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Litchi downy blight, caused by the plant pathogenic oomycete Peronophythora litchii, is one of the most devastating diseases on litchi and resulted in huge economic losses. Autophagy plays an essential role in the development and pathogenicity of the filamentous fungi. However, the function of autophagy in oomycetes remain elusive. Here, an autophagy-related protein Atg3 homolog PlAtg3 was identified and characterized in P. litchii. The absence of PlATG3 through the CRISPR/Cas9 gene replacement strategy compromised vegetative growth and sexual/asexual development. Cytological analyses revealed that the deletion of PlATG3 impaired autophagosome formation with monodansylcadaverine (MDC) staining and significantly disrupted zoospore release due to defects of sporangial cleavage with FM4-64 staining. Atg8 is considered to be an autophagy marker protein in various species. Western blot analysis indicated that PlAtg3 is involved in degradation of PlAtg8-PE. Interestingly, PlAtg3 was unable to interact with PlAtg8 in yeast two hybrid (Y2H) assays, possibly due to the absence of the Atg8 family interacting motif (AIM) in PlAtg3. Furthermore, pathogenicity assays revealed that the deletion of PlATG3 considerably reduced the virulence of P. litchii. Taken together, our data reveal that PlAtg3 plays an important role in radial growth, asexual/sexual development, sporangial cleavage and zoospore release, autophagosome formation, and pathogenicity in P. litchii. This study contributes to a better understanding of the pathogenicity mechanisms of P. litchii and provides insights for the development of more effective strategies to control oomycete diseases.

The increasingly frequent storms pose significant threats to the sustainable development of coastal regions, particularly in densely populated and economically vibrant areas. Comprehending the dynamics and intricate mechanisms underlying runoff generation is crucial in the context of climate change and anthropogenic interference. Based on hydro-meteorological and land-use data from 1980 to 2018, this study investigates the runoff variation and its driving factors in the Coastal Chinese Mainland (CCM). The aims of this study are to reveal the temporal and spatial trends of runoff yield, to clarify the sensitivity of runoff in coastal cities to the integrated and individual parameters of climate change and anthropogenic interference, including precipitation (P), potential evapotranspiration (E0), and land cover factor (n), and to support the establishment of spatially tailored adaptation strategies. The results show that: (1) runoff has generally increased over the study period, particularly in regions such as the Yangtze River Delta, Shandong, and Guangxi, while it has decreased in western Liaoning and eastern Guangdong; (2) in the northern CCM with larger aridity index, the land cover factor plays a dominant role in runoff production, while in the wetter southern CCM, precipitation is more influential, and potential evapotranspiration mainly hinders runoff generation all over CCM; (3) urban expansion tends to negatively impact n, while the loss of grasslands and shrinkage of croplands tend to undermine the value of n. To facilitate the achievement of sustainable development goals in the CCM, it is imperative to introduce a more comprehensive and theoretical framework that encompasses the natural, technical, and social dimensions of human-water systems into traditional flood regulation and water resource management. This framework should promote interdisciplinary collaboration from an integrated perspective, to bridge the administrative and watershed boundaries, to effectively address the complex challenges posed by climate change and anthropogenic activities on runoff and water resources in coastal regions, and to enhance the realization of local sustainable development goals (UN SDGs).

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future.

Water-saving irrigation (WI) is a crucial agricultural management with the benefits to save irrigation water, reduce energy consumption, and suppress methane emissions from paddy lands. Classifying WI practices from traditional flooding irrigation (FI) is a key component in detecting the rice irrigation status, which is significant to estimate the total agriculture-associated greenhouse gas emissions. In this study, we developed an automatic method to map irrigation regimes across Chinese paddy lands. First, we used seven variables related with irrigation facility or vegetation cover as proxy to generate representative WI and FI samples. Besides, we composited 123 features of optical bands and synthetic aperture radar from MODIS and Sentinel-1 data. Then, we trained a random forest model for each province with these samples. Finally, we applied the trained model to generate maps of WI/FI practices at 500 m resolution. Comparisons of the resultant maps with census data indicated highly accurate estimations of the WI area at a city- or province-level, with a R2 higher than 0.92. The overall accuracy of the classification was approximately 0.73, as validated through ground truth samples. Additionally, we also conducted a data quality analysis and confirmed the classification results were reliable in main rice production area of China. With the push towards carbon neutrality goals and the increasing demand for clean management practices, we developed and demonstrated an advanced method to produce near real-time maps of irrigation regimes and provide crucial data support for agricultural emissions reduction and irrigation management decisions.

Objective: The aim of this study is to elucidate the underlying mechanism through which glial cell line-derived neurotrophic factor (GDNF) improves cognitive deficits in adults resulting from neonatal surgical interventions. Methods: Newborn Sprague–Dawley rats, regardless of gender, were randomly allocated into seven groups on postnatal day 7 as follows (n=15): (1) Control group (not subjected to anesthesia, surgery, or any pharmaceutical interventions); (2) GDNF group (received intracerebroventricular injection of GDNF); (3) Surgery group (underwent right carotid artery exposure under anesthesia with 3 % sevoflurane); (4) Surgery plus GDNF group; (5) Surgery plus GDNF and type II JAK inhibitor NVP-BBT594 (BBT594) group (administered intraperitoneal injection of BBT594); (6) BBT group; and (7) Surgery plus BBT group. Starting from postnatal day 33, all rats underwent Barnes maze and fear conditioning tests, followed by decapitation under sevoflurane anesthesia for subsequent analyses. The left hemibrains underwent Golgi staining, while the right hemibrains were used for hippocampal protein extraction to assess Protein kinase Mζ (PKMζ) and Kalirin expression through western blotting. Results: GDNF demonstrated a mitigating effect on spatial learning and memory impairment, as well as context-related fear memory impairment, reductions in dendritic total lengths, and spinal density within the hippocampus induced by surgical intervention. Notably, all of these ameliorative effects of GDNF were reversed upon administration of the RET inhibitor BBT594. Additionally, GDNF alleviated the downregulation of protein expression of PKMζ and Kalirin in the hippocampus of rats subjected to surgery, subsequently reversed by BBT594. Conclusion: The effective impact of GDNF on learning and memory impairment caused by surgical intervention appears to be mediated through the RET pathway. Moreover, GDNF may exert its influence by upregulating the expression of PKMζ and Kalirin, consequently enhancing the development of dendrites and dendritic spines.

Objectives: The study aimed to investigate the relationship between blood pressure (BP) levels and mortality among critically ill older adults in the intensive care unit (ICU), establish optimal BP target for this population, and assess the mediating effect of severe malnutrition on BP-related mortality. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.2 database, focusing on critically ill patients aged 80 years and older. The analysis included various BP parameters, such as systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Results: The study cohort comprised 14,660 critically ill patients, of whom 1558 (10.6 %) experienced ICU mortality and 2493 (17.0 %) experienced in-hospital mortality. Lower BP levels (SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤65 mmHg), were associated with an increased risk of both ICU and in-hospital mortality. Notably, only reduced SBP levels were linked to a higher risk of 1-year mortality, with an adjusted hazard ratio 1.13 (95 % confidence interval 1.05 to 1.23). Additionally, severe malnutrition was identified as a mediator in the relationship between low BP levels and ICU mortality, with BP levels positively correlated with prognostic nutritional indexes. Conclusion: Among critically ill older adults, lower BP levels are significantly associated with higher risks of ICU and in-hospital mortality, while reduced SBP levels are linked to 1-year mortality. These findings emphasize the importance of assessing nutritional status in older ICU patients with low BP levels to potentially mitigate mortality risk.

Aims: The relationship between sarcopenia and cognitive impairment in older adults remains contentious. This study investigates this association and examines the long-term prognosis for individuals with both conditions. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, this study focuses on the correlation between sarcopenia and cognitive impairment, as well as the extended prognosis for individuals managing these conditions. Results: The study cohort comprised 2890 participants, with 648 (22.4 %) diagnosed with sarcopenia. Multivariable logistic regression analysis identified a significant association between sarcopenia and an increased risk of cognitive impairment (adjusted odds ratio [aOR]: 1.68, 95 % confidence interval [CI]: 1.30–2.17). Over a median follow-up period of 48 months, 200 individuals (6.9 %) succumbed to cardiovascular and cerebrovascular diseases (CCVDs), including hypertension, congestive heart failure, coronary artery disease, and stroke, as well as Alzheimer's disease (AD). Participants had comorbid conditions such as CCVDs and diabetes mellitus. Kaplan–Meier survival analysis and the Cox proportional hazards model indicated that individuals with both sarcopenia and cognitive impairment had the highest mortality risk from CCVDs and AD (adjusted hazard ratio [aHR]: 2.73, 95 % CI: 1.48–5.02). Individuals with sarcopenia and comorbidities exhibited a higher mortality risk from CCVDs or AD compared to those without sarcopenia but with comorbidities (aHR: 2.71, 95 % CI: 1.37–5.37). Conclusion: Sarcopenia is independently associated with cognitive impairment. Older adults with both sarcopenia and cognitive impairment or concurrent comorbidities face increased mortality risks from CCVDs or AD compared to their healthy counterparts. Clinical implication: • Sarcopenia is associated with cognitive impairment. • Cognitive impairment and comorbidities increased the risk of mortality from CCVDs and AD for sarcopenia patients.

In the suspension cage culture process, regular cleaning to remove epiphytic organisms from the cage is essential to prevent economic losses due to the sinking of the cage. However, after cleaning, many of attachments from the suspension cage accumulate in the tidal flats, causing environmental pollution and resource wastage. Moreover, because sea cucumbers (Apostichopus japonicus) are sedimentary food organisms, sea mud is typically added to their feed to varying degrees. However, long-term excavation of sea mud can destroy the marine environment. Therefore, developing an alternative new raw feed material to replace sea mud in sea cucumber feed is necessary to promote sustainable development of the A. japonicus aquaculture industry. The aim of this study was to explore the feasibility of using fermented attachments of suspension cage (FASC) as a raw feed material for A. japonicus. Different FASC concentrations (0, 25, 50, 75, and 100 %) were used in A. japonicus feed for 60 d. Replacing Sea mud with 100 % FASC significantly improved sea cucumber growth, reduced the feed coefficient, significantly increased the activity of intestinal digestive enzymes, improved intestinal structure, and enriched intestinal microbiome diversity. Furthermore, expressions of growth genes mapk-7 and fgfr-1 significantly increased in the 100 % FASC treatment compared with that in the control, and that of negative growth regulator gene gdf-8 was inhibited. The results suggested the potential of FASC as a new raw feed material for A. japonicus.

Owing to their remarkable thermal–hydraulic performance, vapor chambers have diverse applications, especially for cooling electronic devices. However, the performances of circular and noncircular pillars throughout the entire vapor chamber under identical wick volume conditions have been compared in very few studies. In this study, a series of noncircular pillar arrays featuring biomimetic tree-like fractal networks is introduced. The incorporation of fractal pillars significantly enhances the thermal–hydraulic performance of the vapor chamber because the gas–liquid interface area is extended. Compared to a vapor chamber with circular pillars, the maximum condensation surface temperature difference, total thermal resistance, and liquid pressure drop of this vapor chamber with fractal pillars are reduced by up to 57.8 %, 13.8 %, and 10.9 %, respectively. In particular, with large branch levels and pillar diameters, the fractal structure is pivotal for boosting the overall performance. When the number of pillars is increased, the fractal structure's impact on the thermal performance reaches a limit, whereas its boosting effect on the flow performance weakens. This study is a pioneering exploration of the application of stretched geometries in pillar-type vapor chambers, with fractal pillars utilized in showcase demonstrations.

Summary: Here, we present a protocol for conducting bibliometric analysis in biomedicine using CiteSpace and VOSviewer. We describe the steps for extracting data from Web of Science, data cleaning, and preprocessing. We then detail procedures for identifying research trends and collaboration networks by visualizing data with CiteSpace; mapping co-authorship, co-citation, and keyword co-occurrence using VOSviewer; and analyzing highly cited literature to identify key publications and trends. Finally, we outline techniques for interpreting the visualizations to draw meaningful conclusions about the research landscape.For complete details on the use and execution of this protocol, please refer to Li et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

This study explores the role of disulfidptosis in monocytes and its relation to postmenopausal osteoporosis (PMOP). Using single-cell RNA sequencing and microarray assays, we identified key genes: LONRF1, ACAP2, IPO9, and PGRMC2. Through differential analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning, these genes were linked to PMOP. Functional enrichment and ROC curve analysis demonstrated their effectiveness in distinguishing postmenopausal fracture patients from healthy individuals. Notably, PGRMC2 exhibited significant expression differences, highlighted by a notable Area Under the Curve (AUC) value of 0.665. Further investigation involved Western blotting and immunohistochemical assays, revealing decreased PGRMC2 expression in ovariectomized (OVX) mice. This decrease was consistent across both experimental methods, emphasizing PGRMC2's role in PMOP. Moreover, PGRMC2 was predominantly present in macrophages compared to monocytes within bone tissue and was significantly located in bone marrow mesenchymal stem cells (BM-MSCs) in PMOP patients. It was also abundantly found in osteoblasts and adipocytes. Additionally, a Mendelian randomization analysis using the TwoSampleMR R package, with data from decode and GWAS databases, was conducted. This analysis showed a significant impact of PGRMC2 on osteoporosis risk (p = 0.0048, OR = 0.6836), suggesting a potential protective effect against the disease. Our results suggest that PGRMC2 may facilitate the differentiation of monocytes into macrophages in bone tissue, influencing the behavior of BM-MSCs. This, in turn, could impact the progression and severity of PMOP. The study provides new insights into the molecular mechanisms underlying postmenopausal osteoporosis and highlights the potential of PGRMC2 as a therapeutic target or biomarker for this condition.

We present an estimate of the yield of hard probes expected for collisions of the isobars 4496Ru and 4096Zr at collision energies reachable at RHIC and the LHC. These yields are proportional to the number of binary nucleon-nucleon interactions, which is characteristically different due to the presence of the large neutron skin in 4096Zr. This provides an independent opportunity to measure the difference between the neutron skin of 4496Ru and 4096Zr, which can provide an important constraint on the Equation of State of cold neutron-rich matter.

Summary: Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

The first measurement of two-particle angular correlations for charged particles with LEP-II data is presented. The study is performed using archived hadronic e+e− data collected by ALEPH at center-of-mass energies up to 209 GeV, above the W+W− production threshold, which provide access to unprecedented charged-particle multiplicities and more complex color-string configurations if compared to previous measurements at LEP-I energies. An intriguing long-range near-side excess is observed in the correlation function measured with respect to the thrust axis in the highest multiplicity interval (Ntrk≥50). Such a structure is not predicted by the Monte-Carlo simulation. The harmonic anisotropy coefficients vn, which result from the Fourier expansion of the two-particle correlation functions, were also measured for the first time in e+e− data, and compared to pythia 6 predictions and to the results obtained in proton-proton collisions. The results presented in the Letter provide novel experimental constraints on the formation of collective phenomena in point-like e+e− collisions.

Summary: Research on returned samples can provide ground truth for the study of the geological evolution history of the Moon. However, previous missions all collected samples from the near side of the Moon, which is significantly different from the far side of the Moon in terms of the thickness of the lunar crust, magma activity, and composition. Therefore, the samples from the far side of the Moon are of great significance for a comprehensive understanding of the history of the Moon. China’s Chang’e-6 (CE-6) probe has successfully landed on the lunar far side and will return samples in the coming days. With the precise location of the CE-6 landing site, a detailed analysis of the geological background is conducted in this research. The landing site of CE-6 is within the Apollo crater, which is inside the largest impact basin on the Moon, i.e., the South Pole-Aitken (SPA) basin. According to the numerical simulation of the formation process of the SPA basin, CE-6 landed at the edge of the SPA impact melting zone, which is presumably composed of impact melt of the lunar mantle. The Apollo crater subsequently excavated deep material again, which constitutes the basement of the CE-6 landing area. Later, erupted basalt covered these basement rocks, and they also constitute the main source of the CE-6 samples. Based on the dating method of crater size-frequency distribution, we find that the basalt is ∼2.50 Ga. The CE-6 samples also possibly contain basement rocks as excavated and ejected by craters, and they can provide crucial information for our understanding of lunar geological history along with the basalt samples.

Nowadays, the issue of electromagnetic pollution has become increasingly prominent, underscoring the critical importance of developing high-performance microwave absorbers. This study put forwards the synthesis process of two-dimensional (2D) FeCo/Co8FeS8/C carbon nanosheets, wherein CoSO4 and FeCl3 serve as inorganic salt templates, and dopamine functions as the carbon source. FeCo alloy nanoparticles and Co8FeS8 nanoparticles are loaded on the surface of the carbon layer. 2D structure forms the conductive network, which proves advantages in establishing efficient electronic channels and minimizing conduction losses. The carbon component increases the dielectric constant of the composite and improves its impedance matching, and the FeCo alloy provides a certain ML. The synergistic effect between these components significantly contributes to the exceptional microwave absorption performance of the composites. Accordingly, the minimum reflection loss (RLmin) of FeCo/Co8FeS8/C composite reaches −47.4 dB, its effective absorption bandwidth (EAB) reaches 5.3 GHz. In particular, CST confirms that radar cross-section reduction value of FeCo/Co8FeS8/C composite can reach 20.2 dB m2 in the range of −90°

Bacillus cereus is a common foodborne pathogen, and its formation of strongly resistant spores renders the pathogen difficult to eliminate completely using traditional sterilization methods. This study aimed to investigate the inactivation effect of ultrasound combined with ultraviolet treatment on Bacillus cereus spores and the underlying mechanism. The inactivation effect, surface properties, structural changes, heat resistance and germination characteristics, as well as Raman spectroscopy results, were examined. It was found that 20 min of ultrasound combined with ultraviolet treatment resulted in the inactivation of 4.61 log CFU/mL. Structurally, the exosporium and coat were damaged. Moreover, the permeability of the inner membrane increased. Damage to the spores’ structure reduced the heat resistance. Raman spectroscopy indicated that the DNA and proteins were severely damaged.In conclusion, ultrasound combined with ultraviolet treatment demonstrated a synergistic inactivation effect on Bacillus cereus spores by destroying the external structures of the spores, as well as the internal DNA and other substances. This study has preliminarily elucidated the mechanism of ultrasound combined with ultraviolet treatment regarding the inactivation of Bacillus cereus spores, providing a theoretical foundation for its application in food sterilization.

Summary: Rime optimization algorithm (RIME) encounters issues such as an imbalance between exploitation and exploration, susceptibility to local optima, and low convergence accuracy when handling problems. This paper introduces a variant of RIME called IRIME to address these drawbacks. IRIME integrates the soft besiege (SB) and composite mutation strategy (CMS) and restart strategy (RS). To comprehensively validate IRIME’s performance, IEEE CEC 2017 benchmark tests were conducted, comparing it against many advanced algorithms. The results indicate that the performance of IRIME is the best. In addition, applying IRIME in four engineering problems reflects the performance of IRIME in solving practical problems. Finally, the paper proposes a binary version, bIRIME, that can be applied to feature selection problems. bIRIMR performs well on 12 low-dimensional datasets and 24 high-dimensional datasets. It outperforms other advanced algorithms in terms of the number of feature subsets and classification accuracy. In conclusion, bIRIME has great potential in feature selection.

In order to study the influence of ventilation parameters on the ventilation of plateau highway construction tunnels, a highway tunnel construction section in Yunnan is taken as the research background, and Fluent software is used for simulation. The results of the study show that: under the conditions of press-in ventilation, the wind speed in the center of the vortex area in the wind flow field is smaller than the wind speed in the surrounding area, and with the diffusion of the flow field, the average wind speed in the tunnel section gradually decreases, and ultimately stabilizes at the level of 0.5 m/s. After blasting, the dust mass concentration on the return side of the tunnel is higher than that on the duct side. Dust with a particle size of 30 μm or more settled rapidly within 100 m from the boring face, while dust with a particle size of 30 μm or less gradually diffused outward under the action of the wind flow. In the vicinity of the tunnel boring face, reducing the distance from the air outlet to the boring face and increasing the air velocity can improve the dust removal effect. This conclusion can provide theoretical basis and certain guidance for the evolution of dust and dust prevention in the tunnel construction process in plateau area.

Background: Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field. Methods: Publications related to CIN (2013–2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords. Results: In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years. Conclusion: Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.

The traditional ‘nine-steam-nine-bask’ method of Polygonatum cyrtonema Hua (PCH) has been controversial due to nine-cycle requirement. This study employed in vitro digestion to investigate changes in bioactive substances, bioaccessibility, and antioxidant activity of PCH at different steam-bask times. It revealed the correlation between bioactive substances and antioxidant activity in PCH, and validated the ‘nine-steam-nine-bask’ process’s efficacy. In undigested samples, total phenol content (TPC), reducing sugar content (RSC), and DPPH and ABTS activities increased with more cycles, peaking in the nine-cycle sample at 7.627 mg GAE/g DW, 465.333 mg GE/g DW, 17.698, and 36.986 μmol VCE/g DW. Similar trends were observed throughout digestion. Total sugar (755.96 mg GE/g DW) and total saponin content (1.35 mg DE/g DW) plateaued during gastrointestinal digestion. Correlation analysis further revealed close relationships between bioactive substances and antioxidant activity. Multivariate statistical analysis confirmed that nine cycles maximized the distinction between steam-bask and non-steam-bask PCH.

Understanding the production of non-volatile particulate matter (nvPM), which is composed primarily of soot, is critical not only for reducing emissions but also for improving engine performance. While there has been significant prior work studying the fundamentals of soot formation, there is significantly less work that investigates soot formation with realistic aeroengine geometries, injectors, and fuels in high pressure conditions. In this work, soot production in a three-sector rich-quench-lean (RQL) aeroengine combustor is studied with Jet A fuel. Global equivalence ratios ranging of 0.10 to 0.20 and pressures ranging from 2.7 to 6.9 bar absolute (40 to 100 psia) are tested. In order to characterize in-situ soot production near the fuel injectors, two-dimensional laser-induced incandescence is utilized to estimate single-shot and average soot volume fractions. Time-resolved laser-induced incandescence is then used to create single camera and single laser-shot incandescence decay time images in order to infer how soot particle sizes evolve. Results show a significant increase in soot production at higher global equivalence ratios and higher pressures. Incandescence decay times, however, do not change significantly over the same range of conditions. These measurements can not only help understand soot distributions in practical RQL systems but also help improve future aeroengine combustor designs.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Enhancing teaching sufficiency is crucial because low teaching efficiency has always been a widespread issue in ideological and political theory course. Evaluating data on the course is obtained from a freshmen class of 2022 using questionnaires. The data is organised and condensed for mining and analysis. Subsequently, an intelligent artificial multi-verse optimizer (AMVO) method s developed to predict the effect of ideological and political theory course. The proposed AMVO approach was tested against various cutting-edge algorithms to demonstrate its effectiveness and stability on the benchmark functions. The experimental results indicated that AMVO ranked first among the 23 test functions. Furthermore, the binary AMVO enhanced k-nearest neighbour classifier had excellent performance in the art ideological and political theory course in terms of error rate, accuracy, specificity and sensitivity. This model can predict the overall evaluation attitude of freshmen towards the course based on the dataset. In addition, we can further analyse the potential correlations between factors that enhance the intellectual and political content of the course. This model can further refine the evaluation of ideological and political courses by teachers and students in our school, thereby achieving the fundamental goal of moral cultivation.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-β. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-β in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rβ）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.

Background: Hepatocellular carcinoma (HCC) is a common cancer that is increasingly becoming a global health problem and a major public health concern. In order to improve patient outcomes, additional biomarkers and targets must be explored. Ubiquitination-related genes (URGs), as tumor regulators, exhibit multiple functions in tumor development. Our objective was to examine the influence of URGs on the prognosis of patients with HCC. Methods: By utilizing unsupervised cluster analysis, we were able to identify URGs in the database and create a risk score profile for predicting the prognosis of patients with HCC. The model's clinical application was explored using subject operating characteristic curves, survival analysis, and correlation analysis. We additionally examined the variances in clinical traits, immune infiltration, somatic genetic alterations, and responsiveness to treatment among high- and low-risk populations identified by the prognostic model. Scores for immune cell infiltration and immune-related pathway activity were determined by performing ssGSEA enrichment analysis. Additionally, to investigate potential mechanisms, we utilized GO, KEGG and GSVA analyses. Results: We developed a risk scoring model that relies on genes associated with ubiquitination. As the risk score increased, the malignancy and prognosis of the tumor worsened. The high-risk and low-risk groups exhibited notable disparities in relation to the immune microenvironment, genes associated with immune checkpoints, sensitivity to drugs, and response to immunotherapy. Conclusion: The utilization of a risk model that relies on genes associated with ubiquitination can serve as a biomarker to assess the prognosis of patients with HCC, and aid in the selection of suitable therapeutic agents.

Background/Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality, and early prediction is critical to reduce the deaths of ACLF patients. To date, however, the prognostic accuracy of current models for ACLF is unsatisfactory, particularly, in patients with hepatitis B virus (HBV) infection. This study aims to develop novel prognostic models based on the dynamic changes in variables to predict the short-term mortality of HBV-associated ACLF (HBV-ACLF). Methods: A retrospective cohort study was conducted, with the population comprised in whom ACLF was confirmed.319 patients were enrolled and their clinical data were collected on Days 1 and 7 following hospital admission. Univariate and multivariate analyses were performed to identify risk factors for 28 and 90-day mortality. The dynamic alterations in the risk factors were further analyzed, and Days 1 and 7 prognostic models were constructed. Receiver operating characteristic (ROC) analysis were used to identify and compared the predictors of prognosis among our model. Results: Univariate and multivariate analyses revealed significant risk factors at Days 1 and 7, which when combined with the clinically important parameters, were used to establish the Days 1 and 7 prognostic models. For 28-day mortality, the predictive accuracy of the Day 1 prognostic model was significantly higher than that of the albumin-bilirubin (ALBI) model. For 90-day mortality, the predictive accuracy of the Days 1 and 7 prognostic models was significantly higher than that of the Model of End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), and ALBI prognostic models. Conclusions: The prognostic models established in this study were superior to the existing prognostic scoring systems to accurately predict short-term mortality, and therefore, could be potential novel prognostic tools for HBV-ACLF.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

At present, surgical resection is the most effective method for the treatment of gastric cancer. However, death caused by inoperable metastasis is still very common, despite research in this area. The mechanisms underlying the occurrence, development, and metastasis of gastric cancer are not fully understood. Ezrin, a plasma membrane-microfilament junction participates in a variety of cellular activities and is closely related to tumorigenesis and development. Few studies have explored the relationship between the tumor immune microenvironment and ezrin expression in gastric cancer. In this study, we used proteomic techniques to analyze the differentially expressed proteins between the gastric cancer cell lines MKN-45 and HGC-27 and screened ezrin as the target protein. We collected patient information from The TCGA and GEO databases, and the results showed that ezrin was positively correlated with adverse clinical features. We further explored the relationship between ezrin expression levels, immune microenvironment, and genomic changes. We found that ezrin was involved in immune regulation and genomic instability in gastric cancer. When the expression of ezrin is high, immune cell infiltration also increases. We also predicted that ezrin is closely related to immunotherapy and chemosensitivity. Single-cell transcriptome data showed that the ezrin gene was mainly expressed in B cells and epithelial cells, and the expression of EZR in these epithelial cells was positively correlated with the epithelial-mesenchymal transformation pathway and Pi3k-AKT pathway score. Through functional verification of the stably transfected cell line constructed by lentivirus, the results of the liver metastasis model in nude mice suggested that high expression of ezrin leads to the formation of more metastatic foci. In summary, our results clarify the prognostic, immunological, and therapeutic value of ezrin in gastric cancer and provide a theoretical basis for more accurate treatment.

Psoriasis is a common chronic inflammatory skin disease, which has seriously affected human health. Berberine is a plant alkaloid with significant anti-inflammatory effect. In this study, we aimed to determine whether topical application of berberine could ameliorate skin inflammation in psoriasis and explore the potential molecular mechanism. Imiquimod (IMQ)-induced psoriasis-like dermatitis in mice was firstly used to reveal the potential pathogenic mechanism. The transcriptome analysis showed that Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) signaling pathway was significantly enriched in IMQ-induced dermatitis, which included the key genes such as Janus kinase 1 (JAK1), Interleukin-2 (IL2), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) and Signal transducer and activator of transcription 1 (STAT1). Network pharmacology and molecular docking then predicted that topical berberine may treat psoriasis by JAK-STAT signaling pathway, especially act on JAK1, IL2, PIK3CA and PIK3CB. Experimental studies in vivo further demonstrated that topical application of berberine could ameliorate IMQ-induced psoriasis-like skin inflammation by suppressing JAK-STAT signaling pathway. In addition, experimental studies in vitro showed that berberine could directly act on and enter into human immortalized keratinocytes (HaCaT cells). Meanwhile, berberine may inhibit the hyperproliferation and proinflammatory functions of HaCaT cells induced by Interferon-gamma (IFN-γ) via suppressing JAK1/STAT1 signaling pathway. In conclusion, this study suggested that berberine may be a promising topical agent to ameliorate skin inflammation in psoriasis.

Understanding how the complexities of biodiversity are maintained on islands has long been one of the central issues studied in conservation biology. With the global onset of anthropogenically driven biodiversity changes, the influence of anthropogenic activities challenges the applicability of the widely accepted Equilibrium Theory of Island Biogeography (ETIB). This study aimed to test how island area, isolation (MD: distance to the mainland, and ND: distance to the nearest island), and human activities (habitat heterogeneity, and proportion of road area relative to island area to refer to the human impact on island) separately and jointly affect the species diversity of vascular plants. The number of plant species with different growth forms (woody plants, herbs, and lianas) was calculated on 35 islands in Sanyang Wetland, which is a human-dominated wetland near the highly populated city of Wenzhou, China. We also evaluated the relative importance of these variables on the number of species using a random forest analysis. The number of species increased with increasing island area and habitat heterogeneity and decreased with increasing isolation for different growth forms. A significant, positive relationship was observed between the number of species and the proportion of road area for herbs, but not for woody plants and lianas. Habitat heterogeneity was the most important predictor for all plants, the proportion of road area was the most important predictor for herbs, and MD was the most important predictor for woody plants and lianas. These results indicate that ETIB remains relevant in the context of human disturbance, but the relative importance of ecological processes on species diversity differs significantly among plant growth forms. Therefore, we should consider plant functional groups when testing multifactorial effects on species diversity on human-dominated islands.

In the detection of metal defects by ultrasonic Lamb waves, the commonly used medical coupling agent is volatile, poor stability, and the coupling effect is easily affected. It is vital to find the coupler materials with better performance. This paper develops sodium alginate hydrogel and acrylamide hydrogel with higher curing degree, and compares them with deionized water and medical coupling agent. At the same time, epoxy glue and organic silicone, which commonly used as adhesives in the aerospace field are selected for performance research. Firstly, analyzing FTIR spectra of the three hydrogels. The results showed that the hydrogel composition are correct and subsequent experiments are reliable. Secondly, the performance characteristics of 6 couplings are studied from 5 aspects of acoustic impedance, ultrasonic energy transfer efficiency, stability, temperature characteristics and oxidation resistance. The results show that the acrylamide gel developed in this paper has higher viscosity and stability than the medical coupling agent, and has a wider application. Based on the five performance studies, it can be concluded that in the measurement environment of long-term fixed sensors in the industrial and aerospace fields, organic silicone can not only play the role of bonding sensors and insulation, but have the advantages of strong stability, high ultrasonic energy transfer efficiency, temperature tolerance, oxidation resistance, etc. It is the optimal coupling material in ultrasonic testing for complex environments. The research in this paper provides a reference for the selection of optimal coupling agent materials for more complex applications, which has important engineering significance.

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

Background: Obesity, which is associated with excessive accumulation of body fat, is emerging as a new public health problem. Bioelectrical impedance analysis (BIA) is a non-invasive and straightforward method to analyze body composition, providing a more accurate estimate of obesity than the commonly used body mass index. The primary objective of this study was to examine the potential impact of Helicobacter pylori (H. pylori) infection on body fat percentage in a population using cross-sectional and cohort studies. Methods: A population of people who underwent physical examinations at Taizhou Hospital between 2017 and 2022 was included. The participants underwent various tests, including urea breath test, hematological examination, and anthropometric measurement, in addition, their body fat percentage was determined through the use of BIA. Univariate and multifactorial regression analyses were conducted to identify factors associated with excess body fat. Results: There was a difference in body fat percentage between H. pylori positive and negative populations. The population was divided into young and middle-aged and elderly according to age, and H. pylori infection was found to differ only in the middle-aged and elderly population. Multifactorial logistic regression showed that H. pylori infection remained associated with excess body fat in the middle-aged and elderly population. A subsequent cohort study confirmed the association of persistent H. pylori infection with excess body fat in the population. Conclusion: H. pylori was negatively associated with excess body fat in middle-aged and elderly populations, and long-term H. pylori infection has a negative effect on body fat in people.

Ulcerative colitis (UC) is an idiopathic, chronic, and progressive inflammatory set of conditions that affects the colonic mucosa. Natural polyphenols are well documented for their excellent antioxidant properties and have obvious advantages in the strategy of anti-oxidation treatment of UC. However, the poor water solubility, low bioavailability, and unstable nature have hindered their clinical application. Therefore, we efficiently encapsulated bioactive polyphenol epigallocatechin gallate (EGCG) with poly(N-vinylpyrrolidone) (PVP) via reliable intermolecular hydrogen-bonded interactions, and conjugated polysaccharide chondroitin sulfate (CS) with excellent gastrointestinal stability and CD44 active targeting capability onto the surface to achieve targeted delivery (EPC). The obtained EPC system showed an average diameter of 54 nm, monodisperse size distribution, and negatively charged surface. In vitro studies demonstrated the obvious reactive oxygen species (ROS)-scavenging and anti-inflammatory abilities of the EPC system. After oral administration, EPC system localized in the inflamed colon and effectively alleviated the symptoms in dextran sulfate sodium salt (DSS)-induced UC mice. Specifically, the EPC system down-regulated the expression of inflammatory cytokines, up-regulated the expression of tight junction-associated proteins to restore intestinal barrier, and modulated the gut microbiota. This oral drug delivery system with a simple self-assembling process may pave new strategy for polyphenol-based therapy in UC.

Hydrogen sulfide (H2S) is a toxic, essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter. These studies have mainly focused on the production and pharmacological side effects caused by H2S. Therefore, effective strategies to remove H2S has become a key research topic. Furthermore, the development of novel nanoplatforms has provided new tools for the targeted removal of H2S. This paper was performed to review the association between H2S and disease, related H2S inhibitory drugs, as well as H2S responsive nanoplatforms (HRNs). This review first analyzed the role of H2S in multiple tissues and conditions. Second, common drugs used to eliminate H2S, as well as their potential for combination with anticancer agents, were summarized. Not only the existing studies on HRNs, but also the inhibition H2S combined with different therapeutic methods were both sorted out in this review. Furthermore, this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail. Finally, potential challenges of HRNs were proposed. This study demonstrates the excellent potential of HRNs for biomedical applications.

Summary: Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway.Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience

Background: Sex differences in health status and life expectancy are widely accepted to exist. The mechanisms underlying it are still poorly understood. In this study, we aimed to clarify the influences and contributions of sex on the gut microbiome in healthy centenarians and to explore the different roles played by the gut microbiome in healthy aging between the sexes. Results: Taking covariates of different dimensions into account (social demographics, anthropometry, the activities of daily living, dietary structure, mental state, blood tests, lifestyle and disease history), our data showed that sex was one of the most significant covariates affecting the gut microbiome of healthy centenarians at both the species and Kyoto Encyclopedia of Genes and Genomes Orthology (KO) levels. The beta diversity between the sexes were significantly different (Adonis test: p = 0.011, R2 = 0.031), and the male centenarians had a greater alpha diversity than the females (Simpson and Shannon test: P

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or

Coal fly ash (CFA), a byproduct of coal combustion, is a hazardous industrial solid waste. Its excessive global production, coupled with improper disposal practices, insufficient utilization and limited awareness of its inherent hazards, poses a significant threat to both ecological environment and human health. Based on the physicochemical properties of CFA and its leachates, we elucidate the forms of CFA and potential pathways for its entry into the human body, as well as the leaching behavior, maximum tolerance and biological half-life of toxic elements present in CFA. Furthermore, we provide an overview of current strategies and methods for mitigating the leaching of these harmful elements from CFA. Moreover, we systemically summarize toxic effect of CFA on organisms across various tiers of complexity, analyze epidemiological findings concerning the human health implications resulting from CFA exposure, and delve into the biotoxicological mechanisms of CFA and its leachates at cellular and molecular levels. This review aims to enhance understanding of the potential toxicity of CFA, thereby promoting increased public awareness regarding the disposal and management of this industrial waste.

Summary: Tissue inhibitors of metalloproteinase (TIMPs) play a pivotal role in regulating extracellular matrix (ECM) dynamics and have been extensively studied in vertebrates. However, understanding their evolution across invertebrate phyla is limited. Utilizing the high-quality Pteria penguin genome, we conducted phylogenomic orthology analyses across metazoans, revealing the emergence and distribution of the TIMP gene family. Our findings show that TIMP repertoires originated during eumetazoan radiation, experiencing independent duplication events in different clades, resulting in varied family sizes. Particularly, Pteriomorphia bivalves within Mollusca exhibited the most significant expansion and displayed the most diverse TIMP repertoires among metazoans. These expansions were attributed to multiple gene duplication events, potentially driven by the demands for functional diversification related to multiple adaptive traits, contributing to the adaptation of Pteriomorphia bivalves as stationary filter feeders. In this context, Pteriomorphia bivalves offer a promising model for studying invertebrate TIMP evolution.

While promoting the rapid development of social economy, new urbanization has brought great pressure to the ecological environment. It is of great significance to explore the interaction mechanism between ecological environment and new urbanization for the sustainable development of metropolitan area. The metropolitan area of Nanchang in China was taken as the research area, and based on remote sensing, meteorological and social statistics data, and considering the functions, structures and effects of urban, agricultural and ecological spaces as well as the realistic demands of new urbanization construction, this research constructed “natural foundation-structure-coerce-benefit” (NSCB) and “land use-economic-population-infrastructure-public service” (LEPIP) comprehensive assessment models to quantitatively analyze the spatial and temporal heterogeneity, spatial correlation and interaction strength of ecological quality and new urbanization level in the study area from mesoscopic and microscopic perspectives by using spatial analysis software such as ENVI, ArcGIS, Fragstats, Geoda and Geodetector. The results showed that the ecological environment quality and urbanization level of the land space in the study area were improved from 2005 to 2018, and the overall gap within the region was gradually reduced. The spatial relationship between land use efficiency and ecological quality was “synergistic-trade-off-synergistic”. The economic development level and ecological quality showed a gradually enhanced synergistic relationship, and the population urbanization, infrastructure construction and ecological quality showed an “N” type synergistic relationship. The results of interaction intensity showed that the combined effects of population urbanization, public service guarantee, land use efficiency and economic development had a great impact on the spatial heterogeneity of territorial ecological quality in the study area. Finally, we suggest that the urbanization construction in the study area should strengthen the industrial agglomeration effect, improve the efficiency of land output, build a good urban ecological network, and promote the coordinated and healthy development of natural resources and urban construction. The results of this study can provide scientific basis for the precise formulation of spatial planning, ecological restoration and spatial collaborative development strategies in the study area, and provide reference experience for the coordinated development of natural environment and social economy in other metropolitan areas and urban agglomerations.

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

Clinical trials play a critical role in drug development which involves a series of phases and requires a significant amount of time and effort. Efficient clinical trial designs are necessary to investigate a new drug. Investigators strongly desire to use the time-to-event endpoint as the primary endpoint for Phase II studies, which evaluates the therapeutic efficacy of the new drug, with the hypothesis that the new drug improves the median survival time. The one-sample log-rank test has been used for single-arm Phase II trials, but it generally requires more samples. Recently, the median event time test was proposed to provide a simple, straightforward decision rule, which compares the observed median survival time for the new drug with the threshold, which is determined through the numerical search. We improve the computation of the method for the two-stage design of single-arm clinical trials based on the median event time test. By utilizing the large sample theory of order statistics, we provide the explicit formulas to calculate the sample size for the first and second stages and propose the testing procedure. The performance of the proposed method is evaluated through simulations and a trial example.

Background: Emerging studies have suggested an essential role of fibroblast metabolic reprogramming in the pathogenesis of arthrofibrosis. The metabolic modulator metformin appears to be a therapeutic candidate for fibrotic disorders. However, whether metformin could alleviate arthrofibrosis has not been defined. In this study we have determined if treatment with metformin has beneficial effect on arthrofibrosis and its underlying mechanism. Methods: Articular capsule samples were collected from patients with/without arthrofibrosis to perform gene and protein expression analysis. Arthrofibrosis animal model was established to examine the anti-fibrotic effect of metformin. Cell culture experiments were conducted to determine the mechanism by which metformin inhibits fibroblast activation. Results: We found that glycolysis was upregulated in human fibrotic articular capsules. In an arthrofibrosis animal model, intra-articular injection of metformin mitigated inflammatory reactions, downregulated expression of both fibrotic and glycolytic markers, improved range of motion (ROM) of the joint, and reduced capsular fibrosis and thickening. At the cellular level, metformin inhibited the activation of fibroblasts and mitigated the abundant influx of glucose into activated fibroblasts. Interestingly, metformin prompted a metabolic shift from oxidative phosphorylation to aerobic glycolysis in activated fibroblasts, resulting in the anti-fibrotic effect of metformin. Conclusion: Metformin decreased glycolysis, causing a metabolic shift toward aerobic glycolysis in activated fibroblasts and has beneficial effect on the treatment of arthrofibrosis.The translational potential of this article: The findings of this study demonstrated the therapeutic effect of metformin on arthrofibrosis and defined novel targets for the treatment of articular fibrotic disorders.

Earth and planetary sciences require extensive microanalyses to quantify most common major and minor elements O, Na, Mg, Al, Si, K, Ca, Ti, Cr, Mn, Fe and Ni in minerals/rocks. With O usually calculated, this is frequently done with expensive electron probe X-ray microanalyzer using a wavelength dispersive method (WDS), and much less so with expensive ground-based scanning electron microscope (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS). Both instruments are not readily accessible to many scientists though. Here we selected eight natural minerals, containing those elements to various amounts, to test the performance of an economical desktop SEM attached with an EDS consisting of just one 10 mm2 silicon drift detector (SDD). The compositions of the minerals were established by extensive electron probe X-ray microanalyses (EPMA)-WDS conducted under routine analytical conditions. They were used to evaluate the performance of the desktop SEM/SDD-EDS system. The examination shows that under modest analytical conditions it can generate accurate results for those elements, with detection limits (∼0.1 wt%) much comparable to routine WDS analyses. Therefore, economical desktop SEM/SDD-EDS system can be an affordable and widely-accessible instrument for extensive and accurate quantification of those most common major and minor elements in minerals/rocks.