A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.

Joint diffusion: mutual consistency-driven diffusion model for PET-MRI co-reconstruction.

OBJECTIVE: Positron Emission Tomography and Magnetic Resonance Imaging (PET-MRI) systems can obtain functional and anatomical scans. But PET suffers from a low signal-to-noise ratio, while MRI are time-consuming. To address time-consuming, an effective strategy involves reducing k-space data collection, albeit at the cost of lowering image quality. This study aims to leverage the inherent complementarity within PET-MRI data to enhance the image quality of PET-MRI. Apporach: A novel PET-MRI joint reconstruction model, termed MC-Diffusion, is proposed in the Bayesian framework. The joint reconstruction problem is transformed into a joint regularization problem, where data fidelity terms of PET and MRI are expressed independently. The regular term, the derivative of the logarithm of the joint probability distribution of PET and MRI, employs a joint score-based diffusion model for learning. The diffusion model involves the forward diffusion process and the reverse diffusion process. The forward diffusion process adds noise to transform a complex joint data distribution into a known joint prior distribution for PET and MRI simultaneously, resembling a denoiser. The reverse diffusion process removes noise using a denoiser to revert the joint prior distribution to the original joint data distribution, effectively utilizing joint probability distribution to describe the correlations of PET and MRI for improved quality of joint reconstruction. MAIN RESULTS: Qualitative and quantitative improvements are observed with the MC-Diffusion model. Comparative analysis against LPLS and Joint ISAT-net on the ADNI dataset demonstrates superior performance by exploiting complementary information between PET and MRI. The MC-Diffusion model effectively enhances the quality of PET and MRI images. SIGNIFICANCE: This study employs the MC-Diffusion model to enhance the quality of PET-MRI images by integrating the fundamental principles of PET and MRI modalities and their inherent complementarity. The MC-Diffusion model facilitates a more profound comprehension of the priors obtained through deep learning.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

Recent advances in nanomaterials for the treatment of femoral head necrosis.

Osteonecrosis of the femoral head (ONFH) is a condition that causes considerable pain and discomfort for patients, and its pathogenic mechanisms are not yet fully understood. While there have been many studies that suggest multiple factors may contribute to its development, current treatments involve both surgical and nonsurgical options. However, there is still much room for improvement in these treatment methods, particularly when it comes to preventing postoperative complications and optimizing surgical procedures. Nanomaterials, as a type of small molecule material, have shown great promise in treating bone tissue diseases, including ONFH. In fact, several nanocomposite materials have demonstrated specific effects in preventing ONFH, promoting bone tissue repair and growth, and optimizing surgical treatment. This article provides a comprehensive overview of current treatments for ONFH, including their advantages and limitations, and reviews the latest advances in nanomaterials for treating this condition. Additionally, this article explores the therapeutic mechanisms involved in using nanomaterials to treat ONFH and to identify new methods and ideas for improving outcomes for patients.

The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease.

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed.

Postweaning sodium citrate exposure induces long-lasting and sex-dependent effects on social behaviours in mice.

BACKGROUND: Postweaning is a pivotal period for brain development and individual growth. As an important chemical used in medicines, foods and beverages, sodium citrate (SC) is commonly available. Although some effects of SC exposure on individual physiology have been demonstrated, the potential long-lasting effects of postweaning dietary SC exposure on social behaviours are still elusive. METHODS: Both postweaning male and female C57BL/6 mice were exposed to SC through drinking water for a total of 3 weeks. A series of behavioural tests, including social dominance test (SDT), social interaction test (SIT), bedding preference test (BPT) and sexual preference test (SPT), were performed in adolescence and adulthood. After these tests, serum oxytocin (OT) levels and gut microbiota were detected. RESULTS: The behavioural results revealed that postweaning SC exposure decreased the social dominance of male mice in adulthood and female mice in both adolescence and adulthood. SC exposure also reduced the sexual preference rates of both males and females, while it had no effect on social interaction behaviour. ELISA results indicated that SC exposure decreased the serum OT levels of females but not males. 16S rRNA sequencing analysis revealed a significant difference in ß-diversity after SC exposure in both males and females. The correlation coefficient indicated the correlation between social behaviours, OT levels and dominant genera of gut microbiota. CONCLUSION: Our findings suggest that postweaning SC exposure may have enduring and sex-dependent effects on social behaviours, which may be correlated with altered serum OT levels and gut microbiota composition.

Population-level exploration of alternative splicing and its unique role in controlling agronomic traits of rice.

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one fifth of potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

Plant height as an indicator for alpine carbon sequestration and ecosystem response to warming.

Growing evidence indicates that plant community structure and traits have changed under climate warming, especially in cold or high-elevation regions. However, the impact of these warming-induced changes on ecosystem carbon sequestration remains unclear. Using a warming experiment on the high-elevation Qinghai-Tibetan Plateau, we found that warming not only increased plant species height but also altered species composition, collectively resulting in a taller plant community associated with increased net ecosystem productivity (NEP). Along a 1,500 km transect on the Plateau, taller plant community promoted NEP and soil carbon through associated chlorophyll content and other photosynthetic traits at the community level. Overall, plant community height as a dominant trait is associated with species composition and regulates ecosystem C sequestration in the high-elevation biome. This trait-based association provides new insights into predicting the direction, magnitude and sensitivity of ecosystem C fluxes in response to climate warming.

Habitat differentiation and environmental adaptability contribute to leaf size variations globally in C3 and C4 grasses.

The grass family (Poaceae) dominates ~43 % of Earth's land area and contributes 33 % of terrestrial primary productivity that is critical to naturally regulating atmosphere CO2 concentration and global climate change. Currently grasses comprise ~11,780 species and ~50 % of them (~6000 species) utilize C4 photosynthetic pathway. Generally, grass species have smaller leaves under colder and drier environments, but it is unclear whether the primary drivers of leaf size differ between C3 and C4 grasses on a global scale. Here, we analyzed 34 environmental variables, such as latitude, elevation, mean annual temperature, mean annual precipitation, and solar radiation etc., through a comparatively comprehensive database of ~3.0 million occurrence records from 1380 C3 and 978 C4 grass species (2358 species in total). Results from this study confirm that C4 grasses have occupied habitats with lower latitudes and elevations, characterized by warmer, sunnier, drier and less fertile environmental conditions. Grass leaf size correlates positively with mean annual temperature and precipitation as expected. Our results also demonstrate that the mean temperature of the wettest quarter of the year is the primary control for C3 leaf size, whereas C4 leaf size is negatively correlated with the difference between summer and winter temperatures. For C4 grasses, phylogeny exerts a significant effect on leaf size but is less important than environmental factors. Our findings highlight the importance of evolutionarily contrasting variations in leaf size between C3 and C4 grasses for shaping their geographical distribution and habitat suitability at the global scale.

DPP: deep phase prior for parallel imaging with wave encoding.

Objective.In Magnetic Resonance (MR) parallel imaging with virtual channel-expanded Wave encoding, limitations are imposed on the ability to comprehensively and accurately characterize the background phase. These limitations are primarily attributed to the calibration process relying solely on center low-frequency Auto-Calibration Signals (ACS) data for calibration.Approach.To tackle the challenge of accurately estimating the background phase in wave encoding, a novel deep neural network model guided by deep phase priors is proposed with integrated virtual conjugate coil (VCC) extension. Concretely, within the proposed framework, the background phase is implicitly characterized by employing a carefully designed decoder convolutional neural network, leveraging the inherent characteristics of phase smoothness and compact support in the transformed domain. Furthermore, the proposed model with wave encoding benefits from additional priors, which incorporate transmission sparsity of the latent image and coil sensitivity smoothness.Main results.Ablation experiments were conducted to ascertain the proposed method's capability to implicitly represent CSM and the background phase. Subsequently, the superiority of the proposed method is demonstrated through confidence comparisons with competing methods, employing 4-fold and 5-fold acceleration experiments. In achieving 4-fold and 5-fold acceleration, the optimal quantitative metrics (PSNR/SSIM/NMSE) are 44.1359 dB/0.9863/0.0008 (4-fold) and 41.2074/0.9846/0.0017 (5-fold), respectively. Furthermore, the generalizability of the proposed method is further validated by conducting acceleration experiments with T1, T2, T2*, and various undersampling patterns. In addition, the DPP delivered much better performance than the conventional methods by exploring accelerated phase-sensitive SWI imaging. In SWI accelerated imaging, it also surpasses the optimal competing method in terms of (PSNR/SSIM/NMSE) with 0.096%/0.009%/0.0017%.Significance.The proposed method enables precise characterization of the background phase in the integrated VCC and wave encoding framework, supported via theoretical analysis and empirical findings. Our code is available at:https://github.com/sober235/DPP.

Synaptic vesicle glycoprotein 2 A in serum is an ideal biomarker for early diagnosis of Alzheimer's disease.

BACKGROUND: Previous studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer's disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD. METHODS: In this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed. RESULTS: Both CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD. CONCLUSIONS: Serum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.

Effect of Aggregation Structure on Capacitive Energy Storage in Conducting Polymer Films.

Conducting polymers (CPs), a significant class of electrochemical capacitor electrode materials, exhibit exceptional capacitive energy storage performance in aqueous electrolytes. Current research primarily concentrates on enhancing the electrical conductivity and capacitive performance of CPs via molecular design and structural control. However, the absence of a comprehensive understanding of the impact of molecular chain spatial order on ion/electron transport and capacitive performance impedes the development and optimization of advanced electrode materials. Here, a solvent treatment strategy is employed to modulate the molecular chain spatial order of PEDOT : PSS films. The results of electrochemical performance tests and Grazing Incidence Wide Angle X-ray Scattering (GIWAXS) show that Poly(3,4-ethylenedioxythiophene) : poly(styrenesulfonic acid) (PEDOT : PSS) films with both face-on and edge-on orientations exhibit exceptional electronic conductivity and ion diffusion efficiency, with capacitive performance 1.33 times higher than that of PEDOT : PSS films with only edge-on orientation. Consequently, molecular chain orientations conducive to charge transport not only enhance inter-chain coupling, but also effectively reduce ion transport resistance, enabling efficient capacitive energy storage. This research provides novel insights for the design and development of higher performance CPs-based electrode materials.

Vertical structural complexity of plant communities represents the combined effects of resource acquisition and environmental stress on the Tibetan Plateau.

The vertical structural complexity (VSC) of plant communities reflects the occupancy of spatial niches and is closely related to resource utilization and environmental adaptation. However, understanding the large-scale spatial pattern of VSC and its underlying mechanisms remains limited. Here, we systematically investigate 2013 plant communities through grid sampling on the Tibetan Plateau. VSC is quantified as the maximum plant height within a plot (Height-max), coefficient of variation of plant height (Height-var), and Shannon evenness of plant height (Height-even). Precipitation dominates the spatial variation in VSC in forests and shrublands, supporting the classic physiological tolerance hypothesis. In contrast, for alpine meadows, steppes, and desert grasslands in extreme environments, non-resource limiting factors (e.g., wide diurnal temperature ranges and strong winds) dominate VSC variation. Generally, with the shifting of climate from favorable to extreme, the effect of resource availability gradually decreases, but the effect of non-resource limiting factors gradually increases, and that the physiological tolerance hypothesis only applicable in favorable conditions. With the help of machine learning models, maps of VSC at 1-km resolution are produced for the Tibetan Plateau. Our findings and maps of VSC provide insights into macroecological studies, especially for adaptation mechanisms and model optimization.

Operando Studies of Bismuth Nanoparticles Embedded in N, O-Doped Porous Carbon for High-Performance Potassium-Ion Hybrid Capacitor.

A highly viable alternative to lithium-ion batteries for stationary electrochemical energy-storage systems is the potassium dual-ion hybrid capacitor (PIHC), especially toward fast-charging capability. However, the sluggish reaction kinetics of negative electrode materials seriously impedes their practical implementation. In this paper, a new negative electrode Bi@RPC (Nano-bismuth confined in nitrogen- and oxygen-doped carbon with rationally designed pores, evidenced by advanced characterization) is developed, leading to a remarkable electrochemical performance. PIHCs building with the active carbon YP50F positive electrode result in a high operation voltage (0.1-4 V), and remarkably well-retained energy density at a high-power density (11107 W kg-1 at 98 Wh kg-1 ). After 5000 cycles the proposed PHICs still show a superior capacity retention of 92.6%. Moreover, a reversible mechanism of "absorption-alloying" of the Bi@RPC nanocomposite is revealed by operando synchrotron X-ray diffraction and Raman spectroscopy. With the synergistic potassium ions storage mechanism arising from the presence of well-structured pores and nano-sized bismuth, the Bi@RPC electrode exhibits an astonishingly rapid kinetics and high energy density. The results demonstrate that PIHCs with Bi@RPC-based negative electrode is the promising option for simultaneously high-capacity and fast-charging energy storage devices.

Research status and challenges of Mycoplasma pneumoniae pneumonia in children: A bibliometric and visualization analysis from 2011 to 2023.

BACKGROUND: Mycoplasma pneumoniae (MP) infections occur in regional outbreaks every 3 to 7 years, lasting up to 2 years. Since this fall, there has been a significant rise in MP infections among children in China, indicating a regional epidemiological trend that imposes an increased national public health burden. To date, bibliometric methods have not been applied to studies on MP infection in children. METHODS: We searched for all relevant English publications on MP pneumonia in children published from 2011 to 2023 using Web of Science. Analytical software tools such as Citespace and VOSviewer were employed to analyze the collected literature. RESULTS: 993 articles on MP pneumonia in children were published in 338 academic journals by 5062 authors affiliated with 1381 institutions across 75 countries/regions. China led in global productivity with 56.19%. Among the top 10 prolific organizations, 8 were Chinese institutions, with Soochow University being the most active, followed by Capital Medical University and Zhejiang University. Zhimin Chen from Zhejiang University School of Medicine exhibited the highest H-index of 32. Keyword co-occurrence network analysis revealed 7 highly relevant clusters. CONCLUSION: The current research hotspots and frontiers in this field are primarily MP pneumonia, refractory MP pneumonia, lactate dehydrogenase, asthma, and biomarker. We anticipate that this work will provide novel insights for advancing scientific exploration and the clinical application of MP pneumonia in children.

High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures.

BACKGROUND: Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women's reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear. METHODS: We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS). RESULTS: The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures. CONCLUSIONS: Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.

Phenotypic and genomic characteristics of clinical IMP-producing Klebsiella spp. Isolates in China.

BACKGROUND: IMP-producing Klebsiella spp. (IMPKsp) strains have spread globally, including in China. Currently, the prevalence and genomic characterization of IMPKsp is largely unknown nationwide. Here we aimed to provide a general overview of the phenotypic and genomic characteristics of IMPKsp strains. METHODS: 61 IMPKsp strains were obtained from 13 provinces in China during 2016-2021. All strains were tested for their susceptibility to antimicrobial agents by the microdilution broth method and sequenced with Illumina next-generation sequencing. We performed conjugation experiments on thirteen representative strains which were also sequenced by Oxford nanopore sequencing technology to characterize blaIMP-encoding plasmids. RESULTS: We find that all IMPKsp strains display multidrug-resistant (MDR) phenotypes. All strains belong to 27 different STs. ST307 emerges as a principal IMP-producing sublineage. blaIMP-4 is found to be the major isoform, followed by blaIMP-38. Seven incompatibility types of blaIMP-encoding plasmids are identified, including IncHI5 (32/61, 52.5%), IncN-IncR (10/61, 16.4%), IncFIB(K)-HI1B (7/61, 11.5%), IncN (5/61, 8.2%), IncN-IncFII (2/61, 3.3%), IncFII (1/61, 1.6%) and IncP (1/61, 1.6%). The strains carrying IncHI5 and IncN plasmids belong to diverse ST types, indicating that these two plasmids may play an important role in the transmission of blaIMP genes among Klebsiella spp. strains. CONCLUSIONS: Our results highlight that multi-clonal transmission, multiple genetic environments and plasmid types play a major role in the dissemination process of blaIMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the blaIMP genes in Klebsiella spp.

Antibiotic resistance occurs when bacteria evolve to withstand antibiotic drugs. We are aware that a bacteria called Klebsiella is rapidly becoming resistant to carbapenems, a class of broad-spectrum antibiotics. In this study, we conducted a genetic and microbiological surveillance study across 13 provinces of China to understand factors that contribute to the growing bacterial drug resistance. We find that the way the multiple bacterial types interact with each other and swap certain genetic material may be the main cause of growing resistance. These findings call for close monitoring of genetic evolution as a matter of public health management strategy.

Natural Disinfection-like Process Unveiled in Soil Microenvironments by Enzyme-Catalyzed Chlorination.

Substantial natural chlorination processes are a growing concern in diverse terrestrial ecosystems, occurring through abiotic redox reactions or biological enzymatic reactions. Among these, exoenzymatically mediated chlorination is suggested to be an important pathway for producing organochlorines and converting chloride ions (Cl-) to reactive chlorine species (RCS) in the presence of reactive oxygen species like hydrogen peroxide (H2O2). However, the role of natural enzymatic chlorination in antibacterial activity occurring in soil microenvironments remains unexplored. Here, we conceptualized that heme-containing chloroperoxidase (CPO)-catalyzed chlorination functions as a naturally occurring disinfection process in soils. Combining antimicrobial experiments and microfluidic chip-based fluorescence imaging, we showed that the enzymatic chlorination process exhibited significantly enhanced antibacterial activity against Escherichia coli and Bacillus subtilis compared to H2O2. This enhancement was primarily attributed to in situ-formed RCS. Based on semiquantitative imaging of RCS distribution using a fluorescence probe, the effective distance of this antibacterial effect was estimated to be approximately 2 mm. Ultrahigh-resolution mass spectrometry analysis showed over 97% similarity between chlorine-containing formulas from CPO-catalyzed chlorination and abiotic chlorination (by sodium hypochlorite) of model dissolved organic matter, indicating a natural source of disinfection byproduct analogues. Our findings unveil a novel natural disinfection process in soils mediated by indigenous enzymes, which effectively links chlorine-carbon interactions and reactive species dynamics.

Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease.

BACKGROUND: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. METHODS: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. RESULTS: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. CONCLUSIONS: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.