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Abstract Objective To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. Methods A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children’s Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. Results Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636–0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759–0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741–0.884). Conclusion We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Lumbar disc herniation (LDH) is a prevalent condition that severely impacts patients' quality of life and work capacity. Traditional surgical treatments like laminectomy, while effective, involve significant invasiveness and potential complications, including long-term spinal instability and recurrent symptoms. With the advancement of minimally invasive techniques, percutaneous endoscopic lumbar discectomy (PELD) has become a popular option due to its reduced trauma and faster recovery. However, PELD, while beneficial, carries risks, including complications that may not be immediately evident. This report presents the case of a 60-year-old female patient who underwent PELD for L4/5 disc herniation but experienced significant postoperative complications, including increased pain and neurological symptoms. Initial conservative management failed, and further investigations suggested possible postoperative infection, though this was later ruled out through surgical exploration and bacterial cultures. The patient subsequently underwent open surgical exploration, which revealed extensive tissue damage and required additional interventions, including a minimally invasive lateral anterior approach for stabilization and fusion (MIS-OLIF). Postoperative recovery was successful, with complete symptom resolution and stable spine alignment at a six-month follow-up. This case highlights the complexity of managing PELD-related complications and underscores the importance of thorough diagnostic evaluation and the potential need for additional surgical interventions to ensure long-term patient outcomes.

The capabilities of 23 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 were evaluated for six extreme precipitation indices from 1961 to 2010 using interannual variability and Taylor skill scores in the Yellow River Basin and its eight subregions. The temporal variations and spatial distributions of extreme precipitation indices were projected from 2021 to 2050 under the shared socioeconomic pathway scenarios (SSP2–4.5 and SSP5–8.5). The results show that most GCMs perform well in simulating extreme values (1-day maximum precipitation (RX1day) and 5-day maximum precipitation (RX5day)), duration (consecutive dry days), and intensity index (simple daily intensity index (SDII)), and perform poor in simulating the threshold indices (precipitation on very wet days (R95p) and number of heavy precipitation days (R10mm)). The projected changes in extreme precipitation indicate that under the SSP2-4.5 scenario, future extreme precipitation will increase by 15.7% (RX1day), 15.8% (RX5day), 30.3% (R95p), 1d (R10mm), and 6.6% (SDII), respectively, decrease by 2.1d (CDD). The aforementioned changes are further enhanced under the SSP5-8.5 scenario. Extreme precipitation changes widely in Hekou Town to Longmen, in the northeastern part of the region from Longmen to Sanmenxia, below Huayuankou, and in the interflow basin. HIGHLIGHTS The study evaluated the biases of 23 global climate models (GCMs) from observations and the spatial distribution of the biases.; Interannual variability score, Taylor diagram, and Taylor skill score were used to evaluate CMIP6 GCMs.; The future changes of the Yellow River Basin and its subregions extreme precipitation under SSP2-4.5 and SSP5-8.5 scenarios were projected by using six ETCCDI indices.;

Background: 8-oxoguanine DNA glycosylase can maintain genomic stability and integrity. However, it can interfere with the regular DNA damage repair process, possibly leading to the development of cancer and various other human diseases when its activity becomes abnormal. Current methods for detecting 8-oxoguanine DNA glycosylase activity often suffer from low sensitivity, time-consuming procedures, labor-intensive requirements, and the need for specialized equipment and trained professionals for execution. Consequently, there is an urgent need for a portable, user-friendly 8-oxoguanine DNA glycosylase assay that offers swift results and supports real-time testing. Results: We've developed a PERFUME method that combines primer exchange reaction and functionalized G-quadruplex/hemin DNAzyme for sensitive detection of Fpg, a typical 8-oxoguanine DNA glycosylase. Utilizing a single probe and T4 Polynucleotide Kinase (PNK) simplifies the experiment to a one-step reaction at 37 °C in 3 h, reducing sample consumption and improving sensitivity. We chose functionalized hemin cofactors, significantly improving catalytic efficiency and enhancing detection capability. This biosensor detects Fpg activity with a sensitivity as low as 0.11 U mL−1, displaying exceptional sensitivity, selectivity, and interference resistance in human serum and bacterial cell extracts under isothermal conditions. The biosensor demonstrates remarkable selectivity and ability for Fpg inhibitors screening. In addition, this biosensor enables reading the sample's RGB values using a smartphone, facilitating accurate quantification of Fpg activity without the necessity for specialized equipment. Significance: PERFUME simplifies Fpg detection by using a single hairpin and PNK in a one-step process. We utilize FUME to enhance catalytic efficiency, it surpassing the performance of traditional G-quadruplex/hemin DNAzyme methods. This approach excels in analyzing Fpg in human serum and bacterial extracts. It allows quantitative Fpg detection using UV–Vis and smartphones under isothermal conditions, making it valuable for clinical diagnosis.

Abstract Single image super-resolution (SISR) refers to the reconstruction from the corresponding low-resolution (LR) image input to a high-resolution (HR) image. However, since a single low-resolution image corresponds to multiple high-resolution images, this is an ill-posed problem. In recent years, generative model-based SISR methods have outperformed conventional SISR methods in performance. However, the SISR methods based on GAN, VAE, and Flow have the problems of unstable training, low sampling quality, and expensive computational cost. These models also struggle to achieve the trifecta of diverse, high-quality, and fast sampling. In particular, denoising diffusion probabilistic models have shown impressive variety and high quality of samples, but their expensive sampling cost prevents them from being well applied in the real world. In this paper, we investigate the fundamental reason for the slow sampling speed of the SISR method based on the diffusion model lies in the Gaussian assumption used in the previous diffusion model, which is only applicable for small step sizes. We propose a new Single Image Super-Resolution with Denoising Diffusion GANS (SRDDGAN) to achieve large-step denoising, sample diversity, and training stability. Our approach combines denoising diffusion models with GANs to generate images conditionally, using a multimodal conditional GAN to model each denoising step. SRDDGAN outperforms existing diffusion model-based methods regarding PSNR and perceptual quality metrics, while the added latent variable Z solution explores the diversity of likely HR spatial domain. Notably, the SRDDGAN model infers nearly 11 times faster than diffusion-based SR3, making it a more practical solution for real-world applications.

Abstract Thermoelectric (TE) generation is becoming a valuable and promising research direction. Many researchers have carried out system analysis and performance optimization of thermoelectric technologies based on the generalized thermoelectric energy balance equations. However, it is assumed that TE legs have no heat exchange with the ambient except at the junctions of the hot and cold ends where heat flows in and out. Based on basic thermoelectric effects and fundamental theories of heat transfer, a detailed derivation of the revised generalized thermoelectric energy equations considering convective heat transfer between TE legs and the ambient has been carried out. Irreversible heat transfer processes have been analyzed by employing energy analysis based on the first law of thermodynamics and exergy analysis based on the second law of thermodynamics. The results show that convective heat transfer leads to a decrease in both energy and exergy efficiencies: the rate and magnitude of the decrease in exergy efficiency are greater than those of the decrease in energy efficiency. The exergy efficiency is relatively high despite the low energy efficiency in operation, revealing the features and advantages of thermoelectric generators (TEGs) in low‐grade energy utilization. For TEG efficient operation, the load resistance value should match the system's internal resistance, or at least be greater than that, to avoid a sharp drop in power output and efficiencies. In an attempt at theoretical analysis, the concept of entransy was first introduced into thermoelectric analysis, yielding two concise relational equations which reflect the intrinsic link between Carnot cycle efficiency, energy efficiency, exergy efficiency, and entransy flow transfer efficiency. The entransy analysis based on the index of entransy flow transfer efficiency, together with energy analysis and exergy analysis, may be a novel and valuable guideline for the operation and optimization of TEGs, which needs to be further investigated.

The relationship between the protective performance of flexible polymer material and material parameters (elastic modulus, viscosity coefficient) is explored, an impact collision motion equation between two bodies is established from the viscoelastic material constitutive, and the relationship between the kinematic response and the material parameters is obtained. Based on the Kelvin constitutive model, a theoretical model for impact between the protective body and the protected body is established, then the dynamic response is obtained. The feasibility of the model was verified by drop hammer experiment, and the material parameters (elastic modulus, viscosity coefficient) were obtained by formula. The model is discretized and the relationship between local impact response and material parameters is analyzed. The discussion results on the relationship between the impact response and the protective material performance indicate that adjusting the elastic modulus, viscosity coefficient, and thickness of the protective material can effectively improve protective effect.

Oil spill pollution seriously endangers human and ecosystem health. Therefore, it is urgent to develop oil-absorbing materials to effectively remove oil spill pollution. Among the traditional oil-absorbing materials, natural organic adsorption material has low oil absorption capacity and hydrophilicity; inorganic adsorption materials are difficult to recover and have low oil absorption efficiency and high price; and although the synthetic organic adsorbent has outstanding oil absorption capacity, its biodegradation is poor. Silica aerogel (SA) has the characteristics of high porosity, low density, and high specific surface area, which make it an excellent oil-absorbing material. However, the hydrophilic surface and pearl necklace structure of SA limit its wide applications in the oil absorption field. Hydrophobically modified hydrophobic silica aerogel (HSA) has not only excellent SA characteristics but also good hydrophobic/lipophilic properties. In this paper, focusing on HSA preparation by surface posttreatment modification and coprecursor modification, the research progress on these two methods combined with supercritical drying and ambient pressure drying is systematically introduced, and the advantages and disadvantages of the two methods are analyzed and summarized. The coprecursor modification is mainly combined with a supercritical drying process to prepare HSA, while the surface posttreatment modification is often combined with an ambient pressure drying process. Both methods normally use silylating agents as hydrophobic modifiers. The surface posttreatment modification does not change the formed pore structure, and the pore size and particle size of HSA are relatively uniform. However, the modification process of surface posttreatment is long, the solvent consumption is large, and the cost is high. In addition, incomplete internal modification may be a problem. In the coprecursor modification method, wet gel is formed and modified simultaneously, shortening the modification time and saving costs. The prepared HSA of coprecursor modification has a larger specific surface area and better hydrophobicity, but its pore size is uneven, and the introduced hydrophobic groups are limited. Excessive silylating agents affect the sol–gel process of HSA. In addition, the current methods for strengthening HSA mechanical properties and the research progress on HSA oil absorption properties are reviewed. Finally, based on the current development of HSA as oil-absorbing materials, the development direction of these materials is discussed, for example, developing low-cost and eco-friendly raw materials, shortening the hydrophobic modification process, preparing bulk HSA, strengthening the mechanical properties, and improving the oil-absorbing properties of HSA.

Abstract Non‐viral vector chimeric antigen receptor (CAR)‐T cells have garnered increasing attention due to their ability to efficiently eradicate cancer cells while mitigating undesirable side effects. However, the current methods for engineering chimeric antigen receptor T (CAR‐T) cells employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution to these challenges, triggering transitory expression of CARs in T cells via messenger RNA (mRNA) has emerged as a promising strategy. Currently, electroporation is a common method used to introduce the mRNA encoding the CAR into the T cells. Moreover, there has been increasing attention on the exploration of innovative mRNA delivery systems, including lipid, polymer‐based nanoparticle, exosomes and peptide transduction domains. Additionally, we also explored the functions of different types of mRNA in mRNA‐based CAR‐T cell therapy. The auxiliary mRNA, exemplified by systems such as megaTAL and nuclease transposon systems, demonstrates its capacity to extend CAR‐T cell viability and survival. This perspective offers the current state of mRNA‐based CAR‐T cell therapy and provides valuable insights into future research avenues.

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross-complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P>0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple-negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han-Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer.

Abstract Cloud lifecycles are influenced by interactions among clouds and mixing with cloud‐free environments. Cloud shapes dictate the length of cloud boundaries, which affects these interactions. This study uses a large eddy simulation to examine the relationships between the shallow cumulus cloud shapes, processes at their boundaries, and lifecycles. To characterize the shape of clouds, two metrics are newly defined: one reflects the overall horizontal cloud shape, and the other defines the cloud edge irregularity. Simulated clouds experience increased irregularity, but little changes in aspect ratio. Irregularity‐driven cloud perimeter growth strongly indicates cloud splitting, with a more pronounced effect than aspect ratio‐driven perimeter growth. Smaller cloud‐shell gradients of properties across cloud boundaries are associated with more irregular clouds, suggesting enhanced mixing of clouds with the cloud‐free environment. These findings indicate that the shallow cumulus evolution is partly driven by the irregularity of the cloud edge through lateral mixing and cloud splitting.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Abstract Objective We aimed to explore the application of three‐dimensional (3D) quantitative scoring of endolymphatic hydrops (EH) based on gadolinium‐contrast MRI in both the diagnosis and differential diagnosis of Ménière's disease (MD). Methods Local threshold method based on signal intensities was used to quantitatively measure volumes, and the degree of EH was scored by 3D quantitative scoring. The receiver‐operating characteristic (ROC) curve was used to compare the diagnostic efficacy of this method against conventional evaluation methods. The scores of MD, sudden sensorineural hearing loss (SSNHL), delayed endolymphatic hydrops (DEH), and vestibular migraine (VM) group were compared and correlated with clinical examination results, including pure tone audiometry (PTA), electrocochleogram, and caloric test. Results The sensitivity and specificity of 3D quantitative scoring were 94.1% and 92.2%, while conventional evaluation methods were 84.3% and 88.2%, respectively. Cochlear score (CR), vestibular score (VR), semicircular canal score (SR), and total scores (TR) in MD group were significantly higher than those in SSNHL group. The rate of diagnosis of MD was significantly higher in the MD group (92.2%) than VM group (27.3%). In MD, PTA was significantly correlated with CR and SR, the ratio of summating potential to action potential (‐SP/AP) of electrocochleogram was significantly correlated with CR, VR, and SR, also canal paresis (CP) value of caloric test was significantly correlated with SR. Conclusion 3D quantitative scoring demonstrated better diagnostic efficacy than conventional evaluation methods for Ménière's disease, and it may be an effective clinical tool to distinguish MD from SSNHL and VM. The clinical practicality of inner ear‐enhanced MRI was further confirmed. Level of Evidence IV.

Abstract Solid‐state thermoelectric (TE) devices offer many interesting features compared with other methods of generation, such as no moving parts, high reliability, low maintenance, and straightforward integration with other heating equipment. In this study, a thermoelectric assembly was integrated into a residential heating boiler to convert a portion of combustion heat to electricity while meeting space and/or water heating needs. A prototype was developed, in which recently developed thermoelectric modules were incorporated into a gas‐fired boiler. The electricity generated by the thermoelectric assembly would be sufficient to power the electrical auxiliary components of the heating system. In this way, the heating system could operate entirely on fuel combustion and provide the consumer with heating system reliability and a reduction in power consumption. A model for the thermoelectric conversion system was established and the thermal resistance analysis was carried out to show the influence of heat transfer coefficients and other parameters on power output and efficiency, and thus improve the system design. In this study, the single‐module integrated assembly can produce a 22.5 W power output. However, each module of the four‐/eight‐module integrated assembly can only generate a power output of 7.85/9.175 W on average. The performance of a single module in a multimodule assembly is worse than that of a single module assembly. The number of modules placed on the furnace wall is not as many as possible but has an optimal value. In this experimental environment, the assembly of eight modules is the optimal choice. Furthermore, it is found that enhancing combustion‐side heat transfer capacity is an effective way to promote system performance. The power output of the assembly composed of four modules will increase by 70% from 7.85 to 13.5 W due to the installation of the fin on the hot end.

Abstract Uncertainties associated with the response of shallow clouds to global warming remain a great challenge for climate projection. Due to the small size of these clouds, parameterizations are required to represent them in both current‐ and next‐generation climate models. We present a quantitative evaluation of several important assumptions used in both mass‐flux and Assumed‐PDF Higher‐Order Closure parameterizations of shallow convection. We use large‐eddy simulations (LESs) of four different shallow convection regimes as benchmarks and apply a qt (total moisture)–w (vertical velocity) quadrant analysis technique to identify the “coherent structures” of moist and dry up/down‐drafts. The statistics of these coherent structures and the environment are then used to evaluate commonly used assumptions in mass‐flux parameterizations related to (a) the convective downdrafts and (b) the subplume variability of convective updrafts. For quantitative evaluation of the PDF closure used in AP‐HOCs, we perform offline calculations with the PDF closure used in the Cloud Layers Unified By Bi‐normals and the Simplified Higher‐Order Closure schemes by supplying the closure with statistical quantities directly calculated from the LESs. Then, the impact of parameterization assumptions embedded in the PDF closure in the same two categories is analyzed and understood through comparisons of the output from the closure with the statistics of the moist and dry up/down‐drafts from the LESs.

Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.

Spleen micro-perfusion level can be evaluated by DDVD (diffusion derived vessel density): DDVD (unit: au/pixel) = Sb0/ROIarea0 – Sb2/ROIarea2, where Sb0 and Sb2 refer to the spleen signal when b is 0 or 2 (s/mm2) and ROI is ‘region-of-interest’. This study investigated whether spleen DDVD is altered in patients with viral hepatitis-b (VHB) liver fibrosis. Three datasets were retrospectively analysed. Shenzhen data-1 had 25 healthy volunteers and 15 VHB liver fibrosis patients. Changsha data had 24 healthy volunteers and 31 patients with VHB liver fibrosis. Shenzhen data-2 had 67 healthy volunteers. Shenzhen data-2 were measured by reader-1. Shenzhen data-1 were measured by reader-1 and reader-2. For Changsha data, reader-1 measured all subjects, while Reader-2 measured a random selection of 10 healthy volunteers and two patients from each liver fibrosis grade (total=8). Shenzhen data-2 showed in healthy volunteers there was no age-dependent change of spleen DDVD during 20 ∼71 years old, and women had higher spleen DDVD values than those of men's (16.17±7.34 vs. 12.88±5.91, p=0.04). Changsha data by reader-1 showed patients with liver fibrosis had lower spleen DDVD values than those of healthy volunteers (median=16.24 vs. 23.54, p=0.0031). Results of reader-2 showed the same trend (median=11.64 vs. 23.33, p=0.0165). Shenzhen data-1 measured by reader-1 showed medians of spleen DDVD for patients and volunteers were 8.535 and 12.33 respectively; and those measured by reader-2 were 13.89 and 14.31 respectively. We conclude that diffusion MRI shows spleen DDVD, i.e., micro-circulation per volume tissue, is decreased in VHB liver fibrosis patients.

Objective: Programmed cell death protein-1 (PD-1) inhibitors are widely u sed for the treatment of hepatocellular carcinoma (HCC). Thyroid dysfunction is common in patients treated with this therapy, although the dynamic changes in thyr oid function and sonographic features remain unclear. Methods: We analyzed 38 patients with HCC who received anti-PD-1 therap y at our hospital. Demographic, clinical, laboratory, and ultrasound data were extracted from electronic medical records. The grading of thyroid nodules was based on the American College of Radiology Thyroid Imaging Reporting and Data System classification. Statistical analyses were performed using GraphPad Prism 5.0. Results: Fifteen patients (40%) had hypothyroidism, among which six had hypothyroidism at baseline, three had overt hypothyroidism, and six had subcli nical hypothyroidism after anti-PD1 therapy. The proportion of patients with euthyro id function and thyroid antibody positivity was significantly lower than that of patient s with thyroid dysfunction (10% vs 39%, P < 0.05). Nine patients (24%) had irregular echo patterns on s onographic imaging, six of whom had irregular echo patterns present during the treatment, but only one had them persist until the end of treatment. At baseline, t he classification of most thyroid nodules was grade 3, with a significant increase in grade 4A and 4B classifications during treatment, though most nodules remained grade 3 at the e nd of treatment. There were no significant differences in survival rates between t he euthyroid and thyroid dysfunction groups. Conclusion: Anti-PD-1 therapy-induced thyroid dysfunction was accompanied by changes in thyroid function, antibodies, and ultrasonography. Therefore, in patients receiving anti-PD-1 therapy, close, dynamic monitoring of thyroid function, antibodies, and ultrasonographic characteristics is necessary.

With the rapid development of industrialization and human civilization, the soil polluted by heavy, toxic lead is becoming increasingly severe worldwide. Thus, it is imperative to control soil pollution due to lead. In this paper, the background, status, and harm of lead-polluted soil were introduced, and the source, mode of occurrence, and extraction of lead from the soil were depicted in detail. Based on the current soil remediation technology, three major methods, namely, physical, chemical, and bioremediation, have been systematically reviewed, and their advantages and disadvantages from the aspects of efficiency, applicability, and economy were evaluated and compared. Results reveal that the most preferred remediation method for heavy, toxic, lead-contaminated soil is chemical remediation. The chemical leaching and immobilization/stabilization methods were subsequently introduced in detail, and the remediation mechanism, effect, applicability, and application prospect of the different types of eluants and curing agents were evaluated and discussed. Finally, the prospect of cleaning and efficient remediation of heavy, toxic, lead-contaminated soil was presented. The restoration should minimize the damage to the soil. For the heavy, lead-contaminated soil, the development of the joint remediation technology is the potential development direction. The mechanism of soil remediation and directional remediation should be determined as soon as possible. Meanwhile, the research and development of multifunctional composite materials should be strengthened.

A small change in the mean climate may lead to a dramatic change in the frequency and intensity of extreme climate events. In this study, the relationship between mean temperature (MT) and extreme precipitation and the influence from large-scale circulation were investigated in Hunan Province. The correlation between MT and the frequency of extreme precipitation events in different seasons (spring, summer, and autumn) and time periods (1960–2009) was used to obtain pairs of spatial patterns by the singular value decomposition method. The temporal expansion series displayed a consistent trend of temperature and extreme precipitation, and a mutation was observed to occur approximately during the 1980s–1990s. Temperature exhibited a warming trend after the mutation, but the frequency of extreme precipitation events exhibited obvious spatio-temporal variations. The causes of seasonal differences in the frequency of extreme precipitation events were determined by comparing interdecadal changes in three atmospheric circulation factors (850 hPa winds, the entire layer of vapor transportation fluxes and vapor flux divergence) before and after the mutation was revealed. HIGHLIGHTS The relationship between temperature and extreme rainfall events was investigated using the SVD method.; The temperature exhibited a sudden change during the 1980s–1990s.; The trend of temperature change was widely varied.; The correlation between temperature and extreme rainfall exhibited a significant spatial variation.; The wind anomaly field revealed the opposite trends before and after the abrupt change.;

Abstract Developing urban land surface models for modeling cities at high resolutions needs to better account for the city‐specific multi‐scale land surface heterogeneities at a reasonable computational cost. We propose using an encoder‐decoder convolutional neural network to develop a computationally efficient model for predicting the mean velocity field directly from urban geometries. The network is trained using the geometry‐resolving large eddy simulation results. Systematic testing on urban structures with increasing deviations from the training geometries shows the prediction error plateaus at 15%, compared to errors sharply increasing up to 35% in the null models. This is explained by the trained model successfully capturing the effects of pressure drag, especially for tall buildings. The prediction error of the aerodynamic drag coefficient is reduced by 32% compared with the default parameterization implemented in mesoscale modeling. This study highlights the potential of combining computational fluid dynamics modeling and machine learning to develop city‐specific parameterizations.

The aim of this study is to evaluate the performance of the Global Climate Model (GCM) of the Coupled Model Intercomparison Project Phase 6 (CMIP6) in historical simulations of temperature and precipitation. The goal is to select the best performing GCMs for future projection of temperature and precipitation in the Second Songhua River Basin under multiple shared socioeconomic pathways (SSPs). Interannual variability skill (IVS) and Taylor diagrams are used to evaluate the spatiotemporal performance of GCMs against temperature and precipitation data published by the China Meteorological Science Commons during 1956–2016. In addition, five relatively independent models are selected to simulate the temperature and precipitation for 2021–2050 using Hierarchical Clustering. The selected models are CMCC-ESM2, EC-Earth3-Veg-LR, IPSL-CM6A-LR, MIROC-ES2L, and MPI-ESM1-2-HR. The projected results find that SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios show an increasing trend of future annual mean temperature and precipitation. However, for annual precipitation, there is a mixed state of increase and decrease among different models on the seasonal scale. In general, future temperature and precipitation changes still show a trend of growth and uneven distribution in the Second Songhua River Basin, which may be further accelerated by human activities.

Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed by an adenine residue in TR RNA and is dependent on the DGR-encoded reverse transcriptase (bRT) and accessory variability determinant (Avd ), but is VR-independent. We also find that the catalytic center of bRT plays an essential role in site-specific cleavage of TR RNA for cDNA priming. Adenine-specific mutagenesis occurs during reverse transcription and does not involve dUTP incorporation, indicating it results from bRT-catalyzed misincorporation of standard deoxyribonucleotides. In vivo assays show that this hybrid RNA-cDNA molecule is required for mutagenic transposition, revealing a unique mechanism of DNA hypervariation for microbial adaptation.

Sinocyclocheilus wenshanensis is a cyprinid fish species endemic to Southwestern China. In this study, we first sequenced and characterized the complete mitochondrial genome (mitogenome) of S. wenshanensis by next-generation sequencing method. The entire length of mitogenome is 16,595 base pairs (bp), containing 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. Its gene arrangement pattern was identical to other previously reported Sinocyclocheilus fishes. The overall base composition is 31.12% A, 16.63% G, 25.45% T, and 26.80% C, with AT content of 56.57%. Phylogenetic analysis using mitogenome of 26 Cyprinidae fishes showed that S. wenshanensis are closely related to S. aluensis and S. oxycephalus. This work would provide molecular information fundamental to future phylogenetic analyses among Sinocyclocheilus species.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin β4 (Tβ4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tβ4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

BackgroundHigh serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain.MethodsA total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan–Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA).ResultsPatients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS.ConclusionThe current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.

ObjectivesTo compare three methods of scoring endolymphatic hydrops in patients with Ménière's disease in order to assess the correlation between endolymphatic hydrops and auditory characteristics.MethodsA retrospective study of 97 patients with unilateral definite Ménière's disease (DMD) who underwent contrast-enhanced three-dimensional fluid attenuated inversion recovery (3D FLAIR) MRI. Each patient was scored by the Inner Ear Structural Assignment Method (IESAM), the Saccule to utricle area ratio (SURI), and the Four Stage Vestibular Hydrops Grading (FSVH), according to their corresponding axial images. Cohen's Kappa and intra-class correlation coefficient were used for consistency testing, combined with binary logistic regression analysis, to compare the sensitivity and specificity of the three methods. The degree of hydrops in different stages of MD was compared. The correlation between endolymphatic hydrops in the inner ear sub-units and hearing thresholds was further analyzed.ResultsThe intra- and inter-reader reliability for the scoring of endolymphatic hydrops were excellent. The IESAM had a high diagnostic value for identifying definite Ménière's disease (sensitivity: 86.6%, specificity: 97.9%). The hearing thresholds were correlated with the degree of endolymphatic hydrops. Stages 3 and 4 were more significant for the severity of hydrops than stage 1. Within the subgroups of the Ménière's disease patients, compared with the non-hydrops group and the pure vestibular hydrops (V group), the cochlear combined vestibular hydrops group (CV group) had significantly higher auditory thresholds. The amplitude ratio of electrocochleogram was significantly higher in the affected ear than in the healthy ear.ConclusionThe IESAM is a more sensitive and specific diagnostic scoring method for the diagnosis of DMD. Diagnostic imaging may improve the detection of inner ear hydrops which is correlated with severity of hearing loss. A comprehensive evaluation of the inner ear sub-unit structures maybe necessary.

In order to clarify the characteristics of non-uniform water invasion in water-bearing gas reservoirs, it is necessary to introduce the non-uniformity coefficient (A) and water invasion constant (B) to characterize the non-uniformity degree of reservoir physical properties and the activity degree of peripheral water, respectively, based on the dual mechanism of water invasion to recharge the formation energy and seal off the gas in the reservoir. Then, the material balance method considering the phenomenon of water sealed gas was established. On this basis, the water invasion characteristic curve chart of water-bearing gas reservoirs was plotted, and the non-uniform water invasion mode was classified based on the example gas reservoir. And the following research results were obtained. First, in the water invasion characteristic curve chart of water-bearing gas reservoirs which is plotted based on the material balance method considering the influence of water sealed gas, the upper right area and the lower left area are defined as recharge area and seal area, respectively. By taking A = 0 and B = 2 as the boundary, the recharge area is divided into strong recharge area and weak recharge area. By taking A = 2 and B = 2 as the boundary, the seal area is divided into strong seal area and weak seal area. And correspondingly there are four water invasion modes, i.e., strong recharge, weak recharge, weak seal and strong seal. Second, for fractured gas reservoirs, the non-uniformity degree of reservoir physical properties is high, and water sealed gas can be formed easily after water invasion. The dimensionless relative pseudo-pressure data of this type of gas reservoir is located in the seal area of the water invasion characteristic curve chart. Third, for the gas reservoirs whose reservoir physical properties are relatively uniform, the dimensionless relative pseudo-pressure data is located in the recharge area of the water invasion characteristic curve chart, and the recharge effect of water invasion on formation energy is greater than the weakening effect of water sealed gas on formation energy. Fourth, with the increase of A, the non-uniformity degree of reservoir physical properties increases, the water invasion characteristic curve shifts from the upper right to the lower left, and the recovery factor of gas reservoir decreases continuously. With the increase of B, the recharge effect of water invasion on formation energy and the weakening effect of water sealed gas on formation energy are both weakened, the distribution range of water invasion characteristic curve narrows to the recharge/seal boundary, and the corresponding range of gas reservoir recovery factor also narrows.

Abstract When a spherical droplet moves parallel to the direction of motion of its surrounding gas medium, it will deform into an ellipsoidal droplet. In this paper, an exposition of a novel model for predicting the minimum flow rate for the continuous removal of liquids from gas wells based on two theories is presented. First, droplet breakup principle is utilized to microscopically obtain the maximum size parameters of ellipsoidal droplets, and second, droplet force equilibrium is adopted to macroscopically calculate the critical droplet entrainment rate. Moreover, effect of variations in the windward area (attributed to droplet deformation) on the drag coefficient is determined. Impacts of variations in pressure, temperature, and pipe diameter on the gas‐liquid two‐phase friction resistance and gas‐liquid surface tension are also considered. For model verification and comparison with other droplet entrainment models, field data from 3436 gas wells are utilized. The field data well validates the results with a 92% accuracy, indicating that the new model has a better comprehensive performance in determining whether or not a gas well is loaded. Besides, parameter sensitivity analyses including the effects of drag coefficient, surface tension, and friction coefficient on the minimum flow rate of gas are performed. Finally, the relationship curve of critical droplet entrainment rates corresponding to different pressures and pipe diameters is established.

The mitochondrial genome of the Disckless-fingered Odorous Frog, Odorrana grahami (Anura: Ranidae), was sequenced using high-throughput sequencing technology. The genome length was 17864 bp, including 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes and 1 control region (D-loop). The AT content of the mitochondrial genome was 55.9%. The composition of mitochondrial genome of O. grahami is similar to that of other species of the genus Odorrana. Phylogenetic analysis of the mitochondrial genomes of six congeners shows that O. grahami is sister to O. margaretae, but the analysis using 16S rRNA gene of additional congeners do not resolve their relationships.