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Abstract Background Retinitis pigmentosa is a neurodegenerative disease with major pathologies of photoreceptor apoptosis and immune imbalance. Mesenchymal stem cells (MSCs) have been approved for clinical application for treating various immune-related or neurodegenerative diseases. The objective of this research was to investigate the mechanisms underlying the safeguarding effects of MSC-derived exosomes in a retinal degenerative disease model. Methods Interferon gamma-stimulated exosomes (IFNγ-Exos) secreted from MSCs were isolated, purified, and injected into the vitreous body of RCS rats on postnatal day (P) 21. Morphological and functional changes in the retina were examined at P28, P35, P42, and P49 in Royal College of Surgeons (RCS) rats. The mechanism was explored using high-throughput sequencing technology and confirmed in vitro. Results Treatment with IFNγ-Exo produced better protective effects on photoreceptors and improved visual function in RCS rats. IFNγ-Exo significantly suppressed the activated microglia and inhibited the inflammatory responses in the retina of RCS rats, which was also confirmed in the lipopolysaccharide-activated microglia cell line BV2. Furthermore, through tRNA-derived small RNA (tsRNA) sequencing, we found that IFNγ-Exos from MSCs contained higher levels of Other-1_17-tRNA-Phe-GAA-1-M3, Other-6_23-tRNA-Lys-TTT-3, and TRF-57:75-GLN-CGG-2-m2 than native exosomes, which mainly regulated inflammatory and immune-related pathways, including the mTOR signaling pathway and EGFR tyrosine kinase inhibitor resistance. Conclusions IFNγ stimulation enhanced the neuroprotective effects of MSC-derived exosomes on photoreceptors of the degenerative retina, which may be mediated by immune regulatory tsRNAs acting on microglia. In conclusion, IFNγ-Exo is a promising nanotherapeutic agent for the treatment of retinitis pigmentosa. Graphical Abstract

Abstract Gas therapy has emerged as a promising approach for treating cancer, with gases like NO, H2S, and CO showing positive effects. Among these, NO is considered a key gas molecule with significant potential in stopping cancer progression. However, due to its high reactivity and short half-life, delivering NO directly to tumors is crucial for enhancing cancer treatment. NO-driven nanomedicines (NONs) have been developed to effectively deliver NO donors to tumors, showing great progress in recent years. This review provides an overview of the latest advancements in NO-based cancer nanotherapeutics. It discusses the types of NO donors used in current research, the mechanisms of action behind NO therapy for cancer, and the different delivery systems for NO donors in nanotherapeutics. It also explores the potential of combining NO donors with other treatments for enhanced cancer therapy. Finally, it examines the future prospects and challenges of using NONs in clinical settings for cancer treatment. Graphical Abstract

Abstract Aims This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country‐specific economic strata. Methods This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio‐demographic Index (SDI) levels. Through age‐period‐cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. Results Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all‐age prevalence and YLDs increased over the 30 year span, age‐standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was −0.26% and −0.25%, respectively. Conclusions This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Moringa oleifera is a perennial medicinal and edible plant, and polyphenols as one of its main active ingredients. This study reviews the current status of development of the polyphenol types and contents of different parts, polyphenol extraction methods, polyphenol efficacy, and polyphenol applications of Moringa oleifera. Additionally, the current research on the antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, and hypoglycemic properties of polyphenols from Moringa oleifera is critically examined. The aim of this review is to provide a theoretical basis as well as new insights into the future research and applications of Moringa oleifera polyphenols.

Abstract Background Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. Methods This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. Results In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host’s inflammatory reaction. Conclusions XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis. Graphical Abstract

Abstract Background The Clinical Dementia Rating (CDR) scale allows to detect the presence of dementia and to assess its severity, however its evaluation requires a significant time (45 min). We evaluated the agreement between two methods of collection of the CDR: face-to-face interview or based on the information available in the patient’s medical record. Methods The CLIMER study was conducted among patients attending a memory center. The CDR scale was evaluated during face-to-face interviews between neuropsychologists and patients and their caregivers and based on blind analysis of the information of the patients’ medical record by neuropsychologists. The agreement of the CDR sum of boxes (CDR-SB), the 5-point scale CDR and the different domains of the CDR evaluated between the different methods was measured using intraclass correlation (ICC) coefficient, Bland and Altman method, and linearly weighted Kappa. Results The study included 139 patients (means ± SD age 80.1 ± 6, 58.3% women, 71.9% with dementia). The ICC for the CDR-SB score assessed by face-to-face and with all the information available in the patient’s medical record was 0.95 (95% CI: 0.93–0.97). The mean difference between the CDR-SB score assessed by face-to-face and with the medical record was 0.098 ± 1.036, and 92.4% of the patients lay within the 95% limits of agreement. The ICC for the 5-point scale CDR assessed by face-to-face and with the patient’s medical record was 0.92 (95% CI: 0.88–0.95) when all the available information of the patient’s medical record was used. The linear weighted Kappa coefficients was 0.79 (95% CI: 0.68–0.91) for the 5-point scale CDR comparison between the two evaluation methods. The analysis by domain of the CDR showed ICC ranging from 0.65 to 0.91 depending of the domains and the methods of evaluation. Conclusion This study showed an excellent level of agreement of the evaluation of the CDR- SB and the 5-point scale CDR when using all the information of the patient’s medical record compared to the face-to-face interview. Trial registration https//clinicaltrials.gov/ct2/show/NCT04763941 Registration Date 02/17/2021.

Abstract Predicting the dynamic mechanical characteristics of rocks during freeze–thaw cycles (FTC) is crucial for comprehending the damage process of FTC and averting disasters in rock engineering in cold climates. Nevertheless, the conventional mathematical regression approach has constraints in accurately forecasting the dynamic compressive strength (DCS) of rocks under these circumstances. Hence, this study presents an optimized approach by merging the Coati Optimization Algorithm (COA) with Random Forest (RF) to offer a reliable solution for nondestructive prediction of DCS of rocks in cold locations. Initially, a database of the DCS of rocks after a series of FTC was constructed, and these data were obtained by performing the Split Hopkinson Pressure Bar Test on rocks after FTC. The main influencing factors of the test can be summarized into 10, and PCA was employed to decrease the number of dimensions in the dataset, and the microtests were used to explain the mechanism of the main influencing factors. Additionally, the Backpropagation Neural Network and RF are used to construct the prediction model of DCS of rock, and six optimization techniques were employed for optimizing the hyperparameters of the model. Ultimately, the 12 hybrid prediction models underwent a thorough and unbiased evaluation utilizing a range of evaluation indicators. The outcomes of the research concluded that the COA-RF model is most recommended for application in engineering practice, and it achieved the highest score of 10 in the combined score of the training and testing phases, with the lowest RMSE (4.570,8.769), the lowest MAE (3.155,5.653), the lowest MAPE (0.028,0.050), the highest R 2 (0.983,0.94).

Abstract In order to explore the damage characteristics and crack development laws of hard rock under laser irradiation, laser irradiation experiments on sandstone were conducted considering the interaction of three laser parameters: spot diameter, laser power, and irradiation time. Subsequently, uniaxial compression experiments were conducted on sandstone samples before and after laser irradiation. In addition, based on the maximum principal stress intensity criterion and finite element software, laser induced fracturing sandstone simulation experiments were conducted. Research has found that: Laser irradiation significantly reduces the uniaxial compressive strength of sandstone, with a maximum reduction of about 88.9%, and is also accompanied by a significant decrease in elastic modulus. The degree of sandstone damage escalates with increasing laser power and irradiation time, alongside a reduction in spot diameter. Strong correlations were observed between the strength reduction rate and crack metrics like opening, area, and depth, enabling the establishment of a high-precision regression model. Cracks originate internally within sandstone, initially extending diagonally upwards toward the specimen’s surface before propagating outward. These findings elucidate the mechanisms behind sandstone’s strength reduction and crack propagation under laser irradiation, providing some insights for the practical application of laser rock breaking technology in engineering.

Abstract Cultural heritage is an important contributor to sustainable urban development, and its conservation is considered a global task. Previous research has primarily focused on the conservation of heritage buildings within architectural contexts and world heritage sites within geographical contexts. However, there is a notable gap in conservation of green cultural heritage (GCH) within a landscape-based framework. This study used the extended theory of planned behavior to explore the factors and pathways that influence the public's behavioral intentions toward GCH conservation. Based on 1075 questionnaires collected in Tokyo, Japan, the hypotheses of the newly constructed theoretical model were tested using partial least squares structural equation modeling. The results show that perceived behavioral control has the greatest positive influence on citizens' GCH conservation intentions and behaviors, while social norms do not influence people's behavioral intention to conserve. In the extended factors, the environmental awareness which including heritage awareness and cultural attachment, significantly influences public attitudes towards conservation. Additionally, environmental perception, including perceived usefulness and perceived quality, significantly affects the public's conservation intentions and behaviors, respectively. Our findings have implications for local governments and policymakers to enhance public participation in GCH, as well as some several new theoretical interests for further studies.

Abstract Background Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. Methods We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. Results In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value

Abstract Rapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban–rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban–rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.

A variety of polyphenols in walnut green husk have shown physiological benefits, but their primary hypoglycemic active ingredients remain unclear. We report the extraction of walnut green husk polyphenols (WGHP) and their hypoglycemic effects in vitro. WGHP was extracted using ultrasound-assisted ethanol extraction, with optimization via response surface methodology resulting in 88.0 ± 0.1 % purity after D101 macroporous resin purification. WGHP effectively inhibited α-glucosidase and α-amylase, with IC50 values of 3.42 μg/mL and 2.56 mg/mL, respectively. It also increased glycogen synthesis in insulin-resistant HepG2 cells and enhanced glucose consumption in 3T3-L1 and insulin-resistant HepG2 cells. Screening six α-glucosidase ligands from WGHP using affinity ultrafiltration and UPLC-MS/MS, combined with molecular docking, identified hydrogen bonds and binding energies between the ligands and the enzyme. These results highlight the hypoglycemic potential of walnut green husk polyphenols and provide a basis for future therapeutic research.

Abstract 2D layered semiconductors have attracted considerable attention for beyond‐Si complementary metal‐oxide‐semiconductor (CMOS) technologies. They can be prepared into ultrathin channel materials toward ultrascaled device architectures, including double‐gate field‐effect‐transistors (DGFETs). This work presents an experimental analysis of DGFETs constructed from chemical vapor deposition (CVD)‐grown monolayer (1L) molybdenum disulfide (MoS2) with atomic layer deposition (ALD) of hafnium oxide (HfO2) high‐k gate dielectrics (top and bottom). This extends beyond previous studies of DGFETs based mostly on exfoliated (few‐nm thick) MoS2 flakes, and advances toward large‐area wafer‐scale processing. Here, significant improvements in performance are obtained with DGFETs (i.e., improvements in ON/OFF ratio, ON‐state current, sub‐threshold swing, etc.) compared to single top‐gate FETs. In addition to multi‐gate device architectures (e.g., DGFETs), the scaling of the equivalent oxide thickness (EOT) is crucial toward improved electrostatics required for next‐generation transistors. However, the impact of EOT scaling on the characteristics of CVD‐grown MoS2 DGFETs remains largely unexplored. Thus, this work studies the impact of EOT scaling on subthreshold swing (SS) and gate hysteresis using current–voltage (I–V) measurements with varying sweep rates. The experimental analysis and results elucidate the basic mechanisms responsible for improvements in CVD‐grown 1L‐MoS2 DGFETs compared to standard top‐gate FETs.

PurposeThis meta-analysis aimed to evaluate the diagnostic efficacy of dual-energy computed tomography (DECT) in detecting cervical lymph node metastasis among papillary thyroid cancer (PTC) patients.MethodsA comprehensive search across PubMed, Embase, and Web of Science databases was conducted to identify pertinent publications up to May 2024. This search focused on studies examining the diagnostic accuracy of DECT in detecting cervical lymph node metastases in PTC patients. We employed a bivariate random-effects model to calculate pooled sensitivity and specificity of DECT. The degree of heterogeneity in the studies was quantified using the I2 statistic. Furthermore, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was utilized to evaluate the methodological quality of the included studies.ResultsThis meta-analysis encompassed 14 articles, collectively involving 1,615 patients. The pooled sensitivity, specificity, and AUC for DECT in detecting cervical lymph node metastases in PTC patients were 0.81 (95% CI: 0.76–0.85), 0.86 (95% CI: 0.80–0.91), and 0.89 (95% CI: 0.86–0.92), respectively. According to Fagan’s nomogram, for DECT, with a pre-test probability of 50%, the post-test probability was calculated as 85% for a positive result and 18% for a negative result. Deeks’ funnel plot asymmetry test showed no significant publication bias was observed for DECT (p = 0.28).ConclusionOur meta-analysis indicates that DECT demonstrates superior sensitivity and specificity in cervical lymph node metastasis among PTC patients. To corroborate these findings and evaluate their clinical applicability, further prospective studies are necessary.

BackgroundGastric intestinal metaplasia is a common pathological feature in patients with Helicobacter pylori (H. pylori) infection. Rabeprazole was widely used as the first-line regimen for H. pylori infectious treatment. The objective of this study is to explore the mechanism of rabeprazole in gastric intestinal metaplasia treatment.MethodsReal-time PCR, Western blotting (WB) and ROS analysis were conducted to confirm that rabeprazole could induce ferroptosis to suppress gastric intestinal metaplasia. Cellular fraction, luciferase and chromatin immunoprecipitation (ChIP) were used to identify the mechanism underlying rabeprazole modulated ferroptosis.ResultsHerein, we found rabeprazole treatment led to inhibit CDX2 and MUC2 expression, alleviating gastric intestinal metaplasia, which was attributed to enhanced ferroptosis characterized by decreased GPX4 expression. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) could reverse decreased CDX2 and MUC2 expression caused by rabeprazole. Mechanically, Rabeprazole could inhibit CREB phosphorylation and nuclear translocation, which further decreased the binding of CREB to GPX4 promoter, reducing GPX4 transactivity. Moreover, endogenous PKA interacted with CREB, and this interaction was drastically destroyed in response to rabeprazole treatment. Most importantly, enhanced ferroptosis was observed in H. pylori-infected gastric intestinal metaplasia in comparison to HC control.ConclusionThese findings suggested that rabeprazole induced ferroptosis to reduce CDX2 expression in gastric epithelial cells through PKA/CREB cascade signaling, implying that targeting ferroptosis could be a promising strategy in improving gastric intestinal metaplasia during H. pylori-infected patients.

BackgroundFew studies have focused on the region-specific relationship between cardiovascular disease (CVD) and low temperature worldwide.ObjectiveWe aimed to provide an overview of trends in mortality and disability-adjusted life years (DALYs) for CVD and its subtypes attributable to low temperature over the past 30 years in 204 countries and regions, along with the associations of these trends with age, period, and birth cohorts.MethodsData on the estimated burden of CVDs (including ischemic heart disease, hypertensive heart disease, and stroke) attributable to low temperature were obtained from the Global Burden of Disease Study 2019. We utilized an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 15 ~ 19 to 81 ~ 85 years (local drifts), and period and cohort relative risk (period/cohort effects) between 1990 and 2019.ResultsAmong noncommunicable diseases, CVDs had the highest mortality rate and DALY loss attributable to low temperature worldwide and has increased from 65.7 to 67.3%, which is mainly attributed to the increase in East Asia and Pacific region. In terms of the level of economic and social development, an inverted U-shape was found in the age-standardized mortality rates (ASMR) due to low-temperature across different sociodemographic indices (SDI) regions. Both high CVD mortality (19.45, 95% CI [14.54, 24.17%]) and a decreasing mortality rate related to low temperature (from 1990 to 2019, net drift, −3.25% [−3.76, 2.73%] per year) was found in high SDI countries or territories, with opposite outcome found in low SDIs regions. The older adults (70+) and men share the highest rate of CVD ASMR and DALY attributed to low temperature across all regions, especially in North America and Europe and Central Asia.ConclusionMortality and DALY loss from CVD attributable to low temperature showed an overall decreasing trend globally except for East Asia and Pacific region. SDI, sex, age and geographic location contributed to the diversity of the CVD disease burden associated with low temperature worldwide. More attention should be given to the older adults, men, and low SDI regions.

The surface plasmon resonance (SPR) biosensor technology is a novel optical analysis method for studying intermolecular interactions. Owing to in-depth research on traditional Chinese medicine (TCM) in recent years, comprehensive and specific identification of components and target interactions has become key yet difficult tasks. SPR has gradually been used to analyze the active components of TCM owing to its high sensitivity, strong exclusivity, large flux, and real-time monitoring capabilities. This review sought to briefly introduce the active components of TCM and the principle of SPR, and provide historical and new insights into the application of SPR in the analysis of the active components of TCM.

Abstracts: Several pre-cooling methods for bok choi were used, such as natural convection pre-cooling (NCPC), strong wind pre-cooling (SWPC), vacuum pre-cooling (VPC), cold water pre-cooling (CWPC), electrolyzed water pre-cooling (EWPC), and fluid ice pre-cooling (FIPC), in order to determine the most suitable precooling method. It was found that VPC reduced the respiration rate, inhibited the increase of malondialdehyde (MDA) and relative electrolyte leakage, and significantly decreased the total bacterial count. This may be due to the rapid decompression process during vacuum pre-cooling, which disrupts the microbial structure and has a certain sterilizing effect. Bok choi pre-cooled by VPC had the best color, hardness value, chlorophyll, titratable acid (TA) content, vitamin C (VC) content, total phenolic (TP) content, soluble sugar content, superoxide dismutase (SOD) activity, ascorbate peroxidase (APX) activity, and catalase (CAT) activity. Therefore, the most suitable pre-cooling method for bok choi among the above pre-cooling methods was the VPC method.

Study region: Xiangjiang River Basin (XRB) in subtropical China. Study focus: Vegetation changes have a substantial impact on the water cycle in watersheds. However, the responses of hydrological processes to vegetation changes in subtropical regions have not yet been thoroughly clarified. The primary objectives of this study were to quantify the sensitivity of hydrological variables to vegetation changes and to elucidate the contributions of vegetation greening and climatic changes to alterations in hydrological variables in the Xiangjiang River Basin (XRB). New hydrological insights for the region: Evapotranspiration (ET) exhibits a significant positive sensitivity to alterations in Leaf Area Index (LAI) in the XRB, while soil water storage (SW) and flow depth (Q) showed a significant negative sensitivity to LAI changes. Changes in LAI primarily result in increased ET and reduced SW and Q, while increased in precipitation leads to augmented ET, SW, and Q. Alterations in potential evapotranspiration have been associated with heightened ET and reduced SW and Q. From the perspective of relative contributions, LAI predominantly influences alterations in ET within the XRB; P and PET are the primary driver of shifts in SW; and P chiefly governs the variations in Q. Our results highlight the important impact of vegetation changes on hydrological variables in subtropical watersheds.

Pakchoi seedlings (Brassica chinensis L.) is susceptible to damage and spoilage during harvest and transport, leading to significant quality deterioration and financial losses. This study explored the use of ammonium glycyrrhizinate (AG) to address these issues. AG self-assembles into macromolecules at room temperature, blocking stomata and regulating respiration rates in Pakchoi seedlings. Additionally, it disrupts bacterial cell biofilm and inhibits its synthesis. While AG has been used in medicine, its application in the food industry remains limited. The study found that incorporating AG in Pakchoi seedlings preserves water content and total soluble solids (TSS), while preventing declines in catalase (CAT), Vitamin C (VC), and chlorophyll during storage. AG also reduced malondialdehyde (MDA) levels and maintained peroxidase (POD) and superoxide dismutase (SOD) activities. At a concentration of 4.25 g L−1, AG enhanced radical scavenging ability and extended the shelf life of Pakchoi seedlings by inhibiting bacteria and postponing senescence.

This study investigated the impact of multi-frequency ultrasound-assisted (20/28/40 kHz) thawing (MUAT) at different power levels (195, 220, 245, and 270 W, respectively) on the flesh quality and protein stability of large yellow croakers. Compared with flowing water thawing (FWT) and the other MUAT sample, flesh quality results indicated that the MUAT-220 W significantly reduced (p

Abstract Previous work that studied hexagonal boron nitride (h‐BN) memristor DC resistive‐switching characteristics is extended to include an experimental understanding of their dynamic behavior upon programming or synaptic weight update. The focus is on the temporal resistive switching response to driving stimulus (programming voltage pulses) effecting conductance updates during training in neural network crossbar implementations. Test arrays are fabricated at the wafer level, enabled by the transfer of CVD‐grown few‐layer (8 layer) or multi‐layer (18 layer) h‐BN films. A comprehensive study of their temporal response under various conditions–voltage pulse amplitude, edge rate (pulse rise/fall times), and temperature–provides new insights into the resistive switching process toward optimized devices and improvements in their implementation of artificial neural networks. The h‐BN memristors can achieve multi‐state operation through ultrafast pulsed switching (< 25 ns) with high energy efficiency (≈10 pJ pulse−1).

Abstract Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

Utilizing excess vacancy to form effective solute clusters has been considered as a potential strategy to strengthen Al alloys. Herein, we designed a cryogenic submerged friction stir processing, by the one-step process in a short time, to realize the coexistence of grain refinement, high-density clusters, and nanoprecipitates, thus enhancing strength and ductility simultaneously. The atomic information showed the unique formation of high-density clusters (1 ∼ 2 nm), which was related to the strain-induced migration of solute atoms. This study may provide a new strategy for alloys with low alloying content that can be enhanced by forming solute clusters.

In-situ stress data are fundamental for deep engineering purposes. Traditional methods of measuring in-situ stress are inefficient and lack standardization. The theoretical framework is predominantly built on numerous assumptions, making it challenging to assess its accuracy. High in-situ stress at significant depths often leads to the formation of various core discing shapes. A more scientific, cost-effective, convenient, and rapid method for calculating in-situ stress involves the inversion of stress through core discing characteristics. To achieve this, understanding the behavior of core discing under deep in-situ stress conditions is essential, as well as defining the intensity coefficient of core discing in two-dimensional settings. By focusing on discing cores from varying depths in the Songke-2 well, their macro-morphology is captured using a three-dimensional data acquisition system. Additionally, the mineral composition and microstructure of the cores are analyzed through the X-ray diffraction and lithofacies thin section tests. Concurrently, the mechanical mechanism governing core discing behavior under different stress conditions are studied using the discrete element method. The analysis reveals five distinct morphological types of discing cores in the Songke-2 well: broken, thin-disc, thick-disc, irregular, and semi-disc. The fracture patterns on the end face of the discs includes staggered step, plane, lamp, and petal formations. These morphological attributes are found to be closely linked to burial depth, mineral hardness, and failure mode. Core discing behavior is primarily controlled by tensile stress, with crack initiation typically occurring at the core's root and propagating outward in a concave or planar manner. The horizontal principal stress emerges as the primary factor influencing core discing behavior, leading to concave core fractures and wide-band tensile cracks, while the vertical principal stress serves as a secondary factor, generally inhibiting discing behavior. During drilling operations, the onset of discing coincides with a systematic energy shift, marked by a gradual decrease in total strain energy and a corresponding increase in dissipation energy. The instantaneous release of total strain energy is identified as the primary cause of core discing. These research findings are expected to offer some novel insights and valuable references for the inversion of in-situ stress based on core discing analysis.

In order to solve the problem of iron source supply for large-scale direct liquefaction catalyst, and meanwhile realize the harmless separated-utilization of extraction residue from coal liquefaction, this paper conducted a research on the recovery of iron catalyst from extraction residue, and explored the feasibility of enriching recovery of iron catalyst by using physical magnetic separation method. Firstly, the characterization methods, such as particle size analysis, XRF, XRD, SEM, TG, SEM-EDX, were used to comprehensively characterize and analyze the physical and chemical properties of the extraction residue, and therefore determine the contents and existence forms of iron catalyst. From the results analysis, it can be seen that the extraction residue from industrial equipment is mainly composed of carbon in unreacted coal and residual carbon, volatile matter and ash, with uniform particle size and no agglomeration. The mass fraction of iron is 5.96%, and the iron species still exist as the active phase of paramagnetic Fe1−xS, which doped and coated by unreacted coal and residual asphalt, and uniformly mixed and distributed in the extracts with various elements such as Ca, Si, Al, O, etc. On this basis, four types of magnetic separation equipment were selected for magnetic separation enrichment under different magnetic field strengths, and the enriched samples were then used as catalysts for direct coal liquefaction reaction to investigate their performances in direct liquefaction reaction. The experimental results show that：On the one hand, the high gradient magnetic force generated by the wet vertical ring pulsating high gradient magnetic separator is applied to the magnetic catalyst fine powder. Together with using water as dispersion medium and washing medium, the fine separation of iron catalyst powder from extraction residue was realized more effectively. With the magnetic field strength of 640 000 A/m, the material enrichment rate of the iron-containing catalyst was 10.48%, and the mass fraction of iron was 11.37%, the extraction oil yield of high-pressure autoclave 41.96%, which was 7.17% higher than that without the catalyst, and 8.99% higher than that with the extraction residue. It can be mixed into fresh catalyst to achieve an effective reuse, to some extent solving the problem of catalyst iron source shortage.

To assess the viability and effectiveness of bioretention cell in enhancing rainwater resource utilization within sponge cities, this study employs field monitoring, laboratory testing, and statistical analysis to evaluate the water purification capabilities of bioretention cell. Findings indicate a marked purification impact on surface runoff, with removal efficiencies of 59.81% for suspended solids (SS), 39.01% for chemical oxygen demand (COD), 37.53% for ammonia nitrogen (NH3-N), and 30.49% for total phosphorus (TP). The treated water largely complies with rainwater reuse guidelines and tertiary sewage discharge standards. Notably, while previous research in China has emphasized water volume control in sponge city infrastructures, less attention has been given to the qualitative aspects and field-based evaluations. This research not only fills that gap but also offers valuable insights and practical implications for bioretention cell integration into sponge city development. Moreover, the methodology and outcomes of this study serve as a benchmark for future sponge city project assessments, offering guidance to relevant authorities. HIGHLIGHTS Explored the purification of bioretention cells on rainwater.; Under the same conditions, the bioretention cell has the best purification effect on suspended solids.; The bioretention cell's effluent quality complies with standards for urban recycled water, wastewater discharge, and sponge city assessments.;

With the accelerated evolution of digital technologies such as big data, cloud computing, and artificial intelligence, the trends of intelligence, informatization, and digitization have become imminent across various domains. Deep earth engineering, as a major strategic scientific and technological issue for the nation, is inevitably poised for intelligent upgrades. However, the complex characteristics of “three highs and one disturbance” in deep rock masses pose some severe challenges to the intelligent transformation of deep earth engineering. In order to achieve an efficient integration of deep earth engineering and digital technology, this study focuses on the intelligent practice path based on “perception, transmission, interpretation, analysis, decision”. The representative research progress in intelligent perception, real-time transmission, information interpretation, data analysis, intelligent decision-making and other fields in underground engineering is systematically reviewed, and the targeted development directions for deep earth engineering intelligent development are proposed, including multi perception, fast response, big data, optimal methods, precise models, strong platforms and easy promotion. Research findings indicate that ① The cutting-edge deep earth engineering perception technologies include fiber optic sensors, MEMS sensors, computer vision, automated robots, etc. After data collection is completed, the real-time response of data is achieved through the wireless communication protocols that combine the advantages of simple configuration, strong fault tolerance, and good mobility, in order to achieve an accurate collection and real-time transmission of deep earth engineering monitoring data. ② Deep earth engineering survey technology yields data types such as images, waves, and point clouds. Numerous models for interpreting and analyzing raw data exist. The application of next-generation artificial intelligence technologies, such as artificial neural networks and deep learning, significantly improves the efficiency of interpretation and analysis. ③ The intelligent decision-making system possesses efficient learning capabilities, adapting to the uncertainty in complex environments through cyclic autonomous learning to provide intelligent solutions for decision-making problems. Currently, China’s policies and industrial systems for the intelligent construction in the deep earth engineering have been essentially established, with a plethora of intelligent construction systems already applied in practical settings. Building upon this foundation, the study envisions the development direction of digital deep earth engineering in four aspects: intelligent collection and information interpretation, surrounding rock evaluation and safety assessment, surrounding rock control and dynamic repair, and platform development and application promotion. Furthermore, a comprehensive evaluation and analysis system for surrounding rock stability of deep earth engineering based on multi-source information is constructed.

Abstract Background Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. Methods The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. Results The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1 + , C1Q + , and GPNMB + showed enhanced contact with tumor cells expressing NR5A1 + , TBX19 + , and POU1F1 +, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1 + macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. Conclusions In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.

Abstract We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Background: Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI. Methods: The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6–8 weeks (weight 200–250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics. Results: Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P

Abstract Background Uterine rupture in pregnant women can lead to serious adverse outcomes. This study aimed to explore the clinical characteristics, treatment, and prognosis of patients with complete uterine rupture. Methods Data from 33 cases of surgically confirmed complete uterine rupture at Chenzhou No.1 People’s Hospital between January 2015 and December 2022 were analyzed retrospectively. Results In total, 31,555 pregnant women delivered in our hospital during the study period. Of these, approximately 1‰ (n = 33) had complete uterine rupture. The average gestational age at complete uterine rupture was 31+4 weeks (13+1–40+3 weeks), and the average bleeding volume was 1896.97 ml (200–6000 ml). Twenty-six patients (78.79%) had undergone more than two deliveries. Twenty-five women (75.76%) experienced uterine rupture after a cesarean section, two (6.06%) after fallopian tube surgery, one (3.03%) after laparoscopic cervical cerclage, and one (3.03%) after wedge resection of the uterine horn, and Fifteen women (45.45%) presented with uterine rupture at the original cesarean section incision scar. Thirteen patients (39.39%) were transferred to our hospital after their initial diagnosis. Seven patients (21.21%) had no obvious symptoms, and only four patients (12.12%) had typical persistent lower abdominal pain. There were 13 cases (39.39%, including eight cases ≥ 28 weeks old) of fetal death in utero and two cases (6.06%, both full term) of severe neonatal asphyxia. The rates of postpartum hemorrhage, blood transfusion, hysterectomy were 66.67%, 63.64%, and 21.21%. Maternal death occurred in one case (3.03%). Conclusions The site of the uterine rupture was random, and was often located at the weakest point of the uterus. There is no effective means for detecting or predicting the weakest point of the uterus. Rapid recognition is key to the treatment of uterine rupture.

Abstract Along with the further integration of demand management and renewable energy technology, making optimal use of energy storage devices and coordinating operation with other devices are key. The present study takes into account the current situation of power storage equipment. Based on one year of measured data, four cases are designed for a composite energy storage system (ESS). In this paper, a two-tiered optimization model is proposed and is used to optimizing the capacity of power storage devices and the yearly production of the system. Furthermore, this paper performs a comparative analysis of the performance of the four cases from the energy, environmental and economic perspectives. It is concluded that this kind of energy storage equipment can enhance the economics and environment of residential energy systems. The thermal energy storage system (TESS) has the shortest payback period (7.84 years), and the CO2 emissions are the lowest. Coupled with future price volatility and the carbon tax, the electrothermal hybrid energy storage system (HESS) has good development potential. However, the current investment cost is very high, and it will not be possible to recover this cost in 10 years. Finally, it is recommended that the cost of equipment be reduced in combination with subsidies and incentives for further promotion. The research results not only fill a gap in the study area, but also provide some suggestions for further development of industry and research on user-side energy storage.

Food is vital to the people, and safety comes first in food. Food safety is crucial to people's livelihood, economic development, and social stability. It represents people's aspiration for a better life and grabs great public attention. In recent years, while China has achieved significant progress in food safety, the situation remains severe, with incidents such as excessive residues of agricultural and veterinary drugs, as well as illegal addition of toxic and harmful substances. As an important technical support for ensuring food safety, food safety inspection and testing institutions also exhibit a mixed bag of performance. Problems such as inadequate personnel management, improper use of facilities and equipment, weak legal awareness resulting in issuance of false reports have frequently occurred, seriously disrupting the normal order of the inspection and testing market and affecting the authority and accuracy of food safety testing. Based on the capacity verification of inspection and testing organizations in Zhejiang Province in recent years, this paper studies the typical problems faced by food inspection and testing institutions in terms of management level and testing capabilities, analyzes the root causes in depth, and proposes specific strategies from three aspects: Strengthening the main responsibility of inspection and testing institutions, combining regulatory departments with supervision and guidance, and enhancing industry self-discipline, aiming to continuously improve their inspection and testing capabilities, promote the high-quality development of food inspection and testing institutions, and effectively ensure the safety of every bite of food.

Abstract Background The informal caregivers of adult patients with β-thalassemia major (β-TM) bear not only physical but also emotional and economic pressures of providing care. This study is the first to evaluate the caregiver burden by Zarit Burden Interview (ZBI) of adult patients with β-TM in mainland China and to identify predictors of caregiver burden. Methods In this cross-sectional study, we conducted an online survey with snowball sampling covering seven provinces between September 1, 2021, and January 31, 2022, of patients aged ≥ 18 years with β-TM and their informal caregivers. Caregiver burden was assessed using the ZBI. Data on patient demographics, disease and therapy characteristics, and informal caregivers’ demographic characteristics were collected and analysed using independent t-tests, analysis of variance, Spearman’s correlation and multiple linear regression. Results Of 75 included patients, more than half (50.7%) were male. The mean patient age was 24.69 ± 5.59 years. The mean age of the informal caregivers was 50.60 ± 9.16 years, with women (74.7%) being predominant. The ZBI score was 38.00 ± 17.02. Multiple linear regression analysis showed that patients with interrupted blood transfusion therapy and informal caregivers required to care of others were positively associated with caregiver burden (p

Transport in water is the most common method for transporting live fish in China, however, transport is a strong stressor. Transport stress could lead to a reduced immune and antioxidant system function of tiger grouper, resulting in sickness and death. Besides, tiger grouper were continuously stressed during transport, which resulted in quality deterioration. It is necessary that find a way to relieve the stress of transportation of tiger grouper. Ascorbic acid is not only a good anti-stress agent, but it is also an effective immunostimulant. β-1,3-glucan is a feed additive that can enhance the immune response of fish. Therefore, this study evaluated the effects of β-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport. Results indicated that adding β-1,3-glucan and ascorbic acid in transport-water muted the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. In addition, β-1,3-glucan and ascorbic acid activated Nrf2 and mediated TOR expression and then up-regulate related mRNA expression of antioxidant and immune enzymes. We concluded that the application of β-1,3-glucan and ascorbic acid inhibit the increase of metabolism enzymes and inflammatory factors and activate immune and antioxidant signaling pathways to relieve oxidant stress, immune response, and apoptosis. Reducing the loss of amino acids provided nutrients to relieve oxidative stress and immune response, which demonstrated immune-nutritional response in live tiger grouper during simulated transport. These results may provide a new solution for alleviating the decline of immune and antioxidant function of tiger grouper caused by transportation stress.

Inappropriate slaughter methods can lead to differences in fish quality. In the past few years, few studies have focused on the effects of different slaughter methods on the postmortem effects of tilapia, especially the cold storage of tilapia after slaughter. The aim of this study was to investigate the effects of different slaughter methods on the biochemical characteristics and quality changes of tilapia during cold storage. In terms of blood and plasma parameters, the CS sample had lower levels of lactate dehydrogenase (LDH), cortisol (COR), and glucose (GLU) than the other samples. The results of K-value and FAAs showed that CS and ASCN groups were beneficial to prolong the freshness life of tilapia during cold storage. The texture properties of CS group were better. In summary, group CS is more conducive to prolonging the fresh life of refrigerated tilapia and is a recommended method of slaughter.

Objective Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice.Materials and methods A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours.Results Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed.Conclusions These results indicated that gut microbiota might affect host’s inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. ‘Limosilactobacillus-3-OMDP-IL-1β/IL-6’ might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

How to reduce the quality loss of aquatic products during storage is a topic worth exploring. This study proposed a method combining orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) and discussed the effects of this combined treatment on the quality, lipid, and protein of large yellow croaker during cold storage (4 °C). The results showed that both ultrasound-assisted treatment (US) and bioactive coating (CMCS) significantly inhibited microbial growth and quality deterioration in the fish, with the combined treatment group (US+CMCS) showing the best effect. The shelf life of large yellow croaker in the control group (CK) was 6 d, while the shelf life for US, CMCS, and US+CMCS treatments was 12 d, 12 d, and 18 d, respectively. Additionally, the combined treatment inhibited lipid oxidation and effectively delayed the oxidative degradation of protein in the large yellow croaker during cold storage. Therefore, the method of orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) combined with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) proposed in this study was a promising approach for the preservation of aquatic products during storage.

Spinal cord injury (SCI) is a severe event that occurs in the central nervous system (CNS). Long noncoding RNAs (lncRNAs) have already been proven to play key roles in different diseases of the CNS. Nevertheless, the roles of messenger RNAs (mRNAs) and lncRNAs one week after SCI remain to be elucidated. We established a rat model of SCI and examined the differential levels of mRNAs and lncRNAs, and then, the differentially expressed mRNAs (DE mRNAs) and lncRNAs (DE lncRNAs) were investigated. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DE lncRNAs and mRNAs were subsequently carried out to explore crucial biological processes and signaling pathways. Moreover, we constructed protein–protein interaction (PPI) networks, the STRING database, and identified the 10 high degree core nodes. We also established a co-expression network by calculating the correlation between lncRNA expression profile and mRNA expression profile. The identified DE lncRNAs and DE mRNAs may potentially be critical targets for the diagnosis and treatment of SCI in the future. Abbreviations: SCI: spinal cord injury; CNS: central nervous system; YLDs: years of life lived with disability; lncRNAs: long noncoding RNAs; mRNAs: messenger RNAs; DE: differentially expressed; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: gene set enrichment analysis; RIN: Renewable Identification Number; PCA: principal component analysis; PPI: protein–protein interaction; MF, molecular function; BP: biological process; CC: cellular component; MCODE: molecular complex detection

Fiber-reinforced polymer (FRP) confined concrete filled steel tube (CFST) structures effectively harness the advantages of FRP materials, improving the performance of CFST structures and overcoming durability issues of steel tubes. Three-dimensional detailed finite element (FE) models are usually employed to estimate the impact-resistant performance of FRP confined CFST members under impact loadings. However, detailed FE models are typically complex in modeling and low in calculation efficiency as well as require high performance in computer hardware. Hence, this paper aims to develop an alternative modeling method that can predict the impact behavior of FRP confined CFST members with high efficiency and low requirements in computer resources. The proposed method includes a contact model using mass-spring-damper elements to describe the contact behavior between the impactor and the impacted FRP confined CFST members and a nonlinear fiber-based beam-column element model to simulate the behavior of FRP-confined CFST members under impact loading. The accuracies of fiber-section beam-column elements are carefully examined for FRP confined CFST members based on quasi-static test data reported in the literature. It is found that the fiber-based elements considering confinement effects provided by FRP and steel tubes can accurately predict the force-deformation relationship of the FRP confined CFST members under monotonic loading. By incorporating the strain-rate effects of concrete, steel, and FRP materials, the validated fiber-section elements are employed to simulate eight impact tests on FRP confined CFST members. Good agreements are observed between the results obtained from the proposed models and the experimental data. The computational efficiency of the developed model is three orders of magnitude faster than that of the conventional detailed FE model.

BackgroundEpilepsy is a non-communicable chronic brain disease that affects all age groups. There are approximately 50 million epilepsy patients worldwide, which is one of the most common neurological disorder. This study reports the time trends in the burden of epilepsy from 1999 to 2019.MethodsWe evaluated the disease burden and its temporal trends of epilepsy using the prevalence and years lived with disability (YLDs), which was estimated based on the Global Burden of Disease (GBD) 2019 study. The age-period-cohort (APC) model was used to estimate the temporal trends of the epilepsy prevalence and YLDs rates, and to analyze the relative risks of age, periods and queues (age/period/queue effects).ResultsIn the past 30 years, the global age-standardized prevalence rate and age-standardized rate has increased by 29.61% and 27.02%, respectively. Globally, the APC model estimated the net drift of prevalence and YLDs were 0.88% (95% CI: 0.83–0.93) and 0.80% (95% CI: 0.75–0.85) per year. Among 204 countries and territories, the YLDs in 146 and prevalence 164 showed an increasing trend. And the risk of YLDs and prevalence increases with age, with the lowest risk among 0–4 years old and the highest risk among 75–79 years old. Unfavorable increasing period and cohort risks of YLDs and prevalence were observed.ConclusionOver the past 30 years, the YLDs and prevalence of epilepsy have gradually increased globally and unfavorable increasing period and cohort risks were observed. Emphasizing epilepsy prevention, strengthening epilepsy health education, optimizing older adults epilepsy diagnosis and treatment plans, and actively promoting epilepsy diagnosis and treatment plans can effectively reduce new cases of epilepsy and related disabilities.

IntroductionMesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.MethodsIn this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).ResultsThe median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.DiscussionThese finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Abstract Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real‐time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self‐adaptive hyperthermia supramolecular cascade nano‐reactor ACFDG is constructed via one‐step supramolecular self‐assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS‐inflammatory cascade through catalytic cascade reactions, up‐regulate the expression of heat shock proteins (HSPs) under near‐infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real‐time non‐invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano‐reactor combined with PA imaging for real‐time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Abstract The Lhasa‐Qiangtang collision closed the Meso‐Tethys Ocean, but the exact timing of this event remains hotly debated. Here, we present geochronological and paleomagnetic analyses conducted on Cretaceous volcanics from western Qiangtang to constrain the Lhasa‐Qiangtang collision in western Tibet. Our investigations yield a paleolatitude of ∼30.5 ± 5.0°N for western Qiangtang during ca. 110–100 Ma. A reanalysis of previously acquired Mesozoic‐Cenozoic paleomagnetic data from western Qiangtang suggests a stationary position during ca. 136–34 Ma. Examination of paleomagnetic data from western Lhasa reveals a significant reduction in northward paleolatitudinal motion during the Early Cretaceous, dropping from ∼12.3 cm/yr to nearly zero. Integration of our paleomagnetic findings with available geological records has led to conclude that the Lhasa‐Qiangtang collision in western Tibet occurred at ca. 132 Ma. Additionally, we infer that crustal shortening on the order of ∼1,000 km happened between Lhasa and Qiangtang during the Early Cenozoic.

AimPlant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles.MethodsWe isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs.ResultsOur findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs.ConclusionOverall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

Background Polygonatum odoratum (Mill.) Druce is a traditional Chinese herb that is widely cultivated in China. Polysaccharides are the major bioactive components in rhizome of P. odoratum and have many important biological functions. Methods To better understand the regulatory mechanisms of polysaccharide accumulation in P. odoratum rhizomes, the rhizomes of two P. odoratum cultivars ‘Y10’ and ‘Y11’ with distinct differences in polysaccharide content were used for transcriptome and metabolome analyses, and the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were identified. Results A total of 14,194 differentially expressed genes (DEGs) were identified, of which 6,689 DEGs were down-regulated in ‘Y10’ compared with those in ‘Y11’. KEGG enrichment analysis of the down-regulated DEGs revealed a significant enrichment of ‘starch and sucrose metabolism’, and ‘amino sugar and nucleotide sugar metabolism’. Meanwhile, 80 differentially accumulated metabolites (DAMs) were detected, of which 52 were significantly up-regulated in ‘Y11’ compared to those in ‘Y10’. The up-regulated DAMs were significantly enriched in ‘tropane, piperidine and pyridine alkaloid biosynthesis’, ‘pentose phosphate pathway’ and ‘ABC transporters’. The integrated metabolomic and transcriptomic analysis have revealed that four DAMs, glucose, beta-D-fructose 6-phosphate, maltose and 3-beta-D-galactosyl-sn-glycerol were significantly enriched for polysaccharide accumulation, which may be regulated by 17 DEGs, including UTP-glucose-1-phosphate uridylyltransferase (UGP2), hexokinase (HK), sucrose synthase (SUS), and UDP-glucose 6-dehydrogenase (UGDH). Furthermore, 8 DEGs (sacA, HK, scrK, GPI) were identified as candidate genes for the accumulation of glucose and beta-D-fructose 6-phosphate in the proposed polysaccharide biosynthetic pathways, and these two metabolites were significantly associated with the expression levels of 13 transcription factors including C3H, FAR1, bHLH and ERF. This study provided comprehensive information on polysaccharide accumulation and laid the foundation for elucidating the molecular mechanisms of medicinal quality formation in P. odoratum rhizomes.

Introduction: Root dentin formation is an important process in tooth development. We tried to identify potential genes that regulate root dentin formation which could be potentially used for the regeneration and repair of defective or damaged dental roots.Methods: Tissues harvested from the labial and lingual sides of mouse incisors were used for microarray analysis. Gene ontology (GO) analysis of differentially expressed genes indicated the critical role of extracellular matrix in the discrepancy of dentin formation between root and crown, for which hemicentin-1 (Hmcn1) was selected as the target gene. Single-cell RNA sequencing analysis the expression pattern of Hmcn1 at different developmental stages in mouse molars. The spatiotemporal expression of HMCN1 in mouse incisors and molars was detected by immunohistochemical staining. The functions of HMCN1 in human dental pulp cells, including proliferation, differentiation and migration, were examined in vitro by CCK8 assay, BrdU assay, wound-healing assay, ALP staining and alizarin red staining, respectively.Results: It was showed that HMCN1 expression was more pronounced in papilla-pulp on the root than crown side in mouse incisors and molars. In vitro experiments presented inhibited dentinogenesis and migration after HMCN1-knockdown in human dental pulp cells, while there was no significant difference in proliferation between the HMCN1-knockdown group and control group.Discussion: These results indicated that HMCN1 plays an important role in dentinogenesis and migration of pulp cells, contributing to root dentin formation.

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at −18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to β-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.