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Abstract Background The association between the oxidative stress gene polymorphism and chronic obstructive pulmonary disease (COPD) risk has been extensively studied but the results have been controversial. This study aimed to investigate the overall association between the oxidative stress gene including glutathione S-transferase (GST), epoxide hydrolase exon (EPHX), superoxide dismutase (SOD), catalase (CAT), cytochrome P450 system (CYP) and heme oxygenase (HO-1) polymorphism and the risk of COPD. Methods We searched the PubMed and EMBASE database to identify studies that investigated the association between the oxidative stress gene polymorphism and risk of COPD. The relevant data were extracted and statistical analyses were performed using the Revman 5.4 and STATA 12 software. Dominant genetic model, recessive model, co-dominant model, heterozygote model, and allele model were analyzed. Venice criteria and publication bias were conducted to access the credibility and reliability. Results In total, 63 publications including 14,733 patients and 50,570 controls were included in the meta-analysis.15 genetic variants of 6 genes were analyzed, and 7 SNPs in GSTP1, CAT, CYP, SOD were first analyses until now. In our study, EPHX T113C C allele, GSTM1 null, GSTT1 null, GSTP1 A313G G and C341T T allele, CYP1A1 MspI C allele, SOD3 A213G G allele and L type in Ho-1 showed increased COPD risk, especially in Asians. T allele in CAT C262T and C allele in SOD2 Val 9 Ala were associated with decreased COPD risk. To avoid high heterogeneity and publications bias, subgroups analysis was performed in accord with HWE and ethnicity. Publication bias was assessed by Begg’s funnel plots and Egger’s test, and no publication bias were found for recessive models. 4 variants were identified with strong levels of epidemiological evidence of associations with the COPD risk. Conclusions Our results confirm that oxidative stress gene polymorphism was associated with COPD risk. These finding can improve human understanding of this disease gene molecular level and enable early intervention and prevention of COPD. Well-designed studies with large sample sizes are essential to clarify the association of these significant variants with the susceptibility to COPD.

Abstract Magnetic actuation has attracted a growing attention due to its non‐contact performance, rapid response and penetrability. The realization of magnetic actuation requires the participation of magneto‐responsive materials (MRMS), and magneto‐responsive polymers (MRPs) are one of the most widely used MRMs. Here, we report the fabrication, characterization and actuation tests of neodymium‐iron‐boron‐polydimethylsiloxane (NdFeB‐PDMS) magnetic films. The NdFeB‐PDMS magnetic film has great flexibility and elasticity, as well as excellent magnetism. The film also shows exceptional deformation and magnetic controllability under magnetic actuation. Besides, it can be driven under a very low magnetic field down to 1mT, and generate an out‐of‐plane displacement of 2.7 mm under the action of magnetic fields. We focus on the tensile deformation of NdFeB‐PDMS films under magnetic driving and provide a possible design for their potential application in the tensile loading system. Preliminary tests demonstrate that the size of tensile deformation is adjusted by controlling the output signal and amplification factor. Highlights Fabrication of NdFeB‐PDMS magnetic films. Mechanical and magnetic characterizations of NdFeB‐PDMS films. Magnetic actuation tests of NdFeB‐PDMS films. Magnetic field‐induced tensile deformation of NdFeB‐PDMS films. Potential application of NdFeB‐PDMS films in the tensile loading system.

The current method of electricity stealing has changed from simple to high-tech. In this paper, combined with HPLC communication technology and measurement equipment, a three-layer progressive analysis model is established. The model fully exploits the advantages of HPLC in deepening application functions. Based on the edge computing resources and processing capabilities of the current electricity consumption information acquisition system, it realizes the identification of electricity theft behavior, the evaluation of user suspicion, the forensics of electricity theft, and the minute-level dispatch response to meet the actual power theft on site.

The number of maize leaves is an important indicator for assessing plant growth and regulating population structure. However, the traditional leaf counting method mainly relies on manual work, which is both time-consuming and straining, while the existing image processing methods have low accuracy and poor adaptability, making it difficult to meet the standards for practical application. To accurately detect the growth status of maize, an improved lightweight YOLOv8 maize leaf detection and counting method was proposed in this study. Firstly, the backbone of the YOLOv8 network is replaced using the StarNet network and the convolution and attention fusion module (CAFM) is introduced, which combines the local convolution and global attention mechanisms to enhance the ability of feature representation and fusion of information from different channels. Secondly, in the neck network part, the StarBlock module is used to improve the C2f module to capture more complex features while preserving the original feature information through jump connections to improve training stability and performance. Finally, a lightweight shared convolutional detection head (LSCD) is used to reduce repetitive computations and improve computational efficiency. The experimental results show that the precision, recall, and mAP50 of the improved model are 97.9%, 95.5%, and 97.5%, and the numbers of model parameters and model size are 1.8 M and 3.8 MB, which are reduced by 40.86% and 39.68% compared to YOLOv8. This study shows that the model improves the accuracy of maize leaf detection, assists breeders in making scientific decisions, provides a reference for the deployment and application of maize leaf number mobile end detection devices, and provides technical support for the high-quality assessment of maize growth.

In the post-harvest phase, fruit is inexorably subjected to extrinsic stressors that expedite energy expenditure and truncate the storage lifespan. The present study endeavors to elucidate the response strategies of litchi to the alterations of energy state caused by 2,4-Dinitrophenol (DNP) treatment through energy metabolism and sugar metabolism. It was observed that the DNP treatment reduced the energy state of the fruit, exacerbated membrane damage and triggered rapid browning in the pericarp after 24 h of storage. Furthermore, the expression of genes germane to energy metabolism (LcAtpB, LcAOX1, LcUCP1, LcAAC1, and, LcSnRK2) reached their peak within the initial 24 h of storage, accompanied by an elevation in the respiratory rate, which effectively suppressed the rise in browning index of litchi pericarp. The study also posits that, to cope with the decrease of energy levels and membrane damage, litchi may augment the concentrations of fructose, glucose, inositol, galactose, and sorbose, thus safeguarding the canonical metabolic functions of the fruit. Collectively, these findings suggest that litchi can modulate energy and sugar metabolism to cope with fruit senescence under conditions of energy deficiency. This study significantly advances the understanding of the physiological responses exhibited by litchi fruit to post-harvest external stressors.

Objective Tongue segmentation as a basis for automated tongue recognition studies in Chinese medicine, which has defects such as network degradation and inability to obtain global features, which seriously affects the segmentation effect. This article proposes an improved model RTC_TongueNet based on DeepLabV3, which combines the improved residual structure and transformer and integrates the ECA (Efficient Channel Attention Module) attention mechanism of multiscale atrous convolution to improve the effect of tongue image segmentation. Methods In this paper, we improve the backbone network based on DeepLabV3 by incorporating the transformer structure and an improved residual structure. The residual module is divided into two structures and uses different residual structures under different conditions to speed up the frequency of shallow information mapping to deep network, which can more effectively extract the underlying features of tongue image; introduces ECA attention mechanism after concat operation in ASPP (Atrous Spatial Pyramid Pooling) structure to strengthen information interaction and fusion, effectively extract local and global features, and enable the model to focus more on difficult-to-separate areas such as tongue edge, to obtain better segmentation effect. Results The RTC_TongueNet network model was compared with FCN (Fully Convolutional Networks), UNet, LRASPP (Lite Reduced ASPP), and DeepLabV3 models on two datasets. On the two datasets, the MIOU (Mean Intersection over Union) and MPA (Mean Pixel Accuracy) values of the classic model DeepLabV3 were higher than those of FCN, UNet, and LRASPP models, and the performance was better. Compared with the DeepLabV3 model, the RTC_TongueNet network model increased MIOU value by 0.9% and MPA value by 0.3% on the first dataset; MIOU increased by 1.0% and MPA increased by 1.1% on the second dataset. RTC_TongueNet model performed best on both datasets. Conclusion In this study, based on DeepLabV3, we apply the improved residual structure and transformer as a backbone to fully extract image features locally and globally. The ECA attention module is combined to enhance channel attention, strengthen useful information, and weaken the interference of useless information. RTC_TongueNet model can effectively segment tongue images. This study has practical application value and reference value for tongue image segmentation.

In the field of geosciences, the integration of artificial intelligence is transitioning from perceptual intelligence to cognitive intelligence. The simultaneous utilization of knowledge and data in the geoscience domain is a universally addressed concern. In this paper, based on the interpretability of deep learning models for rock images, rock features such as structure, texture, mineral and macroscopic identification characteristics were selected to extract a rock identification subgraph from the petrographic knowledge graph and carry out rock type similarity reasoning. Comparative experiments were conducted on few-shot learning of rock images under the supervision of rock type similarity knowledge. The results of the few-shot learning comparisons demonstrate that the supervision of rock type similarity knowledge significantly enhances performance. Additionally, rock type similarity knowledge exhibits a marginal effect on improving few-shot learning performance. Given the absence of Chinese word embedding and large-scale Chinese pre-trained language models in the geological domain, graph embedding based on domain-specific knowledge graphs in geosciences can offer computable geoscience knowledge for research dually propelled by data and knowledge.

Ocean internal waves (IWs) are widespread submesoscale dynamical phenomena in oceans, and they have important impacts on energy transfer, nutrient transport, and human activities. In this study, Sentinel-1 synthetic aperture radar (SAR) images from 2014 to 2023 were collected to construct a global IW dataset (S1-IW-2023) through a series of optimized data processing. S1-IW-2023 was constructed to address the issue of insufficient data and lack of variation in the deep learning IW datasets; it can be used in IW studies using deep learning methods to enhance model generalizability and robustness. Moreover, considering the limitations of existing convolutional neural network (CNN)-based IW detection models in handling complex interferences in SAR images, resulting in frequent false positives, false negatives, or inaccurate bounding box positioning, we employed transfer learning to train a Transformer-based hierarchical IW detector, IWD-Net, that extracts features via Swin Transformer and fuses the visual, semantic, and contextual features of IWs via a multiscale feature fusion network. Experimental results demonstrated the effectiveness of applying Transformer concepts to IW detection for addressing complex interferences. This study provides an efficient and stable new method for extracting IW features from massive SAR data and lays the foundation for applying Transformer concepts to detect IWs in SAR images.

China has entered a period of synchronous development between digitalization and aging. Based on the data from the China Household Finance Survey (CHFS), the partial least squares structural equation model (PLS-SEM) and multi-group analysis were used to analyze the impact mechanism of digital capabilities and digital finance on the wealth of elderly households. The results indicate that digital capabilities and digital finance can improve the wealth level of households headed by the elderly through direct and indirect paths. The indirect effects of digital capabilities and digital finance on elderly household wealth are all exerted through the node of business and property income, and entrepreneurship/investment are mediating variables. Moreover, digital capabilities have a greater impact on the wealth of elderly households in the central and western China regions, while digital finance has a greater impact in the eastern China regions. In addition, there is no significant difference in the effect of digital capabilities on business and property income across regions, while digital finance has a larger effect in the eastern region. The above conclusions can provide theoretical and practical support for realizing active aging and common prosperity in different countries and regions.

Purpose: Platelets could promote tumor growth and metastasis. However, the role of platelets in different subtypes of non-small cell lung cancer (NSCLC) and platelet infiltration in local tumor tissue remain unclear. Methods: Initially, platelet infiltration in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC) was estimated by CD41 expression using immunohistochemistry. Subsequently, co-incubation of NSCLC cell lines and platelets was performed to compare the ability of binding platelets. Subcutaneous tumor models were established to assess the ability of platelets to promote tumor growth. Then, RNA-seq data of NSCLC was used to identify differentially expressed genes and enriched pathways. Lastly, a clinical cohort comprising of ADC and SCC patients as well as meta-analysis was analyzed to compare the difference of coagulation associated clinical parameters. Results: We found high platelet infiltration in ADC, especially of advanced disease and metastases, whereas few platelets were observed in SCC. Moreover, ADC cell lines exhibited strong ability of binding platelets compared with SCC cell lines. Platelets could also promote the growth of ADC cell lines in vivo. Furthermore, coagulation cascades and fibrinogen were upregulated in ADC. And chemical inhibition of GPIIb/IIIa-fibrinogen axis reduced the binding of ADC cells and platelets. ADC patients were also in a hypercoagulable state characterized by higher d-dimer level and shorter clotting time. Finally, meta-analysis identified a higher risk of venous thromboembolism (VTE) in ADC patients and low molecular weight heparin (LMWH) treatment was effective at reducing this risk. Conclusions: This study identified the differences of platelet infiltration and coagulation between ADC and SCC patients, which may inform the development of anticoagulation therapies for NSCLC.

Objective To analyze the current situation of direct exemption of clinical blood fess for voluntary blood donors and their family members in Henan Province, in order to improve and fully implement the policy. Methods According to the policy on blood fees exemption issued by China and Henan Province in 2019,the data of hospitals in 18 prefecture-level cities in Henan from 2020 to 2021 were continuously collected from the system of clinical blood fees exemption,including the way of exemption,the number of people (times) of exemption,exemption amount, the proportion of blood fees exemption and the total exemption rate. The experience gained in the past two years after the implementation of the policy was summarized,and the existing problems and causes were analyzed. Results The rates of direct exemption of blood fees in Henan Province in 2020 and 2021 were 34.53% (8 709/25 221) and 71.68%(23 587/32 906) (P

Abstract Background Human immunodeficiency virus type one (HIV-1) is the leading cause of acquired immunodeficiency syndrome (AIDS). AIDS remains a global public health concern but can be effectively suppressed by life-long administration of combination antiretroviral therapy. Early detection and diagnosis are two key strategies for the prevention and control of HIV/AIDS. Rapid and accurate point-of-care testing (POCT) provides critical tools for managing HIV-1 epidemic in high-risk areas and populations. Methods In this study, a POCT for HIV-1 RNA was developed by CRISPR-Cas13a lateral flow strip combined with reverse transcriptase recombinase-aided amplification (RT-RAA) technology, the results can be directly observed by naked eyes. Results Moreover, with the degenerate base-binding CRISPR-Cas13a system was introduced into the RT-RAA primer designing, the technology developed in this study can be used to test majority of HIV-1 RNA with limit of detection (LOD) 1 copy/μL, while no obvious cross-reaction with other pathogens. We evaluated this method for detecting HIV-1 RNA of clinical samples, the results showed that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 91.81% (85.03- 96.19%), 100% (92.60–100%), 100% (96.41–100%), 39.14% (25.59–54.60%) and 92.22% (86.89–95.88%), respectively. The lowest viral load detectable by this method was 112copies/mL. Conclusion Above all, this method provides a point-of-care detection of HIV-1 RNA, which is stable, simple and with good sensitivity and specificity. This method has potential to be developed for promoting early diagnosis and treatment effect monitoring of HIV patients in clinical.

Abstract Background Currently, there is a lack of research investigating the feasibility of employing anterograde lag screw fixation through the iliac crest for minimally invasive percutaneous treatment of the posterior acetabular column, which encompasses retrograde and anterograde screw fixation in posterior acetabular lag screw fixation. And consequently, the purpose of this study was to examine the anatomical parameters of anterograde lag screw fixation of the posterior column of the pelvis through the iliac crest as well as to investigate the intraoperative fluoroscopy technique, to furnish a scientific rationale supporting the practical utilization of this method within clinical settings. Methods In this study, pelvic CT data of 60 healthy adults, including 30 males and 30 females, were accumulated. The mimics 21.0 software was developed to reconstruct the three-dimensional pelvis model, simulate the anterograde lag screw fixation of the posterior column of the acetabulum through use of the iliac crest, and precisely identify the insertion point: Utilizing the widest iliac tubercle as the starting point, the insertion point was moved toward the anterior superior iliac spine by 1.0 cm at a time until it reached 4.0 cm. With a total of five insertion points, all oriented toward the lesser sciatic notch, the initial diameter of the virtual screw measured 5.0 mm, and it was progressively enlarged by 1.0 mm increments until reaching a final diameter of 8.0 mm. Besides, the longest lengths of virtual screws with distinct diameters at divergent entry points were measured and compared. At the same time, the intraoperative fluoroscopy technique for optimal access was analyzed. Results The cross-section from the iliac crest to the lesser sciatic notch was irregular, with multiple curved shapes. Furthermore, the diameter of the screw was determined by the anteroposterior radians and width of the iliac crest plate, while the screw length was determined by the curvature of the square body. On the condition that the screw diameter of the D channel (3.0 cm outward from the widest part of the iliac tubercle to the lesser sciatic notch) was 5 mm, 6 mm as well as 7 mm, the longest screw lengths were (145.6 ± 12.8) mm, (143.6 ± 14.4) mm and (139.9 ± 16.6) mm, correspondingly, indicating statistically substantial distinctions from other channels (P

Abstract Background The coronavirus disease 2019 outbreak has hit Beijing since mid-Nov, 2022, with soaring growth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. Therefore, it is vital to determine the clinical manifestations of epidemic SARS-CoV-2 strains in paediatric patients. Methods In this study, nucleic acid tests (NATs) for SARS-CoV-2 were performed in paediatric outpatients with symptoms of acute respiratory tract infection during 18 Nov–6 Dec, 2022. Half of the outpatients positive for SARS-CoV-2 were randomly selected to screen for other respiratory pathogens, whereas those with low cycle threshold values in SARS-CoV-2 NATs were amplified and sequenced to determine the SARS-CoV-2 variants. Finally, children positive for SARS-CoV-2 with clinical information in detail were enrolled in a follow-up study to identify potential factors significantly associated with long recovery. Results Among 9625 paediatric outpatients tested for nucleic acid of SARS-CoV-2, 733 (7.62%, 733/9625) were identified as SARS-CoV-2 NAT positive, with only three (0.82%, 3/366) co-infected with other pathogens among 366 randomly selected patients, and 71 (62.83%) determined as Omicron subvariant BF.7 and 42 (37.22%) as BA.5.2 among 113 successfully sequenced. Among the 681 patients with complete clinical information, fever was the most common symptom (96.8%). In a follow-up study of 592 patients, 46.96% became asymptomatic on the third day and 65.71% on the fifth day. Only 1.7% of infected children experienced febrile seizures. Combined with abnormal C-reactive protein, a higher percentage of antibiotics administration was observed. More co-living members and longer duration of first symptoms served as independent risk factors for long-term recovery, especially in children vaccinated for SARS-CoV-2. Conclusions BF.7 and BA.5.2 were the dominate Omicron subvariants and caused milder infections during the SARS-CoV-2 outbreak in Beijing. The number of co-living members and duration of first symptoms were independent risk factors for long-term recovery.

The uptake of ammonium, nitrate, phosphorus, and potassium ions by roots is mediated by specific ion transporter or channel proteins, and protein phosphorylation regulation events occurring on these proteins and their regulators determine their ultimate activity. Elucidating the mechanism by which protein phosphorylation modification regulates nutrient uptake will advance plant breeding for high nutrient-use efficiency. In this review, it is concluded that the root nutrient absorption system is composed of several, but not all, members of a specific ion transporter or channel family. Under nutrient-starvation conditions, protein phosphorylation-based regulation of these proteins and associated transcription factors increases ion transporter- or channel-mediated nutrient uptake capacity via direct function activity enhancement, allowing more protein trafficking to the plasma membrane, by strengthening the interaction of transporters and channels with partner proteins, by increasing their protein stability, and by transcriptional activation. Under excessive nutrient conditions, protein phosphorylation-based regulation suppresses nutrient uptake by reversing these processes. Strengthening phosphorylation regulation items that increase nutrient absorption and weakening phosphorylation modification items that are not conducive to nutrient absorption show potential as strategies for increasing nutrient use efficiency.

Abstract Background Despite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of “ultra high-risk NB” is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years. Methods One hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC). Results Through univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633—0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p

Selenium (Se) is an essential trace element for humans. Low concentrations of Se can promote plant growth and development. Enhancing grain yield and crop Se content is significant, as major food crops generally have low Se content. Studies have shown that Se biofortification can significantly increase Se content in plant tissues. In this study, the genetic transformation of wheat was conducted to evaluate the agronomic traits of non-transgenic control and transgenic wheat before and after Se application. Se content, speciation, and transfer coefficients in wheat grains were detected. Molecular docking simulations and transcriptome data were utilized to explore the effects of selenium-binding protein-A TaSBP-A on wheat growth and grain Se accumulation and transport. The results showed that TaSBP-A gene overexpression significantly increased plant height (by 18.50%), number of spikelets (by 11.74%), and number of grains in a spike (by 35.66%) in wheat. Under normal growth conditions, Se content in transgenic wheat grains did not change significantly, but after applying sodium selenite, Se content in transgenic wheat grains significantly increased. Analysis of Se speciation revealed that organic forms of selenomethionine (SeMet) and selenocysteine (SeCys) predominated in both W48 and transgenic wheat grains. Moreover, TaSBP-A significantly increased the transfer coefficients of Se from solution to roots and from flag leaves to grains. Additionally, it was found that with the increase in TaSBP-A gene overexpression levels in transgenic wheat, the transfer coefficient of Se from flag leaves to grains also increased.

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months.

Bone morphogenetic protein 6 (BMP-6) is a constituent of the TGF-β superfamily, known for its ability to stimulate bone and cartilage formation. The investigation of bmp6’s involvement in the formation of intermuscular bones in fish has garnered significant attention in recent years. The rib cage is an important skeletal structure that plays a protective function for internal organs in fish. However, there has been limited research conducted on the effects of the bmp6 gene on rib development. Silver carp is one of four major fish in China, favoured for its affordability and tender muscle. Nevertheless, the presence of numerous intermuscular bones in silver carp significantly hinders the advancement of its palatability and suitability for processing. This study showcases the effective utilisation of CRISPR/Cas9 technology for the purpose of disrupting the bmp6 gene in silver carp, leading to the creation of chimeras in the P0 generation, marking the first instance of such an achievement. The chimeras exhibited complete viability, normal appearance, and partial intermuscular bones loss, with approximately 30% of them displaying rib bifurcation or bending. Subsequently, a transcriptome analysis on ribs of P0 chimeras and wild-type silver carp was conducted, leading to the identification of 934 genes exhibiting differential expression, of which 483 were found to be up-regulated and 451 were found to be down-regulated. The results of the KEGG analysis revealed that the “NF-kappa B signalling pathway”, “Hippo signalling pathway”, “osteoclast differentiation”, and “haematopoietic cell lineage” exhibited enrichment and displayed a significant correlation with bone development. The up-regulated genes such as tnfα, fos, and ctgf in pathways may facilitate the proliferation and differentiation of osteoclasts, whereas the down-regulation of genes such as tgfb2 and tgfbr1 in pathways may hinder the formation and specialisation of osteoblasts, ultimately resulting in rib abnormalities. This study presents novel findings on the impact of bmp6 gene deletion on the rib development of silver carp, while simultaneously investigating the previously unexplored molecular mechanisms underlying rib defects in fish.

We conducted a systematic investigation into the spectral and pulse characteristics of C and L-band Nonlinear Polarization Rotation (NPR) mode-locked fiber lasers effectively employing nonlinear polarization rotation technology. In our experimental setup, we achieved a stable mode-locked state at 1560.076 nm, exhibiting a 3 dB spectral bandwidth of 9.1 nm. As the pump power increased, we observed spectral shifts accompanied by shifts in the first Kelly sideband and the generation of new Kelly sidebands. In this paper, the phenomenon of spectral deviation is elucidated through the interplay of self-phase modulation, group velocity drift, and polarization-dependent isolator (PD-ISO) filter effect, with an analysis of the formation and deviation of Kelly sidebands. Notably, spectral shift persisted even when the pump power exceeded 200 mW. However, continuous pump power escalation led to soliton splitting, resulting in the formation of new soliton beams. Based on the simultaneous generation of spectral shift and pulse splitting, our study contributes to an enhanced understanding of soliton dynamics in ultrafast fiber lasers and lays a foundation for the application of high-repetition-frequency harmonic mode-locked lasers with tunable wavelengths.

Owing to the substantial benefits in environmental protection and resource saving, recycled aggregate concrete (RAC) is increasingly used in civil engineering; among the different types, RAC-filled steel tubes are an efficient structural form utilizing the advantages of concrete and steel tubes. This paper proposed a novel full-bolted beam-to-concrete-filled steel tube (CFST) joint and investigated the anchoring behavior of the steel plates embedded in RAC-filled steel tubes, which represents the behavior of the tensile zone in this joint, to demonstrate the feasibility of utilizing RAC in composite structures. The specimen consisted of a CFST and a connecting plate embedded in the CFST. In total, 18 specimens were tested to study the effects of concrete type (i.e., recycled aggregate concrete and natural aggregate concrete), anchoring type (i.e., plate with holes, notches, and rebars), and plate thickness on the pullout behavior, such as anchorage strength, load–displacement response, and ductility. Based on experimental results, the aggregate type of the concrete does not affect the pullout behavior obviously but the influence of anchoring type is significant. Among the three anchoring methods, the plate with rebars exhibits the best performance in terms of anchorage strength and ductility, and is recommended for the beam-to-CFST joint. In addition, plate thickness obviously affects the behavior of plates with holes and notches, the bearing area of which is proportional to the thickness, whereas the pullout behavior of the plates with rebars is independent of thickness. Finally, design formulas are proposed to estimate the anchorage strength of the connecting plates, and their reasonability is validated using the experimental results.

A series of Zn-modified HBeta (Zn/HBeta) catalysts were prepared via the wetness impregnation method with different zinc precursors such as ZnSO4·7H2O, ZnCl2, C4H6O4Zn·2H2O and Zn(NO3)2·6H2O, and their catalytic performance in the conversion of ethanol to propylene reaction was evaluated. Results indicate that the amount and strength distribution of the acid sites of the Zn/HBeta catalysts were easily tuned by employing different types of zinc precursors. More importantly, when the zinc species were introduced to the HBeta, the propylene yield was significantly enhanced, whereas the yields of ethylene and C2–C4 alkanes were remarkably suppressed. For the catalyst prepared by using the ZnCl2 precursor, a higher propylene yield of up to 43.4% for Zn/HBeta-C was achieved as a result of the moderate amount and strength distribution of acid sites. The average coking rate of the used Zn/HBeta catalysts strongly depended on the amount of total acid sites, especially the strong acid sites, i.e., the higher the amount of total acid sites of the catalyst, the greater the average coking rate. For the catalyst prepared by using the ZnSO4·7H2O precursor, Zn/HBeta-S exhibited a better stability even after depositing more coke, which was due to the higher amount of strong acid sites.

To study the influence of grain arrangement on the surface profile of the workpiece, a mathematical model and its corresponding analytical algorithm of pyramidal abrasive belt grinding were established. The roughness value was simulated and predicted with Abaqus software. Grinding tests were carried out on the robot grinding system platform with pyramidal abrasive belt, and the surface profile were inspected and then compared with the simulation. The results show that the simulated roughness and the measured values have similar variation trend with good consistency, where the error is within 0.03 μm and the maximum error rate is 16.6%. The theoretical simulation and test results remain consistent, indicating that the model could be used to predict the surface roughness of workpiece ground with pyramidal abrasive belt.

Abstract Background Postoperative cognitive dysfunction (POCD) is a common postoperative disorder that is frequently observed after general anesthesia, which seriously threatens the quality of patients’ life. Existing studies have demonstrated that S-ketamine plays an important role in improving neuroinflammation. This trial aimed to explore the effects of S-ketamine on quality of recovery and cognitive function in patients following modified radical mastectomy (MRM). Methods Ninety patients aged 45 to 70 years with ASA grades of I or II, who underwent MRM, were selected. Patients were randomly assigned to the S-ketamine or control group. In the S-ketamine group, patients were induced with S-ketamine instead of sufentanil and maintained with S-ketamine and remifentanil. In the control group, patients were induced with sufentanil and maintained with remifentanil. The primary outcome was the Mini-Mental State Examination (MMSE) and Quality of Recovery-15 (QoR-15) score. Secondary outcomes including visual analog scale (VAS) score, cumulative propofol and opioids consumption, post anesthesia care unit (PACU) recovery time, occurrence of remedial analgesia, postoperative nausea and vomiting (PONV), other adverse events, as well as patient satisfaction. Results The global QoR-15 scores at postoperative day 1 (POD1) were significantly higher in the S-ketamine group than in the control group (124 [119.5–128.0] vs. 119 [114.0–123.5], P = 0.002), with a median difference of 5 points (95% confidence interval [CI] [-8 to -2]). Similarly, the global QoR-15 scores at postoperative day 2 (POD2) in the S-ketamine group were significantly higher than in the control group (140.0 [133.0–145.0] vs. 132.0 [126.5–141.5], P = 0.004). In addition, among the five subcomponents of the 15-item scale, S-ketamine group had a higher score in terms of physical comfort, pain, and emotional state both at POD1 and POD2. In terms of MMSE score, S-ketamine could promote the recovery of postoperative cognitive function at POD1, but not at POD2. Furthermore, the consumption of opioids, VAS score, and remedial analgesia in the S-ketamine group decreased significantly. Conclusions Collectively, our findings support that general anesthesia with S-ketamine as a potential strategy showed high safety and could not only improve the quality of recovery mainly through improving pain, physical comfort, and emotional state but also promote the recovery of cognitive function on POD1 in patients undergoing MRM. Trial registration The study was registered in the Chinese Clinical Trial Registry (registration No:ChiCTR2200057226, Date of registration: 04/03/2022).

Abstract Background We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it. Methods Male C57BL/6 ApoE−/− mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα. Results After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE−/− mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation. Conclusions Our results revealed that CKN prevented the formation of atherosclerosis in ApoE−/− mice by activating the LXRα pathway.

Introduction: Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC. Objectives: We performed whole-exome sequencing in multiple regions of matched primary and metastatic HGSOC specimens to reveal the genetic mechanisms of ovarian tumourigenesis and malignant progression. Methods: 63 samples (including ovarian carcinoma, omentum metastasis, and normal tissues) were used. We analyzed the genomic heterogeneity, traced the subclone dissemination and establishment history and compared the different genetic characters of cancer evolutionary models in HGSOC. Results: We found that HGSOC had substantial intra-tumour heterogeneity (median 54.2, range 0 ∼ 106.7), high inter-patient heterogeneity (P

In this paper, the active peptides were obtained from Acetes chinensis with protease, and then the immunoregulatory function and mechanism of them on the immunosuppressed mice were explored by establishing an immunosuppressive mouse model. Mice were randomly divided into six groups: Normal control group, model group, positive control group and low, medium and high dose groups, among which, the dose groups were given 0.25 g· kg−1 BW, 0.5 g·kg−1 BW, 1.0 g·kg−1 BW A. chinensis active peptide. The results showed that the body weight of the immunosuppressed mice in dosegroups was significantly increased (P

Abstract Aim To evaluate a new fixation band for tracheal catheter in intensive care unit. Design A cross‐sectional study. Methods A total of 90 patients admitted to the ICU between August 2018–February 2019 were enrolled in the study. Patients were randomly divided into experimental group and control group (N = 45/per each group). 3 M strong adhesive tape and a new tracheal catheter fixation band were applied to patients in two groups, respectively. The fixation effect, incidence of mucosal pressure injury and nursing cost were evaluated. Results Forty‐three patients from the experimental group and 42 patients from the control group participated in this study. Mild, moderate and severe catheter dislocation happened in 2, 0, 0 cases in the experimental group, and 6, 3 and 2 cases in the control group, respectively; the difference was statistically significant. The rates of mucosal pressure injury were 4.7% and 21.4%, which was significantly different, and the experiment group had a lower average daily nursing cost related to tracheal intubation. Conclusions The new tracheal catheter fixation band, which allows for accurate fixation, is simple to operate, may reduce the incidence of mucosal pressure injury, decrease the nursing cost and improve the patients' comfort in clinical practice.

BackgroundBenzo[a]pyrene (BaP) has neurotoxicity, which can induce the loss of hippocampal neurons in humans and animals and lead to spatial learning and memory dysfunction, but its mechanism is still unclear. ObjectiveTo observe the ferroptosis of mouse hippocampal neuron HT22 cells induced by 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), an active metabolite of BaP, and to explore its potential mechanism, so as to provide a basis for the study of BaP neurotoxicity mechanism. MethodMouse hippocampal neuron HT22 cells were selected and divided into four groups: solvent control group and low, medium, and high concentration BPDE exposure groups (0.25, 0.50, and 0.75 μmol·L−1). Cell survival was detected by CCK8 method. Cell morphology and ultrastructure were observed under light and electron microscopes. The levels of reactive oxygen species (ROS) and Fe2+ were detected by fluorescence probe method. Iron, 4-hydroxynonenoic acid (4-HNE), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels were detected with commercial kits. The expression levels of acyl-CoA synthase long chain family member 4 (ACSL4), cyclooxygenase 2 (COX2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were detected by Western blotting. After interventions with ferroptosis inhibitors 20 μmol·L−1 deferoxamine (DFO) and 10 μmol·L−1 ethyl 3-amino-4-cyclohexylaminobenzoate (Fer-1), the cell survival rate of each BPDE exposure group and the changes of the ferroptosis characteristic indicators and protein expression levels were observed. ResultsWith the increase of BPDE concentration, the survival rate of HT22 cells decreased gradually, and the survival rate of each BPDE group was significantly lower than that of the solvent control group (P

Abstract Backgroud To summarize the clinical characteristics and identify the risk factors for pediatric Takayasu arteritis (TAK) with coronary artery lesions (CALs). Methods Clinical data of pediatric TAK patients in our center were retrospectively assessed. Independent risk factors for CALs were identified using multivariate logistic regression analysis. Survival analysis was used to compare differences in survival rates between the groups. Results Among the 66 pediatric TAK cases, the incidence of accompanying CALs was 39.4%. In the CAL group, 19 (73.1%) cases started within 36 months. None of the patients had symptoms of angina or ischemia on electrocardiogram (ECG), the CALs were detected using coronary ultrasound. The CALs most commonly were the left main and right coronary arteries. The lesions were mostly small or middle coronary artery aneurysms; some children may have giant coronary aneurysmal dilations, thrombosis and heart failure. The age of onset and symptom onset to diagnosis in TAK patients with CAL were lower than those in TAK patients without CAL(P

Abstract Background Mitochondrial quality control (MQC) plays a critical role in the progression of tubulointerstitial injury in diabetic kidney disease (DKD). The mitochondrial unfolded protein response (UPRmt), which is an important MQC process, is activated to maintain mitochondrial protein homeostasis in response to mitochondrial stress. Activating transcription factor 5 (ATF5) is critical in the mammalian UPRmt via mitochondria-nuclear translocation. However, the role of ATF5 and UPRmt in tubular injury under DKD conditions is unknown. Methods ATF5 and UPRmt-related proteins including heat shock protein 60 (HSP60) and Lon peptidase 1 (LONP1), in DKD patients and db/db mice were examined by immunohistochemistry (IHC) and western blot analysis. Eight-week-old db/db mice were injected with ATF5-shRNA lentiviruses via the tail vein, and a negative lentivirus was used as a control. The mice were euthanized at 12 weeks, and dihydroethidium (DHE) and TdT-mediated dUTP nick end labeling (TUNEL) assays were performed to evaluate reactive oxygen species (ROS) production and apoptosis in kidney sections, respectively. In vitro, ATF5-siRNA, ATF5 overexpression plasmids or HSP60-siRNA were transfected into HK-2 cells to evaluate the effect of ATF5 and HSP60 on tubular injury under ambient hyperglycemic conditions. Mitochondrial superoxide (MitoSOX) staining was used to gauge mitochondrial oxidative stress levels, and the early stage of cell apoptosis was examined by Annexin V-FITC kits. Results Increased ATF5, HSP60 and LONP1 expression was observed in the kidney tissue of DKD patients and db/db mice and was tightly correlated with tubular damage. The inhibition of HSP60 and LONP1, improvements in serum creatinine, tubulointerstitial fibrosis and apoptosis were observed in db/db mice treated with lentiviruses carrying ATF5 shRNA. In vitro, the expression of ATF5 was increased in HK-2 cells exposed to high glucose (HG) in a time-dependent manner, which was accompanied by the overexpression of HSP60, fibronectin (FN) and cleaved-caspase3 (C-CAS3). ATF5-siRNA transfection inhibited the expression of HSP60 and LONP1, which was accompanied by reduced oxidative stress and apoptosis in HK-2 cells exposed to sustained exogenous high glucose. ATF5 overexpression exacerbated these impairments. HSP60-siRNA transfection blocked the effect of ATF5 on HK-2 cells exposed to continuous HG treatment. Interestingly, ATF5 inhibition exacerbated mitochondrial ROS levels and apoptosis in HK-2 cells in the early period of HG intervention (6 h). Conclusions ATF5 could exert a protective effect in a very early stage but promoted tubulointerstitial injury by regulating HSP60 and the UPRmt pathway under DKD conditions, providing a potential target for the prevention of DKD progression.

Spinal anesthesia by intrathecal administration of local anesthetic (LA) is a routine practice. Local anesthetic system toxicity, occurring in the central nervous system (CNS) and cardiovascular system, is a common and life-threatening adverse event of LA through a variety of routes, but is rarely encountered in spinal anesthesia when a very low dose of LA is injected into the subarachnoid space. Here, we report a case with manifestations of delayed lethal CNS toxicity after spinal anesthesia. A 55-year-old man underwent elective repair surgery for a chronic ulcer after receiving 10 mg intrathecal administration of bupivacaine. He developed nausea, agitation, paresthesia and myoclonus on the arms, legs, and trunk, as well as a gradually reduced level of consciousness one hour after intrathecal administration. He was sedated, intubated, and transferred to the intensive care unit. Both CT and MRI scans of the brain and assessments of blood showed no abnormalities. The electroencephalogram showed spike waves occurring at electrodes C3, C4, P3, P4, and T5. The patient was sedated continuously and treated with valproate. These symptoms were completely resolved in the following days without residual neurological complications. No cardiovascular complications were observed during the entire process. The delayed lethal symptoms in this case were most likely to be CNS toxicity induced by intrathecal bupivacaine administration. CNS toxicity after spinal anesthesia may be underestimated and unpredictable and should be vigilantly cared for in clinical settings.

Background A high fibrinogen‐to‐albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. Methods and Results A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all‐cause death, poor functional outcome (modified Rankin Scale score 3–6), and dependence (modified Rankin Scale score 3–5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064–0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32–5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57–6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49–8.19]). Conclusions A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.

Objective: Fetal growth restriction (FGR) is a severe pathological complication associated with compromised fetal development. The early diagnosis and prediction for FGR are still unclear. Sequencing technologies present a huge opportunity to identify novel biomarkers. However, limitation of individual studies (e.g., long lists of dysregulated genes, small sample size and conflicting results) hinders the selection of the best-matched ones. Study design: A multi-step bioinformatics analysis was performed. We separately reanalyzed data from four public RNA-seq studies, followed by a combined analysis of individual results. The differentially expressed genes (DEGs) were identified based on DESeq2. Then, function enrichment analyses and protein-protein interaction network (PPI) were conducted to screen for hub genes. The results were further verified by using external microarray data. Results: A total of 65 dysregulated genes (50 down and 15 upregulated) were identified in FGR compared to controls. Function enrichment and PPI analysis revealed ten hub genes closely related to FGR. Validation analysis found four downregulated candidate biomarkers (CEACAM6, SCUBE2, DEFA4, and MPO) for FGR. Conclusions: The use of omics tools to explore mechanism of pregnancies disorders contributes to improvements in obstetric clinical practice.

BackgroundThe impact of weight loss and/or improved metabolic status on the risk of non-alcoholic fatty liver disease (NAFLD) has yet to be determined.MethodsA total of 35,322 participants without NAFLD were followed. NAFLD risk was compared between consistently metabolically healthy non-obese (MHNO) and non-MHNO who lost weight to become non-obese and/or improved their metabolic health, using Cox proportional hazards and logistic regression models.ResultsFollowing 148,186 person-years, 8,409 participants had onset NAFLD, with an incidence rate of 56.75 (95% CI: 55.57, 57.94) per 1,000 person-years. Metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), and metabolically unhealthy non-obese (MUNO) at baseline were associated with increased NAFLD risk, with hazard ratios of 4.48 (95%CI:4.24, 4.73), 8.85 (95%CI:7.95, 9.84), and 10.70 (95%CI:9.73, 11.78). Weight loss and/or metabolic status improvements could significantly reduce NAFLD risk by 79.46 to 41.46%. Specifically, after weight loss from MHO to MHNO, the reduction in NAFLD risk [OR decreased from 12.01 (95%CI:9.40, 15.35) to 4.14 (95%CI:3.08, 5.57)] was greater than that of the MUNO subgroup whose metabolic status improved to MHNO [OR decreased from 5.53 (95%CI:5.15, 5.94) to 2.71 (95%CI:2.50, 3.93)]. In the MUO subgroup, the group with the greatest risk reduction of NAFLD was the weight and metabolic state both improvement group [MUO to MHNO, OR decreased from 22.74 (95%CI:17.61, 29.37) to 4.67 (95%CI:3.05, 7.16)], followed by the weight loss only group [MUO to MUNO, OR decreased to 6.83 (95%CI:4.87, 9.57)], and finally the group with the least and insignificant risk reduction was the metabolic state improvement group [MUO to MHO, OR decreased to 13.38 (95%CI:9.17,19.53)]. NAFLD risk was negatively correlated with the duration of improvement (p

Peripheral inflammation-induced chronic pain tends to evoke concomitant anxiety disorders. It's common knowledge that the anterior cingulate cortex (ACC) plays a vital role in maintaining pain modulation and negative emotions. However, the potential mechanisms of chronic inflammation pain and pain-related anxiety remain elusive. Here, it was reported that injecting complete Freund’s adjuvant (CFA) unilaterally resulted in bilateral mechanical allodynia and anxiety-like symptoms in mice via behavioral tests. In addition, CFA induced the bilateral upregulation and activation of calcium homeostasis modulator 2 (Calhm2) in ACC pyramidal neurons by quantitative analysis and double immunofluorescence staining. The knockdown of Calhm2 in the bilateral ACC by a lentiviral vector harboring ribonucleic acid (RNA) interference sequence reversed CFA-induced pain behaviors and neuronal sensitization. Furthermore, the modulating of ACC pyramidal neuronal activities via a designer receptor exclusively activated by designer drugs (DREADD)-hM4D(Gi) greatly changed Calhm2 expression, mechanical paw withdrawal thresholds (PWTs) and comorbid anxiety symptoms. Moreover, it was found that Calhm2 regulates inflammation pain promoting the upregulation of N-methyl-D-aspartic acid (NMDA) receptor 2B (NR2B) subunits. Calhm2 knockdown in ACC exhibited a significant decrease in NR2B expression. These results demonstrated that Calhm2 in ACC pyramidal neurons modulates chronic inflammation pain and pain-related anxiety symptoms, which provides a novel underlying mechanism for the development of inflammation pain.

Hidden ingredients in plant protection products (PPPs) threaten public health, food trade, and the environment. In this study, we developed a high-throughput screening method of 639 hidden ingredients in PPPs using GC-MS/MS in multiple reaction monitoring mode. Results showed that the qualitative criteria of retention time (tR) shift and uncertainty of qualifier to quantifier ratio in the commercially available Shimadzu Smart Pesticides Database were set at

ABSTRACT Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the signaling pathway triggered by zinc excess and its relationship with iron homeostasis remain poorly understood in mycobacteria. Here, we characterize a novel Zur-IdeR-iron homeostasis signaling pathway that modulates the growth of Mycobacterium bovis under zinc toxicity. We found that the regulator Zur interacts with the iron-homeostasis regulator IdeR, enhancing the DNA-binding ability of IdeR. Excess zinc disrupts this interaction and represses ideR transcription through Zur, which promotes the expression of iron uptake genes and leads to the accumulation of intracellular iron in M. bovis. The elevated iron levels lower the bacterial survival ability under excess zinc stress. Consistently, deleting zur hinders intracellular iron accumulation of M. bovis and enhances bacterial growth under stress, while silencing ideR impairs the growth of the wild-type and zur-deleted strains under the same conditions. Interestingly, both Zur and IdeR are conserved in bacteria facing zinc toxicity. Overall, our work uncovers a novel antimicrobial signal pathway whereby zinc excess disrupts iron homeostasis, which may deepen our understanding of the crosstalk mechanism between iron and zinc homeostasis in bacteria. IMPORTANCE As a catalytic and structural cofactor of proteins, zinc is essential for almost all living organisms. However, zinc excess is toxic and represents a vital innate immunity strategy of macrophages to combat intracellular pathogens, especially against mycobacterial pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Here, we first characterize an antibacterial signaling pathway of zinc excess and its relationship with iron homeostasis in M. bovis. We found that excess zinc inhibits the transcription of ideR and its DNA-binding activity through Zur, which, in turn, promotes the expression of iron uptake genes, causes intracellular iron accumulation, and finally impairs the bacterial growth. This study reveals the existence of the Zur-IdeR-iron homeostasis pathway triggered by zinc excess in M. bovis, which will shed light on the crosstalk mechanisms between zinc and iron homeostasis in bacteria and the antimicrobial mechanisms of host-mediated zinc toxicity.

IntroductionIschemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology.MethodsIn our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC.ResultsBoth groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates’ temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%).DiscussionOur results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.

Abstract Background IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN. Methods Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies. Results A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN. Conclusions This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN.

Abstract Background Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome. Methods First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting. Results Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice. Conclusions Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.

Abstract Astringency is a major sensory property and plays an important role in the overall quality of juice and wines. A major contributor to astringency is condensed tannins, which can precipitate with salivary glycoproteins. And thus, it is vital to develop methods to measure the tannin accurately. Recently, the interest in the application of condensed tannin assays has been increasing in various fields. Condensed tannin assays broadly include the determination of concentration, activity, mean degree of polymerization and its derivative flavan‐3‐ol sulfonates content. In this guideline, the mechanisms and the practice of the most common condensed tannin assays applied in research labs are discussed in detail.

Abstract Background Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. Methods This study assessed the preoperative frailty according to the Fried’s frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. Results In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. Conclusion Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. Trial registration The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.

The purpose of this study is to analyze the spatiotemporal variations in wind field measurements obtained from the Chinese FengYun-3E (FY-3E) Wind Radar (WindRAD) scatterometer. To assess the performance of the wind field retrievals, we compare the FY-3E WindRAD measurements to ERA5 winds, which is the fifth-generation reanalysis global atmosphere dataset from the European Centre for Medium-Range Weather Forecasts (ECMWF). The comparative analysis between FY-3E and ERA5 for the period from June 1, 2022, to December 31, 2022, reveals that FY-3E wind speed retrievals have a bias of −0.42 m/s and a standard deviation (STD) of 1.45 m/s. In comparison to the TAO/TRITON array observations, the wind speed retrievals show a bias of −0.70 m/s and a STD of 1.37 m/s. Further improvements in wind direction retrieval precision are necessary for the FY-3E WindRAD scatterometer to meet operational requirements, aiming for an error within 20°. Temporal variations in the bias and STD of FY-3E wind speed retrievals exhibit two states, primarily attributed to the improved precision in wind field accuracy resulting from the implementation of the ocean calibration bias correction and advanced inversion algorithms. The spatial distribution analysis reveals regions characterized by relatively high bias and STD values, which could be associated with the presence of sea ice contamination near the ice shelves in these areas. These findings have the potential to offer valuable insights for improving Earth’s climate monitoring capabilities and enhancing the applications of oceanographic satellite observation systems.

To reduce environmental pollution and improve the efficiency of cascaded energy utilization, regional integrated energy system (RIES) has received extensive attention. An accurate multi-energy load prediction is significant for RIES as it enables stakeholders to make effective decisions for carbon peaking and carbon neutrality goals. To this end, this paper proposes a multivariate two-stage adaptive-stacking prediction (M2ASP) framework. First, a preprocessing module based on ensemble learning is proposed. The input data are preprocessed to provide a reliable database for M2ASP, and highly correlated input variables of multi-energy load prediction are determined. Then, the load prediction results of four predictors are adaptively combined in the first stage of M2ASP to enhance generalization ability. Predictor hyper-parameters and intermediate data sets of M2ASP are trained with a metaheuristic method named collaborative atomic chaotic search (CACS) to achieve the adaptive staking of M2ASP. Finally, a prediction correction of the peak load consumption period is conducted in the second stage of M2ASP. The case studies indicate that the proposed framework has higher prediction accuracy, generalization ability, and stability than other benchmark prediction models.

RGB-D saliency object detection (SOD) is an important pre-processing operation for various computer vision tasks and has received much attention in recent years. However, how to extract more effective features and how to effectively fuse RGB and depth modality features are still challenges that restrict the development of SOD. In this paper, we propose an effective network architecture called FFMA-Net: 1) We replace the backbone network of the baseline with a ResNet34 model to extract more effective features from the input data; 2) We design the HAM module to refine the features extracted by the ResNet34 model at different stages to ensure the effectiveness of features from each stage; 3) We propose the FFU module to perform multi-scale fusion of features from different stages, resulting in more semantic-rich features that are crucial for the decoding stage of the model. Finally, our model performs better than the latest methods on six RGB-D datasets on all evaluation metrics, especially in terms of F-measure metric, which shows significant improvement with approximately 5% on both SSD and LFSD datasets.

The influence of pre-aging treatment on the microstructure, texture and mechanical properties of the Mg–6Zn–1Gd–1Er (wt.%) alloy was investigated. The microstructure analysis shows that the presence of pre-aging is beneficial to {101¯2} twin nucleation at the early stage of extrusion and inhibits the growth of twins and promotes the formation of [101¯0]-fiber texture components, thus accelerating the complex process of recrystallization. In the middle stage of extrusion, the extruded samples under the condition of solid solution were subjected to dynamic precipitation during severe shear deformation. The precipitation of the second phase particles followed the particle stimulating nucleation (PSN) mechanism, which increased the volume fraction of DRX grains during extrusion. In the extruded samples under the peak-aged condition, the particles appear dissolved during the severe shear deformation strain, which slows down the DRX process. In the later stage of extrusion, the small rod-shaped particles followed the PSN mechanism, and finally formed the strong fiber texture. The extruded alloy exhibits the strongest mechanical properties under the peak-aged state, with ultimate tensile strength (UTS) of 346 MPa, tensile yield strength (TYS) of 217 MPa, and elongation to failure (EL) of 13.6%. The improvement of mechanical properties is mainly attributed to the existence of strong fiber texture, small rod-shaped and block-shaped phases.

Abstract Radiochemotherapy (RCT) is a powerful treatment for cervical cancer, which affects not only malignant cells but also the immune and stromal compartments of the tumor. Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer. In this study, we applied single-cell RNA-sequencing to paired pre- and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues. We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes. Moreover, RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+ NK cells with a higher cytotoxic gene expression signature. However, subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT. These results reveal the complex responses of the tumor ecosystem to RCT, providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.

Abstract Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC–MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.