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Abstract Background Despite the link between neuroticism trait and postnatal depression has been confirmed, little is known about the factors that influence this association. This study aimed to examine whether childbirth experience mediated the association between neuroticism trait and postnatal depression, and whether this indirect effect was moderated by perceived social support. Methods A cross-sectional study was conducted with 1686 women within one year postpartum from 38 hospitals in China. Participants completed anonymous questionnaires measuring neuroticism trait, postnatal depression, childbirth experience, perceived social support, and demographic and obstetric variables. Data were analyzed using SPSS 26.0 and PROCESS 4.0. Results The prevalence of postnatal depression among Chinese women was 24.1%, higher than the global pooled prevalence. The results showed a positive correlation between neuroticism trait and postnatal depression, which was partially mediated by childbirth experience. The negative correlation between neuroticism trait and childbirth experience was moderated by perceived social support. Specifically, the negative impact of neuroticism trait on childbirth experience was stronger among women with high perceived social support. Conclusions Our findings highlight the critical importance of interventions dedicated to improving the childbirth experience, which may help reduce postnatal depression. Moreover, neuroticism and perceived social support are highly correlated and must be considered simultaneously to inform individualized interventions for postnatal depression.

Abstract Radiotherapy has been demonstrated to be one of the most significant treatments for cervical cancer, during which accurate and efficient delineation of target volumes is critical. To alleviate the data demand of deep learning and promote the establishment and promotion of auto-segmentation models in small and medium-sized oncology departments and single centres, we proposed an auto-segmentation algorithm to determine the cervical cancer target volume in small samples based on multi-decoder and semi-supervised learning (MDSSL), and we evaluated the accuracy via an independent test cohort. In this study, we retrospectively collected computed tomography (CT) datasets from 71 pelvic cervical cancer patients, and a 3:4 ratio was used for the training and testing sets. The clinical target volumes (CTVs) of the primary tumour area (CTV1) and pelvic lymph drainage area (CTV2) were delineated. For definitive radiotherapy (dRT), the primary gross target volume (GTVp) was simultaneously delineated. According to the data characteristics for small samples, the MDSSL network structure based on 3D U-Net was established to train the model by combining clinical anatomical information, which was compared with other segmentation methods, including supervised learning (SL) and transfer learning (TL). The dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and average surface distance (ASD) were used to evaluate the segmentation performance. The ability of the segmentation algorithm to improve the efficiency of online adaptive radiation therapy (ART) was assessed via geometric indicators and a subjective evaluation of radiation oncologists (ROs) in prospective clinical applications. Compared with the SL model and TL model, the proposed MDSSL model displayed the best DSC, HD95 and ASD overall, especially for the GTVp of dRT. We calculated the above geometric indicators in the range of the ground truth (head-foot direction). In the test set, the DSC, HD95 and ASD of the MDSSL model were 0.80/5.85 mm/0.95 mm for CTV1 of post-operative radiotherapy (pRT), 0.84/ 4.88 mm/0.73 mm for CTV2 of pRT, 0.84/6.58 mm/0.89 mm for GTVp of dRT, 0.85/5.36 mm/1.35 mm for CTV1 of dRT, and 0.84/4.09 mm/0.73 mm for CTV2 of dRT, respectively. In a prospective clinical study of online ART, the target volume modification time (MTime) was 3–5 min for dRT and 2–4 min for pRT, and the main duration of CTV1 modification was approximately 2 min. The introduction of the MDSSL method successfully improved the accuracy of auto-segmentation for the cervical cancer target volume in small samples, showed good consistency with RO delineation and satisfied clinical requirements. In this prospective online ART study, the application of the segmentation model was demonstrated to be useful for reducing the target volume delineation time and improving the efficiency of the online ART workflow, which can contribute to the development and promotion of cervical cancer online ART.

There is an urgent need to determine reasonable water-quality benchmarks and risk assessment results to accurately characterize the relationship between crop yield enhancement and ammonia nitrogen pollution caused by excessive nitrogen fertilizer application. Through the collection of monitoring data from 2016 to 2023 in Chagan Lake, the first development of ecological criteria for ammonia nitrogen and risk evaluation for Northeast China was carried out based on the secondary ecological risk models (the quotient value method and joint probability curve). In addition, the species sensitivity distribution (SSD) model is improved through the use of genetic algorithms to identify more suitable ammonia water-quality benchmarks for ecological risk assessment. The results showed that high ammonia nitrogen concentration in wet season is primarily influenced by agricultural irrigation and drainage activities, whereas the dry season is driven by low temperatures and the nitrogen and phosphorus concentrations. The biological benchmark of improved SSD model with a genetic algorithm has a maximum error reduction of 23.84 % compared with other distributions, which is more than twice that of the median water-quality benchmark under the traditional Class III water-quality standard and empirical formula. Risk evaluation using traditional water-quality standards leads to the overprotection of the biological environment. Evaluations using quotient value methods and joint probability curves yield consistent results. The severity of the ecological risk of ammonia nitrogen follows the order: wet season > flat season > dry season. Using a genetic algorithm to optimize SSD model can effectively reduce the uncertainty of the model, providing a more accurate and reasonable ammonia nitrogen water-quality benchmark. This study improves the evaluation of the ecological risk of ammonia nitrogen in Lake Chagan, provides ideas for reducing the uncertainty of the selection of ammonia nitrogen water-quality benchmarks, and effectively prevents the overprotection of the lake from ammonia nitrogen.

Abstract Traditional warehousing typically needs machine learning or manual tagging to classify objects. However, this method is less robust and consumes a lot of labour and material resources. Based on DenseNet, this work proposes a feature weighting convolutional network recognition model and designs a set of software and hardware for data acquisition, which is applied to the efficient classification of industrial parts in warehouse management. Firstly, this work modifies DenseNet by embedding SE‐Block, and replaces the cross‐entropy loss function with the focus loss function to optimize the model structure. Secondly, a multi‐view hardware and software acquisition system is designed to complete the functions of part image acquisition, image preprocessing, model training and part recognition. Finally, an industrial parts sorting experiment was designed. Compared with the original DenseNet model, the proposed weighted convolutional network identification model showed that the accuracy of the modified model was increased by 3.09% and the convergence rate was significantly improved. The modified model proposed in this work aims to improve the recognition accuracy of industrial parts in modern warehouse management, so as to modify the classification efficiency of warehouse parts in production.

The common carp (Cyprinus carpio) is a crucial freshwater species cultivated worldwide for food consumption. Female carp have better growth performance than males, which fascinates scholars to uncover the mechanism of gonadal differentiation and produce mono-sex populations. However, the mechanism of ovarian development at single-cell resolution is limited. Here, we conducted single-nucleus RNA sequencing in adolescent common carp ovaries. Our study obtained transcriptional profiles of 13,155 nuclei and revealed 13 distinct cell clusters in the ovaries, including three subtypes of germ cells and four subtypes of granulosa cells. We subsequently performed pseudotime trajectory analysis to delineate potential mechanisms underlying the development of germ cells and granulosa cells. We identified 1250 dynamic expression genes in germ cells and 1815 in granulosa cells (q-value < 0.01), including zp3, eif4a2 and aspm in germ cells and fshr and esr1 in granulosa cells. The functional annotation showed that dynamic expression genes in germ cells were involved in sperm–egg recognition and some terms related to meiosis, such as sister chromatid segregation and homologous recombination. Genes expressed dynamically in granulosa cells were related to the TGF-β signaling pathway, response to gonadotropin, and development of primary female sexual characteristics. In addition, the dynamic genes expressed in granulosa cells might relate to the complex communication between different cell types. In summary, our study provided a transcriptome profile of common carp ovaries at single-nucleus resolution, and we further revealed the potential cell type-specific mechanisms underlying oogenesis and the differentiation of granulosa cells, which will facilitate breeding all-female common carp populations.

Abstract The effects of calcium phosphate (CaP) materials on macrophage polarization state vary with their physicochemical properties. The study aims to elucidate the impact of phosphate ion‐mediated energy metabolism on M2 macrophage polarization and the corresponding regulatory mechanism. The phosphate ions released from CaP ceramic as bioenergetic factor is identified; its concentration is closely associated with the polarized state. After being taken up by the sodium‐dependent phosphate transporter 1, extracellular phosphate ions produce energy via oxidative phosphorylation by facilitating tricarboxylic acid flux, thereby contributing to M2 macrophage polarization. Further mechanistic analysis reveals that the elevation of the bioenergetic basis can drive macrophage M2 polarization via the AMP‐activated protein kinase‐mammalian target of rapamycin (AMPK‐mTOR) axis. Another regulatory effect is that of the adenosine triphosphate (ATP), a signaling molecule. Intracellular ATP is released into the extracellular space and degraded to adenosine, which serves as a signaling molecule through the A2b adenosine receptor to activate the cyclic adenosine monophosphate (cAMP) pathway, thereby promoting M2 macrophage polarization. Overall, these findings may transform the existing knowledge on cell metabolism and energy homeostasis from bystanders to pivotal factors guiding M2 macrophage polarization and have implications for the future design of biomimetic CaP scaffolds.

Abstract In this paper, the authors investigate the issue of constructing and incorporating an accurate vehicle dynamic model for model predictive control (MPC) with an application to autonomous vehicle path following. To achieve the desired performance, MPC employs a precise dynamic model. However, the uncertainty of complex systems and their operating environments presents a challenge to the development of an adequately accurate vehicle dynamic model. This paper proposes a Deep Gaussian Process Regression (DGPR) method to improve model precision. Meanwhile, the learning model is incorporated into a novel MPC framework to enhance closed‐loop performance. High‐fidelity simulations using CarSim‐MATLAB demonstrate the validity of the proposed approach in terms of enhancing the path following performance and lateral stability under the condition of large curvature at medium to high speeds on roads with different friction coefficients when compared to the nominal MPC approach.

Abstract Breast cancer (BC) is the most common cancer and the top cause of female mortality worldwide. The prognosis for patients with breast cancer liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated with the progression of BC. Exploration of circRNAs presents a promising avenue for identifying metastasis-targeting agents and improving the prognosis of patients with BCLM. Microarray and bioinformatic analyses were used to analyze differentially expressed circRNAs between three pairs of BCLM and primary BC. The roles of hsa_circ_0060467 (circMYBL2) and its target gene E2F1 in BC cells were explored by multiple functional experiments. And xenograft mouse models and hepatic metastases of BC hemi-spleen models were used to illustrate the function of circMYBL2 in vivo. The intrinsic molecular mechanism involving circMYBL2 was confirmed by bioinformatics analyses, RIP assays, CHIRP assays, luciferase reporter assays, and rescue experiments. CircMYBL2 was overexpressed in BCLM tissues and BC cells. Functionally, circMYBL2 can facilitate the proliferation and liver metastasis of BC. Mechanistically, circMYBL2 upregulated the transcription factor E2F1 by sponging miR-1205 and complexing with eukaryotic translation initiation factor 4A3 (eIF4A3) and then facilitated the epithelial-mesenchymal transition (EMT) process in BC cells. Our findings showed that circMYBL2 promoted the tumorigenesis and aggressiveness of BC through the circMYBL2/miR-1205/E2F1 and circMYBL2/eIF4A3/E2F1 axes, which may provide a novel targeted therapy for patients with BCLM.

Abstract Transforming growth factor β (TGFβ) activity is perturbed in remodelled pulmonary vasculature of patients with pulmonary arterial hypertension (PAH), cancer, vascular diseases and developmental disorders. Inhibition of TGFβ, which signals via activin receptor-like kinase 5 (ALK5), prevents progression and development of experimental PAH. The purpose of this study was to assess two ALK5 targeting positron emission tomography (PET) tracers ([11C]LR111 and [18F]EW-7197) for imaging ALK5 in monocrotaline (MCT)- and Sugen/hypoxia (SuHx)-induced PAH. Both tracers were subjected to extensive in vitro and in vivo studies. [11C]LR111 showed the highest metabolic stability, as 46 ± 2% of intact tracer was still present in rat blood plasma after 60 min. In autoradiography experiments, [11C]LR111 showed high ALK5 binding in vitro compared with controls, 3.2 and 1.5 times higher in SuHx and MCT, respectively. In addition, its binding could be blocked by SB431542, an adenosine triphosphate competitive ALK5 kinase inhibitor. However, [18F]EW-7197 showed the best in vivo results. 15 min after injection, uptake was 2.5 and 1.4 times higher in the SuHx and MCT lungs, compared with controls. Therefore, [18F]EW-7197 is a promising PET tracer for ALK5 imaging in PAH.

Abstract Programmed cell death ligand 1 protein-positive (PD-L1+) exosomes have been found to be a potential biomarker for the diagnosis of non-small cell lung cancer (NSCLC). However, the development of highly sensitive detection technique for PD-L1+ exosomes is still a challenge in clinical applications. Herein, a sandwich electrochemical aptasensor based on ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres (PdCuB MNs) and Au@CuCl2 nanowires (NWs) was designed for the detection of PD-L1+ exosomes. The excellent peroxidase-like catalytic activity of PdCuB MNs and the high conductivity of Au@CuCl2 NWs endow the fabricated aptasensor with intense electrochemical signal, thus enabling the detection of low abundance exosomes. The analytical results revealed that the aptasensor maintained favorable linearity over a wide concentration range of 6 orders of magnitude and reached a low detection limit of 36 particles/mL. The aptasensor is successfully applied to the analysis of complex serum samples and achieves the accurate identification of clinical NSCLC patients. Overall, the developed electrochemical aptasensor provides a powerful tool for early diagnosis of NSCLC.

Female common carp grow faster than male individuals, implying that rearing females could be more profitable in aquaculture. Non-coding RNAs (ncRNAs) serve as versatile regulators with multiple functions in diverse biological processes. However, the roles of ncRNAs in the sex differentiation of common carp are less studied. In this study, we investigated the expression profiles of ncRNAs, including miRNAs, lncRNAs, and circRNAs, in the gonads to comprehend the roles of ncRNAs in sex differentiation in common carp. A substantial number of differentially expressed (DE) ncRNAs in ovaries and testes were identified. Some miRNAs, notably miR-205, miR-214, and miR-460-5p, might modulate hormone synthesis and thus maintain sex. A novel miRNA, novel_158, was predicted to suppress the expression of foxl3. DE lncRNAs were associated with oocyte meiosis, GnRH signaling pathways, and steroid biosynthesis, while DE circRNA target genes were enriched in the WNT signaling pathway and MAPK signaling pathway. We also analyzed ncRNA-mRNA interactions to shed light on the crosstalk between competing endogenous RNAs (ceRNAs), which is the critical mechanism by which lncRNAs and circRNAs function. Some lncRNAs and circRNAs may be able to competitively bind novel_313, a new miRNA, and thus regulate hsd17β3. Our research will provide a valuable resource for understanding the genetic basis of gonadal differentiation and development in common carp.

BackgroundDespite extensive debates about the mental health impacts of the use of social networking sites (SNSs), including WeChat, the association and mechanisms between social interaction of WeChat use intensity and antenatal depression are unclear. ObjectiveWe aimed to test the mediating roles of upward social comparison on social interaction of WeChat and rumination in the association between social interaction of WeChat use intensity and antenatal depression. MethodsA cross-sectional survey was conducted in four hospitals with the self-reported measures of social interaction of WeChat use intensity, upward social comparison on social interaction of WeChat, rumination, antenatal depression, and control variables. The mediation analysis was performed through Model 6 from the PROCESS macro 4.0 in SPSS 26. ResultsResults from 2661 participants showed that antenatal depression was unrelated to social interaction of WeChat use intensity (P=.54), but was significantly positively related to the attitude toward social interaction of WeChat (P=.01). The direct effect of attitude toward social interaction of WeChat use on antenatal depression was not statistically significant (β=–.03, P=.05). The results supported an indirect relationship between attitude toward social interaction of WeChat use and antenatal depression via (1) upward social comparison on social interaction of WeChat (indirect effect value=0.04, 95% CI 0.03 to 0.06); (2) rumination (indirect effect value=–0.02, 95% CI –0.04 to –0.01); and (3) upward social comparison on social interaction of WeChat and rumination in sequence (indirect effect value=0.07, 95% CI 0.06 to 0.08). ConclusionsOur findings highlight the necessity of focusing on attitudes toward SNS use, and the importance of upward social comparison and rumination in understanding the effect of SNS use on antenatal depression.

AimTo define and analyze the concept of psychological birth trauma.DesignThe concept analysis method of Walker and Avant was used.MethodEight databases (PubMed, CINAHL Complete, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and Chinese BioMedicine Literature Database) were searched from inception to July 2022 for studies focused on psychological birth trauma.ResultsOf the 5,372 studies identified, 44 ultimately met the inclusion criteria. The attributes identified were (1) women’s subjective feelings, (2) intertwined painful emotional experiences, (3) originating in the birth process, and (4) lasting until postpartum. Antecedents were divided into two groups: pre-existing antecedents and birth-related antecedents. Consequences were identified as negative and positive.ConclusionPsychological birth trauma is a more complex and comprehensive concept than previously thought, and should be regarded as a separate postpartum mental health problem. This study deepens the understanding of psychological birth trauma through a comprehensive concept analysis and also puts forward some suggestions for the prevention, identification, and intervention of psychological birth trauma, which provides a basis for assisting in the identification of psychological birth trauma and provides a reference for the development of rigorous assessment tools and the design of appropriate interventions in the future. Further research is needed to update and refine this concept.

Niviventer sacer (Rodentia: Muridae) had been regarded as a subspecies of N. confucianus, i.e. N. c. sacer, and was raised as a distinct species recently by our laboratory. We sequenced the complete mitochondrial genome of N. sacer first and annotated the genome structure. The total length of the genome was 16,308 base pairs (bp) containing 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and a control region. We also constructed the phylogenetic tree by maximum-likelihood method and it demonstrated that N. sacer was the sister clade of N. confucianus.

Taenia solium (T. solium) cysticercosis is a serious threat to human health and animal husbandry. During parasitization, Cysticercus cellulosae (C. cellulosae) can excrete and secrete antigens that modulate the host’s T-cell immune responses. However, the composition of C. cellulosae excretory-secretory antigens (ESAs) is complex. This study sought to identify the key molecules in C. cellulosae ESAs involved in regulating T-cell immune responses. Thus, we screened for thioredoxin peroxidase (TPx), with the highest differential expression, as the key target by label-free quantification proteomics of C. cellulosae and its ESAs. In addition, we verified whether TPx protein mainly exists in C. cellulosae ESAs. The TPx recombinant protein was prepared by eukaryotic expression, and ESAs were used as the experimental group to further investigate the effect of TPx protein on the immune response of piglet T cells in vitro. TPx protein induced an increase in CD4+ T cells in piglet peripheral blood mononuclear cells (PBMCs), while CD8+ T cells did not change significantly. This resulted in an imbalance in the CD4+/CD8+ T-cell ratio and an increase in CD4+CD25+Foxp3+ Treg cells in the PBMCs. In addition, TPx protein initiated T helper 2 (Th2)-type immune responses by secreting IL-4 and IL-10 and suppressed Th1/Th17-type immune responses. The results showed that ESAs were involved in regulating piglet T-cell immune responses cells. This suggests that TPx protein found in ESAs plays an essential role to help the parasite evade host immune attack. Moreover, this lays a foundation for the subsequent exploration of the mechanism through which TPx protein regulates signaling molecules to influence T-cell differentiation.

Aiming at the problem of precision driving and vibration suppression for sensitive payloads on-orbit, this paper proposes a new compliant platform based on an embedded superstructure and a smart material actuator. Firstly, the main structure of the platform is designed and optimized to achieve the expected indicators via the response surface method. Then, the vibration reduction mechanism of the platform with the embedded superstructure is studied by establishing an equivalent model. Following that, a four-phase superstructure is matched and designed with a compact space, and the results are verified by finite element modal analysis. Finally, both the tensioning performance and vibration reduction performance under fixed frequency harmonic disturbance are studied via transient dynamic simulation. Based on the obtained results, directions for future improvements are proposed. The relevant conclusions can provide a reference for function integration of precision tensioning and vibration suppression.

The development of chemoresistance reduces the efficacy of anti‐cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT‐hook 2 (HMGA2) is involved in the development and progression of tumors, although its role in chemoresistance of cervical cancer remains unclear. Here, we report that HMGA2 is highly expressed in cervical cancer and negatively correlated with cisplatin‐induced cell death. We performed liquid chromatography‐tandem mass spectrometry to demonstrate that HMGA2 has high potential to interact with casein kinase II A1 (CSNK2A1). Moreover, we observed that HMGA2 co‐localizes with CSNK2A1 in the nucleus by immunofluorescence. Binding of HMGA2‐CSNK2A1 was detected by immunoprecipitation assays. In addition, we identified that cisplatin induces an interaction between CSNK2A1 and HMGA2, thereby promoting the phosphorylation of HMGA2. CX‐4945, a CSNK2A1 inhibitor, could inhibit the phosphorylation of HMGA2 and sensitize tumor cells to cisplatin. Our results reveal that CSNK2A1‐dependent HMGA2 phosphorylation may partially underlie cisplatin‐resistance in cervical cancer, suggesting that HMGA2 phosphorylation may have potential as a predicative biomarker and therapeutic target to improve chemotherapeutic efficacy.

Abstract Background Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated. Methods In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients’ samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry. Results ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients. Conclusion Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.

Abstract Background Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI. Methods An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms. Results Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted. Conclusions Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others. Trial registration ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.

The need to accurately measure the mechanical properties of freestanding thin films such as carbon nanotube reinforced nanocomposite thin films and various buckypaper is increasingly urgent. This paper presents the design and control of a novel compliant tensile testing module based on buckled fixed-guided beams aimed at accurately measuring the mechanical properties of freestanding thin films. The piezoelectric stack actuator that can provide high resolution for the output displacement is chosen to actuate the tensile testing module. The advantages of the module are its compactness, no friction, no wear, low cost and good repeatability. The performance is further evaluated by the established analytical model using the elliptic integral approach and the nonlinear finite-element analysis (FEA). A metal prototype of the tensile testing design has been fabricated and the performance of the fabricated prototype is investigated through open-loop displacement response experiments. Experimental results demonstrate the effectiveness of the proposed ideas for the mechanism. The design holds great potential applications in measuring mechanical properties of freestanding thin-film materials such as carbon nanotube reinforced nanocomposite thin films and various buckypaper as well as other freestanding thin-film materials.

Abstract Background Intestinal microbiota restoration can be achieved by complementing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. Results All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel “transplantation index” metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. Conclusions Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state. Trial registration ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract

Excretory–secretory antigens (ESAs) of Cysticercus cellulosae can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which C. cellulosae ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3+ T cells stimulated by C. cellulosae ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of C. cellulosae ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that C. cellulosae ESAs could upregulate the TGF-β signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. C. cellulosae ESAs activate the TGF-β signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of C. cellulosae-mediated immune evasion.

The complete mitochondrial genome of the Dongyangjiang White-toothed Shrew (Crocidura dongyangjiangensis), a newly discovered Crocidura species, is sequenced and characterized. The total length of the genome is 16,883 bp, and has similar base composition and gene arrangement to other vertebrates. It contains 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA), 22 transfer RNA (tRNA), a replication origin (OL) and a control region. The phylogenetic tree shows that C. dongyangjiangensis was fully resolved in a clade with three other species of Crocidura and it has a sibling relationship with Crocidura tanakae. This analysis reveals the evolutionary relationship of 16 Crocidura species.

The authors investigate the burden and spatiotemporal dynamics of multidrug-resistant bacteria on intensive care unit surfaces from two hospitals in the US and Pakistan over a year. They find Acinetobacter baumannii and Enterococcus faecium co-association, likely due to synergistic biofilm formation.

Mismatch removal is a critical step of feature matching, which is a prerequisite of many vision-based tasks. This paper aims to develop a general and robust method for mismatch removal. To this end, we propose an efficient learning-based mismatch removal method that can significantly improve outlier identification in terms of both accuracy and efficiency. The key idea of our approach is to use a set of properties to describe the putative matches and feed the match representations to a supervised learning procedure learning a binary classifier for mismatch removal. The efficient properties mainly include three aspects: consistency of neighborhood elements, weighted consistency of neighborhood topology, and the stability of correspondence. Different from existing consistency of neighborhood topology, we adopt a weighted strategy to emphasize the effect of different properties with respect to the identified correspondence. The match representations combine the spatial positions of the correspondences with their descriptor reliabilities, which can effectively enlarge the distributions between outliers and inliers. To handle large proportions of outliers, we design a simple strategy to obtain a subset with high ratio inliers guiding the match representations construction process. This strategy can also boost the number of true correspondences without sacrificing the accuracy. Extensive experiments demonstrate our superiority over the state-of-the-art methods.

Abstract Background Schmid‐type metaphyseal chondrodysplasia (SMCD) is a rare autosomal dominant skeletal dysplasia caused by heterozygous mutations in COL10A1, the gene which encodes collagen type X alpha 1 chain. However, its genotype–phenotype relationship has not been fully determined. Subjects and Methods The proband is a 2‐year‐old boy, born of non‐consanguineous Chinese parents. We conducted a systematic analysis of the clinical and radiological characteristics and a follow‐up study of the proband. Whole‐exome sequencing was applied for the genetic analysis, together with bioinformatic analysis of predicted consequences of the identified variant. A homotrimer model was built to visualize the affected region and predict possible outcomes of this variant. Furthermore, a literature review and genotype–phenotype analysis were performed by online searching all cases with SMCD. Results A novel heterozygous variant (NM_000493.4: c.1863_1866delAATG, NP_000484.2: p.(Met622 Thrfs*54)) was identified in COL10A1 gene in the affected child. And it was predicted to be pathogenic by in silico analysis. Protein modeling revealed that the variant was located in the NC1 domain, which was predicted to produce truncated collagen and impair the trimerization of collagen type X alpha 1 chain and combination with molecules in the matrix. Moreover, genotype–phenotype correlation analysis demonstrated that patients with truncating variants or variants in NC1 domain often presented earlier onset and severer symptoms compared with those with non‐truncating or variants in non‐NC1 domains. Conclusion The NC1 domain of COL10A1 was proved to be the hotspot region underlying SMCD, patients with variants in NC1 domain were more likely to present severer manifestations at an earlier age.

In this paper, an innovative three-dimensional braiding piezoelectric composite actuator (3D-BPCA) is proposed. Based on the 3D braiding technology, the geometric model and representative volume unit (RVU) model of the 3D-BPCA are established. The effective elastic constant, dielectric constant and piezoelectric constant of the braiding piezoelectric composite layer (BPCL) are predicted. The electromechanical properties of the 3D-BPCA under the electromechanical coupling field is theoretically analyzed and numerically simulated, and compared with the piezoelectric ceramics actuator (PZT-5A). Numerical results show that the 3D-BPCA has better actuating properties than the PZT-5A and has a wide application prospects.

Access to safe drinking water is one of the fundamental human rights and an important part of healthy living. This study considered various land use methods, used geostatistical analysis, and triangular random model to explore nitrogen pollution and estimate its potential risk to human health for local populations in Songnen Plain of Northeast China and recognize parameter uncertainties. Nitrate concentrations in groundwater ranged from 0.01 to 523.45 mg/L, more than 72.35% of the samples exceeded Grade III threshold (20 mg/L of N) as per China's standard, and nitrate nitrogen content is greater than 20 mg/L accounted for around 60% of the research area, mainly distributed in the eastern and central high plain area. The nitrate-nitrogen content of groundwater in the town land was significantly higher than that of agricultural land, and the ammonia nitrogen content was conversely. The townland's risk value was two times that of agricultural land, considering different land use methods would avoid overestimating or underestimating regional risk value. Non-carcinogenic risks (HI) of two land use were above the safety level (i.e., HI > 1), suggesting that groundwater nitrate would have significant health effects on the age groups, and further threaten children. There was a wide range of fluctuations in the uncertainty of nitrogen concentration and model evaluation parameters; triangular random model was more sensitive to data changes, which could reduce the uncertainty. The contribution rate of nitrate-nitrogen concentration to risk was above 90%, which explained the need for random sampling to improve the evaluation results reliability. The findings in this paper will provide new insight for solving uncertainties in water safety management.

Giant magnetostrictive transducer with micro and nano precision has a wide application prospect in the field of remote sensing. However, excessive heat loss of components could generate during the energy conversion and transfer from electric energy to magnetic energy, and magnetic energy to mechanical energy, thereby affecting its long-term service and also reducing energy utilization. In this paper, a new magnetostrictive transducer is proposed and its excitation coil, internal and external magnetic circuit are optimized from the perspective of reducing heat loss. With the help of theoretical and finite element analysis, the response law between key parameters and heat loss of key components are summarized, which provides a basis for reducing heat loss. Finally, according to the optimization scheme, the prototype is processed, and the temperature rise and dynamic output performance of the transducer are tested by constructing an experimental setup. The results show that the transducer has a low temperature rise and good frequency response characteristics, which can provide support for long-time precise actuation on-orbit.

Bivalve molluscs have evolved various characteristics to adapt to benthic filter-feeding. Here, Li et al investigate the genome, transcriptomes and proteomes of scallop Chlamys farreri, revealing evidences of molecular adaptations to semi-sessile life and neurotoxins.

Most recently, Kan Yang et al. proposed an attribute-keyword based encryption scheme for data publish-subscribe service(AKPS), which is highly useful for cloud storage scenario. Unfortunately, we discover that there is a flaw in the security proof of indistinguishability of the tag and trapdoor against chosen keyword attack under the Bilinear Diffie-Hellman (BDH) assumption. As the security proof is a key component for a cryptographic scheme, based on the Decisional Diffie-Hellman (DDH) assumption, we improve the security proof method and give a new security proof of the AKPS scheme for indistinguishability of the tag and trapdoor in our proposal, which is more rigorous than the original one. Furthermore, we also demonstrate that the AKPS scheme is secure against data Replayable Chosen Ciphertext Attack (RCCA).

ABSTRACT Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one’s feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.) IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one’s feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.

Jujube (Ziziphus jujuba Mill.) belongs to the Rhamnaceae family and is a popular fruit tree species with immense economic and nutritional value. Here, we report a draft genome of the dry jujube cultivar 'Junzao' and the genome resequencing of 31 geographically diverse accessions of cultivated and wild jujubes (Ziziphus jujuba var. spinosa). Comparative analysis revealed that the genome of 'Dongzao', a fresh jujube, was ~86.5 Mb larger than that of the 'Junzao', partially due to the recent insertions of transposable elements in the 'Dongzao' genome. We constructed eight proto-chromosomes of the common ancestor of Rhamnaceae and Rosaceae, two sister families in the order Rosales, and elucidated the evolutionary processes that have shaped the genome structures of modern jujubes. Population structure analysis revealed the complex genetic background of jujubes resulting from extensive hybridizations between jujube and its wild relatives. Notably, several key genes that control fruit organic acid metabolism and sugar content were identified in the selective sweep regions. We also identified S-locus genes controlling gametophytic self-incompatibility and investigated haplotype patterns of the S locus in the jujube genomes, which would provide a guideline for parent selection for jujube crossbreeding. This study provides valuable genomic resources for jujube improvement, and offers insights into jujube genome evolution and its population structure and domestication.

OBJECTIVES/SPECIFIC AIMS: A course of oral broad-spectrum antibiotics frequently has a positive effect on morbidity and mortality in severe acute malnutrition (SAM), but the actual mechanism for this effect is unknown. This mechanism is especially important to find and quantify because of the possibility that using antibiotics prophylactically may accelerate the danger from antibiotic resistant infections. This study aims to answer (1) how antibiotic therapy improves the nutritional recovery and (2) how much it affects the prevalence of resistance genes in the microbiome. METHODS/STUDY POPULATION: Stool samples were collected from children with SAM between 6 and 60 weeks of age who received either one week of amoxicillin or placebo (n=164). The children were followed for 12 weeks with longitudinal sampling, and a subset were followed out to 2 years. All samples were frozen at −80°C and prepared for metagenome shotgun sequencing via the Illumina Nextera platform. RESULTS/ANTICIPATED RESULTS: Antibiotic treatment at the start of the nutritional program is associated with significant improvements in weight gain, mid-upper-arm circumference, and graduation from the treatment program. It is also associated with qualitative decreases in early-life fermenter Lactobacillus and known enteropathogen Campylobacter. Two years after the use of amoxicillin, the Shannon diversity index is significantly higher than that of malnourished children (effect size 0.507, 95% CI: 0.204–0.630, p=0.0007), while children who received placebo are not distinguishable from malnourished children by the same metric (effect size 0.147, 95% CI: −0.311, 0.630, p=0.5878). Sustained antibiotic resistance gene enrichment within the microbiota did not occur, as the enrichment effects disappears by week 4 of follow-up. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of amoxicillin to treat uncomplicated SAM has therapeutic benefits visible by anthropometry and by content of the gut microbiota. The main concern with the use of prophylactic antibiotics for this purpose is the effect on antibiotic resistance gene enrichment in the children’s microbiota. This concern was not supported here. The benefit/cost ratio for the use of prophylactic antibiotics for individuals in this cohort is positive when weighing effects on anthropometry, microbiome, and antibiotic resistance. The results of this study impact the treatment of millions of children each year at nutritional therapy clinics around the world.

Molting is one of the most important biological processes in shrimp growth and development. All shrimp undergo cyclic molting periodically to shed and replace their exoskeletons. This process is essential for growth, metamorphosis, and reproduction in shrimp. However, the molecular mechanisms underlying shrimp molting remain poorly understood. In this study, we investigated global expression changes in the transcriptomes of the Pacific white shrimp, Litopenaeus vannamei, the most commonly cultured shrimp species worldwide. The transcriptome of whole L. vannamei was investigated by RNA-sequencing (RNA-seq) throughout the molting cycle, including the inter-molt (C), pre-molt (D0, D1, D2, D3, D4), and post-molt (P1 and P2) stages, and 93,756 unigenes were identified. Among these genes, we identified 5,117 genes differentially expressed (log2ratio ≥1 and FDR ≤0.001) in adjacent molt stages. The results were compared against the National Center for Biotechnology Information (NCBI) non-redundant protein/nucleotide sequence database, Swiss-Prot, PFAM database, the Gene Ontology database, and the Kyoto Encyclopedia of Genes and Genomes database in order to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. The expression patterns for genes involved in several molecular events critical for molting, such as hormone regulation, triggering events, implementation phases, skelemin, immune responses were characterized and considered as mechanisms underlying molting in L. vannamei. Comparisons with transcriptomic analyses in other arthropods were also performed. The characterization of major transcriptional changes in genes involved in the molting cycle provides candidates for future investigation of the molecular mechanisms. The data generated in this study will serve as an important transcriptomic resource for the shrimp research community to facilitate gene and genome annotation and to characterize key molecular processes underlying shrimp development.

Transforming growth factor (TGF)-β1 is known to play a pivotal role in a diverse range of biological systems including modulation of fibrosis in several organs. The precise role of TGF-β/Smad signaling in the progression of bladder fibrosis secondary to partial bladder outlet obstruction (PBOO) is yet to be conclusively. Using a rat PBOO model, we investigated TGF-β1 expression and exaimined whether sodium tanshinone IIA sulfonate (STS) could inhibit TGF-β/Smad signaling pathway activation and ameliorate bladder fibrosis. Forty-eight female Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 16), PBOO operation without STS treatment group (n = 16) and PBOO operation with STS treatment group (n = 16). Thirty-two rats underwent the operative procedure to create PBOO and subsequently received intraperitoneal injections of STS (10 mg/kg/d; n = 16) or vehicle (n = 16) two days after the surgery. Sham surgery was conducted on 16 rats, which received intraperitoneal vehicle injection two days later. In each of the three groups, an equal number of rats were sacrificed at weeks 4 and 8 after the PBOO or sham operation. The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR). One-way analysis of variance was conducted to draw statistical inferences. At 4 and 8 weeks, the expression of TGF-β1 and phosphorylated Smad2 and Smad3 in STS-treated PBOO rats was significantly lower than in the PBOO rats not treated with STS. Alpha smooth muscle actin (α-SMA), collagen I and collagen III expression at 4 and 8 weeks post PBOO was lower in STS-treated PBOO rats when compared to that in PBOO rats not treated with STS. Our findings indicate that STS ameliorates bladder fibrosis by inhibiting TGF-β/Smad signaling pathway activation, and may prove to be a potential therapeutic measure for preventing bladder fibrosis secondary to PBOO operation.

Malate dehydrogenase (MDH) plays important metabolic roles in bacteria. In this study, the recombinant MDH protein (His-MDH) of Brucella abortus was purified and its ability to catalyze the conversion of oxaloacetate (OAA) to L-malate (hereon referred to as MDH activity) was analyzed. Michaelis Constant (Km) and Maximum Reaction Velocity (Vmax) of the reaction were determined to be 6.45×10−3 M and 0.87 mM L−1 min−1, respectively. In vitro studies showed that His-MDH exhibited maximal MDH activity in pH 6.0 reaction buffer at 40°C. The enzymatic activity was 100%, 60%, and 40% inhibited by Cu2+, Zn2+, and Pb2+, respectively. In addition, six amino acids in the MDH were mutated to investigate their roles in the enzymatic activity. The results showed that the substitutions of amino acids Arg 89, Asp 149, Arg 152, His 176, or Thr 231 almost abolished the activity of His-MDH. The present study will help to understand MDH’s roles in B. abortus metabolism.