Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKß.

Inflammation is associated with a series of diseases like cancer, cardiovascular disease and infection, and phosphorylation/dephosphorylation modification of proteins are important in inflammation regulation. Here we designed and synthesized a novel Brazilin-Ce nanoparticle (BX-Ce NPs) using Brazilin, which has been used for anti-inflammation in cardiovascular diseases but with narrow therapeutic window, and Cerium (IV), a lanthanide which has the general activity in catalyzing the hydrolysis of phosphoester bonds, to conferring de/anti-phosphorylation of IKKß. We found that BX-Ce NPs specifically bound to Asn225 and Lys428 of IKKß and inhibited its phosphorylation at Ser181, contributing to appreciably anti-inflammatory effect in cellulo (IC50 = 2.5 µM). In vivo mouse models of myocardial infarction and sepsis also showed that the BX-Ce NPs significantly ameliorated myocardial injury and improved survival in mice with experimental sepsis through downregulating phosphorylation of IKKß. These findings provided insights for developing metal nanoparticles for guided ion interfere therapy, particularly synergistically target de/anti-phosphorylation as promising therapeutic agents for inflammation and related diseases.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy

ABSTRACT Objectives To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). Materials and methods This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. Results The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P <0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P <0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. Conclusions Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy.

OBJECTIVES: To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). MATERIALS AND METHODS: This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. RESULTS: The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P < 0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P < 0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. CONCLUSIONS: Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.

The Earliest Corotocini (Insecta: Coleoptera: Staphylinidae) from Dominican Amber, with Remarks on Post-Imaginal Growth Influence on Termitophile Taxonomy.

Pareburniola dominicana Zilberman, Yin & Cai gen. et. sp. nov. is the very first fossil record of the tribe Corotocini, reported from Miocene Dominican Republic amber. The new species, which is based on a stenogastric individual, is described and illustrated and is included in the subtribe Corotocina due to the combination of a tarsal formula 4-4-4, an elongated gula, a developed labial palp, a reduced fourth palpomere, separated metacoxae and a glandular structure on the posterior region of the head. Since the taxon belongs to the physogastric tribe Corotocini, which presents post-imaginal growth, this phenomenon is herein discussed, and its current knowledge is used to understand the possible outcomes during morphological changes in the fossil species.

Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting necroptosis and neuroinflammation via MAPK/NF-κB signaling pathway.

PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. METHODS: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. RESULTS: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin­1ß (IL­1ß), IL­6, NF­κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. CONCLUSIONS: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

Experimental study on the deformation localisation and acoustic emission characteristics of coal in Brazilian splitting tests.

This paper presents an experimental study to assess the behaviour of coal samples under tensile loadings to better understand the failure mechanisms and the interactions with the coal characteristics. A set of Brazilian splitting tests were carried out using disk specimens obtained from Tashan Coal Mine in China. The digital speckle correlation method and acoustic emission (AE) were used to capture the deformation localisation and AE characteristics of each specimen during the loading process. The precursor characteristics of AE and the failure mechanism are discussed. It was found that the entire loading process mainly consists of compaction, elastic and post-peak dropping stage without an obvious yielding stage. Two kinds of deformation localisation were observed: central symmetry and axis symmetry. The corresponding AE evolution patterns have different phases, including gradual rise, step rise, transient rise and steady rise. During the subcritical failure stage, AE counts demonstrate a "rapidly increasing + flatten" intermittent feature. The results provide a reference for a better understanding of the damage process of the brittle coal material and its application in ground control design.

Earliest teredid beetle from mid-Cretaceous amber of northern Myanmar (Coleoptera: Coccinelloidea: Teredidae): new genus and species

The earliest fossil member of Teredidae, Delteredolaemus hei Li & Cai gen. et sp. nov., is reported from mid-Cretaceous Burmese amber. Delteredolaemus is assigned to the extant tribe Teredini, and shares a generally similar morphology with the extant genus Teredolaemus Sharp, 1885, although it can be distinguished from all other members in the tribe by the shape of the pronotum and mesoventral process, as well as the anteromedially tumid metaventrite.(AU)

Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting necroptosis and neuroinflammation via MAPK/NF-κB signaling pathway

Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin­1ß (IL­1ß), IL­6, NF­κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

Anomocephalobus, a new genus of minute marsh-loving beetles from mid-Cretaceous Burmese amber (Coleoptera: Limnichidae)

Limnichidae are currently a moderately diverse beetle family with a sparse fossil record. Here we describe a new limnichid genus and species, Anomocephalobus liuhaoi Li, Jäch & Cai gen. et sp. nov., from the mid-Cretaceous amber from northern Myanmar. Anomocephalobus gen. nov. is tentatively assigned to the extant subfamily Cephalobyrrhinae, based on its transverse metacoxae, 5-segmented protarsi, and absence of grooves on the ventral surface for reception of legs, though its oval body shape is somewhat deviating from extant Cephalobyrrhinae. The generic placement of the recently described Erichia cretacea Yu, Ślipiński, Ren & Pang, 2018 is also discussed.(AU)

Effects of polyvinylpyrrolidone and poly (ethylene glycol) on preparation of ibuprofen pharmaceutical cocrystal

Abstract In this study, we investigated the effects of polymers on the pharmaceutical cocrystal formation process. Ibuprofen (IBU) was selected as the active pharmaceutical ingredient (API), nicotinamide (NIC) and saccharin (SAC) as the cocrystal coformer (CCF), ethanol/water as the solvent, polyvinylpyrrolidone (PVP) and poly (ethylene glycol) (PEG) as the representative polymers. We prepared IBU-NIC and IBU-SAC cocrystals in ethanol-water cosolvent in the absence or presence of polymers. Cocrystal screening products were characterized by FTIR, DSC, PXRD, and HPLC. The results showed that the mixture of IBU and IBU-NIC cocrystal can be prepared in ethanol-water cosolvent without polymers. The addition of PVP facilitates the formation of pure IBU-NIC cocrystal; however, no cocrystal was formed in PEG solutions. SAC could not cocrystallize with IBU in the ethanol-water solvent in the absence of polymers. Neither PVP nor PEG could facilitate the formation of the IBU-SAC cocrystal.

Climate influence on the 2019 fires in Amazonia.

Amazonia experienced unusually devastating fires in August 2019, leading to huge regional and global environmental and economic losses. The increase in fires has been largely attributed to anthropogenic deforestation, but anomalous climate conditions could also have contributed. This study investigates the climate influence on Amazonia fires in August 2019 and underlying mechanisms, based on statistical correlation and multiple linear regression analyses of 2001-2019 satellite-based fire products and multiple observational or reanalyzed climate datasets. Positive fire anomalies in August 2019 were mainly located in southern Amazonia. These anomalies were mainly driven by low precipitation and relative humidity, which increased fuel dryness and contributed to 38.9 ± 9.5% of the 2019 anomaly in pyrogenic carbon emissions over the southern Amazonia. The dry conditions were associated with southerly wind anomalies over southern Amazonia that suppressed the climatological southward transport of water vapor originating from the Atlantic. The southerly wind anomalies were caused by the combination of a Gill-type cyclonic response to the warmer North Atlantic sea surface temperature (SST), and enhancement of the Walker and Hadley circulations over South America due to the colder SST in the eastern Pacific, and a mid-latitude wave train triggered by the warmer condition in the western Indian Ocean. Our study highlights, for the first time, the important role of Indian Ocean SST for fires in Amazonia. It also reveals how cold SST anomalies in the tropical eastern Pacific link the warm phase of the El Niño-Southern Oscillation (ENSO) in the preceding December-January to the dry-season fires in Amazonia. Our findings can develop theoretical basis of global tropical SST-based fire prediction, and have potential to improve prediction skill of extreme fires in Amazonia and thus to take steps to mitigate their impacts which is urgency given that dry conditions led to the extreme fires are becoming common in Amazonia.

CRISPR-mediated base editing in mice using cytosine deaminase base editor 4

BACKGROUND: Many human genetic diseases arise from point mutations. These genetic diseases can theoretically be corrected through gene therapy. However, gene therapy in clinical application is still far from mature. Nearly half of the pathogenic single-nucleotide polymorphisms (SNPs) are caused by G:C>A:T or T:A>C:G base changes and the ideal approaches to correct these mutations are base editing. These CRISPR-Cas9-mediated base editing does not leave any footprint in genome and does not require donor DNA sequences for homologous recombination. These base editing methods have been successfully applied to cultured mammalian cells with high precision and efficiency, but BE4 has not been confirmed in mice. Animal models are important for dissecting pathogenic mechanism of human genetic diseases and testing of base correction efficacy in vivo. Cytidine base editor BE4 is a newly developed version of cytidine base editing system that converts cytidine (C) to uridine (U). RESULTS: In this study, BE4 system was tested in cells to inactivate GFP gene and in mice to introduce single-base substitution that would lead to a stop codon in tyrosinase gene. High percentage albino coat-colored mice were obtained from black coat-colored donor zygotes after pronuclei microinjection. Sequencing results showed that expected base changes were obtained with high precision and efficiency (56.25%). There are no off-targeting events identified in predicted potential off-target sites. CONCLUSIONS: Results confirm BE4 system can work in vivo with high precision and efficacy, and has great potentials in clinic to repair human genetic mutations.

Revisiting the morphology and systematic placement of the enigmatic Cretaceous ommatid beetle Bukhkalius lindae(Coleoptera: Archostemata: Ommatidae)

The systematic position of Bukhkalius lindae (Jarzembowski et al. 2017) from mid-Cretaceous Burmese amber is revised based on a re-examination of the type specimen. Our observations confirm that B. lindae lacks unique apomorphies of Tetraphalerus Waterhouse, in which it was originally placed, including complete antennal grooves and mushroom-shaped micro-tubercles. It is well justified to place it into a separate genus, i.e., Bukhkalius Kirejtshuk & Jarzembowski, 2020. The incomplete but distinct antennal grooves and the Tetraphalerus-like mouthparts of B. lindae suggest that it has a close affinity to Tetraphalerus. Therefore, B. lindae may represent a missing link bridging the morphological gap between extant ommatid subfamilies Tetraphalerinae and Ommatinae.(AU)

New species of Paraodontomma from mid-Cretaceous Burmese amber with muscle tissue preservation (Coleoptera: Archostemata: Ommatidae)

The third member of the extinct ommatid genus Paraodontomma is reported from mid-Cretaceous Burmese amber. Our observation confirms the transverse ridges on elytra as a diagnostic character for the genus. Paraodontomma leptocristatumsp. nov. differs from previously reported congeners mainly in head subquadrate and without prominent protuberances, pronotal disc without prominent ridges, elytral ridges indistinct, and teeth along elytral margins not forming a wavy pattern. Musculature is preserved in the newly discovered specimen of P. leptocristatum, which further demonstrates the preservation potential and irreplaceable value of amber fossils.(AU)

Revisiting the morphology of the Cretaceous ommatid beetle Clessidromma palmeri(Coleoptera: Archostemata: Ommatidae)

The morphology of Clessidromma palmeri Jarzembowski et al. from mid-Cretaceous Burmese amber is revised based on a reexamination of the type specimen. Contrary to previous studies, our observation confirms that Clessidromma has open procoxal cavities. The characters such as platform on the ventral side of head, modified metacoxae, and ridges on head and pronotum are suggested to be diagnostic characters for Clessidromma. Clessidromma zengi Kirejtshuk from the same deposit is transferred into a new genus, as Kirejtomma zengicomb. nov.(AU)

Revisiting the morphology and systematic placement of the enigmatic Cretaceous ommatid beetle Bukhkalius lindae (Coleoptera: Archostemata: Ommatidae)

Abstract The systematic position of Bukhkalius lindae (Jarzembowski et al. 2017) from mid-Cretaceous Burmese amber is revised based on a re-examination of the type specimen. Our observations confirm that B. lindae lacks unique apomorphies of Tetraphalerus Waterhouse, in which it was originally placed, including complete antennal grooves and mushroom-shaped micro-tubercles. It is well justified to place it into a separate genus, i.e., Bukhkalius Kirejtshuk & Jarzembowski, 2020. The incomplete but distinct antennal grooves and the Tetraphalerus-like mouthparts of B. lindae suggest that it has a close affinity to Tetraphalerus. Therefore, B. lindae may represent a missing link bridging the morphological gap between extant ommatid subfamilies Tetraphalerinae and Ommatinae.

New species of Paraodontomma from mid-Cretaceous Burmese amber with muscle tissue preservation (Coleoptera: Archostemata: Ommatidae)

Abstract The third member of the extinct ommatid genus Paraodontomma is reported from mid-Cretaceous Burmese amber. Our observation confirms the transverse ridges on elytra as a diagnostic character for the genus. Paraodontomma leptocristatum sp. nov. differs from previously reported congeners mainly in head subquadrate and without prominent protuberances, pronotal disc without prominent ridges, elytral ridges indistinct, and teeth along elytral margins not forming a wavy pattern. Musculature is preserved in the newly discovered specimen of P. leptocristatum, which further demonstrates the preservation potential and irreplaceable value of amber fossils.

Revisiting the morphology of the Cretaceous ommatid beetle Clessidromma palmeri (Coleoptera: Archostemata: Ommatidae)

Abstract The morphology of Clessidromma palmeri Jarzembowski et al. from mid-Cretaceous Burmese amber is revised based on a reexamination of the type specimen. Contrary to previous studies, our observation confirms that Clessidromma has open procoxal cavities. The characters such as platform on the ventral side of head, modified metacoxae, and ridges on head and pronotum are suggested to be diagnostic characters for Clessidromma. Clessidromma zengi Kirejtshuk from the same deposit is transferred into a new genus, as Kirejtomma zengi comb. nov.

New species of Paraodontomma from mid-Cretaceous Burmese amber with muscle tissue preservation (Coleoptera: Archostemata: Ommatidae)

Abstract The third member of the extinct ommatid genus Paraodontomma is reported from mid-Cretaceous Burmese amber. Our observation confirms the transverse ridges on elytra as a diagnostic character for the genus. Paraodontomma leptocristatum sp. nov. differs from previously reported congeners mainly in head subquadrate and without prominent protuberances, pronotal disc without prominent ridges, elytral ridges indistinct, and teeth along elytral margins not forming a wavy pattern. Musculature is preserved in the newly discovered specimen of P. leptocristatum, which further demonstrates the preservation potential and irreplaceable value of amber fossils.