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Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Background Androgen insensitivity syndrome (AIS) is a rare genetic disorder characterized by resistance to androgens, mainly due to mutations in the androgen receptor (AR) gene. It can manifest as complete AIS, partial AIS and mild AIS. While there have been studies linking specific AR gene mutations to AIS phenotypes, different clinical AIS phenotypes are also reported in patients with the same AR gene mutation. So far, the precise correlations between phenotypes and genotypes remain incompletely understood. Methods We conducted a thorough investigation involving four patients diagnosed with different types of AIS from a single Chinese family. Clinical manifestations, laboratory examinations, and fertility outcomes were well-documented. Furthermore, we performed genetic sequencing to detect possible pathogenetic variants. Results Whole exome sequencing identified a hemizygous missense variant (c.2263T > C; p.Phe755Leu) of AR gene in all four affected patients with different degrees of undermasculinisation and heterogeneous spermatogenesis. The proband, diagnosed with partial AIS, opted for treatment with donated sperm due to non-obstructive azoospermia, while their older sibling, diagnosed with complete AIS, was raised as a girl. His two maternal uncles were both diagnosed with mild AIS, the older uncle fathered two girls naturally, whereas the younger uncle utilized assisted reproductive technology to conceive a boy because of severe oligoasthenozoospermia. Conclusion Our study first identified the same AR variant (c.2263T > C;p.Phe755Leu) in four affected patients displaying highly diverse phenotypes of AIS and fertility outcomes, thereby significantly expanding the phenotypic spectrum of AIS. Notably, we presented a clear insight into different fertility outcomes of AIS patients with identical AR (c.2263T > C;p.Phe755Leu) variant, which provided reliable evidence that males harboring this variant may obtain biological offspring naturally or in combination with assisted reproductive technology. Furthermore, our study underscored the potential role of androgen concentration in shaping the phenotypic diversity of AIS, warranting further investigation.

Abstract Background Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. Methods A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. Results In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Abstract A concrete model of extracting the physics from the bulk of a gravitational universe is important to the study of quantum gravity and its possible relationship with experiments. Such a model can be constructed in the AdS/CFT correspondence by gluing a bath on the asymptotic boundary of the bulk anti-de Sitter (AdS) spacetime. This bath models a laboratory and is described by a quantum field theory. In the dual conformal field theory (CFT) description this coupling is achieved by a double-trace deformation that couples the CFT with the bath. This suggests that the physics observed by the laboratory is fully unitary. In this paper, we analyze the quantum aspects of this model in detail which conveys new lessons about the AdS/CFT correspondence, and we discuss the potential usefulness of this model in understanding subregion physics in a gravitational universe.

Abstract Background Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm. Methods A cohort of 35 individuals with normal semen analysis, comprising 17 hepatitis B surface antigen (HBsAg)-positive and 18 negative individuals, was recruited. Based on the previous research and the Online Mendelian Inheritance in Man database (OMIM, https://www.omim.org/ ), targeted promoter methylation sequencing was employed to investigate 28 paternally imprinted genes associated with various diseases. Results Bioinformatic analyses revealed 42 differentially methylated sites across 29 CpG islands within 19 genes and four differentially methylated CpG islands within four genes. At the gene level, an increase in methylation of DNMT1 and a decrease in methylation of CUL7, PRKAG2, and TP53 were observed. DNA methylation haplotype analysis identified 51 differentially methylated haplotypes within 36 CpG islands across 22 genes. Conclusions This is the first study to explore the effects of HBV infection on sperm DNA methylation and the potential underlying mechanisms of intergenerational influence of paternal HBV infection.

Brucellosis, caused by the intracellular pathogen Brucella, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in Brucella. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in B. abortus. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in B. abortus by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of arsR2 attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic Brucella species.

Objective This study aimed to evaluate the effects of tranexamic acid (TXA) in preventing postpartum haemorrhage (PPH) among women with identified risk factors for PPH undergoing vaginal delivery in China.Methods This prospective, randomized, open-label, blinded endpoint (PROBE) trial enrolled 2258 women with one or more risk factors for PPH who underwent vaginal delivery. Participants were randomly assigned in a 1:1 ratio to receive an intravascular infusion of 1 g TXA or a placebo immediately after the delivery of the infant. The primary outcome assessed was the incidence of PPH, defined as blood loss ≥500 mL within 24 h after delivery, while severe PPH was considered as a secondary outcome and defined by total blood loss ≥1000 mL within 24 h.Results 2245 individuals (99.4%) could be followed up to their primary outcome. PPH occurred in 186 of 1128 women in the TXA group and in 215 of 1117 women in the placebo group (16.5% vs. 19.2%; RR, 0.86; 95% CI, 0.72 to 1.02; p = 0.088). Regarding secondary outcomes related to efficacy, women in the TXA group had a significant lower rate of severe PPH than those in the placebo group (2.7% vs. 5.6%; RR, 0.49; 95% CI, 0.32 to 0.74; p = 0.001; adjusted p = 0.002). Similarly, there was a significant reduction in the use of additional uterotonic agents (7.8% vs. 15.6%; RR, 0.50; 95% CI, 0.39 to 0.63; p

Abstract To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1β, IL-6, and Aβ40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

BackgroundPostpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers.MethodsUsing retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort.ResultsFourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1β, TNFβ, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757–0.934), 0.846 (0.749–0.930), and 0.875 (0.789–0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709–0.901), 0.805 (0.701–0.894), and 0.901 (0.824–0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH.ConclusionWe identified novel biomarkers and developed predictive models for atonic PPH in women undergoing “low-risk” vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.

Wire icing seriously threatens the safety and reliability of power systems. Strengthening the simulation study of icing thickness is crucial for disaster prevention and mitigation, as well as the adjustment of power system operation strategies. The meteorological elements, including air temperature, precipitation and wind speed, are the key factors affecting wire icing. In this study, the meteorological elements related to icing thickness are obtained by numerical models, and the relationship between these elements and icing thickness observations is established to develop a model for simulating icing thickness. The model is applied to study typical icing in Yunnan Province, China. The results indicate that the deviation of the simulated icing thickness is about 2 mm, smaller than that from the traditional model. Batch experiments demonstrate that the new model developed in this research is applicable to the vast majority of 238 observation stations in Yunnan Province for icing thickness simulation, and the method can yield lower simulation deviations.

Summary: Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.

Abstract It is very challenging to accurately segment smoke images because smoke has some adverse vision characteristics, such as anomalous shapes, blurred edges, and translucency. Existing methods cannot fully focus on the texture details of anomalous shapes and blurred edges simultaneously. To solve these problems, a Dense Multi‐scale context and Asymmetric pooling Embedding Network (DMAENet) is proposed to model the smoke edge details and anomalous shapes for smoke segmentation. To capture the feature information from different scales, a Dense Multi‐scale Context Module (DMCM) is proposed to further enhance the feature representation capability of our network under the help of asymmetric convolutions. To efficiently extract features for long‐shaped objects, the authors use asymmetric pooling to propose an Asymmetric Pooling Enhancement Module (APEM). The vertical and horizontal pooling methods are responsible for enhancing features of irregular objects. Finally, a Feature Fusion Module (FFM) is designed, which accepts three inputs for improving performance. Low and high‐level features are fused by pixel‐wise summing, and then the summed feature maps are further enhanced in an attention manner. Experimental results on synthetic and real smoke datasets validate that all these modules can improve performance, and the proposed DMAENet obviously outperforms existing state‐of‐the‐art methods.

Abstract There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.

To address the serious issues of leakage, challenging plugging, and significant friction related to the long horizontal section construction in the Fuling shale gas field, a study was conducted to develop a suitable leak-proof agent OBMCP for oil-based drilling fluid. The difficulties of preventing leakage and plugging oil-based drilling fluid were analyzed, and the amount of reactively consolidated polymer HY-1 was controlled at 6.25 – 7.5% while considering the plugging strength requirements and plugging costs. The enhancer ZQJ was controlled at 0.4 – 0.6% to achieve high-strength rapid plugging, and the gelation time was controlled under the premise of safe construction to achieve a controllable curing time. Consequently, the oil-based drilling fluid leakage prevention and plugging technology were formed and applied in the J1 and J2 wells. The field test showed that the optimized drilling fluid had stable performance, a good plugging effect from the consolidation plugging agent, a stable borehole wall, small leakage, and strong anti-pollution ability, thereby achieving high-strength rapid plugging and a controllable curing time.

Oil and gas pipelines are subject to soil corrosion and medium pressure factors, resulting in stress concentration and pipe rupture and explosion. Non-destructive testing technology can identify the stress concentration and defect corrosion area of the pipeline to ensure the safety of pipeline transportation. In view of the problem that the traditional pipeline inspection cannot identify the stress signal at the defect, this paper proposes a detection method using strong and weak magnetic coupling technology. Based on the traditional J-A (Jiles–Atherton) model, the pinning coefficient is optimized and the stress demagnetization factor is added to establish the defect of the ferromagnetic material. The force-magnetic relationship optimization model is used to calculate the best detection magnetic field strength. The force-magnetic coupling simulation of Q235 steel material is carried out by ANSYS 2019 R1 software based on the improved J-A force-magnetic model. The results show that the effect of the stress on the pipe on the magnetic induction increases first and then decreases with the increase in the excitation magnetic field strength, and the magnetic signal has the maximum proportion of the stress signal during the excitation process; the magnetic induction at the pipe defect increases linearly with the increase in the stress trend. Through the strong and weak magnetic scanning detection of cracked pipeline materials, the correctness of the theoretical analysis and the validity of the engineering application of the strong and weak magnetic detection method are verified.

Accurate cloud detection is an important step to improve the utilization rate of remote sensing (RS). However, existing cloud detection algorithms have difficulty in identifying edge clouds and broken clouds. Therefore, based on the channel data of the Himawari-8 satellite, this work proposes a method that combines the feature enhancement module with the Gaussian mixture model (GMM). First, statistical analysis using the probability density functions (PDFs) of spectral data from clouds and underlying surface pixels was conducted, selecting cluster features suitable for daytime and nighttime. Then, in this work, the Laplacian operator is introduced to enhance the spectral features of cloud edges and broken clouds. Additionally, enhanced spectral features are input into the debugged GMM model for cloud detection. Validation against visual interpretation shows promising consistency, with the proposed algorithm outperforming other methods such as RF, KNN and GMM in accuracy metrics, demonstrating its potential for high-precision cloud detection in RS images.

Abstract China contributed nearly one-fifth of the world maize production over the past few years. Mapping the distributions of maize cropland in China is crucial to ensure global food security. Nonetheless, 10 m maize cropland maps in China are still unavailable, restricting the promotion of sustainable agriculture. In this paper, we collect numerous samples to produce annual 10-m maize cropland maps in China from 2017 to 2021 with a machine learning based classification framework. To overcome the temporal variations of plants, the proposed framework takes Sentinel-2 sequence images as input and utilizes deep neural networks and random forest as classifiers to map maize in a zone-specific way. The generated maps have an overall accuracy (OA) spanning from 0.87 to 0.95 and the maize-cultivated areas estimated by the maps are highly consistent with the records in statistical yearbooks (R 2 varying from 0.83 to 0.95). To the best of our knowledge, this is the first annual 10-m maize maps across China, which largely facilitates the sustainable agriculture development in China dominated by smallholder farmlands.

Semi-macrosegregation in continuously cast blooms and its associated carbide banding defects in hot-rolled bars were investigated to explore the characteristics, evolution, and control methods in high-carbon chromium bearing steel. It was found that the semi-macrosegregation exists only in the central equiaxed crystal zone of the blooms, and C, Cr solute elements inside show typical spot-like positive segregation. Carbide banding appears as white bright bands along the rolling direction, composed of high number density M3C carbide particles, with a significant effect on the mechanical properties of the rolled products. The hereditary evolution from semi-macrosegregation to carbide banding was established by means of banded segregation. Morphologically, normal semi-macrosegregation and carbide-typed semi-macrosegregation are formed based on whether Cr-rich primary carbides are generated. These two types of semi-macrosegregation evolved into two kinds of carbide banding respectively, that is, dark bands and bright bands defined according to the ability to reflect light under OM. To alleviate the carbide banding defect in rolling products of high-carbon chromium bearing steel, the morphology and area ratio of equiaxed crystals in continuous cast blooms should be modified. It is observed that the equiaxed crystal ratio in the bloom can be decreased from 62.5 % to 28 % by increasing liquid steel superheat and inhibiting superheat dissipation in the mold through casting practices. Additionally, the morphology of equiaxed crystals is related to the as-cast solidification structure, and when the equiaxed crystal ratio is large, the equiaxed crystals turn out to be coarser ones with only cellular primary dendrite; when the columnar crystals are longer, however, the equiaxed crystals appear as a dendrite structure with fine secondary dendrites. As a result, semi-macrosegregation was improved obviously with the fine dendrite structure splitting the local residual liquid phase, leading to the decrease of the maximum width of carbide banding from 268.41 μm to 73.72 μm, and the increase of mechanical properties in the rolled bar of high-carbon chromium bearing steel.

Intelligent pipeline inspection is necessary to operate submarine pipelines safely. At present, speed excursion and blockage are the challenges in the inspection of low-pressure gas pipelines. Accordingly, this study proposes a novel pneumo-electric hybrid-driven scheme to improve the traveling stability of inspection robots. To adapt to different working conditions, building blocks and CFD numerical simulation methods are used to study the throttling pressure control flow field of the robot. The results proved that the flow clearance had the most evident effect. The flow clearance was reduced from 30 to 5 mm, and the differential pressure of the prototype increased from 0.3 to 17 kPa. The skeleton diameter has a small effect on the differential pressure. The differential pressure increases as the gas velocity increases. By analyzing the prototype in different positions, it was found that the differential pressure of the prototype while passing the elbow decreased by 45% at 45°, which quantified the fluid-driven force gap of the prototype while passing through the elbow. Finally, by comparing the speed of prototype with that of fluid-driven pig, it is demonstrated that a pneumo-electric hybrid-driven scheme is an effective solution to the problem of unstable inspection operation of low-pressure gas pipelines.

The speed control of a pipeline inspection gauge (PIG) directly affects the quality of the comprehensive inspection of submarine pipelines. However, the mechanism of the gas flow behavior in a pipeline under the influence of a pig speed control valve is not well understood. In this study, the driving differential pressure of a pig was modeled based on the building block method and numerical simulations. For the first time, the influence of the pressure and flow rate of the gas in a pipeline on the torque of the speed control valve opening process was studied. The results show that when the opening angle of the speed control valve increased from 4.5° to 22°, the gas differential pressure reduced from 1325 to 73 kPa, realizing a 94.5% pressure reduction. In addition, the torque of the bypass valve increased from 7.7 to 2470 Nm during the closing process. The pressure and flow rate increases were directly correlated with increased torque. The established experimental system for torque measurement confirmed the numerical analysis results. By clarifying the law of torque variation, this study provides theoretical guidance for the structural design and control scheme of a pig speed control unit.

Wire icing events pose a significant threat to the southern power grid’s transmission lines in China. Fifteen such events were identified from 2018 to 2020 on the Guilin-Haiyang Mountain transmission line. Hourly measurements of ice thickness and concurrent meteorological data were analyzed using the Makkonen model’s freezing rate formula to categorize the events into distinct growth patterns: dry and wet. The relationship between wire icing and meteorological factors across different micro-topography (windward slope, leeward slope, and pass) was further explored. Several key conclusions can be drawn. First, the altitude is positively correlated to the icing thickness, but relatively independent of the icing rate; however, such independence between the icing rate and altitude cannot be interpreted by the negative correlation of altitude with temperature and the positive relationship between wind speed and liquid water content. Second, a pronounced connection of the icing rate with meteorological factors is not shown until the wet and dry patterns are separated. Notably, the correlations differ between these two patterns, with icing rate being negatively correlated with temperature for the wet growth process, but positively correlated with wind speed and liquid water content for the dry growth process. Third, both wet and dry growth processes exist across the icing events. A shift from wet to dry growth was evident with increasing altitude. At the mountain’s base, wet growth predominates, with the icing rate determined by the temperature close to the freezing point, whereas the higher temperature and lower liquid water flux account for the shorter wire icing duration, lower icing rate, and thus the thinner icing thickness at the leeward slope compared to the windward slope at a similar altitude. This study sheds light on the variations in icing rates under different micro-topographies and the underlying physical mechanisms governing icing growth patterns and provides a much-needed understanding of these distinct growth processes on the development of a more sophisticated predictive model for conductor icing.

Abstract Background Renal cell carcinoma (RCC) is a malignant tumour that may develop in the kidney. RCC is one of the most common kinds of tumours of this sort, and its most common pathological subtype is kidney renal clear cell carcinoma (KIRC). However, the aetiology and pathogenesis of RCC still need to be clarified. Exploring the internal mechanism of RCC contributes to diagnosing and treating this disease. Pyroptosis is a critical process related to cell death. Recent research has shown that pyroptosis is a critical factor in the initiation and progression of tumour formation. Thus far, researchers have progressively uncovered evidence of the regulatory influence that long noncoding RNAs (lncRNAs) have on pyroptosis. Methods In this work, a comprehensive bioinformatics approach was used to produce a predictive model according to pyroptosis-interrelated lncRNAs for the purpose of predicting the overall survival and molecular immune specialties of patients diagnosed with KIRC. This model was verified from multiple perspectives. Results First, we discovered pyroptosis-associated lncRNAs in KIRC patients using the TCGA database and a Sankey diagram. Then, we developed and validated a KIRC patient risk model based on pyroptosis-related lncRNAs. We demonstrated the grouping power of PLnRM through PCA and used PLnRM to assess the tumour immune microenvironment and response to immunotherapy. Immunological and molecular traits of diverse PLnRM subgroups were evaluated, as were clinical KIRC patient characteristics and predictive risk models. On this basis, a predictive nomogram was developed and analyzed, and novel PLnRM candidate compounds were identified. Finally, we investigated possible medications used by KIRC patients. Conclusions The results demonstrate that the model generated has significant value for KIRC in clinical practice.

Abstracts As the major maize-cultivated areas, the one-season cropland of China is increasingly threatened by rapid urbanization and soybean rejuvenation. Quantifying the area changes of maize cropland is crucial for both food and energy security. Nonetheless, due to the lack of survey data related to planting types, long-term and fine-grained maize cropland maps in China dominated by small-scale farmlands are still unavailable. In this paper, we collect 75,657 samples based on field surveys and propose a deep learning-based method according to the phenology information of maize. With the generalization capability, the proposed method produces maize cropland maps with a resolution of 30 m from 2013 to 2021 in the one-season planting areas of China. The maize-cultivated areas derived from the maps are highly consistent with the data recorded by statistical yearbooks (R 2 = 0.85 on average), which indicates that the produced maps are reliable to facilitate the research on food and energy security.

Compared to conventional vertical wells, horizontal wells with Ultra-Long horizontal sections greatly increase the oil drainage area and can significantly increase oil and gas production from individual wells. In order to analyze the limit of horizontal well extension, an extension limit model was developed, which takes into account formation, rated pump pressure, rated pressure and string buckling, and is used to predict the limit of horizontal well extension under different constraints. The results show that increasing the inside and outside diameter of drill pipe can effectively reduce pressure loss and facilitate the extension of the horizontal section while keeping the hole size unchanged. As the cuttings density, cuttings diameter, mud density, mud performance, pump rates, and ROP increase, the limit extension length of the horizontal section gradually decreases. As the WOB, RPM, friction factor increase, the torque gradually increases and the limit extension length of the horizontal section gradually decreases. Selecting the right combination of drilling tools can reduce the torque, which is beneficial for mechanical extension. This study is instructive for the limit of horizontal well extension with ultra-long horizontal sections in the field.

The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds’ ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A2, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.

The genus Eupatorium belongs to the Asteraceae (Compositae) family and has multiple properties, such as invasiveness and toxicity, and is used in folk medicine. The last review on the chemical constituents of this genus and their biological activities was published in 2015. The present review provides an overview of 192 natural products discovered from 2015 to the present. These products include 63 sesquiterpenoids, 53 benzofuran derivatives, 39 thymol derivatives, 15 fatty acids, 7 diterpenoids, 5 monoterpenoids, 4 acetophenones, and 6 other compounds. We also characterized their respective chemical structures and cytotoxic, antifungal, insecticidal, antibacterial, anti-inflammatory, and antinociceptive activities.

Seasonal (temporal) variations can influence the δ13C, δ2H, δ18O, and δ15N values and nutrient composition of organic (ORG), green (GRE), and conventional (CON) vegetables with a short growth cycle. Stable isotope ratio mass spectrometry (IRMS) and near-infrared spectroscopy (NIRS) combined with the partial least squares-discriminant analysis (PLS-DA) method were used to investigate seasonal effects on the identification of ORG, GRE, and CON Brassica chinensis L. samples (BCs). The results showed that δ15N values had significant differences among the three cultivation methods and that δ13C, δ2H, and δ18O values were significantly higher in winter and spring and lower in summer. The NIR spectra were relatively clustered across seasons. Neither IRMS-PLS-DA nor NIRS-PLS-DA could effectively identify all BC cultivation methods due to seasonal effects, while IRMS-NIRS-PLS-DA combined with Norris smoothing and derivative pretreatment had better predictive abilities, with an 89.80% accuracy for ORG and BCs, 88.89% for ORG and GRE BCs, and 75.00% for GRE and CON BCs. The IRMS-NIRS-PLS-DA provided an effective and robust method to identify BC cultivation methods, integrating multi-seasonal differences.

The compact design of a 500 kV quadruple-circuit transmission line can effectively reduce the line corridor area, but the height of the tower also increases, increasing the probability of suffering a lightning strike. The 500 kV quadruple-circuit transmission lines carry more energy, and because of this, lightning strikes that cause power line trips are more likely to result in large-scale power outages. Therefore, it is necessary to make an accurate assessment of the lightning performance of 500 kV quadruple-circuit transmission lines. First, simulated lightning-striking experiments were carried out on a scaled 500 kV quadruple-circuit transmission line in the laboratory, where transient voltages and currents were measured. Second, a numerical model was established with the Finite-Difference Time Domain (FDTD) method, which was then verified with the experimental results. Third, lightning surge responses of a 500 kV quadruple-circuit transmission line under near-real facility conditions are estimated with the verified FDTD model. In the simulations, influencing factors, such as the rise time of injecting current, the velocity of return-stroke current and the terrains, were taken into consideration, but not in previous lightning surge analysis with the Electromagnetic Transients Program (EMTP). Results show that insulator voltages on the same tower cross-arm are nearly identical, although the length of the cross-arm is large enough. Furthermore, it is found that the rise time and the lightning current velocity have great effects on the lightning surge response, and the terrains are less impactful but not negligible. Therefore, these factors should be considered carefully where higher accuracy lightning protection design is necessary.

Abstract We study the entanglement phase structure of a holographic boundary conformal field theory (BCFT) in a two-dimensional black hole background. The bulk dual is the AdS3 black string geometry with a Karch-Randall brane. We compute the subregion entanglement entropy of various two-sided bipartitions to elucidate the phase space where a Page curve exists in this setup. We do fully analytical computations on both the gravity side and the field theory side and demonstrate that the results precisely match. We discuss the entanglement phase structure describing where a Page curve exists in this geometry in the context of these analytical results. This is a useful model to study entanglement entropy for quantum field theory on a curved background.

Abstract Background Asthenozoospermia is a troublesome disease experienced by men in their reproductive years, but its exact etiology remains unclear. To address this problem, this study aims to identify the hub genes and crucial pathways in asthenozoospermia. Methods We screened two Gene Expression Omnibus (GEO) datasets (GSE92578 and GSE22331) to extract the differentially expressed genes (DEGs) between normozoospermic and asthenozoospermic men using the “Limma” package. Gene enrichment analyses of the DEGs were conducted using the “clusterProfiler” R package. The protein-protein interaction (PPI) network was then established using the STRING database. A miRNA-transcription factor-gene network was constructed based on the predicted results of hub genes using the RegNetwork database. The expression of four hub genes in asthenozoospermia and normal samples were verified using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. Results We identified 271 DEGs, which included 218 upregulated and 53 downregulated in two asthenozoospermia datasets. These DEGs were observed to be markedly enriched in pathways with cell growth and embryonic organ development, phospholipase D signaling pathway, cGMP-PKG signaling pathway, and Wnt signaling pathway. The most significant genes were identified, including COPS7A, CUL3, KLHL7, NEDD4. We then constructed regulatory networks of these genes, miRNAs, and transcription factors. Finally, we found that the COPS7A was significantly upregulated in patients with asthenozoospermia, but CUL3, KLHL7 and NEDD4 were significantly downregulated compared with normal samples. Conclusion We applied bioinformatics methods to analyze the DEGs of asthenozoospermia based on the GEO database and identified the novel crucial genes and pathways in this disease. Our findings may provide novel insights into asthenozoospermia and identify new clues for the potential treatment of this disease.

ObjectivesCranial magnetic resonance imaging (MRI) could be a crucial tool for the assessment for neurological symptoms in patients with Wilson’s disease (WD). Diffusion-weighted imaging (DWI) hyperintensity reflects the acute brain injuries, which mainly occur in specific brain regions. Therefore, this study aimed to develop a weighted cranial DWI scale for patients with WD, with special focus on specific brain regions.Materials and methodsIn total, 123 patients with WD were enrolled, 118 of whom underwent 1.5 T-MRI on admission. The imaging score was calculated as described previously and depended on the following sequences: one point was acquired when abnormal intensity occurred in the T1, T2, and fluid-attenuation inversion recovery sequences, and two points were acquired when DWI hyperintensity were found. Consensus weighting was conducted based on the symptoms and response to treatment.ResultsIntra-rater agreement were good (r = 0.855 [0.798–0.897], p < 0.0001). DWI hyperintensity in the putamen was a high-risk factor for deterioration during de-copper therapy (OR = 8.656, p < 0.05). The high-risk factors for readmission for intravenous de-copper therapies were DWI hyperintensity in the midbrain (OR = 3.818, p < 0.05) and the corpus callosum (OR = 2.654, p < 0.05). Both scoring systems had positive correlation with UWDRS scale (original semi-quantitative scoring system, r = 0.35, p < 0.001; consensus semi-quantitative scoring system, r = 0.351, p < 0.001.). Compared to the original scoring system, the consensus scoring system had higher correlations with the occurrence of deterioration (OR = 1.052, 95%CI [1.003, 1.0103], p < 0.05) and readmission for intravenous de-copper therapy (OR = 1.043, 95%CI [1.001, 1.086], p < 0.05).ConclusionThe predictive performance of the consensus semi-quantitative scoring system for cranial MRI was improved to guide medication, healthcare management, and prognosis prediction in patients with WD. For every point increase in the neuroimaging score, the risk of exacerbations during treatment increased by 5.2%, and the risk of readmission to the hospital within 6 months increased by 4.3%.

Wire icing is a prevalent challenge in both industrial and scientific domains, and it is widely acknowledged that terrain and water vapor are significant contributing factors in the formation of wire icing. Consequently, the identification of terrains that are prone to inducing water vapor uplift serves as the scientific foundation for predicting ice accumulation on power lines. Yunnan Province, a mountainous province in China, features a large elevation difference. In winter, this region is prone to wire, pole and tower icing, which can affect power transmission and cause economic and property losses. Therefore, it is necessary to conduct research on the identification of typical terrain patterns in this region. In previous terrain studies, more attention has been focused on slope and aspect, watershed analysis and terrain profile analysis. When the purpose of the terrain identification is to analyze which terrains are more prone to collecting water vapor, we hope to obtain slightly larger terrain blocks and analyze the water vapor sources for different terrains in order to identify typical terrains that are conducive to icing formation. A new technology for identifying terrain patterns based on the K-means clustering method is proposed in this study to explore the typical terrain in Yunnan province. Additionally, the influences of different terrain patterns on water vapor movement are also analyzed. The results indicate that the typical terrains in Yunnan are “Valley-Air Channel”, “Topographic Uplifting”, “Ravine”, “Mountain Pass” and “Alpine Divide” patterns. The results show that the identified typical terrain is consistent with observations from satellite images, which verifies the effectiveness of this identification method. Among these five typical terrains, the “Valley-Air Channel”, the “Topographic Uplifting” and the “Mountain Pass” terrains are prone to collecting water vapor and forming ice cover. The “Alpine Divide” terrain is also prone to accumulating water vapor on both sides to form ice cover. The identified typical terrain demonstrates that typical terrain patterns near water bodies are more prone to the occurrence of wire, pole and tower icing because these areas are abundant in water vapor, and the extensive water vapor is easily condensed under the effects of terrain uplifting and cooling. In these key areas, existing wires and towers, as well as those to be constructed in the future, deserve our special attention.

Abstract In this paper, we use the Karch-Randall braneworld to study theories of quantum gravity in two dimensional (nearly) anti-de Sitter space (AdS2). We focus on effective gravitational theories in the setup with two Karch-Randall branes embedded in an asymptotically AdS3 bulk forming a wedge. We find the appearance of two-dimensional Einstein-Hilbert gravity (or the Lorenzian version of the theory considered by Marolf and Maxfield) when the branes are rigid but the emergence of a class of dilaton gravity models parameterized by the tensions of the two branes when brane fluctuations are accounted for. A special case of our result is Jackiw-Teitelboim (JT) gravity, which has been proven useful to address many important problems in quantum gravity. An important implication of our work is that these models have holographic duals as one-dimensional quantum mechanics systems. At the end, we discuss a puzzle regarding the energy spectrum and its resolution.

Abstract We compute holographic entanglement entropy for subregions of a BCFT thermal state living on a nongravitating black hole background. The system we consider is doubly holographic and dual to an eternal black string with an embedded Karch-Randall brane that is parameterized by its angle. Entanglement islands are conventionally expected to emerge at late times to preserve unitarity at finite temperature, but recent calculations at zero temperature have shown such islands do not exist when the brane lies below a critical angle. When working at finite temperature in the context of a black string, we find that islands exist even when the brane lies below the critical angle. We note that although these islands exist when they are needed to preserve unitarity, they are restricted to a finite connected region on the brane which we call the atoll. Depending on two parameters — the size of the subregion and the brane angle — the entanglement entropy either remains constant in time or follows a Page curve. We discuss this rich phase structure in the context of bulk reconstruction.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Non-obstructive azoospermia (NOA) is the most severe type of male infertility, affecting 1% of men worldwide. Most of its etiologies remain idiopathic. Although genetic studies have identified dozens of NOA genes, monogenic mutations can also account for a small proportion of idiopathic NOA cases. Hence, this genetic study was conducted to explore the causes of monogenic variants of NOA in a cohort of Chinese patients. Methods Following the screening using chromosomal karyotyping, Y chromosome microdeletion analyses, and sex hormone assessments, subsequent whole-exome sequencing analysis was performed in 55 unrelated idiopathic NOA patients with male infertility to explore potential deleterious variants associated with spermatogenesis. We also performed Sanger sequencing to demonstrate the variants. Testicular biopsy or microsurgical testicular sperm extraction was also performed to confirm the diagnosis of NOA and identify spermatozoa. Hematoxylin and eosin staining was performed to assess the histopathology of spermatogenesis. Results Abnormal testicular pathological phenotypes included Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis. Using bioinformatics analysis, we detected novel variants in two recessive genes, FANCA (NM_000135, c.3263C > T, c.1729C > G) and SYCE1 (NM_001143763, c.689_690del); one X-linked gene, TEX11 (NM_031276, c.466A > G, c.559_560del); and two dominant genes, DMRT1 (NM_021951, c.425C > T, c.340G > A) and PLK4 (NM_001190799, c.2785A > G), in eight patients, which corresponded to 14.55% (8/55) of the patients. Conclusion This study presented some novel variants of known pathogenic genes for NOA. Further, it expanded the variant spectrum of NOA patients, which might advance clinical genetic counseling in the future.

Approaching the peak year of the 25th solar activity cycle, the frequency of strong geomagnetic storms is gradually increasing, which seriously affects the navigation and positioning performance of GNSS. Based on the globally distributed GNSS station data and FORMOSAT-7/COSMIC-2 occultation data, this paper explores for the first time the effects of the G4-class geomagnetic storm that occurred on 23–24 April 2023 on the global ionosphere, especially the ionospheric equatorial anomalies and F-layer perturbations. It reveals the precise point positioning (PPP) accuracy degradation during a geomagnetic storm. The results show that the ionospheric rate of total electron content index (ROTI) and near high latitude GNSS phase scintillations index have varying levels of perturbation during geomagnetic storms, with the maximum ROTI and phase scintillations index exceeding 0.5 TECU/min and 0.8, respectively. The equatorial ionization anomaly (EIA) shows an enhanced state (positive ionospheric storms) during geomagnetic storms, and the cause of this phenomenon is most likely the equatorward neutral wind. The variation of the S4 index of the FORMOSAT-7/COSMIC-2 satellite reveals the uplift of the F-layer during geomagnetic storms. During geomagnetic storms, the PPP accuracy degrades most seriously at high latitudes, the maximum MAE exceeds 2.3 m, and the RMS in the three-dimensional (3D) direction exceeds 2.0 m. These investigations can provide case support for space weather and GNSS studies of the impact of geomagnetic storms during peak solar activity years.

Given the potential of low-earth orbit (LEO) satellites in terms of navigation enhancement, accurately estimating the differential code bias (DCB) of GNSS satellites and LEO satellites is an important research topic. In this study, to obtain accurate DCB estimates, the effects of vertical total electron content (VTEC) modeling parameters of the topside ionosphere on DCB estimation were investigated using LEO observations for the first time. Different modeling parameters were set in the DCB estimations, encompassing modeling spacing in the dynamic temporal mode and degree and order (D&O) in spherical harmonic modeling. The DCB precisions were then evaluated, and the impacts were analyzed. Thus, a number of crucial and beneficial conclusions are drawn: (1) The maximum differences in the GPS DCB estimates after adopting different modeling spacings and different D&Os exhibit that the different modeling spacings or D&Os both affect the GPS DCB estimates and their root-mean square (RMS), and the effects of the two are at the same level. (2) The maximum differences in receiver DCBs using different modeling spacings indicate that the modeling spacing has a significant impact on the receiver DCBs, compared with GPS DCBs. Whereas, the maximum differences in receiver DCBs with different modeling D&Os are inferior to the differences in the GPS DCBs. That is, the modeling spacing has a greater impact on the LEO DCBs than those of the modeling D&O. (3) The experimental results indicate that the GPS DCB estimates using a modeling spacing of 12H have higher precisions than the others, whereas LEO receiver DCBs using a spacing of 4H or 6H obtain optimal STD. In terms of modeling D&O, adopting 8D&O in the LEO-based VTEC modeling can attain superior estimates and precisions for both GPS and LEO DCBs. The research conclusions can provide references for LEO-augmented DCB estimation.

We propose swampland criteria for braneworlds viewed as effective field theories of defects coupled to semiclassical gravity. We do this by exploiting their holographic interpretation. We focus on general features of entanglement entropies and their holographic calculations. Entropies have to be positive. Furthermore, causality imposes certain constraints on the surfaces that are used holographically to compute them, most notably a property known as causal wedge inclusion. As a test case, we explicitly constrain the Dvali-Gabadadze-Porrati term as a second-order-in-derivatives correction to the Randall-Sundrum action. We conclude by discussing the implications of these criteria for the question on whether entanglement islands in theories with massless gravitons are possible in Karch-Randall braneworlds.

Sudden Stratospheric Warming (SSW) events have a strong impact on the tropospheric weather and climate. Past researchers have carried out extensive studies investigating the theories of interactions between the stratosphere and the troposphere. However, detailed studies on the influences of the global tropopause are rarely shown. This study uses Global Navigation Satellite System (GNSS) Radio Occultation (RO) data from the years 2007 to 2013 to investigate the influences of different types of SSW events on the tropopause over latitude bands from 30° S to 90° N. It was found that SSW events have strong influences on the tropopause over 60° N–90° N and over 20° N–30° N regions. In 60° N–90° N, SSW events cause a tropopause temperature increase and, therefore, a tropopause height decrease. The increment in the tropopause temperature are more than 10 K and the decrement in the tropopause height is about to 2 km during strong events. Such influences last for about 1.5 months for strong split events and about 10 days for weaker and/or displacement type events. The influences of SSW events on 20° N–30° N are weaker. Only the January 2009 SSW event shows a visible influence on the tropopause layer with a tropopause temperature decrease of about 4 K and a tropopause height increase of about 1 km. Other SSW events share no common characteristics on the tropical tropopause. This is mainly because SSW events are not strong enough to dominate the tropopause variations and other factors, especially the planetary waves in the troposphere, have stronger impacts on the tropopause layer.

Abstract Background Multiple morphological abnormalities of the sperm flagella (MMAF) is a subtype of severe asthenoteratozoospermia with poorly understood genetic etiology. SPAG6 is a core axonemal component that plays a critical role in the formation of cilia and sperm flagella. Previous studies have reported that mutations in SPAG6 cause primary ciliary dyskinesia (PCD), but the association between SPAG6 gene variants and the MMAF phenotype has not yet been described. Methods We performed whole-exome sequencing (WES) in two unrelated Han Chinese men with MMAF. Sanger sequencing was used to validate the candidate variants. Routine semen analysis was carried out according to the WHO guidelines (5th Edition). Sperm morphology was assessed using modified Papanicolaou staining. Scanning and transmission electron microscopy (S/TEM) was performed to observe the ultrastructural defects of the sperm flagella. Western blot analysis and immunofluorescence (IF) of spermatozoa were performed to examine the expression of SPAG6 protein. Assisted fertilization with intracytoplasmic sperm injection (ICSI) was applied. Results Two homozygous SPAG6 variants were identified by WES and Sanger validation in two patients with MMAF phenotype (F1 II-1: c.308C > A, p. A103D; F2 II-1: c. 585delA, p. K196Sfs*6). Semen analysis showed progressive rates of less than 1%, and most of the spermatozoa presented MMAF by Papanicolaou staining. TEM revealed that the overall axonemal ultrastructure was disrupted and primarily presented an abnormal “9 + 0” configuration. No other PCD-related symptoms were found on physical examination and medical consultations, as well as lung CT screening. The level of SPAG6 protein was significantly decreased in the spermatozoa, and IF analysis revealed that SPAG6 staining was extremely weak and discontinuous in the sperm flagella of the two patients. Notably, F1 II-1 and his wife conceived successfully after undergoing ICSI. Conclusions Our research provides new evidence for a potential correlation between SPAG6 variants and the MMAF phenotype.

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

Abstract Background The incidence of 47, XYY syndrome in live-born male infants is 1/1000. Due to its variable clinical symptoms, the diagnosis is easy to miss. The incidence of congenital bilateral absence of the vas deferens (CBAVD) in infertile men is 1–2%. The main cause is the mutation of CFTR and ADGAG2 genes. Case presentation The patient was a 33-year-old man who visited a doctor 5 years ago due to infertility. The investigation revealed that the patient’s secondary sexual characteristics, testicular, and penis development were normal, and there was no gynecomastia, but the bilateral vas deferens and epididymis were not palpable. Transrectal ultrasound showed that the left seminal vesicle was missing, and the right seminal vesicle was atrophied. No abnormality was observed in Y chromosome microdeletion. Karyotype analysis indicated that the patient was 46, XY/47, XYY mosaic. Genetic testing found heterozygous mutations at two sites of CFTR (c263T > G and c2249C > T). Conclusions Herein, we report the rare case of a male patient with clinical manifestations of infertility, chromosome 46, XY/47, XXY mosaic type, simultaneously manifested as the absence of bilateral vas deferens. Two pathogenic heterozygous CFTR gene mutations were found. Given the low genetic risk of the disease, we recommend that patients undergo intracytoplasmic sperm injection (ICSI) for fertility assessment.

Abstract Background Potassium channels are important for the structure and function of the spermatozoa. As a potassium transporter, the mSlo3 is essential for male fertility as Slo3 knockout male mice were infertile with the series of functional defects in sperm cells. However, no pathogenic variant has been detected in human SLO3 to date. Here we reported a human case with homozygous SLO3 mutation. The function of SLO3 in human sperm and the corresponding assisted reproductive strategy are also investigated. Methods We performed whole-exome sequencing analysis from a large cohort of 105 patients with asthenoteratozoospermia. The effects of the variant were investigated by quantitative RT-PCR, western blotting, and immunofluorescence assays using the patient spermatozoa. Sperm morphological and ultrastructural studies were conducted using haematoxylin and eosin staining, scanning and transmission electron microscopy. Results We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility. This SLO3 variant was rare in human control populations and predicted to be deleterious by multiple bioinformatic tools. Sperm from the individual harbouring the homozygous SLO3 variant exhibited severe morphological abnormalities, such as acrosome hypoplasia, disruption of the mitochondrial sheath, coiled tails, and motility defects. The levels of SLO3 mRNA and protein in spermatozoa from the affected individual were reduced. Furthermore, the acrosome reaction, mitochondrial membrane potential, and membrane potential during capacitation were also afflicted. The levels of acrosome marker glycoproteins and PLCζ1 as well as the mitochondrial sheath protein HSP60 and SLO3 auxiliary subunit LRRC52, were significantly reduced in the spermatozoa from the affected individual. The affected man was sterile due to acrosome and mitochondrial dysfunction; however, intra-cytoplasmic sperm injection successfully rescued this infertile condition. Conclusions SLO3 deficiency seriously impact acrosome formation, mitochondrial sheath assembly, and the function of K+ channels. Our findings provided clinical implications for the genetic and reproductive counselling of affected families.

Abstract In ordinary gravitational theories, any local bulk operator in an entanglement wedge is accompanied by a long-range gravitational dressing that extends to the asymptotic part of the wedge. Islands are the only known examples of entanglement wedges that are disconnected from the asymptotic region of spacetime. In this paper, we show that the lack of an asymptotic region in islands creates a potential puzzle that involves the gravitational Gauss law, independently of whether or not there is a non-gravitational bath. In a theory with long-range gravity, the energy of an excitation localized to the island can be detected from outside the island, in contradiction with the principle that operators in an entanglement wedge should commute with operators from its complement. In several known examples, we show that this tension is resolved because islands appear in conjunction with a massive graviton. We also derive some additional consistency conditions that must be obeyed by islands in decoupled systems. Our arguments suggest that islands might not constitute consistent entanglement wedges in standard theories of massless gravity where the Gauss law applies.

IntroductionInfertility is a major disease affecting human life and health, among which male factors account for about half. Asthenoteratozoospermia accounts for the majority of male infertility. High-throughput sequencing techniques have identified numerous variants in genes responsible for asthenoteratozoospermia; however, its etiology still needs to be studied.MethodIn this study, we performed whole-exome sequencing on samples from 375 patients with asthenoteratozoospermia and identified two HYDIN compound heterozygous variants, a primary ciliary dyskinesia (PCD)-associated gene, in two unrelated subjects. H&E staining, SEM were employed to analyze the varies on sperm of patients, further, TEM was employed to determine the ultrastructure defects. And westernblot and immunostaining were chose to evaluate the variation of structural protein. ICSI was applied to assist the mutational patient to achieve offspring.ResultWe identified two HYDIN compound heterozygous variants. Patient AY078 had novel compound heterozygous splice variants (c.5969-2A>G, c.6316+1G>A), altering the consensus splice acceptor site of HYDIN. He was diagnosed with male infertility and PCD, presenting with decreased sperm progressive motility and morphological abnormalities, and bronchial dilatation in the inferior lobe. Compared to the fertile control, HYDIN levels, acrosome and centrosome markers (ACTL7A, ACROSIN, PLCζ1, and Centrin1), and flagella components (TOMM20, SEPT4, SPEF2, SPAG6, and RSPHs) were significantly reduced in HYDIN-deficient patients. Using intracytoplasmic sperm injection (ICSI), the patient successfully achieved clinical pregnancy. AY079 had deleterious compound heterozygous missense variants, c.9507C>G (p. Asn3169Lys) and c.14081G>A (p. Arg4694His), presenting with infertility; however, semen samples and PCD examination were unavailable.DiscussionOur findings provide the first evidence that the loss of HYDIN function causes asthenoteratozoospermia presenting with various defects in the flagella structure and the disassembly of the acrosome and neck. Additionally, ICSI could rescue this failure of insemination caused by immobile and malformed sperm induced by HYDIN deficiency.

Abstract Background Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. Methods We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. Results Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. Conclusions Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.

According to the big impact hypothesis, the moon should be very dry. However, more and more evidence from the remote sensing of the moon in recent years indicates that there is a lot of water in the moon’s polar regions. Researching the source and distribution of volatiles such as water can provide a key constraint on the formation and evolution of the moon. If there is a large amount of a volatile such as water ice in the polar area of the moon, it can be used as a further resource. Regrettably, there are no detectors in place to detect the amount and presence of water to date. In the new wave of lunar exploration, polar water has become one of the main tasks of NASA, ESA and RKA. The Chang’e-7 spacecraft of China’s fourth lunar exploration phase has also used the Water Molecular Analyzer and the Lunar Soil Volatile Measuring Instrument to detect water content in the lunar polar region. This paper introduces a set of methods and principles for analyzing water content via the heat flux method according to the characteristics of the Lunar Soil Volatile Measuring Instrument that was deployed on the lunar surface. According to the current design, the water content of 0.008~0.17% can be analyzed.

Accurate identification of the rational and standardized use of pesticides is important for the sustainable development of agriculture while maintaining a high quality. The insecticides thiamethoxam and fenvalerate and the vegetables spinach, cabbage, and lettuce were used here as study objects. Descriptive analysis and primary reaction kinetic equations were used to analyze the changes in metabolic residues of the two insecticides after different numbers of application in three vegetables. The effects of pesticide residue levels on the δ13C, δ15N, δ2H, and δ18O values of vegetables were analyzed by one-way analysis of variance and correlation analysis. Partial least squares discriminant analysis (PLS-DA) was applied to build discrimination models of the vegetables with different pesticide residues based on stable isotopes. The results showed that the first degradation residues of thiamethoxam and fenvalerate in spinach, cabbage, and lettuce conformed to primary reaction kinetic equations, but the degradation half-lives were long, and accumulation occurred in the second application. The differences in the four stable isotope ratios in the control group of the three vegetables were statistically significant, and two-thirds of the stable isotope ratios in the three vegetables with different numbers of pesticide applications were significantly different. The δ13C and δ15N values of spinach, the δ13C, δ15N, and δ2H values of cabbage, and the δ13C, δ15N, δ2H, and δ18O values of lettuce were significantly correlated with different residues of thiamethoxam and/or fenvalerate applications. The control groups of the three vegetables, spinach-thiamethoxam-first, spinach-thiamethoxam-second, cabbage-thiamethoxam-second, cabbage-fenvalerate-first, and lettuce-thiamethoxam-first, were fully identified by PLS-DA models, while the identification models of other vegetables containing pesticide residues still need to be further improved. The results provide technical support for identifying the rational use of pesticides in vegetables and provide a reference method for guaranteeing the authenticity of green and organic vegetables.