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Abstract Gastrointestinal cancer is the most common malignancy in humans, often accompanied by poor prognosis. N6-methyladenosine (m6A) modification is widely present in eukaryotic cells as the most abundant RNA modification. It plays a crucial role in RNA splicing and processing, nuclear export, translation, and stability. Human AlkB homolog 5 (ALKBH5) is a type of RNA demethylase exhibiting abnormal expression in various gastrointestinal cancers.It is closely related to the tumorigenesis, proliferation, migration, and other biological functions of gastrointestinal cancer. However, recent studies indicated that the role and mechanism of ALKBH5 in gastrointestinal cancer are complicated and even controversial. Thus, this review summarizes recent advances in elucidating the role of ALKBH5 as a tumor suppressor or promoter in gastrointestinal cancer. It examines the biological functions of ALKBH5 and its potential as a therapeutic target, providing new perspectives and insights for gastrointestinal cancer research.

Abstract Background This study aimed to explore the efficacy of hookwire for computed tomography (CT)-guided pulmonary nodule (PN) localization before video-assisted thoracoscopic surgery (VATS) resection and determine the risk factors for localization-related complications. Methods We enrolled 193 patients who underwent preoperative CT-guided PN hookwire localization. The patients were categorized into groups A (103 patients had no complications) and B (90 patients had complications) according to CT and VATS. Uni- and multivariate logistic regression analyses were used to identify risk factors for localization-related complications. A numerical rating scale was used to evaluate hookwire localization-induced pain. Results We successfully performed localization in 173 (89.6%) patients. Pneumothorax was the main complication in 82 patients (42.5%). Patient gender, age, body mass index, tumor diameter, consolidation tumor ratio, pathologic diagnosis, position adjustment during location, lesion location, waiting time for surgery, and pleural adhesions were not significantly different between the two groups. The number of nodules, number of punctures, scapular rest position, and depth of insertion within the lung parenchyma were significant factors for successful localization. Multivariate regression analysis further validated the number of nodules, scapular rest position, and depth of insertion within the lung parenchyma as risk factors for hookwire-localization-related complications. Hookwire localization-induced pain is mainly mild or moderate pre- and postoperatively, and some patients still experience pain 7 days postoperatively. Conclusions Hookwire preoperative PN localization has a high success rate, but some complications remain. Thus, clinicians should be vigilant and look forward to further improvement.

Abstract Although early solid diet supplementation is a common practice to improve the growth and development in goat kids, its biological mechanism how solid diet induces rumen microbiota and epithelial development is still unknow. In this study, rumen fermentation parameters, 16S rRNA sequencing for rumen content and epithelial microbiota, transcriptomics and proteomics of epithelium were determined to classify the effects of solid diet supplementation. Here, we classified the changes of goat phenotypes (i.e., growth performance, rumen fermentation and development) and linked them to the changes of rumen microbiota, transcriptome and expressed proteins. The mechanism of solid diet improving rumen development was elucidated preliminarily. Moreover, different roles between the rumen content and epithelial microbiota were identified. Thess datasets expands our understanding of the association between the early diet intervention and rumen development, providing the useful information how nutrient strategy affects rumen function and subsequently improves the host growth. The generated data provides insights in the importance of rumen niche microbiota and microbe-host interactions, which benefits future studies.

Abstract Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1–3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79–0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families’ genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.

Abstract Anchor and fissure grouting are used to repair earthen sites. However, the common method to obtain the compressive strength of grouting slurry would cause material, labor, and time losses. In addition the material properties, environmental and economic benefits have gained increasing attention. This study proposes a design framework for multi-objective proportioning optimization based on machine learning and metaheuristics. The results indicated that the eXtreme Gradient Boosting (XGBoost) model, whose hyper-parameters were optimized by a genetic algorithm, can accurately predicted the compressive strength of the slurries. The impact of the variables on development of compressive strength can explain the internal reaction mechanisms. The analytical framework based on meta-heuristic and technique for order of preference by similarity to an ideal solution (TOPSIS) provided Pareto-optimal solutions in design scenario of each sub-dataset. The framework proposed in this study can efficiently achieve mechanical, environmental, and economic design objectives of anchor grouting and fissure grouting slurries for repairing earthen sites.

Abstract The SMALL ACIDIC PROTEIN (SMAP) gene is evolutionarily indispensable for organisms. There are two copies of the SMAP gene in the Arabidopsis thaliana genome, namely, SMAP1 and SMAP2. The function of SMAP2 is similar to that of SMAP1, and both can mediate 2,4-D responses in the root of Arabidopsis. This study cloned the AtSMAP2 genetic promoter sequence. Two promoter fragments of different lengths were designed according to the distribution of their cis-acting elements, and the corresponding β- glucuronidase (GUS) expression vector was constructed. The expression activity of promoters of two lengths, 1993 bp and 997 bp, was studied by the genetic transformation in Arabidopsis. The prediction results of cis-acting elements in the promoter show that there are many hormone response elements in 997 bp, such as three abscisic acid response elements ABRE, gibberellin response elements P-box and GARE-motif and auxin response element AuxRR-core. Through GUS histochemical staining and qRT‒PCR analysis, it was found that the higher promoter activity of PAtSMAP2-997, compared to PAtSMAP2-1993, drove the expression of GUS genes at higher levels in Arabidopsis, especially in the root system. The results provide an important basis for subsequent studies on the regulation of AtSMAP2 gene expression and biological functions.

Abstract According to the latest cancer research data, there are a significant number of new cancer cases and a substantial mortality rate each year. Although a substantial number of clinical patients are treated with existing cancer drugs each year, the efficacy is unsatisfactory. The incidence is still high and the effectiveness of most cancer drugs remains unsatisfactory. Therefore, we evaluated the human proteins for their causal relationship to for cancer risk and therefore also their potential as drug targets. We used summary tumors data from the FinnGen and cis protein quantitative trait loci (cis-pQTL) data from a genome-wide association study, and employed Mendelian randomization (MR) to explore the association between potential drug targets and nine tumors, including breast, colorectal, lung, liver, bladder, prostate, kidney, head and neck, pancreatic caners. Furthermore, we conducted MR analysis on external cohort. Moreover, Bidirectional MR, Steiger filtering, and colocalization were employed to validate the main results. The DrugBank database was used to discover potential drugs of tumors. Under the threshold of False discovery rate (FDR)

Abstract Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 $$\times $$ × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Abstract This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease‐free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154–0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277–0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

Abstract The activation of cyclic GMP‐AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS‐STING pathway activation, macrophage‐selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer‐ or lipid‐based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage‐selective uptake and programmable activation of the cGAS‐STING pathway through precise self‐assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage‐selective uptake, endosomal escape, and cytosolic release of the cGAS‐recognizing DNA segment, leading to robust activation of the cGAS‐STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS‐STING activation.

The fire plume spilled from a window is believed to be one of the main fire sources with respect to a building façade fire, which happened previously in China. To have a deep understanding of vertical temperature distribution at window opening is of significance. In the current contribution, a series of compartment fire tests under over-ventilation were conducted with a 1.35 m × 1.35 m × 1.35 m compartment to clarify the critical discontinuity position (HD) by varying window opening sizes, opening aspect and heat release rate (HRR). Temperature history at the window openings were recorded by a thermocouple net. A theoretical calculation method of HD is detailed according to the compartment configuration. It is found that the critical discontinuity area is observed apparently along the window opening height, which has a big temperature difference. By the comparison of experimental and theoretical results, the constant comprehensive coefficient of 1.68, 1.92 and 3.85 of 300 kW, 600 kW and 900 kW are got for an engineered empirical prediction model are proposed, respectively. It provides an insight for the understanding of critical temperature discontinuity and reference for engineering calculations.

Abstract Controlling the formation of clathrate hydrates is crucial for advancing hydrate-based technologies. However, the microscopic mechanism underlying clathrate hydrate formation through nucleation remains poorly elucidated. Specifically, the critical nucleus, theorized as a pivotal step in nucleation, lacks empirical validation. Here, we report uniform nanoparticles, e.g., graphene oxide (GO) nanosheets and gold or silver nanocubes with controlled sizes, as nanoprobes to experimentally measure the size of the critical nucleus of tetrahydrofuran (THF) clathrate hydrate formation. The capability of the nanoparticles in facilitating THF clathrate hydrate nucleation displays generally an abrupt change at a nanoparticle-size-determined specific supercooling. It is revealed that the free-energy barrier shows an abrupt change when the nanoparticles have an approximately the same size as that of the critical nucleus. Thus, it is inferred that THF clathrate hydrate nucleation involves the creation of a critical nucleus with its size being inversely proportional to the supercooling. By proving the existence and determining the supercooling-dependent size of the critical nucleus of the THF clathrate hydrates, this work brings insights in the microscopic pictures of the clathrate hydrate nucleation.

Weather radar holds the capability to monitor the extensive migration of bird and insect species. In particular, polarimetric weather radar can enhance aerial ecological monitoring by quantifying target shape through the measurement of polarization moments. This article introduces an intelligent algorithm to classify bird and insect migration using polarimetric weather radar data. A radar image dataset was formed by intentionally curating typical migratory data of birds and insects captured by the polarimetric weather radar. Next, point features and spatial texture features were extracted from the radar images in the dataset for training a classifier using a supervised learning approach, resulting in a classification accuracy of 93.56%. Furthermore, the importance of the features was analyzed, uncovering that the most influential attribute was the reflectivity factor at 33.83%, surpassing the cumulative influence of other dual-polarization moments. In addition, spatial textures also played an essential role for the classifier, collectively weighing 35.65%. Lastly, the proposed method was validated with bird radar data, attaining an accuracy level of 95.36%.

Ground clutter poses a significant challenge to the accuracy of weather radar products, especially for aeroecology monitoring. Operational weather radar commonly employs a fixed coherent pulse integration (CPI) for clutter suppression. However, the phenomenon of strong clutter spanning multiple CPIs can result in severe spectral leakage. The independent implementation of clutter suppression within each CPI fails to fully utilize clutter data, significantly compromising clutter suppression effectiveness. Therefore, we propose an adaptive coherent pulse integration (ACPI) method based on the amplitude-phase characteristics of echoes in azimuth. Clutter and nonclutter regions are determined firstly based on the stability of the echo phase in azimuth. Then, the clutter region is further subdivided using phase discontinuities and amplitude notches between different clutter areas. Finally, an appropriate CPI can be assigned to each strong clutter instance. The effectiveness and the practicality of the ACPI are verified through the simulations and measured data from Chinese operational weather radar.

Abstract Background The gut microbiome of domestic animals carries antibiotic resistance genes (ARGs) which can be transmitted to the environment and humans, resulting in challenges of antibiotic resistance. Although it has been reported that the rumen microbiome of ruminants may be a reservoir of ARGs, the factors affecting the temporal dynamics of the rumen resistome are still unclear. Here, we collected rumen content samples of goats at 1, 7, 14, 28, 42, 56, 70, and 84 days of age, analyzed their microbiome and resistome profiles using metagenomics, and assessed the temporal dynamics of the rumen resistome in goats at the early stage of life under a conventional feeding system. Results In our results, the rumen resistome of goat kids contained ARGs to 41 classes, and the richness of ARGs decreased with age. Four antibiotic compound types of ARGs, including drugs, biocides, metals, and multi-compounds, were found during milk feeding, while only drug types of ARGs were observed after supplementation with starter feed. The specific ARGs for each age and their temporal dynamics were characterized, and the network inference model revealed that the interactions among ARGs were related to age. A strong correlation between the profiles of rumen resistome and microbiome was found using Procrustes analysis. Ruminal Escherichia coli within Proteobacteria phylum was the main carrier of ARGs in goats consuming colostrum, while Prevotella ruminicola and Fibrobacter succinogenes associated with cellulose degradation were the carriers of ARGs after starter supplementation. Milk consumption was likely a source of rumen ARGs, and the changes in the rumen resistome with age were correlated with the microbiome modulation by starter supplementation. Conclusions Our data revealed that the temporal dynamics of the rumen resistome are associated with the microbiome, and the reservoir of ARGs in the rumen during early life is likely related to age and diet. It may be a feasible strategy to reduce the rumen and its downstream dissemination of ARGs in ruminants through early-life dietary intervention. Video Abstract

Objective Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently used in clinical microbiology laboratories. This study aimed to determine whether dual-polarity time-of-flight mass spectrometry (DP-TOF MS) could be applied to clinical nucleotide detection. Methods This prospective study included 40 healthy individuals and 110 patients diagnosed with cardiovascular diseases. We used DP-TOF MS and Sanger sequencing to evaluate 17 loci across 11 genes associated with cardiovascular drug responses. In addition, we used DP-TOF MS to test 998 retrospectively collected clinical DNA samples with known results. Results A, T, and G nucleotide detection by DP-TOF MS and Sanger sequencing revealed 100% concordance, whereas the C nucleotide concordance was 99.86%. Genotyping based on the results of the two methods showed 99.96% concordance. Regarding clinical applications, DP-TOF MS yielded a 99.91% concordance rate for known loci. The minimum detection limit for DNA was 0.4 ng; the inter-assay and intra-assay precision rates were both 100%. Anti-interference analysis showed that aerosol contamination greater than 10 13 copies/µL in the laboratory environment could influence the results of DP-TOF MS. Conclusions The DP-TOF MS platform displayed good detection performance, as demonstrated by its 99.96% concordance rate with Sanger sequencing. Thus, it may be applied to clinical nucleotide detection.

Background: Ensuring the rapidity and accuracy of emergency laboratory test results is especially important to save the lives of patients with acute and critical conditions. To better meet the needs of clinicians and patients, detection efficiency can be improved by reducing extra-laboratory sample turnaround times (TATs) through the use of innovative pneumatic tube system (PTS) transport for sample transport. However, concerns remain regarding the potential compromise of sample quality during PTS transit relative to that occurring with manual transportation. This study was performed to evaluate the efficacy of an innovative PTS (Tempus600 PTS) relative to a traditional PTS in terms of sample transit time, sample quality, and the concordance of analytical results with those obtained from manually transported samples. Methods: In total, 30 healthy volunteers aged >18 years were recruited for this study, conducted for five consecutive days. Venous blood samples were collected from six volunteers per day at fixed timepoints. From each volunteer, nine blood samples were collected into tubes with tripotassium ethylene diamine tetraacetic acid anticoagulant, tubes with 3.2 % sodium citrate, and serum tubes with separation gel (n = 3 each) and subjected to all tests conducted in the emergency laboratory in our hospital. 270 blood samples from 30 healthy volunteers were transported and analyzed, yielding 6300 test results. The blood samples were divided randomly into three groups (each containing one tube of each type) and transported to the emergency laboratory manually and with Tempus600 PTS and conventional Swisslog PTS, respectively. The extra-laboratory TATs, sample quality, and test results of the transported blood samples were compared. Results: The sample quality and test results did not differ according to the delivery method. The TAT was much shorter with the Tempus600 than with the other two transport modes (58.40 ± 1.52 s vs. 1711.20 ± 77.56 s for manual delivery and 146.60 ± 1.82 s for the Swisslog PTS; P = 0.002). Conclusion: Blood sample transport with the Tempus600 PTS significantly reduced the extra-laboratory TAT without compromising sample quality or test result accuracy, thereby improving the efficiency of sample analysis and the services provided to clinicians and patients.

Pesticide residues in cowpeas have raised worldwide concern. However, only a few studies have focused on pesticide accumulation and distribution in greenhouse and open-field cowpeas. Field trial results suggest that difenoconazole, dimethomorph, thifluzamide and pyraclostrobin dissipated faster in open fields (mean half-lives, 1.72–1.99 days) than in greenhouses (2.09–3.55 days); moreover, fungicide residues in greenhouse cowpeas were 0.84–8.19 times higher than those in the open-field cowpeas. All fungicides accumulated in the greenhouse and open-field cowpeas after repeated spraying. Fungicide residues in old cowpeas were higher than those in tender cowpeas, and residues in the upper halves of cowpea pods were higher than those in the lower halves. In addition, cowpeas distributed in the lower halves of the plants had higher fungicide residues. Our findings suggest that greenhouse cultivation contributed to the pesticide residues in cowpeas after repeated spraying, although the levels of dietary health risks remained acceptable under both cultivation scenarios.

Abstract As men age, a growing number develop benign prostatic hyperplasia (BPH). According to previous research, diabetes may be a risk factor. Pyruvate dehydrogenase kinase 4 (PDK4) is closely related to glucose metabolism and plays a role in the onset and progression of numerous illnesses. This study aimed to determine the direct effects of high glucose environment on prostate epithelial cells, in particular by altering PDK4 expression levels. In this investigation, normal prostatic epithelial cells (RWPE-1) and human benign prostatic hyperplasia epithelial cells (BPH-1) were treated with 50 mM glucose to show the alteration of high glucose in prostate cells. PDK4-target siRNA, PDK4-expression plasmid were used to investigate the effects of PDK4. Rosiglitazone (RG), a PPARγ agonist, with the potential to up-regulate PDK4 expression was also used for treating prostate cells. The expression of PDK4 in human prostate samples was also analyzed. The effects of high glucose therapy on BPH-1 and RWPE-1 cells were demonstrated to enhance proliferation, epithelial-mesenchymal transition (EMT), suppress apoptosis, and down-regulate PDK4 expression. Additionally, diabetes-related BPH patients had reduced PDK4 expression. Following the application of PDK4-target siRNA, a comparable outcome was seen. The PDK4-expression plasmid therapy, however, produced the opposite results. RG with the ability to elevate PDK4 expression might be used to treat BPH. Changes in the metabolism of lipids and glucose may be the cause of these consequences. These findings showed that high glucose treatment might facilitate BPH development, and may be related to the down-regulation of PDK4. PDK4 might be a potential therapeutic target of BPH.

Abstract Background Little is known about the association of longitudinal dynamics between cognitive function and frailty in Chinese older adults. The temporal sequences between cognitive function and frailty remains unclear. Our study investigates this directionality association using longitudinal data. Methods Latent growth and multivariate latent growth models were employed to examine dynamics of cognition and frailty and their association among 2824 older adults in China. Cross-lagged panel analyses were used to assess the temporal sequences between frailty and cognition. The relation between cognitive domains and frailty was also examined using aforementioned methods. Results Cognitive function was negatively associated with frailty status. Higher initial level of cognition indicated lower baseline level (β=-0.175, P

Abstract Background It is not uncommon for some individuals to retain certain primitive characteristics even after domestication or long-term intensive selection. Wild ancestors or original varieties of animals typically possess strong adaptability to environmental preservation, a trait that is often lacking in highly artificially selected populations. In the case of the Merino population, a world-renowned fine wool sheep breed, a phenotype with primitive coarse wool characteristic has re-emerged. It is currently unclear whether this characteristic is detrimental to the production of fine wool or whether it is linked to the adaptability of sheep. The underlying genetic/epigenetic mechanisms behind this trait are also poorly understood. Results This study identified lambs with an ancestral-like coarse (ALC) wool type that emerged during the purebred breeding of Merino fine wool sheep. The presence of this primitive sheep characteristic resulted in better environmental adaptability in lambs, as well as improved fine wool yield in adulthood. Reciprocal cross experiments revealed that the ALC phenotype exhibited maternal genetic characteristics. Transcriptomic SNP analysis indicated that the ALC phenotype was localized to the imprinted Gtl2-miRNAs locus, and a significant correlation was found between the ALC wool type and a newly identified short Interstitial Telomeric Sequences (s-ITSs) at this locus. We further confirmed that a novel 38-nt small RNA transcribed from these s-ITSs, in combination with the previously reported 22-nt small RNAs cluster from the Gtl2-miRNAs locus, synergistically inhibited PI3K/AKT/Metabolic/Oxidative stress and subsequent apoptotic pathways in wool follicle stem cells, resulting in the ALC wool type. The necessity of Gtl2-miRNAs in controlling primary hair follicle morphogenesis, as well as the wool follicle type for ALC wool lambs, was verified using intergenic differentially methylated region-knockout mice. Conclusion The ALC wool type of Merino sheep, which does not reduce wool quality but increases yield and adaptability, is regulated by epigenetic mechanisms in the imprinted Gtl2-miRNAs region on sheep chromosome 18, with the maternally expressed imprinted gene responsible for the ALC phenotype. This study highlights the significance of epigenetic regulation during embryonic and juvenile stages and emphasizes the advantages of early adaptation breeding for maternal parents in enhancing the overall performance of their offspring.

The aerodynamic configuration design of wide-range hypersonic vehicle has become one of the research hotspots. The new aerodynamic configuration of high-pressure capturing wing (HCW) can meet the requirements of high volume ra-tio, high lift and high lift-to-drag ratio at the same time. The preliminary research of this configuration is mainly aimed at the hypersonic state. Based on this background, this paper took the wide-range hypersonic vehicle as the main target and developed a new bi-wing configuration according to the basic design principle of HCW. The research results show that the lift coefficient of the vehicle can be increased by about 16.6% when the capturing wing is added in the subsonic range. Furthermore, the capturing wing can suppress the jump of the aerodynamic focus of the vehicle in the transonic range, and the vehicle is statically stable in the wide-speed range.

In the passive bistatic radar (PBR) system, methods exist to address the issue of detecting weak targets without being influenced by non-ideal factors from adjacent strong targets. These methods utilize the sparsity in the delay-Doppler domain of the cross ambiguity function (CAF) to detect weak targets. However, the modeling and solving of this method involve substantial memory consumption and computational complexity. To address these challenges, this paper establishes a target detection model for PBR based on batch processing of sparse representation and recovery. This model partitions the CAF into blocks, identifies blocks requiring processing based on the presence of targets, and improves the construction and utilization of the measurement matrix. This results in a reduction in the computational complexity and memory resource requirements for sparse representation and recovery, and provides favorable conditions for parallel execution of the algorithm. Experimental results indicate that the proposed approach increases the number of blocks by a factor of four, and reduces the number of real multiplications by approximately an order of magnitude. Hence, compared with the traditional approach, the proposed approach enables fast and stable detection of weak targets.

BackgroundThe synergistic effectiveness of combining immune checkpoint inhibitors with targeted therapies has shown promise in improving the conversion rate for unresectable hepatocellular carcinoma (HCC) patients to a potentially resectable status. However, the efficacy of this approach in the context of HCC with extrahepatic metastasis remains to be conclusively determined.Case presentationWe report a rare case of advanced HCC with extrahepatic metastasis who achieved long-term survival by a combination of systemic therapy (sintilimab and sorafenib) followed by laparoscopic hepatectomy. A 63-year-old man presented at our hospital with discomfort on the right side of his waist. An enlarged right hepatic lobe mass was subsequently revealed by CT scan. The patient’s medical history, including a prior infection with hepatitis B virus, cirrhosis of the liver and an alpha-fetoprotein (AFP) level measuring 41.28 ng/ml substantiated the clinical diagnosis of HCC. On October 30th, 2019, the patient received 200 mg sintilimab intravenously (q3w) plus 200–400 mg BID sorafenib orally, along with antiviral therapy. After six cycles, his disease achieved partial response (PR). On April 26th, 2021, He underwent a laparoscopic hepatectomy. The patient achieved a sustained period of no evidence of disease for 2.5 years and with drug-free survival for 2 years after the resection. His current overall survival is estimated at approximately 4 years.ConclusionsThis case highlights the potential of combining sintilimab and sorafenib in transforming HCC with extrahepatic metastasis into a condition amenable to surgical resection, suggesting that this treatment approach, followed by surgery, may lead to complete remission.

Abstract Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes‐associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation‐induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation‐associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial‐mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH‐1 and WPMY‐1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation‐triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F‐actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

BackgroundDespite the recognized psychological benefits of traditional dance forms, the impact of newer forms, such as pole dancing, on mental well-being and sexual self-concept remains underexplored. This protocol outlines a systematic review and meta-analysis aimed at elucidating the effects of pole dancing, a burgeoning non-pharmacological intervention, on these dimensions of mental health.MethodsThis systematic review was registered in the PROSPERO. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocol to accomplish the systematic review protocol. This review will systematically search electronic databases, including PubMed, Embase, Web of Science, Medline, and CNKI, for randomized controlled trials (RCTs) assessing the impact of pole dancing on mental well-being and sexual self-concept. Two independent evaluators will screen the literature, extract data, and evaluate study quality and bias. Data synthesis will utilize Stata 14.0 and Revman 5.4, employing random-effects models. The Grading of Recommendations, Development, and Evaluation (GRADE) system will appraise evidence reliability, with subgroup analysis exploring heterogeneity sources. Publication bias will be assessed through funnel plots and Egger's regression tests.DiscussionThis review aims to fill the gap in the current literature by providing a comprehensive evaluation of pole dancing's psychological effects. It is anticipated that this systematic review and meta-analysis will offer valuable insights for health policy and practice, advocating for the inclusion of pole dancing in mental health and sexual well-being interventions.Trial registrationSystematic review registration: PROSPERO CRD42024529369.

ABSTRACT The use of milk replacer (MR) is a modern strategy to ensure the health and growth of neonatal ruminants. Some studies have confirmed that dietary factors have significant effects on ruminal antimicrobial resistance genes (ARGs), which, as a potential threat to livestock, have received more attention. However, the effect of different milk sources (milk or MR) on the rumen resistome of yaks is still largely unknown. Here, using metagenome technology, we investigated the occurrence of ruminal ARGs in yaks and their relationship with rumen bacteria in response to different milk sources. The metagenomic result showed that MR feeding significantly increased the abundance of Prevotella members compared to milk feeding. A total of 138 rumen resistome-conveying ARGs to 17 different classes of antimicrobials were detected, of which tetracycline resistance was the predominant. MR feeding also drove the changes in the rumen resistome, and the predicted bacterial origins of ARGs had complex and various manifestations. Moreover, enzymes of butyrate metabolism and carbohydrate-active enzymes encoding carbohydrate and cellulose degradation were increased. This study revealed that MR feeding increased the abundance of beneficial bacteria Prevotella members, changed the microbial resistome, and promoted the metabolic function of volatile fatty acid biosynthesis in the rumen of yaks, which could provide beneficial evidence for the regulation of the rumen microbiome and the intervention of antimicrobial resistance in ruminants by dietary or nutritional methods. IMPORTANCE Yaks, as ruminants inhabiting high-altitude environments, possess a distinct rumen microbiome and are resistant to extreme living conditions. This study investigated the microbiota, resistome, and functional gene profiles in the rumen of yaks fed milk or milk replacer (MR), providing insights into the regulation of the rumen microbiome and the intervention of antimicrobial resistance in yaks through dietary methods. The abundance of Prevotella members increased significantly in response to MR. Tetracycline resistance was the most predominant. The rumen of yaks contained multiple antimicrobial resistance genes (ARGs) originating from different bacteria, which could be driven by MR, and these ARGs displayed intricate and complex interactions. MR also induced changes in functional genes. The enzymes associated with fiber degradation and butyrate metabolism were activated and showed close correlations with Prevotella members and butyrate concentration. This study allows us to deeply understand the ruminal microbiome and ARGs of yaks and their relationship with rumen bacteria in response to different milk sources.

Abstract Focused exploration of earth‐abundant and cost‐efficient non‐noble metal electrocatalysts with superior hydrogen evolution reaction (HER) performance is very important for large‐scale and efficient electrolysis of water. Herein, a sandwich composite structure (designed as MS‐Mo2C@NCNS) of β‐Mo2C hollow nanotubes (HNT) and N‐doped carbon nanosheets (NCNS) is designed and prepared using a binary NaCl–KCl molten salt (MS) strategy for HER. The temperature‐dominant Kirkendall formation mechanism is tentatively proposed for such a three‐dimensional hierarchical framework. Due to its attractive structure and componential synergism, MS‐Mo2C@NCNS exposes more effective active sites, confers robust structural stability, and shows significant electrocatalytic activity/stability in HER, with a current density of 10 mA cm−2 and an overpotential of only 98 mV in 1 M KOH. Density functional theory calculations point to the synergistic effect of Mo2C HNT and NCNS, leading to enhanced electronic transport and suitable adsorption free energies of H* (ΔGH*) on the surface of electroactive Mo2C. More significantly, the MS‐assisted synthetic methodology here provides an enormous perspective for the commercial development of highly active non‐noble metal electrocatalysts toward efficient hydrogen evolution.

Abstract Background As the COVID-19 pandemic continues to evolve, novel vaccines need to be developed that are readily manufacturable and provide clinical efficacy against emerging SARS-CoV-2 variants. Virus-like particles (VLPs) presenting the spike antigen at their surface offer remarkable benefits over other vaccine antigen formats; however, current SARS-CoV-2 VLP vaccines candidates in clinical development suffer from challenges including low volumetric productivity, poor spike antigen density, expression platform-driven divergent protein glycosylation and complex upstream/downstream processing requirements. Despite their extensive use for therapeutic protein manufacturing and proven ability to produce enveloped VLPs, Chinese Hamster Ovary (CHO) cells are rarely used for the commercial production of VLP-based vaccines. Methods Using CHO cells, we aimed to produce VLPs displaying the full-length SARS-CoV-2 spike. Affinity chromatography was used to capture VLPs released in the culture medium from engineered CHO cells expressing spike. The structure, protein content, and glycosylation of spikes in VLPs were characterized by several biochemical and biophysical methods. In vivo, the generation of neutralizing antibodies and protection against SARS-CoV-2 infection was tested in mouse and hamster models. Results We demonstrate that spike overexpression in CHO cells is sufficient by itself to generate high VLP titers. These VLPs are evocative of the native virus but with at least three-fold higher spike density. In vivo, purified VLPs elicit strong humoral and cellular immunity at nanogram dose levels which grant protection against SARS-CoV-2 infection. Conclusions Our results show that CHO cells are amenable to efficient manufacturing of high titers of a potently immunogenic spike protein-based VLP vaccine antigen.

Abstract Changes in precipitation, temperature and humidity can lead to the weathering of rock masses in grottoes; these changes are common in sandstone grottoes. To simulate this cyclic process, different salt solutions were designed according to the main precipitated components. Sandstone specimens taken from Longshan Grottoes were soaked in these solutions for 48 h and then placed in a simulated environment with temperature and humidity changes for 5 cycles (50 h) to study the effects of hydrochemical, temperature and humidity changes on the sandstone. Physical indexes, such as mass, wave velocity, surface hardness and tensile strength, of the rock samples were measured every three cycles, and the damage characteristics and mechanisms of the sandstone were discussed based on SEM and XRD test results. The results showed that the macroindicators and microstructures of the samples gradually decreased with increasing number of cycles. The physical indexes of the rock samples in different solutions changed at different rates, the changes in surface hardness and tensile strength were consistent, and the responses were less sensitive to deterioration than to longitudinal wave velocity. In different solutions, the microstructures and mineral compositions of the samples showed different trends with increasing number of cycles. This damage was caused by a combination of various actions, such as feldspar dissolution, chemical erosion, water scouring, clay mineral expansion and disintegration, and salt crystallization, which increased the number of pores, enlarged the holes and expanded the cracks inside the rock samples.

Abstract Recycled aggregate concrete (RAC) has become a popular building material due to its eco-friendly features, but the difficulty in predicting the crack resistance of RAC is increasingly impeding its application. In this study, splitting tensile strength is adopted to describe the crack resistance ability of RAC, and physics-assisted machine learning (ML) methods are used to construct the predictive models for the splitting tensile strength of RAC. The results show that the AdaBoost model has excellent predictive performance with the help of the Firefly algorithm, and physical assistance plays a remarkable role in selecting features and verifying the ML models. Due to the limit in data size and the generalizability of the model, the dataset should be supplemented with more representative data, and an algorithm for small sample sizes could be studied in the future.

Algorithmic trading is playing an increasingly important role in the financial market, achieving more efficient trading strategies by replacing human decision-making. Among numerous trading algorithms, deep reinforcement learning is gradually replacing traditional high-frequency trading strategies and has become a mainstream research direction in the field of algorithmic trading. This paper introduces a novel approach that leverages reinforcement learning with human feedback (RLHF) within the double DQN algorithm. Traditional reward functions in algorithmic trading heavily rely on expert knowledge, posing challenges in their design and implementation. To tackle this, the reward-driven double DQN (R-DDQN) algorithm is proposed, integrating human feedback via a reward function network trained on expert demonstrations. Additionally, a classification-based training method is employed for optimizing the reward function network. The experiments, conducted on datasets including HSI, IXIC, SP500, GOOGL, MSFT, and INTC, show that the proposed method outperforms all baselines across six datasets and achieves a maximum cumulative return of 1502% within 24 months.

A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor–acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of “Visualized Drug Delivery Systems”. Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.

Background: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. Materials and Methods: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. Results: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. Conclusions: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

The gut microbiota of fish is crucial for their growth, development, nutrient uptake, physiological balance, and disease resistance. Yet our knowledge of these microbial communities in wild fish populations in their natural ecosystems is insufficient. This study systematically examined the gut microbial communities of seven wild fish species in Chaohu Lake, a fishing-restricted area with minimal water turnover, across four seasons. We found significant variations in gut microbial community structures among species. Additionally, we observed significant seasonal and regional variations in the gut microbial communities. The Chaohu Lake fish gut microbial communities were predominantly composed of the phyla Firmicutes, Proteobacteria(Gamma), Proteobacteria(Alpha), Actinobacteriota, and Cyanobacteria. At the genus level, Aeromonas, Cetobacterium, Clostridium sensu stricto 1, Romboutsia, and Pseudomonas emerged as the most prevalent. A co-occurrence network analysis revealed that C. auratus, C. carpio, and C. brachygnathus possessed more complex and robust gut microbial networks than H. molitrix, C. alburnus, C. ectenes taihuensis, and A. nobilis. Certain microbial groups, such as Clostridium sensu stricto 1, Romboutsia, and Pseudomonas, were both dominant and keystone in the fish gut microbial network. Our study offers a new approach for studying the wild fish gut microbiota in natural, controlled environments. It offers an in-depth understanding of gut microbial communities in wild fish living in stable, limited water exchange natural environments.

Sequentially timed all-optical mapping photography is one of the main emerging ultra-fast detection technologies that can be widely applicable to ultra-fast detection at the picosecond level in fields such as materials and life sciences. We propose a new optical structure for an all-optical spatial mapping module that can control the optical field of two-dimensional imaging while improving spectral resolution and detector sensor utilization. The model of optical parameters based on geometrical optics theory for the given structure has been established, and the theoretical analysis of the inter-frame energy crosstalk caused by incident beam spot width, chromatic aberration, and main errors of the periscope array has been conducted. The optical design of the two-dimensional (2D) all-optical spatial mapping module was finally completed using ZEMAX OpticStudio 2018 software. The results show that our optical module can realize targets of 16 frames and 1.25 nm spectral resolution.

Abstract Aim To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options. Methods We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed. Results A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery. Conclusions By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.

Abstract Each year, billions of birds migrate across the globe, and interpretation of weather radar signals is increasingly being used to document the spatial and temporal migration patterns in Europe and America. Such approaches are yet to be applied in the East Asian‐Australasian Flyway (EAAF), one of the most species‐rich and threatened flyways in the world. Logistical challenges limit direct on‐ground monitoring of migratory birds in many parts of the EAAF, resulting in knowledge gaps on population status and site use that limit evidence‐based conservation planning. Weather radar data have great potential for achieving comprehensive migratory bird monitoring along the EAAF. In this study, we discuss the feasibility and challenges of using weather radar to complement on‐ground bird migration surveys in the flyway. We summarize the location, capacity and data availability of weather radars across EAAF countries, as well as the spatial coverage of the radars with respect to migrants' geographic distribution and migration hotspots along the flyway, with an exemplar analysis of biological movement patterns extracted from Chinese weather radars. There are more than 430 weather radars in EAAF countries, covering on average half of bird species' passage and non‐breeding distributions, as well as 70% of internationally important sites for migratory shorebirds. We conclude that the weather radar network could be a powerful resource for monitoring bird movements over the full annual cycle throughout much of the EAAF, providing estimates of migration traffic rates, site use, and long‐term population trends, especially in remote and less‐surveyed regions. Analyses of weather radar data would complement existing ornithological surveys and help understand the past and present status of the avian community in a highly threatened flyway.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective: According to the 2020 data from the World Health Organization (WHO), cancers stand as one of the foremost contributors to global mortality. Revealing novel cancer risk factors and protective factors is of paramount importance in the prevention of disease occurrence. Studies on the relationship between chemokines and cancer are ongoing; however, due to the coordination of multiple potential mechanisms, the specific causal association remains unclear.Methods: We performed a bidirectional Mendelian randomization analysis to explore the causal association between serum chemokines and pan-carcinoma. All data is from the GWAS catalog and IEU Open GWAS database. The inverse-variance weighted (IVW) method is primarily employed for assessing the statistical significance of the findings. In addition, the significance threshold after the multiple hypothesis test (Bonferroni) was 0.0013, and the evidence of a potential association was considered if the p-value < 0.05, but remained greater than Bonferroni’s threshold.Results: The results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR = 1.04), CCL8 (OR = 1.36), CCL14 (Colorectal, OR = 1.08, Small intestine, OR = 0.77, Lung, OR = 1.11), CCL15 (OR = 0.85), CCL18 (Breast, OR = 0.95, Prostate, OR = 0.96), CCL19 (Lung, OR = 0.66, Prostate, OR = 0.92), CCL20 (Lung, OR = 0.53, Thyroid, OR = 0.76), CCL21 (OR = 0.62), CCL22 (OR = 2.05), CCL23 (OR = 1.31), CCL24 (OR = 1.06), CCL27 (OR = 1.49), CCL28 (OR = 0.74), CXCL5 (OR = 0.95), CXCL9 (OR = 3.60), CXCL12 (Breast, OR = 0.87, Small intestine, OR = 0.58), CXCL13 (Breast, OR = 0.93, Lung, OR = 1.29), CXCL14 (Colon, OR = 1.40) and CXCL17 (OR = 1.07) are potential risk factors for cancers. In addition, there was a reverse causal association between CCL1 (OR = 0.94) and CCL18 (OR = 0.94) and breast cancer. Sensitivity analysis results were similar. The results of the other four MR Methods were consistent with the main results, and the leave-one-out method showed that the results were not driven by a Single nucleotide polymorphism (SNP). Moreover, there was no heterogeneity and pleiotropy in our analysis.Conclusion: Based on the two-sample MR Analysis method, we found that chemokines might be upstream factors of cancer pathogenesis. These results might provide new insights into the future use of chemokines as potential targets for cancer prevention and treatment. Our results also provide important clues for tumor prevention, and changes of serum chemokine concentration may be recognized as one of the features of precancerous lesions in future clinical trials.

Abstract Evaluating variations in reproductive traits and the response of the variations to geo‐climate conditions are essential for understanding the persistence, evolution, and range dynamics of plant populations. However, there are insufficient studies to attempt to analyze the importance of geo‐climate factors in explaining within‐ or among‐population variation in reproductive traits. We examined 14 traits for 2671 cones of Pinus yunnanensis collected from nine populations in the mountains of Southwest China to characterize the patterns of phenotypic variation of traits and estimate environmental effects on these trait performances and trait variation. We found the contribution of intrapopulation variation to the overall variation was greater than the interpopulation variation and the larger coefficients of variation for the populations lying at the edge of northern and southern regions. Climatic variables are more important than geographical and tree size variables in their relationships to cone and seed traits. Populations in more humid and warmer climate expressed greater cone and seed weight and seed number but lower seed abortion rate, while the larger coefficients of variation in seed weight and number were detected in northern and southern marginal regions with drier or colder climate. Our study illustrates that intraspecific trait variation should be considered when examining plant species response to changing climate and suggests that the high variability rather than high quality of seed traits in the marginal regions with drier or colder climate might foster plant‐population persistence in stressful conditions.

Transformers, being the largest oil-bearing equipment, are susceptible to high-temperature hot oil fires and large-area flowing fires that can be challenging to extinguish. To investigate the effectiveness of compressed air foams (CAFs) agents in extinguishing fires in ultra-high voltage (UHV) converter transformers, this work examines the fire suppression capabilities of three typical CAFs agents. A test model of a hot oil fire in a transformer with a burning area of 1 m2 was constructed for this purpose. The fire test was conducted by heating the transformer oil using an electric heating system, and the test process was monitored using an unmanned aerial vehicle. The results indicate that three CAFs agents used in the tests are capable of extinguishing a 1 m2 transformer hot oil fire without causing boiling over phenomenon. 1% MJBP CAFs is the fastest with a fire extinguishing time of 168 s, and is even more efficient when the gas to liquid ratio is 9:1. CAFs have the advantage of uniformity and stability, making it suitable for extinguishing hot oil fires in extra high voltage transformers as it does not cause boiling fires during firefighting.

Abstract This paper presents a modified unified critical state model to predict the mechanical responses of both clays and sands under over-consolidation and cyclic loading conditions on the basis of clay and sand model (CASM), which is named as CASM-kII. Through the application of subloading surface concept, CASM-kII is able to describe the plastic deformation inside the yield surface and the reverse plastic flow, and is thus expected to capture the over-consolidation and cyclic loading behaviours of soils. CASM-kII is numerical implemented by the using of the forward Euler scheme with automatic substepping and error control. Then, a sensitivity study is carried out to check the influences of the three new parameters of CASM-kII on the mechanical response of soils in over-consolidation and cyclic loading conditions. Through the comparisons of experimental data and simulated results, it is found that CASM-kII is able to satisfactorily describe the mechanical responses of both clays and sands in over-consolidation and cyclic loading conditions.

The influence of solar and geomagnetic activities on electrical propulsion system of ultra-low orbit gravity satellite was evaluated for the current 25th solar cycle. The orbit simulation was carried out and the data of GOCE mission was analyzed. The variation of atmospheric drag was analyzed. The influence of solar activity on propellant consumption and the influence of geomagnetic storm on drag-free operation were obtained. The results show that the orbit altitude of the satellite in the low solar activity years can be reduced by about 20 km compared with that in the high solar activity years, which is conducive to improving the gravity signal intensity. Strong geomagnetic storms usually increase the drag by 30% to 90% at ultra-low orbit, so thrust margin is required for geomagnetic storms. Designer should ensure high specific impulse in thrust range of 10% to 70% of the maximum thrust. The life consideration of this range is important.

In deep learning based stock trading strategy models, most of the research just use simple convolutional neural networks (CNN) to process stock data. But task-specific neural network structures have been proposed extensively, and their effectiveness has been demonstrated in computer vision (CV) and natural language processing (NLP) tasks. In this paper, we proposed a multi-scale convolutional neural feature extraction network (MS-CNN) for stock data, which can better extract stock trend features and thus make better decisions. The network structure inspired by the human stock trading model: in human behavior, we do not only look at a single set of stock data, but rather combine all the stock data, such as opening, closing, and trading volume, to make a comprehensive judgment. And humans will consider the current stock trend on different time scales, such as 3-Day Line and 5-Day Line. This is consistent with the two-dimensional convolution kernels commonly used in CV tasks, so we used convolution kernels of $3\times 3$ and $5\times 5$ in the network with two-dimensional convolution size and constructed a novel network structure for stock data. With double deep Q networks (DDQN) algorithm, we get the best performance for our network. The experimental results show that we can obtain high yield on the datasets of Dow Jones (DJI), AAPLE (AAPL), and General Electric (GE).

Abstract Microbial electrosynthesis (MES) is a promising technology for CO2 fixation and electrical energy storage. Currently, the low current density of MES limits its practical application. The H2-mediated and non-biofilm-driven MES could work under higher current density, but it is difficult to achieve high coulombic efficiency (CE) due to low H2 solubility and poor mass transfer. Here, we proposed to enhance the hydrogen mass transfer by adding silica nanoparticles to the reactor. At pH 7, 35 ℃ and 39 A·m− 2 current density, with the addition of 0.3wt% silica nanoparticles, the volumetric mass transfer coefficient (k La) of H2 in the reactor increased by 32.4% (from 0.37 h− 1 to 0.49 h− 1), thereby increasing the acetate production rate and CE of the reactor by 69.8% and 69.2%, respectively. The titer of acetate in the reactor with silica nanoparticles (18.5 g·L− 1) was 56.9% higher than that of the reactor without silica nanoparticles (11.8 g·L− 1). Moreover, the average acetate production rate of the reactor with silica nanoparticles was up to 2.14 g·L− 1·d− 1 in the stable increment phase, which was much higher than the other reported reactors. These results demonstrated that the addition of silica nanoparticles is an effective approach to enhancing the performance of H2-mediated MES reactors. Graphical Abstract

Purpose: To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms. Materials and Methods: Eight-week-old fasting male SD rats were intraperitoneally injected with streptozotocin to construct diabetic rat models. Diabetic ED rats were treated with miRNA-92a inhibitor. The cavernous nerves were electrically stimulated to measure the intracavernous pressure and mean arterial pressure of rats in each group. After the detection, the penile cavernous tissues are properly stored for subsequent experiments. Rat aortic endothelial cells were used in in vitro studies. Results:The expression of miR-92a was significantly increased in the corpus cavernosum of Streptozocin (STZ)-induced diabetic rats and injection of miR-92a antagomir into the corpus cavernosum of diabetic rats significantly increased eNOS/NO/ cGMP signaling pathway activities, cavernous endothelial cell proliferation, endothelial cell-cell junction protein expression and decreased the levels of oxidative stress. These changes restored erectile function in STZ-induced diabetic rats. Moreover, in vitro study demonstrated that the miR-92a expression increased significantly in endothelial cells treated with high glucose, inhibiting AMPK/eNOS and AMPK/Nrf2/HO-1 signaling pathways in rat aortic endothelial cells via targeting Prkaa2, causing endothelial dysfunction and overactive oxidative stress, miR-92a inhibitor can improve the above parameters. Conclusions: miRNA-92a inhibitor could exert an inhibition role on oxidative stress and endothelial dysfunction to improve diabetic ED effectively.