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Abstract The capacity to discern and locate positions in three-dimensional space is crucial for human-machine interfaces and robotic perception. However, current soft electronics can only obtain two-dimensional spatial locations through physical contact. In this study, we report a non-contact position targeting concept enabled by transparent and thin soft electronic skin (E-skin) with three-dimensional sensing capabilities. Inspired by the active electrosensation of mormyroidea fish, this E-skin actively ascertains the 3D positions of targeted objects in a contactless manner and can wirelessly convey the corresponding positions to other devices in real-time. Consequently, this E-skin readily enables interaction with machines, i.e., manipulating virtual objects, controlling robotic arms, and drones in either virtual or actual 3D space. Additionally, it can be integrated with robots to provide them with 3D situational awareness for perceiving their surroundings, avoiding obstacles, or tracking targets.

Abstract Colorectal cancer (CRC) is a common malignant tumor of the digestive tract in China; its incidence rates and mortality rates have been on the rise in recent years, ranking third in terms of incidence and second in mortality. Rational dietary intervention plays an important role in human health, and prevention and adjuvant treatment of CRC through dietary supplementation is the most ideal and safest way to treat the disease at present. More importantly, dietary protein is the basis of our diet and the key nutrient to maintain the normal function of the human body. Therefore, this narrative review delivered an overview of the common causes and therapeutic treatments for CRC. It emphasized the importance of dietary interventions, with a particular focus on elucidating the distinct regulatory impacts of plant proteins, animal proteins, and their mixed proteins.

Abstract Cyamophila willieti (Hemiptera: Psyllidae) is a significant pest that adversely affects the growth of Styphnolobium japonicum and its variant, Styphnolobium japonicum f. pendula. Despite its impact, research on this species remains limited. In this study, we successfully assembled a chromosome-level genome for Cyamophila willieti using a comprehensive approach that integrated Illumina sequencing, PacBio sequencing, and Hi-C technology. The genome size was determined to be 361.61 Mb, with a scaffold N50 length of 28.90 Mb. Additionally, the genome was mapped to 13 chromosomes (N = 12 A + X), and a total of 15,841 genes were predicted, with 90.38% of them functionally annotated. In summary, the high-quality genome of Cyamophila willieti provides valuable data to support further research, including pest management strategies.

Abstract Recent studies indicate that replication checkpoint modulators (RCMs) such as inhibitors of CHK1, ATR, and WEE1 have promising monotherapy activity in solid tumors, including platinum-resistant high grade serous ovarian cancer (HGSOC). However, clinical response rates are generally below 30%. While RCM-induced DNA damage has been extensively examined in preclinical and clinical studies, the link between replication checkpoint interruption and tumor shrinkage remains incompletely understood. Here we utilized HGSOC cell lines and patient-derived xenografts (PDXs) to study events leading from RCM treatment to ovarian cancer cell death. These studies show that RCMs increase CDC25A levels and CDK2 signaling in vitro, leading to dysregulated cell cycle progression and increased replication stress in HGSOC cell lines independent of homologous recombination status. These events lead to sequential activation of JNK and multiple BH3-only proteins, including BCL2L11/BIM, BBC3/PUMA and the BMF, all of which are required to fully initiate RCM-induced apoptosis. Activation of the same signaling pathway occurs in HGSOC PDXs that are resistant to poly(ADP-ribose) polymerase inhibitors but respond to RCMs ex vivo with a decrease in cell number in 3-dimensional culture and in vivo with xenograft shrinkage or a significantly diminished growth rate. These findings identify key cell death-initiating events that link replication checkpoint inhibition to antitumor response in ovarian cancer.

Abstract Heteroptera (the true bugs), one of the most diverse lineages of insects, diversified in feeding strategies and living habitats, and thus become an ideal lineage for studies on adaptive evolution. Chinese water scorpion Ranatra chinensis (Heteroptera: Nepidae) is a predaceous bug living in lentic water systems, representing an ideal model for studying habitat transition and adaptation to water environment. However, genetic studies on this water bug remain limited. Here, we obtained a chromosome-level genome of R. chinensis using PacBio HiFi long reads and Hi-C sequencing reads. The total assembly size of genome is 867.89 Mb, with a scaffold N50 length of 26.48 Mb and the GC content of 39.50%. All contigs were assembled into 23 pseudo-chromosomes (N = 19 A + X1X2X3X4), and we predicted 18,424 protein-coding genes in this genome. This study will provide valuable genomic resources for future studies on the biology, water adaptation, and genome evolution of water bugs.

Abstract Background To discuss whether decreasing the pressure of endotracheal tube cuff slowly with a constant speed can decrease the incidence of coughing during extubation. Methods Ninety patients undergoing elective noncardiac surgery under general anesthesia with endotracheal intubation were randomly divided into two groups: group P, the pilot balloon was connected to a syringe and an aneroid manometer through a three-way stopcock, respectively, and the decrease of cuff pressure was controlled at 3 cmH2O/s during deflating before extubation; group C, the pressure in endotracheal tube cuff was decreased suddenly with a syringe extracting the air from the cuff rapidly at once exactly before extubation. The incidence of coughing during extubation period was recorded. Mean arterial pressure (MAP) and heart rate (HR) were recorded before general anesthesia induction (T0), just before cuff deflation (T1), immediately after deflation (T2), at 1 min (T3), 3 min (T4), and 5 min after extubation (T5). The occurrence of adverse reactions was also recorded. Results The initiation of coughing during extubation period occurs at immediately the time of balloon deflation. Compared with group C, the incidence of coughing was significantly decreased (P = 0.001), MAP and HR were significantly decreased at T2-T4 and T2-T5, respectively (P

Abstract Background With the demand for more effective and engaging teaching strategies in higher education, there is an imperative to blend traditional and innovative methods to optimize student learning outcomes. To address this educational need, this study sets out to design and evaluate a hybrid learning approach that integrates a flipped classroom based on working process systematization (termed “W + flipped classroom”) teaching design with blended online and offline methods based on the BOPPPS (bridge-in, objective/outcome, preassessment, participatory learning, post assessment, summary, termed “B + BOPPPS”) teaching model and explore its application effects in the field of biological separation engineering. Methods The undergraduate class of 2020 majoring in biomedical engineering from Huanghuai University was designated the control group (n = 74), while the undergraduate class of 2021 was chosen as the experimental group (n = 79). The control group received traditional teaching methods. The experimental group adopted the integrated “W + flipped classroom” and B + BOPPPS teaching models. After the conclusion of the teaching period, comparisons were made between the two groups in terms of course objective achievement, academic performance, and critical thinking skills. A survey was distributed to assess learning effectiveness. Semistructured interviews were conducted with teachers and students from the experimental group to evaluate teaching effectiveness. Results The integrated “W + flipped classroom” and B + BOPPPS teaching models significantly improved the academic performance and critical thinking skills of the experimental group. The teaching evaluation revealed high levels of acceptance among both teachers and students, along with improved satisfaction with the teaching methodology. Conclusion The integration of the “W + flipped classroom” teaching design with the “B + BOPPPS” teaching model provides a scientific foundation for future teaching reforms. This study serves as a valuable reference for implementing the OBE philosophy, enhancing learning outcomes, achieving engineering education accreditation, and cultivating high-quality applied talents in the field of bioengineering at applied universities.

Abstract Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

Abstract Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g.,

Adar-mediated adenosine-to-inosine (A-to-I) mRNA editing is a conserved mechanism that exerts diverse regulatory functions during the development, evolution, and adaptation of metazoans. The accurate detection of RNA editing sites helps us understand their biological significance. In this work, with an improved genome assembly of honeybee (Apis mellifera), we used a new orthology-based methodology to complement the traditional pipeline of (de novo) RNA editing detection. Compared to the outcome of traditional pipeline, we retrieved many novel editing sites in CDS that are deeply conserved between honeybee and other distantly related insects. The newly retrieved sites were missed by the traditional de novo identification due to the stringent criteria for controlling false-positive rate. Caste-specific editing sites are identified, including an Ile>Met auto-recoding site in Adar. This recoding was even conserved between honeybee and bumblebee, suggesting its putative regulatory role in shaping the phenotypic plasticity of eusocial Hymenoptera. In summary, we proposed a complementary approach to the traditional pipeline and retrieved several previously unnoticed CDS editing sites. From both technical and biological aspects, our works facilitate future researches on finding the functional editing sites and advance our understanding on the connection between RNA editing and the great phenotypic diversity of organisms.

Abstract Background A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Abstract Deep shale has the characteristics of large burial depth, rapid changes in reservoir properties, complex pore types and structures, and unstable production. The whole-rock X-ray diffraction (XRD) analysis, reservoir physical property parameter testing, scanning electron microscopy (SEM) analysis, high-pressure mercury intrusion testing, CO2 adsorption experimentation, and low-temperature nitrogen adsorption–desorption testing were performed to study the pore structure characteristics of marine shale reservoirs in the southern Sichuan Basin. The results show that the deep shale of the Wufeng Formation Longyi1 sub-member in the Luzhou area is superior to that of the Weiyuan area in terms of factors controlling shale gas enrichment, such as organic matter abundance, physical properties, gas-bearing properties, and shale reservoir thickness. SEM is utilized to identify six types of pores (mainly organic matter pores). The porosities of the pyrobitumen pores reach 21.04–31.65%, while the porosities of the solid kerogen pores, siliceous mineral dissolution pores, and carbonate dissolution pores are low at 0.48–1.80%. The pores of shale reservoirs are mainly micropores and mesopores, with a small amount of macropores. The total pore volume ranges from 22.0 to 36.40 μL/g, with an average of 27.46 μL/g, the total pore specific surface area ranges from 34.27 to 50.39 m2/g, with an average of 41.12 m2/g. The pore volume and specific surface area of deep shale gas are positively correlated with TOC content, siliceous minerals, and clay minerals. The key period for shale gas enrichment, which matches the evolution process of shale hydrocarbon generation, reservoir capacity, and direct and indirect cap rocks, is from the Middle to Late Triassic to the present. Areas with late structural uplift, small uplift amplitude, and high formation pressure coefficient characteristics favor preserving shale gas with high gas content and production levels.

Abstract This study comprehensively explores the clinical characteristics, diagnostic approaches, and treatment methods for liver mucinous cystic neoplasms (MCN). A retrospective analysis was conducted on seven individuals diagnosed with MCN, admitted to the Fifth Medical Center of the PLA General Hospital between October 2016 and May 2023. Preoperative AFP was negative, while CA19-9 was elevated in two cases. Surgical resection was performed for all patients. The patients showed favorable postoperative recovery. Follow-up revealed an excellent overall survival rate, except for one case of invasive carcinoma resulting in tumor recurrence and metastasis 6 months after surgery. MCN poses a diagnostic challenge due to the absence of distinct clinical and radiological features, leading to potential misdiagnosis and inappropriate treatment. Patients with suspected liver cystic diseases should consider the possibility of MCN. Surgical resection has proven to be a practical approach with satisfactory therapeutic outcomes.

Abstract Background Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80–90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies. Methods We performed a genome-wide study to identify hormone/drug-induced single nucleotide polymorphism (SNP) genotype - dependent gene-expression, known as PGx-eQTL, mediated by either an AR agonist (dihydrotestosterone) or a partial antagonist (enzalutamide), utilizing a previously well characterized lymphoblastic cell line panel. The association of the identified SNPs-gene pairs with breast cancer phenotypes were then examined using three genome-wide association (GWAS) studies that we have published and other studies from the GWAS catalog. Results We identified 13 DHT-mediated PGx-eQTL loci and 23 Enz-mediated PGx-eQTL loci that were associated with breast cancer outcomes post ER antagonist or aromatase inhibitors (AI) treatment, or with pharmacodynamic (PD) effects of AIs. An additional 30 loci were found to be associated with cancer risk and sex-hormone binding globulin levels. The top loci involved the genes IDH2 and TMEM9, the expression of which were suppressed by DHT in a PGx-eQTL SNP genotype-dependent manner. Both of these genes were overexpressed in breast cancer and were associated with a poorer prognosis. Therefore, suppression of these genes by AR agonists may benefit patients with minor allele genotypes for these SNPs. Conclusions We identified AR-related PGx-eQTL SNP-gene pairs that were associated with risks, outcomes and PD effects of endocrine therapy that may provide potential biomarkers for individualized treatment of breast cancer.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed –1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.

Paeonia have diverse flower colors, rich flower types, varying bloom periods, and delightful fragrances, rendering them highly valuable for both ornamental and economic purposes in horticulture. Investigating the developmental mechanisms of morphology, flower color, flowering and floral fragrance in Paeonia holds significant value for enhancing their ornamental traits and conducting germplasm improvement. This review provides an overview of research progress on Paeonia flower morphology (including flower bud differentiation, classification, omics applications in shape studies, and functional genes regulating flower morphology), flower colors (omics applications in color research and functional genes regulating flower colors), bloom periods (flower bud dormancy, flowering time), and fragrances (preparation, analysis, components, and molecular biology research of flower fragrances) within the Paeonia. Additionally, it offers a comprehensive analysis of current research challenges and future directions.

Background The aim of this study was to characterize the burden of valvular heart disease (VHD)‐related heart failure (HF) in Group of 20 (G20) countries. Methods and Results Using data from the 2019 Global Burden of Disease Study, we estimated VHD‐related HF burdens (cases, age‐standardized prevalence rates, and years lived with disabilities rates) in G20 countries from 1990 to 2019 by age, sex, and sociodemographic index. The burden of VHD‐related HF increased in G20 countries from 1990 to 2019, exhibiting heterogeneity across VHD subtypes. In 2019, Italy, the United States, and the Russian Federation had the highest age‐standardized prevalence rates of nonrheumatic VHD‐related HF, whereas India, Brazil, and Mexico had the lowest. Rheumatic VHD‐related HF was most prevalent in China, India, and Italy, whereas the Republic of Korea, Brazil, and Turkey had the lowest. Nonrheumatic VHD‐related HF prevalence peaked among G20 countries in individuals ≥85 years of age, whereas rheumatic VHD‐related HF peaked in those 75 to 84 years of age in several countries, including China, India, the Russian Federation, Mexico, Argentina, and Turkey. Age‐standardized prevalence rates of nonrheumatic VHD‐related HF showed a decreasing trend, more pronounced in women, whereas rheumatic VHD‐related HF increased in both sexes, with a lower increase in men. Nonrheumatic VHD‐related HF burden correlated with age and sociodemographic index, whereas rheumatic VHD‐related HF burden was highest in middle sociodemographic index countries for those

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

Abstract Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well‐supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

Recent exploration efforts have revealed significant industrial gas flow from the Wujiaping Formation marine shale in the Longmen–Wushankan area of the eastern Sichuan Basin, underscoring its considerable exploration potential. In this study, the reservoir characteristics and exploration potential of the Wujiaping Formation shale gas in this area are further evaluated. On the basis of well rock electrical properties, experimental analyses, and depositional and structural patterns in the eastern region, we characterize the reservoir properties and identify the primary factors controlling shale gas accumulation. The results indicate that the Wujiaping shale is characterized by a high organic matter content, favorable pore types, high porosity, and a high content of brittle minerals, which are conducive to subsequent development and fracturing. A positive correlation is observed between the total organic carbon (TOC) content, porosity, brittle mineral content, and shale gas content. The TOC content is strongly correlated with the gas content (the correlation coefficient is 0.75). The high shale gas yield of the Wujiaping Formation is attributed to a combination of favorable sedimentary environments, pore conditions, roof and floor conditions, and fracturing capabilities. However, compared with the Longmaxi Formation in the Sichuan Basin, the Wujiaping Formation shale is characterized by a lower porosity, thinner shale, and deeper burial, posing challenges for exploration and development. In this study, criteria for evaluating Wujiaping Formation shale gas are established, and four favorable exploration areas are identified. Overall, the Permian Wujiaping Formation marine shale in the Longmen–Wushankan area holds promising exploration and development potential. Further exploration and an enhanced understanding of this formation will provide valuable guidance for future marine shale gas exploration and development in this area.

To systematically investigate the factors affecting the performance of permeable concrete on road surfaces, blocks with different porosity, particle sizes, water-to-cement ratios, and cement-to-aggregate ratios were prepared. Additionally, varying amounts of admixtures were added to some blocks to explore the influence of the admixture types and content on the performance of permeable concrete. The results indicate that the larger the particle size of the aggregate used in the block preparation, the higher the permeability coefficient of the blocks and the lower the compressive strength. The water-to-cement ratio affects the strength of the cement matrix, resulting in variations in the block strength. A higher cement-to-aggregate ratio leads to a lower porosity in the permeable concrete, a higher cement matrix content, a reduced permeability coefficient, and an increased compressive strength of the blocks.

Abstract The Da’anzhai Member limestone in the central Sichuan Basin holds significant importance as a tight oil-producing formation. Despite its crucial role, the intricate patterns of hydrocarbon enrichment and the elusive geological factors dictating high-yield production have impeded tight oil exploration and development in the Sichuan Basin. This study delves into the geological characteristics of tight oil and identifies key factors influencing high-yield production, utilizing comprehensive data derived from cores, thin sections, well logging, seismic studies, and production tests of the Da’anzhai Member in the western Gongshanmiao within the central Sichuan Basin. Our findings reveal that the primary productive strata for tight oil are the Da 1 (1st Submember of the Da’anzhai Member) and Da 3 (3rd Submember of the Da’anzhai Member) Submembers, characterized by high-energy and low-energy shell beach microfacies. The kerogen type is sapropelic, ranging from mature to highly mature, positioning it as a moderately good hydrocarbon source rock. The predominant lithology of the reservoir consists of coquina and argillaceous coquina, with secondary dissolved pores, fractures, and nano-scale micropores serving as the predominant reservoir spaces. The overall lithology represents a dense limestone reservoir of the pore-fracture type, featuring low porosity and permeability. Critical controlling factors for achieving high-yield production of tight oil encompass lithological composition, fracture development, tectonic position, and source-reservoir configuration. Notably, substantial coquina thickness, fracture development, and the strategic relationship between the lower reservoir and upper source rocks contribute significantly to unlocking high tight oil yields. Additionally, thin-layer coquina emerges as a potential area for realizing increased oil and gas production capacity during later stages of development. This comprehensive analysis sheds light on the intricate dynamics governing tight oil production in the Da’anzhai Member, offering valuable insights for advancing exploration and development strategies in the Sichuan Basin.

Abstract Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Acamprosate and naltrexone are anti-craving drugs used in AUD pharmacotherapy. However, molecular mechanisms underlying their anti-craving effect remain unclear. This study utilized a patient-derived induced pluripotent stem cell (iPSC)-based model system and anti-craving drugs that are used to treat AUD as “molecular probes” to identify possible mechanisms associated with alcohol craving. We examined the pathophysiology of craving and anti-craving drugs by performing functional genomics studies using iPSC-derived astrocytes and next-generation sequencing. Specifically, RNA sequencing performed using peripheral blood mononuclear cells from AUD patients with extreme values for alcohol craving intensity prior to treatment showed that inflammation-related pathways were highly associated with alcohol cravings. We then performed a genome-wide assessment of chromatin accessibility and gene expression profiles of induced iPSC-derived astrocytes in response to ethanol or anti-craving drugs. Those experiments identified drug-dependent epigenomic signatures, with IRF3 as the most significantly enriched motif in chromatin accessible regions. Furthermore, the activation of IRF3 was associated with ethanol-induced endoplasmic reticulum (ER) stress which could be attenuated by anti-craving drugs, suggesting that ER stress attenuation might be a target for anti-craving agents. In conclusion, we found that craving intensity was associated with alcohol consumption and treatment outcomes. Our functional genomic studies suggest possible relationships among craving, ER stress, IRF3 and the actions of anti-craving drugs.

Abstract Experience replay has been instrumental in achieving significant advancements in reinforcement learning by increasing the utilization of data. To further improve the sampling efficiency, prioritized experience replay (PER) was proposed. This algorithm prioritizes experiences based on the temporal difference error (TD error), enabling the agent to learn from more valuable experiences stored in the experience pool. While various prioritized algorithms have been proposed, they ignored the dynamic changes of experience value during the training process, merely combining different priority criteria in a fixed or linear manner. In this paper, we present a novel prioritized experience replay algorithm called PERDP, which employs a dynamic priority adjustment framework. PERDP adaptively adjusts the weights of each criterion based on average priority level of the experience pool and evaluates experiences’ value according to current network. We apply this algorithm to the SAC model and conduct experiments in the OpenAI Gym experimental environment. The experiment results demonstrate that the PERDP exhibits superior convergence speed when compared to the PER.

The biological signaling molecule nitric oxide (NO) has recently emerged as a metabolic precursor for the creation of microbial natural products with diversified structures and biological activities. Within the biosynthetic gene clusters (BGCs) of these compounds, genes associated with NO production pathways have been pinpointed. In this study, we employ a nitric oxide synthase (NOS)-guided genome mining strategy for the targeted discovery of NO-derived bacterial natural products and NO-utilizing biocatalysts. We show that a conserved NOS-containing BGC, distributed across several actinobacterial genomes, is responsible for the biosynthesis of lajollamycin, a unique nitro-tetraene-containing antibiotic whose biosynthetic mechanism remains elusive. Through a combination of in vivo and in vitro studies, we unveil the first cytochrome P450 enzyme capable of catalyzing olefin nitration in natural product biosynthesis. These results not only expand the current knowledge about biosynthetic nitration processes but also offer an efficient way for targeted identification of NO-utilizing metabolic pathways and novel nitrating biocatalysts.

Adenosine-to-inosine (A-to-I) RNA editing recodes the genome and confers flexibility for the organisms to adapt to the environment. It is believed that RNA recoding sites are well suited for facilitating adaptive evolution by increasing the proteomic diversity in a temporal-spatial manner. The function and essentiality of a few conserved recoding sites are recognized. However, the experimentally discovered functional sites only make up a small corner of the total sites, and there is still the need to expand the repertoire of such functional sites with bioinformatic approaches. In this study, we define a new category of RNA editing sites termed ‘conserved editing with non-conserved recoding’ and systematically identify such sites in Drosophila editomes, figuring out their selection pressure and signals of adaptation at inter-species and intra-species levels. Surprisingly, conserved editing sites with non-conserved recoding are not suppressed and are even slightly overrepresented in Drosophila. DNA mutations leading to such cases are also favoured during evolution, suggesting that the function of those recoding events in different species might be diverged, specialized, and maintained. Finally, structural prediction suggests that such recoding in potassium channel Shab might increase ion permeability and compensate the effect of low temperature. In conclusion, conserved editing with non-conserved recoding might be functional as well. Our study provides novel aspects in considering the adaptive evolution of RNA editing sites and meanwhile expands the candidates of functional recoding sites for future validation.

ABSTRACTAlthough A-to-I RNA editing leads to similar effects to A-to-G DNA mutation, nonsynonymous RNA editing (recoding) is believed to confer its adaptiveness by ‘epigenetically’ regulating proteomic diversity in a temporospatial manner, avoiding the pleiotropic effect of genomic mutations. Recent discoveries on the evolutionary trajectory of Ser>Gly auto-editing site in insect Adar gene demonstrated a selective advantage to having an editable codon compared to uneditable ones. However, apart from pure observations, quantitative approaches for justifying the adaptiveness of individual RNA editing sites are still lacking. We performed a comparative genomic analysis on 113 Diptera species, focusing on the Adar Ser>Gly auto-recoding site in Drosophila. We only found one species having a derived Gly at the corresponding site, and this occurrence was significantly lower than genome-wide random expectation. This suggests that the Adar Ser>Gly site is unlikely to be genomically replaced with G during evolution, and thus indicating the advantage of editable status over hardwired genomic alleles. Similar trends were observed for the conserved Ile>Met recoding in gene Syt1. In the light of evolution, we established a comparative genomic approach for quantitatively justifying the adaptiveness of individual editing sites. Priority should be given to such adaptive editing sites in future functional studies.

ABSTRACTAdar-mediated adenosine-to-inosine (A-to-I) RNA editing mainly occurs in nucleus and diversifies the transcriptome in a flexible manner. It has been a challenging task to identify beneficial editing sites from the sea of total editing events. The functional Ser>Gly auto-recoding site in insect Adar gene has uneditable Ser codons in ancestral nodes, indicating the selective advantage to having an editable status. Here, we extended this case study to more metazoan species, and also looked for all Drosophila recoding events with potential uneditable synonymous codons. Interestingly, in D. melanogaster, the abundant nonsynonymous editing is enriched in the codons that have uneditable counterparts, but the Adar Ser>Gly case suggests that the editable orthologous codons in other species are not necessarily edited. The use of editable versus ancestral uneditable codon is a smart way to infer the selective advantage of RNA editing, and priority might be given to these editing sites for functional studies due to the feasibility to construct an uneditable allele. Our study proposes an idea to narrow down the candidates of beneficial recoding sites. Meanwhile, we stress that the matched transcriptomes are needed to verify the conservation of editing events during evolution.

ABSTRACTGut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy. Bacteroides genus, the enriched gut symbionts, has shown promise in treating fatty liver. However, further investigation is needed to identify specific beneficial Bacteroides strains for metabolic disorders in NAFLD and elucidate their underlying mechanisms. In this study, we observed a positive correlation between the abundance of Bacteroides thetaiotaomicron (B. theta) and the alleviation of metabolic syndrome in the early and end stages of NAFLD. Administration of B. theta to HFD-fed mice for 12 weeks reduced body weight and fat accumulation, decreased hyperlipidemia and insulin resistance, and prevented hepatic steatohepatitis and liver injury. Notably, B. theta did not affect these indicators in low-fat diet (LFD)-fed mice and exhibited good safety. Mechanistically, B. theta regulated gut microbial composition, characterized by a decreased Firmicutes/Bacteroidetes ratio in HFD-Fed mice. It also increased gut-liver folate levels and hepatic metabolites, alleviating metabolic dysfunction. Additionally, treatment with B. theta increased the proportion of polyunsaturated fatty acid in the mouse liver, offering a widely reported benefit for NAFLD improvement. In conclusion, this study provides evidence that B. theta ameliorates NAFLD by regulating gut microbial composition, enhancing gut-liver folate and unsaturated fatty acid metabolism, highlighting the therapeutic role of B. theta as a potential probiotic for NAFLD.

The aim of this study was to establish a regeneration system of watermelon. Watermelon W1 was selected as the experimental material using seedling shoots as a receptor. The effects of different concentrations of 6-Benzylaminopurine (6-BA) on the shoot-tip of watermelon seedlings were studied. Number of shoots at the stem tip were counted every other day until the new buds reached 2 cm. The new stem tip was cut, and the effect of different concentrations of Murashige and Skoog (MS) medium on the number of regenerated roots and root length of shoots were studied. The results showed that the differentiation rate was highest when the 6-BA concentration was 0.7 mg/mL to 0.8 mg/mL. The optimum concentration for root regeneration was 1/8 MS. At this concentration, the number rooted was the highest, and root length was also promoted.

Developing high‐performance, high‐stability, and low‐cost nonprecious metal catalysts to enhance the performance of zinc–air batteries (ZABs) holds significant importance. A bifunctional catalyst consisting of cobalt oxide (CoO) nanocrystals on nitrogen‐doped reduced graphene oxide nanoribbons (N‐rGONR) as a novel substrate is successfully synthesized in this work. This synthesized bifunctional catalyst exhibits mesoporous structure, and remarkable synergistic effects between CoO nanocrystals and N‐rGONR, demonstrating excellent activity and durability in both oxygen reduction reactions and oxygen evolution reactions. Notably, the resulting aqueous electrolyte ZABs show a high discharge peak power density of 196 mW cm−2, a high specific capacity of 615.9 mAh g−1, and long‐time stability for 648 h. Furthermore, the assembly of 1D and 2D flexible solid‐state ZABs fabricated using this bifunctional catalyst exhibits stable electrochemical performance, even under severe deformation. These results underscore the considerable promise of implementing the CoO@N‐rGONR catalyst structure in next‐generation advanced energy storage and conversion devices.

Summary: Genetic basis underlying the biodiversity and phenotypic plasticity are fascinating questions in evolutionary biology. Such molecular diversity can be achieved at multi-omics levels. Here, we sequenced the first chromosome-level genome of assassin bug Rhynocoris fuscipes, a polyphagous generalist predator for biological control of agroecosystems. Compared to non-predatory true bugs Apolygus lucorum and Riptortus pedestris, the R. fuscipes-specific genes were enriched in diet-related genes (e.g., serine proteinase, cytochrome P450) which had higher expression level and more exons than non-diet genes. Extensive A-to-I RNA editing was identified in all three species and showed enrichment in genes associated with diet in R. fuscipes, diversifying the transcriptome. An extended analysis between five predaceous and 27 phytophagous hemipteran species revealed an expansion of diet-related genes in R. fuscipes. Our findings bridge the gap between genotype and phenotype, and also advance our understanding on genetic and epigenetic bases governing the diet shifts in ture bugs.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a frequently utilized organophosphorus flame retardant (OPFR) and has been extensively detected in environmental media. Prolonged daily exposure to EHDPP has been linked to potential retinal damage, yet the adverse impacts on the retina are still generally underexplored. In this research, we explored oxidative stress, inflammation, and the activating mechanisms initiated by EHDPP in mouse retinal photoreceptor (661 W) cells following a 24 h exposure period. Our research demonstrated that EHDPP led to a decline in cell viability that was directly proportional to its concentration, with the median lethal concentration (LC50) being 88 µM. Furthermore, EHDPP was found to elevate intracellular and mitochondrial levels of reactive oxygen species (ROS), trigger apoptosis, induce cell cycle arrest at the G1 phase, and modulate the expression of both antioxidant enzymes (Nrf2, HO-1, and CAT) and pro-inflammatory mediators (TNF-α, IL-1β, and IL-6) within 661 W cells. These findings indicate that retinal damage triggered by EHDPP exposure could be mediated via the Nrf2/HO-1 signaling pathway in these cells. Collectively, our investigation revealed that oxidative stress induced by EHDPP is likely a critical factor in the cytotoxic response of 661 W cells, potentially leading to damage in retinal photoreceptor cells.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

BackgroundPrevious observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D.MethodGenetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane’s Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results.ResultIn our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding.ConclusionThis study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.

Abstract Global human‐induced warming has intensified water circulation in the atmospheric environment and altered the streamflow generation regime. The VIC hydrological model approach for impact assessment of climate change and human activities mainly focuses on variations in streamflow, but ignores other critical flooding characteristics induced by extreme streamflow, especially bivariate flooding characteristics. In this work, the copula functions are employed to structure the flooding risk under the shared socioeconomic pathway (SSP) across the Yellow River basin (YRB). This is based on the multi‐model ensemble (MME) and Delta downscaling outputs (Delta‐MME) of the CMIP6 global climate models (GCMs), as well as the flooding characteristics simulated by VIC hydrological model. Compared to the reference period (1995–2014), Delta‐MME reveals a significant warming and humidifying trend under three SSPs over the YRB. Despite uncertainties originating from climate variables and hydrological model, multiple findings underscore the substantial influence of climate change on the flooding generation regime in YRB. This includes: (a) an increase in the streamflow under all SSPs; (b) a larger flooding peak (Q) and volume (W) under SSP585, with Q and W at the Huayuankou hydrologic station (HYK) increasing by 52.7% and 44.8%, respectively; (c) an advancement in the bivariate flooding risk, particularly in SSP585 where flooding co‐occurrence return period at HYK may be more than 50 times earlier. This study underscores that the urgent need to enhance social resilience to climate change in the YRB.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3β as the major kinase hub in MASH. GSK3β-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

The high‐value utilization of biomass feedstock is fascinating but limited by efficient C─H activation to break C─C bonds. Herein, F‐Fe2O3‐Mn photoanodes with modulable compressive strain are fabricated by gradient infusion of Mn into F‐doped hematite (F‐Fe2O3), which is illustrated to be highly efficient for oxidative C─C bond cleavage of various bio‐based 1,2‐diols to produce benzoic acids or aromatic ketones (94.5–97.2% yields) in photoelectrocatalytic (PEC) device, coupling with a high H2 production of 1180 μmol cm−2 (≈96% yield). The gradient doping of Mn species into the photoelectrode bulk results in improved photoexcited carriers separation and transfer efficiency of the photoelectrode (3.41 mA cm−2). On the other hand, the lattice distortion induced by Mn doping also leads to a strain effect on F─Fe2O3─Mn, which can precisely modulate the photoelectrode electronic structure. Control experiments, in situ characterization, and theoretical calculations elaborate that compressive strain is capable of adjusting the position of the d‐band center to facilitate C─H activation, remarkably enabling PEC oxidative C─C bond breaking of 1,2‐diol and the desorption of the oxidized product. This “one‐stone‐two‐bird” strategy presents a straightforward protocol for efficiently breaking C─C bonds in organic and biomass transformations via PEC oxidation.

PurposeThis study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.Material and methodA dual-sample Mendelian randomization (MR) analysis was conducted using the publicly available genome-wide association study (GWAS) data. The inverse variance weighted based on the random effects model (Re-IVW) method was used as the main statistical analysis. Complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were applied to detect or correct the impact of horizontal pleiotropy.ResultRe-IVW showed a genetic predictive causal relationship of phimosis on glomerulonephritis (odds ratio [OR]: 1.37 [1.13–1.65], p = 0.00149) and IgA glomerulonephritis (OR: 1.57 [1.18–2.09), p = 0.00187). Suggestive evidence indicated that phimosis was associated with chronic nephritis syndrome (OR: 1.23 (1.00–1.51), p = 0.0481], acute nephritis syndrome (OR: 1.50 [1.13–2.01], p = 0.0058), and impotence (OR: 1.39 [1.11–1.73], p = 0.0035). Kidney and ureteral stone (OR: 1.14 [1.04–1.26], p = 0.0069), urethral strictures (OR: 1.26 [1.07–1.48], p = 0.0050), benign prostatic hyperplasia (OR: 1.07 [1.01–1.13], p = 0.0242), and decreased testicular function (OR: 0.72 [0.56–0.94], p = 0.0141) have genetically predictive causal relationships.ConclusionIn summary, we employed a series of reliable analytical methods to investigate the association between phimosis and 26 urogenital diseases. We have reported several strong associations, but more research is needed to evaluate whether this discovery is replicated in other environments and to gain a better understanding of potential mechanisms.

PurposeDiabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic “druggable” genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.Material and methodWe used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.ResultOverall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P

Abstract The Tibetan Plateau (TP) is the highest and one of the most extensive plateaus in the world and serves as a hotspot of climate change. In the context of climate warming, changes in evapotranspiration (ET) and external water vapor transport have a significant impact on assessing atmospheric water cycle processes over the TP. By using the Weather Research and Forecasting (WRF) model for long-term simulations and the finer box model for the calculation of water vapor along the boundary of the TP, the external atmospheric water vapor transport and its spatiotemporal characteristics over the TP are finely described. The simulated precipitation and ET are well-simulated compared with observation. Research results show that: (1) The total water path on the TP decreases from southeast to northwest. Water vapor is mainly transported into the TP from the western and southern boundaries. The net water vapor flux transported from the western boundary to the TP by westerly wind is negative, while the net water vapor flux transported from the southern boundary to the TP by southerly wind is positive. (2) In spring and winter, water vapor is mainly transported into the TP by mid-latitude westerlies from the western boundary. In summer, water vapor transport controlled by mid-latitude westerlies weakens, and water vapor is mainly transported into the TP from the southern boundary. In autumn, water vapor controlled by mid-latitude westerlies gradually strengthens, and water vapor is mainly transported into the TP from the western boundary. In addition, the ratio of ET to precipitation on the TP is about 0.48, and the moisture recycling is about 0.37. Water vapor mainly comes from external water vapor transport.

Abstract Aphidius gifuensis is a parasitoid wasp and primary endoparasitoid enemy of the peach potato aphid, Myzus persicae. Artificially reared, captive wasps of this species have been extensively and effectively used to control populations of aphids and limit crop loss. However, the consequences of large-scale releasing of captive A. gifuensis, such as genetic erosion and reduced fitness in wild populations of this species, remains unclear. Here, we sequence the genomes of 542 A. gifuensis individuals collected across China, including 265 wild and 277 human-intervened samples. Population genetic analyses on wild individuals recovered Yunnan populations as the ancestral group with the most complex genetic structure. We also find genetic signature of environmental adaptation during the dispersal of wild populations from Yunnan to other regions. While comparative genomic analyses of captive wasps revealed a decrease in genetic diversity during long-term rearing, population genomic analyses revealed signatures of natural selection by several biotic (host plants) or abiotic (climate) factors, which support maintenance of the gene pool of wild populations in spite of the introduction of captive wasps. Therefore, the impact of large-scale release is reduced. Our study suggests that A. gifuensis is a good system for exploring the genetic and evolutionary effects of mass rearing and release on species commonly used as biocontrol agents.

Self-powered photodetectors which operate without external power sources hold immense promise in future photodetection systems. To achieve high-performance self-powered optoelectronic devices, efficient electron-hole pair separation is critical to generate high photocurrents. In this work, we successfully synthesized semiconducting graphene nanoribbons (GNRs) with a direct bandgap of 1.80 eV and employed them to construct a high-performance GNR/Al2O3/IGZO heterostructure photodetector. The built-in electric field in the heterojunctions enables this photodetector to exhibit remarkable performance, showing a responsivity of up to 68 mA/W, a detectivity of 8.34 × 1010 Jones, and rapid response times of 21/20 ms at zero bias. Furthermore, the photodetector features a wide spectral detection range of 405 to 1550 nm. These results highlight the promising potential of GNR/IGZO p-n heterojunction-based self-powered photodetectors in optoelectronic applications.

Microdroplets have many unique features such as small size and high electric field, therefore they can be accelerated to initiate chemical reactions and even promote some reactions that cannot be carried out in liquid phase. N, N-Dimethylaniline (DMA) is commonly used in medicine as a raw material for the synthesis of pharmaceutical intermediates. At present, the study involving in the detection of DMA is mainly focused on quantitative detection, and there is few reports on oxidation reaction and gas phase dissociation reaction of DMA. In this paper, the oxidation behavior and dissociation reaction of DMA and related compounds were studied by microdroplet spray mass spectrometry and tandem mass spectrometry. It was found that the ultra-high electric field spontaneously generated by microdroplets at the air-water interface can enable the oxidation reaction of DMA and related compounds to form abundant radical cation DMA+·. By changing the reaction distance, carrier gas pressure, injection velocity, sample concentration and substituent groups, the influence of experimental conditions and substituent modes on the generation of DMA+· was explored. The result showed that the presence of electron donor groups is benefit for the stability of radical cations. After the dissociation of DMA+·, the main product ions were generated by elimination of hydrogen radical and a successive elimination of HC≡N via methyl migration reaction. In addition, when the electron-donating CH3 group was connected with DMA, the intensity of related radical cation increased obviously, indicating that the electron-donating groups promoted the migration reaction. In conclusion, the stable transient intermediate DMA+· that is difficult to prepare by other means, was obtained by microdroplet reaction in this study. This method is helpful to deepen the understanding of the chemical promoted oxidation reaction characteristics of water droplets and enriches the rearrangement reaction types of aniline compounds in gas phase dissociation. It is expected that the prepared active species such as high reactivity radical cations will be applied to chemical industry or pharmaceutical fields in the future.

Designed to enhance the privacy of user transactions, mixed coin technology has created disruptions to the address clustering rules typically used for cryptocurrency regulation.Consequently, hackers have begun utilizing mixed coin technology as a tool for money laundering and fund evasion, which has raised concerns among financial regulators regarding the detection of mixed coin transactions.Currently, most detection methods for mixed coin transactions rely on data analysis and statistics, lacking a comprehensive understanding of the internal workings of these transactions.This lack of knowledge may undermine the credibility and effectiveness of detection methods due to the absence of reliable verification data.CoinJoin, a decentralized mixed coin concept, represents one approach, and commercial implementations like Wasabi have gained popularity.Drawing from the characteristics of CoinJoin and its restriction on the size of anonymous transaction sets and mixed coin amounts, a general detection method for CoinJoin mixed coin transactions was devised.Such transactions typically involved multiple inputs and outputs, with more output items than UTXOs in the input, and a high occurrence of duplicate values among the output amounts.A basic detection method for Wasabi was developed by combining the generic detection method for CoinJoin with specific features of Wasabi, as identified in related studies, to complete the detection process.A trusted validation dataset was acquired from the Wasabi platform service interface, and this dataset was analyzed to achieve two objectives.First, the alignment of rule parameters in the Wasabi base detection method was accomplished.Second, a new metric was proposed, measuring the ratio of the highest frequency of duplicate values in the output amount of transactions to the number of UTXOs in the input.This metric assessed the level of user participation in mixed coin transactions, providing a measure of user freedom.Using these two approaches, significant progress is made in the detection of mixed coin transactions.The experiments show that the recall rate of Wasabi’s basic detection method is 94.2% and the accuracy rate is 67.2%.After the analytical feedback from the credible validation dataset, the recall rate of the improved detection method reaches 100% and the accuracy rate is above 99%.The total market size of the entire CoinJoin type of mixed coin transactions was evaluated and predicted based on a common test methodology.It is concluded that the number of CoinJoin mixed coin transactions in today’s mixed coin market represents 1.9 per 1 000 of all Bitcoin transactions and 3.7 per 1 000 of the transaction value at most.

The late Quaternary chronostratigraphic framework and marine transgression have long been research focal points in the Yangtze River Delta. The frequent channel oscillation and river incision in the Yangtze Delta have led to the frequent absence of complete stratigraphic records. Complete marine transgression records have yet to be discovered within the same borehole in this region. Based on lithostratigraphy, biostratigraphy, paleomagnetic chronology, and OSL dating studies of the ZKA01 borehole in the Dongtai area of the northern wing of the Yangtze River Delta region, the stratigraphic chronology framework since Marine Isotope Stage 5 (MIS5) was established. The ZKA01 borehole was found to have comprehensively recorded five marine transgression events in the Yangtze Delta region since late Pleistocene. The results indicate that the B/M boundary of the ZKA01 borehole is located at 108 m, and the M/G boundary is at 300.25 m. The boundary between the Middle and Upper Pleistocene is positioned at the bottom of the third marine transgression layer, precisely at 92.95 m. The boundary between the Upper Pleistocene and Holocene boundaries is located at the bottom of the first marine transgression layer discovered in the borehole, precisely at 16.65 m. The first three transgressions occurred during MIS5 (128–74 ka), of which MIS 5.1 had a larger scale, second only to the scale of the transgressions during the Holocene. The fourth transgression occurred during MIS3 (60–24 ka), equivalent in depth and age to the "II marine phase layer" of MIS3. The fifth transgression occurred during MIS1 (12 ka to present), depositing in a nearshore shallow marine environment, with the largest scale observed. Additionally, it was identified that the first transgression layer (MIS5) is approximately equivalent in burial depth across various regional boreholes, serving as a distinctive stratigraphic marker for stratigraphic division and comparative studies in the Yangtze River Delta. These research findings hold significant importance for Quaternary stratigraphic division and comparative analysis of sedimentary environments in the Yangtze River Delta.