Search

Abstract Amniotic fluid exosomes (AF-Exos) from term labor (TL) cause amniotic membrane senescence and induce labor. However, the intrinsic mechanism through which this occurs remains unknown. Therefore, we performed microRNA (miRNA) microarray chip screening of AF-Exos obtained from TL and terms not in labor and discovered that the expression of miR-548az-5p was significantly upregulated in TL. This study aimed to explore the role of miR-548az-5p in AF-Exos-induced human amniotic epithelial cells (hAECs) senescence for labor initiation. Bioinformatics analysis revealed that Katanin catalytic subunit A1 like 1 (KATNAL1) is a potential miR-548az-5p target. In hAECs, the upregulation of miR-548az-5p suppressed KATNAL1 expression, disorganized microtubules, increased senescence-associated secretory phenotype-related biomarkers, and inhibited cell proliferation by cyclin D1 and cyclin-dependent kinase 6 (CDK6). This study identified that miR-548az-5p is involved in the senescence of amniotic epithelial cells by targeting KATNAL1 to induce labor. Notably, this study offers new perspectives on the mediation of cellular senescence using AF-Exos miRNAs, which results in labor.

A straw interlayer added to soil can effectively reduce soil salinity effects on plant growth, however, the effects of soil moisture, salt and microbial community composition on plant growth under a straw interlayer are unclear. A rhizobox study was conducted to investigate the role of straw interlayer thickness on soil moisture, salt migration, microbial community composition, as well as root growth in sunflower. The study included four treatments: Control (no straw interlayer); S3 (straw interlayer of 3.0 cm); S5 (straw interlayer of 5.0 cm); S7 (straw interlayer of 7.0 cm). Straw interlayer treatments increased soil moisture by 8.2–11.0% after irrigation and decreased soil salt content after the bud stage in 0–40 cm soil. Total root length, total root surface area, average root diameter, total root volume and the number of root tips of sunflower plants were higher under straw interlayer treatments than in the control, and were the highest under the S5 treatment. This stimulated root growth was ascribed to the higher abundance of Chloroflexi and Verrucomicrobia bacteria in soil with a straw interlayer, which was increased by 55.7 and 54.7%, respectively, in the S5 treatment. Addition of a straw interlayer of 5 cm thickness is a practical and environmentally feasible approach for improving sunflower root growth in saline-alkali soil.

Abstract Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondromatosis phenotype. Here we compared growth plates from E18.5 mice expressing a mutant Idh1 with control littermates using single cell RNA sequencing. Data from Col2 expressing cells were analysed using UMAP and RNA pseudo-time analyses. A unique cluster of cells was identified in the mutant growth plates that expressed genes known to be upregulated in enchondromas. There was also a cluster of cells that was underrepresented in the mutant growth plates that expressed genes known to be important in longitudinal bone growth. Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data supports the notion that a subpopulation of chondrocytes become enchondromas at the expense of contributing to longitudinal growth.

Abstract Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention. One emerging machine learning paradigm that addresses this concern is federated learning (FL). FL enables multiple entities to collaboratively build machine learning models while preserving data privacy and security. In this study, we present a multicenter BCa magnetic resonance imaging (MRI) dataset. The dataset comprises 275 three-dimensional bladder T2-weighted MRI scans collected from four medical centers, and each scan includes diagnostic pathological labels for muscle invasion and pixel-level annotations of tumor contours. Four FL methods are used to assess the baseline of the dataset for both the task of diagnosing muscle-invasive bladder cancer and automatic bladder tumor lesion segmentation.

The dense and nearly continuous spectral bands in hyperspectral images result in strong inter-band correlations, which can diminish performance of the model in classification tasks. Moreover, most convolutional neural network-based methods for hyperspectral image classification typically depend on a fixed scale to extract spectral–spatial features, which ignore the detail features of some objects. To address the above issues, a novelty Spectral Spatial Adaptive Weighted Fusion and Residual Dense Network (S2AWF-RDN) is proposed for Hyperspectral image classification. Specifically, the proposed S2AWF-RDN consists of spectral–spatial adaptive weighted fusion module, multi-channel feature concatenation residual dense module, and spatial feature fusion module. Firstly, the spectral information optimization branch is developed to adjust the weights assigned to various spectral channels. Similarly, the spatial information optimization branch is developed to adjust the weights for different spatial regions. Secondly, to obtain rich spectral spatial information from different levels, multi-channel feature concatenation residual dense module has been proposed. In addition, a multi-channel feature concatenation block is designed guiding the model to extract spectral spatial information at different scales. Finally, spatial feature fusion module is introduced to retain more spatial information. The experimental outcomes illustrate that the proposed network model exhibits superior classification performance on three renowned hyperspectral image datasets. Furthermore, the efficacy of the proposed network model is further corroborated through comparative and ablation studies.

Abstract Background Accurate assessment of basal bone width is essential for distinguishing individuals with normal occlusion from patients with maxillary transverse deficiency who may require maxillary expansion. Herein, we evaluated the effectiveness of a deep learning (DL) model in measuring landmarks of basal bone width and assessed the consistency of automated measurements compared to manual measurements. Methods Based on the U-Net algorithm, a coarse-to-fine DL model was developed and trained using 80 cone-beam computed tomography (CBCT) images. The model’s prediction capabilities were validated on 10 CBCT scans and tested on an additional 34. To evaluate the performance of the DL model, its measurements were compared with those taken manually by one junior orthodontist using the concordance correlation coefficient (CCC). Results It took approximately 1.5 s for the DL model to perform the measurement task in only CBCT images. This framework showed a mean radial error of 1.22 ± 1.93 mm and achieved successful detection rates of 71.34%, 81.37%, 86.77%, and 91.18% in the 2.0-, 2.5-, 3.0-, and 4.0-mm ranges, respectively. The CCCs (95% confidence interval) of the maxillary basal bone width and mandibular basal bone width distance between the DL model and manual measurement for the 34 cases were 0.96 (0.94–0.97) and 0.98 (0.97–0.99), respectively. Conclusion The novel DL framework developed in this study improved the diagnostic accuracy of the individual assessment of maxillary width. These results emphasize the potential applicability of this framework as a computer-aided diagnostic tool in orthodontic practice.

Abstract Recent advances in computer vision and deep learning techniques have facilitated significant progress in video scene understanding, thus helping film and television practitioners achieve accurate video editing. However, so far, publicly available semantic segmentation datasets are mostly limited to indoor scenes, city streets, and natural images, often ignoring example objects in action movies, which is a research gap that needs to be urgently filled. In this paper, we introduce a large-scale, high-precision semantic segmentation dataset of props in Chinese martial arts movie clips, named ChineseMPD. Specifically, this dataset first establishes segmentation rules and general review criteria for audiovisual data, and then provides semantic segmentation annotations for six weapon props (Gun, Sword, Stick, Knife, Hook, and Arrow) with a summary of 32,992 objects.To the best of our knowledge, this dataset is the largest semantic segmentation dataset for movie props to date. ChineseMPD dataset not only significantly expands the application of traditional tasks of computer vision such as object detection and scene understanding, but also opens up new avenues for interdisciplinary research.

Abstract Background Deep learning, as an artificial intelligence method has been proved to be powerful in analyzing images. The purpose of this study is to construct a deep learning-based model (ToothNet) for the simultaneous detection of dental caries and fissure sealants in intraoral photos. Methods A total of 1020 intraoral photos were collected from 762 volunteers. Teeth, caries and sealants were annotated by two endodontists using the LabelMe tool. ToothNet was developed by modifying the YOLOX framework for simultaneous detection of caries and fissure sealants. The area under curve (AUC) in the receiver operating characteristic curve (ROC) and free-response ROC (FROC) curves were used to evaluate model performance in the following aspects: (i) classification accuracy of detecting dental caries and fissure sealants from a photograph (image-level); and (ii) localization accuracy of the locations of predicted dental caries and fissure sealants (tooth-level). The performance of ToothNet and dentist with 1year of experience (1-year dentist) were compared at tooth-level and image-level using Wilcoxon test and DeLong test. Results At the image level, ToothNet achieved an AUC of 0.925 (95% CI, 0.880–0.958) for caries detection and 0.902 (95% CI, 0.853–0.940) for sealant detection. At the tooth level, with a confidence threshold of 0.5, the sensitivity, precision, and F1-score for caries detection were 0.807, 0.814, and 0.810, respectively. For fissure sealant detection, the values were 0.714, 0.750, and 0.731. Compared with ToothNet, the 1-year dentist had a lower F1 value (0.599, p

Abstract The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen‐carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption‐caused insufficient hypoxia relief. Herein, a carrier‐free oxygen nano‐tank based on modular fluorination prodrug design and co‐assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano‐tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co‐assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on‐demand laser‐triggerable ATO release, closed‐loop tumor hypoxia relief, and significant enhancement to PPa‐mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention‐enhanced cancer therapy.

Organic orchard management has been widely adopted to enhance soil fertility by improving the sequestration of soil organic carbon (SOC). Microbial residue carbon plays an essential role in SOC accumulation; nevertheless, how fungal and bacterial residue carbon (FRC and BRC) changes with different orchard management practices (organic vs. conventional) and the factors influencing their accumulation remain poorly understood. In this study, we quantified the FRC and BRC in the two management practices, compiled this data with the comparisons of plant, soil and microbial properties, and the dominant factor affecting their sequestration was ascertained with a 4-year orchard experiment on the Jiaodong Peninsula. Compared with conventional management, organic management significantly enhanced SOC and the accumulation of FRC and BRC, while it did not alter the contribution of FRC or BRC to SOC. Furthermore, we identified that the primary determinant affecting FRC varied with management type: Plant (AGR, BGG)-soil (SOC, density)-microbe (Nitrospirae) collectively governed FRC in organic soil, whereas soil (pH, density) and microbial (Ascomycota) properties regulated FRC in conventional soil. Nitrospirae abundance and soil pH played pivotal roles in FRC accumulation under organic and conventional management, respectively. Meanwhile, the primary factor influencing BRC was independent of management type: Soil and microbial properties consistently served as the principal determinants of BRC in both management systems, with soil pH and clay being the pivotal factors in organic and conventional managements, respectively. These findings illustrate the divergent regulatory mechanisms of FRC and BRC in organic and conventional management, thereby enhancing our comprehension of microbial-mediated SOC sequestration in organic orchard management.

The successful launch of the first spaceborne CO2 IPDA LIDAR onboard Daqi-1 (DQ-1) in April 2022 marks a milestone in advancing scientific research. However, a notable discrepancy in the physical definitions of ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products between the IPDA LIDAR and TCCON presents a challenge for directly using TCCON for verifying and evaluating the performance of DQ-1’s ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products. To address this, we propose a method based on statistical hypothesis testing to globally validate the ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products derived from the spaceborne LIDAR. Our validation method does not compare DQ-1’s observations with the TCCON observations. We only utilize the useful information from TCCON to simulate the probability distribution of the true ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ value in the LIDAR definition, and then hypothesis testing is adopted for deriving the systematic error. Our method improves the accuracy of computing the systematic error of DQ-1 by over 50% compared to the traditional approach. Up to now, we have produced the first four months (June 2022–September 2022) of DQ-1’s ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products. In this context, we present preliminary validation results based on the four months of data. Based on our method, we have validated that the accuracy of DQ-1’s ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products is 0.1 ± 1 ppm. This approach not only sets the stage for future official global validations of DQ-1’s ${{\mathrm{X}}_{\mathrm{C}{{\mathrm{O}}_2}}}$ products but also holds promise for application in upcoming similar missions such as MERLIN and DQ-2.

Abstract Prime editing allows precise installation of any single base substitution and small insertions and deletions without requiring homologous recombination or double-strand DNA breaks in eukaryotic cells. However, the applications in bacteria are hindered and the underlying mechanisms that impede efficient prime editing remain enigmatic. Here, we report the determination of vital cellular factors that affect prime editing in bacteria. Genetic screening of 129 Escherichia coli transposon mutants identified sbcB, a 3ʹ→5ʹ DNA exonuclease, as a key genetic determinant in impeding prime editing in E. coli, combinational deletions of which with two additional 3ʹ→5ʹ DNA exonucleases, xseA and exoX, drastically enhanced the prime editing efficiency by up to 100-fold. Efficient prime editing in wild-type E. coli can be achieved by simultaneously inhibiting the DNA exonucleases via CRISPRi. Our results pave the way for versatile applications of prime editing for bacterial genome engineering.

Accurate water content detection is crucial for optimizing chemical reactions, ensuring product quality in pharmaceutical manufacturing, and maintaining food safety. In this study, nitrogen and sulfur co-doped graphene quantum dots (R-GQDs) were synthesized via a one-step hydrothermal method using o-phenylenediamine as the carbon source. The synthesis conditions, including reaction time, temperature, o-phenylenediamine concentration, and H2SO4/water ratio, were optimized using the Box-Behnken response surface methodology. The R-GQDs exhibited excellent fluorescence stability and distinct solvent-dependent characteristics, alongside a broad linear detection range and high sensitivity, making them highly suitable for dual-mode water content detection (colorimetric and fluorescent). To enhance the accuracy of visual detection, R-GQDs were incorporated into portable test strips with smartphone-assisted analysis, compensating for the human eye’s limitations in distinguishing subtle color changes. The sensor’s practical utility was validated through spiked recovery experiments in food samples, and the R-GQDs demonstrated good biocompatibility for in vivo imaging in shrimp. These findings highlight a novel strategy for developing portable, real-time water content sensors with potential applications in both portable detection systems and biological imaging.

Exploring the bacterial community in the S. glauca rhizosphere was of great value for understanding how this species adapted to the saline-alkali environment and for the rational development and use of saline-alkali soils. In this study, high-throughput sequencing technology was used to investigate the diversity characteristics and distribution patterns of soil bacterial communities in the rhizosphere of S.glauca-dominated communities in the Hetao Irrigation Distract, Inner Mongolia, China. The relationships among bacterial characteristics, soil physicochemical properties and vegetation in four sampling sites were analyzed. The soil bacterial communities in the rhizosphere of S. glauca-dominated communities were mainly composed of 16 phyla (i.e., Proteobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Chloroflexi, Acidobacteria, Firmicutes, Planctomycetes, Deinococcus-Thermus, Verrucomicrobia, Saccharibacteria, Cyanobacteria, Nitrospirae, JL-ETNP-Z39, Parcubacteria and Chlorobi), and these populations accounted for more than 99% of the total bacterial community. At the genus level, the main bacterial communities comprised Halomonas, Nitriliruptor, Euzebya and Pelagibius, which accounted for 15.70% of the total bacterial community. An alpha diversity analysis indicated that the richness and diversity of rhizosphere soil bacteria differed significantly among the sampling sites, and the bacterial richness and diversity indices of severe saline-alkali land were higher than those of light and moderate saline-alkali land. The principal component analysis (PCA) and linear discriminant analysis effect size (LEfSe) showed significant differences in the species composition of the rhizosphere soil bacterial community among different sampling sites. A correlation analysis showed that the number of bacterial species exhibited the highest correlation with the soil water content (SWC). The richness and evenness indices were significantly correlated with the SWC and SO42–, K+ and Mg2+ concentrations. The electrical conductivity (EC), soluble ions (Na+, CO32– + HCO3–, K+, Ca2+, Mg2+, and SO42+), SWC and vegetation coverage (VC) were the main drivers affecting the changes in its community structure. The bacterial community in the rhizosphere of S. glauca enhanced the adaptability of S. glauca to saline-alkali environment by participating in the cycling process of nutrient elements, the decomposition of organic matter and the production of plant growth regulating substances. These results provided a theoretical reference for further study on the relationship among rhizosphere soil microorganisms and salt tolerance in halophytes.

Because the problem of global land degradation is very prominent, it is necessary to effectively manage the degraded land. Common management modes of degraded land include vegetation restoration, rational grazing, and application of new technologies. In order to derive the applicable range of various degraded land management modes, this paper constructs three differential game models and compares and analyzes the equilibrium results obtained by the models. Finally, the study shows that if the return of the degraded land is small, the vegetation restoration mode can maximize the benefit of the government; if the return of the degraded land is large, the mode of application of new technologies can maximize the benefit of the government. Under the condition of the small cost of the degraded land, if the return of the degraded land is small, the rational grazing mode can maximize the benefit of the community. Under the condition of the large cost of the degraded land, if the return of the degraded land is small, the rational grazing mode can maximize the benefit of the community; if the return of the degraded land is large, the mode of application of new technologies can maximize the benefit of the community.

Time-varying meshing stiffness is one of the important excitations of gear transmission system, and its accurate calculation is an important basis for gear dynamics research. This paper proposes an improved potential energy method to calculate the theoretical time-varying meshing stiffness of healthy gears and helical gears with root crack faults, taking into account the non coincidence between the tooth root circle and the base circle of the helical gear, as well as the angle of the tooth root transition circle, the simulation results of KISSsoft were used to verify the rationality and effectiveness of the improved method; analyzed the influence of basic parameters and fault severity of helical gears on time-varying meshing stiffness. The results show that the accuracy of meshing stiffness obtained by the improved method has increased by about 5%; changes in the basic gear parameters cause changes in the contact ratio, which in turn leads to changes in the fluctuation and average value of the gear meshing stiffness; the fluctuation of meshing stiffness is in the minimum value when overlap contact ratio is close to an integer, the fluctuation of meshing stiffness is in the maximum value when total overlap is near an integer; the variation of crack depth and angle leads to local attenuation of time-varying meshing stiffness of helical gears. As the degree of failure increases, the local attenuation of meshing stiffness becomes more pronounce and compared to crack angle, meshing stiffness is more sensitive to changes in crack depth. Compared with the traditional potential energy method, the improved method improves the calculation accuracy of the time-varying meshing stiffness of helical gears, which is highly practical in the accurate calculation of helical gear meshing stiffness excitation and provide the theoretical basis for the calculation of the meshing stiffness of helical gears.

Abstract Background Serum albumin (ALB) and hemoglobin (HGB) are important serum biochemical indices of the nutritional status of patients and are associated with cancer development. We investigated the relationship between ALB and HGB levels and clinicopathologic characteristics of early-stage cervical cancer to determine the influence of ALB and HGB on the prognosis of early-stage cervical cancer. Methods The clinical data of 560 patients with International Federation of Gynaecology and Obstetrics (FIGO, 2009) stage IA1-IIA2 cervical cancer from January 2005 to December 2010 were retrospectively analyzed. The relationship between serum ALB and HGB levels and clinicopathological characteristics of patients were analyzed. The patients were followed-up for 12–138 months. The effects of ALB and HGB levels on the prognosis were analyzed by Cox regression, log-rank test, and the Kaplan–Meier method. Results The rate of patients with pelvic lymph node metastasis (PLNM), tumor diameter ≥ 4 cm, lymphovascular space invasion (LVSI), and deep stromal invasion was significantly higher in the anemia and hypoalbuminemia group than in the normal group (P

Abstract Background The composition and content of fatty acids in the breast muscle are important factors influencing meat quality. In this study, we investigated the fatty acid composition and content in the breast muscle of Gushi chickens at different developmental stages (14 weeks, 22 weeks, and 30 weeks). Additionally, we utilized transcriptomic data from the same tissue and employed WGCNA and module identification methods to identify key genes associated with the fatty acid composition in Gushi chicken breast muscle and elucidate their regulatory networks. Results Among them, six modules (blue, brown, green, light yellow, purple, and red modules) showed significant correlations with fatty acid content and metabolic characteristics. Enrichment analysis revealed that these modules were involved in multiple signaling pathways related to fatty acid metabolism, including fatty acid metabolism, PPAR signaling pathway, and fatty acid biosynthesis. Through analysis of key genes, we identified 136 genes significantly associated with fatty acid phenotypic traits. Protein–protein interaction network analysis revealed that nine of these genes were closely related to fatty acid metabolism. Additionally, through correlation analysis of transcriptome data, we identified 51 key ceRNA regulatory networks, including six central genes, 7 miRNAs, and 28 lncRNAs. Conclusion This study successfully identified key genes closely associated with the fatty acid composition in Gushi chicken breast muscle, as well as their post-transcriptional regulatory networks. These findings provide new insights into the molecular regulatory mechanisms underlying the flavor characteristics of chicken meat and the composition of fatty acids in the breast muscle.

This study addresses the limitations of and the common challenges faced by one-dimensional river-routing methods in hydrological models, including the National Water Model (NWM), in accurately representing coastal regions. We developed a two-way coupling between the NWM and the Semi-implicit Cross-scale Hydroscience Integrated System Model (SCHISM). The approach demonstrated improvements in modeling coastal river dynamics, particularly during extreme events like Hurricane Matthew. The coupled model successfully captured tidal influences, storm surge effects, and complex river–river interactions that the standalone NWM missed. The approach revealed more accurate representations of peak discharge timing and magnitude as well as water storage and release in coastal floodplains. However, we also identified challenges in reconciling variable representations between hydrological and hydraulic models. This work not only enhances the understanding of coastal–riverine interactions but also provides valuable insights for the development of next-generation hydrological models. The improved modeling capabilities have implications for flood forecasting, coastal management, and climate change adaptation in vulnerable coastal areas.

PLCPs (papain-like cysteine proteases) are one of the most abundant groups of cysteine proteases and play vital roles in multiple processes. The pepper (Capsicum annuum) is an important Solanaceae vegetable crop; its commercial hybrid seeds are widely used in production. Male sterility is a valuable trait for hybrid seed production. However, the function of PLCPs and the underlying mechanisms of male sterility in peppers remain unclear. In this study, we comprehensively identified the PLCP gene family in peppers, identifying 31 CaPLCPs. A phylogenetic analysis classified 31 members into eight clades. These CaPLCPs were unevenly distributed across eight chromosomes, and five segmental duplicated pairs were observed. The promoter cis-acting element analysis indicated that CaPLCP promoters contained abundant hormone-responsive and stress-responsive cis-elements, suggesting that CaPLCPs may play important roles in responding to abiotic stress, such as drought and low temperatures, as well as in plant immunity. The qRT-PCR analysis demonstrated that the expression levels of CaPLCP1, CaPLCP5, CaPLCP11, CaPLCP12, CaPLCP13, CaPLCP17, CaPLCP19, and CaPLCP21 were significantly reduced in the flowers of MS (male sterile pepper) at least at one stage, indicating their potential roles as regulatory factors in pepper male sterility. These findings provide important insights into the functional analysis of the PLCP gene family in peppers and other species, laying a crucial foundation for understanding the mechanisms of male sterility in peppers.

Abstract Purpose To investigate clinicopathological differences between typical endometrial polypoid adenomyomas (TPAs) and endometrial polyps (EPs) and to determine the risk factors and recurrence of TPA and further clarify the pathogenesis and treatment of TPA. Methods We reviewed the medical records of 488 women with TPA and 500 women with EP. Then, we analyzed the clinical features and manifestations, ultrasonic manifestations, hysteroscopic morphology, and pathological results. In addition, 360 cases of TPA and 367 cases of EP were followed up for 22–77 months and the risk factors TPA recurrence were assessed. Results We detected significant differences in age, menopausal status, body mass index (BMI), the number of pregnancies, and parity between the two groups (P 3 cm in diameter and multiple polyps in the TPA group was significantly higher than that in the EP group (P

Abstract Background Fatty acids composition in poultry muscle is directly related to its tenderness, flavour, and juiciness, whereas its genetic mechanisms have not been elucidated. In this study, the genetic structure and key regulatory genes of the breast muscle fatty acid composition of local Chinese chicken, Gushi-Anka F2 resource population by integrating genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) strategies. GWAS was performed based on 323,306 single nucleotide polymorphisms (SNPs) obtained by genotyping by sequencing (GBS) method and 721 chickens from the Gushi-Anka F2 resource population with highly variable fatty acid composition traits in the breast muscle. And then, according to the transcriptome data of the candidate genes that were obtained and phenotypic data of fatty acid composition traits in breast muscle of Gushi chickens at 14, 22, and 30 weeks of age, we conducted a WGCNA. Results A total of 128 suggestive significantly associated SNPs for 11 fatty acid composition traits were identified and mapped on chromosomes (Chr) 2, 3, 4, 5, 13, 17, 21, and 27. Of these, the two most significant SNPs were Chr13:5,100,140 (P = 4.56423e-10) and Chr13:5,100,173 (P = 4.56423e-10), which explained 5.6% of the phenotypic variation in polyunsaturated fatty acids (PUFA). In addition, six fatty acid composition traits, including C20:1, C22:6, saturated fatty acid (SFA), unsaturated fatty acids (UFA), PUFA, and average chain length (ACL), were located in the same QTL intervals on Chr13. We obtained 505 genes by scanning the linkage disequilibrium (LD) regions of all significant SNPs and performed a WGCNA based on the transcriptome data of the above 505 genes. Combining two strategies, 9 hub genes (ENO1, ADH1, ASAH1, ADH1C, PIK3CD, WISP1, AKT1, PANK3, and C1QTNF2) were finally identified, which could be the potential candidate genes regulating fatty acid composition traits in chicken breast muscle. Conclusion The results of this study deepen our understanding of the genetic mechanisms underlying the regulation of fatty acid composition traits, which is helpful in the design of breeding strategies for the subsequent improvement of fatty acid composition in poultry muscle.

Abstract Background The development of abdominal fat and meat quality are closely related and can impact economic efficiency. In this study, we conducted transcriptome sequencing of the abdominal fat tissue of Gushi chickens at 6, 14, 22, and 30 weeks, and selected key miRNA-mRNA regulatory networks related to abdominal fat development through correlation analysis. Results A total of 1893 differentially expressed genes were identified. Time series analysis indicated that at around 6 weeks, the development of chicken abdominal fat was extensively regulated by the TGF-β signaling pathway, Wnt signaling pathway, and PPAR signaling pathway. However, at 30 weeks of age, the apoptosis signaling pathway was the most significant, and correlation analysis revealed several genes highly correlated with abdominal fat development, including Fatty Acid Binding Protein 5 (FABP5). Based on miRNA transcriptome data, it was discovered that miR-122-5p is a potential target miRNA for FABP5. Cell experiments showed that miR-122-5p can directly target FABP5 to promote the differentiation of preadipocytes. Conclusion The present study confirms that the key gene FABP5 and its target gene miR-122-5p are critical regulatory factors in the development of chicken abdominal fat. These results provide new insights into the molecular regulatory mechanisms associated with the development of abdomen-al fat in chickens.

The objective of the study was to evaluate the clinical application potential of quantitatively detecting human papillomavirus (HPV) E7 oncoprotein in HPV-positive women, with the goal of detecting potential high-grade cervical squamous intraepithelial lesions (HSIL) and cervical cancer improving the accuracy of colposcopic shunting in these patients.HPV-positive women (N = 611) were selected for quantitatively detecting HPV E7 protein levels by magnetic particle-based chemiluminescence immunoassay before colposcopy. Receiver operating characteristic (ROC) curve analysis was performed (n = 400) to determine diagnostic detection thresholds for HPV E7 oncoprotein. ThinPrep cytology test (TCT) and Aptima HPV E6/E7 mRNA analysis were also performed (n = 211). The diagnostic performance of these three diagnostic methods in detecting HSIL and cervical cancer was compared with the gold standard of pathological diagnosis. The area under the ROC curve was 0.724. The diagnostic detection threshold of HPV E7 oncoprotein was ≥10.88 ng/mL. The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Youden index of HPV E7 oncoprotein for the identification of HSIL and cervical cancer were 78.7 %, 77.9 %, 72.2 %, 83.3 %, and 56.6 %, respectively, which were higher than those of TCT and HPV E6/E7 mRNA.The results indicate that quantitative detection of HPV E7 oncoprotein can effectively shunt HPV-positive women and reduce unnecessary colposcopy and biopsy. It can detect potential HSIL and cervical cancer in a timely manner and prevent high-risk patients from missing diagnosis.

Abstract Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance.

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA1, ENB and ENB1, using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The results show that the predominant toxin was BEA, which had a maximum of 387.67 μg/kg and an average of 37.69 μg/kg. With regard to ENNs, the prevalence and average concentrations of ENB and ENB1 were higher than those of ENA and ENA1. The geographical distribution of BEA and ENNs varied. Hubei and Shandong exhibited the highest and lowest positive rates of BEA and ENNs (13.46% and 87.5%, respectively). However, no significant difference was observed among these six provinces. There was a co-occurrence of BEA and ENNs, and 42.26% of samples were simultaneously detected with two or more toxins. Moreover, a significant linear correlation in concentrations was observed between the four ENN analogs (r range: 0.75~0.96, p < 0.05). This survey reveals that the contamination and co-contamination of BEA and ENNs in Chinese wheat kernels were very common.

Quantitative evaluation of the effects of diverse greenhouse vegetable production systems (GVPS) on vegetable yield, soil water consumption, and nitrogen (N) fates could provide a scientific basis for identifying optimum water and fertilizer management practices for GVPS. This research was conducted from 2013 to 2015 in a greenhouse vegetable field in Quzhou County, North China. Three production systems were designed: conventional (CON), integrated (INT), and organic (ORG) systems. The WHCNS-Veg model was employed for simulating vegetable growth, water dynamics, and fates of N, as well as water and N use efficiencies (WUE and NUE) for four continuous growing seasons. The simulation results revealed that nitrate leaching and gaseous N emissions constituted the predominant N loss within GVPS, which separately accounted for 11.5–59.4% and 6.0–21.1% of the N outputs. The order of vegetable yield, N uptake, WUE, and NUE under different production systems was ORG > INT > CON, while the order of nitrate leaching and gaseous N loss was CON > INT > ORG. Compared to CON, ORG exhibited a significant increase in yield, N uptake, WUE, and NUE by 24.6%, 24.2%, 26.1%, and 89.7%, respectively, alongside notable reductions in nitrate leaching and gaseous N loss by 67.7% and 63.2%, respectively. The ORG system should be recommended to local farmers.

Eggplant is a highly significant vegetable crop and extensively cultivated worldwide. Sepal color is considered one of the major commercial traits of eggplant. Eggplant sepals develop from petals, and sepals have the ability to change color by accumulating anthocyanins, but whether the eggplants in sepal and their biosynthetic pathways are the same as those in petals is not known. To date, little is known about the underlying mechanisms of sepal color formation. In this study, we performed bulked segregant analysis and transcriptome sequencing using eggplant sepals and obtained 1,452,898 SNPs and 182,543 InDel markers, respectively, as well as 123.65 Gb of clean data using transcriptome sequencing. Through marker screening, the genes regulating eggplant sepals were localized to an interval of 2.6 cM on chromosome 10 by bulked segregant analysis sequencing and transcriptome sequencing and co-analysis, combined with screening of molecular markers by capillary electrophoresis. Eight possible candidate genes were then screened to further interpret the regulatory incentives for the eggplant sepal color.

As the core component of the wind turbine generation gearbox, the gear-rotor-bearing transmission system typically operates in harsh environments, inevitably leading to the occurrence of composite faults in the system, which exacerbates system vibration. Therefore, it is necessary to study the vibration characteristics of wind turbine helical gear-rotor-bearing transmission systems with composite faults. This paper uses an improved energy method to calculate the theoretical time-varying mesh stiffness of a helical gear with a root crack failure. On the premise of considering the time-varying meshing stiffness of the faulty helical gear, the gear eccentric fault, and the nonlinear support force of the faulty bearing, a multi-degree-of-freedom helical gear-rotor-bearing transmission system with compound faults was established by using the lumped parameter method. The dynamic model of the system was solved based on the Runge–Kutta method, and the vibration response of the system under healthy conditions, single faults with gear eccentricity, single faults with tooth root cracks, and coupled bearing composite faults were simulated and analyzed. The results show that the simulation results based on KISSsoft software 2018 version verify the effectiveness of the improved energy method; the existence of single faults and composite faults will cause the fault characteristics in the time domain and frequency domain responses. In this paper, the influence of a single fault and a complex fault on the time domain and frequency domain of the system is mainly discovered through the fault study of the helical rotor-bearing system, and the influence of the fault degree on the vibration of the gear motion system is discussed. The greater the degree of the fault, the more vibration of the system occurs; accordingly, when the system is under the coupling of tooth root crack and bearing fault, there is a significant difference compared with the healthy system and the single fault system. The system vibration has obvious time domain and frequency domain signal characteristics, including periodic pulse impacts caused by gear faults and time domain impact caused by bearing. The fault characteristic frequencies can also be found in the frequency domain. In this paper, the fault study of a helical gear of wind turbine generation provides a reference for the theoretical analysis of the vibration characteristics of the helical gear-rotor-bearing system under various fault conditions, lays a solid foundation for the simulation and subsequent diagnosis of the composite fault signal of the system, and provides help for the fault diagnosis of wind turbine gearboxes in the future.

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.

In accordance with the requirements of the "Jiangsu Provincial Institutional Reform Plan", Jiangsu abolished the marine administrative agency in the provincial administrative reform in 2018, and the marine management function was split into other government management departments. This has optimized the marine management system, and to a certain extent, the previous shortcomings such as the division of land and the sea and the overlapping of responsibilities have been alleviated. But it also has brought some problems, such as the decentralization of marine management functions, the obvious weakening of marine administrative institutions, and the governments of the three coastal cities insufficient synergy effects, etc., have hindered the high-quality development of Jiangsu′s marine economy. Based on the actual marine management of the Jiangsu government, the theory of collaborative government endows the government with management efficiency. The paper proposed to establish an open and collaborative administrative concept, set up a task-based organization, and promote the institutionalized sharing of marine information, in order to promote the efficiency of collaborative management among various government departments and promote the construction of a powerful marine province, give play to the effective momentum of the government.

Photodynamic therapy (PDT) has been extensively investigated as a spatiotemporally noninvasive and controllable modality for cancer treatment. However, the intracellular antioxidant systems mainly consisting of thioredoxin (Trx) and glutathione (GSH) significantly counteract and prevent reactive oxygen species (ROS) accumulation, resulting in a serious loss of PDT efficiency. To address this challenge, we propose that PDT can be improved by precisely blocking antioxidant systems. After molecular engineering and synergistic cytotoxic optimization, a DSPE-PEG2K-modified dual-drug nanoassembly (PPa@GA/DSPE-PEG2K NPs) of pyropheophorbide a (PPa) and gambogic acid (GA) is successfully constructed. Interestingly, GA can effectively destroy intracellular antioxidant systems by simultaneously inhibiting Trx and GSH. Under laser irradiation, the cell-killing effects of PPa is significantly enhanced by GA-induced inhibition of the antioxidant systems. As expected, PPa@GA/DSPE-PEG2K nanoparticles demonstrate potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Such a carrier-free self-sensitized nanotherapeutic offers a novel co-delivery strategy for effective PDT.

Potato starch has been widely used in the processing of various gel products due to its high viscosity, easy gelatinization and high stability and transparency of starch paste. Environmental factors, such as temperature and pH, as well as edible components, such as salts, polysaccharides, and proteins exhibites different effects on the pasting properties of potato starch and the retrogradation properties, rheological properties and microstructure of starch gel, which in turn affects the quality of potato starch gel products. Based on the analysis of the formation mechanism of potato starch gel, the influence of different environmental factors and edible components on the quality characteristics of potato starch gel are summarized in this paper, and the interaction principles between different edible components and potato starch molecules are revealed. The objective is to provide reference for the research and industrial production of high-quality, high-nutrition potato starch gel and its products.

Solanum torvum (Swartz) (2n = 24) is a wild Solanaceae plant with high economic value that is used as a rootstock in grafting for Solanaceae plants to improve the resistance to a soil-borne disease caused by root-knot nematodes (RKNs). However, the lack of a high-quality reference genome of S. torvum hinders research on the genetic basis for disease resistance and application in horticulture. Herein, we present a chromosome-level assembly of genomic sequences for S. torvum combining PacBio long reads (HiFi reads), Illumina short reads and Hi-C scaffolding technology. The assembled genome size is ~1.25 Gb with a contig N50 and scaffold N50 of 38.65 Mb and 103.02 Mb, respectively as well as a BUSCO estimate of 98%. GO enrichment and KEGG pathway analysis of the unique S. torvum genes, including NLR and ABC transporters, revealed that they were involved in disease resistance processes. RNA-seq data also confirmed that 48 NLR genes were highly expressed in roots and fibrous roots and that three homologous NLR genes (Sto0288260.1, Sto0201960.1 and Sto0265490.1) in S. torvum were significantly upregulated after RKN infection. Two ABC transporters, ABCB9 and ABCB11 were identified as the hub genes in response to RKN infection. The chromosome-scale reference genome of the S. torvum will provide insights into RKN resistance.

New therapeutic strategies for the rapid and effective treatment of drug-resistant tuberculosis are highly desirable, and their development can be drastically accelerated by facile genetic manipulation methods in Mycobacterium tuberculosis (M. tuberculosis). Clustered regularly interspaced short palindromic repeat (CRISPR) base editors allow for rapid, robust, and programmed single-base substitutions and gene inactivation, yet no such systems are currently available in M. tuberculosis. By screening distinct CRISPR base editors, we discovered that only the unusual Streptococcus thermophilus CRISPR associated protein 9 (St1Cas9) cytosine base editor (CBE)—but not the widely used Streptococcus pyogenes Cas9 (SpCas9) or Lachnospiraceae bacterium Cpf1 (LbCpf1) CBEs—is active in mycobacteria. Despite the notable C-to-T conversions, a high proportion of undesired byproducts exists with St1Cas9 CBE. We therefore engineered St1Cas9 CBE by means of uracil DNA glycosylase inhibitor (UGI) or uracil DNA glycosylase (UNG) fusion, yielding two new base editors (CTBE and CGBE) capable of C-to-T or C-to-G conversions with dramatically enhanced editing product purity and multiplexed editing capacity in Mycobacterium smegmatis (M. smegmatis). Because wild-type St1Cas9 recognizes a relatively strict protospacer adjacent motif (PAM) sequence for DNA targeting, we engineered a PAM-expanded St1Cas9 variant by means of structure-guided protein engineering for the base editors, substantially broadening the targeting scope. We first developed and characterized CTBE and CGBE in M. smegmatis, and then applied CTBE for genome editing in M. tuberculosis. Our approaches significantly reduce the efforts and time needed for precise genetic manipulation and will facilitate functional genomics, antibiotic-resistant mechanism study, and drug-target exploration in M. tuberculosis and related organisms.

Abstract Introduction This study was designed to compare the outcomes of standard cardiopulmonary resuscitation (STD-CPR) and combined chest compression and abdominal compression–decompression cardiopulmonary resuscitation (CO-CPR) with a new device following out-of-hospital cardiac arrest (OHCA). Moreover, we investigated whether patient prognosis improved with this combination treatment. Methods This trial was a single-centre, prospective, randomized trial, and a blinded assessment of the outcomes was performed. A total of 297 consecutive patients with OHCA were initially screened, and 278 were randomized to the STD-CPR group (n = 135) or the CO-CPR group (n = 143). We compared the proportions of patients who achieved a return of spontaneous circulation (ROSC), survived to hospital admission and survived to hospital discharge. In addition, we also performed the Kaplan–Meier analysis with a log-rank test at the end of the follow-up period to compare the survival curves of the two groups. Results The differences were not statistically significant in the proportion of patients who achieved ROSC [31/135 (23.0%) versus 35/143 (24.5%)] and survived to hospital admission [28/135 (20.7%) versus 33/143 (23.1%)] between the CO-CPR group and STD-CPR group. However, there was a significant difference in the proportion of patients who survived to hospital discharge [16/135 (11.9%) versus 7/143 (4.9%)] between the two groups. Nine patients (6.7%) in the CO-CPR group and 2 patients (1.4%) in the STD group showed good neurological outcomes according to the cerebral performance category (CPC) scale score, and the difference was statistically significant (P = 0.003). The Kaplan–Meier curves showed that the patients in the CO-CPR group achieved better survival benefits than those in the STD-CPR group at the end of the follow-up period (log-rank P = 0.007). Conclusion CO-CPR was more beneficial than STD-CPR in terms of survival benefits in patients who have suffered out-of-hospital cardiac arrest. Trial registration Chinese Clinical Trial Registry, registered number: ChiCTR2100049581 . Registered 30 July 2021- Retrospectively registered. http://www.medresman.org.cn/uc/index.aspx .

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1‐7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro‐X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR‐associated protein 9–mediated global prolylcarboxylpeptidase‐knockout and adeno‐associated virus serotype 9–mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg per day) for 4 weeks, aiming to investigate the cardioprotective effect of prolylcarboxylpeptidase against hypertensive cardiac hypertrophy. Prolylcarboxylpeptidase expression was upregulated after 2 weeks of angiotensin II infusion and then became downregulated afterward in wild‐type mouse myocardium, suggesting its compensatory function against angiotensin II stress. Moreover, angiotensin II–treated prolylcarboxylpeptidase‐knockout mice showed aggravated cardiac remodeling and dampened cardiac contractility independent of hypertension. We also found that prolylcarboxylpeptidase localizes in cardiomyocyte lysosomes, and loss of prolylcarboxylpeptidase led to excessive angiotensin II levels in myocardial tissue. Further screening demonstrated that hypertrophic prolylcarboxylpeptidase‐knockout hearts showed upregulated extracellular signal‐regulated kinases 1/2 and downregulated protein kinase B activities. Importantly, adeno‐associated virus serotype 9–mediated restoration of prolylcarboxylpeptidase expression in prolylcarboxylpeptidase‐knockout hearts alleviated angiotensin II–induced hypertrophy, fibrosis, and cell death. Interestingly, the combination of adeno‐associated virus serotype 9–mediated prolylcarboxylpeptidase overexpression and an antihypertensive drug, losartan, likely conferred more effective protection than a single treatment protocol to mitigate angiotensin II–induced cardiac dysfunction. Conclusions Our data demonstrate that prolylcarboxylpeptidase protects the heart from angiotensin II–induced hypertrophic remodeling by controlling myocardial angiotensin II levels.

Brillouin microscopy based on spontaneous Brillouin scattering has emerged as a unique elastography technique because of its merit of non-contact, label-free, and high-resolution mechanical imaging of biological cell and tissue. Recently, several new optical modalities based on stimulated Brillouin scattering have been developed for biomechanical research. As the scattering efficiency of the stimulated process is much higher than its counterpart in the spontaneous process, stimulated Brillouin-based methods have the potential to significantly improve the speed and spectral resolution of existing Brillouin microscopy. Here, we review the ongoing technological advancements of three methods, including continuous wave stimulated Brillouin microscopy, impulsive stimulated Brillouin microscopy, and laser-induced picosecond ultrasonics. We describe the physical principle, the representative instrumentation, and biological application of each method. We further discuss the current limitations as well as the challenges for translating these methods into a visible biomedical instrument for biophysics and mechanobiology.

Promoting the low-carbon development of the electricity market is the key to controlling CO2 emissions and achieving carbon neutrality in China. It requires the coordinated development between investment and carbon emissions in the electricity industry. Based on the panel data on electricity investment and carbon emissions from 2000 to 2019, this study systematically explains the coupling coordination mechanism between electricity investment and carbon emissions. We use the coupling coordination model to calculate the coupling coordination degree of each province. Then, the research uses the GM (1, 1) model to predict the coupling coordination development from 2020 to 2030. The study finds that the development of China’s electricity industry is in good shape. Although the coupling coordination degree has entered barely or primary coordination in most provinces, there are certain fluctuations in recent years; there are spatial differences in coupling and coordinated development among regions: the central region has a high coupling coordination degree, while the eastern and northeastern regions are relatively lagging behind. In the next 10 years, the coupling coordination degree will continue to grow, and all regions will reach the primary coordination. Among them, the central region will reach the intermediate coordination.

Fungi are considered to be one of the wealthiest sources of bio-metabolites that can be employed for yielding novel biomedical agents. Alternaria, including parasitic, saprophytic, and endophytic species, is a kind of dark fungi that can produce a broad array of secondary metabolites (SMs) widely distributed in many ecosystems. These are categorized into polyketides, nitrogen-containing compounds, quinones, terpenes, and others based on the unique structural features of the metabolites. New natural products derived from Alternaria exhibit excellent bioactivities characterized by antibacterial, antitumor, antioxidative, phytotoxic, and enzyme inhibitory properties. Thus, the bio-metabolites of Alternaria species are significantly meaningful for pharmaceutical, industrial, biotechnological, and medicinal applications. To update the catalog of secondary metabolites synthesized by Alternaria fungi, 216 newly described metabolites isolated from Alternaria fungi were summarized with their diverse chemical structures, pharmacological activity, and possible biosynthetic pathway. In addition, possible insights, avenues, and challenges for future research and development of Alternaria are discussed.

The second production test of natural gas hydrate (referred to as hydrate) reservoir in the Shenhu sea area of the northern South China Sea shows that horizontal wells have greater potential than vertical wells in the depressurization production of hydrate reservoirs, but the length of horizontal section to achieve remarkable development effect has not been determined. To this end, a set of production simulation experiment device was independently designed. After the influences of horizontal well section length on gas and water production behaviors and temperature and pressure change laws during the depressurization development of hydrate reservoirs were studied by means of physical experiment, an equal-scale numerical simulation model was established by numerical simulation method. And based on history matching, the change laws of hydrate saturation and gas saturation were analyzed. And the following conclusions were reached. First, for the hydrate reservoirs where water and hydrate coexist, a great amount of high-pressure movable water is produced in the early stage of depressurization development while the formation pressure drops quickly and hydrates are mostly dissociated. In the later stage of depressurization development, there is no stable heat supply. Therefore, the gas production rate presents a trend of fast rise to the peak in the early stage and then concussive decline. Second, horizontal well can effectively increase the water and gas drainage areas, so the longer the horizontal well section is, the higher the peak gas production rate and cumulative gas production are and the shorter time it takes to reach the peak gas production rate, but the faster the gas production decline is in the case of no heat supply. Third, an obvious low hydrate saturation area is formed near the horizontal well, so a long horizontal section is helpful to enlarge the hydrate dissociation area, but in the later stage of depressurization development, there are still a lot of undissociated hydrates in hydrate reservoirs, so the development mode shall be modified to further promote the dissociation of hydrates. Fourth, due to the heat transfer of cap rocks and the gas/water gravity difference, a secondary gas cap is formed easily in the process of depressurization development, so if the horizontal well is drilled near the upper part of a hydrate reservoir, the overlay of dissociated gas can be alleviated, and consequently the production and development effect of dissociated gas are improved.

Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed as a potential therapeutic strategy for hearing loss. ATOH1 expression in the developing cochlea can efficiently induce hair cell regeneration but the efficiency of hair cell reprogramming declines rapidly as the cochlea matures. We developed Cre-inducible mice to compare hair cell reprogramming with ATOH1 alone or in combination with two other hair cell transcription factors, GFI1 and POU4F3. In newborn mice, all transcription factor combinations tested produced large numbers of cells with the morphology of hair cells and rudimentary mechanotransduction properties. However, 1 week later, only a combination of ATOH1, GFI1 and POU4F3 could reprogram non-sensory cells of the cochlea to a hair cell fate, and these new cells were less mature than cells generated by reprogramming 1 week earlier. We used scRNA-seq and combined scRNA-seq and ATAC-seq to suggest at least two impediments to hair cell reprogramming in older animals. First, hair cell gene loci become less epigenetically accessible in non-sensory cells of the cochlea with increasing age. Second, signaling from hair cells to supporting cells, including Notch signaling, can prevent reprogramming of many supporting cells to hair cells, even with three hair cell transcription factors. Our results shed light on the molecular barriers that must be overcome to promote hair cell regeneration in the adult cochlea.

Non-typhoidal Salmonella (NTS) is a major cause of human salmonellosis globally. Food animals are major NTS reservoirs. An increase in antimicrobial resistance (AMR) in foodborne NTS has led to clinical treatment failures. Here, to examine the prevalence and perform characterization of foodborne NTS with AMR in China, we tested the antimicrobial susceptibility of 1,256 NTS isolates cultured from retail foods in 2020 in China. The antimicrobial susceptibility of 26 antimicrobial agents representing 12 classes was evaluated with the broth-microdilution method; the presence of ten mcr genes was screened with multi-PCR. The complete closed genomes of mcr -gene-carrying isolates were generated by hybrid assembly through whole genome sequencing on both the PacBio and Illumina platforms. Genomic features and genetic environments of the mcr-1 gene were analysed. The overall drug resistance rate was 92.28%, and the multi-drug resistance (MDR) rate was 76.53%. A total of 341 AMR profiles were determined, and resistance was highest to nalidixic acid (63.38%). Among 887 NTS isolates with MDR, 232 showed co-resistance to cefotaxime and ciprofloxacin, and 25 were resistant to ten classes of antimicrobial agents. The resistance of NTS isolated from different regions varied. Isolates from raw chicken sources most frequently showed resistance. Four NTS carried the mcr-1 gene and represented four different serotypes. Four mcr-1 gene-bearing plasmids from the four Salmonella isolates were classified into two replicon types (IncI2 and IncHI2A). Two mcr-1 genes in IncI2 type plasmids were found to be located between a PAP2 family protein-encoding gene and a relaxase-encoding gene, whereas the other two mcr-1 gene structures in IncHI2A type plasmids showed variations in the presence of insertion sequences. Our data demonstrated severe AMR among foodborne NTS isolated from food in China, thus highlighting the importance of antimicrobial susceptibility surveillance to decrease the spread of AMR, particularly to critical drugs in human medicine.

Abstract Background Majority of chondrosarcomas are associated with a number of genetic alterations, including somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, but the downstream effects of these mutated enzymes on cellular metabolism and tumor energetics are unknown. As IDH mutations are likely to be involved in malignant transformation of chondrosarcomas, we aimed to exploit metabolomic changes in IDH mutant and non-mutant chondrosarcomas. Methods Here, we profiled over 69 metabolites in 17 patient-derived xenografts by targeted mass spectrometry to determine if metabolomic differences exist in mutant IDH1, mutant IDH2, and non-mutant chondrosarcomas. UMAP (Uniform Manifold Approximation and Projection) analysis was performed on our dataset to examine potential similarities that may exist between each chondrosarcoma based on genotype. Results UMAP revealed that mutant IDH chondrosarcomas possess a distinct metabolic profile compared with non-mutant chondrosarcomas. More specifically, our targeted metabolomics study revealed large-scale differences in organic acid intermediates of the tricarboxylic acid (TCA) cycle, amino acids, and specific acylcarnitines in chondrosarcomas. Lactate and late TCA cycle intermediates were elevated in mutant IDH chondrosarcomas, suggestive of increased glycolytic metabolism and possible anaplerotic influx to the TCA cycle. A broad elevation of amino acids was found in mutant IDH chondrosarcomas. A few acylcarnitines of varying carbon chain lengths were also elevated in mutant IDH chondrosarcomas, but with minimal clustering in accordance with tumor genotype. Analysis of previously published gene expression profiling revealed increased expression of several metabolism genes in mutant IDH chondrosarcomas, which also correlated to patient survival. Conclusions Overall, our findings suggest that IDH mutations induce global metabolic changes in chondrosarcomas and shed light on deranged metabolic pathways.

In order to examine the key determinants of carbon dioxide emissions and judge whether China’s carbon dioxide emissions can reach their peak value before 2030, this study first uses the extended STIRPAT model to analyze the determinants of China’s carbon dioxide emissions from 1995 to 2019 and then uses the model regression result to forecast the carbon dioxide emissions from 2020 to 2040 under six scenarios to investigate their prospect. It is found that population size, GDP per capita, energy intensity, the share of coal consumption, urbanization level, the share of secondary industry, and investment have significant positive effects on carbon dioxide emissions. Among them, the influence of population size is the biggest and energy intensity is the weakest. China’s carbon dioxide emissions can reach their peak in 2029 under the baseline scenario. Increasing the rate of population growth, energy intensity, and share of coal consumption will push back the peak year. A lower rate of economic growth and share of the secondary industry will bring the peak year forward. Therefore, it is necessary to optimize the industrial structure and energy consumption structure, reduce the energy intensity, and control the population size in order to achieve the goal of peaking carbon dioxide emissions as soon as possible.

Ageing is a progressive physiological process mediated by changes in biological pathways, resulting in a decline in tissue and cellular function. It is a driving factor in numerous age-related diseases including cardiovascular diseases (CVDs). Cardiomyopathies, hypertension, ischaemic heart disease, and heart failure are some of the age-related CVDs that are the leading causes of death worldwide. Although individual CVDs have distinct clinical and pathophysiological manifestations, a disturbance in cellular homeostasis underlies the majority of diseases which is further compounded with aging. Three key evolutionary conserved signalling pathways, namely, autophagy, mitophagy and the unfolded protein response (UPR) are involved in eliminating damaged and dysfunctional organelle, misfolded proteins, lipids and nucleic acids, together these molecular processes protect and preserve cellular homeostasis. However, amongst the numerous molecular changes during ageing, a decline in the signalling of these key molecular processes occurs. This decline also increases the susceptibility of damage following a stressful insult, promoting the development and pathogenesis of CVDs. In this review, we discuss the role of autophagy, mitophagy and UPR signalling with respect to ageing and cardiac disease. We also highlight potential therapeutic strategies aimed at restoring/rebalancing autophagy and UPR signalling to maintain cellular homeostasis, thus mitigating the pathological effects of ageing and CVDs. Finally, we highlight some limitations that are likely hindering scientific drug research in this field.

The aim of this study was to perform an epidemiological analysis of the viral strains isolated from outpatients with acute gastroenteritis in Dalian, Liaoning province, China to determine the epidemiology of Norovirus (NoV). Fecal samples were collected from 789 outpatients with acute gastroenteritis in the Xigang district of Dalian, Liaoning province, China from July 2015 to December 2016. Norovirus was detected by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). A selection of the positive samples identified was subsequently sequenced, and these data were analyzed by using the Norovirus Typing tool. Results showed that 38.02% (300/789) of the fecal samples were positive for NoV, of which 95.67% (287/300) were identified as genotype GII with 1.33% (4/300) identified as GI. A further 3.00% (9/300) were combined infections with both GI and GII Norovirus. When analyzing the age distribution, the infections primarily occurred in adults especially the elderly whose NoV positive rate was much higher than the average. Winter was the season when most cases were recorded during 2015 and 2016; however, another infection peak was observed in July 2016. Thirty Norovirus positive samples were successfully sequenced, and results showed that GII.4 was the most commonly identified genotype, along with GII.3 and GII.17. Norovirus is the most common pathogen for acute gastroenteritis in Dalian, Liaoning province of China. The current NoV genotype prevalence in Dalian was found to be similar to that in other regions of China. Genotype GII.4 was the most common genotype in our study, GII.3 and GII.17 were also identified.

In this study, we report the biodiversity and functional characteristics of microplastic-attached biofilms originating from two freshwater bacterial communities. Even though the microplastic-biofilm (MPB) diversities are mostly determined by original bacteria instead of microplastic types, the results from 16S rRNA amplicon sequencing still showed that the dynamic biofilm successions on different microplastics were highly dissimilar. Furthermore, the analysis of biomarkers indicated distinct bacterial species with significant dissimilarities between different MPBs, which further determined the associated functions. The co-occurrence networks showed distinct interconnective characteristics in different MPBs: The structure of MPB incubated in the lake water sample was more robust under environmental stresses, and bacteria in the tap water MPB interacted more cooperatively. Regarding this cooperative interaction, the analysis of functional prediction, in this study, also showed that more symbionts and parasites colonized on microplastics in the tap water than in the lake water. Moreover, it was suggested that MPBs were more easily formed in the tap water sample. The overall results revealed significant dissimilarities in bacterial diversity, succession, and associated functions between MPBs, in which bacterial species with specific functions should be taken seriously.

Abstract Thrombotic cardio‐cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off‐target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co‐assembly engineering optimization, a fibrin‐targeting peptide‐decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus‐homing delivery, abbreviated as FT‐DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co‐loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus‐targeted accumulation with self‐indicating function, as well as photothermal‐potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT‐DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co‐delivery nanoplatform for imaging‐guided photothermal/antiplatelet dual‐modality thrombolysis.

Some physical processes such as oil and gas development, metal deposit collection, and groundwater resource migration can cause density changes, for which microgravity monitoring is the most intuitive method to monitor the density change process. Based on the basic principle of microgravity measurement and the idea of multiscale separation, a multiscale, second-order, surface-fitting, residual gravity anomaly extraction method is proposed to separate superimposed microgravity fields. In this method, regional fields of different scales are fitted and calculated successively with the measurement points as the center, so as to separate the gravity anomalies produced by different-depth density bodies. Results from actual data show that this method extracts the reservoir’s residual density characteristics of plane gravity anomaly on the basis of remaining oil distribution characteristics, consistent with reservoir numerical simulation results. A three-dimensional least-squares inversion of the method for extracting residual gravity anomaly was carried out, with the inversion results consistent with the results of vertical remaining oil distribution characteristics and well-test production results.