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Abstract The recent colder winters in midlatitude Eurasia have been proposed to result from Arctic sea-ice decline. However, large uncertainties remain regarding this link in the present variable climate. Here, we present ice-rafted debris records from the eastern Arctic and geochemical data from the temperate East China Sea to reconstruct Holocene changes in sea ice and the East Asian winter monsoon. Our reconstructions and climate numerical simulations revealed enhanced Arctic sea-ice decline but warmer winters in East Asia in the mid-Holocene than in the late Holocene. In the warmer mid-Holocene, enhanced Arctic sea-ice loss transferred more heat from intensive summer solar insolation to the winter atmosphere, suppressing meridional heat transport; thus, less high-latitude cold air moved to lower latitudes in Asia due to the weakened winter monsoon. Our findings imply that the colder winters in East Asia may not change the long-term trend toward winter warming in the context of Arctic sea-ice decline.

Abstract Objective Shift work and Shift Work Sleep Disorder (SWSD) are known to affect the secretion of several neurotransmitters and hormones associated with premature ejaculation (PE). However, their specific influence on the regulation of male ejaculation remains unclear. This study explores the relationship between shift work, SWSD, and PE. Methods From April to October 2023, a cross-sectional survey was conducted across five regions of China to explore the work schedules, sleep quality, and sexual function of male workers. Participants' sleep quality was evaluated using a validated SWSD questionnaire, and their erectile function and ejaculatory control were assessed with the International Inventory of Erectile Function (IIEF-5) scores and Premature Ejaculation Diagnostic Tool (PEDT) scores, respectively. Univariate and multivariate linear regression analyses were employed to identify risk factors associated with PE. Confounders were controlled using multiple regression models, and clinical prediction models were developed to predict PE onset and assess the contribution of risk factors. Results The study included 1239 eligible participants, comprising 840 non-shift workers and 399 shift workers (148 with SWSD and 251 without SWSD). Compared to non-shift working males, those involved in shift work (β 1.58, 95% CI 0.75 – 2.42, p

Abstract While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a “three-dimensional” control for the era of slidetronics.

Chronic absenteeism can impact high school students’ long- and short-term development, especially in socio-economically challenged areas such as the Texas-Mexico border. We aimed to identify effective public school absenteeism policies and provide a roadmap for further investigation and state policy advocacy. This study analyzed four district-level school absenteeism policies in 88 public school districts along the Texas-Mexico border: requiring parental notification after one absence, offering incentives for student attendance, assignment of a Truancy Prevention Facilitator, and punishing students for absenteeism. District policies were collected through a review of district websites, student handbooks, codes of conduct, District Improvement Plans, and District of Innovation Plans. The chronic absenteeism and emergent bilingual/English learner (EB/EL) absenteeism rates reported in Texas Education Agency Texas Academic Performance Reports for grades 9-12 were utilized as attendance indicators. Hierarchical linear modeling, an ordinary least square regression-based analysis, was used to examine association relationships between the policies as independent variables and absenteeism rates as the dependent variables. School districts that do not offer attendance incentives and assign officers as truancy prevention facilitators have the highest predicted total chronic absenteeism rate; districts that do not offer attendance incentives and assign support services personnel as truancy prevention facilitators have the highest predicted EB/EL absenteeism rate. Districts with attendance incentives also are associated with higher EB/EL absenteeism. Identifying effective school policies to reduce chronic absenteeism will help districts better tailor the implementation of state policies and promote access to education and services.

Global climate change has intensified the water cycle, leading to frequent extreme precipitation events, posing a significant threat to railway infrastructure and safety operations. Based on the analysis of past and future precipitation changes in China, this study investigates the impact of climate change on railway safety operations. The study reveals the following findings: (1) Under the influence of the intensified East Asian summer monsoon and the northward shift of the subtropical high during the 2017–2021 compared to the 2012–2016, precipitation has significantly decreased (120 mm) in the regions south of the Yangtze River and South China, while it has increased (60 mm) in the regions from the eastern of Northwest China to the middle and lower reaches of Yangtze River; The operational precipitation risk has decreased for Urumqi, Lanzhou, Qinghai-Tibet Group, Xi’an, and Wuhan railway bureaus (abbreviated as Bureau), while it has increased for Nanchang, Chengdu, Zhengzhou, Shanghai, and Shenyang Bureaus. Particularly noteworthy is that despite a decrease in total annual precipitation for Nanchang bureau (15.3 mm/a), the frequency of intense precipitation events has increased, leading to an increased operational precipitation risk. (2) During the 21st century, under high (SSP5-8.5), medium (SSP2-4.5), and low (SSP1-2.6) forcing scenarios, all projections indicate that most of the China will experience an increasing trend in precipitation, with significant increases in precipitation observed in the regions south of the Yangtze Rive, South and Southwest China. The higher the greenhouse gas emissions, the more pronounced the increasing trend in precipitation. (3) Compared to the 20th century, under high (SSP5-8.5), medium (SSP2-4.5), and low (SSP1-2.6) forcing scenarios, all projections indicate that the total annual precipitation hours, railway inspection, speed limit, and closure risk hours have all increased on a national scale during the 21st century. The operational precipitation risk for railways has also increased. The higher the alert level for railway precipitation (precipitation < inspection < speed limit < closure), the higher the proportion of risk hours compared to the 20th century. By the late 21st century, the railway inspection, speed limit, and closure risk hours have increased by 175%, 463%, and 647%, respectively, compared to the 20th century.

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material.Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson’s trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies.Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05).Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

Exploring simple, efficient and applicable interfacial optimisation methods is important to enhance the overall performance of basalt fibre (BF) fabric-reinforced thermoplastic composite laminates. Graphene oxide (GO) was introduced on the surface of BF fabric through electrostatic self-assembly to improve the interfacial bonding of BF fabric-reinforced polyamide 6 (PA6) composites laminates (BF/PA6) for enhancing the mechanical and frictional wear properties of the composites. It was concluded that surface electrostatic assembly of GO resulted in a significant increase in surface roughness, wettability, surface energy and surface chemical activity of BF fabrics without damaging the fibre backbone structure. With the GO concentration of 0.8 g/L, the interlaminar shear strength, impact strength, flexural strength and flexural modulus of the BF/PA6 composites were increased by 85.1 %, 43.2 %, 53.2 % and 63.4 %, and the average friction coefficient and wear rate was reduced by 15.2 % and 40.5 %, respectively. The introduced homogeneous GO strengthens the interfacial bonding of such fibre-fabric reinforced thermoplastic composites by creating mechanical engagement, similar compatibility and chemical cross-linking between the BF fabrics and the PA6 matrix. With enhanced interfacial bonding, the BF fabric reinforced thermoplastic composites possess enhanced stress damage resistance. Under frictional reciprocating stress, the introduced GO inhibited the generation and expansion of microcracks, formed frictional transfer film to play solid lubrication and anti-wear role, and enhanced the thermal stability of the composites to mitigate the frictional thermal damage. The interfacial enhancement method of BF fabric-reinforced thermoplastic composites provided in this study is simple, green, efficient and has good potential for application.

Background Circular RNAs (circRNAs) and their derived peptides represent largely unchartered areas in cellular biology, with many potential roles yet to be discovered. This study aimed to elucidate the role and molecular interactions of circSHPRH and its peptide derivative SHPRH-146aa in the pathogenesis of neuroblastoma (NB). Methods NB samples in the GSE102285 dataset were analyzed to measure circSHPRH expression, followed by in vitro experiments for validation. The role of SHPRH-146aa in NB cell proliferation, migration, and invasion was then examined, and luciferase activity assay was performed after SHPRH-146aa and RUNX1 transfection. Finally, the regulation of NB cell apoptosis by SHPRH-146aa combined with NFKBIA was tested. Results The GSE102285 dataset indicated overexpression of circSHPRH in NB samples, further supported by in vitro findings. Overexpression of circ-SHPRH and SHPRH-146aa inhibited proliferation, migration, and invasion of NB cells. A significant increase in apoptosis was observed, with upregulation of Caspase-3 and downregulation of Bcl-2. Furthermore, the peptide derivative SHPRH-146aa, derived from circSHPRH, suppressed NB cell malignancy traits, suggesting its role as a therapeutic target. A direct interaction between SHPRH-146aa and the transcription factor RUNX1 was identified, subsequently leading to increased NFKBIA expression. Notably, NFKBIA knockdown inhibited the pro-apoptotic effect of SHPRH-146aa on NB cells. Conclusion The study demonstrates that circ-SHPRH and SHPRH-146aa play significant roles in inhibiting the malignant progression of NB. They induce apoptosis primarily by modulating key apoptotic proteins Caspase-3 and Bcl-2, a process that appears to be regulated by NFKBIA. The SHPRH-146aa-RUNX1 interaction further elucidates a novel pathway in the regulation of apoptosis in NB. These findings indicate that circ-SHPRH and its derived peptide SHPRH-146aa could be potential therapeutic targets for NB treatment.

Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.

Abstract Background The development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis–trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development. Results We generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content. Conclusions Our results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.

The growth and development of apricot flower organs are severely impacted by spring frosts. To better understand this process, apricot flowers were exposed to temperatures ranging from 0 °C to −8 °C, including a control at 18 °C, in artificial incubators to mimic diverse low-temperature environments. We aimed to examine their physiological reactions to cold stress, with an emphasis on changes in phenotype, membrane stability, osmotic substance levels, and antioxidant enzyme performance. Results reveal that cold stress induces significant browning and cellular damage, with a sharp increase in browning rate and membrane permeability below −5 °C. Soluble sugars and proteins initially rise as osmoprotectants, but their content decreases at lower temperatures. Proline content consistently increases, suggesting a protective role. Antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), exhibit a complex pattern, with initial increases followed by declines at more severe cold conditions. Correlation and principal component analyses highlight the interplay between these responses, indicating a multifaceted adaptation strategy. The findings contribute to the understanding of apricot cold tolerance and inform breeding efforts for improved crop resilience.

Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.

Abstract Background We investigated the association between premature ejaculation (PE) and the quality of residential environment from a new perspective to explore the influencing factors of PE, especially in four PE subtypes. We selected 499 adult males to participate in this study from September 2021 to September 2022. The satisfaction of residential environment was assessed by the Perceived Residential Environment Quality Indicators (PREQIs) scale, the control ability over ejaculation was assessed using the premature ejaculation diagnostic tool (PEDT), and their depression was assessed using the self-rating depression scale (SDS). Results The Architectural and Town-planning Spaces (ATS), Green Spaces (GS), and Commercial Services (CS) of PE patients (N = 346) were compared with those of control group (N = 153), showed a significant difference (p

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar epithelial cell injury and lung fibroblast overactivation. At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. Avitinib (AVB) is a novel oral and potent third-generation tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC). However, the role of avitinib in pulmonary fibrosis has not yet been established. In the present study, we used in vivo and in vitro models to evaluate the role of avitinib in pulmonary fibrosis. In vivo experiments first verified that avitinib significantly alleviated bleomycin-induced pulmonary fibrosis in mice. Further in vitro molecular studies indicated that avitinib inhibited myofibroblast activation, migration and extracellular matrix (ECM) production in NIH-3T3 cells, mainly by inhibiting the TGF-β1/Smad3 signalling pathways. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation.

Abstract Stimulated by the enhancing requirements for system safety as well as process reliability in complex industrial processes, this paper investigates a data‐driven fault detection and fault‐tolerant control scheme for large‐scale systems. To this end, a pair‐wise decomposition approach is first presented based on the inclusion principle, which expands the original large‐scale system into a set of disjointed pair‐wise subsystems. Then, for the pair‐wise subsystems, the observer‐based residual generators and observer‐based state feedback controllers for fault detection and fault‐tolerant control purpose are further developed in a decentralized way. On this basis, the fault‐tolerant controller for the original large‐scale system is obtained by the coordination and contraction of the decentralized observer‐based state feedback controllers. Finally, the feasibility and effectiveness of the proposed scheme are demonstrated through the case study on a multi‐area interconnected power system.

Idiopathic pulmonary fibrosis (IPF) is an incurable chronic progressive disease with a low survival rate and ineffective therapeutic options. We examined the effects of imrecoxib, a nonsteroidal anti-inflammatory drug, on experimental pulmonary fibrosis. The mouse IPF model was established by intratracheal instillation of bleomycin. From Day 0 to Day 13, the mice were orally administered imrecoxib (100 mg/kg) and pirfenidone (200 mg/kg) daily, and from Day 7 to Day 13, the mice were orally administered pirfenidone and imrecoxib daily. The tissues were dissected on the 14th day. Mouse body weight was measured, and histopathological examination and hydroxyproline content analysis confirmed that the administration of imrecoxib exerted a similar effect to pirfenidone. Compared with bleomycin-induced mice, imrecoxib-treated mice showed significantly reduced inflammatory factor expression (IL-1 and TNF-α) and inflammatory cell numbers (macrophages, lymphocytes, and neutrophils) in BALF (bronchoalveolar lavage fluid). Our experiment tested the ability of imrecoxib to inhibit the signal pathway involved in gene expression induced by TGF-β1 in the NIH-3T3 cell line in vitro. Western blotting showed that imrecoxib (20 μM and 40 μM) inhibited the expression of fibronectin, type I collagen and CTGF. In addition, imrecoxib reduced the levels of p-ERK1/2. The changes in the expression of related proteins in mouse lung tissue were similar to those in cells. In summary, our findings suggested that the administration of imrecoxib prevented and treated murine IPF by inhibiting inflammation and the TGF-β1-ERK1/2 signaling pathway.

Abstract A communication channel should be built to transmit information from one place to another. Imaging is 2 or higher dimensional information communication. Conventionally, an imaging channel comprises a lens with free space at its both sides, whose transfer function is usually known and hence the response of the imaging channel can be well defined. Replacing the lens with a thin scattering medium, the image can still be extracted from the detected optical field, suggesting that the scattering medium retains or reconstructs not only energy but also information transmission channels. Aided by deep learning, we find that unlike the lens system, there are different channels in a scattering medium: the same scattering medium can construct different channels to match the manners of source coding. Moreover, it is found that without a valid channel, the convolution law for a spatial shift-invariant system (the output is the convolution of the point spread function and the input object) is broken, and in this scenario, information cannot be transmitted onto the detection plane. Therefore, valid channels are essential to transmit information through even a spatial shift-invariant system. These findings may intrigue new adventures in imaging through scattering media and reevaluation of the known spatial shift-invariance in various areas.

IntroductionAlzheimer's disease (AD) is a neurodegenerative disease that significantly impacts the quality of life of patients and their families. Neuroimaging-driven brain age prediction has been proposed as a potential biomarker to detect mental disorders, such as AD, aiding in studying its effects on functional brain networks. Previous studies have shown that individuals with AD display impaired resting-state functional connections. However, most studies on brain age prediction have used structural magnetic resonance imaging (MRI), with limited studies based on resting-state functional MRI (rs-fMRI).MethodsIn this study, we applied a graph neural network (GNN) model on controls to predict brain ages using rs-fMRI in patients with AD. We compared the performance of the GNN model with traditional machine learning models. Finally, the post hoc model was also used to identify the critical brain regions in AD.ResultsThe experimental results demonstrate that our GNN model can predict brain ages of normal controls using rs-fMRI data from the ADNI database. Moreover the differences between brain ages and chronological ages were more significant in AD patients than in normal controls. Our results also suggest that AD is associated with accelerated brain aging and that the GNN model based on resting-state functional connectivity is an effective tool for predicting brain age.DiscussionOur study provides evidence that rs-fMRI is a promising modality for brain age prediction in AD research, and the GNN model proves to be effective in predicting brain age. Furthermore, the effects of the hippocampus, parahippocampal gyrus, and amygdala on brain age prediction are verified.

IntroductionThe gender disparity in autism spectrum disorder (ASD) has been one of the salient features of condition. However, its relationship between the pathogenesis and genetic transcription in patients of different genders has yet to reach a reliable conclusion.MethodsTo address this gap, this study aimed to establish a reliable potential neuro-marker in gender-specific patients, by employing multi-site functional magnetic resonance imaging (fMRI) data, and to further investigate the role of genetic transcription molecules in neurogenetic abnormalities and gender differences in autism at the neuro-transcriptional level. To this end, age was firstly used as a regression covariate, followed by the use of ComBat to remove the site effect from the fMRI data, and abnormal functional activity was subsequently identified. The resulting abnormal functional activity was then correlated by genetic transcription to explore underlying molecular functions and cellular molecular mechanisms.ResultsAbnormal brain functional activities were identified in autism patients of different genders, mainly located in the default model network (DMN) and precuneus-cingulate gyrus-frontal lobe. The correlation analysis of neuroimaging and genetic transcription further found that heterogeneous brain regions were highly correlated with genes involved in signal transmission between neurons’ plasma membranes. Additionally, we further identified different weighted gene expression patterns and specific expression tissues of risk genes in ASD of different genders.DiscussionThus, this work not only identified the mechanism of abnormal brain functional activities caused by gender differences in ASD, but also explored the genetic and molecular characteristics caused by these related changes. Moreover, we further analyzed the genetic basis of sex differences in ASD from a neuro-transcriptional perspective.

Abstract PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins.

AbstractBackground Previous research has shown that testosterone deficiency (TD) increases the risk of anemia, but it is unclear whether anemia affects testosterone levels. This study investigated the influence of anemia on testosterone levels.Methods Utilizing data from six NHANES cycles, including demographic, testosterone levels, and hemoglobin concentrations, we employed multivariable-adjusted logistic regression to investigate the relationship between anemia and testosterone levels. Moreover, a two-sample Mendelian randomization (MR) study employing genome-wide association study (GWAS) data examined the causal relationship. Kaplan–Meier survival estimation was used to compared the overall survival (OS) of anemic and nonanemic patients with low testosterone and normal testosterone levels.Results The inclusion of 21,786 participants (2318 with anemia and19,468 without anemia) revealed that nonanemic patients exhibited higher testosterone levels than did anemic patients (β = 22.616, 95% CI: 3.873–41.359, p = 0.01807). MR analysis confirmed anemia as a cause of TD (OR = 1.045, 95% CI: 1.020–1.071, p

Abstract Introduction To describe our initial experience with ileal ureteral replacement (IUR) for the management of ureteral avulsion (UA) during ureteroscopic lithotripsy. Methods Between September 2010 and April 2021, ten patients received ileal ureteral replacement for ureteral avulsion during ureteroscopic lithotripsy. Anterograde urography and computed tomography urography (CTU) were applied to evaluate the lesion. Follow-up was performed with magnetic resonance urography and renal ultrasound as well as clinical assessment of symptoms. We retrospectively analysed the clinical data of ten patients treated with ileal ureteral replacement for the treatment of ureteral avulsion. Results Four patients underwent open ileal ureteral replacement, two underwent laparoscopic ileal ureteral replacement, and four underwent robotic-assisted ileal ureteral replacement. The mean operative time (OT) was 310 min (range 191–530). The mean estimated blood loss (EBL) was 193 mL (range 10–1000). The mean length of the ileal graft was 21 cm (range 12–25). The median postoperative hospital time was 13 days (range 7–19). All surgeries were effectively completed, and no case required open conversion in laparoscopic and robotic-assisted surgeries. There was no obvious hydronephrosis according to contrast-enhanced computed tomography 3-dimensional reconstruction images without serious complications or progressive hydronephrosis during a median follow-up duration of 51 months (range 5–131), and the success rate was 100%. Conclusions Our initial results and experience showed that ileal ureteral replacement for the management of ureteral avulsion during ureteroscopic lithotripsy is safe and feasible.

Objective: To explore the mechanical properties, biological activity, and osteogenic ability of 3D printed TC4 titanium (Ti) alloy dental implants treated with surface modification.Methods: Dental implants with 30% porosity were manufactured using selective laser melting (SLM) technology (group 3D), while traditional numerically-controlled machine tools (CNC) were used to manufacture implants without porosity (group SL). The implants were then surface modified through sandblasting and acid etching (groups 3DA1 and SLA1), and then alkali etching (groups 3DA2 and SLA2). The physicochemical properties of the implants were measured using a Vickers hardness instrument, scanning electron microscope (SEM), X-ray diffraction (XRD), energy dispersive spectrometer (EDS), and profilograph before and after surface modification. Next, the biocompatibility, bioactivity, and osteogenic ability of the implants were evaluated using apatite deposition experiments, alkaline phosphatase (ALP) activity, and semiquantitative analysis of extracellular matrix mineralization.Results: There were significant differences in morphology, geometric accuracy, mechanical properties, surface roughness, and hydrophilicity between groups 3D and SL. Furthermore, surface modification improved the physicochemical properties of the porous implants. Implants with sandblasting, acid etching, and alkali etching demonstrated better biocompatibility, bioactivity, and osteogenic ability than implants without surface modification in both groups 3D and SL. Additionally, the implants of groups 3D have higher bioactivity than that of groups SL.Conclusion: Surface modification and the macroporous structure of implants can improve their bioactivity and osteogenic ability, enhancing the application of Ti alloy dental implants.

Pertussis is a severe human respiratory tract infectious disease caused by Bordetella pertussis that primarily affects infants and young children. However, the acellular pertussis vaccine currently administered can induce antibody and Th2 immune responses but fails to prevent the nasal colonization and transmission of B. pertussis, causing a resurgence of pertussis, so improved pertussis vaccines are urgently needed. In this study, we created a two-component pertussis vaccine candidate containing a conjugate prepared from oligosaccharides and pertussis toxin. After demonstrating the ability of the vaccine to induce a mixed Th1/Th2/Th17 profile in a mouse model, the strong in vitro bactericidal activity and IgG response of the vaccine were further demonstrated. In addition, the vaccine candidate further induced efficient prophylactic effects against B. pertussis in a mouse aerosol infection model. In summary, the vaccine candidate in this paper induces antibodies with bactericidal activity to provide high protection, shorten the duration of bacterial existence, and further reduce disease outbreaks. Therefore, the vaccine has the potential to be the next generation of pertussis vaccines.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.

Non f-electron systems containing narrow electronic band and localized moments are a useful platform to study the Kondo lattice problem. Here, by using scanning tunneling microscopy, the authors show a transition from the insulating gap to a tuneable Kondo resonance in 1T-TaS2 by Pb intercalation.

Drug resistance remains a major challenge in the clinical treatment of gastrointestinal stromal tumours (GISTs). While acquired on‐target mutations of mast/stem cell growth factor receptor (KIT) kinase is the major resistance mechanism, activation of alternative signalling pathways may also play a role. Although several second‐ and third‐generation KIT kinase inhibitors have been developed that could overcome some of the KIT mutations conferring resistance, the low clinical responses and narrow safety window have limited their broad application. The present study revealed that nintedanib not only overcame resistance induced by a panel of KIT primary and secondary mutations, but also overcame ERK‐reactivation‐mediated resistance caused by the upregulation of fibroblast growth factor (FGF) activity. In preclinical models of GISTs, nintedanib significantly inhibited the proliferation of imatinib‐resistant cells, including GIST‐5R, GIST‐T1/T670I and GIST patient‐derived primary cells. In addition, it also exhibited dose‐dependent inhibition of ERK phosphorylation upon FGF ligand stimulation. In vivo antitumour activity was also observed in several xenograft GIST models. Considering the well‐documented safety and pharmacokinetic profiles of nintedanib, this finding provides evidence for the repurposing of nintedanib as a new therapy for the treatment of GIST patients with de novo or acquired resistance to imatinib.

Abstract High-resolution optical imaging through or within thick scattering media is a long sought after yet unreached goal. In the past decade, the thriving technique developments in wavefront measurement and manipulation do not significantly push the boundary forward. The optical diffusion limit is still a ceiling. In this work, we propose that a scattering medium can be conceptualized as an assembly of randomly packed pinhole cameras and the corresponding speckle pattern as a superposition of randomly shifted pinhole images. The concept is demonstrated through both simulation and experiments, confirming the new perspective to interpret the mechanism of information transmission through scattering media under incoherent illumination. We also analyze the efficiency of single-pinhole and dual-pinhole channels. While in infancy, the proposed method reveals a new perspective to understand imaging and information transmission through scattering media.

All along, safety accidents in the field of bridge construction have continued to arise, costing society's development financial and material resources and taking away people’s personal safety, turning into an urgent need for safety managers in the field to solve the subject research. Researchers look forward to continued innovative exploration to find new ways of working safely and using them in the construction industry. On this basis, BIM virtual scenes are introduced to create a universal scene specification dataset in the field of bridge construction and a dataset of unsafe potential hazard characteristics in the field of bridge construction. Nanobots are artificial intelligence systems built to simulate biological nanomachine constructions in life activities and important biological events in life processes. In this paper, BIM virtual scenarios incorporating intelligent nanomaterial robot mapping technology are migrated to bridge engineering safety management. According to the collected construction scene images and BIM (building information model) virtual scenes, build the construction scene dataset, use intelligent robots to obtain construction scenes, and load them into the trained construction on-the-spot neural network modeling to complete the bridge construction scene identification safety discrimination to select more comprehensive and more stringent management solutions as safety management personnel management methods on-the-spot.

Abstract Respiratory pathogens transmit primarily through particles such as droplets and aerosols. Although often overlooked, the resuspension of settled droplets is also a key facilitator of disease transmission. In this review, we discuss the three main mechanisms of aerosol generation: direct generation such as coughing and sneezing, indirect generation such as medical procedures, and resuspension of settled droplets and aerosols. The size of particles and environmental factors influence their airborne lifetime and ability to cause infection. Specifically, humidity and temperature are key factors controlling the evaporation of suspended droplets, consequently affecting the duration in which particles remain airborne. We also suggest material‐based approaches for effective prevention of disease transmission. These approaches include electrostatically charged virucidal agents and surface coatings, which have been shown to be highly effective in deactivating and reducing resuspension of pathogen‐laden aerosols.

Abstract The electronic evolution of doped Mott insulators has been extensively studied for decades in search of exotic physical phases. The proposed Mott insulator 1T-TaS2 provides an intriguing platform to study the electronic evolution via doping. Here we apply scanning tunneling microscopy (STM) to study the evolution in Ti-doped 1T-TaS2 at different doping levels. The doping Ti atom locally perturbs the electronic and spin state inside the doped star of David and induces a clover-shaped orbital texture at low-doping levels (x

In responding to climate change, energy efficiency is one of the key factors for sustainable development, where the high-tech industry can play an important role. However, whether the development of high-tech industry impacts energy efficiency as well as the mechanisms behind still remain unclear. Thus, based on the dynamic spatial Durbin model, this study aims to investigate: 1) the impact of high-tech industry development on energy efficiency from three perspectives of high-tech industry development, i.e., scale, productivity, and agglomeration, and 2) the mechanisms behind such impact especially through technological innovation and industrial structure. The results confirm the influence of high-tech industry development on energy efficiency both directly and indirectly. On the one hand, our analysis contributes on the existing body of scientific knowledge by expounding the relationship between scale, productivity, and agglomeration of high-tech industry development and energy efficiency. On the other hand, it further deepens the understanding on such relationship by revealing two underlying mechanisms behind, i.e., through promoting technological innovation, the productivity and agglomeration of high-tech industries can either completely or partially improve energy efficiency, while the scale and agglomeration of high-tech industries can hinder energy efficiency to a certain level through the industrial restructuring. Based on these findings, this paper provides some policy implications, which are believed to facilitate the practices of energy conservation and emission reduction in China.

Based on meteorological observations, traffic flow data and information of traffic accidents caused by fog or agglomerate fog along the expressways in Jiangsu Province and Anhui Province in China from 2012 to 2021, key impact factors including meteorological conditions, road hidden dangers and traffic flow conditions are integrated to establish the prediction model for risk levels of expressway agglomerate fog-related accidents. This model takes the discrimination of the occurrence conditions of agglomerate fog as the starting term, and determines the hazard levels of agglomerate fog-related accidents by introducing the probability prediction value of meteorological conditions for fog-related accident as the disaster-causing factor. On this basis, the hourly road traffic flow and the location of road sections with a hidden danger of agglomerate fog are taken as traffic and road factors to construct the correction scheme for the hazard levels, and the final predicted risk level of agglomerate fog-related accident is obtained. The results show that for the criteria of disaster-causing factor classification threshold, 72.3% of fog-related accidents correspond to a hazard of a medium level or above, and 86.2% of the road traffic flow conditions are consistent with the levels of the traffic factor defined based on parametric indexes. For risk level prediction, six out of the seven agglomerate fog-related accidents correspond to the level of higher risk or above, which can help provide meteorological support for traffic safety under severe weather conditions. Moreover, the model takes into account the impacts of traffic flow and the road environment, which is conducive to further improving the reliability of the risk assessment results.

The objective of this work was to study the influence of palm oil on the VOCs emitted during the heat treatment of Afromosia (Pericopsis Elata Van Meeuwen) and Newtonia (Newtonia paucijuga Harms) wood by comparing to the VOCs emitted during the heat treatment under air. Two batches of Afrormosia and Newtonia wood samples were heated under air and palm oil at temperatures of 160 °C, 180 °C, and 200 °C for 2 h. Then, the VOCs were collected by Solid Phase Micro Extraction (SPME) and measured using a Gas Chromatograph and Mass Spectrometer (GC-MS). The results showed that the temperature, the wood species, and the treatment medium have a great influence on the categories and percentages of VOCs emitted. In the air heat treatment, ethers were the most emitted VOCs from Afrormosia and Newtonia when these woods were thermally treated at 160 °C. Newtonia treated under air at 180 °C emitted more esters, while Afrormosia continued to emit more ethers under the same conditions. Moreover, Afrormosia and Newtonia treated at 200 °C emitted more ketones and aldehydes, respectively. Regarding the heat treatment of Afrormosia and Newtonia wood under palm oil, a similarity of the VOCs emitted from Newtonia with those emitted from Afrormosia under the same conditions was observed. Furthermore, palm oil was the main factor conditioning the nature of the VOCs emitted during the heat treatment. In general, for the treatment of Afrormoshia wood with palm oil, the VOCs emitted, such as alcohols, alkanes, and ethers, decreased with the treatment temperature. Ethers and ketones increased with the processing temperature. At 160 °C and 180 °C, the percentage of aldehydes was highest, while, at 200 °C, the percentage of esters was highest. Similarly, for Newtonia treated under palm oil, adehydes, ethers, and alcohols were the most abundant VOCs emitted at 160 °C. However, their percentages decreased with the increase in the treatment temperature; on the contrary, esters and ketones were weakly emitted at 160 °C and became abundant with the increase in temperature. Additionally, the ethers formed during the heat treatment of Afrormosia and Newtonia wood treated under air carry acetyl groups, while those formed during the treatment of the said wood under palm oil carry hydroxyl groups.

Background: High intake of food away from home is associated with poor diet quality. This study examines how the COVID-19 pandemic period and Food Away from Home (FAFH) inflation rate fluctuations influenced dining out behaviors. Methods: Approximately 2800 individuals in Texas reported household weekly dining out frequency and spending. Responses completed prior to the COVID-19 pandemic (2019 to early 2020) were compared to the post-COVID-19 period (2021 through mid-2022). Multivariate analysis with interaction terms was used to test study hypotheses. Results and Conclusion: From the COVID-19 period (before vs. after), the unadjusted frequency of dining out increased from 3.4 times per week to 3.5 times per week, while the amount spent on dining out increased from $63.90 to $82.20. Once the relationship between dining out (frequency and spending) was adjusted for FAFH interest rate and sociodemographic factors, an increase in dining out frequency post-COVID-19 remained significant. However, the unadjusted increase in dining out spending did not remain significant. Further research to understand the demand for dining out post-pandemic is warranted.

Certain materials without inversion symmetry may allow for a nonlinear anomalous Hall effect with conserved time reversal symmetry. Here, the authors report an extremely large c-axis nonlinear anomalous Hall effect in the non-centrosymmetric Td phase of MoTe2 and WTe2 without intrinsic magnetic order that is dominated by extrinsic scattering.

Résumé Contexte L’éjaculation précoce (EP) est. un problème multifactoriel, avec une étiologie compliquée, qui a des effets néfastes sur la fonction sexuelle des partenaires féminines. Cependant, il existe un manque d’études en Chine portant sur la relation entre les facteurs liés à l’EP et la dysfonction sexuelle féminine (DSF). Nos objectifs étaient d’identifier et d’explorer la relation entre les facteurs associés à l’EP et la DSF. Résultats Finalement, des informations ont été recueillies auprès de 761 couples: 445 couples avec plaintes d’EP et 316 couples sans plaintes d’EP. L’âge moyen des hommes avec et sans plaintes d’EP était respectivement de 36,29 ± 9,87 ans et 31,48 ± 10,77 ans. Les partenaires féminines du groupe avec plaintes d’EP ont obtenu des valeurs abaissées des scores, totaux et par sous-domaines, de l’indice de la fonction sexuelle féminine (IFSF), et environ 65% d’entre elles ont eu un diagnostic de DSF (pour 31,96% dans le groupe témoin). Une durée d’EP de plus de 14 mois, un temps intravaginal auto-estimé de latence d’éjaculation (IELT auto-estimé) de moins de 2 min, une attitude négative envers des problèmes d’EP, une introversion des hommes, et une dépression chez les hommes étaient des facteurs de risque de la DSF dans le groupe avec EP. Conclusions L’EP affecte non seulement le patient lui-même, mais aussi la conjointe. L’analyse complète révèle une relation et une interaction claires entre la fonction sexuelle féminine et l’EP. En outre, dans le traitement de l’EP, nous ne devrions pas ignorer l’apparition de la DSF et son impact, et nous devrions mettre l’accent sur le traitement du couple.

In recent years, China is increasingly dependent on imported wood. Afrormosia and Newtonia are some of the imported species with good utilization potential. However, both of them also have problems with poor dimensional stability. In order to make better use of these two types of wood, the influence of heat treatment under air and palm oil conditions on the color, dimensional stability, and hygroscopicity of Afrormosia and Newtonia was investigated. The Afrormosia and Newtonia wood samples were heated in air or palm oil medium for two hours at 160 °C, 180 °C and 200 °C, respectively. Then, the color, weight changes, swelling, moisture absorption and chemical structure were evaluated for each case. As results, the heat treatments with air or palm oil increased the dark color of Newtonia and Afrormosia wood and this increase was proportional to the treatment temperature. The tangential and radial swelling coefficient for air heat treatment of Afrormosia wood at 200 °C were, respectively, reduced by 24.59% and 19.58%, while this reduction for Newtonia was 21.32% and 14.80%. The heat treatment in palm oil further improved the stability and hygroscopicity of the wood, showing that the Afrormosia samples treated by palm oil at 200 °C underwent a decrease of its tangential and radial swelling coefficient, respectively, by 49.34% and 45.88%, whereas the tangential and radial swelling coefficient of Newtonia treated under the same conditions were reduced by 42.85% and 33.63%, respectively. The heat treatments of Afrormosia and Newtonia samples under air at 200 °C diminished the water absorption by 21.67% and 22.12%. The water absorption of Afrormosia and Newtonia heat-treated under palm oil at 200 °C was reduced, respectively, by 39.40% and 37.49%. Moreover, the FTIR analysis showed the decrease of hydroxyl groups in proportion to the wood treatment temperature.

The reluctance of people to receive safe and recommended available vaccines is a well-documented public health challenge. As information and communication technologies evolve, this challenge gets more complex and even harder to manage during complex public health situations. In this experimental study, we examine the relationship between vaccine information frames (with scientific information vs. without scientific information) and channels (through government vs. religious organizations) and vaccination willingness in the U.S. in the context of a pandemic. Additionally, we evaluate the interaction between vaccine skepticism, vaccine information frames, and vaccine information channels on vaccination willingness. This experimental study uses data from Amazon Mechanical Turk (MTURK) to evaluate the relationships between vaccine skepticism, vaccine information frames, and channels on vaccination willingness. We find that contrary to our hypothesis, a vaccine advisory framed with scientific information decreases people’s vaccination willingness compared to one framed without scientific information. Additionally, the impact of framing on vaccination willingness is conditioned on participants’ skepticism—participants who hold skepticism toward the vaccine but received information framed with scientific information score significantly higher in vaccination willingness compared to participants who do not hold skepticism toward a vaccine. The results suggest that the factors impacting vaccination willingness are complex and nuanced. Thus, policymakers should be more strategic with the delivery of vaccination information, especially during complex health crises.

Ejaculation is a complex biphasic process involving a series of neurophysiological activities, such as the contraction of a large number of muscle groups and the ejaculation of semen from the urethra anterior. Due to the complexity of the process, many related factors have not been fully clarified, resulting in ejaculation dysfunction. As a common ejaculation dysfunction, lifelong premature ejaculation (LPE) is a problem for many people. Notably, gene polymorphism might play an important role in the etiology of LPE. However, the quest for identifying the actual genetic loci that contribute to LPE etiology has not been successful. Due to discrepancies in the design and methods of research, the correlation of most reports was not obtained in subjective replication experiments, and the conclusions may be inconsistent. In our study, three groups of ejaculation rats, namely, “rapid, normal, and delayed,” were selected based on the animal model of premature ejaculation (PE) in rats and the theory of ejaculation. Among them, the rats in the “rapid” ejaculation group can be used to stimulate humans with PE. Subsequently, we used the rat brain tissue for whole-transcriptome sequencing to screen the differential genes among the three groups. We tried to identify the actual genetic loci that contribute to PE etiology and provide a theoretical basis for the targeted therapy of PE.

Abstract Searching multiple types of terahertz (THz) irradiation source is crucial for the THz technology. In addition to the conventional fermionic cases, bosonic quasi‐/particles also promise energy‐efficient THz wave emission. Here, by utilizing a 2D ferromagnetic Cr2Ge2Te6 crystal, first a phonon‐related magneto‐tunable monochromatic THz irradiation source is demonstrated. With a low‐photonic‐energy broadband THz pump, a strong THz irradiation with frequency ≈0.9 THz and bandwidth ≈0.25 THz can be generated and its conversion efficiency could even reach 2.1% at 160 K. Moreover, it is intriguing to find that such monochromatic THz irradiation can be efficiently modulated by external magnetic field below 160 K. According to both experimental and theoretical analyses, the emergent THz irradiation is identified as the emission from the phonon‐polariton and its temperature and magnetic field dependent behaviors confirm the large spin‐lattice coupling in this 2D ferromagnetic crystal. These observations provide a new route for the creation of tunable monochromatic THz source which may have great practical interests in future applications in photonic and spintronic devices.

Cotton is an excellent model for studying crop polyploidization and domestication. Chromatin profiling helps to reveal how histone modifications are involved in controlling differential gene expression between A and D subgenomes in allotetraploid cotton. However, the detailed profiling and functional characterization of broad H3K4me3 and H3K27me3 are still understudied in cotton. In this study, we conducted H3K4me3- and H3K27me3-related ChIP-seq followed by comprehensively characterizing their roles in regulating gene transcription in cotton. We found that H3K4me3 and H3K27me3 exhibited active and repressive roles in regulating the expression of genes between A and D subgenomes, respectively. More importantly, H3K4me3 exhibited enrichment level-, position-, and distance-related impacts on expression levels of related genes. Distinct GO term enrichment occurred between A/D-specific and homeologous genes with broad H3K4me3 enrichment in promoters and gene bodies, suggesting that broad H3K4me3-marked genes might have some unique biological functions between A and D subgenome. An anticorrelation between H3K27me3 enrichment and expression levels of homeologous genes was more pronounced in the A subgenome relative to the D subgenome, reflecting distinct enrichment of H3K27me3 in homeologous genes between A and D subgenome. In addition, H3K4me3 and H3K27me3 marks can indirectly influence gene expression through regulatory networks with TF mediation. Thus, our study provides detailed insights into functions of H3K4me3 and H3K27me3 in regulating differential gene expression and subfunctionalization of homeologous genes, therefore serving as a driving force for polyploidization and domestication in cotton.

Introduction: Premature ejaculation (PE) is widely regarded as one of the most common sexual dysfunctions in men. The neurobiogenesis of PE is complex and involves the serotoninergic (5-HT) system. Aim: In this study, we investigated whether polymorphisms in the tryptophan hydroxylase 2 (TPH2) gene were associated with lifelong PE (LPE). Methods: A total of 121 men diagnosed with LPE were recruited from our outpatient clinics and 94 healthy controls from the health examination center. Intravaginal ejaculation latency time (IELT) was measured using a stopwatch. The PE diagnostic tool (PEDT) data were collected at the same time. All subjects with LPE and healthy controls were genotyped for polymorphisms in the TPH2 gene. Allele and genotype frequencies of single-nucleotide polymorphisms (SNPs) were compared between the patients and controls. Main Outcome Measure: The main outcome measures are IELT and PEDT to diagnose LPE. The association of LPE with TPH2 gene polymorphisms in these areas was investigated. Results: The IELT, PEDT scores, and education levels in the LPE group were significantly different from those in the control group. Statistically significant differences were found in the SNPs of SNV019 and rs4290270. The frequencies of the G allele and G/A genotype of SNV019 were significantly higher in the patients with LPE than in the controls (P = .045 and .037, respectively). The A allele and A/A genotype of rs4290270 were more frequent in the patients with LPE than in the controls (P = .037 and .049, respectively). In the dominant model of inheritance, the SNV019 polymorphism in the patients with LPE was significantly different from that in the controls (odds ratio [95% confidence interval] = 2.936 [1.066–8.084], P = .037). In men with LPE, there was no statistically significant association between genotype and median IELT. Conclusion: The SNPs SNV019 and rs4290270 of the TPH2 gene seemed to be associated with LPE in the Han population. Men with the A allele of SNV019 or the T allele of rs4290270 may be less likely to suffer from LPE.Fu X, Zhang X, Jiang T, et al. Association Between Lifelong Premature Ejaculation and Polymorphism of Tryptophan Hydroxylase 2 Gene in the Han Population. Sex Med 2020;8:223–229.

Abundant ferromanganese oxide deposits were recovered from the Chukchi Sea in the Arctic Ocean during the 7th Chinese Arctic Scientific Expedition in August 2016. Representative samples were collected to perform a mineralogical and geochemical analysis and elucidate their origin. Their mineral phases consist of todorokite, buserite, and birnessite, along with a small quantity of detrital minerals (quartz, feldspar, serpentine, kaolinite, and illite). Their elemental composition is rich in Ni and Mn compared to ferromanganese oxide deposits from other locations in the Chukchi Sea. The total rare earth element (REE) concentration varied from 138.95 to 207.23 μg/g with an average of 164.75 μg/g. The post-Archean Australian shale–normalized REE patterns have a slightly negative Ce anomaly and a positive Eu anomaly. The comprehensive geochemical and mineral data show that they have a mixed hydrothermal and diagenetic origin.

Climate change is a great threat to global biodiversity and has resulted in serious ecological consequences. Although the potential effects of climate change on genetic diversity have recently received much research attention, little research has focused on the impacts of climate change on genetic connectivity and the relationship between climate stability and genetic divergence. Here, we combined population connectivity with genetic data to predict the impacts of future climate change on genetic connectivity. Coupled with climatic variables and genetic data, we used POPS software to create spatially explicit simulations and predict the dynamics in genetic clusters in response to climate changes. A generalized additive model was employed to test the correlation between climatic stability and genetic diversification. Our findings indicated that a reduction in species distribution due to severe climate change would lead to a substantial loss of genetic connectivity. More severe future climatic scenarios would likely cause greater loss of variability or more distinct homogenization in genetic variation of species. Relatively low interpolated genetic distances are generally associated with areas of greater losses in climatic suitability from the present to the future. The displacement of climatic genetic clusters will challenge species adaptation to future climate change because of the loss of fundamental evolutionary potential. The persistence capacity of plant species may be weakened in the face of future climate change.

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders, which brings enormous burdens to the families of patients and society. However, due to the lack of representation of variance for diseases and the absence of biomarkers for diagnosis, the early detection and intervention of ASD are remarkably challenging. In this study, we proposed a self-attention deep learning framework based on the transformer model on structural MR images from the ABIDE consortium to classify ASD patients from normal controls and simultaneously identify the structural biomarkers. In our work, the individual structural covariance networks are used to perform ASD/NC classification via a self-attention deep learning framework, instead of the original structural MR data, to take full advantage of the coordination patterns of morphological features between brain regions. The self-attention deep learning framework based on the transformer model can extract both local and global information from the input data, making it more suitable for the brain network data than the CNN- structural model. Meanwhile, the potential diagnosis structural biomarkers are identified by the self-attention coefficients map. The experimental results showed that our proposed method outperforms most of the current methods for classifying ASD patients with the ABIDE data and achieves a classification accuracy of 72.5% across different sites. Furthermore, the potential diagnosis biomarkers were found mainly located in the prefrontal cortex, temporal cortex, and cerebellum, which may be treated as the early biomarkers for the ASD diagnosis. Our study demonstrated that the self-attention deep learning framework is an effective way to diagnose ASD and establish the potential biomarkers for ASD.

It is well-known that ultrasound has been studied for its cavitation, mechanical and thermal effects. As a pretreatment technology, ultrasonic alkali treatment has attracted much attention in the field of biomass biochemical transformation. In this study, the structural and dynamic changes of wood cell walls during ultrasound-water, alkali, and ultrasound-alkali treatments were investigated by stereoscopic microscopy, confocal Raman microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The results indicated that the ultrasound-water, alkali, and ultrasound-alkali treatments had the effect of removing extractives from conduits. The uniform self-shrinking samples with shrinkage conduits were obtained by the alkali and ultrasound-alkali treatments. All of the treatments affected the relative content, structure and distribution of the chemical components in the wood cell walls. Compared with water-immersion samples, the relative content of hemicellulose of the treated samples reduced from 32.31% to 7.02% for ultrasound-8% NaOH treated samples. For the signal intensity of lignin, ultrasound-water treated and ultrasound-alkali treated samples displayed a more significant reductions than the alkali treated samples in the cell wall region. The crystal zone and amorphous zone of cellulose coexisted before and after the treatment, for all of the treated samples, and particularly for the ultrasound-assisted treated samples, the crystallinity increased from 38.15% for water-immersion samples to 57.42% for ultrasound-8% NaOH treated samples.

BackgroundFew studies have explored the optimal examined lymph node count and lymph node density cutoff values that could be used to predict the survival of patients with penile cancer. We further clarify the prognostic value of lymph node density and examined lymph node count in penile cancer.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit penile cancer patients from 2010 to 2015. A retrospective analysis of penile cancer patients’ data from the First Affiliated Hospital of Anhui Medical University was performed for verification (2006–2016). The cutoff values of examined lymph node count and lymph node density were performed according to the ROC curve. Kaplan-Meier survival analysis was used to compare survival differences among different groups. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the significant variables. On the basis of Cox proportional hazards regression model, a nomogram was established and validated by calibration plot diagrams and concordance index (C-index).ResultsA total of 528 patients in the Surveillance, Epidemiology, and End Results cohort and 156 patients in the Chinese cohort were included in this study. Using the ROC curve, we found that the recommended cutoff values of ELN and LND were 13 and 9.3%, respectively (P 9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.

The potential technical and economic advantages and flexible operability of modular equipment make it increasing widely used in gas field production and development. In addition to considering the manufacturing process, the selection and serialization of modular equipment should be made according to the productivity prediction of a gas well, so as to meet the field demand to the greatest extent and enhance the flexibility of gathering and transportation system. This article proposes a method to determine the use planning of modular equipment in shale gas field. Considering the processing capacity, processing cost, floor area, construction cost of modular equipment, and the changes of market supply and demand, an optimization model is established. On the basis of the abovementioned model, the method of serialization of modular equipment is proposed. The effectiveness of the model is verified by an actual case study. It is proved that the model can optimize the layout of modular equipment, make the modular equipment run efficiently and economically, reduce costs, and increase efficiency. This study provides a reference for optimizing the equipment management strategy and promoting green production practice of shale gas production.

Background and Purpose: A large number of COVID-19 infections and deaths and the ensuing socioeconomic problems created widespread public fear around COVID-19. Fear around COVID-19 greatly influences people’s attitudes towards receiving the COVID-19 vaccines. The purpose of this study is examining (a) the impact of the public fear of COVID-19 (PFC) on the number of COVID-19 vaccinations at the county level; (b) the interaction effect between the PFC and per capita income, unemployment rates, and COVID-19 vaccines incentive policies, on the number of COVID-19 vaccinations at the county level. Method: This is a longitudinal analysis across states in the U.S. by using county-level data of 2856 counties from 1 February to 1 July. Random-effects models were adopted to analyze the associations between the PFC and the number of COVID-19 vaccinations. Result: the PFC was positively associated with the number of COVID-19 vaccinations at county-level, as PFC increases from 0 to 300, the predicted vaccination number increases from 10,000 to 230,000. However, the associations were divergent when the PFC interacts with county-level per capita income, unemployment rates, and incentive policies. Conclusion: public fear is an important indicator for the county-level vaccination numbers of COVID-19. However, it is critical to consider public fear and socioeconomic factors when making policies that aim to increase COVID-19 vaccination rates.