glucose Dual-targeting Probe: Synthesis and Application.

In this work, we developed a dual-targeting probe consisted of well-defined hyaluronan (HA) oligosaccharide and glucose (Glc) labeled with Rhodamine B (HGR). The probe was designed to enhance tumor targeting both in vitro and in vivo, by simultaneously targeting CD44 and Glc transporter 1 (GLUT1). The HA oligosaccharide component was crucial for accurately assessing the impact of sugar chain structure on targeting efficacy, while its unoccupied carboxyl groups could minimize interference with HA's binding affinity to CD44. In vitro studies demonstrated that HGR possessed remarkable cytocompatibility and superior targeting abilities compared to single-targeting probes. It displayed a marked preference for CD44high/GLUT1high cells rather than CD44low/GLUT1low cells. In vivo studies using murine models further confirmed the significantly enhanced targeting efficacy and excellent biocompatibility of HGR. Therefore, this designed dual-targeting probe holds potential for clinical tumor detection.

Association between the systemic immune-inflammation index and erectile dysfunction: A cross-sectional study.

BACKGROUND: Erectile dysfunction (ED) is associated with inflammation. The systematic immune-inflammation index (SII), as a new inflammation marker, was applied to predict the risk of diseases. However, no research explores the relationship between SII and ED. Hence, the purpose of this study was to investigate the association between SII and ED. METHODS: Related data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. Based on self-report, all participants were classified into ED and non-ED group. Weighted multivariate regression analysis the relationship between categorical SII and ED in unadjusted and adjusted models. Restricted cubic spline (RCS) was used to examine the association of continuous SII and ED risk. Furthermore, the association between categorical SII and the risk of ED was evaluated among subgroups of age, body mass index, hypertension, diabetes and cardiovascular disease. Finally, weighted multivariate regression analysis and RCS were performed to assessed the connection between SII and the risk of severe ED. RESULTS: Initially, data on 21,161 participants were obtained. After implementing the inclusion and exclusion criteria, 3436 participants were included in analyses. Weighted multivariate regression analysis demonstrated that Q4 group SII was associated with an increased risk of ED (OR = 1.03, 95% confidence intervals: 1.00-1.05, p = .03). RCS showed SII was nonlinearly associated with the risk of ED, and the inflection point of SII was at 485.530. In addition, subgroup analyses demonstrated that participants in the SII > 485.530 group had a higher ED risk than SII ≤ 485.530 group among subgroups of age ≥50, hypertension, and non-diabetes. Weighted multivariate regression analysis and RCS found no relationship of SII and the risk of severe ED. CONCLUSION: In US adults, SII > 485.530 was correlated with an increased risk of ED. While, no significant association between SII and severe ED risk. Additional studies are required to support our results.

Horizontal gene transfer and symbiotic microorganisms regulate the adaptive evolution of intertidal algae, Porphyra sense lato.

Intertidal algae may adapt to environmental challenges by acquiring genes from other organisms and relying on symbiotic microorganisms. Here, we obtained a symbiont-free and chromosome-level genome of Pyropia haitanensis (47.2 Mb), a type of intertidal algae, by using multiple symbiont screening methods. We identified 286 horizontal gene transfer (HGT) genes, 251 of which harbored transposable elements (TEs), reflecting the importance of TEs for facilitating the transfer of genes into P. haitanensis. Notably, the bulked segregant analysis revealed that two HGT genes, sirohydrochlorin ferrochelatase and peptide-methionine (R)-S-oxide reductase, play a significant role in the adaptation of P. haitanensis to heat stress. Besides, we found Pseudomonas, Actinobacteria, and Bacteroidetes are the major taxa among the symbiotic bacteria of P. haitanensis (nearly 50% of the HGT gene donors). Among of them, a heat-tolerant actinobacterial strain (Saccharothrix sp.) was isolated and revealed to be associated with the heat tolerance of P. haitanensis through its regulatory effects on the genes involved in proline synthesis (proC), redox homeostasis (ggt), and protein folding (HSP20). These findings contribute to our understanding of the adaptive evolution of intertidal algae, expanding our knowledge of the HGT genes and symbiotic microorganisms to enhance their resilience and survival in challenging intertidal environments.

Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization.

Although deubiquitinases (DUBs) have been well described in liver tumorigenesis, their potential roles and mechanisms have not been fully understood. In this study, we identified ubiquitin-specific protease 1 (USP1) as an oncogene with essential roles during hepatocellular carcinoma (HCC) progression. USP1, with elevated expression levels and clinical significance, was identified as a hub DUB for HCC in multiple bioinformatics datasets. Functionally, USP1 overexpression significantly enhanced the malignant behaviors in HCC cell lines and spheroids in vitro, as well as the zebrafish model and the xenograft model in vivo. In contrast, genetic ablation or pharmacological inhibition of USP1 dramatically impaired the phenotypes of HCC cells. Specifically, ectopic USP1 enhanced aggressive properties and metabolic reprogramming of HCC cells by modulating mitochondrial dynamics. Mechanistically, USP1 induced mitochondrial fission by enhancing phosphorylation of Drp1 at Ser616 via deubiquitination and stabilization of cyclin-dependent kinase 5 (CDK5), which could be degraded by the E3 ligase NEDD4L. The USP1/CDK5 modulatory axis was activated in HCC tissues, which was correlated with poor prognosis of HCC patients. Furthermore, Prasugrel was identified as a candidate USP1 inhibitor for targeting the phenotypes of HCC by an extensive computational study combined with experimental validations. Taken together, USP1 induced malignant phenotypes and metabolic reprogramming by modulating mitochondrial dynamics in a CDK5-mediated Drp1 phosphorylation manner, thereby deteriorating HCC progression.

The prognostic significance and immune characteristics of bone morphogenetic proteins (BMPs) family: A pan-cancer multi-omics analysis.

BACKGROUND: Bone morphogenetic proteins (BMPs) are a group of cancer-related proteins vital for development and progression of certain cancer types. Nevertheless, function of BMP family in pan-cancer was not detailedly researched. OBJECTIVE: Investigating expression pattern and prognostic value of the BMPs family (BMP1-8A and BMP8B) expression across multiple cancer types. METHODS: Our research integrated multi-omics data for exploring potential associations between BMPs expression and prognosis, clinicopathological characteristics, copy number or somatic mutations, immune characteristics, tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint genes and drug sensitivity in The Cancer Genome Atlas (TCGA) tumors. Furthermore, association of BMPs expression and immunotherapy effectiveness was investigated in some confirmatory cohorts (GSE111636, GSE78220, GSE67501, GSE176307, IMvigor210 and mRNA sequencing data from currently undergoing TRUCE01 clinical research included), and biological function and potential signaling pathways of BMPs in bladder cancer (BCa) was explored via Gene Set Enrichment Analysis (GSEA). Eventually, immune infiltration analysis was done via BMPs expression, copy number or somatic mutations in BCa, as well as validation of the expression levels by reverse transcription-quantitative PCR and western blot, and in vitro functional experiments of BMP8A. RESULTS: Discoveries displayed BMPs expression was related to prognosis, clinicopathological characteristics, mutations, TME, TMB, MSI and immune checkpoint genes of TCGA tumors. Anticancer drug sensitivity analysis displayed BMPs were associated with various drug sensitivities. What's more, it was discovered that expression level of certain BMP family members related to objective response to immunotherapy. By GSEA, we discovered multiple immune-associated functions and pathways were enriched. Immune infiltration analysis on BCa also displayed significant associations among BMPs copy number variations, mutation status and infiltration level of diverse immune cells. Furthermore, differential expression validation and in vitro phenotypic experiment indicated that BMP8A significantly promoted BCa cell proliferation, migration and invasion. CONCLUSIONS: Current results confirmed significance of both BMPs expression and genomic alteration in the prognosis and treatment of diverse cancer types, and suggested that BMPs may be vital for BCa and can possibly be utilized as biomarkers for immunotherapy.

Hydroxide and Hydronium Ions Modulate the Dynamic Evolution of Nitrogen Nanobubbles in Water.

It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.

Counter-Doping Effect by Trivalent Cations in Tin-Based Perovskite Solar Cells.

Tin (Sn) -based perovskite solar cells (PSCs) normally show low open circuit voltage due to serious carrier recombination in the devices, which can be attributed to the oxidation and the resultant high p-type doping of the perovskite active layers. Considering the grand challenge to completely prohibit the oxidation of Sn-based perovskites, a feasible way to improve the device performance is to counter-dope the oxidized Sn-based perovskites by replacing Sn2+ with trivalent cations in the crystal lattice, which however is rarely reported. Here, the introduction of Sb3+, which can effectively counter-dope the oxidized perovskite layer and improve the carrier lifetime, is presented. Meanwhile, Sb3+ can passivate deep-level defects and improve carrier mobility of the perovskite layer, which are all favorable for the photovoltaic performance of the devices. Consequently, the target devices yield a relative enhancement of the power conversion efficiency (PCE) of 31.4% as well as excellent shelf-storage stability. This work provides a novel strategy to improve the performance of Sn-based PSCs, which can be developed as a universal way to compensate for the oxidation of Sn-based perovskites in optoelectronic devices.

Facet-Dependent Surface Restructuring on Nickel (Oxy)hydroxides: A Self-Activation Process for Enhanced Oxygen Evolution Reaction.

Unraveling the catalyst surface structure and behavior during reactions is essential for both mechanistic understanding and performance optimization. Here we report a phenomenon of facet-dependent surface restructuring intrinsic to ß-Ni(OH)2 catalysts during oxygen evolution reaction (OER), discovered by the correlative ex situ and operando characterization. The ex situ study after OER reveals ß-Ni(OH)2 restructuring at the edge facets to form nanoporous Ni1-xO, which is Ni deficient containing Ni3+ species. Operando liquid transmission electron microscopy (TEM) and Raman spectroscopy further identify the active role of the intermediate ß-NiOOH phase in both the OER catalysis and Ni1-xO formation, pinpointing the complete surface restructuring pathway. Such surface restructuring is shown to effectively increase the exposed active sites, accelerate Ni oxidation kinetics, and optimize *OH intermediate bonding energy toward fast OER kinetics, which leads to an extraordinary activity enhancement of ∼16-fold. Facilitated by such a self-activation process, the specially prepared ß-Ni(OH)2 with larger edge facets exhibits a 470-fold current enhancement than that of the benchmark IrO2, demonstrating a promising way to optimize metal-(oxy)hydroxide-based catalysts.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia.

AIMS: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Peptide-Based Hydrogel Scaffold Facilitates Articular Cartilage Damage Repair.

Articular cartilage injury is a common disease in clinical medicine. Because of its special physiological structure and lack of blood, lymph, and nerves, its ability to regenerate once damaged is very limited. In this study, we designed and synthesized a series of self- and coassembled cartilage-inducing functional peptide molecules and constructed a coassembled functional peptide hydrogel based on phenylboronic acid-o-dihydroxy "click chemistry" cross-linking to promote aggregation and signal transduction of mesenchymal stem cells (MSCs) in the early stage and differentiation toward cartilage, thereby promoting the repair of cartilage damage. Three functional peptide molecules were produced using solid-phase peptide synthesis technology, yielding a purity higher than 95%. DOPA-FEFEFEFEGHSNGLPL (DFP) and PBA-FKFKFKFKGHAVDI (BFP) were coassembled at near-neutral pH to form hydrogels (C Gels) based on phenylboronic acid-o-dihydroxy click chemistry cross-linking and effectively loaded transforming growth factor (TGF)-ß1 with a release period of up to 2 weeks. Furthermore, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) were cocultured with functional peptide hydrogels, and the results displayed that the coassembled functional peptide hydrogel group C Gels significantly promoted the proliferation of chondrocytes and MSCs. The chondrocyte markers collagen type I, collagen type II, and glycosaminoglycan (GAG) in the coassembled functional peptide hydrogel group were significantly higher than those in the control group, indicating that it can induce the differentiation of MSCs into cartilage. In vivo experiments demonstrated that the size and thickness of the new cartilage in the compound gel group were the most beneficial to cartilage regeneration. These results indicated that peptide hydrogels are a promising therapeutic option for cartilage regeneration.

Exploring the Dual Functions of Distal Acyl Group Direction in Various Nucleophilic Environments.

A universal glycosylation strategy could significantly simplify glycoside synthesis. One approach to achieving this goal is through acyl group direction for the corresponding 1,2-, 1,3-, 1,4-, or 1,6-trans glycosylation; however, this approach has been challenging for glycosidic bonds that require distal equatorial-acyl group direction. We developed an approach in weakly nucleophilic environments for selective 1,4-trans glycosylation directed by the equatorial-4-O-acyl group. Here, we explored this condition in other distal acyl groups and found that, besides 1,n-trans direction, acyl groups also mediated hydrogen bonding between acyl groups and alcohols. The latter showed a diverse effect and classified the acyl group direction into axial and equatorial categories. Corresponding glycosylation conditions were distinguished as guidance for acyl group direction from either category. Hence, acyl group direction may serve as a general glycosylation strategy.

A Mendelian randomization study on causal effects of inflammatory bowel disease on the risk of erectile dysfunction.

This study aimed to evaluate the causal effects of inflammatory bowel disease (IBD) and erectile dysfunction (ED) using Mendelian randomization (MR). All datasets were obtained from the public genome-wide association study database. In the exposure group, 12,882 IBD patients and 21,770 controls were included. A total of 1154 ED patients and 94,024 controls were included in the outcome group. Two-sample MR was conducted to estimate the causal effect of IBD on ED. Furthermore, Crohn's disease (CD) and ulcerative colitis (UC) were exposure factors in subgroup analyses. Weighted median, MR-egger, Inverse-variant weighted (IVW), weighted mode, and simple mode methods were used in MR analysis. Horizontal pleiotropy test, heterogeneity test, and leave-one-out method were utilized to evaluate the sensitivity and stability of results. After analysis, 62, 52, and 36 single nucleotide polymorphisms (SNPs) that IBD-ED, CD-ED, and UC-ED were included, respectively. The incidence of ED was increased by IBD (IVW: OR = 1.110, 95% CI = 1.017-1.211, P = 0.019; P-heterogeneity > 0.05) and, in addition, ED was affected by CD (IVW: OR = 1.085, 95% CI = 1.015-1.160, P = 0.016; P-heterogeneity > 0.05). However, there was no causal effect of UC on ED (IVW: OR = 1.018, 95% CI = 0.917-1.129, P = 0.743; P-heterogeneity < 0.05). All SNPs showed no significant horizontal pleiotropy (P > 0.05). These results indicate that IBD and CD can cause ED; However, UC did not cause ED. Additional research was required to determine causality and potential mechanisms further.

Characteristic Plasmon Energies for 2D In2Se3 Phase Identification at Nanoscale.

Two-dimensional (2D) materials with competing polymorphs offer remarkable potential to switch the associated 2D functionalities for novel device applications. Probing their phase transition and competition mechanisms requires nanoscale characterization techniques that can sensitively detect the nucleation of secondary phases down to single-layer thickness. Here we demonstrate nanoscale phase identification on 2D In2Se3 polymorphs, utilizing their distinct plasmon energies that can be distinguished by electron energy-loss spectroscopy (EELS). The characteristic plasmon energies of In2Se3 polymorphs have been validated by first-principles calculations, and also been successfully applied to reveal phase transitions using in situ EELS. Correlating with in situ X-ray diffraction, we further derive a subtle difference in the valence electron density of In2Se3 polymorphs, consistent with their disparate electronic properties. The nanometer resolution and independence of orientation make plasmon-energy mapping a versatile technique for nanoscale phase identification on 2D materials.

Large-Area Fabrication of Hexaazatrinaphthylene-Based 2D Metal-Organic Framework Films for Flexible Photodetectors and Optoelectronic Synapses.

2D conjugated metal-organic frameworks (c-MOFs) have emerged as promising materials for (opto)electronic applications due to their excellent charge transport properties originating from the unique layered-stacked structures with extended in-plane conjugation. The further advancement of MOF-based (opto)electronics necessitates the development of novel 2D c-MOF thin films with high quality. Cu-HHHATN (HHHATN: hexahydroxyl-hexaazatrinaphthylene) is a recently reported 2D c-MOF featuring high in-plane conjugation, strong interlayer π-π stacking, and multiple coordination sites, while the production of its thin-film form has not yet been reported. Herein, large-area Cu-HHHATN thin films with preferential orientation, high uniformity, and smooth surfaces are realized by using a convenient layer-by-layer growth method. Flexible photodetectors are fabricated, showing broadband photoresponse ranging from UV to short-wave infrared (370 to 1450 nm). The relatively long relaxation time of photocurrent, which arises from the trapping of photocarriers, renders the device's synaptic plasticity similar to that of biological synapses, promising its use in neuromorphic visual systems. This work demonstrates the great potential of Cu-HHHATN thin films in flexible optoelectronic devices for various applications.

Hollow-Carbon Confinement Annealing: A New Synthetic Approach to Make High-Entropy Solid-Solution and Intermetallic Nanoparticles.

High-entropy alloy (HEA) nanoparticles (NPs) have been emerging with superior compositional tunability and multielemental synergy, presenting a unique platform for material discovery and performance optimization. Here we report a synthetic approach utilizing hollow-carbon confinement in the ordinary furnace annealing to achieve the nonequilibrium HEA-NPs such as Pt0.45Fe0.18Co0.12Ni0.15Mn0.10 with uniform size ∼5.9 nm. The facile temperature control allows us not only to reveal the detailed reaction pathway through ex situ characterization but also to tailor the HEA-NP structure from the crystalline solid solution to intermetallic. The preconfinement of metal precursors is the key to ensure the uniform distribution of metal nanoparticles with confined volume, which is essential to prevent the thermodynamically favored phase separation even during the ordinary furnace annealing. Besides, the synthesized HEA-NPs exhibit remarkable activity and stability in oxygen reduction catalysis. The demonstrated synthetic approach may significantly expand the scope of HEA-NPs with uncharted composition and performance.

Machine Learning Models for Blood Glucose Level Prediction in Patients With Diabetes Mellitus: Systematic Review and Network Meta-Analysis.

BACKGROUND: Machine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. OBJECTIVE: In a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. METHODS: PubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. RESULTS: In total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. CONCLUSIONS: Statistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. TRIAL REGISTRATION: PROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250.

ß-l-Rhamnosylation and ß-d-Mannosylation Mediated by 4-O-Ester Groups in a Weakly Nucleophilic Environment.

eq-4-O-Acyl group directed ß-rhamnosylation and ß-mannosylation are achieved in a carborane or BARF anion formed weakly nucleophilic environment with the assistance of a 2,3-orthocarbonate group. The 4-O-acyl group plays a critical role in directing the ß-selectivity, and the weakly coordinating anion is essential to amplify this direction. The orthocarbonate group could be readily removed with 1,3-propanediol in the presence of BF3·Et2O.

No Difference Between Tacrolimus and Cyclosporine A on Depression Among Kidney Transplantation Recipients.

BACKGROUND: The 2 main types of calcineurin inhibitors (CNI) are tacrolimus (TAC) and cyclosporine A (CsA); both are needed by patients who receive kidney transplants. A common adverse reaction of TAC is depression, which is listed in its instructions. However, depression occurred rarely, according to the instructions manual for CsA. METHODS: Scales measuring depression were sent to recipients who had taken TAC or CsA to observe whether there was a difference in depression between patients who consumed the 2 drugs. From September 23rd-December 8th 2022, a questionnaire was sent to kidney transplant recipients online to investigate depression by PHQ-9 score. Then, the questionnaires returned were divided into 2 groups: TAC group and CsA group. The difference of basic characteristics was made to equal by means of propensity score matching (PSM). The scores, degrees of depression, and prevalence of major depression between the 2 groups were compared. RESULTS: Of 259 questionnaires returned, 220 questionnaires were valid. Among them, 170 recipients used TAC and 50 recipients used CsA. There were no significant differences in baseline characteristics after PSM. After PSM, there was no statistically significant difference in PHQ-9 (0.8) score, degree of depression (P = .7), or rate of major depression between the 2 groups. CONCLUSIONS: There was no significant difference between kidney transplant recipients taking TAC or CsA in PHQ-9 score, degree of depression, or prevalence of major depression.