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Abstract Parkinson’s disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra. Despite progress, the pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as a promising model for studying PD, drug screening, and potential treatments. This review discusses the development of hMLOs, their application in PD research, and current challenges in organoid construction, highlighting possible optimization strategies.

Background Successful liberation from mechanical ventilation is one of the most crucial processes in critical care, because it is the first step through which a respiratory failure patient begins to transition out of the intensive care unit, and return to normal life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider scientific and systematic approaches, as well as the individual experiences of healthcare professionals. Recently, numerous studies have investigated methods and tools to identify when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians for liberation from the ventilator. Methods Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. These evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved the recommendations. Results Recommendations for nine questions on ventilator liberation about Population, Intervention, Comparator, and Outcome (PICO) are presented in this document. This guideline presents seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusion We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Abstract Background The representativeness of cohort studies compared to nationwide data is a major concern. This study evaluated the similarity and seasonality of causative respiratory viruses for chronic obstructive pulmonary disease (COPD) and asthma exacerbations between retrospective multicenter cohort study and nationwide data. Methods We compared data from the retrospective multicenter cohort study with Korean Influenza and Respiratory Surveillance System data between 2015 and 2018. Correlation, dynamic time warping (DTW), and seasonal autoregressive integrated moving average (SARIMA) analyses were performed. Results Spearman correlation coefficients [ρ] indicated very strong (respiratory syncytial virus [RSV] [ρ = 0.8458] and influenza virus [IFV] [ρ = 0.8272]), strong (human metapneumovirus [HMPV] [ρ = 0.7177] and parainfluenza virus [PIV] [ρ = 0.6742]), and moderate (rhinovirus [RV] [ρ = 0.5850] and human coronavirus [HCoV] [ρ = 0.5158]) correlations. DTW analyses showed moderate (PIV) and high (IFV, RSV, and HMPV) synchronicity between the two datasets, while RV and HCoV showed low synchronicity. SARIMA analyses revealed 12-month seasonality for IFV, RSV, PIV, and HMPV. The peak season was winter for RSV and IFV, spring to summer for PIV, and spring for HMPV. Conclusions This was the first study to report the synchronicity between a retrospective multicenter cohort study of viruses that can cause COPD or asthma exacerbations and nationwide surveillance system data.

Electric vehicle (EV) is more environmental-friendly than gasoline vehicle because the main power is not petrol. For the heating system, the waste heat generated by engines is recycled to heat the cabin of gasoline ones, while the EV need extra electric energy consumption for heating the cabin which decreases the driving range. Personal comfort system (PCS) has been reported that it is an alternative technique to improve occupant thermal comfort and indirectly save building heating energy. This study aims to investigate the occupants’ thermal sensation under four heating modes in the EV cabin in winter, including no heating, only PCS, only air conditioning, and both air conditioning and PCS. The field survey is conducted in a parked EV with 12 subjects. Three thermal comfort indexes (PMV, SET*, and operative temperature Top) are used and assessed for their applicability in the thermal environment of the EV. Results show that the thermal environment in the cabin is non-uniform and dynamic with the air conditioning mode, while the PCS mode just slightly affects the temperature differences inside. Meanwhile, the subjects’ thermal sensations cannot maintain neutral or warmer under the PCS mode only. The results of PMV are lower than the subjects’ actual thermal sensation votes (TSV), while the results of SET* and Top show significant linear relationships with the TSV for the correlation coefficients above 0.80. Compare to the air conditioning mode, the neutral SET* and neutral Top are decreased by 2.7 °C and 1.6 °C under the mode with PCS and air conditioning, respectively. The findings indicate that PCS not only has a positive effect on improving the cabin environment and occupant's thermal sensation but also has the potential to lower the setting temperature of air conditioner of EVs in winter.

Musk deer (Moschus spp.) are widely known for its musk and are globally endangered as a result of poaching, habitat loss, and fragmentation. To facilitate restoration of the alpine musk deer (M. chrysogaster) in existing areas, reliable estimates of population size and influencing factors are essential to assess effectiveness of conservation interventions, particularly for isolated musk deer populations in patches. In this paper, we used line transect and camera trap data collected from 2020 to 2022 in the Helan mountains to assess the population status and characterized the influencing factors of alpine musk deer. Our findings indicate that musk deer are patchily distributed in three areas of high elevation, with the population limited to less than 200 individuals, remaining below historic levels (compared to 1995). There was a significant positive correlation between the role of sympatric species on musk deer, with red fox (Vulpes vulpes), badger (Meles meles) and blue eared-pheasant (Crossoptilon auritum) having a significant effect on the out-modeled pathway. Variable but insignificant effects of anthropogenic activities were observed across all species categories, which could be due to mutual adaptation over time. Our results imply that the recovery of sensitive population in island-like habitats remains challenging and may be exacerbated by limited environment and resources. Our study underscores the necessity of establishing ecological corridors to enhance habitat connectivity for alpine musk deer, undertaking conservation genetics research on isolated populations, controlling stray dogs to maintain interspecific balance, and implementing electronic fencing to mitigate human disturbance and resource competition. This study provides basic information for understanding the population status of alpine musk deer and offers insights for conservation efforts.

Abstract Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p

Background Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P

Abstract Disaster information content is an objective mapping of disaster situations, social response, and public opinions. Social response to emergency is an important mechanism for implementing and guaranteeing emergency management of major natural hazard-related disasters. Understanding how disaster information content affects social response to emergencies is helpful for managing risk communication and efficient disaster response. Based on the 2008 freezing-rain and snowstorm disasters in southern China, this study used Python to extract 7,857 case-related media reports and applied natural language processing for text analysis. It used three typical cases to identify and analyze disaster media report content and the relationship between these reports and the social response to the emergency. Eight categories of disaster response—such as prewarning and forecasting, announcements by the authorities, and social mobilization—appeared in the disaster information in the media, along with disaster impact information, that is, real-time disaster status. Disaster response information and an appropriate amount of disaster impact information played important roles in prewarning, disaster relief, public opinion guidance, and social stability maintenance and can serve important functions in communicating with all stakeholders of emergency management, assisting or influencing emergency departments or individuals in decision making, and eliminating “information islands.” Empathy caused the general public to become “disaster responders” through receiving information. Rumors and an excess of negative information may have a perverse amplification effect on public opinion and increase the unpredictability of the disaster situation and the risk of social crisis.

Ship detection in synthetic aperture radar (SAR) images is crucial in both civilian and military fields, offering extensive application prospects. Nonetheless, owing to the distinctive characteristics of SAR imaging, this task confronts numerous challenges. Specifically, ships with high aspect ratios, dense arrangements and small sizes in complex environments frequently yield in suboptimal positioning effects, consequently impacting detection performance. In response to the challenges in ship target detection, this article introduces a novel approach, termed Inner-alpha-CIOU (IA-CIOU), that relies on an enhanced intersection over union (IOU). Primarily, the method introduces Inner IOU, which effectively regulates generation of auxiliary bounding boxes through scale factor r. This ensures a better fit for dimensions of ship target frames, thereby enhancing target detection performance as well as expediting model convergence. Subsequently, this method introduces Alpha IOU, enhancing robustness of small-size ship targets in complex backgrounds by adjusting α. This allows the detector to achieve greater flexibility in ship regression accuracy. Following numerous experimental validations, proposed algorithm consistently outperforms on both SAR-Ship-Dataset, MSAR-1.0 dataset, and SAR ship detection dataset (SSDD) dataset. This groundbreaking innovation not only possesses immeasurable practical worth, but also introduces a fresh perspective together with enlightening insights for future research efforts.

Accurate and efficient wildlife monitoring is essential for conservation efforts. Traditional image-based methods often struggle to detect small, occluded, or camouflaged animals due to the challenges posed by complex natural environments. To overcome these limitations, an innovative multimodal target detection framework is proposed in this study, which integrates textual information from an animal knowledge base as supplementary features to enhance detection performance. First, a concept enhancement module was developed, employing a cross-attention mechanism to fuse features based on the correlation between textual and image features, thereby obtaining enhanced image features. Secondly, a feature normalization module was developed, amplifying cosine similarity and introducing learnable parameters to continuously weight and transform image features, further enhancing their expressive power in the feature space. Rigorous experimental validation on a specialized dataset provided by the research team at Northwest A&F University demonstrates that our multimodal model achieved a 0.3% improvement in precision over single-modal methods. Compared to existing multimodal target detection algorithms, this model achieved at least a 25% improvement in AP and excelled in detecting small targets of certain species, significantly surpassing existing multimodal target detection model benchmarks. This study offers a multimodal target detection model integrating textual and image information for the conservation of rare and endangered wildlife, providing strong evidence and new perspectives for research in this field.

Studying the mechanisms by which climate change interacted with human societies during the historical period can provide historical insights and cultural roots for climate policy building in the region. In this study, we constructed Stability-Robustness-Resilience Model (SSR model) and used the TOPSIS method (Technique for Order Preference by Similarity to Ideal Solution) and the entropy weight method to assess the change processes of robustness, resilience, and stability of Ming's society in response to climate threats. We have also compared three extreme droughts that occurred in different periods of social robustness-resilience combinations by using the SRR model. The results are as follows. (1) The stability of the Ming society was high in YongLe - HongZhi period (1402–1505 CE), when both social robustness and resilience were higher than the average level of Ming Dynasty (0.5611 for the former and 0.4215 for the latter), but there was a significant decline in social stability in TianShun period (1457–1464 CE). In ZhengDe - ChongZhen period (1506–1644 CE), the stability of Ming society gradually decreased, and it rebounded shortly in the LongQing-WanLi period (1506–1620 CE). (2) The high stability benefited from higher socio-economic levels, better government finance levels, larger national food reserves, safer social environments (high robustness), and higher levels of ruling class governance and risk response (high resilience); whereas insecure social environment induced by war, declining socio-economic levels and government finance levels were the main reasons for the decline in society's stability. (3)The ChengHua and WanLi droughts both happened at a time with high social robustness, so although their meteorological anomalies were severe, their impact on society was small. While the JiaJing drought happened at a time with low social robustness and resilience, so although the meteorological anomaly was relatively weak, it resulted in a more severe social consequence than the other two events.

Myostatin (Mstn) was reported to be involved in multiple biological processes including the regulation of skeletal muscle growth, lipid metabolism and reproduction in vertebrates, therefore, it might play an essential role in the fine balance between growth and reproduction. In order to clarify the roles of Mstn in fish reproduction, we systematically investigated the gonadal development and fertility of mstnb mutants in Nile tilapia (Orochromis niloticus). In the present study, mstnb was found to be expressed in the different cell types of gonads by fluorescence in situ hybridization (FISH). Mutation of mstnb resulted in excessive proliferation of phase II follicles in the ovaries while the numbers of phase III follicles were significantly reduced at 210 days after hatching (dah). Interestingly, significant decline of cyp19a1a gene expression, the serum 17β-estradiol (E2), vitellogenin (VTG) were detected at 210 dah. At 360 dah, the ovarian development of mstnb-/- XX tilapia was partially recovered and female fish spawn regularly, however, they were subfertile and produced the poor-quality eggs with significantly lower offspring survival rate. The dramatic up-regulation of cyp19a1a gene expression and serum E2 level at 360 dah might account for the recovery of ovarian development. In mstnb-/- males, excessive proliferation of spermatogonia and retardation of testicular differentiation were found throughout the whole development stages. In mstnb-/- males, evident declines of gonadosomatic index (GSI), cyp11b2 gene expression, and 11-Ketotestosterone (11-KT) were detected at 210 dah, while the mRNA level of cyp11b2 and serum 11-KT level were significantly upregulated at 360 dah. However, mstnb-/- males were infertile since mutation of mstnb gene led to excessive increase of apoptosis of testicular cells and spermiation obstacle. Taken together, these results indicated that Mstn might be an essential regulator for the maintenance of fish fertility.

Introduction Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient’s family and significantly affects the patient’s quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS.Methods and analysis PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software.Ethics and dissemination Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal.PROSPERO registration number CRD42022359208.

With the development of integrated energy system, energy flow analysis of coupling energy network has attracted much attention. In this study, based on the unified energy path theory, energy flow analysis of electricity-heating coupled energy system is implemented considering different time characteristic of each system. Considering the instantaneous change process of heat transfer in the heating system, the dynamic model of heat network is constructed based on unified energy path theory. On this basis, the dynamic models of electric and heating systems are coupled, and the dynamic energy flow calculation method of the coupling system is proposed. Through a case study, the feasibility of the proposed model and calculation method are verified. In addition, the effect of heat source on the dynamic process of heat transfer in the heating system is analyzed.

Considering the volatility and randomness of renewable energy, the integrated demand response (IDR) has proved to be an efficient way to solve the imbalance problem between the supply and demand sides. To manage the flexible loads of customers, as an intermediate participant, the residential load aggregator (RLA) is introduced, which can provide a motivational measure to attract customers to participate in electric and heating IDR. In this study, an incentive-based reward mechanism (RM) is proposed for a RLA based on classified residential customers, to obtain the best bidding contracts in the load market. A novel multi-objective optimization model is developed and calculated by an NSGA-II artificial algorithm maximizing profits of the RLA and customers simultaneously. The customers’ profit is described as the monetization of dissatisfaction degree considering both psychology and comfort aspects. Furthermore, to demonstrate the practicality and advantage of the RM, the price-based IDR mechanism is also included in the numerical study for comparison. According to the simulation results, although both RM-based and price-based responses have their own advantages and disadvantages on various performances, the RM performs better since it can reduce more energy demand and save more costs for end-users.

PurposeComparing the outcomes of video-laryngoscopy and flexible fiberoptic bronchoscopy for endotracheal intubation in patients with cervical spine immobilization.MethodsAll of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 8 Jan 2024 were included. All outcomes were analyzed using Review Manager 5.4. The primary outcomes were the successful first-attempt intubation rate, intubation time, heart rate after intubation, mean arterial pressure after intubation, overall intubation success rate, risk of tissue damage and sore throat.ResultsThe meta-analysis included six randomized controlled studies with a total of 694 patients. The outcomes of the meta-analysis revealed that the use of video laryngoscopy was better than flexible fiberoptic bronchoscopy in terms of the successful first-attempt intubation rate (P0.05) between the video laryngoscopy and flexible fiberoptic bronchoscopy groups.ConclusionsCompared with flexible fiberoptic bronchoscopy, video laryngoscopy has superior tracheal intubation performance in terms of the first-attempt success rate and intubation speed. This finding was observed in patients with cervical spine immobilization who utilized a cervical collar to simulate a difficult airway. Additionally, both types of scopes demonstrated similar complication rates. Current evidence suggests that video laryngoscopy is better suited than flexible fiberoptic bronchoscopy for endotracheal intubation in patients immobilized with a cervical collar.Trial registrationSystematic review protocol: CRD42024499868.

Human life is affected by the intensity of near-surface wind fields， so obtaining high-precision wind field meteorological live products is essential. Precise and accurate wind field simulation can provide data support for real-time weather products. At present， the spatial-temporal resolution of the mesoscale model is low， which cannot meet the requirement of local fine-scale simulation. In this study， based on the large eddy simulation （LES） nested in the medium-scale Weather Research and Forecast Model （WRF）， we simulated the near-surface wind field in the eastern part of the Mentougou region， which has five layers of two-way nesting. Meanwhile， combined with ground meteorological observation， we designed sensitivity experiments of boundary layer and Subgrid-Scale （SGS） models to compare the effects of YSU and LES boundary layer schemes on inner layer nesting at 1 km resolution， and examined and evaluated the applicability of different SGS models in the real atmosphere. The results show that the YSU boundary layer can perform better simulation than the LES boundary scheme when turned on at the mesoscale transition resolution of 1 km， with fewer errors and the ability to capture turbulence details. In the different SGS models sensitivity experiments （1.5TKE， SMAG， 1.5TKE_NBA and SMAG_NBA）， there is little difference in the NBAs. SMAG had the slightest root-mean-square error and the highest correlation coefficient for statistical indicators. However， the wind speed simulation of four models still underestimates the high value and overestimates the low value.SMAG is closest to the observation in the wind vector distribution and probability density distribution of the wind. In the instantaneous spatial distribution of the wind field， SMAG_NBA shows a competitive advantage in capturing fine turbulence.

Abstract The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an immunologically active site. Meningeal immunity has emerged as a key factor in modulating proper brain function and social behavior, performing constant immune surveillance of the CNS, and participating in several neurological diseases. However, it remains to be determined how meningeal immunity contributes to CNS physiology and pathophysiology. With the advances in single-cell omics, new approaches, such as single-cell technologies, unveiled the details of cellular and molecular mechanisms underlying meningeal immunity in CNS homeostasis and dysfunction. These new findings contradict some previous dogmas and shed new light on new possible therapeutic targets. In this review, we focus on the complicated multi-components, powerful meningeal immunosurveillance capability, and its crucial involvement in physiological and neuropathological conditions, as recently revealed by single-cell technologies.

Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.

Currently, the visual detection of a target’s shock flow field through background schlieren technology is a novel detection system. However, there are very few studies on the long-distance background schlieren imaging mechanism and its application in system design in the field of target detection. This paper proposes a design optimization method for space-based BOS detection system metrics. By establishing sensitivity evaluation models and image signal-to-noise ratio evaluation models for BOS detection systems, the influence of the different flight parameters and key parameters of BOS systems (detection spectral bands and spatial resolution) on target detection efficiency is explored. Furthermore, an optimization method based on the image signal-to-noise ratio of the BOS system and the overall metrics for specific scenarios are provided. The simulation results demonstrate that under satellite background images and speckle background images, the system metrics can detect and identify the schlieren of high-speed targets, with better applicability to disordered and complex real background images. This research contributes to advancing the development of high-speed target detection technology based on BOS.

Parkinson’s disease: genetic risk factors in a Korean population A whole-genome sequencing study of Korean individuals with Parkinson’s disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to larger DNA deletions. PD is the second most prevalent neurodegenerative disease globally, but most studies have focused on SNVs in European populations. Using whole-genome sequencing, Ji-Hye Oh at the University of Ulsan, Seoul, South Korea, and co-workers were able to identify genetic differences between PD patients and healthy controls, including deletions, gains, and several new SNVs. In particular, deletions of small non-coding regions that regulate gene expression may be key contributors to PD. These results provide a whole-genome perspective on genetic risk factors for PD in a Korean population, and illuminate how a whole-genome sequencing approach may be helpful in identifying genetic factors underlying other diseases.

A co-benefits assessment index system is developed for the introduction of a regional integrated energy system (RIES). Following which, by analyzing the interest demands of each stakeholder and determining the beneficiaries of each unit benefit, the initial benefit distribution model based on attribution relationship is established. According to the networked relationship of stakeholders, a fair and reasonable cost sharing mechanism for RIES is established. On this basis, the benefit–cost (B/C) analysis is carried out from various stakeholders to evaluate the commercial feasibility. According to the simulation results of a numerical study, the project as a whole and all stakeholders have B/C values greater than 1 to coordinate and balance related issues such as system income distribution according to the designed benefit distribution mechanism. In this way, the win-win situation of overall interests and individual interests can be realized.

(1) Background: This study explored the optimal energy level in advanced virtual monoenergetic images (VMI+) from dual-energy computed tomography angiography (DE-CTA) for adrenal veins visualization before adrenal venous sampling (AVS). (2) Methods: Thirty-nine patients were included in this prospective single-center study. The CT value, noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in both adrenal veins and abdominal solid organs and were then compared between VMI+ within the range of 40–80 kiloelectron volt (keV). The visualization rate of the adrenal veins and the overall image quality of solid organs were subjectively compared among different keV VMI+. The AVS success rate was recorded for 20 patients. (3) Results: For the adrenal veins, 40 keV VMI+ had the peak CT value, noise and CNR (p < 0.05). Subjectively, the visualization rate was the highest at 40 keV (100% for the right adrenal vein, and 97.4% for the left adrenal vein) (p < 0.05). For solid organs, the CT value, noise and CNR at 50 keV were lower than those at 40 keV (p < 0.05), but the SNR was similar between 40 keV and 50 keV. The overall subjective image quality of solid organs at 50 keV was the best (p < 0.05). The AVS success rate was 95%. (4) Conclusions: For VMI+, 40 keV was the preferential energy level to obtain a high visualization rate of the adrenal veins and a high success rate of AVS, while 50 keV was the favorable energy level for the depiction of abdominal organs.

The Brillouin scattering spectrum has been used to investigate the properties of a liquid medium. Here, we propose an improved method based on the double-edge technique to obtain the Brillouin spectrum of a liquid. We calculated the transmission ratios and deduced the Brillouin shift and linewidth to construct the Brillouin spectrum by extracting the Brillouin edge signal through filtered double-edge data. We built a detection system to test the performance of this method and measured the Brillouin spectrum for distilled water at different temperatures and compared it with the theoretical prediction. The observed difference between the experimental and theoretical values for Brillouin shift and linewidth is less than 4.3 MHz and 3.2 MHz, respectively. Moreover, based on the double-edge technique, the accuracy of the extracted temperatures and salinity is approximately 0.1 °C and 0.5%, respectively, indicating significant potential for application in water detection and oceanography.

Abstract Background Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. Case presentation Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. Conclusion These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Abstract Background LINC00173 had been reported as a cisplatin (cis-diamminedichloroplatinum, DDP) chemotherapy-resistant inducer in small-cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). This study aimed to display reverse data for LINC00173 as a DDP chemosensitivity-inducing factor in lung adenocarcinoma (LUAD). Methods LINC00173 was screened from the Gene Expression Omnibus database (GSE43493). The expression level of LINC00173 in LUAD tissues and cell lines was detected using in situ hybridization and quantitative reverse transcription–polymerase chain reaction. Colony formation, cell viability, half-maximal inhibitory concentration, flow cytometry, and xenograft mouse model were used to evaluate the role of LINC00173 in the chemosensitivity of LUAD to DDP. The mechanism of LINC00173 in DDP resistance by mediating miR-1275/PROCA1/ZFP36L2 axis to impair BCL2 mRNA stability was applied, and co-immunoprecipitation, chromatin immunoprecipitation, RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays were performed. Results LINC00173 downregulation in patients with DDP-resistant LUAD was correlated with poor prognosis. Further, LINC00173 expression was significantly reduced in DDP-resistant LUAD cells and DDP-treated human LUAD tissues. Suppressed LINC00173 expression in LUAD cells enhanced DDP chemoresistance in vivo and in vitro, while restored LINC00173 expression in DDP-resistant LUAD cells markedly regained chemosensitivity to DDP. Mechanistically, DDP-resistant LUAD cells activated PI3K/AKT signal and further elevated the c-Myc expression. The c-Myc, as an oncogenic transcriptional factor, bound to the promoter of LINC00173 and suppressed its expression. The reduced LINC00173 expression attenuated the adsorption of oncogenic miR-1275, downregulating the expression of miR-1275 target gene PROCA1. PROCA1 played a potential tumor-suppressive role inducing cell apoptosis and DDP chemosensitivity via recruiting ZFP36L2 to bind to the 3′ untranslated region of BCL2, reducing the stability of BCL2 mRNA and thus activating the apoptotic signal. Conclusions This study demonstrated a novel and critical role of LINC00173. It was transcriptionally repressed by DDP-activated PI3K/AKT/c-Myc signal in LUAD, promoting DDP-acquired chemotherapeutic resistance by regulating miR-1275 to suppress PROCA1/ZFP36L2-induced BCL2 degradation, which led to apoptotic signal reduction. These data were not consistent with the previously described role of LINC00173 in SCLC or LUSC, which suggested that LINC00173 could play fine-tuned DDP resistance roles in different pathological subtypes of lung cancer. This study demonstrated that the diminished expression of LINC00173 might serve as an indicator of DDP-acquired resistance in LUAD.

Abstract Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)‐based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene‐assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual‐intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision‐restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.

Shear wave velocity (VS) is a vital prerequisite for rock geophysics. However, due to historical, cost, and technical reasons, the shear wave velocity of some wells is missing. To reduce the deviation of the description of underground oil and gas distribution, it is urgent to develop a high-precision neural network prediction method. In this paper, an attention module is designed to automatically calculate the weight of each part of the input value. Then, the weighted data are fed into the long short-term memory network to predict shear wave velocities. Numerical simulations demonstrate the efficacy of the proposed method, which achieves a significantly lower MAE of 38.89 compared to the LSTM network’s 45.35 in Well B. In addition, the relationship between network input length and prediction accuracy is further analyzed.

In recent years, the synergy between artificial intelligence and turbulence big data has given rise to a new data-driven paradigm in turbulence research. Data-driven turbulence modeling has emerged as one of the forefront directions in fluid mechanics. Most existing studies focus on feature construction, selection, and the development of modeling frameworks, often overlooking the practical deployment and application of trained models. This paper examines the entire process from model construction to real-world deployment, using data-driven turbulence modeling for high Reynolds number flows over complex three-dimensional configurations as a case study. Key stages include data generation, input-output feature construction, model training, model compilation and optimization, deployment, and validation. We successfully implemented the entire workflow in a heterogeneous supercomputing environment and, through mixed programming techniques, integrated the resulting turbulence model into the Platform for Hybrid Engineering Simulation of Flows (PHengLEI) open-source software framework. This allowed for mixed-precision simulations, with the main equations solved in double precision and the turbulence model in half precision. The new computational framework was validated through large-scale parallel numerical simulations on grids with tens of millions of elements for three-dimensional complex configurations. The results highlight the efficiency of our model deployment, with overall computational efficiency improving by 13.35% and the turbulence model’s solution speed increasing by approximately 3.9 times. The accuracy of the computations was also confirmed, with the average relative error in the lift and drag coefficients calculated by the data-driven turbulence model within 3%. Across various computing nodes, the relative error in the computed aerodynamic coefficients remained within 1%, demonstrating the framework’s scalability. Notably, our contributions have been incorporated as a case study in the latest PHengLEI open-source project ^5 .

Remote sensing image object detection is a challenging task in the field of computer vision due to the complex backgrounds and diverse arrangements of targets in remote sensing images, forming intricate scenes. To overcome this challenge, existing object detection models adopt rotated target detection methods. However, these methods often lead to a loss of semantic information during feature extraction, specifically regarding the insufficient consideration of element correlations. To solve this problem, this research introduces a novel attention module (EuPea) designed to effectively capture inter-elemental information in feature maps and generate more powerful feature maps for use in neural networks. In the EuPea attention mechanism, we integrate distance information and Pearson correlation coefficient information between elements in the feature map. Experimental results show that using either type of information individually can improve network performance, but their combination has a stronger effect, producing an attention-weighted feature map. This improvement effectively enhances the object detection performance of the model, enabling it to better comprehend information in remote sensing images. Concurrently, this also improves missed detections and false alarms in object detection. Experimental results obtained on the DOTA, NWPU VHR-10, and DIOR datasets indicate that, compared with baseline RCNN models, our approach achieves respective improvements of 1.0%, 2.4%, and 1.8% in mean average precision (mAP).

Abstract Background Bronchial artery embolisation (BAE) is an effective treatment option to control haemoptysis in primary lung cancer. However, no studies have investigated optimal embolisation material for BAE in lung cancer patients. Thus, this study aimed to compare the safety and efficacy of BAE performed using n-butyl-2-cyanoacrylate (NBCA) and polyvinyl alcohol (PVA) particles in primary lung cancer patients to determine which embolic material is better for patients with haemoptysis. Methods This retrospective study was approved by the institutional review board, and consent was waived. The rates of hemostasis, complications, procedure time, dose–area product, and haemoptysis-free survival were retrospectively compared between primary lung cancer (non-small cell [n = 111] and small cell [n = 11]) patients who underwent BAE using NBCA (n = 58) or PVA particles (n = 64) between January 2004 and December 2019. Predictors of recurrent haemoptysis were analysed using the Cox proportional hazard regression model. Results Among 122 patients (mean age, 66 ± 10 years; range 32–86 years; 103 men), more patients in the NBCA group (81.0%; 47 of 58) achieved complete hemostasis than did patients in the PVA group (53.1%; 34 of 64) (P = 0.002). No major complications were observed in either group. The procedure time (36.4 ± 21.6 vs. 56.3 ± 27.4 min, P

Solid-state polymer electrolytes are crucial for developing future rechargeable batteries, but they are still limited in performance. Here, the authors designed a topological polymeric solid electrolyte, enabling an all-solid-state high-voltage lithium metal pouch cell to cycle 200 times efficiently.

Abstract Although several studies have identified a distinct gut microbial composition in Parkinson’s disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P

In order to evaluate the hydrological utility of CLDAS-Prcp multi-source fusion precipitation products and the simulation effect of WRF-Hydro model in small and medium-scale watersheds， Firstly CLDAS-Prcp and IMERG-Final multi-source fusion precipitation products are used to analyze the spatial distribution characteristics of cumulative precipitation and the time series change characteristics of hourly rainfall in seven typical flood cases in the Qijiang River basin， then the two products are respectively used to drive the WRF-Hydro models to simulate 7 typical flood cases in the Qijiang River basin.The outputs of the process are analyzed and compared with the measured flow.The results show that： （1） CLDAS-Prcp depicts more details than IMERG-Final in the spatial distribution of accumulated precipitation， and it is more accurate in terms of large-value drop areas and total precipitation； both precipitation products can well describe the change trend of the hourly surface rainfall in the basin during the flood period， and CLDAS-Prcp is closer to the observation data on the peak and the change trend of surface rainfall.（2） Based on the 4 runoff simulations of the CLDAS-Prcp multi-source fusion precipitation product， 3 runoff simulations have a Nash coefficient higher than 0.9， showing excellent performance； among the 4 runoff models based on the IMERG-Final multi-source fusion precipitation product， except for the 20200622 flood event， the Nash coefficients of the other simulations are all lower than 0.7， indicating that the parameter calibration and runoff simulation based on the CLDAS-Prcp fusion precipitation product are superior to the IMERG-Final fusion precipitation product.（3） The WRF-Hydro model is able to simulate the individual flood peak flow， which can accurately reproduces the time when the flood peak appears， and well describe the details of the flood process.In general， the CLDAS-Prcp multi-source fusion precipitation product and the WRF-Hydro model can be well applied in the hydrological simulation of small and medium-scale watersheds.

In this paper, the preparation process condition of chondroitin sulfate chelated zinc was optimized by orthogonal test. Chondroitin sulfate and zinc sulfate were selected as the raw materials, chelating rate of zinc as evaluation index, the effects of pH, reaction time, mass ratio of chondroitin sulfate to zinc sulfate heptahydrate, and reaction temperature on chelating rate of zinc were investigated by single factor test and orthogonal test. The structural characterization of chondroitin sulfate chelated zinc was analyzed by UV spectroscopy, fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric and X-ray diffraction analysis. The bioavailability of zinc irons in chondroitin sulfate chelated zinc was determined by in vitro simulated gastrointestinal digestion and absorption. The results showed that optimal preparation conditions of chondroitin sulfate chelated zinc were as follows: pH4, reaction time was 1 h, mass ratio was 1:1, and reaction temperature was 30 ℃. Under these conditions, chelating rate of zinc was (80.6%±1.31%). UV spectrum combined with Fourier infrared spectrum analysis showed that chondroitin sulfate chelated zinc was formed by zinc ions combine with hydroxyl, carboxyl, sulfonic groups in chondroitin sulfate. Scanning electron microscopy and X-ray diffraction analysis showed that the micromorphology of chondroitin sulfate chelated zinc was microparticles with crystal structure. Thermogravimetric analysis proved that thermal stability of chondroitin sulfate chelated zinc was better than that of chondroitin sulfate. In vitro simulated gastrointestinal digestion and absorption analysis showed that the bioavailability of chondroitin sulfate chelated zinc was better than that of inorganic zinc salt. The research results would provide theoretical basis and technical support for the development of new zinc supplements.

Background/Aims There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. Methods International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. Results Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% vs. 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016. Conclusions There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Background We evaluated the long-term effects of domiciliary noninvasive positive-pressure ventilation (NIPPV) used to treat patients with chronic obstructive pulmonary disease (COPD). Methods Databases were searched to identify randomized controlled trials of COPD with NIPPV for longer than 1 year. Mortality rates were the primary outcome in this meta-analysis. The eight trials included in this study comprised data from 913 patients. Results The mortality rates for the NIPPV and control groups were 29% (118/414) and 36% (151/419), suggesting a statistically significant difference (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.65–0.95). Mortality rates were reduced with NIPPV in four trials that included stable COPD patients. There was no difference in admission, acute exacerbation and quality of life between the NIPPV and control groups. There was no significant difference in withdrawal rates between the two groups (RR, 0.99; 95% CI, 0.72–1.36; p=0.94). Conclusion Maintaining long-term nocturnal NIPPV for more than 1 year, especially in patients with stable COPD, decreased the mortality rate, without increasing the withdrawal rate compared with long-term oxygen treatment.

Background Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

The separation of acetylene and carbon dioxide by porous materials requires delicate control over the pore size. Herein, the authors fine-tune the pore size at sub-nanometer scale in a series of isoreticular metal-organic frameworks to control the acetylene/carbon dioxide separation performance; subtle structural differences lead to remarkable performance enhancement.

IntroductionUnderstanding the underlying mechanisms of microbial community assembly is a fundamental topic in microbial ecology. As an integral part of soil organisms, ectomycorrhizal (EM) fungi play vital roles in ecosystems. Picea crassifolia is an important pine species in the Helan Mountains in Inner Mongolia, China, with high ecological and economic values. However, studies of EM fungal diversity and mechanisms underlying community assembly on this pine species are limited.MethodsIn this study, we investigated EM fungal communities associated with P. crassifolia from 45 root samples across three sites in the Helan Mountains using Illumina Miseq sequencing of the fungal rDNA ITS2 region.ResultsA total of 166 EM fungal OTUs belonging to 24 lineages were identified, of which Sebacina and Tomentella-Thelephora were the most dominant lineages. Ordination analysis revealed that EM fungal communities were significantly different among the three sites. Site/fungus preference analysis showed that some abundant EM fungal OTUs preferred specific sites. Ecological process analysis implied that dispersal limitation and ecological drift in stochastic processes dominantly determined the community assembly of EM fungi.DiscussionOur study indicates that P. crassifolia harbors a high EM fungal diversity and highlights the important role of the stochastic process in driving community assembly of mutualistic fungi associated with a single plant species in a semi-arid forest in northwest China.

Purpose – The intended nationally determined contributions (INDCs) is a major outcome of the Paris Agreement on international cooperation to reduce emissions, and is likely to be the future scenario for carbon emissions. This paper aims to obtain the fine spatial pattern of carbon emissions in 2030, identify hot spots and analyze changes of carbon emissions with a spatial grid method. Design/methodology/approach – Based on the integrated quantified INDCs of each economy in 2030, the authors predict the population density pattern in 2030 by using the statistics of current population density, natural growth rates and differences in population growth resulting from urbanization within countries. Then the authors regard population density as a comprehensive socioeconomic indicator for the top-bottom allocation of the INDC data to a 0.1° × 0.1° grid. Then, the grid spatial pattern of carbon emissions in 2030 is compared with that in 2016. Findings – Under the unconditional and conditional scenarios, the global carbon emission grid values in 2030 will be within [0, 59,200.911] ktCO2 and [0, 51,800.942] ktCO2, respectively; eastern China, northern India, Western Europe and North America will continue to be the major emitters; grid carbon emissions will increase in most parts of the world compared to 2016, especially in densely populated areas. Originality/value – While many studies have explored the overall global carbon emissions or warming under the INDC scenario, attention to spatial details is also required to help us make better emissions attributions and policy decisions from the perspective of the grid unit rather than the administrative unit.

Saccharomyces cerevisiae is the dominant fermentative producer of ethanol in industry and a preferred host for production of other biofuels. That said, rewiring the metabolism of S. cerevisiae to produce other fermentation products, such as isobutanol, remains an academic challenge. Many studies report aerobic production of isobutanol, but ethanol remains a substantial by-product under these conditions due to the Crabtree effect. These studies indicate that the native isobutanol pathway is incapable of carrying sufficient flux to displace ethanol. In this report, we screened a combinatorial library of pathway enzymes to identify an isobutanol pathway cassette capable of supporting the growth of a non-ethanol producing S. cerevisiae. We began by identifying a diverse set of isobutanol pathway enzyme homologs and combined each open reading frame with varied-strength promoters in a combinatorial, pooled fashion. We applied a growth-coupled screen where a functional isobutanol pathway restored NAD+ regeneration during glucose catabolism that is otherwise repressed via the Crabtree effect. Using this screen, we isolated a cassette consisting of a mosaic of bacterial and cytosol-localized fungal enzymes that conferred under aerobic conditions the ability to produce 364 mg/L isobutanol (8.8% of the theoretical maximum yield). We next shifted the cofactor usage of the isolated ketol-acid reductoisomerase enzyme in the cassette from NADPH to NADH-preferring to improve redox balance. The approach used herein isolated isobutanol producing strains that approach the best in the literature without producing substantial ethanol titers. Still, the best isolated cassette was insufficient to support anaerobic growth in the absence of ethanol fermentation - indicating the presence of further fundamental gaps in our understanding of yeast fermentation.

BackgroundSteroid hormones play an essential role in many reproductive processes of vertebrates. Previous studies revealed that teleost-specific Cyp17a2 (cytochrome P450 family 17 subfamily a 2) might be required for the production of cortisol in the head-kidney and 17α,20β-dihydroxy-4-pregnen-3-one (DHP) in ovary during oocyte maturation. However, the role of Cyp17a2 in male reproduction remains to be largely unknown. The aim of this study was to explore the essentiality of cyp17a2 gene in male steroidogenesis, spermatogenesis, and male fertility.MethodsA homozygous mutation line of cyp17a2 gene was constructed in tilapia by CRISPR/Cas9 gene editing technology. The expression level of germ cell and meiosis-related genes and steroidogenic enzymes were detected by qRT-PCR, IHC, and Western blotting. EIA and LC-MS/MS assays were used to measure the steroid production levels. And sperm quality was examined by Sperm Quality Analyzer software.ResultsIn this study, cyp17a2 gene mutation resulted in the significant decline of serum DHP and cortisol levels. On the contrary, significant increases in intermediate products of cortisol and DHP were found in cyp17a2-/- male fish. The deficiency of cyp17a2 led to the arrest of meiotic initiation in male fish revealing as the reduction of the expression of germ cell-related genes (vasa, piwil, oct4) and meiosis-related genes (spo11 and sycp3) by 90 dah. Afterwards, spermatogenesis was gradually recovered with the development of testis in cyp17a2-/- males, but it showed a lower sperm motility and reduced fertility compared to cyp17a2+/+ XY fish. Deletion of cyp17a2 led to the abnormal upregulation of steroidogenic enzymes for cortisol production in the head-kidney. Moreover, unaltered serum androgens and estrogens, as well as unchanged related steroidogenic enzymes were found in the testis of cyp17a2-/- male fish.ConclusionThis study proved that, for the fist time, Cyp17a2 is indispensable for cortisol and DHP production, and cyp17a2 deficiency associated curtailed meiotic initiation and subfertility suggesting the essentiality of DHP and cortisol in the male fertility of fish.

Introdução: O câncer colorretal (CCR) é o segundo mais incidente e, quando metastático, apresenta taxa de sobrevida de 14% em cinco anos. Regorafenibe é um inibidor de tirosina-quinase (ITQ) aprovado para CCR metastático (CCRm) com aumento comprovado de sobrevida global (SG). Objetivo: Explorar resultados de eficácia e segurança de regorafenibe em pacientes com CCRm e características de bom prognóstico (CBP). Método: Análise de subgrupo do estudo CORRECT, com participantes divididos de acordo com CBP, seguindo os critérios: Eastern Cooperative Oncology Group (ECOG) 0, tempo de doença metastática maior que 18 meses, até três sítios metastáticos e ausência de metástase hepática. Eficácia comparada com teste de log-rank estratificado e hazad ratios (HR) calculados com o modelo de Cox. Resultados: Dos 760 participantes randomizados, 292 (34,5%) apresentavam CBP; 185 (63,4%) receberam regorafenibe; 107 (35,6%), placebo. Para o grupo CBP, a mediana SG foi 10,9 meses (IC95%:8,8-12,3) para regorafenibe e 7,3 meses (IC95%:5,6-9,1) para placebo, com 39% de redução no risco de morte (HR 0,61; IC95%:0,43-0,88; p=0,0069). A mediana de sobrevida livre de progressão (SLP) foi de 3,5 meses (IC95%:3,0-3,9) versus 1,8 mês (IC95%:1,7-1,8) respectivamente, com 61% de redução no risco de progressão da doença ou morte (HR 0,39; IC95%:0,30-0,52; p

Introduction: The tyrosine kinase inhibitors regorafenib and cabozantinib remain the mainstay in second-line treatment of advanced hepatocellular carcinoma (HCC). There is currently no clear evidence of superiority in efficacy or safety to guide choice between the two treatments. Methods: We conducted an anchored matching-adjusted indirect comparison using individual patient data from the RESORCE trial of regorafenib and published aggregate data from the CELESTIAL trial of cabozantinib. Second-line HCC patients with prior sorafenib exposure of >3 months were included in the analyses. Hazard ratios (HRs) and restricted mean survival time (RMST) were estimated to quantify differences in overall survival (OS) and progression-free survival (PFS). Safety outcomes compared were rates of grade 3 or 4 adverse events (AEs) occurring in >10% of patients, and discontinuation or dose reduction due to treatment-related AEs. Results: After matching adjustment for differences in baseline patient characteristics, regorafenib showed a favorable OS (HR, 0.80 [95% CI: 0.54, 1.20]) and ~3-month longer RMST over cabozantinib (RMST difference, 2.76 months [95% CI: −1.03, 6.54]), although not statistically significant. For PFS, there was no numerical difference in HR (HR, 1.00 [95% CI: 0.68, 1.49]) and no clinically meaningful difference based on RMST analyses (RMST difference, −0.59 months [95% CI: −1.83, 0.65]). Regorafenib showed significantly lower incidence of discontinuation (risk difference, −9.2% [95% CI: −17.7%, −0.6%]) and dose reductions (−15.2% [95% CI: −29.0%, −1.5%]) due to treatment-related AEs (any grade). Regorafenib was also associated with lower incidence (not statistically significant) of grade 3 or 4 diarrhea (risk difference, −7.1% [95% CI: −14.7%, 0.4%]) and fatigue (−6.3% [95% CI: −14.6%, 2.0%]). Conclusion: This indirect treatment comparison suggests, relative to cabozantinib, regorafenib could be associated with favorable OS (not statistically significant), lower rates of dose reductions and discontinuation due to treatment-related AEs, and lower rates of severe diarrhea and fatigue.

Non-contact and non-destructive polarization 3D imaging uses a passive, single-frame array image to calculate 3D information, making it possible to obtain high-precision 3D information about tunnel cracks, and offering outstanding technical advantages. Based on the introduction of the principle of crack detection with polarization 3D imaging, a tunnel lining crack detection plan was developed and a detection equipment was designed. The method and process of polarization 3D imaging for lining crack detection are described in detail. A model of the impact of the tunnel environment on 3D detection and a method for obtaining absolute information have been established to obtain high-precision 3D information about cracks. In a real tunnel environment, tests were conducted to detect wide cracks, narrow cracks, and artificial cracks. The crack detection accuracy with respect to the crack width was 0.2–0.3 mm, and with respect to crack length was 0.2–0.3 mm. At the same time, crack depth information could be obtained. The present research results can provide technical support for the application of polarization 3D imaging in tunnel crack detection.