Structure and activity of the septal peptidoglycan hydrolysis machinery crucial for bacterial cell division.

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.

An Effective Strategy on Synthesizing a Stable SiOx-Based Anode for High Density Lithium-Ion Batteries.

Silicon oxides (SiOx) have received extensive attention as an promising anode candidate for next-generation lithium-ion batteries (LIBs). However, their commerical applications have been seriously hindered by low conductivity, large volume expansion and unstable soild-electrolyte interface (SEI) layer, which result in low intial coulombic efficiency, poor rate performance and short cycling lifepan. In this work, we demonstrate a simple way to prepare a series of SiOx materials with lithium fluoride (LiF) modified by hydrothermal method and carbothermal modification. When the mass ratio of SiOx and LiF equals 1:0.15, the long-term cycling capacity retention can be greatly improve form 30.2% to 76.7% after 200 cycles. The result is primarily because the enhancement of electrons and Li+-ions transport and the stability of SEI layer due to LiF addition. However, excess LiF addition can hinder the diffusion of Li+-ions. This study presents the great potential of LiF modified on SiOx anode materials for LIBs.

V-Based MXene/MAX Heterostructure Composites with Enhancing Dielectric Loss for Broadband Microwave Absorption.

Electromagnetic wave absorption performance is strictly dependent on attenuation and impedance matching, which are directly influenced by the ratio of MXene/MAX in the multilayer structured MXene/MAX composites. However, there is still a challenge to achieve collaborative optimization of dielectric loss and impedance matching by precisely regulating the proportional relationship of MXene/MAX. Herein, V-based MXene/MAX heterostructure composites with different V2C/V2AlC ratios were successfully synthesized by rationally controlling the temperature and time of the hydrothermal reaction. Experimental results indicated that V2C-100 °C-1 harvested the balance between reduced impedance matching and enhanced dielectric losses, which was attributed to the mildly enhanced conduction loss and polarization loss. The first principles indicated that abundant electrons migrate from the V atoms of the MXene to the C atoms of the MAX phase. The charge redistributed and accumulated at the interface, exciting the increase in the dielectric loss of V2C-100 °C-1. As a result, the V2C-100 °C-1 heterostructure composite had an excellent electromagnetic absorption effect with a minimum reflection loss of -50.06 dB and a wide effective absorption bandwidth of 4.0 GHz (12.72-16.72 GHz). This work provides a valuable experience for the development of efficient MXene-based microwave absorbing materials.

Interleukin-1 receptor-associated kinase 2 promotes inflammatory reactions by activating the nuclear factor kappa-B signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is a major complication of diabetes. Interleukin-1 receptor-associated kinase 2 (IRAK2) has been implicated in various diseases. This study aimed to investigate the role of IRAK2 in DN progression and its association with inflammation and the nuclear factor-kappa B (NF-κB) signaling pathway. DN model mice were generated by intraperitoneal injection of streptozotocin. IRAK2 expression was upregulated in the DN model mice. IRAK2 knockdown increased weight and reduced blood glucose levels in DN model mice. In addition, IRAK2 downregulation improved glomerular morphology in DN mice. IRAK2 knockdown reduced the levels of kidney damage biomarkers (24-h urinary protein, urine albumin-creatinine ratio, and plasma creatinine) and inflammatory cytokines (IL-6, tumor necrosis factor [TNF]-α, TNF-1R, and TNF-2R). Moreover, IRAK2 activated the NF-κB signaling pathway in DN model mice. Overexpression of NF-κB exacerbated DN progression, and IRAK2 knockdown reversed these effects. IRAK2 promoted DN progression and inflammation by activating the NF-κB signaling pathway. These findings suggest that IRAK2 is a potential therapeutic target for DN treatment.

Future land use simulation model-based landscape ecological risk prediction under the localized shared socioeconomic pathways in the Xiangjiang River Basin, China.

Landscape ecological risk (LER) is an effective index to identify regional ecological risk and measure regional ecological security. The localized shared socioeconomic pathways (LSSPs) can provide multi-scenario parameters of social and economic development for LER research. The research of LER under LSSPs is of scientific significance and practical value in curbing the breeding and spread of LER risk areas. In this study, land-cover raster files from 2010 to 2020 were used as the foundational data. Future land use simulation (FLUS), regression, and Markov chain models were used to predict the land cover patterns under the five LSSP scenarios in the Xiangjiang River Basin (XJRB) in 2030. Thus, an evaluation model was established, and the LER of the watershed was evaluated. We found that the rate of land cover change (LCC) in the XJRB between 2010 and 2020 had a higher intensity (increasing at an average of 18.89% per decade) than that projected under the LSSPs for 2020-2030 (averaging an increase of 8.58% per decade). Among the growth rates of all land use types in the XJRB, that of urban land was the highest (33.3%). From 2010 to 2030, the LER in the XJRB was classified as lower risk (33.73%), lowest risk (33.11%), and moderate risk (24.13%) for each decade. Finally, the LER exhibited significant heterogeneity among different scenarios. Specifically, the percentages of regions characterized by the highest (9.77%) and higher LER (9.75%) were notably higher than those in the remaining scenarios. The higher-level risk area under the localized SSP1 demonstrated a clear spatial reduction compared to those of the other four scenarios. In addition, in order to facilitate the differential management and control of LER by relevant departments, risk zoning was carried out at the county level according to the prediction results of LER. And we got three types of risk management regions for the XJRB under the LSSPs.

[Retracted] miR­141 inhibits prostatic cancer cell proliferation and migration, and induces cell apoptosis via targeting of RUNX1.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that a number of plates showing colony formation assay data in Fig. 3A appeared to be overlapping, such that data purportedly showing the results from differently performed experiments may have been derived from the same original source(s); furthermore, certain of the cell­cycle histograms shown in Fig. 4B were duplicated, again where they were intended to have shown results obtained under different experimental conditions. Subsequently, following an independent enquiry in the office, it was also noted that, in Fig. 2B, the data shown for the RUNX1 western blots were apparently the same for both the DU145 and PC­2 cell lines. Although a corrigendum was requested by the authors, given the extent of the errors that were identified with respect to the compilation of as many as three of the figures in this paper, the Editor of Oncology Reports has decided that this article should be retracted from the publication owing to a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience that might result from the retraction of this article. [Oncology Reports 39: 1454­1460, 2018; DOI: 10.3892/or.2018.6209].

A perspective of spatial variability and ecological risks of antibiotics in the agricultural-pastoral ecotone soils in eastern Inner Mongolia.

Antibiotics have garnered growing attention as pharmaceuticals ubiquitously present in human society. Within the soil environment, antibiotics exhibit a propensity for high environmental persistence, thereby posing a potential threat to the ecosystem. However, research on antibiotics in agricultural-pastoral ecotone soils is scarce. This study investigates the occurrence, distribution and risk of 11 common antibiotics in agricultural soils of the agro-pastoral transition zone in Horqin Left Middle Banner, eastern Inner Mongolia. The total concentration varies from not detectable to 609.62 µg/kg. Tetracyclines are the dominant antibiotic, with a higher detection frequency than Macrolides and Sulfonamides. The detection rates of the three types of antibiotics differ significantly. The study also finds that soil properties (organic matter content, pH, bulk density, clay, cation exchange capacity have no significant correlation with antibiotics in soil. Moreover, spatial regression analysis reveals that population density is the primary factor influencing the spatial distribution of antibiotics in soil. Ecological risk assessment shows that clarithromycin and erythromycin are the two most harmful factors in the ecological risk of agricultural soil.

Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization.

Doxorubicin is an important class of anthracycline antitumor antibiotics produced by Streptomyces peucetius. The doxorubicin fermentation yield of the wild-type strain was very low, so it could not be produced directly by fermentation at an industrial scale due to the high cost. In the present study, S. peucetius SIPI-7-14 was obtained from SIPI-14 through several rounds of doxorubicin resistance screening. Then, the ketoreductase gene dnrU was knocked out to reduce (13S)-13-dihydrodaunorubicin production, and the resistance gene drrC was overexpressed to further enhance resistance to doxorubicin. The resulting engineered strain S. peucetius △U1/drrC produced 1128 mg/L doxorubicin, a 102.1% increase compared to that of SIPI-14. Then, fermentation medium was optimized using the response surface method. In the optimized fermentation medium, the yield of doxorubicin was increased to 1406 mg/L in shake flask on the 7th day. Furthermore, batch culture was carried out in a 10 L fermenter, and the concentration of doxorubicin reached 1461 mg/L after 7 days of culture, which was the highest yield reported to date, indicating the potential for industrial production of doxorubicin by fermentation.

Considering microplastic characteristics in ecological risk assessment: A case study for China.

Microplastics (MPs) pose a significant global concern, requiring a multifaceted approach to their risk assessment procedures, especially concerning their characteristics in the environment. The Horqin Left Middle Banner in Northeast China was chosen for the research region to investigate the abundance, composition, distribution, and ecological impact of MPs in surface agricultural soils. The concentrations of MPs ranged from 300 to 12800 items/kg, with a median concentration of 1550 items/kg (average = 1994 items/kg). The normal-sized MPs (500-5000 µm) had a higher relative abundance than small MPs (<500 µm). MPs were mainly derived from textiles and packaging and were affected by atmospheric transportation. Rayon and PET fibers were the main polymers identified. Furthermore, the potential environmental risks posed by the fundamental characteristics (abundance, chemical composition, and size) of MPs were quantified using multiple risk assessment models. The conditional fragmentation model indicated a propensity for MPs to degrade into smaller particles. Ecological risk assessments using pollution load index, pollution hazard index, and potential ecological risk index models revealed varying levels of risk. This study conducted a comprehensive assessment of the ecological risks of MPs based on their environmental characteristics, emphasizing the importance of considering multiple factors in the risk assessment process. ENVIRONMENT IMPLICATION: This study investigates the occurrence, distribution, and ecological risk of microplastics (MPs) in agricultural soils of the Northeast Plain of China, a major food production area. MPs are persistent organic pollutants that can pose threats to soil health, crop quality, and food security. By analyzing the composition, size, and source of MPs, as well as their fragmentation and stability in soil, this study provides valuable data for assessing the environmental risk of MPs in agricultural regions. The study also suggests strategies for mitigating MPs pollution and protecting soil ecosystems.

Mapping trends and hotspots in research on global influenza vaccine hesitancy: A bibliometric analysis.

Background and Aims: Influenza is one of the most widespread respiratory infections and poses a huge burden on health care worldwide. Vaccination is key to preventing and controlling influenza. Influenza vaccine hesitancy is an important reason for the low vaccination rate. In 2019, Vaccine hesitancy was identified as one of the top 10 threats to global health by the World Health Organization. However, there remains a glaring scarcity of bibliometric research in that regard. This study sought to identify research hotspots and future development trends on influenza vaccine hesitation and provide a new perspective and reference for future research. Methods: We retrieved publications on global influenza vaccine hesitancy from the Web of Science Core Collection database, Scopus, and PubMed databases from inception to 2022. This study used VOSviewer and CiteSpace for visualization analysis. Results: Influenza vaccine hesitancy-related publications increased rapidly from 2012 and peaked in 2022. One hundred and nine countries contributed to influenza vaccine hesitation research, and the United States ranked first with 541 articles and 7161 citations. Vaccines-Basel was the journal with the largest number of published studies on influenza vaccine hesitations. MacDonald was the most frequently cited author. The most popular research topics on influenza vaccine hesitancy were (1) determinants of influenza vaccination in specific populations, such as healthcare workers, children, pregnant women, and so on; (2) influenza and COVID-19 vaccine hesitancy during the COVID-19 pandemic. Conclusions: The trend in the number of annual publications related to influenza vaccine hesitancy indicating the COVID-19 pandemic will prompt researchers to increase their attention to influenza vaccine hesitancy. With healthcare workers as the key, reducing vaccine hesitancy and improving vaccine acceptance in high-risk groups will be the research direction in the next few years.

Essential and multifunctional mpox virus E5 helicase-primase in double and single hexamer.

An outbreak of mpox virus in May 2022 has spread over 110 nonpandemic regions in the world, posing a great threat to global health. Mpox virus E5, a helicase-primase, plays an essential role in DNA replication, but the molecular mechanisms are elusive. Here, we report seven structures of mpox virus E5 in a double hexamer (DH) and six in single hexamer in different conformations, indicating a rotation mechanism for helicase and a coupling action for primase. The DH is formed through the interface of zinc-binding domains, and the central channel density indicates potential double-stranded DNA (dsDNA), which helps to identify dsDNA binding residues Arg249, Lys286, Lys315, and Lys317. Our work is important not only for understanding poxviral DNA replication but also for the development of novel therapeutics for serious poxviral infections including smallpox virus and mpox virus.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

Structural basis of human mpox viral DNA replication inhibition by brincidofovir and cidofovir.

Mpox virus has wildly spread over 108 non-endemic regions in the world since May 2022. DNA replication of mpox is performed by DNA polymerase machinery F8-A22-E4, which is known as a great drug target. Brincidofovir and cidofovir are reported to have broad-spectrum antiviral activity against poxviruses, including mpox virus in animal models. However, the molecular mechanism is not understood. Here we report cryogenic electron microscopy structures of mpox viral F8-A22-E4 in complex with a DNA duplex, or dCTP and the DNA duplex, or cidofovir diphosphate and the DNA duplex at resolution of 3.22, 2.98 and 2.79 Å, respectively. Our structural work and DNA replication inhibition assays reveal that cidofovir diphosphate is located at the dCTP binding position with a different conformation to compete with dCTP to incorporate into the DNA and inhibit DNA synthesis. Conformation of both F8-A22-E4 and DNA is changed from the pre-dNTP binding state to DNA synthesizing state after dCTP or cidofovir diphosphate is bound, suggesting a coupling mechanism. This work provides the structural basis of DNA synthesis inhibition by brincidofovir and cidofovir, providing a rational strategy for new therapeutical development for mpox virus and other pox viruses.

Selective microRNA expression of exosomes from retinal pigment epithelial cells by oxidative stress.

The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1ß, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future.

A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.

Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases.