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Abstract Objective Premenstrual Syndrome is also known as premenstrual tension syndrome because of the pronounced premenstrual mental and emotional anomalies. This study focuses on the association between occupational stress, sleep quality and premenstrual syndrome in clinical nurses and the mediating role of sleep quality. Methods A cross-sectional study was conducted to measure occupational stress, sleep quality and premenstrual syndrome in 415 clinical nurses using the Chinese Nurses Stressor Scale, the Pittsburgh Sleep Quality Index Scale, and the Premenstrual Syndrome Scale. SPSS was used to explore the relationship between the variables, and AMOS was used to explore the mediating role between the variables. Results Nurses’ occupational stress positively predicted PMS (β = 0.176, p

Abstract This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence.

Abstract Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target.

Abstract Objective This study aims to clarify the uncertain association between vasopressor administration and the development of intensive care unit‐acquired weakness (ICUAW) in critically ill adult patients. Methods We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials up to October 10, 2023. Titles and abstracts were independently screened by two authors, who then reviewed full texts and extracted relevant data from the studies that met the inclusion criteria. This review included prospective and retrospective cohort studies that explored the relationship between vasopressor use and ICUAW utilizing univariate or multivariate analysis in adult ICU patients. Results A total of 15 studies were included in our review, collectively indicating a statistically significant association between the use of vasopressors and the occurrence of ICUAW (odds ratio [OR], 3.43; 95% confidence intervals [CI], 1.95–6.04), including studies utilizing multivariate analysis (OR, 3.43; 95% CI, 1.76–6.70). Specifically, the use of noradrenaline was significantly associated with ICUAW (OR, 4.42; 95% CI, 1.69–11.56). Subgroup and sensitivity analyses further underscored the significant relationship between vasopressor use and ICUAW, particularly in studies focusing on patients with clinical weakness, varying study designs, different sample sizes, and relatively low risk of bias. However, this association was not observed in studies limited to patients with abnormal electrophysiology. Conclusions Our review underscores a significant link between the use of vasopressors and the development of ICUAW in critically ill adult patients. This finding helps better identify patients at higher risk of ICUAW and suggests considering targeted therapies to mitigate this risk.

Salt marshes are pivotal in the global carbon cycle, serving as significant contributors to the blue carbon sink. Accurately estimating carbon stock in salt marshes relies on precise vegetation classification. Here, we developed the Salt Marsh Vegetation Classification Network (SVCN), a deep learning algorithm designed to classify three primary vegetation canopies (S. alterniflora, P. australis, and S. mariqueter) spanning from 2016 to 2023 over the Yangtze River estuary, China. The SVCN was initially trained using 412 vegetation samples and Sentinel-1 Synthetic Aperture Radar (SAR) data in 2018. Additionally, we trained three traditional machine learning models – Classification and Regression Trees, Random Forests, and K-Nearest Neighbors – to facilitate a comparative analysis of model performance. Leveraging the classified vegetation outcomes, we conducted salt marsh carbon stock estimations using the InVEST model. The results showed that the SVCN model outperformed the other three models, achieving an overall accuracy of 0.97. Salt marsh carbon stocks in the Yangtze River estuary exhibited an overall increasing trend from 2016 to 2023, with an average annual increase of 3.13 ×103Mg⋅year−1. However, there was a notable decrease of 10.36% in 2017, primarily attributed to reductions in the area covered by S. alterniflora and P. australis, which decreased by 11.18% and 10.11%, respectively. These findings highlight the potential of deep learning models and the incorporation of salt marshes in carbon stock estimates to enhance accuracy.

Summary: Fundus fluorescein angiography (FFA) examinations are widely used in the evaluation of fundus disease conditions to facilitate further treatment suggestions. Here, we present a protocol for performing deep learning-based FFA image analytics with classification and segmentation tasks. We describe steps for data preparation, model implementation, statistical analysis, and heatmap visualization. The protocol is applicable in Python using customized data and can achieve the whole process from diagnosis to treatment suggestion of ischemic retinal diseases.For complete details on the use and execution of this protocol, please refer to Zhao et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments. Methods Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A protein‒protein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot. Results A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-β-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins. Conclusions AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.

Abstract Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme -/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1β, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Objective: Delays in the diagnosis and treatment of pulmonary tuberculosis (PTB) can increase the risk of transmission, thereby posing a significant risk to public health. Early diagnosis is considered to play a crucial role in eliminating TB. Rapid testing, active case finding, and health education are effective strategies for reducing tuberculosis diagnosis delays (TDDs). This study aimed to quantitatively compare the impact of reducing the TDD on incidence rates among student and non-student groups, thus exploring the efficacy of shortening the TDD for ending the TB epidemic and providing a reference for achieving the target incidence rate for ending TB. Methods: We used unsupervised hierarchical clustering analysis and non-parametric tests to characterize the epidemiological characteristics of TDD. Additionally, a dynamic transmission model was used to quantify the impact of shortening the TDD on the incidence rates of TB among the two groups. Results: There was an initial increase in the TDD, followed by a decrease. Longer TDDs were observed in the northeastern region of China. Farmers, middle and high school students, middle-aged, elderly individuals and males exhibited relatively longer TDDs. A significant reduction in the incidence rate of PTB was observed when the TDD was decreased by 50 %. However, only reducing the TDD among non-students could achieve the goal of ending TB (i.e., achieving a minimum reduction of 63.00 %). Conclusions: TDD remains a serious risk to public health, and non-students were shown to experience longer TDD. Shortening the TDD is crucial for reducing the incidence rates of TB, especially among non-students. It is essential to develop a highly sensitive and effective system for eliminating TB among non-students.

Background: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent. Methods: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes. Results: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis. Conclusions: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.

Abstract Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well‐being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface‐modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over‐expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances in various ligand‐modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.

Salted duck eggs are a type of traditional Chinese pickled delicacy, and moisture and lipid content are important indexes for evaluating the quality during processing. This study used a hyperspectral imaging (HSI) system in conjunction with chemometrics to investigate the content change and distribution of moisture and lipid during different salting stages of duck eggs. The HSI was used to obtain reflectance spectral information of salted duck eggs in the 432~961 nm wavelength range. To minimize the noise in spectral signals, three preprocessing methods including Savitzky-Golay smoothing (SG), Gauss filter smoothing (Gauss), and standard normal variation (SNV) were used. The competitive adaptive reweighted sampling (CARS) was used to select the optimal wavelengths for predicting moisture and lipid content, and then the partial least squares regression (PLSR) and artificial neural network (ANN) methods were used to predict moisture and lipid content quantitatively. Results showed that ANN model could exhibited a better performance in predicting moisture and lipid content with coefficients of determination of the protein moisture, yolk moisture and yolk lipid of 0.9306, 0.9552 and 0.8896 respectively. Finally, the ANN model was used to create a distribution map of moisture and lipid content in the profile of salted duck eggs. The visualization distribution maps successfully display the distribution of moisture and lipid content during different salting periods. This study could lead to the development of a rapid detection method based on spectrum technology for production and processing of salted duck egg industry.

Abstract Background Gastric cancer (GC) is associated with high mortality and heterogeneity and poses a great threat to humans. Gene therapies for the receptor tyrosine kinase RON and its spliceosomes are attracting increasing amounts of attention due to their unique characteristics. However, little is known about the mechanism involved in the formation of the RON mRNA alternative spliceosome RONΔ160. Methods Fourteen human GC tissue samples and six normal gastric tissue samples were subjected to label-free relative quantitative proteomics analysis, and MAGOH was identified as a candidate protein for subsequent studies. The expression of MAGOH in clinical specimens was verified by quantitative real-time PCR and western blotting. We then determined the biological function of MAGOH in GC through in vitro and in vivo experiments. RNA pulldown, RNA sequencing and RNA immunoprecipitation (RIP) were subsequently conducted to uncover the underlying mechanism by which MAGOH regulated the formation of RONΔ160. Results Proteomic analysis revealed that MAGOH, which is located at key nodes and participates in RNA processing and mRNA splicing, was upregulated in GC tissue and GC cell lines and was associated with poor prognosis. Functional analysis showed that MAGOH promoted the proliferation, migration and invasion of GC cells in vitro and in vivo. Mechanistically, MAGOH inhibited the expression of hnRNPA1 and reduced the binding of hnRNPA1 to RON mRNA, thereby promoting the formation of RONΔ160 to activate the PI3K/AKT signaling pathway and consequently facilitating GC progression. Conclusions Our study revealed that MAGOH could promote the formation of RONΔ160 and activate the PI3K/AKT signaling pathway through the inhibition of hnRNPA1 expression. We elucidate a novel mechanism and potential therapeutic targets for the growth and metastasis of GC based on the MAGOH-RONΔ160 axis, and these findings have important guiding significance and clinical value for the future development of effective therapeutic strategies for GC.

Abstract Rechargeable lithium batteries using 5 V positive electrode materials can deliver considerably higher energy density as compared to state-of-the-art lithium-ion batteries. However, their development remains plagued by the lack of electrolytes with concurrent anodic stability and Li metal compatibility. Here we report a new electrolyte based on dimethyl 2,5-dioxahexanedioate solvent for 5 V-class batteries. Benefiting from the particular chemical structure, weak interaction with lithium cation and resultant peculiar solvation structure, the resulting electrolyte not only enables stable, dendrite-free lithium plating-stripping, but also displays anodic stability up to 5.2 V (vs. Li/Li+), in additive or co-solvent-free formulation, and at low salt concentration of 1 M. Consequently, the Li | |LiNi0.5Mn1.5O4 cells using the 1 M LiPF6 in 2,5-dioxahexanedioate based electrolyte retain >97% of the initial capacity after 250 cycles, outperforming the conventional carbonate-based electrolyte formulations, making this, and potentially other dicarbonate solvents promising for future Lithium-based battery practical explorations.

Abstract Background The predictive correlation of tumor depth of invasion changes after neoadjuvant therapy, and the 8th American Joint Committee on Cancer (AJCC) ypTNM system for gastric cancer may not accurately predict patient prognosis following neoadjuvant therapy. Methods A retrospective analysis was conducted on a total of 258 patients who underwent radical surgery for gastric cancer after neoadjuvant therapy. The Newstage system was established based on tumor regression grade and pathological lymph node status. The 3-year survival rates of patients classified by the Newstage system were compared with those classified by the AJCC ypTNM system. Results In a cohort of 258 patients, the 3-year overall survival rates based on the Newstage system were: (I) 94.6%, (II) 79.3%, (III) 54.5%, and (IV) 30.2%. The Newstage system exhibited a lower Akaike information criterion value (902.57 vs. 912.03). Additionally, the area under the ROC curve (0.756 vs. 0.733) and the C-index (0.731 vs. 0.718) was higher than the AJCC ypTNM system. Furthermore, a multivariate analysis indicated that the Newstage system was an independent prognostic factor (p = 0.001). Conclusion The Newstage system exhibits superior predictive performance in estimating survival rates for neoadjuvant therapy in gastric cancer. It also functions as an independent prognostic factor.

Abstract Background The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active. Methods Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis. Results Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) ‘unpredictable’ troubles: they tended to favor the ‘optimal’ solution of keeping their lives in order rather than the best medical treatment options. Conclusion This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the ‘inaccessibility’ of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.

The aim of this study was to overcome the impact of vibration generated by agricultural machinery on the monitoring accuracy and performance of vehicle-mounted crop growth monitoring systems during field operation. This paper developed a vehicle-mounted crop growth monitoring system with vibration damping capability to achieve this goal. The system consists of a multispectral crop growth sensor, signal conditioning module, and truss-type sensor bracket with self-vibration damping capability. The commercial finite element analysis software ABAQUS 6.10 was used to conduct modal and dynamic simulation analyses of the sensor bracket, which indicate that the truss-type sensor bracket can damp vibrations effectively. The p-values (least significant differences) of crop canopy DNRE (red edge normalized difference vegetation index) under different operating speeds (1.5, 3, and 4.5 km/h) are 0.454, 0.703, 0.81, and 0.838, respectively, for four different crop growth stages. In a comparative experiment between the proposed monitoring system and two similar vehicle-mounted sensors (CropSpec and GreenSeeker RT 200) for measuring agronomic parameters at different stages of crop growth, the proposed monitoring system yielded R2 values of 0.8757, 0.7194, and 0.795, respectively, and RMSE values of 0.7157, 2.2341, and 2.0952, respectively, in the tillering stage, jointing stage, and tillering and jointing stage, outperforming the other two sensors.

The Ordos Basin is the main tight gas-producing basin in China. Under the background of strong heterogeneous physical property, there is still high porosity and permeability “sweet spot” in tight reservoirs. Feldspar dissolution exerts a significant effect on porosity/permeability, while its genetic mechanism is unclear, which restricts the prediction of effective reservoir. In this paper, genesis of feldspar dissolution and its effect on reservoir heterogeneity were studies. Carboniferous-Permian Formation, which is the main gas-producing strata in northeast margin of Ordos Basin, is taken as the target. Based on the methods of thin section observation, physical property test, inclusion, isotope and productivity analysis, mechanism of feldspar dissolution, and its positive modification to tight sandstone reservoir are studied. The results show that the target sandstone is dominantly made up of litharenite and feldspathic litharenite. About 98.6% of the samples possess permeability less than 1 mD, while 89.7% of the samples possess porosity less than 10%. The high porosity/permeability space within tight reservoirs is dominated by dissolved pores, accounting for more than 80% of the total pore space. The dissolution minerals are mainly associated with feldspar, and the amount of feldspar dissolution is positively correlated with porosity and permeability. According to the fluid chemical information of quartz overgrowth and ankerite (related to feldspar dissolution), feldspar dissolved pores are caused by organic acid derived from the thermal maturity of organic matter. According to production data, no daily production can be achieved in single well, when the porosity and permeability are less than 7% and 0.1 mD, respectively. However, once it exceeds this porosity/permeability threshold value, the production capacity is exponentially improved. Furthermore, when surface porosity of feldspar dissolution exceeds 7%, most values of the porosity and permeability exceed the threshold values of the allowable productivity, indicating that extensive feldspar dissolution is favorable factor for effective reservoir space development in tight reservoirs.

Metaphor affects how people focus, remember, and process information and significantly influences children’s language development. The study explored metaphorical comprehension by Chinese children of different ages (5–8 years). We collected response times and accuracy rates when they processed metaphorical and literal sentences with the graded salience. Linear mixed-effects modeling showed that Chinese children’s metaphorical ability improved with age. Subsequent analysis found that the perception period of metaphorical knowledge was at age 5, the development stage of metaphorical knowledge was at age 6 and 7, and the rational decision period of metaphorical ability was at age 8. After 8-year-old, children can invoke the knowledge of the intention schema while activating the source domain, and this knowledge can be automatically and quickly mapped to the target domain. Meanwhile, language development and cognitive processing influenced the metaphorical comprehension of Chinese children, especially children of 8 years of age who had the highest correct rate and the shortest reaction time to process low-saliency metaphorical sentences, while 5-year-old children had the highest accuracy in high-saliency metaphorical sentence and 6-year-old children got the longest reaction time to process sentence in high-saliency metaphor. This study may provide evidence for improving and training metaphor comprehension in children with special needs such as those with an autism spectrum disorder.

Abstract Narrowband photodetectors conventionally rely on optical structure design or bandpass filters to achieve the narrowband regime. Recently, a strategy for filterless narrowband photoresponse based on the charge collection narrowing (CCN) mechanism was reported. However, the CCN strategy requires an electrically and optically “thick” photoactive layer, which poses challenges in controlling the narrowband photoresponse. Here we propose a novel strategy for constructing narrowband photodetectors by leveraging the inherent ion migration in perovskites, which we term “band modulation narrowing” (BMN). By manipulating the ion migration with external stimuli such as illumination, temperature, and bias voltage, we can regulate in situ the energy‐band structure of perovskite photodetectors (PPDs) and hence their spectral response. Combining the Fermi energy levels obtained by the Kelvin probe force microscopy, the internal potential profiles from solar cell capacitance simulator simulation, and the anion accumulation revealed by the transient ion‐drift technique, we discover two critical mechanisms behind our BMN strategy: the extension of an optically active but electronically dead region proximal to the top electrode and the down‐bending energy bands near the electron transport layer. Our findings offer a case for harnessing the often‐annoying ion migration for developing advanced narrowband PPDs.

AbstractObjectives The scope of lateral neck lymph node dissection (LND) in papillary thyroid carcinoma (PTC) remains controversial. Our research aimed to explore the value of central lymph node metastasis (CLNM) in frozen sections for predicting neck lateral lymph node metastasis (NLLNM) and to guide clinical surgeons in performing surgical lymph node dissection.Patients A total of 275 patients with PTC with suspected ‘Cervical lymph node metastasis (LNM, including CLNM and NLLNM)’ underwent unilateral or bilateral thyroidectomy and an intraoperative frozen diagnosis of central lymph nodes (LNs), as well as central and neck lateral LND. Validity indices and consistency of central LNs in frozen sections were calculated. In total, 216 patients then met the inclusion criteria and were enrolled in the follow-up study. The clinical and pathological data of the patients were retrospectively analyzed. The relationship between the number, metastatic diameter, and the ratio of CLNM to NLLNM was investigated.Results CLNM in frozen and paraffin-embedded sections was associated with NLLNM. Univariate and multivariate analyses revealed the following risk factors for NLLNM metastasis: maximum diameter, total number, and ratio of metastatic LNs. A significant result was obtained when a cut-off value of 2.050 mm for the maximum metastatic diameter, 5.5 in the total number, and 0.5342 for the CLNM ratio level was used. Interaction term analyses showed that the association between the number of CLNM and NLLNM differed according to maximum diameter.Conclusion Central LNs in frozen sections accurately predicted NLLNM. In patients with PTC with >5 CLNMs, ≥2 and ≤5 CLNMs and maximum metastatic diameter > 2 mm, neck lateral LND should be considered. Our findings will facilitate the identification of patients who are likely to benefit from extended lateral neck LND.

Non-negative matrix factorization (NMF) has been widely used in machine learning and data mining fields. As an extension of NMF, non-negative matrix tri-factorization (NMTF) provides more degrees of freedom than NMF. However, standard NMTF algorithm utilizes Frobenius norm to calculate residual error, which can be dramatically affected by noise and outliers. Moreover, the hidden geometric information in feature manifold and sample manifold is rarely learned. Hence, a novel robust capped norm dual hyper-graph regularized non-negative matrix tri-factorization (RCHNMTF) is proposed. First, a robust capped norm is adopted to handle extreme outliers. Second, dual hyper-graph regularization is considered to exploit intrinsic geometric information in feature manifold and sample manifold. Third, orthogonality constraints are added to learn unique data presentation and improve clustering performance. The experiments on seven datasets testify the robustness and superiority of RCHNMTF.

Abstract With the continuous improvement of oil and gas exploration in the middle and shallow layers, the deep Paleogene in Raoyang sag has become an important exploration field of “increasing reserves and production” in North China. The recognition and control factors of deep effective reservoirs are unclear, which restricts the recognition effect of oil and gas exploration. The key to identify effective reservoirs is to determine the lower limit standard of reservoir physical properties. The single method for calculating the lower limit of physical properties has limitations. The lower limit of the effective reservoir physical properties of the Shahejie Formation in the Dawangzhuang area was obtained by comprehensively using physical property, well logging and oil test data. The data were analysed by oil testing method, metre oil production index test method and frequency curve intersection method. On this basis, combined with the cast thin-section observations, scanning electron microscopy and other test results, the comprehensive control of effective reservoir development of the Shahejie Formation in the Dawangzhuang area of the Raoyang sag was studied from various factors, such as formation pressure, sand body thickness and diagenesis. The results show that the lower limit of porosity was 9.73, 9.44 and 8.85% at depths of Es1, Es2 and Es3, respectively. The lower limit of permeability was 1.21 × 10–3, 1.18 × 10–3 and 0.59 × 10–3 μm2, respectively. Effective reservoirs are easier to form in areas with formation pressure coefficient greater than 1.2. Formation overpressure inhibits compaction and promotes dissolution. The proportion of effective reservoirs of sand bodies with thicknesses greater than 2 m can reach more than 75%. The influence of diagenesis on the reservoir is mainly manifested in compaction and cementation making the reservoir compact. The porosity reduction rate caused by compaction can reach 20–75%, while dissolution makes the reservoir form secondary pores. The average pore throat radius of secondary pores can reach 4 ~ 6.3 µm. This study makes use of the applicability of different methods, which is more instructive for predicting the effective reservoir of the Shahejie Formation in the study area. In addition, the research results provide a reference for the development mechanism of medium-deep clastic reservoirs.

Recently, community detection has emerged as a prominent research area in the analysis of complex network structures. Community detection models based on non-negative matrix factorization (NMF) are shallow and fail to fully discover the internal structure of complex networks. Thus, this article introduces a novel constrained symmetric non-negative matrix factorization with deep autoencoders (CSDNMF) as a solution to this issue. The model possesses the following advantages: (1) By integrating a deep autoencoder to discern the latent attributes bridging the original network and community assignments, it adeptly captures hierarchical information. (2) Introducing a graph regularizer facilitates a thorough comprehension of the community structure inherent within the target network. (3) By integrating a symmetry regularizer, the model’s capacity to learn undirected networks is augmented, thereby facilitating the precise detection of symmetry within the target network. The proposed CSDNMF model exhibits superior performance in community detection when compared to state-of-the-art models, as demonstrated by eight experimental results conducted on real-world networks.

In recent years, community detection has received increasing interest. In network analysis, community detection refers to the identification of tightly connected subsets of nodes, which are called “communities” or “groups”, in the network. Non-negative matrix factorization models are often used to solve the problem. Orthogonal non-negative matrix tri-factorization (ONMTF) exhibits significant potential as an approach for community detection within multiplex networks. This paper explores the application of ONMTF in multiplex networks, aiming to detect both shared and exclusive communities simultaneously. The model decomposes each layer within the multiplex network into two low-rank matrices. One matrix corresponds to shared communities across all layers, and the other to unique communities within each layer. Additionally, graph regularization and the diversity of private communities are taken into account in the algorithm. The Hilbert Schmidt Independence Criterion (HSIC) is used to constrain the independence of private communities. The results prove that ONMTF effectively addresses community detection in multiplex networks. It also offers strong interpretability and feature extraction capabilities. Therefore, it is an advanced method for community detection in multiplex networks.

Summary: DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

Abstract Background To investigate the relationship between cyclin D2 (CCND2) and miR-206 expression in fine-needle aspiration cytology of thyroid carcinoma. Methods A total of 65 patients with thyroid carcinoma were selected as the subjects and 65 patients with benign thyroid nodules were in control group. The fine-needle aspiration cytology of thyroid nodules was performed. CCND2 and miR-206 levels were detected by PCR. Results Compared with the patients with benign thyroid nodules, the expression level of miR-206 in fine-needle aspiration cytology of thyroid cancer patients decreased significantly and the expression level of CCND2 increased significantly. CCND2 and miR-206 expression was negatively correlated in thyroid cancer tissues. Area under curve (AUC) of miR-206 level in the diagnosis of thyroid cancer was 0.889, and the sensitivity and specificity were 92.3% and 81.5%, respectively. AUC of CCND2 level in the diagnosis of thyroid cancer was 0.837, and the sensitivity and specificity were 67.7% and 89.2%, respectively. The AUC of combined detection of CCND2 and miR-206 in the diagnosis of thyroid cancer was 0.959, and the sensitivity and specificity were 93.8% and 87.7%, respectively. The levels of miR-206 and CCND2 were significantly correlated with TNM staging and lymph node metastasis. Conclusions miR-206 and CCND2 may become new biomarkers for clinical diagnosis of thyroid cancer based on the fine-needle aspiration cytology of thyroid nodules.

Abstract Background Recently, despite the steady decline in the tuberculosis (TB) epidemic globally, school TB outbreaks have been frequently reported in China. This study aimed to quantify the transmissibility of Mycobacterium tuberculosis (MTB) among students and non-students using a mathematical model to determine characteristics of TB transmission. Methods We constructed a dataset of reported TB cases from four regions (Jilin Province, Xiamen City, Chuxiong Prefecture, and Wuhan City) in China from 2005 to 2019. We classified the population and the reported cases under student and non-student groups, and developed two mathematical models [nonseasonal model (Model A) and seasonal model (Model B)] based on the natural history and transmission features of TB. The effective reproduction number (R eff ) of TB between groups were calculated using the collected data. Results During the study period, data on 456,423 TB cases were collected from four regions: students accounted for 6.1% of cases. The goodness-of-fit analysis showed that Model A had a better fitting effect (P

Abstract Background There is a raising concern of a higher infectious Omicron BA.2 variant and the latest BA.4, BA.5 variant, made it more difficult in the mitigation process against COVID-19 pandemic. Our study aimed to find optimal control strategies by transmission of dynamic model from novel invasion theory. Methods Based on the public data sources from January 31 to May 31, 2022, in four cities (Nanjing, Shanghai, Shenzhen and Suzhou) of China. We segmented the theoretical curves into five phases based on the concept of biological invasion. Then, a spatial autocorrelation analysis was carried out by detecting the clustering of the studied areas. After that, we choose a mathematical model of COVID-19 based on system dynamics methodology to simulate numerous intervention measures scenarios. Finally, we have used publicly available migration data to calculate spillover risk. Results Epidemics in Shanghai and Shenzhen has gone through the entire invasion phases, whereas Nanjing and Suzhou were all ended in the establishment phase. The results indicated that Rt value and public health and social measures (PHSM)-index of the epidemics were a negative correlation in all cities, except Shenzhen. The intervention has come into effect in different phases of invasion in all studied cities. Until the May 31, most of the spillover risk in Shanghai remained above the spillover risk threshold (18.81–303.84) and the actual number of the spillovers (0.94–74.98) was also increasing along with the time. Shenzhen reported Omicron cases that was only above the spillover risk threshold (17.92) at the phase of outbreak, consistent with an actual partial spillover. In Nanjing and Suzhou, the actual number of reported cases did not exceed the spillover alert value. Conclusions Biological invasion is positioned to contribute substantively to understanding the drivers and mechanisms of the COVID-19 spread and outbreaks. After evaluating the spillover risk of cities at each invasion phase, we found the dynamic zero-COVID strategy implemented in four cities successfully curb the disease epidemic peak of the Omicron variant, which was highly correlated to the way to perform public health and social measures in the early phases right after the invasion of the virus. Graphical Abstract

Abstract Background Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. Methods Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. Results 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. Conclusions This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions.

Abstract Background Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA. Methods The concentrations of amino acids and cytokines in the synovial fluid of RA (n = 9) and osteoarthritis (OA, n = 9) were detected by LC–MS/MS and CBA assay, respectively. The mRNA and protein expression of cationic amino acid transporter-1 (CAT-1) were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion, and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo. Results L-rginine was upregulated in the synovial fluid of RA patients and was positively correlated with the elevation of the cytokines IL-1β, IL-6, and IL-8. Further examination demonstrated that CAT-1 was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration, and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice. Conclusion CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.

Abstract A novel endoglucanase (BcelFp) was identified from Fervidobaterium pennivorans DSM9078 which had biotransformation activity for protopanaxadiol (PPD)-type ginsenosides. Sequence analysis of BcelFp revealed that it could be classified into glycoside hydrolase family 5 (GH5). The gene encoding a 323-amino acid protein was cloned and expressed in Escherichia coli. The recombinant enzyme was purified, and its molecular weight was approximate 37 kDa. The recombinant BcelFp exhibited an optimal activity at 95 oC and pH 5.5 and showed high thermostability. The endoglucanase had high selectivity for cleaving the outer glucose moiety at the C3 carbon of ginsenoside Rb1, Rb2, Rc and Rd, which produced stronger pharmacologically active gypenoside XVII (GypXVII), Compound O (CO), Compound Mc1 (CMc1) and F2, respectively. The Km values for Rb1, Rb2, Rc and Rd were 3.66 ± 0.04 µM, 4.02 ± 0.12 µM, 5.95 ± 0.03 µM, 0.67 ± 0.006 µM, respectively. The kcat/Km value of BcelFp for ginsenoside Rd was 27.91 mM-1s-1, which was much higher than that of the previously enzymes. This study was the first report of the highly efficient and selective transformation of GypXVII, CO, CMc1 and F2 from Rb1, Rb2, Rc and Rd by a GH5-family thermophilic endoglucanase.

Introduction: Pathogenic mutations in RPGRORF15, one of two major human RPGR isoforms, were responsible for most X-linked retinitis pigmentosa cases. Previous studies have shown that RPGR plays a critical role in ciliary protein transport. However, the precise mechanisms of disease triggered by RPGRORF15 mutations have yet to be clearly defined. There are two homologous genes in zebrafish, rpgra and rpgrb. Zebrafish rpgra has a single transcript homologous to human RPGRORF15; rpgrb has two major transcripts: rpgrbex1-17 and rpgrbORF15, similar to human RPGRex1-19 and RPGRORF15, respectively. rpgrb knockdown in zebrafish resulted in both abnormal development and increased cell death in the dysplastic retina. However, the impact of knocking down rpgra in zebrafish remains undetermined. Here, we constructed a rpgra mutant zebrafish model to investigate the retina defect and related molecular mechanism.Methods: we utilized transcription activator-like effector nuclease (TALEN) to generate a rpgra mutant zebrafish. Western blot was used to determine protein expression. RT-PCR was used to quantify gene transcription levels. The visual function of embryonic zebrafish was detected by electroretinography. Immunohistochemistry was used to observe the pathological changes in the retina of mutant zebrafish and transmission electron microscope was employed to view subcellular structure of photoreceptor cells.Results: A homozygous rpgra mutant zebrafish with c.1675_1678delins21 mutation was successfully constructed. Despite the normal morphological development of the retina at 5 days post-fertilization, visual dysfunction was observed in the mutant zebrafish. Further histological and immunofluorescence assays indicated that rpgra mutant zebrafish retina photoreceptors progressively began to degenerate at 3-6 months. Additionally, the mislocalization of cone outer segment proteins (Opn1lw and Gnb3) and the accumulation of vacuole-like structures around the connecting cilium below the OSs were observed in mutant zebrafish. Furthermore, Rab8a, a key regulator of opsin-carrier vesicle trafficking, exhibited decreased expression and evident mislocalization in mutant zebrafish.Discussion: This study generated a novel rpgra mutant zebrafish model, which showed retinal degeneration. our data suggested Rpgra is necessary for the ciliary transport of cone-associated proteins, and further investigation is required to determine its function in rods. The rpgra mutant zebrafish constructed in this study may help us gain a better understanding of the molecular mechanism of retinal degeneration caused by RPGRORF15 mutation and find some useful treatment in the future.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a lasting threat to public health. To minimize the viral spread, it is essential to develop more reliable approaches for early diagnosis of the infection and immediate suppression of the viral replication. Herein, through computational prediction of SARS-CoV-2 genome and screening analysis of specimens from covid-19 patients, we predicted 15 precursors for SARS-CoV-2-encoded miRNAs (CvmiRNAs) containing 20 mature CvmiRNAs, in which CvmiR-2 was successfully detected by quantitative analysis in both serum and nasal swab samples of patients. CvmiR-2 showed high specificity in distinguishing covid-19 patients from normal controls, and high conservation between SARS-CoV-2 and its mutants. A positive correlation was observed between the CvmiR-2 expression level and the severity of patients. The biogenesis and expression of CvmiR-2 were validated in the pre-CvmiR-2-transfected A549 cells, showing a dose-dependent pattern. The sequence of CvmiR-2 was validated by sequencing analysis of human cells infected by either SARS-CoV-2 or pre-CvmiR-2. Target gene prediction analysis suggested CvmiR-2 may be involved in the regulation of the immune response, muscle pain and/or neurological disorders in covid-19 patients. In conclusion, the current study identified a novel v-miRNA encoded by SARS-CoV-2 upon infection of human cells, which holds the potential to serve as a diagnostic biomarker or a therapeutic target in clinic.

Overfishing and habitat destruction have decimated wild sea cucumber (Apostichopus japonicus) stocks, causing this species to become endangered. Several conservation measures have been implemented to assist in the recovery of A. japonicus. Due to the low efficiency of conventional domestication methods and the current prevalence of bottom-sowing culture in marine ranches, it is urgent to evaluate the genetic diversity and population structure of sea cucumber geographical groups in the natural seas of northern China using genome-wide molecular markers. In this study, six sea cucumber geographical groups were collected from marine ranches in Shandong, Hebei, and Liaoning provinces. A total of 18,191 high-quality genome-wide single nucleotide polymorphisms (SNPs) were identified in 70 A. japonicus individuals using 2b-RAD technology. These SNPs were used to assess the genetic diversity and population structure of the six groups. Compared with previous studies, these six geographical groups showed much lower levels of genetic diversity both among and between groups, with all individuals clustering into one population. These findings demonstrate the necessity of continuous genetic monitoring of A. japonicus in the natural seas of northern China. Furthermore, this study serves as a valuable reference for future genome-assisted breeding and germplasm improvement in this economically critical species.

The quantitative characterization of the thermal conditions in the Tibetan Plateau has long been a focal point of global research. Downward shortwave radiation, as a crucial component, plays an important role in numerous land surface processes while also serving as a significant indicator of the plateau’s thermal state. In order to gain a more comprehensive understanding of the Earth’s radiation budget in the Tibetan Plateau region, this study undertook an evaluation of six radiation products (ISCCP-FH, CERES-SYN, GLASS DSR, Himawari-8, MCD18A1, and ERA5). Two sets of ground measurements (downward shortwave radiation values from 10 CMA sites and 6 sites provided by the National Tibetan Plateau Data Center) in 2015 and 2016 were used as validation data to verify the accuracy of the remote sensing products. The results show that in the Tibetan Plateau region, CERESC products show the highest accuracy among the six data products with a bias (relative bias) of −7.57 W/m2 (3.46%), RMSE (relative RMSE) of 32.77 W/m2 (14.99%), and coefficient of determination of 0.80. Among all products, only the ERA5 products overestimated the value of downward shortwave radiation in the Tibetan Plateau region with a bias (relative bias) of 15.62 W/m2 (7.14%). By employing a spatial resolution upscaling approach, we assessed the influence of varying spatial resolutions on the validation accuracy, with the results indicating minimal impact. Through an analysis of the impact of cloud factors and aerosol factors on the validation accuracy, it is deduced that ERA5, Himawari-8, and MCD18A1 products are significantly influenced by cloud factors, whereas the CERES-SYN product is notably affected by aerosol factors.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), one kind of tick-borne acute infectious disease, is caused by a novel bunyavirus. The relationship between meteorological factors and infectious diseases is a hot topic of current research. Liaoning Province has reported a high incidence of SFTS in recent years. However, the epidemiological characteristics of SFTS and its relationship with meteorological factors in the province remain largely unexplored. Methods Data on reported SFTS cases were collected from 2011 to 2019. Epidemiological characteristics of SFTS were analyzed. Spearman’s correlation test and generalized linear models (GLM) were used to identify the relationship between meteorological factors and the number of SFTS cases. Results From 2011 to 2019, the incidence showed an overall upward trend in Liaoning Province, with the highest incidence in 2019 (0.35/100,000). The incidence was slightly higher in males (55.9%, 438/783), and there were more SFTS patients in the 60–69 age group (31.29%, 245/783). Dalian City and Dandong City had the largest number of cases of SFTS (87.99%, 689/783). The median duration from the date of illness onset to the date of diagnosis was 8 days [interquartile range (IQR): 4–13 days]. Spearman correlation analysis and GLM showed that the number of SFTS cases was positively correlated with monthly average rainfall (r s = 0.750, P

m6A is the most abundant RNA modification of eukaryotic mRNAs and is involved in various physiological and pathological processes. Here the authors show a role for Mettl3-mediated RNA m6A modification in postnatal liver development by regulating the Hnf4a-centered transcriptional network

ObjectivesAiming at the operation support scheduling of carrier-based aircraft, this paper proposes a scheduling optimization algorithm based on apprenticeship learning which can quickly generate a operation support schedule for a carrier-based aircraft fleet. MethodsUsing the apprenticeship learning method, the executed and unexecuted tasks in expert demonstrations are compared in pairs to construct a sample set, and the support task scheduling classifier is trained based on the deck features of aircraft carrier. On this basis, a support task apprenticeship learning algorithm for a carrier-based aircraft fleet is designed and compared with the traditional genetic algorithm （GA） in terms of solving solution, solving time and resource allocation. ResultsThe results show that the operation support schedule obtained by the apprenticeship scheduling algorithm is equivalent to that by the traditional GA, but the rate of convergence is increased nearly fourfold, and the support resources are more evenly distributed. ConclusionsThe apprenticeship scheduling algorithm proposed in this paper can adequately learn from expert experiences and solve the problem of static single-objective carrier-based aircraft support scheduling. As such, this study provides references for further research in the field of dynamic multi-objective carrier-based aircraft support scheduling.

Abstract Background The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC). Methods The mRNA and protein levels of SLC6A14 were detected using TCGA database, real-time polymerase chain reaction, western blot, and tissue microarrays, respectively. Amino acids concentration was determined by LC-MS/MS. Cell proliferation and apoptosis were determined using MTT assay and flow cytometry. Transwell invasion assay and wound healing assay were employed to analyze cell migration and invasion. The protein levels of Akt-mTOR signaling pathway and MMPs proteins were detected by western blot. Results Both of the mRNA and protein levels of SLC6A14 were upregulated in CRC tissues, and the protein levels of SLC6A14 were closely related to the tumor cells differentiation: the higher the expression of SLC6A14 was, the poorer the differentiation of the tumor cells was. Further knockdown SLC6A14 with siRNA or treatment with α-MT in CRC cell lines reduced cell proliferation and migration in vitro and inhibited xenograft tumor growth in vivo. Mechanistically, SLC6A14 was demonstrated to regulate the expression and phosphorylation of Akt-mTOR, which mediates the promoting tumor growth function of SLC6A14. Blockade of SLC6A14 with α-MT inhibited the activation of mTOR signaling. Conclusion SLC6A14 was upregulated in CRC and could promote tumor progression by activating the Akt-mTOR signaling pathway, which may serve as an effective molecular target for the treatment of CRC.

Abstract Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Brain–computer interfaces (BCIs) have garnered extensive interest and become a groundbreaking technology to restore movement, tactile sense, and communication in patients. Prior to their use in human subjects, clinical BCIs require rigorous validation and verification (V&V). Non-human primates (NHPs) are often considered the ultimate and widely used animal model for neuroscience studies, including BCIs V&V, due to their proximity to humans. This literature review summarizes 94 NHP gait analysis studies until 1 June, 2022, including seven BCI-oriented studies. Due to technological limitations, most of these studies used wired neural recordings to access electrophysiological data. However, wireless neural recording systems for NHPs enabled neuroscience research in humans, and many on NHP locomotion, while posing numerous technical challenges, such as signal quality, data throughout, working distance, size, and power constraint, that have yet to be overcome. Besides neurological data, motion capture (MoCap) systems are usually required in BCI and gait studies to capture locomotion kinematics. However, current studies have exclusively relied on image processing-based MoCap systems, which have insufficient accuracy (error: ≥4° and 9 mm). While the role of the motor cortex during locomotion is still unclear and worth further exploration, future BCI and gait studies require simultaneous, high-speed, accurate neurophysiological, and movement measures. Therefore, the infrared MoCap system which has high accuracy and speed, together with a high spatiotemporal resolution neural recording system, may expand the scope and improve the quality of the motor and neurophysiological analysis in NHPs.

Abstract Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), which are all complex metabolic disorders. Selenoprotein S (SelS) is an endoplasmic reticulum (ER) resident selenoprotein involved in regulating ER stress and has been found to participate in the occurrence and development of IR and T2DM. However, the potential role and mechanism of SelS in NAFLD remains unclear. Here, we analyzed SelS expression in the liver of high-fat diet (HFD)-fed mice and obese T2DM model (db/db) mice and generated hepatocyte-specific SelS knockout (SelS H-KO ) mice using the Cre-loxP system. We showed that hepatic SelS expression levels were significantly downregulated in HFD-fed mice and db/db mice. Hepatic SelS deficiency markedly increased ER stress markers in the liver and caused hepatic steatosis via increased fatty acid uptake and reduced fatty acid oxidation. Impaired insulin signaling was detected in the liver of SelS H-KO mice with decreased phosphorylation levels of insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/Akt), which ultimately led to disturbed glucose homeostasis. Meanwhile, our results showed hepatic protein kinase Cɛ (PKCɛ) activation participated in the negative regulation of insulin signaling in SelS H-KO mice. Moreover, the inhibitory effect of SelS on hepatic steatosis and IR was confirmed by SelS overexpression in primary hepatocytes in vitro. Thus, we conclude that hepatic SelS plays a key role in regulating hepatic lipid accumulation and insulin action, suggesting that SelS may be a potential intervention target for the prevention and treatment of NAFLD and T2DM.

Clouds are a critical factor in regulating the climate system, and estimating cloudy-sky Surface Downward Longwave Radiation (SDLR) from satellite data is significant for global climate change research. The models based on cloud water path (CWP) are less affected by cloud parameter uncertainties and have superior accuracy in SDLR satellite estimation when compared to those empirical and parameterized models relying mainly on cloud fraction or cloud-base temperature. However, existing CWP-based models tend to overestimate the low SDLR values and underestimate the larger SDLR. This study found that this phenomenon was caused by the fact that the models do not account for the varying relationships between cloud radiative effects and key parameters under different Liquid Water Path (LWP) and Precipitable Water Vapor (PWV) ranges. Based upon this observation, this study utilized Fengyun-4A (FY-4A) cloud parameters and ERA5 data as data sources to develop a new CWP-based model where the model coefficients depend on the cloud phase and cloud water path range. The accuracy of the new model’s estimated SDLR is 20.8 W/m2 for cloudy pixels, with accuracies of 19.4 W/m2 and 23.5 W/m2 for overcast and partly cloudy conditions, respectively. In contrast, the accuracy of the old CWP-based model was 22.4, 21.2, and 24.8 W/m2, respectively. The underestimation and overestimation present in the old CWP-based model are effectively corrected by the new model. The new model exhibited higher accuracy under various station locations, cloud cover scenarios, and cloud phase conditions compared to the old one. Comparatively, the new model showcased its most remarkable improvements in situations involving overcast conditions, water clouds with low PWV and low LWP values, ice clouds with large PWV, and conditions with PWV ≥ 5 cm. Over a temporal scale, the new model effectively captured the seasonal variations in SDLR.

Due to climate change and human activities, seagrass is in crisis as the coverage of seagrass declines at an accelerated rate globally. In this paper, the severe challenges of seagrass ecosystem were briefly reviewed, including adverse effects of natural factors and human activities on seagrass beds. The research status of pollutants and pollution in seagrass bed ecosystem was reviewed, the future research directions in related fields were proposed as well. The eutrophication in coastal waters and discharge of pollutants such as sulfide, heavy metals, organic matter and microplastics caused by human activities are important reasons for seagrass loss. In addition, environmental stressors lead to reduced immunity and decreased resistance of seagrass to various pathogens, leading to seagrass wasting diseases. Future studies concerning the influence of novel pollutants, i.e., plastic waste on non-native algae, microorganisms and seagrasses, as well as their interrelationships, will be of vital importance. In addition, researches on seagrass wasting diseases and their pathogens should be much accounted in China, to fill in gaps in related fields and improve the response ability to emergent seagrass diseases. In conclusion, this review was proposed to arouse the concern about the seagrass bed pollution, and provide possible enlightening information for the protection and restoration of this significant ecosystem.

Vegetation plays a fundamental role within terrestrial ecosystems, serving as a cornerstone of their functionality. Presently, these crucial ecosystems face a myriad of threats, including deforestation, overgrazing, wildfires, and the impact of climate change. The implementation of remote sensing for monitoring the status and dynamics of vegetation ecosystems has emerged as an indispensable tool for advancing ecological research and effective resource management. This study takes a comprehensive approach by integrating ecosystem monitoring indicators and aligning them with the objectives of SDG15. We conducted a thorough analysis by leveraging global 500 m resolution products for vegetation Leaf Area Index (LAI) and land cover classification spanning the period from 2016 to 2020. This encompassed the calculation of annual average LAI, identification of anomalies, and evaluation of change rates, thereby enabling a comprehensive assessment of the global status and transformations occurring within major vegetation ecosystems. In 2020, a discernible rise in the annual Average LAI of major vegetation ecosystems on a global scale became evident when compared to data from 2016. Notably, the ecosystems demonstrating a slight increase in area constituted the largest proportion (34.23%), while those exhibiting a significant decrease were the least prevalent (6.09%). Within various regions, such as Eastern Europe, Central Africa, and South Asia, substantial increases in both forest ecosystem area and annual Average LAI were observed. Furthermore, Eastern Europe and Central America recorded significant expansions in both grassland ecosystem area and annual average LAI. Similarly, regions experiencing notable growth in both cropland ecosystem areas and annual average LAI encompassed Southern Africa, Northern Europe, and Eastern Africa.

The enzymatic transformation of the sugar moiety of the gypenosides provides a new way to obtain more pharmacologically active components. A gene encoding a family 1 glycosyl hydrolase from Bifidobacterium dentium was cloned and expressed in Escherichia coli. The recombinant enzyme was purified, and its molecular weight was approximately 44 kDa. The recombinant BdbglB exhibited an optimal activity at 35 °C and pH 5.4. The purified recombinant enzyme, exhibiting β-glucosidase activity, was used to produce gypenoside XVII (Gyp XVII) via highly selective and efficient hydrolysis of the outer glucose moiety linked to the C-3 position in ginsenoside Rb1 (G-Rb1). Under the optimal reaction conditions for large scale production of gypenoside XVII, 40 g ginsenoside Rb1 was transformed by using 45 g crude enzyme at pH 5.4 and 35 °C for 10 h with a molar yield of 100%. Furthermore, the anti-inflammatory effects of the product gypenoside XVII and its conversion precursor ginsenoside Rb1 were evaluated by using lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages and the xylene-induced acute inflammation model of mouse ear edema, respectively. Gypenoside XVII showed improved anti-inflammatory activity, which significantly inhibited the generation of TNF-α and IL-6 more effectively than its precursor ginsenoside Rb1. In addition, the swelling inhibition rate of gypenoside XVII was 80.55%, while the rate of its precursor was 40.47%, the results also indicated that gypenoside XVII had better anti-inflammatory activity than ginsenoside Rb1. Hence, this enzymatic method would be useful in the large-scale production of gypenoside XVII, which may become a new potent anti-inflammatory candidate drug.