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Abstract Background UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. Results We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8 groupA contributes to UV-B resistance in rice. Conclusions Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.

Abstract A wide variety of metabolic gene clusters exist in eukaryotic genomes, but fatty acid metabolic gene clusters have not been discovered. Here, combining with metabolic and phenotypic genome-wide association studies, we identify a major locus containing a six-gene fatty acid metabolic gene cluster on chromosome 3 (FGC3) that controls the cutin monomer hydroxymonoacylglycerols (HMGs) contents and rice yield, possibly through variation in the transcription of FGC3 members. We show that HMGs are sequentially synthesized in the endoplasmic reticulum by OsFAR2, OsKCS11, OsGPAT6, OsCYP704B2 and subsequently transported to the apoplast by OsABCG22 and OsLTPL82. Mutation of FGC3 members reduces HMGs, leading to defective male reproductive development and a significant decrease in yield. OsMADS6 and OsMADS17 directly regulate FGC3 and thus influence male reproduction and yield. FGC3 is conserved in Poaceae and likely formed prior to the divergence of Pharus latifolius. The eukaryotic fatty acid and plant primary metabolic gene cluster we identified show a significant impact on the origin and evolution of Poaceae and has potential for application in hybrid crop breeding.

Abstract Background Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. Case presentation A patient with primary aldosteronism (PA) associated with severe Cushing’s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. Conclusion Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

Abstract Pneumonia is a serious disease that can be fatal, particularly among children and the elderly. The accuracy of pneumonia diagnosis can be improved by combining artificial-intelligence technology with X-ray imaging. This study proposes X-ODFCANet, which addresses the issues of low accuracy and excessive parameters in existing deep-learning-based pneumonia-classification methods. This network incorporates a feature coordination attention module and an omni-dimensional dynamic convolution (ODConv) module, leveraging the residual module for feature extraction from X-ray images. The feature coordination attention module utilizes two one-dimensional feature encoding processes to aggregate feature information from different spatial directions. Additionally, the ODConv module extracts and fuses feature information in four dimensions: the spatial dimension of the convolution kernel, input and output channel quantities, and convolution kernel quantity. The experimental results demonstrate that the proposed method can effectively improve the accuracy of pneumonia classification, which is 3.77% higher than that of ResNet18. The model parameters are 4.45M, which was reduced by approximately 2.5 times. The code is available at https://github.com/limuni/X-ODFCANET .

ObjectiveTo investigate the situation and influencing factors of recall colposcopy attendance among women with positive cervical cancer screening results in Ordos city, in order to provide a reference for improving colposcopy recall compliance. MethodsFrom a cervical cancer screening program conducted at maternal and child health hospitals in different banners (districts) of Ordos city, Inner Mongolia Autonomous Region between January 2016 and December 2020, we extracted the data of 4 094 women (aged 35 – 64 years) who tested positive in the first detection. Data on the urbanization rate and gross domestic product (GDP) of the banners (districts) were also collected simultaneously. A multilevel logistic regression model was used to analyze the main factors influencing women′s attendance at for colposcopy recall. ResultsOf the 4 094 women who were recalled, 2 724 (67.0%) actually underwent the recall colposcopy. Of the 2 742 women who had a recall colposcopy, 2 681 (97.8%) had the recall examination at the original screening facilities and only 61 (2.2%) had the recall re-examination or colposcopy at other medical facilities. The multilevel logistic regression analysis showed that women aged 55 to 64 years, with an education of junior high school and above, with abnormal vaginal discharge, and with a history of cervical cancer screening were more likely to have the recall colposcopy; whereas, the women from banners with urbanization rate of more than 80% and GDP between 11 and 27 billion yuan RMB were less likely to have the recall colposcopy, in addition, those from regions with urbanization rate of 70% to 80% and GDP of 11 to 27 billion yuan and above were more likely to have the re-examination or colposcopy at medical facilities other than the original screening facilities. ConclusionAmong women with positive cervical cancer screening results in Ordos city, the recall colposcopy rate is low and is mainly influenced by individual factors such as age, education, abnormal vaginal discharge, and history of cervical cancer screening, as well as the urbanization rate and GDP of residential areas.

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear. Methods First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients. Results Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD. Conclusion In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications. Graphical Abstract

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.

Microplastics are widespread pollutants in aquatic environments, posing a significant threat to the health of marine ecosystems. However, little is known about the impact of plastics on deep-sea microbial communities. In this paper, we investigated the effects of polystyrene (PS) microplastics with three particle sizes (60 nm, 600 nm and 1 µm) and three concentrations (10, 50, 150 mg/L) as well as PS films (1 × 1 cm) on the deep-sea microbial community inoculated with water of 3370 m water depth from Pacific Ocean by using reactive oxygen species (ROS) detection, growth rate, scanning electron microscope (SEM) and high-throughput sequencing. Microplastics surface rotting (600 nm and 1 µm) and further fragmentation (60 nm) were observed caused by plastic-degrading microbial erosion after 50 days’ incubation. Similarly, deformation of PS film, including formation of obvious wrinkles and deep pits and the generation of microplastics and nanoplastics were also observed. Microplastics from commercial and plastic films could stimulate the bacterial community to secrete extracellular polymeric substance (EPS), favouring biofilm formation and resistance to external stress. Compared with larger microplastics, 60 nm microplastics and plastic films significantly inhibited the growth of bacterial communities with enhanced ROS production. The abundance of Moraxellaceae dominated in all enriched samples with the addition of microplastics, while the abundance of Alcanivoracaceae also increased in the 60 nm and plastic film enrichments, in contrast to dominant bacteria of Colwelliaceae, Marinobacteraceae, Rhodobacteraceae and Alcanivoracaceae the deep seawater in situ. Correspondingly, the functional changes of the communities were observed via functional prediction by 16S rRNA gene based on their alterations in bacterial community structure. The study provides insights into the effects of microplastics and nanoplastics on deep-sea microbial communities.

Abstract Background Cardiovascular disease continues to be a leading cause of mortality worldwide, highlighting the need to explore innovative approaches to improve cardiovascular health outcomes. Time-restricted fasting (TRF) is a dietary intervention that involves limiting the time window for food consumption. It has gained attention for its potential benefits on metabolic health and weight management. This study aims to investigate the impact of TRF on key risk factors, including body weight, glucose metabolism, blood pressure, and lipid profile. Methods We conducted a systematic search in five databases (Scopus, Embase, PubMed, Cochrane, and Web of Science) for relevant studies up to January 2023. After applying inclusion criteria, 12 studies were eligible for analysis. Quality assessment was conducted using the ROB-2.0 tool and ROBINS-I. Risk of bias was mapped using Revman 5.3, and data analysis included Hartung-Knapp adjustment using R 4.2.2. Results The group that underwent the TRF intervention exhibited a significant decrease in body weight (SMD: -0.22; 95%CI: -0.41, -0.04; P 0.05). Conclusion TRF has shown potential as a treatment strategy for reducing total body weight by targeting adipose tissue, with potential improvements in cardiometabolic function.

ABSTRACTTo assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18–45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

Monteggia fracture is a relatively uncommon injury in pediatric patients, accounting for less than 2% of forearm fractures, characterized by a combination of ulna fracture and radial head dislocation. Neglected Monteggia fractures define as those that have not received treatment within 3 weeks. In children, ulna fractures are easily diagnosed while radial head dislocation may be overlooked, necessitating open reduction after neglecting the Monteggia fracture and potentially causing additional trauma to the child. This study aims to review the pathological characteristics of neglected Monteggia fractures based on the length ratio of the ulna and radius, relative positions between the proximal ends of the ulna and radius, the integrality of annular ligament and the pathological change of proximal radioulnar joint. The findings will provide valuable insights and guidance for managing neglected Monteggia fractures.

BackgroundPrevious structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition.MethodsThirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE.ResultsCompared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment.ConclusionThis study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.

ABSTRACT Mixotrophy is an important trophic strategy for bacterial survival in the ocean. However, the global relevance and identity of the major mixotrophic taxa remain largely elusive. Here, we combined phylogenetic, metagenomic, and metatranscriptomic analyses to characterize ubiquitous Arcobacteraceae based on our deep-sea in situ incubations and the global data. The phylogenomic tree of Arcobacteraceae is divided into three large clades, among which members of clades A and B are almost all from terrestrial environments, while those of clade C are widely distributed in various marine habitats in addition to some terrestrial origins. All clades harbor genes putatively involved in chitin degradation, sulfide oxidation, hydrogen oxidation, thiosulfate oxidation, denitrification, dissimilatory nitrate reduction to ammonium, microaerophilic respiration, and metal (iron/manganese) reduction. Additionally, in clade C, more unique pathways were retrieved, including thiosulfate disproportionation, ethanol fermentation, methane oxidation, fatty acid oxidation, cobalamin synthesis, and dissimilatory reductions of sulfate, perchlorate, and arsenate. Within this clade, two mixotrophic Candidatus genera represented by UBA6211 and CAIJNA01 harbor genes putatively involved in the reverse tricarboxylic acid pathway for carbon fixation. Moreover, the metatranscriptomic data in deep-sea in situ incubations indicated that the latter genus is a mixotroph that conducts carbon fixation by coupling sulfur oxidation and denitrification and metabolizing organic matter. Furthermore, global metatranscriptomic data confirmed the ubiquitous distribution and global relevance of Arcobacteraceae in the expression of those corresponding genes across all oceanic regions and depths. Overall, these results highlight the contribution of previously unrecognized Arcobacteraceae to carbon, nitrogen, and sulfur cycling in global oceans.IMPORTANCEMarine microorganisms exert a profound influence on global carbon cycling and ecological relationships. Mixotrophy, characterized by the simultaneous utilization of both autotrophic and heterotrophic nutrition, has a significant impact on the global carbon cycling. This report characterizes a group of uncultivated bacteria Arcobacteraceae that thrived on the “hot time” of bulky particulate organic matter and exhibited mixotrophic strategy during the in situ organic mineralization. Compared with clades A and B, more unique metabolic pathways were retrieved in clade C, including the reverse tricarboxylic acid pathway for carbon fixation, thiosulfate disproportionation, methane oxidation, and fatty acid oxidation. Global metatranscriptomic data from the Tara Oceans expeditions confirmed the ubiquitous distribution and extensive transcriptional activity of Arcobacteraceae with the expression of genes putatively involved in carbon fixation, methane oxidation, multiple sulfur compound oxidation, and denitrification across all oceanic regions and depths.

ObjectivePatients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE.MethodsThirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients.ResultsAlthough small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p

The large water demand, insufficient deposition on the back of the leaf and the uneven distribution of droplets are the problems of traditional agricultural ground plant protection machinery, which leads to low agricultural control efficiency. Combined with the advantages of electrostatic spray technology and the characteristics of high working efficiency and low probability of droplets drift of ground sprayer, an inductive electrostatic boom spray system based on embedded electrode structure is designed and mounted on a large self-propelled boom sprayer for field testing. Based on the working characteristics of the fan nozzle and the analysis of the theory of charge, the inductive electrostatic spray device is designed. The performance of the device is tested and the rationality of the system design is verified by COMSOL numerical simulations, charge-to-mass ratio, and particle size distribution measurements. The spray deposition scanning software and the Box-Behnken experimental design method are used to analyze the spray droplet deposition rate and coverage density of the sprayer on the front and back of the target leaves. The results show that the embedded closed electrode structure designed in this paper can avoid the problem of electrode wetting, and the electric field generated by it is mainly concentrated in the spray liquid film area, and the intensity reaches 6~7 V/m. At the conventional application height (500 mm), the maximum charge-to-mass ratio is 2.91 mC/kg, and the average particle size is 168.22 μm, which is 12.87% lower than that of ordinary spray, when the spray pressure is 0.3 MPa and the electrostatic voltage is 12 kV. The results of field experiments show that the optimum combination of the working parameters with the spray speed is 8.40 m/s, the spray pressure is 0.35 MPa, the charging voltage is 11.50 kV, the amount of droplet deposition in the lower dorsal area of the blade is 1.44 µL·cm-2. This study can provide a certain basis for the application of electrostatic spray technology in ground sprayers.

Clinical Data Interchange Standards Consortium (CDISC) is a global non-profit standard development organization. Based on the consensus of clinical research, it has established a set of standard systems, including core standards, data interchange standards, controlled terminology standards, and treatment domain standards. These standards play different roles in research and span various stages of the research process. With the development of automated software, international regulatory agencies and large pharmaceutical companies have implemented the application of CDISC standards. The standard system is gradually gaining recognition and promotion in China, and professional technical services are also being gradually developed and popularized. This article provided a detailed introduction to various standards under the CDISC standard system, including their relationships, and application processes. It summarized the application status at home and abroad and provides suggestions, aiming to provide important references for the standardization of relevant research.

The dc systems consisting of power electronic converters always suffer from various stability problems, and the mixed potential theory (MPT) has been widely applied to study these problems in recent years because the stability criterion in analytical form can be derived easily. However, the models of the dc-dc converters in most studies are simplified, and thus only the control parameters at system level are considered. Some work has done to propose the MPT criterion based on complete converter models which involve the control parameters of the converters but such improved MPT criterion is optimistic for system stability. This paper proposes the MPT criterion of a boost converter with different loads based on complete converter models and expounds the mathematical features and the physical implication of the proposed MPT criterion. The proposed MPT criterion can be used for the design of system parameters but it is a necessary condition for system stability. The reasons for the optimism of the proposed criterion are revealed from the expounded mathematical features and physical implication. Finally, real-time simulations are conducted in RT-LAB to verify the correctness of the theoretical analyses.

Abstract Background The assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population. Methods The analysis included a total of 26,692 women aged 25–64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated. Results Among 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35–64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (Ptrend

We evaluated the operational, financial, and management challenges within China’s Toilet Revolution by surveying 656 rural households across 10 provinces. The results revealed that the majority of households which renovated their toilets under the Toilet Revolution perceived positive impacts of this on their quality of life and living conditions. Households that had undertaken toilet renovations viewed the program more favorably than households which had not undertaken renovation, and were more willing to engage with the program. Despite the perceived benefits, households were generally hesitant to personally invest in toilet renovation. We uncovered a gap in strategic sanitation planning for post-construction operation and maintenance of toilets, reflecting a “build first, manage later” approach in the Toilet Revolution. We also identified a widespread lack of formal models for management of toilets and toilet products, coupled with high reliance among households on government support and subsidies to fund renovation. To address operational inefficiencies and financial sustainability issues in the program, we propose a novel “Toilet Business” model that leverages a sanitation value chain approach. In this model, private sector engagement, cost management, and market revitalization are crucial components that must be implemented to ensure the program’s long-term success. Overall, our study provides valuable insights into the complexities of implementing large-scale sanitation programs such as the Toilet Revolution.

Abstract Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator‐activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone‐induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta‐alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post‐dose. Pioglitazone‐dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.

Root-knot nematodes (RKNs) pose a serious threat to crop production. Flooding soil with biogas slurry, combined with soil heating before crop planting, has the potential for RKN disease suppression. However, the actual effect of this method has not been verified under field conditions. Here, we present the results of a two-year field experiment in a greenhouse demonstrating the control effect on RKN disease and plant growth using this method, as well as its influence on the soil nematode community. Four treatments were set: untreated control (CK), local control method for RKN (CC), soil flooded with 70 % biogas slurry (BS70), and soil flooded with undiluted biogas slurry (BS100). In the first year, all three RKN control treatments significantly reduced the root-knot index (p 0.05), indicating that biogas slurry application did not increase the soil food web complex. Principal component analysis showed that the application of biogas slurry changed the nematode community, especially under BS70, which presented a more lasting influence. The high-level input of biogas slurry also caused soil NH4+-N and heavy-metal and arsenic accumulation in the first year, but these soil-pollution risks disappeared in the second year.

Abstract Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac/LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild‐type LacI. An in‐depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild‐type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high‐value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven‐fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto‐oligosaccharides (GOS).

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd.

Summary: Aging is considered a critical factor of poor prognosis in allogenic hemopoietic stem cell transplantation (allo-HSCT). To elucidate the underlying mechanisms, we comprehensively reintegrated our clinical data from patients after allo-HSCT and public single-cell transcriptomic profile from post-allo-HSCT and healthy individuals, demonstrating that old donors were more prone to acute GVHD (aGVHD) with pronounced inflammation accumulation and worse overall survival (OS). We also found the presence of inflammation-related CXCL2+ HSC subpopulation during aging with significantly enriched pro-inflammatory pathways. Shifting attention to the HSC microenvironment, we deciphered that IL-1/IL-6 and TRAIL (i.e., TNFSF10) ligand‒receptor pair serves as the crucial bridge between CD14/CD16 monocytes and hematopoietic stem/progenitor cells (HSPCs). The profound upregulation of these signaling pathways during aging finally causes HSC dysfunction and lineage-biased differentiation. Our findings provide the theoretical basis for achieving tailored GVHD management and enhancing allo-HSCT regimens efficacy for aged donors.

Abstract Background Cardiometabolic comorbidities have been associated with a higher risk of COVID‐19 severity and mortality, but more investigations are needed to determine which comorbidity is more detrimental. Methods Embase, Emcare, and MEDLINE were searched systematically for prospective and retrospective studies assessing the associations of cardiometabolic risk factors and COVID‐19 outcomes of hospitalization, severity, and mortality among COVID‐19‐diagnosed patients. Literature search was performed from first publication to May 19, 2021. Study quality was assessed by the Newcastle‐Ottawa Scale. Results From the literature search, 301 studies suggested that all included cardiometabolic risk factors were associated with a higher risk of COVID‐19 hospitalization, severity, and mortality, except that overweight was associated with a decreased risk of mortality (relative risk [RR] 0.88; 95% CI, 0.80–0.98). Patients with diabetes (RR 1.46; 95% CI, 1.45–1.47) were most likely to be hospitalized; patients with heart failure had the highest risk for severe COVID‐19 outcomes (RR 1.89; 95% CI, 1.71–2.09); while patients with stroke were most susceptible to overall mortality (RR 1.99; 95% CI, 1.90–2.08). In the network meta‐analysis, cerebrovascular disease had the highest impact (RR 1.69; 95% CI, 1.65–1.73) on COVID‐19 outcomes compared to other cardiometabolic risk factors. For different combinations of risk factors, cardiovascular disease and diabetes combined (RR 6.98; 95% CI, 5.28–9.22) was more detrimental than others. Conclusions Considering the high prevalence of cardiometabolic comorbidities and risk of all severe outcomes, patients with cardiometabolic comorbidities should be prioritized in vaccination and treatment development of COVID‐19.

Abstract Background Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR. Methods ARPE-19 cells were exposed to high glucose (HG) condition for developing a cellular model of DR. The CCK-8 assay and flow cytometry were used to assess ARPE-19 cell proliferation and apoptosis, respectively. Furthermore, the GSH content, MDA content, ROS level, and Fe2+ level were measured by using a colorimetric GSH test kit, a Lipid Peroxidation MDA Assay Kit, a DCFH-DA assay and the phirozine technique, respectively. Immunofluorescence labelling was used to detect protein levels of ACSL4 and PTGS2. Messenger RNA and protein expression of HO-1, GPX4 and Nrf2 was evaluated through western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). To establish a diabetic mouse model, mice were intraperitoneally injected 150 mg/kg streptozotocin. The MDA content, ROS level and the iron level were detected by using corresponding commercial kits. Results Maresin-1 promoted cell proliferation while reducing the apoptotic process in HG-induced ARPE-19 cells. Maresin-1 significantly reduced ferroptosis induced by HG in ARPE-19 cells, as demonstrated as a result of decreased MDA content, ROS level, Fe2+ level, PTGS2 expression, ACSL4 expression and increased GSH content. With respect to mechanisms, maresin-1 treatment up-regulated the mRNA expression and protein expression of HO-1, GPX4 and Nrf2 in HG-induced ARPE-19 cells. Nrf2 inhibitor reversed the inhibitory effects of maresin-1 on ferroptosis in HG-induced ARPE-19 cells. In vivo experiments, we found that Maresin-1 evidently repressed ferroptosis a mouse model of DR, as evidenced by the decreased MDA content, ROS level and iron level in retinal tissues of mice. Conclusion Maresin-1 protects ARPE cells from HG-induced ferroptosis via activating the Nrf2/HO-1/GPX4 pathway, suggesting that maresin-1 prevents DR development.

Environmental and design factors determine the stormwater management capacity of green roofs; however, the design and environmental factors that impact their hydrological performance in subtropical humid regions are poorly understood. In particular, meteorological factors have received little attention. Meteorological factors vary greatly at different stages of a rainfall event (e.g., during the rainfall and outflow). Therefore, the impact of meteorological factors at different stages on hydrological performance should be considered separately to obtain a more accurate picture of their effects on hydrological performance. In this study, experimental green roofs were established based on four substrate types and two depths. For the first time, this study systematically explored the effects of design factors for the substrate (type and depth) and multi-stage environmental factors on the hydrological performance of green roofs. Environmental factors, including meteorological factors, from three critical stages (before and during a rainfall event and during the outflow), and rainfall characteristics (e.g., rainfall depth and rainfall duration) were incorporated to determine the variation in hydrological performance. The effects of multi-stage environmental factors on retention and peak reduction were analyzed, with a ranking of each factor’s relative importance. Environmental factors played a leading role in determining hydrological performance. However, the impact of multi-stage environmental factors was not as important as that of rainfall depth and antecedent volumetric water content. Differences in hydrological performance were compared across combinations of design factors. No significant differences were observed across substrate types and depths. However, potential interactive effects might exist, though these were not significant compared to environmental factors (e.g., rainfall depth and rainfall duration). These results confirmed that the meteorological factors in the different event-related stages significantly impacted the hydrological performance. Quantifying the effects of design and environmental factors is critical for hydrological performance evaluation. The results provided a broader perspective on understanding influence mechanisms of hydrological performance and highlighted the impact of microclimates on hydrological performance.

Abstract The application of pesticides in mixtures often exerts multiple pressures on agricultural soils in the short term. Therefore, it is necessary to assess the effects of mixed application on the environmental behavior and ecotoxicity of pesticides in soil. In this study, we assessed the effects of three common pesticides through mixed application on soil degradation and toxicity toward the earthworm Eisenia fetida. Compared with the degradation half-lives (DT50) the single pesticide, the DT50 values of avermectin, imidacloprid and carbendazim in the binary mixtures were similar. However, their DT50 values in the ternary mixtures were approximately 1.5 times longer than those in the individual applications, enhancing their stable in soil after two or three applications. The ternary mixtures of the pesticides showed significantly synergistic toxicity toward E. fetida, while their binary mixtures exhibited a changing interaction throughout the entire effect level range. The ternary mixtures activated higher SOD and CAT activities in E. fetida than the individual treatments, confirming their synergistic effects. By conducting avoidance tests with E. fetida, ternary toxic interactions were effectively assessed within a relatively short testing period. In summary, the three pesticides in ternary mixtures exhibited longer degradation half-lives and synergistic toxicity toward earthworms compared to individual or binary mixtures.

The current sales model combining online and offline channels meets the diverse requirements of consumers. However, consumers’ inter-channel switching behavior and strategic behavior also pose significant challenges to pricing decisions in the hybrid channel. Using game theory and consumer utility theory, a retailer-driven pricing model is developed to study the optimal pricing problem for each channel in a mixed-channel supply chain considering the characteristics of channel competition and the waiting behavior of strategic consumers. Study results show there is a negative correlation between the proportion of strategic consumers and the optimal pricing and profit of each channel, and as the proportion of strategic consumers rises, the optimal pricing and profit of manufacturers and retailers all trend downward. Incorporating strategic consumers into the pricing model will assist the supply chain in elucidating the behavior of consumer heterogeneity during various decision-making periods and in making reasonable pricing decisions. Effective guiding strategies, such as pre-discount and purchase restrictions, can reduce the profit loss caused by strategic consumer behavior. The optimal combination of pre-announcement discount and strategic consumer ratio can generate the greatest profit for retailers and the supply chain.

BackgroundLong-COVID (LC) refers to post-acute COVID-19 symptoms that can last for months or longer after the initial infection, affecting the physical health of infected patients. This study aims to investigate the association between the symptomology of LC and the mental health of patients in China. It also aims to examine the relationship between the perceived symptom burden and mental health of these patients.MethodsA population-based stratified cluster sample was recruited, using a standard sampling procedure, from a prefecture-level city in Northern China. Participants included patients who had tested positive for COVID-19 after December 2022. LC symptomology was assessed using a LC symptoms checklist where the perceived symptom burden was measured by the included 5-point Likert scales. Mental health of patients was measured using the Depression, Anxiety, and Stress Scale (DASS), the original Connor-Davidson Resilience Scale (CD-RISC), and the Duke-UNC Functional Social Support Questionnaire (DUFSS). Data were analysed using multiple linear regression models.ResultsAbout 25% of respondents, experienced COVID symptoms lasting longer than two months that could only be explained by the infection. Post-exertional malaise (22.2%) and fatigue (21.2%) were the most common symptoms. After controlling for potential confounding variables, LC symptomology was significantly and positively associated with depression (t=2.09, p=0.037) and anxiety (t=4.51, p

Plastic film mulching and nitrogen (N) fertilization are two important field management practices used to increase crop yields in rain-fed agriculture in arid and semi-arid areas. These two practices, however, can have opposing effects on soil organic carbon (SOC) stock and turnover. To clarify and analyze the combined effects of these practices, we conducted a 7-year continuous maize cultivation experiment with four treatments: (1) no plastic film mulching without N fertilization (Control), (2) plastic film mulching without N fertilization (PFM), (3) N fertilization without plastic film mulching (N), and (4) plastic film mulching with N fertilization (PFM + N). The 13C natural abundance of in the light and heavy fractions of organic carbon (LFOC and HFOC) was used to differentiate “old” (>7 years) and “new” (

ABSTRACTSpecial attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18–45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38–1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74–8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

Abstract In this paper, a novel flyback synchronous rectification (SR) strategy for both continuous conduction mode (CCM) and discontinuous conduction mode (DCM) is proposed. The hybrid mode is suitable for the wide input voltage range, and large load range, which can widen the application range. The proposed strategy can reduce the body diode conduction time in the turning‐on interval in both the DCM and CCM and eliminate the cross‐conduction between the primary switch and secondary switch that existed in the conventional CCM SR converter by adding several logic units. A 12‐V/3‐A output mixed‐mode flyback converter prototype is designed and fabricated to verify the strategy. Measurement results show that with the proposed SR strategy, the efficiency is improved by approximately 5.5% in CCM and 0.5% in DCM.

As a repository of genetic information of above-ground vegetation, the soil seed bank plays an important role in the natural succession and renewal of vegetation and the construction of ecological restoration. In this paper, three typical plant communities in the rocky desertification area of Gongcheng Yao Autonomous County were selected for the study, and soil seed bank structure and diversity in different communities and their response to soil nutrient characteristics were analyzed. The results were as follows：(1) A total of 3 648 seedlings belonging to 55 species in 51 genera and 33 families were detected, which included 20 species of 1, 2-year-old herbs, 21 species of perennial herbs, 5 species of vines, 3 species of shrubs and 6 species of trees; the average density of soil seed bank of different plant communities in karstic desertification areas of Gongcheng was Prunus salicina economic forest (22 493 grain·m-2) > Cyclobalanopsis glauca secondary forest (1 033 grain·m-2) > Phyllostachys sulphurea shrub (793 grain·m-2). (2) As for the plant life type of the soil seed bank, the soil seed bank life type of Prunus salicina economic forest was mainly annual malignant weeds, the plant life type of the soil seed banks in the Cyclobalanopsis glauca secondary forest and Phyllostachys sulphurea shrub was dominated by perennial herbs, while woody plants account for a relatively small proportion; the species diversity and similarity of the soil seed banks of different vegetation types were generally low, while the species composition of the soil seed banks also had low similarity with the aboveground communities. (3) The soil elements in the study area had higher nitrogen content and lower phosphorus content, and phosphorus was a limiting factor for plant growth in Phyllostachys sulphurea shrub and Quercus glauca secondary forest. In conclusion, the plant community in the stone desertification area of Gongcheng has some native germplasm resources, but overall shows a low species diversity, and it is urgent to introduce native tree species artificially to accelerate the positive vegetation succession on the basis of natural sequestration, and pay attention to nutrient management, especially the regulation of phosphorus elements. The results provide a theoretical reference for karst stone desertification management and vegetation restoration in Gongcheng.

Abstract Background Plant cells usually sustain a stable membrane potential due to influx and/or efflux of charged ions across plasma membrane. With the growth and development of plants, different tissues and cells undergo systemic or local programmed decline. Whether the membrane potential of plasma membrane could report senescence signal of plant tissues and cells is unclear. Results We applied a maneuverable transmembrane potential (TMP) detection method with patch-clamp setup to examine the senescence signal of leaf tissue cells in situ over the whole life cycle in Arabidopsis thaliana. The data showed that the TMPs of plant tissues and cells were varied at different growth stages, and the change of TMP was higher at the vegetative growth stage than at the reproductive stage of plant growth. The distinct change of TMP was detectable between the normal and the senescent tissues and cells in several plant species. Moreover, diverse abiotic stimuli, such as heat stress, hyperpolarized the TMP in a short time, followed by depolarized membrane potential with the senescence occurring. We further examined the TMP of plant chloroplasts, which also indicates the senescence signal in organelles. Conclusions This convenient TMP detection method can report the senescence signal of plant tissues and cells, and can also indicate the potential of plant tolerance to environmental stress.

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 μg/mL against G. zeae, EC50 = 1.01 μg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 μg/mL against A. alternata, EC50 = 0.20 μg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

Climate change and human activities have caused various ecological risks to coastal urban agglomerations. Ecological security refers to the state of health of an ecosystem and its integrity. An objective and comprehensive evaluation of ecological security is significant for protecting the structure and function of coastal ecosystems. The driving force–pressure–state–impact–response (DPSIR) model was used to construct a dynamic simulation model of ecological security in the Xiamen–Zhangzhou–Quanzhou region (XZQR), located on the eastern coast of China. The ecological security level (ESL) characteristics of the spatial and temporal patterns were evaluated by calculating the ecological security index (ESI). Obstacle factors were analyzed as well. The results show the following: (1) From 2011 to 2021, the average ESI rose from 0.238 to 0.686 and went through a relatively insecure stage (2011–2015), a critical stage (2016–2019), and a relatively secure stage (2020–2021). (2) The ESI level in Quanzhou was higher in the early stage, and the level of ecological security in Zhangzhou showed a significant rising trend, increasing by 0.541. Its increase depended on increases in the impact layer. (3) The impact layer is the main obstacle layer affecting the ESL, and the main obstacles include CO2 emissions (0.117), annual rainfall (0.091), general public budget expenditures (0.082), GDP growth rates (0.082), and green coverage in built-up areas (0.075). Therefore, we recommend promoting the complementary advantages of the XZQR and implementing ecological restoration projects.

BackgroundPatients with head and neck cancer (HNC) often experience various types and degrees of complications and functional impairment following surgery or radiotherapy. Consequently, these patients require extensive postdischarge rehabilitation, either at home or in the community. Numerous studies have shown the advantages of mobile Health (mHealth) technology in assisting patients with cancer with self-management and rehabilitation during the postdischarge period. However, few reviews have focused on the intervention, management, and evaluation of mHealth technology in postdischarge patients with HNC. ObjectiveThis study aimed to conduct a scoping review of mHealth technology apps and interventions currently available to patients discharged from hospitals after receiving treatment for HNC. This study sought to identify and summarize the types and effectiveness of existing mHealth interventions as well as the differences in their outcome assessments. MethodsThe PubMed, Embase, Web of Science, and CINAHL databases were used to identify studies with no publication time limits. The keywords “mobile health technology” and “head and neck cancer” were combined to address the main concepts of the research questions. ResultsOf the 1625 papers identified, 13 (0.8%) met the inclusion and exclusion criteria. Most studies (n=8, 61.5%) were randomized controlled trials (RCTs) and cohort studies. These studies were conducted in 6 countries. The main aims of the mHealth interventions in these studies are as follows: (1) symptom monitoring and assessment, (2) rehabilitation training, (3) access to medical health information, (4) telehealth advisers, (5) peer communication and support, and (6) follow-up/review reminders. The outcome evaluations of the 13 included studies were grouped into 4 categories: (1) technology usability and patient satisfaction, (2) self-management of symptoms and patient-reported outcome–related indicators, (3) adherence, and (4) health-related quality of life. ConclusionsA limited number of studies have investigated the use of mHealth technology in the postdischarge self-management of patients with HNC. The existing literature suggests that mHealth technology can effectively assist patients with HNC in self-management and postdischarge interventions. It plays an important role in addressing patients’ health information needs, reducing both their somatic and psychological burdens, and improving their overall quality of life. Future research should prioritize conducting additional high-quality RCTs to evaluate the usability and analyze the cost-effectiveness of mHealth technology.

Objective This work aims to screen drugs for preventing and treating vascular calcification. Method: We screened a series of 3-arylcoumarins for the detection of vascular calcification-associated factors using human aortic vascular smooth muscle cells.Results We found that compounds 14 and 32 significantly inhibited alkaline phosphatase (ALP) activity similar to aminoguanidine hydrochloride (AGH) in a cellular model of AGEs-induced calcification. We also found that compounds 14 and 32 could significantly decrease the levels of factors such as AGEs, intracellular calcium ions, and total ROS in the calcified cell model. Further study indicates that compound 14 could significantly inhibit the expression of P-ERK1/2, PKC, NF-κB, RAGE and OPN proteins and increased the expression of SM22-α and PPAR-γ proteins in the calcified cells.Conclusion We speculate that compound 14 inhibits vascular calcification by inhibiting oxidative stress and inhibiting AGEs production, suggesting that 3-arylcoumarin derivatives are potential candidates for the treatment of vascular calcification.

Objective This study explores LncRNA TM1‐3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism. Methods Bioinformatics was performed to analyze OA disease‐related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1‐3P and miR‐144‐3p, ONECUT2 and miR‐144‐3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin–eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT‐qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one‐way analysis of variance of repeated measurement data was applied for multi‐group comparison, following Tukey's post‐test. Results ONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P

Abstract Industrial robots are increasingly being used in machining tasks because of their high flexibility and intelligence. However, the low structural stiffness of a robot significantly affects its positional accuracy and the machining quality of its operation equipment. Studying robot stiffness characteristics and optimization methods is an effective method of improving the stiffness performance of a robot. Accordingly, aiming at the poor accuracy of stiffness modeling caused by approximating the stiffness of each joint as a constant, a variable stiffness identification method is proposed based on space gridding. Subsequently, a task-oriented axial stiffness evaluation index is proposed to quantitatively assess the stiffness performance in the machining direction. In addition, by analyzing the redundant kinematic characteristics of the robot machining system, a configuration optimization method is further developed to maximize the index. For numerous points or trajectory-processing tasks, a configuration smoothing strategy is proposed to rapidly acquire optimized configurations. Finally, experiments on a KR500 robot were conducted to verify the feasibility and validity of the proposed stiffness identification and configuration optimization methods.

Wearable sensors with edge computing are desired for human motion monitoring. Here, the authors demonstrate a topographic design for wearable MXene sensor modules with wireless streaming or in-sensor computing models for avatar reconstruction.

Accumulating evidence indicates that m 6 A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m 6 A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m 6 A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo , whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m 6 A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m 6 A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.

The cause mechanism of collapse disasters is complex and there are many influencing factors. Convolutional Neural Network (CNN) has a strong feature extraction ability, which can better simulate the formation of collapse disasters and accurately predict them. Taihe town’s collapse threatens roads, buildings, and people. In this paper, road distance, water distance, normalized vegetation index, platform curvature, profile curvature, slope, slope direction, and geological data are used as input variables. This paper generates collapse susceptibility zoning maps based on the information value method (IV) and CNN, respectively. The results show that the accuracy of the susceptibility assessment of the IV method and the CNN method is 85.1% and 87.4%, and the accuracy of the susceptibility assessment based on the CNN method is higher. The research results can provide some reference for the formulation of disaster prevention and control strategies.

A fast spraying speed, wide working area, and easy operation are the operational advantages of high-clearance boom sprayers. To address the issue of spray boom mechanical vibration affecting the spraying effect, a double-link trapezoidal boom suspension is designed for the 3WPYZ sprayer. This suspension can achieve passive vibration reduction, active balance, and ground profiling. The kinematic model of the boom suspension is established based on D’Alembert’s principle and the principle of multi-body dynamics, and the design factors affecting the stability of the boom are determined. Through orthogonal experimental design and virtual kinematics simulation, the influence of the boom length and orifice diameter of each part on the swing angle and the natural frequency of the boom suspension is investigated. Design-Expert 8.0.6 software is used to analyze and optimize the test results. The optimization results show that, when the connecting boom length LAB is 265 mm, the inner boom suspension boom length LAD is 840 mm, the outer boom suspension boom length LBC is 1250 mm, and the throttle hole diameter d is 4 mm; the maximum swing angle of the boom suspension is reduced by 53.02%. In addition, the natural frequency of the boom is reduced from 1.3143 rad/s to 1.1826 rad/s, and the dynamic characteristic optimization effect is remarkable. The modal analysis results show that the first sixth-order vibration test frequency of the boom sprayer suspension designed in this paper meets the requirements and avoids the influence of external factors. Field tests show that, when the sprayer is excited by the environment at 3.5° to 4°, the boom suspension can reduce the vibration transmitted by the body to a reasonable range. The static analysis shows that the structural design of this study reduces the stress at the connection of the end boom suspension, the maximum displacement, and the maximum stress of the inner boom suspension. The test results of the dynamic characteristics of the implement are basically consistent with the virtual model simulation test results, thus achieving the optimization objectives.

Abstract During the manufacturing process of tubing and casing, manufacturing deviations can occur in quality parameters, such as yield strength, outer diameter, and wall thickness, which can lead to uncertainty in the actual strength of the tubing string. Specifically, tubing string failures periodically occur in high‐temperature, high‐pressure, and ultra‐deep gas wells owing to the uncertainty in string strength, attenuation of high‐temperature material properties, and influence of complex load fluctuations. Therefore, in this study, Monte Carlo method is adopted to simulate the local fluctuation of downhole actual load, and the load variation rule of tubing string in high‐temperature and high‐pressure ultra‐deep well is obtained. By considering the effect of manufacturing tolerance and corrosion, variation law of string strength is obtained. Additionally, the influence of load, temperature, manufacturing tolerance, and other uncertainties on the strength and stress of the tubing string is analyzed, and a quantitative evaluation method for the mechanical integrity of the tubing string is established. The calculation results show that the uncertainty of complex loads and influence of high temperature increase the failure probability of the mechanical integrity of tubing string. Furthermore, a failure risk can potentially exist under conditions wherein conventional verification results denote no failure. It is determined via sensitivity analysis that temperature, corrosion rate, and steel grade are the main factors for the failure of the tubing string mechanical integrity. By considering the influence of high temperature, the failure probability of the tubing string is increased by 25.33% when compared to the original basis. However, considering the manufacturing tolerance of tubing string, the actual yield strength of tubing string is higher than the nominal yield strength, which reduces the failure probability of the tubing string. This implies that reduction of the subjective influence in the risk assessment process can lead to precise and quantitative analysis of the failure risk of the tubing string mechanical integrity and optimization of the structure of the tubing string in high‐temperature, high‐pressure, and ultra‐deep gas wells.

Introduction: Chronic stress exposure is the main environmental factor leading to cognitive impairment, but the detailed molecular mechanism is still unclear. Adenosine Deaminase acting on double-stranded RNA1(ADAR1) is involved in the occurrence of chronic stress-induced cognitive impairment. In addition, dopamine and Adenosine 3′5′-monophosphate-regulated phospho-protein (DARPP-32) gene variation affects cognitive function. Therefore, we hypothesized that ADAR1 plays a key role in chronic stress-induced cognitive impairment by acting on DARPP-32.Methods: In this study, postnatal 21-day-old male BALB/c mice were exposed to chronic unpredictable stressors. After that, the mice were treated with ADAR1 inducer/inhibitor. The cognitive ability and cerebral DARPP-32 protein expression of BALB/c mice were evaluated. In order to explore the link between ADAR1 and DARPP-32, the effects of ADAR1 high/low expression on DARPP-32 protein expression in vitro were detected.Results: ADAR1 inducer alleviates cognitive impairment and recovers decreased DARPP-32 protein expression of the hippocampus and prefrontal cortex in BALB/c mice with chronic unpredictable stress exposure. In vivo and in vitro studies confirm the results predicted by bio-informatics; that is, ADAR1 affects DARPP-32 expression via miR-874-3p.Discussion: The results in this study demonstrate that ADAR1 affects the expression of DARPP-32 via miR-874-3p, which is involved in the molecular mechanism of pathogenesis in chronic unpredictable stress-induced cognitive impairment. The new findings of this study provide a new therapeutic strategy for the prevention and treatment of stress cognitive impairment from epigenetics.