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Abstract Background Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. Methods This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. Results A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients’ death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563–0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699–0.878), p

Exploring stable and robust catalysts to replace the current toxic CuCr based catalysts for dehydrogenative coupling of ethanol to ethyl acetate is a challenging but promising task. Herein, novel NiIn based catalysts were developed by tailoring Ni catalysts with Indium (In) for this reaction. Over the optimal Ni0.1Zn0.7Al0.3InOx catalyst, the ethyl acetate selectivity reached 90.1% at 46.2% ethanol conversion under the conditions of 548 K and a weight hourly space velocity of 1.9 h−1 in the 370 h time on stream. Moreover, the ethyl acetate productivity surpassed 1.1 gethylacetategcatalyst−1h−1, one of the best performance in current works. According to catalyst characterizations and conditional experiments, the active sites for dehydrogenative coupling of ethanol to ethyl acetate were proved to be Ni4In alloys. The presence of In tailored the chemical properties of Ni, and subsequently inhibited the C–C cracking and/or condensation reactions during ethanol conversions. Over Ni4In alloy sites, ethanol was dehydrogenated into acetaldehyde, and then transformed into acetyl species with the removal of H atoms. Finally, the coupling between acetyl species and surface-abundant ethoxyde species into ethyl acetate was achieved, affording a high ethyl acetate selectivity and catalyst stability.

Abstract Background Rice is one of the most important food crops in the world, and with the development of direct seeding methods for rice, exposure to anaerobic stress has become a major factor limiting its growth. Results In this experiment, we tested the tolerance to anaerobic germination of rice varieties NIP and HD84, and they were used as parents to construct a DH (doubled-haploid) population. The transcriptomes of NIP (highly tolerant) and HD86 (intolerant), and their progeny HR (highly tolerant) and NHR (intolerant) were sequenced from normal and anaerobic environments. The differentially-expressed genes (DEGs) were subjected to GO (Gene ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and WGCNA analyses. QTL mapping of the DH population identified tolerance to anaerobic germination-related chromosomal segments. The transcriptome results from 24 samples were combined with the anaerobic stress QTL results for 159 DH population lines to construct a metabolic network to identify key pathways and a gene interaction network to study the key genes. Essential genes were initially subjected to rigorous functional validation, followed by a comprehensive analysis aimed at elucidating their potential utility in domestication and breeding practices, particularly focusing on the exploitation of dominant haplotypes. Conclusion The results show that pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) are the starting signals of energy metabolism for coleoptile length growth, the auxin transporter EXPA is the determining signal for coleoptile length growth. The pivotal genes Os05g0498700 and Os01g0866100 exert a negative regulatory influence on coleoptile length, ultimately enhancing tolerance to anaerobic germination in rice. Analyses of breeding potential underscore the additional value of Os05g0498700-hyp2 and Os01g0866100-hyp2, highlighting their potential utility in further improving rice through breeding programs. The results of our study will provide a theoretical basis for breeding anaerobic-tolerant rice varieties.

Laser directed energy deposition (LDED), a highly promising metal additive manufacturing (AM) technology, has garnered widespread attention across various industries. However, local high-energy input during AM can generate residual stress (RS), which may cause deformation and even cracking of the parts. Due to the evolution of RS is influenced by temperature gradients, cooling rates and solid-state phase transformation(SSPT), accurately predicting RS remains challenging. To tackle this issue, a thermal-metallurgical-mechanical coupled model of 30CrNi2MoVA steel in LDED is established. To account for the influence of SSPT on the evolution of RS, the phase transformation kinetics model for 30CrNi2MoVA steel is developed based on thermal expansion experiments and integrated into mechanical computations. Using this model, the thermal cycle history, microstructure distribution and RS level of LDED fabricated parts are discussed in detail, and the accuracy of the model is verified through characterization experiments such as thermocouples, scanning electron microscopy and X-ray diffraction. The simulation results show that the RS of thin-walled parts is related to the scanning direction, and the maximum principal stress along the scanning direction is the highest. The microstructure of thin-walled parts is mainly composed of martensite with a small amount of bainite. Compared to models that do not consider SSPT effects, the overall stress magnitude of models that consider SSPT significantly decreases, and the surface RS state transitions from tensile stress to compressive stress. The proposed thermal-metallurgical-mechanical coupled model has the potential to accurately predict and understand the stress behavior and performance changes of 30CrNi2MoVA steel in LDED.

Hypervirulent K. pneumoniae (hvKp) have emerged as clinically important pathogens, posing a serious threat to human health. RfaH, a transcriptional elongation factor, has been regarded as implicated in facilitating the transcription of long virulence operons in certain bacterial species. In K. pneumoniae, RfaH plays a vital role in promoting CPS synthesis and hypermucoviscosity, as well as mediating bacterial fitness during lung infection. In this study, we aim to conduct a systematic investigation of the roles of rfaH in the survival, dissemination, and colonization of hvKp through in vitro and in vivo assays. We found that bacterial cells and colonies displayed capsule -deficient phenotypes subsequent to the deletion of rfaH in K. pneumoniae NTUH-K2044. We confirmed that rfaH is required for the synthesis of capsule and lipopolysaccharide (LPS) by positively regulating the expression of CPS and LPS gene clusters. We found that the ΔrfaH mutant led to a significantly decreased mortality of K. pneumoniae in a mouse intraperitoneal infection model. We further demonstrated that the absence of rfaH was associated with slower bacterial growth under conditions of low nutrition or iron limitation. ΔrfaH displayed reduced survival rates in the presence of human serum. Besides, the engulfment of the ΔrfaH mutant was significantly higher than that of NTUH-K2044 by macrophages in vivo, indicating an indispensable role of RfaH in the phagocytosis resistance of hvKp in mice. Both mouse intranasal and intraperitoneal infection models revealed a higher bacterial clearance rate of ΔrfaH in lungs, livers, and spleens of mice compared to its wild type, suggesting an important role of RfaH in the bacterial survival, dissemination, and colonization of hvKp in vivo. Histopathological results supported that RfaH contributes to the pathogenicity of hvKp in mice. In conclusion, our study demonstrates crucial roles of RfaH in the survival, colonization and full virulence of hvKp, which provides several implications for the development of RfaH as an antibacterial target.

BackgroundSerious games (SGs) have emerged as engaging and instructional digital simulation tools that are increasingly being used for military medical training. SGs are often compared with traditional media in terms of learning outcomes, but it remains unclear which of the 2 options is more efficient and better accepted in the process of knowledge acquisition. ObjectiveThis study aimed to create and test a scenario-based system suitable for enhancing rescue reasoning skills in tactical combat casualty care. MethodsTo evaluate the effectiveness of the SGs, a randomized, observational, comparative trial was conducted. A total of 148 members from mobile medical logistics teams were recruited for training. Pre- and posttraining assessments were conducted using 2 different formats: a video-based online course (n=78) and a game simulation (n=70). We designed 3 evaluation instruments based on the first 2 levels of the Kirkpatrick model (reaction and learning) to measure trainees’ satisfaction, knowledge proficiency, and self-confidence. ResultsThere were 4 elements that made up the learning path for the SGs: microcourses (video-based online courses), self-test, game simulation, and record query. The knowledge test scores in both groups were significantly higher after the intervention (t154=–6.010 and t138=–7.867, respectively; P

Abstract Background Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. Methods A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. Results A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. Conclusion The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.

Augmented Reality (AR) is increasingly recognized as a transformative tool for creating restorative environments within museums. It has the potential to provide psychological benefits for visitors, including attention restoration, stress reduction, and anxiety alleviation. This study explores how AR can foster these benefits within museum spaces. By adopting AR technology, museums can go beyond their traditional roles of knowledge dissemination. The immersive, adaptive, and interactive features of AR can enhance the museum experience, transforming it into an innovative therapeutic space. By combining real exhibits with virtual elements, AR can restore visitors’ psychological energy within museum settings. This integration of digital innovation into restorative contexts surpasses the traditional functions of visual service. Through empirical investigation of multiple dimensions of restorative environments, AR museum experiences offer comprehensive attention restoration. In this study, a survey was conducted with 279 participants to assess the impact of AR museum experiences on visitors’ psychology. The results revealed that such experiences contribute to heightened attention restoration levels, stress reduction, and anxiety relief. With the latest advancements in generative artificial intelligence, AR technology is empowered to integrate within museums. This integration will merge individuals with customized technology, expanding human perceptual experiences and highlighting AR's significant influence within the museum environment.

With the intensification of global climate change and the increasing complexity of agricultural environments, the improvement of rice stress tolerance is an important focus of current breeding research. This review summarizes the current knowledge on the impact of various abiotic stresses on rice and the associated epigenetic responses (DNA methylation). Abiotic stress factors, including high temperature, drought, cold, heavy metal pollution, and high salinity, have a negative impact on crop productivity. Epigenetic changes are key regulatory factors in plant stress responses, and DNA methylation is one of the earliest discovered and thoroughly studied mechanisms in these epigenetic regulatory mechanisms. The normal growth of rice is highly dependent on the environment, and changes in the environment can lead to rice sterility and severe yield loss. Changes in the regulation of the DNA methylation pathway are involved in rice’s response to stress. Various DNA methylation-regulating protein complexes that function during rice development have been identified. Significant changes in DNA methylation occur in numerous stress-responsive genes, particularly those in the abscisic acid signaling pathway. These findings underscore the complex mechanisms of the abiotic stress response in rice. We propose the effective improvement of tolerance traits by regulating the epigenetic status of rice and emphasize the role of DNA methylation in abiotic stress tolerance, thereby addressing global climate change and ensuring food security.

Mitochondria-associated ferroptosis exacerbates cardiac microvascular dysfunction in diabetic cardiomyopathy (DCM). Nicorandil, an ATP-sensitive K+ channel opener, protects against endothelial dysfunction, mitochondrial dysfunction, and DCM; however, its effects on ferroptosis and mitophagy remain unexplored. The present study aimed to assess the beneficial effects of nicorandil against endothelial ferroptosis in DCM and the underlying mechanisms. Cardiac microvascular perfusion was assessed using a lectin perfusion assay, while mitophagy was assessed via mt-Keima transfection and transmission electron microscopy. Ferroptosis was examined using mRNA sequencing, fluorescence staining, and western blotting. The mitochondrial localization of Parkin, ACSL4, and AMPK was determined via immunofluorescence staining. Following long-term diabetes, nicorandil treatment improved cardiac function and remodeling by alleviating cardiac microvascular injuries, as evidenced by the improved microvascular perfusion and structural integrity. mRNA-sequencing and biochemical analyses showed that ferroptosis occurred and Pink1/Parkin-dependent mitophagy was suppressed in cardiac microvascular endothelial cells after diabetes. Nicorandil treatment suppressed mitochondria-associated ferroptosis by promoting the Pink1/Parkin-dependent mitophagy. Moreover, nicorandil treatment increased the phosphorylation level of AMPKα1 and promoted its mitochondrial translocation, which further inhibited the mitochondrial translocation of ACSL4 via mitophagy and ultimately suppressed mitochondria-associated ferroptosis. Importantly, overexpression of mitochondria-localized AMPKα1 (mitoAα1) shared similar benefits with nicorandil on mitophagy, ferroptosis and cardiovascular protection against diabetic injury. In conclusion, the present study demonstrated the therapeutic effects of nicorandil against cardiac microvascular ferroptosis in DCM and revealed that the mitochondria-localized AMPK-Parkin-ACSL4 signaling pathway mediates mitochondria-associated ferroptosis and the development of cardiac microvascular dysfunction.

Purpose: Although chromosome 21 is the smallest human chromosome, it is highly relevant in the pathogenicity of both cancer and congenital diseases, including Alzheimer disease and trisomy 21 (Down syndrome). In addition, cases with rare structural variants (SVs) of chromosome 21 have been reported. These events vary in size and include large chromosomal events, such as ring chromosomes and small partial aneuploidies. The p-arm of the acrocentric chromosome 21 was devoid of reference genomic sequence in GRCh37 and GRCh38, which hampered our ability to solve genomic rearrangements and find the mechanism of formation of disease-causing SVs. We hypothesize that conserved satellite structures and segmental duplications located on the p-arm play an important role in the formation of complex SVs involving chromosome 21. Methods: Three cases with complex chromosome 21 rearrangements were studied with a combination of short-read and long-read genome sequencing, as well as optical genome mapping. The data were aligned to the T2T-CHM13 assembly. Results: We were able to resolve all 3 complex chromosome 21 rearrangements in which 15, 8, and 26 breakpoints were identified, respectively. By comparing the identified SV breakpoints, we were able to pinpoint a region between 21p13 and 21p12 that appears to be frequently involved in chromosome 21 rearrangements. Importantly, we observed acrocentric satellite DNA at several breakpoint junctions suggesting an important role for those elements in the formation of complex SVs. Conclusion: Taken together, our results provide further insights into the architecture and underlying mechanisms of complex rearrangements on acrocentric chromosomes.

The concept of gait synergy provides novel human–machine interfaces and has been applied to the control of lower limb assistive devices, such as powered prostheses and exoskeletons. Specifically, on the basis of gait synergy, the assistive device can generate/predict the appropriate reference trajectories precisely for the affected or missing parts from the motions of sound parts of the patients. Optimal modeling for gait synergy methods that involves optimal combinations of features (inputs) is required to achieve synergic trajectories that improve human–machine interaction. However, previous studies lack thorough discussions on the optimal methods for synergy modeling. In addition, feature selection (FS) that is crucial for reducing data dimensionality and improving modeling quality has often been neglected in previous studies. Here, we comprehensively investigated modeling methods and FS using 4 up-to-date neural networks: sequence-to-sequence (Seq2Seq), long short-term memory (LSTM), recurrent neural network (RNN), and gated recurrent unit (GRU). We also conducted complete FS using 3 commonly used methods: random forest, information gain, and Pearson correlation. Our findings reveal that Seq2Seq (mean absolute error: 0.404° and 0.596°, respectively) outperforms LSTM, RNN, and GRU for both interlimb and intralimb synergy modeling. Furthermore, FS is proven to significantly improve Seq2Seq’s modeling performance (P < 0.05). FS-Seq2Seq even outperforms methods used in existing studies. Therefore, we propose FS-Seq2Seq as a 2-stage strategy for gait synergy modeling in lower limb assistive devices with the aim of achieving synergic and user-adaptive trajectories that improve human–machine interactions.

Prior studies have investigated the relationship between fairness and honesty. However, the differences in the focus of these studies have rendered cross-comparisons between them challenging and of limited value. Thus, this study explored how fairness impacts honest decision-making, focusing specifically on the effect of individuals’ experiences of fairness on their honest behavior. Experiment 1 explored the influence of different experiences of fairness on honest behavior in an altruistic context. In Experiment 2, we measured event-related potentials to further demonstrate the brain mechanisms of these experiences on altruistic dishonest behavior. In Experiment 1, we found that the reaction time for dishonest behavior was shorter for individuals who had positive unfairness experiences with high altruistic objects compared to low altruistic objects. Individuals who had negative unfairness experiences had shorter reaction times when engaging in dishonest behaviors for the sake of high altruistic objects compared to those with equitable experiences. In Experiment 2, in which there was an opportunity to lie for a highly altruistic object, those with fair experiences had greater N2 volatility and smaller P3 volatility than those with positive unfairness experiences. These findings highlight the value of integrating moral psychology and behavioral economics. Discriminant validity across fairness experiences can help illuminate the different motivations behind moral decisions.

Each application of neurostimulators requires unique stimulation parameter specifications to achieve effective stimulation. Balancing the current magnitude with stimulation resolution, waveform, size, and channel count is challenging, leading to a loss of generalizability across broad neural interfaces. To address this, this paper proposes a highly scalable, programmable neurostimulator with a System-on-Chip (SOC) capable of 32 channels of independent stimulation. The compliance voltage reaches up to ±22.5 V. A pair of 8-bit current-mode DACs support independent waveforms for source and sink operations and feature a user-selectable dual range for low-current intraparenchymal microstimulation with a resolution of 4.31 μA/bit, as well as high current stimulation for spinal cord and DBS applications with a resolution of 48.00 μA/bit, achieving a wide stimulation range of 12.24 mA while maintaining high-resolution biological stimulation. A dedicated communication protocol enables full programmable control of stimulation waveforms, effectively improving the range of stimulation parameters. In vivo electrophysiological experiments successfully validate the functionality of the proposed stimulator. This flexible stimulator architecture aims to enhance its generality across a wide range of neural interfaces and will provide more diverse and refined stimulation strategies.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has driven us to explore alternative treatments for the limitation of antimicrobial agents. Lytic phages are considered a promising alternative treatment for CR-hvKP infection. In this study, we reported three novel lytic phages, vB_KpnA_SCNJ1-Z, vB_KpnS_SCNJ1-C, and vB_KpnM_SCNJ1-Y, against a CR-hvKP strain SCNJ1, and they possess genomes of double-stranded DNA with a size of 43,428 bp, 46,039 bp, and 50,360 bp, respectively. Phylogenetic analysis demonstrated that vB_KpnA_SCNJ1-Z belongs to the family Autographiviridae within the class Caudoviricetes, while vB_KpnS_SCNJ1-C and vB_KpnM_SCNJ1-Y are unclassified Caudoviricetes. The phages showed a narrow host range only lysing 1 of 50 tested clinical bacterial strains. The one-step growth curves and stability results showed that the phages displayed relatively short latency periods, with broad pH (pH 3-14) and thermal stabilities (20–60°C). The phages showed significant inhibition of the biofilm formation by SCNJ1 and strong antibacterial activity in vitro. In the mouse model, we demonstrated that administration of a single phage or phage cocktail significantly reduced bacteria loads in the lung, liver, and spleen, and effectively rescued mice from the infection of the SCNJ1 strain, with a survival rate of 70-80%. These findings suggested the three phages have great potential as an alternative therapy with favorable stability and strong antibacterial activity both in vivo and in vitro for the treatment of CR-hvKP infection.

IntroductionThe tigecycline-resistant Enterobacterales have emerged as a great public concern, and the mobile tet(X) variants and tmexCD-toprJ efflux pump are mainly responsible for the spread of tigecycline resistance. Hospital sewage is considered as an important reservoir of antimicrobial resistance, while tigecycline resistance in this niche is under-researched.MethodsIn this study, five Escherichia coli and six Klebsiella pneumoniae strains were selected from a collection of tigecycline-resistant Enterobacterales for further investigation by antimicrobial susceptibility testing, conjugation, whole-genome sequencing, and bioinformatics analysis.ResultsAll five E. coli strains harbored tet(X4), which was located on different plasmids, including a novel IncC/IncFIA(HI1)/IncHI1A/IncHI1B(R27) hybrid structure. In addition, tet(X4)-bearing plasmids were able to transfer by conjugation and be stabilized in the recipient in the absence of antibiotics. tmexCD1-toprJ1 was identified in two K. pneumoniae (LZSFT39 and LZSRT3) and it was carried by a novel multidrug-resistance transposon, designated Tn7368, on a novel IncR/IncU hybrid plasmid. In addition, we found that two K. pneumoniae (LZSFZT3 and LZSRT3) showed overexpression of efflux genes acrB and oqxB, respectively, which was most likely to be caused by mutations in ramR and oqxR.DiscussionIn conclusion, the findings in this study expand our knowledge of the genetic elements that carry tigecycline resistance genes, which establishes a baseline for investigating the structure diversity and evolutionary trajectories of human, animal, and environmental tigecycline resistomes.

Broadband second-harmonic generation (SHG) has important applications in many fields, such as femtosecond laser technology, optical communication, and biomedicine. The broadband SHG has been implemented in some crystals; however, it is not clear for forward and backward broadband quasi-phase-matching (QPM) SHGs in orientation-patterned Ⅱ-Ⅵ crystals. In this paper, the characters of orientation-patterned ZnS (OP-ZnS), orientation-patterned ZnSe (OP-ZnSe), and orientation-patterned CdTe (OP-CdTe) are, respectively, studied, including the forward broadband SHG and backward broadband SHG bandwidths at different temperatures. In addition, the influences of temperature on the forward broadband SHG bandwidth are investigated. The forward broadband QPM SHGs of OP-ZnS, OP-ZnSe, and OP-CdTe are obtained, and the backward broadband QPM SHGs cannot be obtained. The influence of temperature on the forward bandwidth is small.

Deep learning has found widespread application in diabetic retinopathy (DR) screening, primarily for lesion detection. However, this approach encounters challenges such as information loss due to convolutional operations, shape uncertainty, and the high similarity between different lesions types. These factors collectively hinder the accurate segmentation of lesions. In this research paper, we introduce a novel dual-branch U-Net architecture, referred to as Dual-Branch (DB)-U-Net, tailored to address the intricacies of small-scale lesion segmentation. Our approach involves two branches: one employs a U-Net to capture the shared characteristics of lesions, while the other utilizes a modified U-Net, known as U2Net, equipped with two decoders that share a common encoder. U2Net is responsible for generating probability maps for lesion segmentation as well as corresponding boundary segmentation. DB U-Net combines the outputs of U2Net and U-Net as a dual branch, concatenating their segmentation maps to produce the final result. To mitigate the challenge of imbalanced data, we employ the Dice loss as a loss function. We evaluate the effectiveness of our approach on publicly available datasets, including DDR, IDRiD, and E-Ophtha. Our results demonstrate that DB U-Net achieves AUPR values of 0.5254 and 0.7297 for Microaneurysms and soft exudates segmentation, respectively, on the IDRiD dataset. These results outperform other models, highlighting the potential clinical utility of our method in identifying retinal lesions from retinal fundus images.

Quasi-phase matching optical parametric oscillators (OPOs) are widely used for mid-infrared laser generation. However, the traditional OPO bulk material using high voltage electric field poling limits the flexibility of the poling period. In this paper, we propose a novel OPO design based on all-optical poled silicon nitride, allowing for adjustable poling period. Two OPO design schemes are presented, each offering unique advantages in terms of operational characteristics and performance. The output characteristics of the OPO are investigated in three modes: OPO pump tuning, poling fundamental wave (PFW) tuning, and OPO pump tuning and PFW tuning with the same laser. For OPO pump tuning, the OPO achieves output wavelengths of 3.319- $5.265 ~\mu \text{m}$ and 2.225- $3.769 ~\mu \text{m}$ with PFW wavelengths of 1450 nm and 1700 nm. For PFW tuning, the OPO produces output wavelengths of 5.502- $3.722 ~\mu \text{m}$ and 5.497- $3.577 ~\mu \text{m}$ using OPO pump wavelengths of 1310 nm and 1654 nm, respectively. Furthermore, for OPO pump tuning and PFW tuning with the same laser, the OPO generates output wavelengths ranging from $5.504 ~\mu \text{m}$ to $3.941 ~\mu \text{m}$ with OPO pump and PFW wavelengths ranging from $1.420 ~\mu \text{m}$ to $1.610 ~\mu \text{m}$ . This new OPO design offers enhanced flexibility in controlling the poling period for efficient mid-infrared laser generation.

Abstract Background/aims This study explores the relationship between the E3 ubiquitin ligase Ring finger protein 126 (RNF126) and early breast cancer metastasis and tests the hypothesis that RNF126 determines the efficacy of inhibitors targeting Ataxia telangiectasia mutated and Rad3-related kinase (ATR). Methods Various metastasis-related genes were identified by univariable Cox proportional hazards regression analysis based on the GSE11121 dataset. The RNF126-related network modules were identified by WGCNA, whereas cell viability, invasion, and migration assays were performed to evaluate the biological characteristics of breast cancer cells with or without RNF126 knockdown. MTT, immunoblotting, immunofluorescence, and DNA fiber assays were conducted to determine the efficiency of ATR inhibitor in cells with or without RNF126 knockdown. Results RNF126 was associated with early breast cancer metastasis. RNF126 promoted breast cancer cell proliferation, growth, migration, and invasion. ATR inhibitors were more effective at killing breast cancer cells with intact RNF126 due to replication stress compared with the corresponding cells with RNF126 knockdown. Cyclin-dependent kinase 2 (CDK2) was involved in regulating replication stress in breast cancer cells with intact RNF126. Conclusion A high level of expression of RNF126 in early breast cancer patients without lymph node metastases may indicate a high-risk type of metastatic disease, possibly due to RNF126, which may increase breast cancer cell proliferation and invasion. RNF126-expressing breast cancer cells exhibit CDK2-mediated replication stress that makes them potential targets for ATR inhibitors.

Abstract Aim Our study aimed to evaluate the sleep status of psychiatric nurses in Chinese population and analyse the influencing factors. Design Cross‐sectional, correlation design with logistic regression analysis. Methods We investigated 1,044 psychiatric nurses from seven psychiatric hospitals in China. Pittsburgh Sleep Quality Index and Maslach Burnout Inventory General Survey were used as main measures. Results The average Pittsburgh Sleep Quality Index score of 1,044 psychiatric nurses was 7.00 ± 3.59, and 38.63% of nurses had a total Pittsburgh Sleep Quality Index score >7. Our study found that middle‐night shift nurses had poor sleep quality and sleep disorders are positively correlated with emotional exhaustion and cynical disregard for job burnout. Middle‐night shift nurses showed 1.586 times more likely to suffer from sleep disorders than those non‐middle‐night shift. The higher the score of emotional exhaustion, the greater the risk of sleep disorders.

ObjectiveProteus mirabilis is the one of most important pathogens of catheter-associated urinary tract infections. The emergence of multidrug-resistant (MDR) P. mirabilis severely limits antibiotic treatments, which poses a public health risk. This study aims to investigate the resistance characteristics and virulence potential for a collection of P. mirabilis clinical isolates.Methods and resultsAntibiotic susceptibility testing revealed fourteen MDR strains, which showed high resistance to most β-lactams and trimethoprim/sulfamethoxazole, and a lesser extent to quinolones. All the MDR strains were sensitive to carbapenems (except imipenem), ceftazidime, and amikacin, and most of them were also sensitive to aminoglycosides. The obtained MDR isolates were sequenced using an Illumina HiSeq. The core genome-based phylogenetic tree reveals the high genetic diversity of these MDR P. mirabilis isolates and highlights the possibility of clonal spread of them across China. Mobile genetic elements SXT/R391 ICEs were commonly (10/14) detected in these MDR P. mirabilis strains, whereas the presence of resistance island PmGRI1 and plasmid was sporadic. All ICEs except for ICEPmiChn31006 carried abundant antimicrobial resistance genes (ARGs) in the HS4 region, including the extended-spectrum β-lactamase (ESBL) gene blaCTX-M-65. ICEPmiChn31006 contained the sole ARG blaCMY-2 and was nearly identical to the global epidemic ICEPmiJpn1. The findings highlight the important roles of ICEs in mediating the spread of ARGs in P. mirabilis strains. Additionally, these MDR P. mirabilis strains have great virulence potential as they exhibited significant virulence-related phenotypes including strong crystalline biofilm, hemolysis, urease production, and robust swarming motility, and harbored abundant virulence genes.ConclusionIn conclusion, the prevalence of MDR P. mirabilis with high virulence potential poses an urgent threat to public health. Intensive monitoring is needed to reduce the incidence of infections by MDR P. mirabilis.

BackgroundThe optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking.MethodsWe retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan–Meier method.ResultsThe median age was 64 (range 31–84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5–7.6) and the median OS was 9 months (95% CI, 7.6–12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18–7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08–3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance.ConclusionsLE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.

This article presents the design of a low-power, low-noise neural signal amplifier for neural recording. The structure reduces the current consumption of the amplifier through current scaling technology and lowers the input-referred noise of the amplifier by combining a source degeneration resistor and current reuse technologies. The amplifier was fabricated using a 0.18 μm CMOS MS RF G process. The results show the front-end amplifier exhibits a measured mid-band gain of 40 dB/46 dB and a bandwidth ranging from 0.54 Hz to 6.1 kHz; the amplifier’s input-referred noise was measured to be 3.1 μVrms, consuming a current of 3.8 μA at a supply voltage of 1.8 V, with a Noise Efficiency Factor (NEF) of 2.97. The single amplifier’s active silicon area is 0.082 mm2.

Abstract Background Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. Methods Using a case–control design, 68 subjects (34 patients and 34 healthy controls) underwent clinical assessment, blood sampling, and resting-state functional Magnetic Resonance Imaging (fMRI). The total Hamilton depression-17 (HAMD-17) score was used to assess depression severity. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-18 levels. Rest-state fMRI was conducted to explore spontaneous brain activity. Results The level of IL-18 was higher in patients with depression in comparison with healthy controls. IL-18 was negatively correlated with degree centrality of the left posterior cingulate gyrus in the depression patient group, but no correlation was found in the healthy control group. Conclusion This study suggests the involvement of IL-18 in the pathophysiological mechanism for depression and interference with brain activity.

Abstract Background Immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy and toxicity beyond the first‐line setting remain poorly defined. Methods We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI/TKI in any line of treatment at two academic centers as of 05/01/2020. We collected clinical, pathological, and treatment‐related variables. Outcomes including objective response rate (ORR), progression‐free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan–Meier method. Results Patients received pembrolizumab, nivolumab, avelumab, or nivolumab–ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty‐three patients received first‐line ICI/TKI therapy, while 52 received ≥ second‐line ICI/TKI. The efficacy of ICI/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS [mPFS]: 15.2, 14.2, 10.1, and 6.8 months, for first, second, third, and ≥ fourth line therapy, respectively). In the ≥ second‐line setting, ICI/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1 months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5 months. Overall, ≥ second‐line ICI/TKI was tolerable with 25 of 52 (52%) patients developing grade ≥3 adverse events. Conclusions ICI/TKI combination therapy is feasible and safe beyond the first‐line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.

How to view the reform of the Catholic Church in the sixteenth century and its relationship with virtue as an important issue in studying humanist philosophy. Humanists emphasize that virtue education is the foundation for cultivating personality and believe restoring the virtues of the church is the “cure” for the ills of the early modern church. Consilium de emendanda ecclesia (1537) is the Catholic humanists’ practice of virtue. This is reflected in proposals to strengthen educational norms and socio-moral disciplines and emphasize perfecting clerical virtue as the driving force for reform. In addition, under the guidance of virtue ethics, virtue politics becomes the guiding ideology of those humanists’ political practice, where they recognize the Pope´s authority and the one of the Church, associating virtue with the legitimacy of power. The virtue philosophy in Consilium forms the ideological foundation for the Reformation of the Catholic Church. The ancient Chinese scholar Dong Zhongshu (179-104 B.C.) practiced a similar politics of virtue. In Luxuriant Gems of the Spring and Autumn, he combined the legitimacy of rule with virtue based on the kings’ divine right, thus perpetuating the Confucian concept of the “sage”. Both Catholic humanists and Dong emphasized the importance of the rulers’ virtue as agents of God.

BackgroundRandomized controlled phase III trials have reported significant improvements in disease response and survival with the addition of chemotherapy to androgen deprivation therapy for men presenting with metastatic prostate cancer. We examined the implementation of such knowledge and its impact within the Surveillance, Epidemiology, and End Results (SEER) database.MethodThe administration of chemotherapy for men with an initial presentation of metastatic prostate cancer from 2004 to 2018 in the SEER database and its association with survival outcomes was examined. Kaplan–Meier estimates were applied to compare survival curves. Cox proportion hazard survival models were used to analyze the association of chemotherapy and other variables with both cancer- specific and overall survival.ResultA total of 727,804 patients were identified with 99.9% presenting with adenocarcinoma and 0.1% with neuroendocrine histopathology. Chemotherapy as initial treatment for men with de novo distant metastatic adenocarcinoma increased from 5.8% during 2004–2013 to 21.4% during 2014–2018. Chemotherapy was associated with a poorer prognosis during 2004–2013 but was associated with improved cancer-specific (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.78–0.93, p=0.0004) and overall survival (HR= 0.78, 95% CI: 0.71–0.85, p < 0.0001) during 2014–2018. The improved prognosis during 2014–2018 was observed in patients with visceral or bone metastasis and most impactful for patients aged 71–80 years. These findings were confirmed by subsequent propensity score matching analyses. Furthermore, chemotherapy was consistently provided to 54% of patients with neuroendocrine carcinoma at diagnosis from 2004 to 2018. Treatment was associated with improved cancer-specific survival (HR= 0.62, 95% CI: 0.45–0.87, p=0.0055) and overall survival (HR= 0.69, 95% CI: 0.51–0. 94, p=0.0176) during 2014–2018 but not significant in earlier years.ConclusionChemotherapy at initial diagnosis was increasingly employed in men with metastatic adenocarcinoma after 2014 and consistent with the evolution of National Comprehensive Cancer Network (NCCN) guidelines. Benefits for chemotherapy are suggested after 2014 in the treatment of men with metastatic adenocarcinoma. The use of chemotherapy for neuroendocrine carcinoma at diagnosis has remained stable, and outcomes have improved in more recent years. Further development and optimization of chemotherapy continues to evolve for men with de novo diagnosis of metastatic prostate cancer.

Brain–computer interfaces (BCIs) have garnered extensive interest and become a groundbreaking technology to restore movement, tactile sense, and communication in patients. Prior to their use in human subjects, clinical BCIs require rigorous validation and verification (V&V). Non-human primates (NHPs) are often considered the ultimate and widely used animal model for neuroscience studies, including BCIs V&V, due to their proximity to humans. This literature review summarizes 94 NHP gait analysis studies until 1 June, 2022, including seven BCI-oriented studies. Due to technological limitations, most of these studies used wired neural recordings to access electrophysiological data. However, wireless neural recording systems for NHPs enabled neuroscience research in humans, and many on NHP locomotion, while posing numerous technical challenges, such as signal quality, data throughout, working distance, size, and power constraint, that have yet to be overcome. Besides neurological data, motion capture (MoCap) systems are usually required in BCI and gait studies to capture locomotion kinematics. However, current studies have exclusively relied on image processing-based MoCap systems, which have insufficient accuracy (error: ≥4° and 9 mm). While the role of the motor cortex during locomotion is still unclear and worth further exploration, future BCI and gait studies require simultaneous, high-speed, accurate neurophysiological, and movement measures. Therefore, the infrared MoCap system which has high accuracy and speed, together with a high spatiotemporal resolution neural recording system, may expand the scope and improve the quality of the motor and neurophysiological analysis in NHPs.

Aims: Altered lipid, energy metabolism and sleep disorders had been linked with coronary heart disease (CHD), however, the metabolic signatures and sleep rhythm in non-obstructive coronary atherosclerosis-CHD remain unclear. This pilot study aims to investigate the lipidome and central carbon metabolites profiles and associated sleep characteristics among CHD patients without traditional risk factors. Methods: From January to July 2021, 15 CHD patients and 15 healthy controls were randomly selected from the cardiology unit of Zhongshan Hospital, Shanghai. A total of 464 lipids and 45 central carbon metabolites (CCM) were quantified in blood plasma. Metabolic signatures were selected through orthogonal projections to latent structures discriminant analysis (OPLS-DA) and principal component analysis (PCA) was conducted to link the profiles of identified metabolites with CHD risk, sleep patterns, cardiometabolic traits and cardiac electrophysiologic parameters. Results: Using OPLS-DA, we identified 40 metabolites (variable influence on projection >1) that were altered in CHD patients, with 38 lipids, including 25 triacylglycerols (TAGs), 8 diacylglycerols (DAGs), being elevated and two CCM metabolites (i.e., succinic acid and glycolic acid) being reduced. Using PCA, four principal components (PCs) were identified and associated with increased risk of CHD. Specifically, one standard unit increasement in the PC that was characterized by high levels of DAG (18:1) and low succinic acid and the PC that was characterized by high levels of two sphingomyelins [SM (26:0) and SM (24:0)] was associated with 21% [odds ratio (OR) = 1.21, 95% CI: 1.02,1.43] and 14% (OR = 1.14,1.02,1.29) increased risk of CHD, respectively. Further regression analyses confirmed that the identified metabolites and the four PCs were positively associated with TG and ALT. Interestingly, glycolic acid was negatively associated with sleep quality and PSQI. Participants with night sleep mode tended to have a high level of the identified lipids, especially FFA (20:4). Conclusion: In the present pilot study, our findings provide clues on alterations of lipid and energy metabolism in CHD patients without traditional risk factors, with multiple triacylglycerols and diacylglycerols metabolites seemingly elevated and certain nonlipids metabolites (e.g., succinic acid and glycolic acid) decreased in cases. Considering the limit sample size, further studies are warranted to confirm our results.

Abstract Background Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy is frequently used off‐label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available to guide such therapy. We performed a meta‐analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab. Methods We conducted a systematic review in accordance with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review. The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values. Results A total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09–0.21) and median progression‐free survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9–10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti‐PD‐1/PD‐L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19–0.33). There were no new safety signals observed in this study. Conclusion Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti‐PD‐1/PD‐L1 therapy. Implication for Practice Patients with metastatic renal cell carcinoma have limited treatment options after progressive disease on anti‐PD‐1/PD‐L1 therapy. The role of salvage nivolumab and ipilimumab in this patient population is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs. This information will be beneficial to guide clinical decision‐making and accurately estimating toxicity.

In the post-pandemic era, the need for accessible urban green open spaces has increased. There is an urgent need to accurately identify large-scale unit-affiliated green spaces and focus on the potential for open sharing. Therefore, using POI data from the Gaode map of Shanghai obtained via web crawler, combined with remote sensing image data and the current green space data, the subjects of unit-affiliated green spaces in the main urban area and five new towns of Shanghai were identified in 2021. On this basis, in-depth explorations were carried out in terms of the type and number of subjects, the overall layout, and the grading of potential open sharing. A new application path for identifying subjects of unit-affiliated green spaces based on the POI data was established. The analysis of the potential openness of the subjects strongly supports the open sharing of unit-affiliated green spaces; the open sharing of unit-affiliated green spaces can compensate for the deficiencies in the fairness and efficiency of urban green spaces.

The internal defect detection of magnetic tile is extremely significant before mounting. Currently, this task is completely realized by manual operation in the magnetic tile manufacturing industry, which results in inefficiency and diseconomy. In this work, we develop an intelligent system based on the acoustic sound for internal defect detection of magnetic tile to overcome these drawbacks. Due to the non-Gaussian and non-stationary characteristics of the acoustic sound, adopting the single modality of the data for internal defect detection of magnetic tile cannot achieve good accuracy. Therefore, we design a multimodal fusion convolutional neural network (MMFCNN) for internal defect detection of magnetic tile. We train the network in an end-to-end way. Our proposed MMFCNN consists of three blocks, i.e., feature extraction block, feature fusion block and internal defect detection block, whose purposes are to extract features from generated modal data, fuse multimodal feature maps and analyze whether the magnetic tile has internal defects, respectively. Moreover, to realize the information interaction and emphasize more representative information at feature extraction stage, we propose a novel attention mechanism, i.e., cross-attention mechanism. Extensive experimental results demonstrate our proposed MMFCNN is effective for internal defect detection of magnetic tile. Our code is available at https://github.com/Clarkxielf/Multimodal-Fusion-Convolutional- Neural-Network-for-Internal-Defect-Detection-of-Magnetic-Tile.

Background. There are very few professional recommendations or guidelines on the needle thoracentesis decompression (NTD) for the tension pneumothorax in the elderly. This study aimed to investigate the safety and risk factors of tension pneumothorax NTD in patients over 75 years old based on CT evaluation of the chest wall thickness (CWT). Methods. The retrospective study was conducted among 136 in-patients over 75 years old. The CWT and closest depth to vital structure of the second intercostal space at the midclavicular line (second ICS-MCL) and the fifth intercostal space at the midaxillary line (fifth ICS-MAL) were compared as well as the expected failure rates and the incidence of severe complications of different needles. We also analyzed the influence of age, sex, presence or absence of chronic obstructive pulmonary disease (COPD), and body mass index (BMI) on CWT. Results. The CWT of the second ICS-MCL was smaller than the fifth ICS-MAL both on the left and the right side (P

Microexpressions are very transitory expressions lasting about 1/25∼1/2 s, which can reveal people’s true emotions they try to hide or suppress. The PREMERT (pseudorandom ecological microexpression recognition test) could test the individual’s microexpression recognition ability with six microexpression Ms (the mean of accuracy rates of a microexpression type under six expression backgrounds), and six microexpression SDs (the standard deviation of accuracy rates of this microexpression type under six expression backgrounds), but it and other studies did not explore the general microexpression recognition ability (the GMERA) or could not test the GMERA effectively. Therefore, the current study put forward and established the GMERA with the behavioral data of the PREMERT. The spontaneous brain activity in the resting state is a stable index to measure individual cognitive characteristics. Therefore, the current study explored the relevant resting-state brain activity of the GMERA indicators to prove that GMERA is an individual cognitive characteristic from brain mechanisms with the neuroimaging data of the PREMERT. The results showed that (1) there was a three-layer hierarchical structure in human microexpression recognition ability: The GMERA (the highest layer); recognition of a type of microexpression under different expression backgrounds (the second layer); and recognition of a certain microexpression under a certain expression background (the third layer). A common factor GMERA was extracted from the six microexpression types recognition in PREMERT. Four indicators of the GMERA were calculated from six microexpression Ms and six microexpression SDs, such as GMERAL (level of GMERA), GMERAF (fluctuation of GMERA), GMERAB (background effect of GMERA), and GMERABF (fluctuation of GMERAB), which had good parallel-forms reliability, calibration validity, and ecological validity. The GMERA provided a concise and comprehensive overview of the individual’s microexpression recognition ability. The PREMERT was proved as a good test to measure the GMERA. (2) ALFFs (the amplitude of low-frequency fluctuations) in both eyes-closed and eyes-opened resting-states and ALFFs-difference could predict the four indicators of the GMERA. The relevant resting-state brain areas were some areas of the expression recognition network, the microexpression consciousness and attention network, and the motor network for the change from expression backgrounds to microexpression. (3) The relevant brain areas of the GMERA and different types of microexpression recognition belonged to the three cognitive processes, but the relevant brain areas of the GMERA were the “higher-order” areas to be more concise and critical than those of different types of microexpression recognition.

Idiopathic short stature (ISS) is the most common clinical cause of the short stature with an unclear aetiology and a lack of effective treatment. Circular RNAs have been shown to play a significant regulatory role through various signal transduction pathways in a variety of diseases in recent years. However, the role of circular RNAs on ISS is not yet well-understood and requires a special attention. The differentially expressed circular RNAs were screened by microarray chip analysis, and RT-qPCR was used to verify the expression of hsa_circ_0008870 in ISS patients. Subsequently, in vitro and in vivo experiments were conducted to determine the biological functions of hsa_circ_0008870 in ISS. The authors first confirmed that hsa_ circ_0008870 was downregulated in ISS children. Meanwhile, we also observed that the downregulated hsa_circ _0008870 significantly inhibited chondrocyte proliferation and endochondral ossification in vivo and in vitro. Mechanistically, hsa_circ_0008870 regulates MAPK1 expression by sponge miR-185-3p. This mechanism of action was further verified through rescue experiments. Finally, the authors revealed that the silencing of hsa_circ_0008870 induces low expression of MAPK1 by impairing the sponge action of miR-185-3p, thereby inhibiting chondrocyte proliferation, hypertrophy, and endochondral ossification, which results in a short stature phenotype. In addition to these, we also observed an interesting phenomenon that upregulated of miR-185-3p can in turn inhibit the expression of hsa_circ_0008870 in chondrocytes. This suggests that hsa_circ_0008870 could potentially serve as a therapeutic target for the treatment of ISS.

Object detection in images captured by unmanned aerial vehicles (UAVs) holds great potential in various domains, including civilian applications, urban planning, and disaster response. However, it faces several challenges, such as multi-scale variations, dense scenes, complex backgrounds, and tiny-sized objects. In this paper, we present a novel scale-adaptive YOLO framework called SMFF-YOLO, which addresses these challenges through a multi-level feature fusion approach. To improve the detection accuracy of small objects, our framework incorporates the ELAN-SW object detection prediction head. This newly designed head effectively utilizes both global contextual information and local features, enhancing the detection accuracy of tiny objects. Additionally, the proposed bidirectional feature fusion pyramid (BFFP) module tackles the issue of scale variations in object sizes by aggregating multi-scale features. To handle complex backgrounds, we introduce the adaptive atrous spatial pyramid pooling (AASPP) module, which enables adaptive feature fusion and alleviates the negative impact of cluttered scenes. Moreover, we adopt the Wise-IoU(WIoU) bounding box regression loss to enhance the competitiveness of different quality anchor boxes, which offers the framework a more informed gradient allocation strategy. We validate the effectiveness of SMFF-YOLO using the VisDrone and UAVDT datasets. Experimental results demonstrate that our model achieves higher detection accuracy, with AP50 reaching 54.3% for VisDrone and 42.4% for UAVDT datasets. Visual comparative experiments with other YOLO-based methods further illustrate the robustness and adaptability of our approach.

Transshipment hubs are important components of the global container shipping network. Nowadays, hybrid ports are emerging, handling both gateway and transshipment container traffic depending on their significant maritime connectivity. Effectively identifying transshipment hubs, including traditional transshipment hubs with high transshipment incidences and hybrid ports with sufficient transshipment capabilities, is crucial to gain a good understanding of container shipping networks. The method of reinforced structural holes (RSHs) has been introduced from the sociology to detect transshipment hubs at the global level, as it can fully consider the existence of separated cohesive port communities. The results show that the RSH-based approach is feasible to identify those hubs playing the role of bridges across different port communities worldwide, which is demonstrated from the perspective of maritime connectivity. The higher ranked hubs with higher RSH values generally have better maritime connections with ports from various port communities. Several policy implications have been further elaborated for relevant decision makers, such as liner companies and port operators.

It is important to detect foodborne pathogens in food and water, such as Listeria monocytogenes (L.monocytrogenes), which can cause foodborne illness in people with compromised immune systems. Volatile organic compounds (VOC) and 3‑hydroxy-2-butanone (3H-2B) produced by L.monocytrogenes can be used as biomarkers for indirect detection of microbial contamination. In this study, the mesoporous ZnO@CO3O4 nanosphere was prepared through the simple hydrothermal synthesis method of ZIF-l-Zn@Co, the cage construction of mesoporous ZnO@CO3O4 nanosphere was remained unchanged after the calcination of the ZIF-l-Zn@Co at 600 °C for 2 h in air. The mesoporous ZnO@CO3O4 nanosphere was selected as the gas sensor showed the strongest response to 3H-2B, and 7–12 times higher than the response of other test gases. In addition, compared with ZnO and Co3O4 single metal oxide gas sensor, the ZnO@CO3O4 sensor possessed better repeatability and stability after repeated repeatability tests under the same conditions.

The applications of human extended pluripotent stem cells (which can form both embryonic and extraembryonic lineages) demand a xeno-free culture condition; here, the authors provide a chemically defined and xeno-free culture system to do so.

Abstract Background Severe hypercalcemia is often associated with uncontrolled malignancy through several mechanisms. However, calcitriol-mediated hypercalcemia is a rare etiology for advanced solid tumors. Case presentation We report a case of calcitriol-mediated hypercalcemia secondary to immune checkpoint inhibition in a responder with metastatic clear cell renal cell carcinoma (ccRCC). In this case, a 68 year old male with metastatic ccRCC to the liver within 4 months of right radical nephrectomy went on to develop hypercalcemia (12.8 mg/dL) shortly following 2 cycles of nivolumab and ipilimumab. Additional testing showed an elevated calcitriol level (142 pg/mL), low parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) levels, and a normal 25-hydroxyvitamin D level. FDG-PET imaging showed hypermetabolic mediastinal, hilar, and intra-abdominal lymphadenopathy, however the subsequent lymph node biopsy only showed reactive lymphoid cells without malignancy or granuloma. The hypercalcemia was resistant to initial therapy with calcitonin, hydration, and zoledronic acid but quickly responded to high-dose prednisone (1 mg/kg), followed by normalization of calcitriol levels. The patient was rechallenged with nivolumab and ipilimumab which provided a partial response after 4 cycles. He was maintained on low dose prednisone (10 mg daily) leading to a sustained resolution of his hypercalcemia. Conclusion This case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event.

The use of advanced preclinical models has become increasingly important in drug development. This is particularly relevant in bladder cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (chemotherapy, radiotherapy, immunotherapy, and/or surgery) are largely absent. Patient-derived and clinically relevant models including patient-derived xenografts (PDX), organoids, and conditional reprogramming (CR) of cell cultures efficiently generate numerous models and are being used in both basic and translational cancer biology. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have utilized CR technology to conduct bladder cancer research.

Abstract Background Cannabis, an important industrial crop, has a high sensitivity to photoperiods. The flowering time of cannabis is one of its important agronomic traits, and has a significant effect on its yield and quality. The CONSTANS-like (COL) gene plays a key role in the regulation of flowering in this plant. However, the specific roles of the COL gene family in cannabis are still unknown. Results In this study, 13 CsCOL genes were identified in the cannabis genome. Phylogenetic analysis implied that the CsCOL proteins were divided into three subgroups, and each subgroup included conserved intron/exon structures and motifs. Chromosome distribution analysis showed that 13 CsCOL genes were unevenly distributed on 7 chromosomes, with chromosome 10 having the most CsCOL members. Collinearity analysis showed that two syntenic gene pairs of CsCOL4 and CsCOL11 were found in both rice and Gossypium raimondii. Of the 13 CsCOL genes, CsCOL6 and CsCOL12 were a pair of tandem duplicated genes, whereas CsCOL8 and CsCOL11 may have resulted from segmental duplication. Furthermore, tissue-specific expression showed that 10 CsCOL genes were preferentially expressed in the leaves, 1 CsCOL in the stem, and 2 CsCOL in the female flower. Most CsCOL exhibited a diurnal oscillation pattern under different light treatment. Additionally, sequence analysis showed that CsCOL3 and CsCOL7 exhibited amino acid differences among the early-flowering and late flowering cultivars. Conclusion This study provided insight into the potential functions of CsCOL genes, and highlighted their roles in the regulation of flowering time in cannabis. Our results laid a foundation for the further elucidation of the functions of COL genes in cannabis.

BackgroundAlthough sleep quality is clearly associated with job burnout as shown in the existing research, the mechanism underpinning such relationship remains undefined. This work, thus, aimed to assess the current situation of sleep quality and burnout in Chinese psychiatric nurses, and to analyze the relationships between sleep quality, burnout and coping style, in order to provide possible targets to enhance mental health and wellbeing among psychiatric nurses.MethodThis cross-sectional study was carried out in seven rehabilitation centers located in four different regions of China. The Pittsburgh Sleep Quality Index, the Epworth Sleeping Scale, the Maslach Burnout Inventory General Survey, and the Coping Style Questionnaire were distributed to 853 nurses in various mental hospitals, with a total of 664 participants being recruited in the final research.ResultsThe results of this current study showed a high prevalence of sleep disorders and burnout in Chinese psychiatric nurses. Moreover, emotional exhaustion (r = 0.456), cynicism (r = 0.323) and negative coping style (r = 0.191) in nurses were all positively correlated with total Pittsburgh Sleep Quality Index (PSQI) score, while professional efficacy (r = −0.079) and positive coping style (r = −0.140) were negatively correlated with total PSQI score. More interestingly, of all negative coping strategies, we found that self-blame had the most significant effect (β = 0.156).ConclusionsThe above results showed that coping style mediates the association of poor sleep quality with job burnout in Chinese psychiatric nurses. This study claimed that there is an urgent need to development the coping skills to sustain a healthy work life for nurses.

In this paper, an electrochemical sensing platform based on gold nanoparticle modified carbon nanofiber (CNF@AuNPs) as working electrode is proposed for the high sensitivity and selective determination of metronidazole. Meanwhile, the sensor has a large linear response range from 0.1 to 2000 μM, the limit of detection for metronidazole (MNZ) is as low as 0.024 μM. The sensor is simple to prepare and reproducible, and it shows good results in MNZ analysis of tap water.

Study ObjectivesThe purpose of this study was to determine the effects of daytime transcranial direct current stimulation (tDCS) on sleep electroencephalogram (EEG) in patients with depression.MethodsThe study was a double-blinded, randomized, controlled clinical trial. A total of 37 patients diagnosed with a major depression were recruited; 19 patients (13 females and 6 males mean age 44.79 ± 15.25 years) received tDCS active stimulation and 18 patients (9 females and 9 males; mean age 43.61 ± 11.89 years) received sham stimulation. Ten sessions of daytime tDCS were administered with the anode over F3 and the cathode over F4. Each session delivered a 2 mA current for 30 min per 10 working days. Hamilton-24 and Montgomery scales were used to assess the severity of depression, and polysomnography (PSG) was used to assess sleep structure and EEG complexity. Eight intrinsic mode functions (IMFs) were computed from each EEG signal in a channel. The sample entropy of the cumulative sum of the IMFs were computed to acquire high-dimensional multi-scale complexity information of EEG signals.ResultsThe complexity of Rapid Eye Movement (REM) EEG signals significantly decreased intrinsic multi-scale entropy (iMSE) (1.732 ± 0.057 vs. 1.605 ± 0.046, P = 0.0004 in the case of the C4 channel, IMF 1:4 and scale 7) after tDCS active stimulation. The complexity of the REM EEG signals significantly increased iMSE (1.464 ± 0.101 vs. 1.611 ± 0.085, P = 0.001 for C4 channel, IMF 1:4 and scale 7) after tDCS sham stimulation. There was no significant difference in the Hamilton-24 (P = 0.988), Montgomery scale score (P = 0.726), and sleep structure (N1% P = 0.383; N2% P = 0.716; N3% P = 0.772) between the two groups after treatment.ConclusionDaytime tDCS changed the complexity of sleep in the REM stage, and presented as decreased intrinsic multi-scale entropy, while no changes in sleep structure occurred. This finding indicated that daytime tDCS may be an effective method to improve sleep quality in depressed patients. Trial registration This trial has been registered at the ClinicalTrials.gov (protocol ID: TCHIRB-10409114, in progress).

According to the development status of various security services for mobile applications,the mainstream mobile application security detection and monitoring technology was studied.Based on the concept of full life cycle management in software industry,a variety of security concepts and security technologies were reasonably integrated into each stage of the whole life cycle of mobile applications.Based on this,a mobile application lifecycle management platform with comprehensive security functions and multi system cooperation was designed and constructed.