Whole transcriptome sequencing analyses of islets reveal ncRNA regulatory networks underlying impaired insulin secretion and increased ß-cell mass in high fat diet-induced diabetes mellitus.

AIM: Our study aims to identify novel non-coding RNA-mRNA regulatory networks associated with ß-cell dysfunction and compensatory responses in obesity-related diabetes. METHODS: Glucose metabolism, islet architecture and secretion, and insulin sensitivity were characterized in C57BL/6J mice fed on a 60% high-fat diet (HFD) or control for 24 weeks. Islets were isolated for whole transcriptome sequencing to identify differentially expressed (DE) mRNAs, miRNAs, IncRNAs, and circRNAs. Regulatory networks involving miRNA-mRNA, lncRNA-mRNA, and lncRNA-miRNA-mRNA were constructed and functions were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: Despite compensatory hyperinsulinemia and a significant increase in ß-cell mass with a slow rate of proliferation, HFD mice exhibited impaired glucose tolerance. In isolated islets, insulin secretion in response to glucose and palmitic acid deteriorated after 24 weeks of HFD. Whole transcriptomic sequencing identified a total of 1324 DE mRNAs, 14 DE miRNAs, 179 DE lncRNAs, and 680 DE circRNAs. Our transcriptomic dataset unveiled several core regulatory axes involved in the impaired insulin secretion in HFD mice, such as miR-6948-5p/Cacna1c, miR-6964-3p/Cacna1b, miR-3572-5p/Hk2, miR-3572-5p/Cckar and miR-677-5p/Camk2d. Additionally, proliferative and apoptotic targets, including miR-216a-3p/FKBP5, miR-670-3p/Foxo3, miR-677-5p/RIPK1, miR-802-3p/Smad2 and ENSMUST00000176781/Caspase9 possibly contribute to the increased ß-cell mass in HFD islets. Furthermore, competing endogenous RNAs (ceRNA) regulatory network involving 7 DE miRNAs, 15 DE lncRNAs and 38 DE mRNAs might also participate in the development of HFD-induced diabetes. CONCLUSIONS: The comprehensive whole transcriptomic sequencing revealed novel non-coding RNA-mRNA regulatory networks associated with impaired insulin secretion and increased ß-cell mass in obesity-related diabetes.

Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Effect of iodine nutritional status on the recurrence of hyperthyroidism and antithyroid drug efficacy in adult patients with Graves' disease: a systemic review.

Aim: To probe the appropriate iodine nutritional status for patients with Graves'disease (GD) hyperthyroidism and on antithyroid drugs (ATD) or after drugwithdrawal. Method: Studies were retrieved from three databases (Embase, Medline, and Cochrane Library) and were screened and evaluated using predefined criteria. The risk of bias of each trial was assessed using a tool from Cochrane. The iodine nutritional status of the subjects was redefined according to the World Health Organization (WHO) criteria and classified as insufficient/adequate/above requirements/excessive iodine intake. Result: Two randomized controlled trials (RCTs) and 3 observational studies were selected from the 376 retrieved papers, which had different degrees of risk of bias in study design. The heterogeneity among them prevented us from further synthesizing effect indicators and subsequent statistical analyses. Two RCTs with high quality showed that insufficient or above requirements iodine intake was detrimental for ATD-treated GD patients; adequate iodine intake was associated with a lower risk of recurrence and better efficacy in controlling thyrotoxicosis. It could be speculated from three low-quality observational studies that excessive iodine intake may be associated with higher (or similar) recurrence rates and lower remission rates compared to above requirements iodine intake in these patients, but none of them could answer the question of the effect of insufficient or adequate iodine intake on this issue. Conclusion: Although the available evidence is suboptimal, this systematic review tentatively suggests that in adult patients with GD hyperthyroidism receiving ATDs and according to WHO criteria for iodine nutritional status, adequate iodine intake is associated with a lower recurrence rate, a higher remission rate and a better efficacy to control thyrotoxicosis than insufficient, above requirement, or excessive iodine intake. Future RCTs with large samples are expected to elucidate the actual impact of different iodine nutritional statuses on the recurrence rate of hyperthyroidism and the efficacy of ATD to control thyrotoxicosis in these patients. Systematic review registration: identifier CRD42022359451.

Power of the Sine Hamiltonian Operator for Estimating the Eigenstate Energies on Quantum Computers.

Quantum computers have been shown to have tremendous potential in solving difficult problems in quantum chemistry. In this paper, we propose a new classical-quantum hybrid method, named as power of sine Hamiltonian operator (PSHO), to evaluate the eigenvalues of a given Hamiltonian (H). In PSHO, for any reference state |φ0⟩, the normalized energy of the sinn(H^τ)|φ0⟩ state can be determined. With the increase of the power, the initial reference state can converge to the eigenstate with the largest |sin(Eiτ)| value in the coefficients of the expansion of |φ0⟩, and the normalized energy of the sinn(H^τ)|φ0⟩ state converges to Ei. The ground- and excited-state energies of a Hamiltonian can be determined by taking different τ values. The performance of the PSHO method is demonstrated by numerical calculations of the H4 and LiH molecules. Compared with the current popular variational quantum eigensolver method, PSHO does not need to design the ansatz circuits and avoids the complex nonlinear optimization problems. PSHO has great application potential in near-term quantum devices.

Orthogonal State Reduction Variational Eigensolver for the Excited-State Calculations on Quantum Computers.

Variational quantum eigensolver (VQE) is a promising method for ground-state calculations on current noisy intermediate-scale quantum computers. However, the research progress of excited-state calculations on quantum computers is relatively slow. In order to extend the framework of VQE for excited-state calculations, we propose a new algorithm, orthogonal state reduction variational eigensolver (OSRVE), to determine the energies of excited states. Theoretical derivations prove that the optimized state in the OSRVE method can ensure the energy minimum and orthogonality constraint simultaneously, and OSRVE is also applicable for the degenerate state. The performance of OSRVE is demonstrated by numerical calculations of the H4 and H2O molecules. Compared with other excited-state calculation algorithms, OSRVE has obvious advantages in calculating lower-order excited states. This work extends the VQE algorithm to excited-state calculations, and OSRVE can be implemented on near-term quantum computers.

Human coronaviruses and therapeutic drug discovery.

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.

Two novel triangular borophenes B3H and B6O: first-principles prediction.

By means of density functional theory calculations, we successfully predict two stable 2D triangular borophenes, namely B3H and B6O. Our results indicate that B3H is a Dirac material and its cone point is located at the K point of the Brillouin zone (BZ). B6O is identified as having a node-line ring and Dirac cones together. Its node-line ring formed by the intersection of the extended energy band from the two Dirac cones located on K point. This modified 2D borophene has great thermal and dynamic stability due to the electron transfer from the triangular boron lattice to the O atoms. The electronic structure of B6O nanofilm demonstrates novel properties such as two Dirac cones, more than 1.3 eV linear dispersion bands at some points of the BZ, as well as excellent transport properties for the extremely high mobility brought by the combination of the node-line semimetal and Dirac cones. Our study may motivate potential applications of 2D materials in nanoelectronics.