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Superconducting cyclotron can generate high-energy proton beams and are mainly used for radiation therapy of tumors and cancers. In the superconducting cyclotron SC200, the maximum magnetic induction intensity can typically reach up to 4.6 T, and the magnetic field accuracy is 1e-4. Hall probes are commonly used tools for measuring high-intensity magnetic fields.

Abstract The aim of this study was to evaluate the serum level of 25-hydroxyvitamin D (25(OH)D) in children with febrile seizures (FS) in Luzhou, Sichuan Province, China, and in particular its association with gender and age. This should inform possible strategies for supplementation with vitamin D, and hence for prevention of FS in the local pediatric population. The Febrile seizures group consisted of 747 children hospitalized with FS at the Southwest Medical University Affiliated Hospital from January 2020 to January 2024. The healthy control group was comprised of 750 children aged from 0 to 8 years who underwent health checkups during this period. The serum 25(OH)D level was analyzed in relation to gender and age to explore its association with FS. The median serum vitamin D level in the FS group (28.8 ng/mL; IQR 21.64, 33.64) was significantly lower than in the healthy control group (37.51 ng/mL; IQR 31.05, 37.51). The incidence of vitamin D deficiency in the FS group was 10.8%, which was significantly higher than in the healthy control group (P

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Abstract Endometrial cancer (EC), as one of the most common cancers, severely threatens female reproductive health. Our previous study has shown that Kinesin family member C1 (KIFC1) played crucial roles in the progression of EC. In addition, abnormal centrosome amplification, which was reported to be partially regulated by KIFC1, usually occurred in different cancers. However, whether KIFC1 promoted EC through centrosome amplification and the potential mechanism remain to be revealed. The present study demonstrated that overexpressed KIFC1, which exhibited a worse prognosis, had a positive correlation with an increased number of centrosomes in human EC samples. In addition, KIFC1 overexpression in EC cells prompted centrosome amplification, chromosomal instability, and cell cycle progression. Moreover, we demonstrated that KIFC1 inhibited E3 ubiquitin-protein ligase TRIM37 to maintain the stability of PLK4 by reducing its ubiquitination degradation, and finally promoting centrosome amplification and EC progression in vitro. Finally, the contributing role of KIFC1 and the inhibitory effect of TRIM37 on EC development and metastasis was verified in a nude mouse xenograft model. Our study elucidated that KIFC1 depends on TRIM37-mediated reduced ubiquitination degradation of PLK4 to promote centrosome amplification and EC progression, thus providing a potential prognostic marker and promising therapeutic target for EC in the future.

Abstract Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included. Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20. Conclusions Our results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

Abstract Objective The aim of this study was to propose a comprehensive maxillary sinus (MS) contour classification system based on the evaluation of anatomical characteristics from cone beam computed tomography (CBCT) examination and investigate the relationship between sinus contours and sinus floor elevation (SFE). Methods A total of 283 CBCT scans from patients who had single tooth loss in the posterior maxilla and underwent SFE were analyzed. The MS was classified at each tooth position. For buccal-palatal evaluation, the classification from Type A to E was narrow-taper, taper, ovoid, square, and irregular, respectively. For mesial-distal evaluation, the classification from Type 1 to 4 was flat, slope, concave, and septa, respectively. The major anatomical parameters evaluated were (1) residual bone height (RBH), (2) sinus width (SW), (3) maxillary sinus angle (MSA), (4) buccal dip angle (BDA), (5) palatonasal recess (PNR), and (6) sinus depth. Results Eleven groups of MS contour were classified after detailed calculation. Differences in the RBH, MSA, BDA, and SW among different groups were statistically significant. The narrow-taper and slope MS (A2) group had the highest RBH (8.66 ± 0.77 mm), largest BDA (79.9° ± 3.18°), smallest MSA (19.8° ± 2.01°), and narrowest SW (6.30 ± 1.23 mm). The lowest RBH was in the square and concave sinus (D3) group (5.11 ± 2.70 mm). The ovoid and concave sinus (C3) group had the smallest BDA (50.64 ± 8.73 mm) and largest MSA (74.11° ± 11.52°). The square and flat MS (D1) group had the widest SW (19.13 ± 3.69 mm). A strongly significant positive correlation was observed between the SW and MSA (r = 0.67) and a strongly negative correlation between the SW and BDA (r = − 0.65). The prevalence of PNR (mean angle: 104.06° ± 16.83°, mean height: 14.72 ± 11.78 mm) was 38% and frequently observed in the ovoid and slope MS (C2) group. Conclusion Despite certain characteristics at different tooth sites, the same tooth position was categorized differently using different classification systems, indicating large anatomical variations in the MS. The classification system proposed herein allows for classification based on general characteristics at a single tooth site, aiming to help surgeons in improving presurgical evaluation.

Abstract Background Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood. Methods An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with 159Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed. Results CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4+ T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8+ T cells. Conclusions To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.

Abstract GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor’s structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Abstract Background Weaning stress reduces growth performance and health of young pigs due in part to an abrupt change in diets from highly digestible milk to fibrous plant-based feedstuffs. This study investigated whether dietary galactooligosaccharide (GOS), supplemented both pre- and post-weaning, could improve growth performance and intestinal health via alterations in the hindgut microbial community. Methods Using a 3 × 2 factorial design, during farrowing 288 piglets from 24 litters received either no creep feed (FC), creep without GOS (FG–) or creep with 5% GOS (FG+) followed by a phase 1 nursery diet without (NG–) or with 3.8% GOS (NG+). Pigs were sampled pre- (D22) and post-weaning (D31) to assess intestinal measures. Results Creep fed pigs grew 19% faster than controls (P

Abstract Background Countries abroad have implemented pediatric palliative treatment for several years; however, complete pediatric palliative treatment guidelines and legal guidance remain lacking in China, making the implementation of palliative care difficult. Purpose This study aimed to understand the current situation, similarities, and differences in the knowledge, attitudes, and needs of caregivers and healthcare providers regarding palliative care for children. Methods This cross-correlation study collected data from pediatric and neonatal intensive care units of four hospitals in China. The participants comprised 180 caregivers and 172 healthcare providers. The measurement tools included the palliative care knowledge scale, palliative care attitude scale, and pediatric palliative care needs scale. This study adhered to the STROBE reporting guidelines. Results Significant differences in palliative care knowledge, attitudes, and needs were observed between caregivers and healthcare providers (p

Soil heavy metal pollution in mining areas poses severe challenges to the ecological environment. In recent years, machine learning has been widely used in heavy metal inversion by hyperspectral data. However, deterministic algorithms and probabilistic algorithms may confront local optimal solutions in practical applications. The local optimal solution is not the optimal value obtained within the entire defined interval, and as a result will affect the reliability of these approaches. This paper proposes a Levy Flight Cauchy Gaussian perturbation Sparrow Search algorithm Support Vector Regression (LSSA-SVR) soil heavy metal content prediction model. It introduces Levy Flight (LF) measurement and Cauchy Gaussian perturbation based on the Sparrow search algorithm. The LSSA-SVR model was shown to increase the breadth of solutions searched, avoiding the local optimal solution problem. When applied to mining soil heavy metal experiments, we found that the LSSA-SVR model gave a good fit for the elements Cu, Zn, As, and Pb. The correlation coefficients between the predicted results and the actual results of the four elements were all above 0.94. The heavy metal predicted results of LSSA-SVR have a small error margin in both the overall distribution and in individual differences. This study provides an efficient and accurate monitoring method for mining soil heavy metal inversion. It also provides strong support for environmental management and soil remediation.

Objectives: To introduce our method managing nasal septal spurs during endoscopic septoplasty. Methods: We conducted a prospective study of cases treated with endoscopic septoplasty between March 2022 and June 2023. We innovated a surgical method to reduce the local mucosal tension at the spur by cutting the spur above and below the bony connection, and reducing the chance of mucosal tear and loss during dissection. The authors performed these cases at the First Affiliated Hospital of Fujian Medical University, where 40 surgeries were performed with regular postoperative follow-ups for 6–12 months. Results: All patients' clinical symptoms improved significantly after surgery. After 2–4 weeks of follow-up, the mucosa could recover to the preoperative state on both sides of the nasal septum. Conclusion: This surgical method is suitable for most patients with nasal septal deviation, especially those with a spur, which can effectively reduce the chance of nasal septal mucosa tear and accelerate postoperative recovery. Level of evidence: Ⅳ.

Background The planting of mangroves is extensively used to control the invasive plant Spartina alterniflora in coastal wetlands. Different plant species release diverse sets of small organic compounds that affect rhizosphere conditions and support high levels of microbial activity. The root-associated microbial community is crucial for plant health and soil nutrient cycling, and for maintaining the stability of the wetland ecosystem. Methods High-throughput sequencing was used to assess the structure and function of the soil bacterial communities in mudflat soil and in the rhizosphere soils of S. alterniflora, mangroves, and native plants in the Oujiang estuarine wetland, China. A distance-based redundancy analysis (based on Bray–Curtis metrics) was used to identify key soil factors driving bacterial community structure. Results S. alterniflora invasion and subsequent mangrove afforestation led to the formation of distinct bacterial communities. The main soil factors driving the structure of bacterial communities were electrical conductivity (EC), available potassium (AK), available phosphorus (AP), and organic matter (OM). S. alterniflora obviously increased EC, OM, available nitrogen (AN), and NO3−-N contents, and consequently attracted copiotrophic Bacteroidates to conduct invasion in the coastal areas. Mangroves, especially Kandelia obovata, were suitable pioneer species for restoration and recruited beneficial Desulfobacterota and Bacilli to the rhizosphere. These conditions ultimately increased the contents of AP, available sulfur (AS), and AN in soil. The native plant species Carex scabrifolia and Suaeda glauca affected coastal saline soil primarily by decreasing the EC, rather than by increasing nutrient contents. The predicted functions of bacterial communities in rhizosphere soils were related to active catabolism, whereas those of the bacterial community in mudflat soil were related to synthesis and resistance to environmental factors. Conclusions Ecological restoration using K. obovata has effectively improved a degraded coastal wetland mainly through increasing phosphorus availability and promoting the succession of the microbial community.

Study region: Inner Mongolia Autonomous Region, North China Study focus: Sensible heat flux (H) quantifies the intensity of water evapotranspiration, making the factors influencing H pivotal to water consumption. North China's semi-arid grasslands are characterized by widespread grazing and strong wind conditions. Grazing strategy modifies surface air heat transfer resistance via vegetation and consequently alters H. Nevertheless, the majority of studies overlook the impact of the observed variables' time scale on H estimation. This paper employs a ''big-leaf'' model to estimate H, incorporating both grazing management strategy and data time scale, validated using the Bowen ratio, and attempted to analyze the factors that affect H. New hydrological insights for the region: Aerodynamic characteristics estimated from daily data typically exceed estimates derived from hourly data. The influence of surface radiative temperature and air temperature on H outweighs that of aerodynamic resistance, whereas aerodynamic resistance accounts for the disparity in estimating H between daily and hourly data. In grazing-prohibited grasslands, the daily H values estimated by the Big Leaf model closely match those obtained from the Bowen ratio. When estimating the hourly H value for grazing prohibited and grazing grasslands, the increase was 25.95 w/m2 and 52.27 w/m2 compared to the daily scale, respectively. For the estimation of water and heat fluxes across different regions, the temporal scale of input data is a pivotal factor.

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for P. aeruginosa in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant P. aeruginosa L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and ɑ-hydroxybutyrate, which, like lactate, are ɑ-hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays reveal that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa–eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote P. aeruginosa’s success as a resident of contaminated environments and animal hosts.IMPORTANCEPseudomonas aeruginosa is a major cause of lung infections in people with cystic fibrosis, of hospital-acquired infections, and of wound infections. It consumes L-lactate, which is found at substantial levels in human blood and tissues. In this study, we investigated the spatial regulation of two redundant enzymes, called LldD and LldA, which enable L-lactate metabolism in P. aeruginosa biofilms. We uncovered mechanisms and identified compounds that control the preference of P. aeruginosa for LldD versus LldA. We also showed that both enzymes contribute to its ability to survive within macrophages, a behavior that is thought to augment the chronicity and recalcitrance of infections. Our findings shed light on a key metabolic strategy used by P. aeruginosa and have the potential to inform the development of therapies targeting bacterial metabolism during infection.

Highlights Ag nanoparticles are evenly plated on BN-embedded fibers as a thermally conductive sheath, bridging the insulating interface between fibers to construct a 3D heat transfer network. The LM-printed e-textile shows outstanding capability for the monitoring of human ECG, sEMG, and EEG signals even under intense EM interference, when commercial electrodes cannot work properly. The e-textile simultaneously manifests excellent EMI shielding (SET > 65, X-band) and UV protection (UPF = 143.1) performance, thus protecting the device and skin from harmful radiation.

Abstract Background Emerging evidence has indicated that a number of circular RNAs (circRNAs) participate in renal cell carcinoma (RCC) carcinogenesis. Nevertheless, the activity and molecular process of circPRELID2 (hsa_circ_0006528) in RCC progression remain unknown. Methods CircPRELID2, miR-22-3p and ETS variant 1 (ETV1) levels were gauged by qRT-PCR. Effect of the circPRELID2/miR-22-3p/ETV1 axis was evaluated by detecting cell growth, motility, and invasion. Immunoblotting assessed related protein levels. The relationships of circPRELID2/miR-22-3p and miR-22-3p/ETV1 were confirmed by RNA immunoprecipitation (RIP), luciferase reporter or RNA pull-down assay. Results CircPRELID2 was up-regulated in RCC. CircPRELID2 silencing suppressed RCC cell growth, motility and invasion. Moreover, circPRELID2 silencing weakened M2-type macrophage polarization in THP1-induced macrophage cells. CircPRELID2 sequestered miR-22-3p, and circPRELID2 increased ETV1 expression through miR-22-3p. Moreover, the inhibitory impact of circPRELID2 silencing on RCC cell malignant behaviors was mediated by the miR-22-3p/ETV1 axis. Furthermore, circPRELID2 knockdown in vivo hampered growth of xenograft tumors. Conclusion Our study demonstrates that circPRELID2 silencing can mitigate RCC malignant development through the circPRELID2/miR-22-3p/ETV1 axis, highlighting new therapeutic targets for RCC treatment.

This study aimed to investigate the dose-effect of iron on growth performance, antioxidant function, intestinal morphology, and mRNA expression of jejunal tight junction protein in 1- to 21-d-old yellow-feathered broilers. A total of 720 1-d-old yellow-feathered male broilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage. The dietary treatments were consisted of a basal diet (contained 79.6 mg Fe kg–1) supplemented with 0, 20, 40, 60, 80, 160, 320, 640, and 1,280 mg Fe kg–1 in the form of FeSO4·7H2O. Compared with the birds in the control group, birds supplemented with 20 mg Fe kg–1 had higher average daily gain (ADG) (P

Abstract Ovarian cancer, a group of heterogeneous diseases, presents with extensive characteristics with the highest mortality among gynecological malignancies. Accurate and early diagnosis of ovarian cancer is of great significance. Here, we present OvcaFinder, an interpretable model constructed from ultrasound images-based deep learning (DL) predictions, Ovarian–Adnexal Reporting and Data System scores from radiologists, and routine clinical variables. OvcaFinder outperforms the clinical model and the DL model with area under the curves (AUCs) of 0.978, and 0.947 in the internal and external test datasets, respectively. OvcaFinder assistance led to improved AUCs of radiologists and inter-reader agreement. The average AUCs were improved from 0.927 to 0.977 and from 0.904 to 0.941, and the false positive rates were decreased by 13.4% and 8.3% in the internal and external test datasets, respectively. This highlights the potential of OvcaFinder to improve the diagnostic accuracy, and consistency of radiologists in identifying ovarian cancer.

Abstract Zero-knowledge succinct non-interactive arguments of knowledge (zk-SNARKs) are cryptographic protocols that offer efficient and privacy-preserving means of verifying NP language relations and have drawn considerable attention for their appealing applications, e.g., verifiable computation and anonymous payment protocol. Compared with the pre-quantum case, the practicability of this primitive in the post-quantum setting is still unsatisfactory, especially for the space complexity. To tackle this issue, this work seeks to enhance the efficiency and compactness of lattice-based zk-SNARKs, including proof length and common reference string (CRS) length. In this paper, we develop the framework of square span program-based SNARKs and design new zk-SNARKs over cyclotomic rings. Compared with previous works, our construction is without parallel repetition and achieves shorter proof and CRS lengths than previous lattice-based zk-SNARK schemes. Particularly, the proof length of our scheme is around $$23.3\%$$ 23.3 % smaller than the recent shortest lattice-based zk-SNARKs by Ishai et al. (in: Proceedings of the 2021 ACM SIGSAC conference on computer and communications security, pp 212–234, 2021), and the CRS length is $$3.6\times$$ 3.6 × smaller. Our constructions follow the framework of Gennaro et al. (in: Proceedings of the 2018 ACM SIGSAC conference on computer and communications security, pp 556–573, 2018), and adapt it to the ring setting by slightly modifying the knowledge assumptions. We develop concretely small constructions by using module-switching and key-switching procedures in a novel way.

Highlights Graphene-like 2D V2O5 nanosheets rich in oxygen vacancies are designed as multi-functional catalysts to fabricate MgH2-H-V2O5 composites. Hydrogen release starts from 185 °C and capacity retention is as high as 99% after 100 cycles at 275 °C. The composites present rapid kinetics and impressive hydrogen absorption capability at near room temperature. The oxygen vacancies could directly enhance kinetics of MgH2 while indirectly exciting “hydrogen pump” effect of VH2/V.

The spatial and temporal variations of net surface radiation (Rn) are critical for comprehending ecological environments. Nonetheless, the intricate interplay among Rn dynamics, vegetation growth, climate, and natural factors remains inadequately elucidated. In this study, we estimated net surface radiation based on Landsat data and ERA5 meteorological data in the Google Earth Engine (GEE) platform, which closely matched the observable spatial distribution (R2 = 0.96), with an average growth rate of 0.15 MJ m−2 mth−1. Trend analyses and spatial autocorrelation were used to explore the spatial and temporal changes in net radiation from 2000 to 2020, the global Moran's index for net radiation was found to exceed 0.76, with fluctuating increases, showing a highly positive spatial distribution of Rn. Local Moran's I predominantly fell into two categories: ‘High-High’ and ‘Low-Low’, with the first increasing in range and the latter decreasing. Combining GeoDetector and PLS-SEM analyses, temperature and vegetation emerge as predominant drivers of net surface radiation variation within the study area, each contributing more than 17% to Rn change. Furthermore, interactions between any two factors typically exhibits nonlinear enhancement. PLS-SEM underscores the influence of vegetation and climate on Rn, with other factors indirectly affecting net radiation changes by influencing vegetation growth.

Abstract Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well‐controlled study, straight‐leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6‐lb load and 21.0% ± 1.3% with 12‐lb load (p

The convergence of green growth is not only very important for the sustainable development of mankind, but also plays a key role in the coordinated development of eastern, Midwest regions of China. The effect of innovative human capital (IHC) on the convergence of regional green growth in China needs to be explored. This paper empirically explores the impact of IHC on the convergence of regional green growth in China from spatial perspective for the first time. Through the regression analysis of the convergence models, three main conclusions are obtained: (1) there are obvious conditional β space convergence characteristics of green growth among inter-provincial units in China. Under the spatial correlation expressed by distance weights and adjacent weights, the conditional β space convergence characteristics of green growth are quite different. (2) Compared with the adjacency weight, under the distance weight, the spatial diffusion effect of innovative knowledge and technologies created by IHC is stronger. (3) There is club convergence of green growth in the East and the Midwest regions, and the quantity and quality of IHC in the Midwest region play a stronger role in the convergence of green growth than in the East region. Based on the above conclusions, this paper proposes some policies for the East and Midwest regions.

This study explored the impact of integrating ChatGPT into asynchronous online discussions. The analysis encompassed students’ log data from Canvas and their perspectives on using ChatGPT. Results revealed a significant enhancement in overall discussion participation when ChatGPT is encouraged, emphasizing its potential as a catalyst for constructive conversations and the development of generic skills. Students also acknowledge ChatGPT’s positive influence on critical thinking and knowledge exploration. In summary, integrating ChatGPT not only enhances participation and engagement but also fosters a sense of community, promotes online interaction, and cultivates essential skills. This study concluded by discussing issues associated with using ChatGPT for online discussions and highlighting implications for its appropriate integration into online discussion boards.

ABSTRACT: Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 μmol Zn/L was more effective than 100 μmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 μmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 μmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.

Abstract Background Identifying breast cancer (BC) patients with germline breast cancer susceptibility gene (gBRCA) mutation is important. The current criteria for germline testing for BC remain controversial. This study aimed to develop a nomogram incorporating ultrasound radiomic features and clinicopathological factors to predict gBRCA mutations in patients with BC. Materials and methods In this retrospective study, 497 women with BC who underwent gBRCA genetic testing from March 2013 to May 2022 were included, including 348 for training (84 with and 264 without a gBRCA mutation) and 149 for validation(36 patients with and 113 without a gBRCA mutation). Factors associated with gBRCA mutations were identified to establish a clinicopathological model. Radiomics features were extracted from the intratumoral and peritumoral regions (3 mm and 5 mm) of each image. The least absolute shrinkage and selection operator regression algorithm was used to select the features and logistic regression analysis was used to construct three imaging models. Finally, a nomogram that combined clinicopathological and radiomics features was developed. The models were evaluated based on the area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. Results Age at diagnosis, family history of BC, personal history of other BRCA-related cancers, and human epidermal growth factor receptor 2 status were independent predictors of the clinicopathological model. The AUC of the imaging radiomics model combining intratumoral and peritumoral 3 mm areas in the validation set was 0.783 (95% confidence interval [CI]: 0.702—0.862), which showed the best performance among three imaging models. The nomogram yielded better performance than the clinicopathological model in validation sets (AUC: 0.824 [0.755—0.894] versus 0.659 [0.563—0.755], p = 0.007). Conclusion The nomogram based on ultrasound images and clinicopathological factors performs well in predicting gBRCA mutations in BC patients and may help to improve clinical decisions about genetic testing.

Abstract The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

Abstract The pursuit of designing superconductors with high Tc has been a long‐standing endeavor. However, the widespread incorporation of doping in high Tc superconductors significantly impacts electronic structure, intricately influencing Tc. The complex interplay between the structural composition and material performance presents a formidable challenge in superconductor design. Based on a novel generative model, diffusion model, and doping adaptive representation: three‐channel matrix, we have designed a high Tc superconductors inverse design model called Supercon‐Diffusion. It has achieved remarkable success in accurately generating chemical formulas for doped high Tc superconductors. Supercon‐Diffusion is capable of generating superconductors that exhibit high Tc and excels at identifying the optimal doping ratios that yield the peak Tc. The doping effectiveness (55%) and electrical neutrality (55%) of the generated doped superconductors exceed those of traditional GAN models by more than tenfold. Density of state calculations on the structures further confirm the validity of the generated superconductors. Additionally, we have proposed 200 potential high Tc superconductors that have not been documented yet. This groundbreaking contribution effectively reduces the search space for high Tc superconductors. Moreover, it successfully establishes a bridge between the interrelated aspects of composition, structure, and property in superconductors, providing a novel solution for designing other doped materials.

Mitochondrial respiratory chain complex I is an important component of the oxidative respiratory chain, with the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) being one of the core subunits. MT-ND1 plays a role in the assembly of complex I and its enzymatic function. MT-ND1 gene mutation affects pathophysiological processes, such as interfering with the early assembly of complex I, affecting the ubiquinone binding domain and proton channel of complex I, and affecting oxidative phosphorylation, thus leading to the occurrence of diseases. The relationship between MT-ND1 gene mutation and disease has been has received increasing research attention. Therefore, this article reviews the impact of MT-ND1 mutations on disease progression, focusing on the impact of such mutations on diseases and their possible mechanisms, as well as the application of targeting MT-ND1 gene mutations in disease diagnosis and treatment. We aim to provide a new perspective leading to a more comprehensive understanding of the relationship between MT-ND1 gene mutations and diseases.

Abstract IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.

The field of carborane research has witnessed continuous development, leading to the construction and development of a diverse range of crystalline porous materials for various applications. Moreover, innovative synthetic approaches are expanding in this field. Since the first report of carborane-based crystalline porous materials (CCPMs) in 2007, the synthesis of carborane ligands, particularly through innovative methods, has consistently posed a significant challenge in discovering new structures of CCPMs. This paper provides a comprehensive summary of recent advances in various synthetic approaches for CCPMs, along with their applications in different domains. The primary challenges and future opportunities are expected to stimulate further multidisciplinary development in the field of CCPMs.

Abstract Objectives The objective of this study is to develop a deep learning (DL) model for fast and accurate mandibular canal (MC) segmentation on cone beam computed tomography (CBCT). Methods A total of 220 CBCT scans from dentate subjects needing oral surgery were used in this study. The segmentation ground truth is annotated and reviewed by two senior dentists. All patients were randomly splitted into a training dataset (n = 132), a validation dataset (n = 44) and a test dataset (n = 44). We proposed a two-stage 3D-UNet based segmentation framework for automated MC segmentation on CBCT. The Dice Similarity Coefficient (DSC) and 95% Hausdorff Distance (95% HD) were used as the evaluation metrics for the segmentation model. Results The two-stage 3D-UNet model successfully segmented the MC on CBCT images. In the test dataset, the mean DSC was 0.875 ± 0.045 and the mean 95% HD was 0.442 ± 0.379. Conclusions This automatic DL method might aid in the detection of MC and assist dental practitioners to set up treatment plans for oral surgery evolved MC.

Abstract IscU2 is a scaffold protein that is critical for the assembly of iron–sulfur (Fe–S) clusters and the functions of Fe–S-containing mitochondrial proteins. However, the role of IscU2 in tumor development remains unclear. Here, we demonstrated that IscU2 expression is much higher in human pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent normal pancreatic tissues. In PDAC cells, activated KRAS enhances the c-Myc-mediated IscU2 transcription. The upregulated IscU2 stabilizes Fe–S cluster and regulates the activity of tricarboxylic acid (TCA) cycle enzymes α-ketoglutarate (α-KG) dehydrogenase and aconitase 2, which promote α-KG catabolism through oxidative and reductive TCA cycling, respectively. In addition to promoting mitochondrial functions, activated KRAS-induced and IscU2-dependent acceleration of α-KG catabolism results in reduced α-KG levels in the cytosol and nucleus, leading to an increase in DNA 5mC due to Tet methylcytosine dioxygenase 3 (TET3) inhibition and subsequent expression of genes including DNA polymerase alpha 1 catalytic subunit for PDAC cell proliferation and tumor growth in mice. These findings underscore a critical role of IscU2 in KRAS-promoted α-KG catabolism, 5mC-dependent gene expression, and PDAC growth and highlight the instrumental and integrated regulation of mitochondrial functions and gene expression by IscU2 in PDAC cells.

Abstract Background Genetic testing plays an important role in guiding screening, diagnosis, and precision treatment of breast cancer (BC). However, the appropriate genetic testing criteria remain controversial. The current study aims to facilitate the development of suitable strategies by analyzing the germline mutational profiles and clinicopathological features of large‐scale Chinese BC patients. Methods BC patients who had undergone genetic testing at the Sun Yat‐sen University Cancer Center (SYSUCC) from September 2014 to March 2022 were retrospectively reviewed. Different screening criteria were applied and compared in the population cohort. Results A total of 1035 BC patients were enrolled, 237 pathogenic or likely pathogenic variants (P/LPV) were identified in 235 patients, including 41 out of 203 (19.6%) patients tested only for BRCA1/2 genes, and 194 out of 832 (23.3%) received 21 genes panel testing. Among the 235 P/LPV carriers, 222 (94.5%) met the NCCN high‐risk criteria, and 13 (5.5%) did not. While using Desai's criteria of testing, all females diagnosed with BC by 60 years and NCCN criteria for older patients, 234 (99.6%) met the high‐risk standard, and only one did not. The 21 genes panel testing identified 4.9% of non‐BRCA P/LPVs and a significantly high rate of variants of uncertain significance (VUSs) (33.9%). The most common non‐BRCA P/LPVs were PALB2 (11, 1.3%), TP53 (10, 1.2%), PTEN (3, 0.4%), CHEK2 (3, 0.4%), ATM (3, 0.4%), BARD1 (3, 0.4%), and RAD51C (2, 0.2%). Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs showed a significantly low incidence of NCCN criteria listed family history, second primary cancer, and different molecular subtypes. Conclusions Desai's criteria might be a more appropriate genetic testing strategy for Chinese BC patients. Panel testing could identify more non‐BRCA P/LPVs than BRCA1/2 testing alone. Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs exhibited different personal and family histories of cancer and molecular subtype distributions. The optimal genetic testing strategy for BC still needs to be investigated with larger continuous population studies.

IntroductionUrban–Rural Resident Basic Medical Insurance (URRBMI) is an important system for effectively transferring disease risks to the rural older adult. As China experiences rapid aging, maintaining the physical health of the rural older adult is key to achieving the goal of healthy aging.MethodsThe study explores the impact of URRBMI on physical health of the rural older adult in China using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2018. Ordinary least square models were used to analyze the relationship between URRBMI and physical health of the rural older adult, and we used instrumental variable method to address the potential endogenous problem.ResultsWe find that URRBMI greatly improves physical health of the rural older adult. The heterogeneity analysis indicates that URRBMI contributes more significantly to the rural older adult in eastern areas and the advanced rural older adult. The results also suggested that URRBMI improves physical health of the rural older adult through increasing life satisfaction and enhancing the timeliness of medical services.RecommendationsThis study implies that we need to further improve the participation rate, increase the actual reimbursement ratio and increase financial subsidies for URRBMI in central and western areas, and further integrate the distribution of medical resources to promote physical health of the rural older adult.

Previous research has indicated that natural landscapes exhibit a greater capacity for ameliorating negative emotional states in individuals when compared to urban landscapes. Nevertheless, significant scientific inquiries, such as the uniformity of the rejuvenating effect across distinct categories of natural landscapes on college students and the choice of the optimal plant community for achieving the most potent restorative effect, remain unexplored. This study aimed to address these questions by selecting four plant communities (single-layer grassland, single-layer woodland, tree-grass composite woodland, tree-shrub-grass composite woodland) and using an electroencephalography method to capture the neuroelectric activity of the participants in combination with the Positive and Negative Affect Schedule score to explore the effects of plant community types on emotional recovery. The results showed that all four plant communities significantly increased positive emotions and significantly reduced negative emotions. There was no significant difference in the recovery effect of positive emotions among the four plant community types, but there was a significant difference in the recovery effect of negative emotions. The effect of tree-shrub-grass composite woodland on the negative emotion recovery effect is the best; the EEG results found that the alpha wave amplitude induced by the tree-shrub-grass composite woodland was significantly higher than that of the other three groups of plant communities, and the EEG and behavioral results were consistent. The results show that the tree-shrub-grass composite woodland has the best restoration effect and has stronger planning and design significance.

Abstract Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell‐secreted extracellular vesicles (EVs) offer a new cell‐free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid‐derived retinal progenitor cells (hERO‐RPCs) are an easily accessible and advanced cell source for RD treatment. However, hERO‐RPCs‐derived EVs require further characterisation. Here, we compared the characteristics of EVs from hERO‐RPCs (hRPC‐EVs) with those of human embryonic stem cell (hESC)‐derived EVs (hESC‐EVs) as controls. Based on in‐depth proteomic analysis, we revealed remarkable differences between hRPC‐EVs and hESC‐EVs. A comparison between EVs and their respective cells of origin demonstrated that the protein loading of hRPC‐EVs was more selective than that of hESC‐EVs. In particular, hESC‐EVs were enriched with proteins related to angiogenesis and cell cycle, whereas hRPC‐EVs were enriched with proteins associated with immune modulation and retinal development. More importantly, compared with that of hESC‐EVs, hRPC‐EVs exhibited a lower correlation with cell proliferation and a unique capacity to regulate lipid metabolism. It was further confirmed that hRPC‐EVs potentially eliminated lipid deposits, inhibited lipotoxicity and oxidative stress, and enhanced phagocytosis and survival of oleic acid‐treated ARPE‐19 cells. Mechanistically, hRPC‐EVs are integrated into the mitochondrial network of oleic acid‐treated ARPE‐19 cells, and increased the level of mitochondrial fatty acid β‐oxidation‐related proteins. Thus, organoid‐derived hRPC‐EVs represent a promising source of cell‐free therapy for RD, especially for blinding diseases related to abnormal lipid metabolism in RPE cells.

Abstract The increased use of low‐dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single‐cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin‐1 and angiotensin II receptor type 2 and a basal‐like molecular character. Furthermore, it identifies that cathepsin B+ tumor‐associated macrophages may over‐activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.

Highlights A comprehensive discussion of the recent advances in the nanostructure engineering of Mg-based hydrogen storage materials is presented. The fundamental theories of hydrogen storage in nanostructured Mg-based hydrogen storage materials and their practical applications are reviewed. The challenges and recommendations of current nanostructured hydrogen storage materials are pointed out.

A quantized plateau is typically considered to be the feature of a fractional quantum Hall state. Yan et al. report a series of plateaus quantized at unusual fractions in a confined two-dimensional electron gas, which is attributed to enhanced density in the confined region.

To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARα) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( ± clofibrate) × 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-14C] palmitic acid (1 mM) as a substrate (0.265 μCi/μmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 μM) or acetoacetate-CoA deacylase (iodoacetamide, 50 μM). Without clofibrate stimulation, 14C accumulation in CO2 was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased 14C-ASP (P

Summary: Immune checkpoint blockade therapies are still ineffective for most patients with colorectal cancer (CRC). Immunogenic cell death (ICD) enables the release of key immunostimulatory signals to drive efficient anti-tumor immunity, which could be used to potentiate the effects of immune checkpoint inhibitors. Here, we showed that inhibition of valosin-containing protein (VCP) elicits ICD in CRC. Meanwhile, VCP inhibitor upregulates PD-L1 expression and compromises anti-tumor immunity in vivo. Mechanistically, VCP transcriptionally regulates PD-L1 expression in a JAK1-dependent manner. Combining VCP inhibitor with anti-PD1 remodels tumor immune microenvironment and reduces tumor growth in mouse models of CRC. Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating PD-L1 expression by VCP and suggests that inhibition of VCP has the potential to increase the efficacy of immunotherapy in CRC.

BackgroundAeromonas species have been identified as agents responsible for various diseases in both humans and animals. Multidrug-resistant Aeromonas strains pose a significant public health threat due to their emergence and spread in clinical settings and the environment. The aim of this study was to determine a novel resistance mechanism against aminoglycoside antimicrobials in a clinical isolate.MethodsThe function of aac(6′)-Va was verified by gene cloning and antibiotic susceptibility tests. To explore the in vivo activity of the enzyme, recombinant proteins were expressed, and enzyme kinetics were tested. To determine the molecular background and mechanism of aac(6′)-Va, whole-genome sequencing and bioinformatic analysis were performed.ResultsThe novel aminoglycoside N-acetyltransferase gene aac(6′)-Va confers resistance to several aminoglycosides. Among the antimicrobials tested, ribostamycin showed the highest increase (128-fold) in the minimum inhibitory concentration (MIC) compared with the control strains. According to the MIC results of the cloned aac(6′)-Va, AAC(6′)-Va also showed the highest catalytic efficiency for ribostamycin [kcat/Km ratio = (3.35 ± 0.17) × 104 M−1 s−1]. Sharing the highest amino acid identity of 54.68% with AAC(6′)-VaIc, the novel aminoglycoside N-acetyltransferase constituted a new branch of the AAC(6′) family due to its different resistance profiles. The gene context of aac(6′)-Va and its close relatives was conserved in the genomes of species of the genus Aeromonas.ConclusionThe novel resistance gene aac(6′)-Va confers resistance to several aminoglycosides, especially ribostamycin. Our finding of a novel resistance gene in clinical A. hydrophila will help us develop more effective treatments for this pathogen’s infections.

Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) but exhibits significantly lower affinities than canonical flaviviral MTases. Structures of ALSV MTase in the free and SAM/SAH-bound forms reveal that the viral enzyme possesses a unique loop-element lining side-wall of the SAM/SAH-binding pocket. While the equivalent loop in flaviviral MTases half-covers SAM/SAH, contributing multiple hydrogen-bond interactions; the pocket-lining loop of ALSV MTase is of short-length and high-flexibility, devoid of any physical contacts with SAM/SAH. Subsequent mutagenesis data further corroborate such structural difference affecting SAM/SAH-binding. Finally, we also report the structure of ALSV MTase bound with sinefungin, an SAM-analogue MTase inhibitor. These data have delineated the basis for the low-affinity interaction between ALSV MTase and SAM/SAH and should inform on antiviral drug design.

BackgroundAchromobacter is a genus of gram-negative bacteria that can act as opportunistic pathogens. Recent studies have revealed that some species of Achromobacter show inherent resistance to β-lactams, but the resistance mechanisms of Achromobacter mucicolens have rarely been reported.MethodThe bacterium was isolated using standard laboratory procedures. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs). Genome sequencing was performed using the PacBio RS II and Illumina HiSeq 2500 platforms, and the Comprehensive Antibiotic Resistance Database (CARD) was used to annotate the drug resistance genes. The localization of the novel β-lactamase AMZ-1 was determined, and its characteristics were determined via molecular cloning and enzyme kinetic analysis. The phylogenetic relationship and comparative genomic analysis of the resistance gene-related sequences were also analyzed.ResultAchromobacter mucicolens Y3, isolated from a goose on a farm in Wenzhou, showed resistance to multiple antibiotics, including penicillins and cephalosporins. BlaAMZ–1 showed resistance to amoxicillin, penicillin G, ampicillin, cephalothin and cefoxitin, and the resistance activity could be inhibited by β-lactamase inhibitors. Enzyme kinetic analysis results showed that AMZ-1 has hydrolytic activity against a wide range of substrates, including cephalothin, amoxicillin, penicillin G, and cefoxitin but not ampicillin. The hydrolytic activity of AMZ-1 was greatly inhibited by avibactam but much more weakly inhibited by tazobactam. Mobile genetic elements could not be found around the blaAMZ–1-like genes, which are conserved on the chromosomes of bacteria of the genus Achromobacter.ConclusionIn this study, a novel AmpC gene, blaAMZ–1, from the animal-origin bacterium A. mucicolens Y3 was identified and characterized. It conferred resistance to some penicillins and first- and second-generation cephalosporins. The identification of this novel resistance gene will be beneficial for the selection of effective antimicrobials to treat associated infections.

Background: Maternal body fluids contain abundant cell-free fetal RNAs which have the potential to serve as indicators of fetal development and pathophysiological conditions. In this context, this study aimed to explore the potential diagnostic value of maternal circulating long non-coding RNAs (lncRNAs) in ventricular septal defect (VSD).Methods: The potential of lncRNAs as non-invasive prenatal biomarkers for VSD was evaluated using quantitative polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curve analysis. The biological processes and regulatory network of these lncRNAs were elucidated through bioinformatics analysis.Results: Three lncRNAs (LINC00598, LINC01551, and GATA3-AS1) were found to be consistent in both maternal plasma and amniotic fluid. These lncRNAs exhibited strong diagnostic performance for VSD, with AUC values of 0.852, 0.957, and 0.864, respectively. The bioinformatics analysis revealed the involvement of these lncRNAs in heart morphogenesis, actin cytoskeleton organization, cell cycle regulation, and protein binding through a competitive endogenous RNA (ceRNA) network at the post-transcriptional level.Conclusion: The cell-free lncRNAs present in the amniotic fluid have the potential to be released into the maternal circulation, making them promising candidates for investigating epigenetic regulation in VSD.

Abstract GPR20 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for gastrointestinal stromal tumors (GIST) owing to its differentially high expression. An antibody-drug conjugate (ADC) containing a GPR20-binding antibody (Ab046) was recently developed in clinical trials for GIST treatment. GPR20 constitutively activates Gi proteins in the absence of any known ligand, but it remains obscure how this high basal activity is achieved. Here we report three cryo-EM structures of human GPR20 complexes including Gi-coupled GPR20 in the absence or presence of the Fab fragment of Ab046 and Gi-free GPR20. Remarkably, the structures demonstrate a uniquely folded N-terminal helix capping onto the transmembrane domain and our mutagenesis study suggests a key role of this cap region in stimulating the basal activity of GPR20. We also uncover the molecular interactions between GPR20 and Ab046, which may enable the design of tool antibodies with enhanced affinity or new functionality for GPR20. Furthermore, we report the orthosteric pocket occupied by an unassigned density which might be essential for exploring opportunities for deorphanization.

The accuracy of RGB-D SLAM systems is sensitive to the image quality, and can be significantly compromised in adverse situations such as when input images are blurry, lacking in texture features, or overexposed. In this paper, based on Continuous Direct Sparse Visual Odometry (CVO), we present a novel Keyframe-based CVO (KF-CVO) with intrinsic keyframe selection mechanism that effectively reduces the tracking error. We then extend KF-CVO to a RGB-D SLAM system, CVO SLAM, equipped with place recognition via ORB features, and joint bundle adjustment & pose graph optimization. Comprehensive evaluations on publicly available benchmarks show that the proposed RGB-D SLAM system achieves a higher success rate than current state-of-the-art-methods. The proposed system is more robust to difficult benchmark sequences than current state-of-the-art methods, where adverse situations such as rapid camera motions, environments lacking in texture, and overexposed images when strong illumination exists.