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AIM: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies. METHODS: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay. RESULTS: CRX overexpression and knockdown significantly increased (n=3, P

Ophiocordyceps sinensis, an entomopathogenic fungus, infects larvae from the Lepidoptera: Hepialidae family, forming the valuable Chinese cordyceps. Mycoviruses are widespread across major lineages of filamentous fungi, oomycetes, and yeasts and have the potential to influence fungal biology and ecology. This study aimed to detect mycovirus within O. sinensis by isolating double-stranded RNA from six stains for transcriptomic sequencing and analyzing publicly available transcriptome data from 13 O. sinensis representative samples. Our analysis revealed 13 mycoviruses, with nine reported for the first time in O. sinensis. These mycoviruses are distributed across five families—Partitiviridae, Mitoviridae, Narnaviridae, Botourmiaviridae, Deltaflexiviridae—and two unclassified lineages, Ormycovirus and Vivivirus. This study also revealed frequent coinfections within individual O. sinensis strains and dynamic shifts in viral composition during fungal development. These findings enhance our knowledge of mycovirus diversity within O. sinensis and provide new insights into their taxonomy.

Abstract Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma‐derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV‐miR‐29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR‐29s in RGC pathophysiology. It is showed that the overexpression of miR‐29b‐3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR‐29b‐3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV‐miR‐29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV‐based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Abstract Addition of organic compounds containing O/N heteroatoms to aqueous electrolytes such as ZnSO4 (ZS) solutions is one of the effective strategies to inhibit Zn anode dendrites and side reactions. However, addressing the stability of Zn plating/stripping at high current densities and areal capacities by this method is still a challenge, especially in capacitors known for high power and long life. Herein, an organic heterocyclic compound of 1, 4, 7, 10‐tetraazacyclododecane (TC) containing four symmetrically distributed N atoms is employed as ZS additive, expanding the life of Zn anodes from ≈ 30 h to 1000 and 240 h at deep plating/stripping conditions of 10 and 20 mA cm−2/mAh cm−2, respectively; the cumulative capacity is as high as 5.0 Ah cm−2 with 99% Coulombic efficiency, far exceeding reported additives. TC with higher binding energies than H2O for Zn species tends to adsorb to Zn (002) in a lying manner and participate in the solvation shell of Zn2+, thus avoiding Zn dendrites and side‐reaction damage, especially at high current densities. The TC‐endowed Zn anode's stability under such extreme conditions is verified in Zn‐ion capacitors (i.e., > 94.6% capacity retention after 28 000 cycles), providing new insights into the development of high‐power Zn‐based energy storage devices.

AbstractDisturbed circadian rhythms have been a risk factor for type 2 diabetes mellitus (T2DM). Melatonin is the major chronobiotic hormone regulating both circadian rhythm and glucose homeostasis. The rs10830963 (G allele) of the melatonin receptor 1B (MTNR1B) gene has the strongest genetic associations with T2DM according to several genome-wide association studies. The MTNR1B rs10830963 G allele is also associated with disturbed circadian phenotypes and altered melatonin secretion, both factors that can elevate the risk of diabetes. Furthermore, evolutionary studies implied the presence of selection pressure and ethnic diversity in MTNR1B, which was consistent with the “thrifty gene” hypothesis in T2DM. The rs10830963 G risk allele is associated with delayed melatonin secretion onset in dim-light and prolonged duration of peak melatonin. This delayed melatonin secretion may help human ancestors adapt to famine or food shortages during long nights and early mornings and avoid nocturnal hypoglycemia but confers susceptibility to T2DM due to adequate energy intake in modern society. We provide new insight into the role of MTNR1B variants in T2DM via disturbed circadian rhythms from the perspective of the “thrifty gene” hypothesis; these data indicate a novel target for the prevention and treatment of susceptible populations with the thrifty genotype.

Abstract Background The entomogenous fungus Beauveria bassiana is used as a biological insecticide worldwide, wild B. bassiana strains with high pathogenicity in the field play an important role in controlling insect pests via not only screening of highly virulent strains but also natural infection, but the pathogenicity degeneration of wild strains severely affected aforementioned effects. Previous studies have showed that multiple factors contributed to this phenomenon. It has been extensively proved that the mycovirus infection caused hypovirulence of phytopathogenic fungi, which has been used for plant disease biocontrol. However, it remains unknown whether the mycovirus epidemics is a key factor causing hypovirulence of B. bassiana naturally in the field. Methods Wild strains of B. bassiana were collected from different geographic locations in Jilin Province, China, to clarify the epidemic and diversity of the mycoviruses. A mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) we have previously identified was employed to clarify its impact on the pathogenicity of host fungi B. bassiana against the larvae of insect pest Ostrinia furnacalis. The serological analysis was conducted by preparing polyclonal antibody against a BbCV2 coat protein, to determine whether it can dissociate outside the host fungal cells and subsequently infect new hosts. Transcriptome analysis was used to reveal the interactions between viruses and hosts. Results We surprisingly found that the mycovirus BbCV2 was prevalent in the field as a core virus in wild B. bassiana strains, without obvious genetic differentiation, this virus possessed efficient and stable horizontal and vertical transmission capabilities. The serological results showed that the virus could not only replicate within but also dissociate outside the host cells, and the purified virions could infect B. bassiana by co-incubation. The virus infection causes B. bassiana hypovirulence. Transcriptome analysis revealed decreased expression of genes related to insect epidermis penetration, hypha growth and toxin metabolism in B. bassiana caused by mycovirus infection. Conclusion Beauveria bassiana infected by hypovirulence-associated mycovirus can spread the virus to new host strains after infecting insects, and cause the virus epidemics in the field. The findings confirmed that mycovirus infection may be an important factor affecting the pathogenicity degradation of B. bassiana in the field.

AIM: To introduce and evaluate the clinical efficacy of a new technique, the use of viscoelastic substances (VS) to close leaking sclerotomy in 23G microincision vitrectomy, and to observe its effect on the visual acuity and intraocular pressure (IOP) of patients. METHODS: Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique (June 2019 to September 2020) and after the use of VS technique (October 2020 to December 2021) were selected as the subjects of this study. The above cases underwent operation by the same surgeon and were retrospectively analyzed. VS technique was used as the alternative to suturing, in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure. RESULTS: A total of 174 eyes were covered in the study, including 84 eyes in the control group (before the use of VS technique) and 90 eyes in the VS technique group. The number of eyes that needed to be sutured decreased considerably from 42.9% in the control group to 3.3% in the VS technique group, and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7% in the control group to 2.2% in the VS technique group. No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group. No major complications associated with VS technique were identified during the study. CONCLUSION: In 23G microincision vitrectomy, VS technique is a safe, simple, and effective method to close leaking sclerotomy.

Recent advances in near-field technology with an ultrahigh spatial resolution breaking optical diffraction limit, make it possible to further identify surface-enhanced Raman scattering (SERS) enhancement theories, and to monitor the SERS substrates. Here we verify the electromagnetic enhancement mechanism for SERS with a close-up view, using scattering-type scanning near-field optical microscopy. The array of metal-insulator-metal (MIM) subwavelength structures is studied, in which the field enhancement comes from the strong coupling between gap plasmon polariton and surface plasmon polariton modes. The near-field optical measurements reveal that SERS enhancement factor (EF) varies from one MIM subwavelength unit to another in a finite array. Besides the enhancement of isolated unit, the loss exchange phenomenon in strong coupling with a large Rabi splitting can give rise to an additional enhancement of more than 2 orders of magnitude in periodic arrays and close to 3 orders of magnitude in finite arrays. The SERS EF of the array composed of only 5 units is demonstrated to yield the best SERS performance. Our near-field optical measurements show evidence that finite-size structures embodied with strong coupling effect are a key way to develop practical high-performance SERS substrates.

Food safety has become a topic of global concern in the recent decades. The significant food safety incidents occur from time to time around the world, seriously threatening the public health and causing extensive economic losses. In particular, the occurrence of COVID-19 highlights the importance of the food safety for the public health. Therefore, there is an urgent need to establish a fast, simple, sensitive, and efficient method for the detection of food safety. In recent years, the upconversion (UC) nanotechnology has been widely used in the field of food detection. The UC fluorescence analysis technology possesses the advantages of ultra-sensitivity detection, non-invasiveness, light stability, etc., and has broad application prospects in the field of food safety. After cladding and surface modification, it can be combined with other substances through a variety of mechanisms, such as electrostatic interaction, thereby expanding its application in the food safety detection. Thus, overall, there is a vital need to evaluate and utilize the potential of UC nanoparticles in the field of rapid detection of food safety.