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Abstract Background Elucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai’s animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province’s population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep. Result In this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8. Conclusion By genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.

Abstract Background The increasing use of intracardiac echocardiography (ICE) in the ablation of premature ventricular complexes (PVCs) has raised questions about its true efficacy and safety. Methods This retrospective study collected the periprocedural complications and PVC burden post ablation. The risk factors of PVC recurrence was further explored. Results The study included patients treated without ICE (control group, n = 451) and with ICE (ICE group, n = 155) from May 2019 to July 2022. The ICE group demonstrated significantly lower fluoroscopy times and X-ray doses. There were no major complications in the ICE group, and the difference in the occurrence of periprocedural complications between the groups was not statistically significant (p = 0.072). The long-term success rates were similar for the control and ICE groups (89.6% and 87.1%, respectively). The origin of PVCs was identified as the independent factor for ablation success. Conclusions The use of ICE did not confer an advantage with regard to long-term success in PVCs ablation. To thoroughly evaluate the safety and effectiveness of ICE in PVCs ablation, a prospective, multicenter, randomized study is warranted.

Abstract Objective To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). Methods This retrospective cohort study was conducted at a large children’s hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. Results A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. Conclusion This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

Abstract Background Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression. Methods We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model. Results We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity. Conclusions These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.

Abstract The strategy using water as a medium for dynamic modulation of competitive plasticity and viscoelasticity provides a unique perspective to attain adaptive materials. We reveal sustainable polymers, herein cellulose phenoxyacetate as a typical example, with unusual water-responsive dual-mechanic functionalities addressed via a chronological water training strategy. The temporal significance of such water-responsive mechanical behaviors becomes apparent considering that a mere 3-minute exposure or a prolonged 3-hour exposure to water induced different types of mechano-responsiveness. This endows the materials with multiple recoverable shape-changes during water and air training, and consequently even underlines the switchability between the pre-loaded stable water shapes (> 20 months) and the sequentially fixed air shapes. Our discovery exploits the competitive mechanics initiated by water training, enabling polymers with spatially regulated microstructures via their inherently distinct mechanical properties. Insights into the molecular changes represents a considerable fundamental innovation, can be broadly applicable to a diverse array of hydroadaptive polymers.

Abstract Background In sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice. Both the Furosemide Stress Test (FST) and measurements of the urinary biomarkers TIMP-2*IGFBP-7, if applied solely, do not provide sufficient guidance. We tested the hypothesis that a combination of two tests, i.e., an upstream FST combined with downstream measurements of urinary TIMP-2*IGFBP-7 concentrations improves the accuracy in predicting RRT necessity. Methods In this prospective, multicenter study 100 patients with sepsis (diagnosed

Abstract Anal swabs of 1-month-old Holstein calves with diarrhea were collected from an intensive cattle farm, and a highly pathogenic Escherichia coli strain was obtained by isolation and purification. To study the virulence and resistance genes of pathogenic E. coli that cause diarrhea in calves, a strain of E. coli E12 isolated from calf diarrhea samples was used as experimental material in this experiment, and the virulence of the E12 strain were identified by the mouse infection test, and the whole genome map of the E12 strain were obtained by whole-genome sequencing and analyzed for genome characterization. The results showed that the lethality of strain E12 was 100%, the total length of E12-encoded genes was 4,294,530 bp, Cluster of Orthologous Groups of proteins (COG) annotated to 4,194 functional genes, and the virulence genes of sequenced strain E12 were compared with the virulence genes of sequenced strain E12 from the Virulence Factors of Pathogenic Bacteria (VFDB), which contained a total of 366 virulence genes in sequenced strain E12. The analysis of virulence genes of E12 revealed a total of 52 virulence genes in the iron transferrin system, 56 virulence genes in the secretory system, 41 virulence genes in bacterial toxins, and a total of 217 virulence genes in the Adhesin and Invasins group. The antibiotic resistance genes of sequenced strain E12 were identified through the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Research Database, and it was found that its chromosome and plasmid included a total of 127 antibiotic resistance genes in four classes, and that E12 carried 71 genes related to the antibiotic efflux pumps, 36 genes related to antibiotic inactivation, and 14 antibiotic target alteration and reduced penetration into antibiotics, and 6 antibiotic resistance genes, and the resistance phenotypes were consistent with the genotypes. The pathogenic E. coli that causes diarrhea in calves on this ranch contains a large number of virulence and resistance genes. The results provide a theoretical basis for the prevention and treatment of diarrhea and other diseases caused by E. coli disease.

The fracture behaviours of pearlite structures in several typical carbon steels were investigated by scanning electron microscopy (SEM). Microstructural analysis indicated that the fracture of pearlite is a mixed ductile-brittle fracture, and brittle fracture has cleavage fracture characteristics, which often occur inside the pearlite structure. The fracture surface can exhibit any orientation relationship with the ferrite/cementite interface plane in the pearlite structure. The two phases in the pearlite structure (ferrite (α-Fe) and cementite (θ-Fe3C)) are fine grains rather than single-crystal platelets. The cleavage fracture mechanism in any direction of pearlite structure occurs due to the fine grain substructure.

Background Surgical treatment for hinge failure in mega‐prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. Case Presentation We here present two patients who underwent mega‐prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega‐prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. Conclusions Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old‐fashioned mega‐prosthesis hinges.

The newly opened Trans-Asian Railway offers opportunities for trade logistics between China and ASEAN (Association of Southeast Asian Nations). This study selected six factors including cost, time, transport volume, reliability, safety, and environmental friendliness to investigate the impact on logistics for trade between China and ASEAN. It explores the most ideal solution for the Sino-Thai logistics route by using the AHP-TOPSIS approach and ranks the current five Sino-Thai logistics routes. The results indicate that the Sea-land transport (0.787) is still the best option, the Kunming-Bangkok Roadway (0.452) came in second, followed by the newly opened Trans-Asian Railway (0.431); The Nanning-Bangkok Roadway (0.373) ranks second to last, and the river-land transport service (0.249) is the last resort. In this sense, the newly opened Trans-Asian Railway would influence the current pattern of Sino-Thai logistics to some extent. The results will offer insight into the managerial decisions for the Sino-Thai trade.

Multi-object tracking (MOT) aims at estimating locations and identities of objects in videos. Many modern multiple-object tracking systems follow the tracking-by-detection paradigm, consisting of a detector followed by a method for associating detections into tracks. Tracking by associating detections through motion-based similarity heuristics is the basic way. Motion models aim at utilizing motion information to estimate future locations, playing an important role in enhancing the performance of association. Recently, a large-scale dataset, DanceTrack, where objects have uniform appearance and diverse motion patterns, was proposed. With existing hand-crafted motion models, it is hard to achieve decent results on DanceTrack because of the lack of prior knowledge. In this work, we present a motion-based algorithm named TLtrack, which adopts a hybrid strategy to make motion estimates based on confidence scores. For high confidence score detections, TLtrack employs transformers to predict its locations. For low confidence score detections, a simple linear model that estimates locations through trajectory historical information is used. TLtrack can not only consider the historical information of the trajectory, but also analyze the latest movements. Our experimental results on the DanceTrack dataset show that our method achieves the best performance compared with other motion models.

Understanding how environmental factors influence the responsiveness of crop yield to growing season precipitation (GSP) can reduce the risk of yield fluctuations, ensuring stable crop production. This study involved the cultivation of rainfed potatoes at three locations within the climatic transition zone of Northwest China. We employed stepwise linear regression and machine learning techniques to pinpoint the key environmental factors influencing potato tuber yield and the yield-precipitation relationship. The slope of the water-limited yield potential relationship for potatoes was determined to be 172.1 ​kg ​ha−1 ​mm−1, with an intercept at 121.2 ​mm. The potato tuber yield exhibited an upward trend with increasing GSP but declined once the precipitation exceeded 400 ​mm. However, GSP alone explained up to 30% of the variability in potato tuber yield. Factors such as soil moisture at planting, maximum temperatures during the tuber stolon initiation and bulking stages, diurnal temperature fluctuations at maturity, and excessive precipitation events during the growing season significantly influenced potato tuber yield, and consequently, the relationship between yield and GSP. Conversely, climatic factors accounted for more than 63% of the variation in potato tuber yield, with the multiple linear regression model yielding the best results. This was especially evident when the yield-precipitation relationship was categorized into two groups based on the amount and distribution of GSP, maximum temperature, and radiation levels. This analysis suggested that preventing unnecessary water evaporation when precipitation is low, improving drainage when precipitation is high, and planting potato on an optimal date can advance potato production.

Producing renewable e-methanol from e-hydrogen and diverse carbon sources is an essential way for clean methanol preparation. Despite this, the technical and economic feasibility of different e-methanols has yet to be thoroughly compared, leaving the most promising pathway to achieve commercialization yet evident. This paper reports a preliminary analysis of the lifecycle greenhouse gas (GHG) emissions and costs of four renewable e-methanols with different carbon sources: bio-carbon, direct air capture (DAC), fossil fuel carbon capture (FFCC), and fossil. The results indicate that renewable e-methanol costs (4167−10250 CNY/tonne) 2−4 times the market rate of grey methanol. However, with the carbon tax and the projected decline in e-H2 costs, blue e-methanol may initially replace diesel in inland navigation, followed by a shift from heavy fuel oil (HFO) to green e-methanol in ocean shipping. Furthermore, the e-H2 cost and the availability of green carbon are vital factors affecting cost-effectiveness. A reduction in e-H2 cost from 2.1 CNY/Nm3 to 1.1 CNY/Nm3 resulting from a transition from an annual to a daily scheduling period, could lower e-methanol costs by 1200 to 2100 CNY. This paper also provides an in-depth discussion on the challenges and opportunities associated with the various green carbon sources.

Abstract Background Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. Methods Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). Results Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45–49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35–39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P

Abstract Background Streptococcus mutans (S. mutans) is an important pathogenic bacterium that causes dental caries, while Streptococcus gordonii (S. gordonii) is a non-cariogenic bacterium that inhibits the growth of S. mutans. The SepM protein can promote the inhibitory ability of S. mutans against S. gordonii by cleaving CSP-21 and activating the ComDE two-component system. This study was designed to explore sepM mutation in S. mutans clinical isolates and related function in the regulation of interactions with S. gordonii. Methods The S. mutans clinical strains that can inhibit the growth of S. gordonii constitute the inhibitory group. 286 C-serotype S. mutans strains were categorized into S. gordonii inhibitory (n = 114) and non-inhibitory bacteria (n = 172). We detected sanger sequencing of sepM gene, the expression levels of related genes and proteins in clinical isolates, obtained prokaryotic expression and purification of mutated proteins, and analyzed the effect of the target mutations on the binding between SepM and CSP-21. Results We found that C482T, G533A, and G661A missense mutations were presented at significantly higher frequency in the inhibitory group relative to the non-inhibitory group. There was no significant difference in the expression of the sepM gene between selected clinical isolates harboring the G533A mutation and the control group. The expression levels of SepM, phosphorylated ComD, and ComE in the mutation group were significantly higher than those in the control group. SepM_control and SepM_D221N (G661A at the gene level) were found to contain two residues close to the active center while SepM_G178D (G533A at the gene level) contained three residues close to the active center. At 25 °C and a pH of 5.5, SepM_D221N (G661A) exhibited higher affinity for CSP-21 (KD = 8.25 µM) than did the SepM control (KD = 33.1 µM), and at 25 °C and a pH of 7.5, SepM_G178D (G533A) exhibited higher affinity (KD = 3.02 µM) than the SepM control (KD = 15.9 µM). It means that it is pH dependent. Conclusions Our data suggest that increased cleavage of CSP-21 by the the mutant SepM may be a reason for the higher inhibitory effect of S. mutans on S. gordonii .

Abstract In carbonate reservoirs characterized by the fracture‐cavity system as storage spaces, the drilling process is highly prone to the loss of drilling fluid. This not only affects drilling efficiency but can also lead to severe accidents, such as blowouts. Therefore, it is crucial to understand the distribution pattern of these fractures. However, the formation of carbonate rock fracture‐cavity system systems, being controlled by various factors, is difficult to precisely identify. This limitation hampers the efficient development of such types of oil and gas fields. This paper presents a case study of the M55 sub‐section carbonate gas reservoir in the Sulige gasfield, proposing an improved You Only Look Once v5s (YOLOv5s) deep learning algorithm. It utilizes enhanced training with conventional logging data to identify response characteristics of fractures in the carbonate reservoirs. And its identification results have been confirmed to be accurate by various fracture data obtained through different means, such as the core samples, cast thin section photographs, imaging logging data, and seismic attributes. This method incorporates the Ghost convolution module to replace the Conv module in the backbone network of the YOLOv5s model, and modifies the C3 module into a Ghost Bottleneck module, effectively making the model more lightweight. Additionally, a Convolutional Block Attention Module is integrated into the Neck network, enhancing the model's feature extraction capabilities. Finally, the method employs the Efficient Intersection over Union Loss function instead of the Complete Intersection over Union Loss, reducing the network's regression loss. The validation results using actual data demonstrate that this method achieves an average recognition accuracy of 87.3% for the fracture‐cavity system, which is a 3% improvement over the baseline model (YOLOv5s). This enhancement is beneficial for precisely locating the drilling fluid loss positions in carbonate reservoirs.

Abstract Background Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. Methods In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. Results The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. Conclusions High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.

Abstract The field of levitated optomechanics has experienced significant advancements in manipulating the translational and rotational dynamics of optically levitated particles and exploring their sensing applications. The concept of using optically levitated particles as gyroscopes to measure angular motion has long been explored but has not yet been proven either theoretically or experimentally. In this study, we present the first rotor gyroscope based on optically levitated high-speed rotating particles. The gyroscope is composed of a micrometer-size ellipsoidal vaterite particle that is driven to rotate at MHz frequencies in a vacuum environment. When an external angular velocity is input, the optical axis deviates from its initial position, resulting in changes in the frequency and amplitude of the rotational signal. By analyzing these changes, the angular velocity of the input can be accurately detected, making it the smallest rotor gyroscope in the world. The angular rate bias instability of the gyroscope is measured to be 0.08°/s and can be further improved to as low as 10−9°/h theoretically by cooling the motion and increasing the angular moment of the levitated particle. Our work opens a new application paradigm for levitated optomechanical systems and may pave the way for the development of quantum rotor gyroscopes.

Abstract Background Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. Case presentation We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. Conclusion Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

Abstract Background Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging. Methods In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT. Results In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P

Abstract Background Chelerythrine is an important alkaloid used in agriculture and medicine. However, its structural complexity and low abundance in nature hampers either bulk chemical synthesis or extraction from plants. Here, we reconstructed and optimized the complete biosynthesis pathway for chelerythrine from (S)-reticuline in Saccharomyces cerevisiae using genetic reprogramming. Results The first-generation strain Z4 capable of producing chelerythrine was obtained via heterologous expression of seven plant-derived enzymes (McoBBE, TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, and PsCPR) in S. cerevisiae W303-1 A. When this strain was cultured in the synthetic complete (SC) medium supplemented with 100 µM of (S)-reticuline for 10 days, it produced up to 0.34 µg/L chelerythrine. Furthermore, efficient metabolic engineering was performed by integrating multiple-copy rate-limiting genes (TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, PsCPR, INO2, and AtATR1), tailoring the heme and NADPH engineering, and engineering product trafficking by heterologous expression of MtABCG10 to enhance the metabolic flux of chelerythrine biosynthesis, leading to a nearly 900-fold increase in chelerythrine production. Combined with the cultivation process, chelerythrine was obtained at a titer of 12.61 mg per liter in a 0.5 L bioreactor, which is over 37,000-fold higher than that of the first-generation recombinant strain. Conclusions This is the first heterologous reconstruction of the plant-derived pathway to produce chelerythrine in a yeast cell factory. Applying a combinatorial engineering strategy has significantly improved the chelerythrine yield in yeast and is a promising approach for synthesizing functional products using a microbial cell factory. This achievement underscores the potential of metabolic engineering and synthetic biology in revolutionizing natural product biosynthesis.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

The total saline-alkaline land area in China is about 99.13 million hectares distributed across northern China, coastal areas, and areas along the bank of the Huanghe River. About 46 million hectares of saline-alkaline water areas are distributed around these saline-alkaline lands, most of which are thalassic and characterized by a high pH value in excess of 8.8 associated with high-carbonate alkalinity concentrations and various types of ion imbalances. Saline-alkaline waters are stressful environments in which only relatively few organisms are able to survive. Consequently, most of the saline-alkaline water resources have been desolate for a long time. The effective utilization of saline-alkaline water resources will benefit restoration of saline-alkaline habitats and the expansion of aquaculture space. Naked carp (Gymnocypris przewalskii) are endemic to the austere saline-alkaline environment of Qinghai Lake. Due to overfishing in the 1960s and environmental changes in the lake area, the resources necessary for naked carp survival in Qinghai Lake declined substantially. At present, the major measures to protect the naked carp and maintain the ecological balance of Qinghai Lake are through a fishing ban and artificial stocking and releasing. The feeding behavior of fish under natural conditions has obvious rhythm characteristics, which is an important research topic for healthy aquaculture. To explore the characteristics of self-feeding rhythm and growth performance of fish in a saline-alkaline environment and provide basic data for the protection of native saline-alkaline fish, naked carp were taken as representative in this study. First, the freshwater and lake water group with natural photoperiod (14L: 10D) and the lake water group with darkness (24D) were set. The artificial lake water was prepared according to the ionic composition of Qinghai Lake, with the contents of Na+ 23.05%, K+ 1.34%, Ca2+ 0.11%, Mg2+ 6.88%, HCO3– 7.09%, CO32– 5.07%, Cl– 40.39%, and SO42– 16.07%. The measured salinity of the artificial lake water was 15.08, and the carbonate alkalinity was 27.53 mmol/L. According to the local photoperiod of Qinghai Province, the whole day was divided into five periods as 05:00–08:00, 8:00–11:00, 11:00–15:00, 15:00–19:00, and 19:00–05:00. The feeding rhythm experiment lasted for 5 d, and the average food intake of each period was calculated. The results showed that naked carp had an obvious daily feeding rhythm during their natural photoperiod. In the natural photoperiod, the feeding peak was from 08:00 to 11:00, and the low feeding period was from 05:00 to 08:00 in freshwater. In the lake water, naked carp showed high and continuous feeding from 08:00 to 19:00, and their average hourly feed intake was significantly higher than that from 05:00 to 08:00 and 19:00 to 05:00. Therefore, naked carp were determined to be the daytime feeding fish type. In addition, the high proportion and the continuous feeding in daytime in lake water indicated that the osmotic and acid-base regulation of naked carp in saline-alkaline water may enhance their diurnal feeding rhythm. Whereas in the continuous dark environment, the feeding rhythm of naked carp was weakened, and the average hourly food intake of each period was similar. To explore the growth performance of naked carp under a self-feeding rhythm, the lake water group and the freshwater control group with natural photoperiod were set up. After 63 days of self-feeding, the individual body length and weight of the naked carp were measured after being anesthetized with MS-222. The length growth rate (1.19±0.17)%, weight growth rate (10.66±0.98)%, and specific growth rate (0.16±0.02)%/d of naked carp in the lake water group were significantly lower than those in the freshwater group [length growth rate (18.66±0.41)%, weight growth rate (67.32±3.05)%, and specific growth rate (0.82±0.03)%/d)], indicating that the growth of naked carp was inhibited by high salinity and carbonate alkalinity environment. The parameter b of body length-weight relationship curve of the naked carp in both the lake water group and the freshwater group was less than three, which showed that the naked carp was a negative allometric growth fish. The b value of the lake water group was lower than that of the freshwater group, and the body length of naked carp increased faster than body weight in the lake water. The growth characteristics of naked carp were affected by the high saline-alkaline environment. The self-feeding rhythm and growth performance of naked carp provided a basic knowledge for creating a feeding strategy for fish cultured in a saline-alkaline environment and recovering endangered native saline-alkaline fish.

Abstract The disc overhang diameter can significantly affect the uplift bearing capacity of new concrete expanded-plate pile groups, affecting their design and practical applications. Accordingly, this effect was investigated considering the failure laws of the soil surrounding various pile types and groups. Based on the uplift bearing capacities of single and double piles, a finite element simulation was adopted to establish models for the four-, six-, and nine-pile groups. The relationship between the disc overhang diameter and uplift-bearing capacity of each pile group was explored: as the disk overhang diameter increased, the uplift-bearing capacities of the pile groups increased; however, this relationship is nonlinear. The optimal disc overhang diameter was determined as 1.5–1.75 times the pile diameter. For a constant disc overhang diameter, corner piles have a greater uplift bearing capacity than side piles in the six-pile group, and a greater uplift bearing capacity than the side and center piles in the nine-pile group. Thus, the pile-group effect depends on the pile position. The uplift bearing capacity did not increase linearly with the number of piles, and the average uplift bearing capacity of a pile in a pile group was less than that of a single pile. Therefore, the uplift bearing capacity of the pile groups decreased as the number of piles increased. The reliability of the simulation was verified via visual testing of a small-scale half-cut pile model.

Abstract Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8–9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7–8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17–2.44, p = 0.005), 1.62 (95% CI 1.11–2.36, p = 0.013), and 1.57 (95% CI 1.1–2.24, p = 0.012) respectively. The dose–response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.

Abstract Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases. Graphical Abstract

Abstract Objective The objective of this study is to evaluate and compare the surgical outcomes and complications of Percutaneous Endoscopic Lumbar Decompression (PELD) and traditional revision surgery in treating symptomatic Adjacent Segment Degeneration (ASD). This comparison aims to delineate the advantages and disadvantages of these methods, assisting spine surgeons in making informed surgical decisions. Methods 66 patients with symptomatic ASD who failed conservative treatment for more than 1 month and received repeated lumbar surgery were retrospectively collected in the study from January 2015 to November 2018, with the average age of 65.86 ± 11.04 years old. According to the type of surgery they received, all the patients were divided in 2 groups, including 32 patients replaced the prior rod in Group A and 34 patients received PELD at the adjacent level in Group B. Patients were followed up routinely and received clinical and radiological evaluation at 3, 6, 12 months and yearly postoperatively. Complications and hospital costs were recorded through chart reviews. Results The majority of patients experienced positive surgical outcomes. However, three cases encountered complications. Notably, Group B patients demonstrated superior pain relief and improved postoperative functional scores throughout the follow-up period, alongside reduced hospital costs (P

Abstract The biodegradable polymer poly-β-hydroxybutyrate (PHB) is a promising carbon source for biological mitigation of nitrogen pollution, a significant problem in aquaculture that physical and chemical methods have not provided a comprehensive solution. Here we investigated the impact of PHB on the zero-water-change largemouth bass culture by 30- and 40-day experiments. PHB loaded into the filter circulation pump at 4 g L− 1, optimum value determined by the first experiment, significantly reduced the levels of nitrate by 99.65%, nitrite by 95.96%, and total nitrogen by 85.22% compared to the control without PHB. PHB also significantly increased denitrifying bacteria (e.g., Proteobacteria and Fusobacteria) and expression of denitrification genes (e.g., nirK and nirS) in the microbial community, improving growth and health parameters of largemouth bass. While the impact may vary in other culture systems, PHB thus demonstrated its remarkable utility in aquaculture, highlighting ecological assessment and application to larger aquaculture operations as future considerations.

Abstract Background The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive. Results A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-β, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir’s role in the ceRNA regulatory network mechanism, we identified 113 circRNA–miRNA pairs and 14 miRNA–mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1. Conclusions Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed.

Abstract Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs

Abstract Understanding the determinants of biodiversity in fragmented habitats is fundamental for informing sustainable landscape development, especially in urban landscapes that substantially fragment natural habitat. However, the relative roles of landscape and habitat characteristics, as emphasized by two competing frameworks (the island biogeography theory and the habitat diversity hypothesis), in structuring species assemblages in fragmented habitats have not been fully explored. This study investigated bird assemblages at 26 habitat patches (ranging in size from 0.3 to 290.4 ha) in an urban landscape, southwest China, among which habitat type composition and woody plant species composition varied significantly. Through 14 bird surveys conducted over six breeding seasons from 2017 to 2022, we recorded 70 breeding bird species (excluding birds recorded only once and fly-overs, such as raptors, swallows and swifts), with an average of 26 ± 10 (SD) species per patch. We found that patch area had significant direct and indirect effects on bird richness, with the indirect effects mediated by habitat richness (i.e., the number of habitat types). Isolation (measured as the distance to the nearest patch), perimeter to area ratio (PAR), and woody plant richness did not significantly predict variation in bird richness. Furthermore, none of these factors significantly sorted bird species based on their functional traits. However, the overall makeup of bird assemblages was significantly associated with the specific habitat types and woody plant species present in the patches. The results suggest that neither the island biogeography theory nor the habitat diversity hypothesis can fully explain the impacts of habitat fragmentation on bird richness in our study system, with their roles primarily being linked to patch area. The findings that habitat and plant compositions were the major drivers of variation in bird assemblage composition offer valuable insights into urban planning and green initiatives. Conservation efforts should focus not only on preserving large areas, but also on preventing urban monocultures by promoting diverse habitats within those areas, contributing to the persistence of meta-communities.

Abstract Organic waste treatment is a major driver of global carbon emissions, thus its low-carbon utilization is essential yet unclear. Through a life cycle assessment of organic waste data from 34 provincial-level regions in China, we have determined that the synergistic and integrated utilization scheme (URIRP) with organic fertilizer and biochar as the primary products can reduce the annual life cycle carbon emissions from 6.9 Mt CO2e to 2.83 Mt CO2e. This reduction can offset 6% of the carbon emissions from the electricity industry mainly through carbon sequestration by application of biochar-based fertilizer, and fossil fuel displacement by bio-energy. Moreover, URIRP can promote the recycling of N and P, reduce annual emission of air pollutants by 866 Mt, and increase topsoil organic matter content by 0.25‰ and economic efficiency by 135%. These findings indicate that URIRP could realize sustainable management of UROSW with significant environmental and economic benefits, and contribute to the realization of China’s carbon neutrality goal.

Abstract Background The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence. Methods Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease. Results In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations. Conclusions This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.

Abstract Collagen, known for its excellent biocompatibility and biological properties, has limited in vivo maintenance duration after implantation, while hyaluronic acid faces challenges such as various complications and insufficient support for cell proliferation. In this study, an injectable hyaluronic acid/collagen (HCol) hydrogel was developed to achieve enhanced cell-material interactions and accelerated skin regeneration. Physical and chemical characterizations demonstrated that the HCol hydrogel was injectable and stable after the implantation. In vitro cell culture results illustrated that the hydrogel promoted the proliferation of human dermal fibroblasts, extracellular matrix expression and angiogenesis. The subcutaneous implantation in rats showed the superior biocompatibility of HCol hydrogel and enhanced secretion and deposition of extracellular matrix, compared with commercial hyaluronic acid dermal filler. MRI analysis showed that the hydrogel stably remained in vivo for at least three months. The histological examination and SHG signals further demonstrated that the hydrogel modulated fibroblast phenotype and stimulated vascular ingrowth and collagen synthesis, without inducing significant inflammation, swelling or erythema in vivo. Graphical Abstract

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu2+, although the underlying mechanism of this enhancement remains unclear. In this study, we investigated the mechanistic basis of Cu2+-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate (CuET) complex. CuET exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of action. However, despite its potent activity, CuET suffered from poor solubility and limited permeability, as revealed by our druggability studies. To overcome these intrinsic limitations, we developed a scalable method to prepare CuET nanocrystals (CuET NCs) using a metal coordination-driven self-assembly approach. Pharmacokinetic studies demonstrated that CuET NCs exhibited a 6-fold improvement in bioavailability. Notably, CuET NCs exhibited high biodistribution in the intestine, suggesting their potential application for the treatment of inflammatory bowel diseases (IBDs). To evaluate their therapeutic efficacy in vivo, we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis symptoms. Our findings highlight the discovery of CuET as a potent anti-pyroptotic agent, and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

The multi-channel transcranial magnetic stimulator is commonly used for rehabilitation treatment of ischemic cerebrovascular disease, neurosis, and brain injury diseases in the elderly. And multiple high coherency signals are required as inputs for its test, which are with consistent frequency, adjustable amplitude, equal magnitude, and long-time phase consistency ⩽±1°. But ordinary signal sources have only one output channel, which is far from meeting the test requirements. If the traditional power division is used for the duplication, the phase difference between the channels will be larger than ±1°. If the multi-throw Radio Frequency (RF) switch is used, it will seriously affect the phase consistency of the input signal and increase the distortion of the signal. In order to solve the above problems, the method to extend the output of the microwave signal source has been proposed in the paper by using the integrated transceiver AD9361. The proposed method can realize the duplication of the number of signal channels according to user requirements. Then a signal replicator has been designed by combining AD9361 chip and Field-Programmable Gate Array (FPGA) control module. The experimental platform has been built to test the performance of the designed device. Experimental results show that the duplicated signals are highly consistent with the source signal in the power amplitude and frequency, meanwhile the phase of the duplicated signals are all highly consistent with each other.

Introduction: The toxicity of fine particulate matter (PM2.5) is determined by its components, while the evidence regarding associations of PM2.5 components with blood pressure (BP) is limited, especially in rural areas. Objectives: This study aimed to explore the associations of PM2.5 and its chemical components with systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), mean artery pressure (MAP) levels and hypertension prevalence, and to identify key components in Chinese rural areas. Methods: 39,211 adults from the Henan Rural Cohort were included during 2015–2017. Different periods of PM2.5 and chemical components were estimated by hybrid satellite model. The single-pollutant, component-PM2.5 model, component-residual model and component-proportion model were applied to explore the associations of pollutants with BP levels and hypertension prevalence. Exposure-response (E-R) relationships, stratified analyses and sensitivity analyses were used to explore these associations further. Results: 12,826 (32.71%) were identified with hypertension. For each 1 μg/m3 increase of pollutants, the adjusted odds ratio (OR) for hypertension prevalence was 1.03 for PM2.5 mass, 1.40 for BC, 1.16 for NH4+, 1.08 for NO3–, 1.17 for OM, 1.12 for SO42− and 1.25 for SOIL in the single-pollutant model. BC and SOIL were statistically significant in the component-PM2.5 model, component-residual model and component-proportion model. Similarly, associations of these pollutants with elevated BP levels were also found in aforementioned four models. These pollutants produced a stronger association with SBP than DBP, PP and MAP. Most of associations were non-linear in E-R relationships. The groups of older, the men, with lower per capita monthly income, lower educational level and higher BMI were more vulnerable to these pollutants in stratified analyses. The results remained stable in sensitivity analyses. Conclusion: Long-term exposure to PM2.5 and its components, especially BC and SOIL, was associated with elevated BP and hypertension prevalence in rural adults, and decreasing pollutants may provide additional benefits.

Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

Bashang suancai is one of the most wellknown traditional fermented vegetables in North China. The study examined the variations in bacterial diversity, physicochemical properties, and volatile flavor compounds (VFCs) of Bashang suancai over a 7-day fermentation period, utilizing Illumina NovaSeq sequencing and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The leading bacterial phyla were Firmicutes, Proteobacteria, and Cyanobacteria, while the predominant bacterial species included Vibrio, Lactiplantibacillus, Cyanobacteriales, Weissella, and Latilactobacillus. The bacterial community diversity decreased significantly following 7 days of fermentation. The microbial profiles were markedly affected by pH, reducing sugar content (RSC), and salt content (SC). A total of 187 VFCs were identified from the specimens. Following 5 days of fermentation, the taste compounds achieved equilibrium, with isothiocyanates, alcohols, and esters predominating among the volatile molecules. Spearman correlation analysis revealed that a strong link between Latilactobacillus, Levilactobacillus, Lactiplantibacillus, Weissella, and Vibrio with the flavor of pickles. This study established a significant foundation for identifying strains that enhance taste development and improve the nutritional and sensory quality of Bashang suancai.

A novel emergency steel pier, assembled from market-available profiles, has been developed to address the challenges associated with the ''regular stockpiling and rapid emergency deployment'' of bridge pier repair equipment. These challenges often involve significant labor and financial costs for manufacturing and maintenance. The buckling modes of the columns and pier-girder connections were considered. Using energy methods and plate-shell theory, an analytical formula for the critical load-bearing capacity of the steel pier under emergency conditions was derived. Numerical simulations were conducted for comparison and validation, resulting in an optimized and simplified method for calculating the critical load capacity, which is suitable for engineering applications.The study shows that the critical load-bearing capacity of the emergency steel pier exhibits distinct patterns under the influence of column buckling modes and pier-girder connection methods. In cases where the column is fixed at one end and hinged at the other, or fixed at both ends, the critical load for axisymmetric buckling is affected by factors such as elastic modulus, Poisson's ratio, height, radius, wall thickness, and the number of buckling waves. When considering non-axisymmetric buckling, the number of circumferential buckling waves becomes an additional factor. A simplified method for calculating the critical load-bearing capacity was developed. The simplified formula depends only on a correction factor, modified buckling stress, the number of columns, and cross-sectional area. This makes it highly practical for emergency engineering applications.

Soil has an intricate pore structure, with the macropore structure serving as a pivotal component of gas exchange, liquid flow, and solute transport within the soil matrix. Scientifically understanding the macropore structure is important for the exploration of soil ecological functions. Drawing upon research literature from diverse nations, this study presents a comprehensive summary of past research findings, thoroughly examining the definition and taxonomy of soil macropores. Additionally, we delve into the factors that affect macropore structure, the effects of macropores on soil ecological functions, and the indicators that describe the nature of macropores. Furthermore, the principles, suitability conditions, benefits, and limitations of the widely utilized techniques for characterizing soil macropore structure were outlined, including staining observation, soil water retention curve, mercury intrusion porosimetry, gas adsorption, nuclear magnetic resonance, scanning electron microscopy, and computed tomography (CT). A comparative analysis was conducted to assist scholars in comprehending the theory of soil macropores, facilitating the selection of suitable macropore structure characterization techniques, and enabling the development of collaborative application modes among these techniques. Using the Web of Science core collection database, bibliometric software such as VOSviewer and CiteSpace were employed to explore the research hotspots and trends in CT, which is currently the most popular technique for characterizing soil macropore structure. This analysis offers insights into the future prospects of CT in the field of soil macropore structure characterization techniques. This article is of particular interest to readers engaged in the characterization of soil macropores.

In the course of this investigation, three machine learning models (Gaussian Process Regression, Decision Tree Regression, and Kernel Ridge Regression) were examined for determining the correlation between the input variables (x and y) which are spatial coordinates of model’s geometry, and the content of species in adsorption for sulfur capture. For the process modeling, mass transfer was analyzed, and the concentration distribution of sulfur compound was obtained via numerical solution of mass transfer equations, and then used for machine learning models. The machine learning models were trained using a dataset of 19,000 observations, and their performance was assessed through metrics including R2 score, MAE, and RMSE. Analysis of the results reveals that Decision Tree Regression surpassed the other two models in performance, with an R2 score of 0.9989, MAE of 6.64405E-01, and RMSE of 1.1277E+00. Gaussian Process Regression had an R2 score of 0.97106, MAE of 3.65541E+00, and RMSE of 5.6821E+00, while Kernel Ridge Regression had an R2 score of 0.86347, MAE of 8.26121E+00, and RMSE of 1.1330E+01. The Clonal Selection Algorithm was used for hyper-parameter optimization for all models. These findings demonstrate the potential of machine learning techniques for accurately and reliably predicting the concentration of chemical species and highlight the importance of considering the choice of model and hyper-parameter optimization for optimal performance.

Physical activity among university students significantly influences anxiety, yet the underlying mechanisms require further exploration. This study examines mental toughness as a mediator and social support as a moderator to elucidate these relationships.MethodsUsing a cross-sectional design, convenient sampling was employed to select 997 first to fourth-year students from Jishou University for a self-reported survey. Measures included assessments of physical activity, mental toughness, social support, anxiety, and basic demographic variables. Descriptive statistics, correlations, and a moderated mediation model were conducted.ResultsPhysical activity was significantly negatively correlated with anxiety and positively correlated with mental toughness. Mental toughness was significantly negatively correlated with anxiety, mediating the relationship between physical activity and anxiety to a certain extent. Social support moderated the latter part of the mediated model pathways.ConclusionPhysical activity negatively correlates with anxiety among university students. Mental toughness mediates the relationship between physical activity and anxiety, while social support moderates the latter stages of this mediated model (mental toughness → anxiety).

Dietary flavonoids are regarded as potent inhibitors of gut bacterial β-glucuronidase (β-GUS), although the precise structure-activity relationship between dietary flavonoids and β-GUS remains elusive. In this study, 24 dietary flavonoids of 6 common different structural types were selected as model molecules to investigate this relationship through enzymatic inhibition kinetics and molecular docking simulations. The findings revealed that delphinidin (1) and baohuoside I (16) exhibited robust inhibitory activities, while the formation of ionic bond and hydrogen bonds was found to play crucial roles in these interactions. Moreover, the core structure, position, and quantity of hydroxyl groups; type and number of glycosyls, and the presence of isopentenyl group all played pivotal roles in influencing inhibitory activities against β-GUS derived from Escherichia coli. These results offer valuable insights into the relationship between flavonoid structure and enzyme inhibition, which could prove invaluable for the development of novel drugs and flavonoid dietary supplements.

ABSTRACT Introduction Individuals who develop new‐onset diabetes have been identified as a high‐risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high‐risk individuals among those with new‐onset diabetes. Methods Employing the UK Biobank cohort, we focused on those developing new‐onset diabetes during follow‐up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5‐fold cross‐validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development. Results Among 12,735 patients with new‐onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865–0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut‐offs were established: 1.28% and 5.26%. The recommended 1.28% cut‐off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high‐risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases. Conclusions We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new‐onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high‐risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources.

The rising incidence of colistin (COL) resistance poses a significant challenge, undermining the therapeutic efficacy of COL against life-threatening bacterial infections. Therefore, the urgent identification and development of new therapeutics are imperative. It has been proven that combinations of antibiotics and promising non-antibiotic agents could be a potential strategy to combat infections caused by MDR pathogens. Due to various antimicrobial properties, medicinal plants have attracted significant attention, which could be promising adjuvant. In this study, we investigated the synergistic effects of combining COL with resveratrol (RST) and baicalin (BAI) against mcr-1-positive Escherichia coli through antibiotic susceptibility testing, checkerboard method and time-killing assays. The mechanisms of combination treatment were analyzed using SEM, fluorometric assays and transcriptome analysis. The molecular docking assay was conducted to elucidate potential interactions between RST, BAI and the MCR-1 protein. Finally, we assessed the in vivo efficacy of combination against mcr-1-positive Escherichia coli. The results demonstrated that the combination of RST, BAI and COL showed significant synergistic activity both in vitro and in vivo. Further mechanistic study revealed that the combination could increase the membrane-damaging ability of COL, disrupt the homeostasis of proton motive force (PMF), inhibit the activity of efflux pumps and impair ATP supply. The molecular docking revealed that RST and BAI could bind to MCR-1 stably, indicating the combination of RST and BAI may be an effective MCR-1 inhibitor. Our findings demonstrated that the combination of RST and BAI might be potential COL adjuvant, providing an alternative approach to address mcr-1-positive Escherichia coli infections.

The ecosystem of semi-arid watersheds is influenced by a combination of natural climate factors, rainfall, and habitat destruction, resulting in complex mechanisms of spatial differentiation and evolution of water ecological health. Indicator selection in mainstream water ecological health assessment methods, such as the Index of Biotic Integrity (IBI), often relies on subjective reference point choices. This approach tends to overlook the comprehensive impacts and interactions among various environmental stressors. For watersheds significantly influenced by natural climatic factors, considerable uncertainties arise, leading to a lack of scientific justification for establishing water ecological health protection goals. In this study, the nonlinear capabilities of the random forest (RF) model were applied to reduce subjectivity in traditional water ecological health assessments and to more accurately reveal the emerging spatial differentiation patterns and underlying causes of water ecological health in the Wei River Basin (WRB), the largest typical semi-arid watershed of the Yellow River in China. Our findings indicate: (1) Traditional evaluation indices indicate that the overall water ecological health of the WRB is classified as sub-healthy (60 %). The core indicators include dominant species, total algal density, and the percentage of diatom density, with no significant spatial differentiation observed. (2) An improved water ecological health assessment method for semi-arid watersheds, based on the RF model, has been developed to replace traditional subjective judgment steps. This method establishes a complex multi-input–output response relationship (R2>0.85) between environmental stress indicators and the biological integrity index for the WRB. (3) The model results identify key driving factors affecting changes in water ecological health in semi-arid watersheds, with the sensitivity of the new model increasing nearly 11-fold compared to traditional IBI methods. (4) Following improvements, the water ecological health characteristics of the WRB exhibit significant spatial heterogeneity, with a higher dispersion coefficient (1.21), and demonstrate enhanced nonlinear response trends to climatic factors. The application of machine learning models indicates that traditional methods may underestimate the extent of ecological health degradation in watersheds and tend to oversimplify spatial heterogeneity characteristics.

Background Six randomized trials have not detected a difference between intravenous alteplase plus endovascular thrombectomy and endovascular thrombectomy alone in stroke. Tenecteplase, a recombinant human tenecteplase tissue‐type plasminogen activator, is a genetically modified variant of alteplase. It is unclear whether the outcomes are different if alteplase is replaced with tenecteplase. This trial aims to determine whether intravenous tenecteplase within 4.5 hours of time last known well confers benefit in patients with acute ischemic stroke with large‐vessel occlusion who undergo endovascular thrombectomy. Methods BRIDGE‐TNK (Thrombectomy With Versus Without rhTNK‐tPA in Stroke) is an investigator‐initiated, multicenter, prospective, randomized, open‐label trial with blinded end point evaluation conducted at 40 thrombectomy‐capable centers in China. This trial will randomize 544 patients with intravenous thrombolysis–eligible stroke (272 in each arm) with large‐vessel occlusion within 4.5 hours of last known well to receive bridging intravenous tenecteplase with endovascular thrombectomy (tenecteplase‐plus‐thrombectomy group) or endovascular thrombectomy alone (thrombectomy‐alone group). The primary outcome is the proportion of patients achieving functional independence, defined as a score of 0 to 2 on the modified Rankin Scale, at 90 days. Safety will be assessed via symptomatic intracranial hemorrhage at 48 hours and death at 90 days. Conclusions BRIDGE‐TNK will provide important data on the role of intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke with large‐vessel occlusion who can be treated within 4.5 hours of last known well. Registration URL: https://clinicaltrials.gov. Unique identifier: NCT04733742.