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Abstract Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

Abstract Background Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. Methods Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. Results In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. Conclusion We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

The color of flour products has an important influence on consumer acceptance. Flour color is largely determined and measured by the index of flour whiteness (FW) in China. In this study, an association population comprising 207 wheat (Triticum aestivum) accessions originating from seven countries was used for dissection of FW-related genetic loci through genome-wide association analysis. Six quantitative trait loci (QTLs) significantly associated with FW were identified, accounting for 7.87–16.53 % of the total phenotypic variation. Four KASP markers were developed from single-nucleotide polymorphisms associated with the QTLs QFW.HAAS-1AS, QFW.HAAS-1BL, QFW.HAAS-5AL, and QFW.HAAS-7AL. The phytoene synthase-encoding gene TraesCS7A03G1357000 (TaPsyA1) was identified as a candidate gene for QFW.HAAS-7AL. Two allelic variants of TaPsyA1 (designated PsyA1-a and PsyA1-b) were differentiated on the basis of a 37 bp insertion/deletion polymorphism in the second intron. PsyA1-b included the 37 bp insertion, which led to a translational frameshift in the gene and was associated with higher FW. The PsyA1-a allele lacked the 37 bp insertion and was classified into two haplotypes according to the number of repeated ‘TC’ units in a simple sequence repeat in the promoter region. Of the two PsyA1-a haplotypes, the Type 1 haplotype conferred higher FW, flour brightness, and flour redness, and lower yellow pigment content and flour yellowness. The KASP markers and PsyA1 polymorphic markers developed in the present study are suitable for use in molecular marker-assisted selection for improvement of wheat FW.

Abstract 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.

Abstract 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.

The ionic transport in sub-nanochannels plays a key role in energy storage, yet suffers from a high energy barrier. Wetting sub-nanochannels is crucial to accelerate ionic transport, but the introduction of water is challenging because of the hydrophobic extreme confinement. We propose wetting the channels by the exothermic hydration process of pre-intercalated ions, the effect of which varies distinctly with different ionic hydration structures and energies. Compared to the failed pre-intercalation of SO42−, HSO4− with weak hydration energy results in a marginal effect on the HOMO (Highest Occupied Molecular Orbital) level of water to avoid water splitting during the electrochemical intercalation. Meanwhile, the ability of water introduction is reserved by the initial incomplete dissociation state of HSO4−, so the consequent exothermic reionization and hydration processes of the intercalated HSO4− promote the water introduction into sub-nanochannels, finally forming the stable confined water through hydrogen bonding with functional groups. The wetted channels exhibit a significantly enhanced ionic diffusion coefficient by ∼9.4 times.

Abstract 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 bla IMP-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. bla IMP-4 is found to be the major isoform, followed by bla IMP-38. Seven incompatibility types of bla IMP-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 bla IMP 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 bla IMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the bla IMP genes in Klebsiella spp.

Abstract 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.

Abstract The relationship between stomatal traits and environmental drivers across plant communities has important implications for ecosystem carbon and water fluxes, but it has remained unclear. Here, we measure the stomatal morphology of 4492 species-site combinations in 340 vegetation plots across China and calculate their community-weighted values for mean, variance, skewness, and kurtosis. We demonstrate a trade-off between stomatal density and size at the community level. The community-weighted mean and variance of stomatal density are mainly associated with precipitation, while that of stomatal size is mainly associated with temperature, and the skewness and kurtosis of stomatal traits are less related to climatic and soil variables. Beyond mean climate variables, stomatal trait moments also vary with climatic seasonality and extreme conditions. Our findings extend the knowledge of stomatal trait–environment relationships to the ecosystem scale, with applications in predicting future water and carbon cycles.

Abstract Freestanding MXene‐based macroforms have gained significant attention as versatile components in electrochemical energy storage applications owing to their interconnected conductive network, strong mechanical strength, and customizable surface chemistries derived from MXene nanosheets. This comprehensive review article encompasses key aspects related to the synthesis of MXene nanosheets, strategies for structure design and surface medication, surface modification, and the diverse fabrication methods employed to create freestanding MXene‐based macroform architectures. The review also delves into the recent advancements in utilizing freestanding MXene macroforms for electrochemical energy storage applications, offering a detailed discussion on the significant progress achieved thus far. Notably, the correlation between the macroform's structural attributes and its performance characteristics is thoroughly explored, shedding light on the critical factors influencing efficiency and durability. Despite the remarkable development, the review also highlights the existing challenges and presents future perspectives for freestanding MXene‐based macroforms in the realms of high‐performance energy storage devices. By addressing these challenges and leveraging emerging opportunities, the potential of freestanding MXene‐based macroforms can be harnessed to enable groundbreaking advancements in the field of energy storage.

MXene has great potential in the application of thermoelectric materials due to its high conductivity, but its application in this field is limited by the low Seebeck coefficient. In this work, a laminated composite film with a regular 2-dimensional heterogeneous interface was constructed by using 2-dimensional MXene and TiS2. The results show that the sandwich structure composite film has a high Seebeck coefficient (−80.4 μV K−1) while maintaining a high electrical conductivity (322.12 S cm−1). The power factor of the sandwich structure film is higher than that of the disordered structure film, which is 22 times that of the Ti3C2Tx film. The simple flexible device prepared by MTM film has an ideal power density (26.6 W m−2) at a temperature difference of 70 K. This work provides strong evidence and feasible reference for optimizing and improving the thermoelectric properties of MXene-based materials by using high-quality heterostructures.

Abstract Singapore grouper iridovirus (SGIV), one of the nucleocytoviricota viruses (NCVs), is a highly pathogenic iridovirid. SGIV infection results in massive economic losses to the aquaculture industry and significantly threatens global biodiversity. In recent years, high morbidity and mortality in aquatic animals have been caused by iridovirid infections worldwide. Effective control and prevention strategies are urgently needed. Here, we present a near-atomic architecture of the SGIV capsid and identify eight types of capsid proteins. The viral inner membrane-integrated anchor protein colocalizes with the endoplasmic reticulum (ER), supporting the hypothesis that the biogenesis of the inner membrane is associated with the ER. Additionally, immunofluorescence assays indicate minor capsid proteins (mCPs) could form various building blocks with major capsid proteins (MCPs) before the formation of a viral factory (VF). These results expand our understanding of the capsid assembly of NCVs and provide more targets for vaccine and drug design to fight iridovirid infections.

As important auxiliary equipment, rehabilitation robots are widely used in rehabilitation treatment and daily life assistance. The rehabilitation robot proposed in this paper is mainly composed of an omnidirectional mobile platform module, a lower limb exoskeleton module, and a support module. According to the characteristics of the robot’s omnidirectional mobility and good stiffness, the overall kinematic model of the robot is established using the analytical method. Passive and active training control strategies for an omnidirectional mobile lower limb exoskeleton robot are proposed. The passive training mode facilitates the realization of the goal of walking guidance and assistance to the human lower limb. The active training mode can realize the cooperative movement between the robot and the human through the admittance controller and the tension sensor and enhance the active participation of the patient. In the simulation experiment, a set of optimal admittance parameters was obtained, and the parameters were substituted into the controller for the prototype experiment. The experimental results show that the admittance-controlled rehabilitation robot can perceive the patient’s motion intention and realize the two walking training modes. In summary, the passive and active training control strategies based on admittance control proposed in this paper achieve the expected purpose and effectively improve the patient’s active rehabilitation willingness and rehabilitation effect.

A large-scale series of cyclic triaxial tests were conducted to explore the evolution of the dynamic resilient modulus of silty clay for the heavy-haul railway subgrade. A novel loading sequence for measuring the dynamic resilient modulus was established, which characterized the dynamic stress state of the subgrade induced by the heavy-haul train load. In the experimental investigation, the deviatoric stresses, confining stress, initial moisture content, and compaction degree were considered as variables, and the effects of the aforementioned variables were evaluated quantitatively. The experimental results showed that the dynamic resilient modulus was negatively related to deviatoric stresses and initial moisture content, where the average decreased rates were 14.65% and 27.79% with the increase in deviatoric stresses from 60 kPa to 150 kPa and increase in the initial moisture content from 9.8% to 15.8%, respectively. Furthermore, the dynamic resilient modulus was positively related to confining stress and compaction degree, where the average increased rates were 23.25% and 27.48% with the increase in confining stress from 20 kPa to 60 kPa and increase in compaction degree from 0.91 to 0.95. To provide a better application, the two high-accuracy predicted methods were established through the empirical model and artificial neural network approach including the aforementioned variables. This study can provide useful guidelines for the effective and safe design of the heavy-haul railway subgrade filled with silty clay.

Summary: The molecular mechanisms that trigger Tau aggregation in Alzheimer’s disease (AD) remain elusive. Fungi, especially Saccharomyces cerevisiae (S. cerevisiae), can be found in brain samples from patients with AD. Here, we show that the yeast protein Ure2p from S. cerevisiae interacts with Tau and facilitates its aggregation. The Ure2p-seeded Tau fibrils are more potent in seeding Tau and causing neurotoxicity in vitro. When injected into the hippocampus of Tau P301S transgenic mice, the Ure2p-seeded Tau fibrils show enhanced seeding activity compared with pure Tau fibrils. Strikingly, intracranial injection of Ure2p fibrils promotes the aggregation of Tau and cognitive impairment in Tau P301S mice. Furthermore, intranasal infection of S. cerevisiae in the nasal cavity of Tau P301S mice accelerates the aggregation of Tau. Together, these observations indicate that the yeast protein Ure2p initiates Tau pathology. Our results provide a conceptual advance that non-mammalian prions may cross-seed mammalian prion-like proteins.

Abstract Background OXA-232-producing Klebsiella pneumoniae was first identified in China in 2016, and its clonal transmission was reported in 2019. However, there are no prevalence and genotypic surveillance data available for OXA-232 in China. Therefore, we investigated the trends and characteristics of OXA-232 type carbapenemase in Zhejiang Province, China from 2018 to 2021. Methods A total of 3278 samples from 1666 patients in the intensive care units were collected from hospitals in Zhejiang Province from 2018 to 2021. Carbapenem-resistant isolates were initially selected by China Blue agar plates supplemented with 0.3 μg/ml meropenem, and further analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry identification, immune colloidal gold technique, conjugation experiment, antimicrobial susceptibility testing and whole genome sequencing. Results A total of 79 OXA-producing strains were recovered, with the prevalence increased from 1.8% [95% confidence interval (CI): 0.7–3.7%] in 2018 to 6.0% (95% CI: 4.4–7.9%) in 2021. Seventy-eight strains produced OXA-232 and one produced OXA-181. The bla OXA-232 gene in all strains was located in a 6141-bp ColKP3-type non-conjugative plasmid and the bla OXA-181 gene was located in a 51,391-bp ColKP3/IncX3-type non-conjugative plasmid. The bla OXA-232-producing K. pneumoniae was dominated (75/76) by isolates of sequence type 15 (ST15) that differed by less than 80 SNPs. All OXA-producing strains (100%, 95% CI: 95.4–100.0%) were multidrug-resistant. Conclusions From 2018 to 2021, OXA-232 is the most prevalent OXA-48-like derivative in Zhejiang Province, and ST15 K. pneumoniae isolates belonging to the same clone are the major carriers. The transmission of ColKP3-type plasmid to E. coli highlighted that understanding the transmission mechanism is of great importance to delay or arrest the propagation of OXA-232 to other species.

THADA has been identified as a type 2 diabetes-associated gene whose function is not fully understood. Here the authors report that THADA deficiency protects mice from hyperglycemia and glucose intolerance by promoting insulin secretion and inhibiting β-cell apoptosis, suggesting THADA could be explored as a potential therapeutic target for diabetes.

A large number of bone stick fragments were unearthed at the Weiyang Palace, and the manual stitching method is inefficient and time-consuming, therefore Image Stitching Method of Bone Stick Fragment Based on Similarity Freeman code Matching is proposed by this paper to improve bone stick stitching efficiency. The Freeman code is used to represent the contour of the true color RGB image of bone stick fragments, and the direction change dense feature of the bone stick fragment fracture is fused with the Freeman code difference to represent the change direction feature to locate the fracture boundary. At the same time, the integer basic operation is used to replace the complex calculus calculation to improve the efficiency of the algorithm; The longest common subsequence algorithm is used to perform local similarity rough matching on Freeman code of the contour at the fragment fracture, and then the angle and distance error threshold is set according to the prior knowledge of manual stitching to reduce the matching error; Finally, according to the matching results, the complete bone stick contour binary image is drawn. Compared with other algorithms, the contour Cosine similarity accuracy of the bone stick image stitched by this algorithm is improved by 21.68%, which can be accurate to 97.80%; the Editing distance similarity accuracy is improved by 14.29%, which can be accurate to 91.87%;the Peak signal-to-noise ratio is improved by 83%, which can be accurate to 31.13%;the Structural Similarity is improved by 29%, which can be accurate to 0.87; the Figure of merit is improved by 39%, which can be accurate to 0.85. The experiment results show that the algorithm proposed in this paper can effectively assist the stitching work of bone stick cultural relics.

Emergence of the colistin resistance gene, mcr-1, has attracted worldwide attention. Despite the prevalence of mcr-1-positive Escherichia coli (MCRPEC) strains in human carriage showing a significant decrease between 2016 and 2019, genetic differences in MCRPEC strains remain largely unknown. We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019. We identified three major differences in MCRPEC strains between these two time points. First, the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019. Second, the antibiotic resistance genes (ARGs), aac(3)-IVa and blaCTX-M-1, emerged and coexisted with mcr-1 in 2019. Third, MCRPEC strains in 2019 contained more virulence genes, resulting in an increased proportion of extraintestinal pathogenic E. coli (ExPEC) strains (36.1%) in MCRPEC strains in 2019 compared to that in 2016 (10.5%), implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria. Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019, MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes, which may pose a potential public health threat.

Acinetobacter baumannii is one of the key Gram-negative pathogens that can cause serious nosocomial infections. In China, a large proportion of clinical A. baumannii strains are multidrug resistant, among which strains resistant to carbapenems are particularly worrisome, as infections caused by such strains may limit the choice of existing antibiotics. We conducted a nationwide and genome-based surveillance on the prevalence and antibiotic susceptibility profile of carbapenem-resistant A. baumannii (CRAB) strains collected from intensive care units (ICUs) in hospitals in different provinces and investigated the routes of transmission and mechanism of resistance by whole-genome sequencing and phylogenetic analysis. We found that CRAB strains were prevalent in 71.4% (55/77) of the ICUs surveyed. Clonal spread of CRAB was found in 37.6% (29/77) of ICUs and a total of 22 different clones were identified. Most clones were transmissible within one ICU, but up to six clones could be detected in at least three hospitals. In addition, carbapenem-hydrolysing class D β-lactamases (CHDL) were found to be mainly responsible for carbapenem-resistance in A. baumannii and the ST2 global-clone is the predominant type of CRAB in China. Importantly, we found that CRAB isolates currently exhibited an extremely low rate of resistance to colistin (0.4%) and tigecycline (2.5%), but a high rate of resistance to ceftazidime–avibactam (70.2%). Findings in this work shall facilitate development of appropriate antimicrobial regimens for treatment of CRAB infections. Further surveillance and research on the evolutionary and epidemiological features of clinical CRAB strains are necessary.

Abstract Background Numerous studies have shown that gluten aggregation properties directly affect the processing quality of wheat, however, the genetic basis of gluten aggregation properties were rarely reported. Results To explore the genetic basis of gluten aggregation properties in wheat, an association population consisted with 207 wheat genotypes were constructed for evaluating nine parameters of aggregation properties on GlutoPeak across three-year planting seasons. A total of 940 significant SNPs were detected for 9 GlutoPeak parameters through genome-wide association analysis (GWAS). Finally, these SNPs were integrated to 68 non-redundant QTL distributed on 20 chromosomes and 54 QTL was assigned as pleiotropic loci which accounting for multiple parameters of gluten aggregation property. Furthermore, the peak SNPs representing 54 QTL domonstrated additive effect on all the traits. There was a significant positive correlation between the number of favorable alleles and the phenotypic values of each parameter. Peak SNPs of two novel QTL, q3AL.2 and q4DL, which contributing to both PMT (peak maximum time) and A3 (area from the first minimum to torque 15 s before the maximum torque) parameters, were selected for KASP (Kompetitive Allele Specific PCR) markers development and the KASP markers can be used for effectively evaluating the quality of gluten aggregation properties in the association population. Conclusion The rapid and efficient GlutoPeak method for gluten measurement can be used for early selection of wheat breeding. This study revealed the genetic loci related to GlutoPeak parameters in association population, which would be helpful to develop wheat elite lines with improved gluten aggregation through molecular marker-assisted breeding.

BackgroundTau phosphorylation is a pathological hallmark of Alzheimer’s disease (AD). Previously, we reported that the γ-adducin 1–357 fragment is present in the brains of AD patients. However, it remains unknown how γ-adducin regulates tau phosphorylation.ObjectiveThe aim of this project is to investigate the effects of the γ-adducin 1–357 fragment on tau phosphorylation and the kinases involved in this process.MethodsFull-length γ-adducin or the γ-adducin 1–357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length γ-adducin or γ-adducin 1–357 fragment to determine the phosphorylation of tau.ResultsThe γ-adducin 1–357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the γ-adducin 1–357 fragment leads to the activation of glycogen synthase kinase-3β (GSK-3β). This effect was mitigated by the GSK-3β inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8).ConclusionThe γ-adducin 1–357 fragment enhances tau phosphorylation by activating GSK3β. These results support that the fragmentation of γ-adducin may play a pivotal role in tau pathology.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.

IntroductionMassilia bacteria are widely distributed and have various ecological functions. Preliminary studies have shown that Massilia is the dominant species in constructed wetland ecosystems, but its species composition and distribution in constructed wetlands are still unclear.MethodsIn this paper, the in-house-designed primers were used to construct a 16S rDNA clone library of Massilia. The RFLP sequence analysis method was used to analyze the diversity of Massilia clone library and the composition of Massilia in sewage, substrate, plant rhizosphere, plant phyllosphere and air in a constructed wetland sewage treatment system. Redundancy analysis (RDA) and canonical correspondence analysis (CCA) were used to analyze the correlation between environmental factors and the population characteristics of Massilia in the corresponding environment. The dominant species of Massilia were analyzed for differences.ResultsThe results showed that the 16S rDNA clone library in primer 5 worked well. According to the clone library diversity index analysis, the richness of Massilia varied significantly in different environments in different seasons, where the overall summer and autumn richness was higher than that in the spring and winter. The relative abundance of 5 Massilia in the constructed wetland ecosystem was greater than 1% in all samples, which were M. alkalitolerans, M. albidiflava, M. aurea, M. brevitalea, and M. timonae. The seasonal variation of dominant genera was significantly correlated with environmental factors in constructed wetlands.DiscussionThe above results indicated that the species of Massilia were abundant and widely distributed in the constructed wetland ecosystem, and there were significant seasonal differences. In addition, the Massilia clone library of constructed wetland was constructed for the first time in this study and the valuable data of Massilia community structure were provided, which was conducive to the further study of microbial community in constructed wetland.

Wearing a face mask during fMRI has little to no significant effect on resting-state and task activations.

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Cool executive dysfunction is a crucial feature in people living with schizophrenia which is related to cognition impairment and the severity of the clinical symptoms. Based on electroencephalogram (EEG), our current study explored the change of brain network under the cool executive tasks in individuals living with schizophrenia before and after atypical antipsychotic treatment (before_TR vs. after_TR). 21 patients with schizophrenia and 24 healthy controls completed the cool executive tasks, involving the Tower of Hanoi Task (THT) and Trail-Marking Test A-B (TMT A-B). The results of this study uncovered that the reaction time of the after_TR group was much shorter than that of the before_TR group in the TMT-A and TMT-B. And the after_TR group showed fewer error numbers in the TMT-B than those of the before_TR group. Concerning the functional network, stronger DMN-like linkages were found in the before_TR group compared to the control group. Finally, we adopted a multiple linear regression model based on the change network properties to predict the patient’s PANSS change ratio. Together, the findings deepened our understanding of cool executive function in individuals living with schizophrenia and might provide physiological information to reliably predict the clinical efficacy of schizophrenia after atypical antipsychotic treatment.

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.

Background: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. Methods: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. Results: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13–1.38) and 1.24 (95% CI, 1.11–1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9–28% and 9–27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. Conclusion: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Antimicrobial resistance is a quintessential One Health issue, among the most serious 21st century global threats in human and veterinary medicine. Wild animals are usually not directly exposed to clinically relevant antibiotics; however, antibacterial resistance in wild animals has been increasingly reported worldwide in parallel to the situation in human and veterinary medicine. In this work, we collected 100 fecal samples from the crested ibis protected areas. A total of eight Escherichia coli (E. coli) isolates positive for mcr-1 were obtained, and all of them were analyzed using WGS (whole genome sequencing). The WGS analysis showed that the isolates were assigned to four different sequence types (ST) overall. The antibiotic susceptibility profile showed that of eight E. coli isolates, six strains exhibited resistance to tetracycline and all mcr-1-positive E. coli (MCREC) strains showed resistance to colistin. Our findings importantly document the epidemic spread of MCREC in crested ibis in China.

Corrosion behavior of laser cladding Ni–Cr–Mo alloy C22 coating, Hastelloy C22 alloy, and Ti–6Al–4V alloy in simulated desulfurized flue gas condensates (50wt.% H2SO4, 2wt.% HCl, 1.5wt.% HNO3, and 0.2wt.% HF) at 50–70 °C were investigated by combination of immersion testing, surface analyses, and electrochemical measurements. C22 coating exhibited similar excellent corrosion resistance but higher sensitivity to localized corrosion compared to C22 alloy. TC4 alloy exhibited poorer corrosion resistance but more stable passivation. The passive film of three materials possesses similar bilayer structure consisting of an outer porous layer and an inner barrier layer. The electrochemical behavior of C22 coating and C22 alloy is predominantly controlled by the charge transfer process through the solution in the defects of the outer porous layer, while that of TC4 alloy is controlled by the combination of charge transfer processes through outer porous layer and electrochemical process within the inner layer. The increase in temperature aggravates the corrosion of three materials by facilitating the degradation of passive film and changing the surface state. The effect of NO3- and halide ions at different temperature results in the different variation of passive film properties and/or surface state on each materials.

Summary Klebsiella pneumoniae has become the number one bacterial pathogen that causes high mortality in clinical settings worldwide. Clinical K. pneumoniae strains with carbapenem resistance and/or hypervirulent phenotypes cause higher mortality comparing with classical K. pneumoniae strains. Rapid differentiation of clinical K. pneumoniae with high resistance/hypervirulence from classical K. pneumoniae would allow us to develop rational and timely treatment plans. In this study, we developed a convolution neural network (CNN) as a prediction method using Raman spectra raw data for rapid identification of ARGs, hypervirulence‐encoding factors and resistance phenotypes from K. pneumoniae strains. A total of 71 K. pneumoniae strains were included in this study. The minimum inhibitory concentrations (MICs) of 15 commonly used antimicrobial agents on K. pneumoniae strains were determined. Seven thousand four hundred fifty‐five spectra were obtained using the InVia Reflex confocal Raman microscope and used for deep learning‐based and machine learning (ML) algorithms analyses. The quality of predictors was estimated in an independent data set. The results of antibiotic resistance and virulence‐encoding factors identification showed that the CNN model not only simplified the classification system for Raman spectroscopy but also provided significantly higher accuracy to identify K. pneumoniae with high resistance and virulence when compared with the support vector machine (SVM) and logistic regression (LR) models. By back‐testing the Raman‐CNN platform on 71 K. pneumoniae strains, we found that Raman spectroscopy allows for highly accurate and rationally designed treatment plans against bacterial infections within hours. More importantly, this method could reduce healthcare costs and antibiotics misuse, limiting the development of antimicrobial resistance and improving patient outcomes.

Introduction: Gliadins are the major components of gluten proteins with vital roles on properties of end-use wheat product and health-relate quality of wheat. However, the function and regulation mechanisms of γ-gliadin genes remain unclear. Objectives: Dissect the effect of DNA methylation in the promoter of γ-gliadin gene on its expression level and gluten strength of wheat. Methods: The prokaryotic expression and reduction–oxidation reactions were performed to identify the effect of TaGli-γ-2.1 on dough strength. Bisulfite analysis and 5-Aza-2′-deoxycytidine treatment were used to verify the regulation of TaGli-γ-2.1 expression by pTaGli-γ-2.1 methylation. The content of gluten proteins composition was measured by RP-HPLC, and the gluten strength was measured by Gluten Index and Farinograph. Results: TaGli-γ-2.1 was classified into a subgroup of γ-gliadin multigene family and was preferentially expressed in the later period of grain filling. Addition of TaGli-γ-2.1 protein fragment into strong gluten wheat flour significantly decreased the stability time. Hypermethylation of three CG loci of pTaGli-γ-2.1 conferred to lower TaGli-γ-2.1 expression. Treatment with 5-Aza-2′-deoxycytidine in seeds of strong gluten wheat varieties increased the expression levels of TaGli-γ-2.1. Furthermore, the accumulations of gliadin and γ-gliadin were significantly decreased in hypermethylated wheat varieties, corresponding with the increasing of gluten index and dough stability time. Conclusion: Epigenetic modification of pTaGli-γ-2.1 affected gluten strength by modulating the proportion of gluten proteins. Hypermethylation of pTaGli-γ-2.1 is a novel genetic resource for enhancing gluten strength in wheat quality breeding.

Abstract Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion. Here, we present the structure of infective GETV at a resolution of 2.8 Å with the atomic models of the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans indicate a possible impact on viral immune evasion and host cell invasion. The S-acylation sites might be involved in stabilizing the transmembrane assembly of E1 and E2. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The cholesterol and phospholipid stabilize the hydrophobic pocket in the viral envelope membrane. The structural information will assist structure-based antiviral and vaccine screening, design, and optimization.

Abstract Previous deep learning methods have not captured graph or network representations of brain structural or functional connectome data. To address this, we developed the BrainNet-Global Covariance Pooling-Attention Convolutional Neural Network (BrainNet-GA CNN) by incorporating BrainNetCNN and global covariance pooling into the self-attention mechanism. Resting-state functional magnetic resonance imaging data were obtained from 171 patients with schizophrenia spectrum disorders (SSDs) and 161 healthy controls (HCs). We conducted an ablation analysis of the proposed BrainNet-GA CNN and quantitative performance comparisons with competing methods using the nested tenfold cross validation strategy. The performance of our model was compared with competing methods. Discriminative connections were visualized using the gradient-based explanation method and compared with the results obtained using functional connectivity analysis. The BrainNet-GA CNN showed an accuracy of 83.13%, outperforming other competing methods. Among the top 10 discriminative connections, some were associated with the default mode network and auditory network. Interestingly, these regions were also significant in the functional connectivity analysis. Our findings suggest that the proposed BrainNet-GA CNN can classify patients with SSDs and HCs with higher accuracy than other models. Visualization of salient regions provides important clinical information. These results highlight the potential use of the BrainNet-GA CNN in the diagnosis of schizophrenia.

Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing severe nosocomial infections for its patterns of multidrug resistance, particularly for carbapenems. Timely epidemiological surveillance could greatly facilitate infection control of P. aeruginosa and many deadly pathogens alike. IR Biotyper (IRBT), is a novel real-time typing tool, based on a Fourier-transform infrared (FTIR) spectroscopy system. It is critical to comprehensively establish and evaluate the feasibility of IRBT in P. aeruginosa strain typing. In the current study, we first established standards and schemes for its routine laboratory application, and we found that Mueller–Hinton agar plates give better discriminatory power than blood agar plates. Data showed that the cut-off value of 0.15 with an additional 0.025 range was optimal. Secondly, 27 clinically isolated carbapenem-resistant P. aeruginosa (CRPA) strains collected from October 2010 to September 2011 were evaluated for typing effectiveness by comparing IRBT to the other commonly used typing methods, such as multi-locus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS)-based typing. When using WGS-based typing as the reference method, the typing method of FTIR spectroscopy (AR = 0.757, SID = 0.749) could better cluster P. aeruginosa strains than MLST and in silico serotyping (AR = 0.544, SID = 0.470). Though PFGE showed the highest discriminatory power, low concordance was observed between PFGE and the other methods. Above all, this study demonstrates the utility of the IRBT as a quick, low-cost, real-time typing tool for the detection of CRPA strains.

The present study examines whether self-reported trust in humans and self-reported trust in [(different) products with built-in] artificial intelligence (AI) are associated with one another and with brain structure. We sampled 90 healthy participants who provided self-reported trust in humans and AI and underwent brain structural magnetic resonance imaging assessment. We found that trust in humans, as measured by the trust facet of the personality inventory NEO-PI-R, and trust in AI products, as measured by items assessing attitudes toward AI and by a composite score based on items assessing trust toward products with in-built AI, were not significantly correlated. We also used a concomitant dimensional neuroimaging approach employing a data-driven source-based morphometry (SBM) analysis of gray-matter-density to investigate neurostructural associations with each trust domain. We found that trust in humans was negatively (and significantly) correlated with an SBM component encompassing striato-thalamic and prefrontal regions. We did not observe significant brain structural association with trust in AI. The present findings provide evidence that trust in humans and trust in AI seem to be dissociable constructs. While the personal disposition to trust in humans might be “hardwired” to the brain’s neurostructural architecture (at least from an individual differences perspective), a corresponding significant link for the disposition to trust AI was not observed. These findings represent an initial step toward elucidating how different forms of trust might be processed on the behavioral and brain level.

The South China Block is located on the eastern margin of the Eurasian Plate and the western margin of the Pacific Plate. The South China Block is currently in a tectonically compressed environment, while the Tibetan Plateau is moving eastward and the Philippine Sea Plate is moving westward from geodetic observations. The South China Block is an ideal place to revisit tectonic history from the Archean to Cenozoic, where its information could be well preserved in the crust. In this study, we aim to build the crustal and uppermost mantle component of the Seismological Reference Earth Model in South China (SREM-SC) to provide a background velocity model for geological interpretations and fine-scale velocity inversion. The S-wave velocity model comes from combining models inverted by ambient noise tomography and surface wave tomography. The P-wave velocity model is obtained from converted S-wave velocity and joint inversion tomography. The density model is inferred from an empirical relationship with P-wave velocity. The Moho depth is obtained by a weighted averaging scheme of previously published receiver function results. The P-wave and S-wave velocity models have a grid interval of 0.5° in both latitude and longitude, and with a vertical sampling interval of 5 km down to the 60 km depth. This work provides the 3-D crust and uppermost mantle structures and a representative reference model beneath South China.

Abstract Background Peroxidase (POD) activity plays an important role in flour-based product quality, which is mainly associated with browning and bleaching effects of flour. Here, we performed a genome-wide association study (GWAS) on POD activity using an association population consisted with 207 wheat world-wide collected varieties. Our study also provide basis for the genetic improvement of flour color-based quality in wheat. Results Twenty quantitative trait loci (QTLs) were detected associated with POD activity, explaining 5.59–12.67% of phenotypic variation. Superior alleles were positively correlated with POD activity. In addition, two SNPs were successfully developed to KASP (Kompetitive Allele-Specific PCR) markers. Two POD genes, TraesCS2B02G615700 and TraesCS2D02G583000, were aligned near the QTLs flanking genomic regions, but only TraesCS2D02G583000 displayed significant divergent expression levels (P

Abstract Background Glutenin contents and compositions are crucial factors influencing the end-use quality of wheat. Although the composition of glutenin fractions is well known, there has been relatively little research on the genetic basis of glutenin fractions in wheat. Results To elucidate the genetic basis for the contents of glutenin and its fractions, a population comprising 196 recombinant inbred lines (RILs) was constructed from two parents, Luozhen No.1 and Zhengyumai 9987, which differ regarding their total glutenin and its fraction contents (except for the By fraction). Forty-one additive Quantitative Trait Loci (QTL) were detected in four environments over two years. These QTL explained 1.3% - 53.4% of the phenotypic variation in the examined traits. Forty-three pairs of epistatic QTL (E-QTL) were detected in the RIL population across four environments. The QTL controlling the content of total glutenin and its seven fractions were detected in clusters. Seven clusters enriched with QTL for more than three traits were identified, including a QTL cluster 6AS-3, which was revealed as a novel genetic locus for glutenin and related traits. Kompetitive Allele-Specific PCR (KASP) markers developed from the main QTL cluster 1DL-2 and the previously developed KASP marker for the QTL cluster 6AS-3 were validated as significantly associated with the target traits in the RIL population and in natural varieties. Conclusions This study identified novel genetic loci related to glutenin and its seven fractions. Additionally, the developed KASP markers may be useful for the marker-assisted selection of varieties with high glutenin fraction content and for identifying individuals in the early developmental stages without the need for phenotyping mature plants. On the basis of the results of this study and the KASP markers described herein, breeders will be able to efficiently select wheat lines with favorable glutenin properties and develop elite lines with high glutenin subunit contents.

ABSTRACT With the globally prevailing carbapenemase-producing (CP) Citrobacter spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was conducted to investigate the prevalence of mcr-9 in Citrobacter species. From October to November 2021, 650 fecal samples and 215 Citrobacter isolates were collected from healthy individuals and infected patients, respectively. Isolates were screened for the presence of the mcr-9 gene by the PCR method. mcr-9-carrying strains were identified by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Due to the susceptibility to colistin, Citrobacter spp. isolates were first induced to increase the expression of mcr-9 on China blue agar plates containing colistin and were then subjected to conjugation experiments. Whole-genome sequencing was performed on the Illumina NovaSeq PE150 system. The prevalence of mcr-9 in the Citrobacter genus from healthy guts and infected patients was 0.62% and 1.86%, respectively. In all mcr-9-positive strains, MICs of polymyxin B were observed at ≤2 μg/mL, displaying a nonresistant phenotype. As for conjugation experiments, only one isolate successfully transferred the mcr-9 gene to Escherichia coli C600. Whole-genome sequencing showed that eight mcr-9-positive Citrobacter isolates carried mcr-9 and genes encoding resistance to beta-lactam antibiotics, including blaCMY, blaDHA, blaSHV, blaTEM, and blaCTX-M. We also discovered that mcr-9 could be located on the pKPC-CAV1321 plasmid. Our study investigated the prevalence of mcr-9 in Citrobacter spp. in both healthy individuals and infected patients and described the carriage of mcr-9 on the pKPC-CAV1321 plasmid for the first time. IMPORTANCE The emergence of mcr homologues posed a serious threat to the therapeutic efficiency of polymyxin antibiotics. Citrobacter freundii is generally regarded as an opportunistic pathogen associated with a variety of nosocomial infections. In this study, we investigated the prevalence of mcr-9 in Citrobacter spp. isolates from healthy individuals and infected patients and highlighted the importance of the rational use of antibiotics. In addition, this epidemiological investigation is the first to describe the carriage of mcr-9 on plasmid pKPC-CAV1321 and confirms the horizontal transfer of this plasmid. Our research may shed new light on further studies of mcr-9 dissemination in humans.

ABSTRACT This study reports an extensively drug resistant Pseudomonas aeruginosa strain PA166-2 which was of chicken origin and carrying blaIMP-45, tet(X6) and tmexCD3-toprJ3 on a single plasmid. The strain was characterized by antimicrobial susceptibility testing, resistance gene screening, conjugation assay, whole-genome sequencing, and bioinformatics analysis. Strain PA166-2 was resistant to tigecycline and carbapenems. It belonged to ST313 and carried a plasmid pPA166-2-MDR, which belongs to the incompatibility group IncpRBL16. pPA166-2-MDR harbored a 78 Kb multidrug resistance (MDR) region carrying an array of antimicrobial resistance genes, including blaIMP-45, tet(X6), and tmexCD3-toprJ3. The gene blaIMP-45 was inserted into the backbone of plasmid pPA166-2-MDR within a class 1 integron, In786. tmexCD3-toprJ3 in plasmid pPA166-2-MDR was inserted in umuC, constituting the genetic context of ISCfr1-tnfxB3-tmexC3-tmexD3-toprJ3-△umuC. The genetic context of tet(X6) in this plasmid was identical to that of other reported plasmid-borne tet(X) variants, namely, tet(X6)-abh-guaA-ISVsa3. To the best of our knowledge, this is the first report of the cooccurrence of blaIMP-45, tet(X6), and tmexCD3-toprJ3 in one plasmid in Pseudomonas sp. The emergence of plasmid-mediated tigecycline resistance genes tmexCD3-toprJ3 and tet(X6), as well as carbapenemase genes from chickens expanded the global transmission of vital resistance genes. Findings from us and from others indicate that plasmids of the incompatibility group IncpRBL16 may serve as a reservoir for carbapenem and tigecycline resistance determinants. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that causes infections that are difficult to treat. This study reported, for the first time, the occurrence of last-resort antibiotic resistance determinants blaIMP-45, tet(X6), and tmexCD3-toprJ3 on a single plasmid in P. aeruginosa from chickens. The P. aeruginosa strain belonged to ST313 and was resistant to last-line antibiotics, namely, carbapenems and tigecycline. The plasmid carrying the last-line resistance genes belonged to the incompatibility group IncpRBL16, which was reported to contain different profiles of accessory modules and thus carried diverse collections of resistance genes. The emergence of plasmid-mediated tigecycline resistance genes tmexCD3-toprJ3 and tet(X6), as well as carbapenemase genes, from chickens expanded the global transmission of vital resistance genes. The results in this study highlighted that IncpRBL16 plasmids may serve as a reservoir for the dissemination of resistance genes. Control measures should be implemented to prevent the further dissemination of such strains.

Abstract Atmospheric wet deposition has attracted much attention because of its removal function of aerosol particles and impact on ecosystem. It is a complex multi‐component process due to various pollutants emission sources and reaction processes. However, traditional studies mainly focused on single components, ignoring the internal relationships and the comprehensive deposition level; this has hindered the comprehensive understanding and the assessment of ecological effects of deposition. Here, based on the monitoring of wet deposition across 52 stations during 2013–2018 in China, we used two novel multidimensional methods to investigate multi‐component atmospheric wet deposition: network analysis and comprehensive index. Network analysis is a new method that can help better explore the overall relationship between multiple components. We found that due to the improvement of human development level and the diversification of energy sources, the air pollutants sources became more diversified, which reduced the relationship between different deposition components and made the multi‐component deposition network looser. Comprehensive index is a method to realize the fusion of multiple parameters, which can explore the comprehensive effect of multi‐component atmospheric deposition on ecosystems. The high deposition comprehensive index occurred in the central and south China, and mainly influenced by human activities (energy consumption, fertilization, and vehicle ownership) and precipitation, which means that ecosystems in these regions are exposed to greater impacts by wet deposition. The findings provide new insights into understanding multi‐component atmospheric deposition and its comprehensive ecological effects.

Background: Depression is a common and potentially life-threatening mental illness, and currently, there is a lack of effective treatment. It has been reported that dehydrocorydaline (DHC) can inhibit monoamine transporter uptake in depressed CUMS mice, but more possible mechanisms of action remain to be further studied.Methods: C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for five consecutive weeks. The mice were administrated with dehydrocorydaline or fluoxetine (FLU) for four consecutive weeks. Behavioral tests including sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST) were applied. In parallel, hematoxylin and eosin (H&E) staining and Nissl staining were used to explore the effect of DHC on pathological changes in the hippocampus. The concentrations of depression-related factors (5-HT and DA) and inflammatory factors (TNF-α, IL-6, and IL-1β) in the hippocampus and serum were assessed by ELISA assay. NLRP3 inflammasome pathway-related proteins (NLRP3, IL-18, IL-1 IL-1α, and caspase-1) were detected by western blot. The activation of microglia and astrocytes was subjected to immunofluorescent staining. Additionally, microglia were treated with DHC (100 mg/L) for 24 h following incubation with 100 ng/ml LPS for 12 h. ov-NC or ov-NLRP3 plasmid was transfected into microglia 6 h before LPS induction for exploring the effect of NLRP3 overexpression on DHC-inhibited microglia activation. Then, conditioned media of microglia were collected from each group, followed by intervention of astrocytes for 24 h to explore the effect of NLRP3 overexpression of microglia on astrocyte activation.Results:In vivo administration of DHC was found to ameliorate depressive-like behaviors and attenuate neuron damage of CUMS mice. DHC increased neurotransmitter concentration, reduced the proinflammatory factor levels, attenuated NLRP3 inflammasome activation, and decreased A1 astrocyte and microglia activation in the hippocampus of CUMS mice. Furthermore, in vivo results showed that activated microglia induced activation of A1 astrocytes but not A2 astrocytes.Conclusion: Taken together, we provided evidence that DHC exhibited antidepressive effects on CUMS mice possibly via NLRP3 inflammasome-mediated astrocyte activation.

Germanium oxide (GeO2) is a high theoretical capacity electrode material due to its alloying and conversion reaction. However, the actual cycling capacity is rather poor on account of suffering low electron/ion conductivity, enormous volume change and agglomeration in the repeated lithiation/delithiation process, which renders quite a low reversible electrochemical lithium storage reaction. In this work, highly amorphous GeO2 particles are uniformly distributed in the carbon nanofiber framework, and the amorphous carbon nanofiber not only improves the conduction and buffers the volume changes but also prevents active material agglomeration. As a result, the present GeO2 and carbon composite electrode exhibits highly reversible alloying and conversion processes during the whole cycling process. The two reversible electrochemical reactions are verified by differential capacity curves and cyclic voltammetry measurements during the whole cycling process. The corresponding reversible capacity is 747 mAh g−1 after 300 cycles at a current density of 0.3 A g−1. The related reversible capacities are 933, 672, 487 and 302 mAh g−1 at current densities of 0.2, 0.4, 0.8 and 1.6 A g−1, respectively. The simple strategy for the design of amorphous GeO2/carbon composites enables potential application for high-performance LIBs.

Summary Klebsiella pneumoniae has emerged as one of the most important pathogens that frequently encounter in community‐acquired or hospital‐acquired infections. Timely epidemiological surveillance could greatly facilitate infection control of K. pneumoniae and many deadly pathogens alike. In this study, we evaluated the performance of the IR Biotyper, a Fourier transform infrared (FTIR) spectroscopy system for K. pneumoniae isolates typing through (i) optimizing the culture scheme and defining the cutoff value (COV) range and (ii) comparing with commonly used typing tools such as multi‐locus sequence typing (MLST), pulsed‐field gel electrophoresis (PFGE) and whole‐genome sequencing (WGS). We found that a non‐selective and non‐chromogenic medium with 24 ± 2 h incubation gives the best discriminatory power for the IR Biotyper (IRBT). COV evaluation indicated that the IRBT is a robust typing method with good reproducibility. Besides, we observed that the modified H2O‐EtOH suspensions preparation method could enhance the quality of the spectrum, especially for those hypermucoviscous strains. For the method comparison study, our data demonstrated that FTIR spectroscopy could accurately cluster K. pneumoniae strains. The typing results of the IRBT were almost entirely in concordance with those from PFGE and WGS. Together with the advantages such as low costs and short turnaround time (less than 3h), the IRBT is a promising tool for strain typing that could make real‐time outbreak investigation a reality.

ABSTRACT Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus-related enterovirus species B serotypes in our previous study. Echovirus 18 (E18), as a member of enterovirus species B, is a significant causative agent of aseptic meningitis and viral encephalitis in children. However, it does not use CD55 as a critical host factor. We conducted CRISPR/Cas9 knockout screening to determine the receptors and entry mechanisms and identified FcRn working as a dual-function receptor for E18. Knockout of FCGRT and B2M, which encode the two subunits of FcRn, prevented infection by E18 and other echoviruses in the same physiological cluster. We then elucidated the underlying molecular mechanism of receptor recognition by E18 using cryogenic electron microscopy. The binding of the FCGRT subunit to the canyon region rotates the residues around the pocket, triggering the release of the pocket factor as observed for other enterovirus species B members. IMPORTANCE E18 is a member of enterovirus species B. As one of the most common enterovirus serotypes in nonpolio enterovirus detection, it easily infects children and causes various clinical symptoms. Aseptic meningitis and viral encephalitis are the most commonly reported syndromes associated with E18. No effective antiviral drugs or approved vaccines are available. Previous studies showed that CD55 and FcRn were the binding and uncoating receptors for some echoviruses. However, we found that CD55 is not the critical host factor for E18. Thus, we want to determine the receptors and elucidate the entry mechanism of E18. Our findings reveal that FcRn is a two-in-one attachment-uncoating receptor for E18.