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Traditionally, it was believed that the human brain lacked lymphatic vessels. However, recent studies have progressively confirmed the existence of meningeal lymphatic vessels and the glymphatic system. Alzheimer disease (AD) is a neurodegenerative disorder, and brain lymphatic circulatory dysfunction may contribute to its development. This article reviews the current status and challenges of treating AD through the brain lymphatic system, examining the relationship between circulatory disorders and AD. Additionally, it explores the feasibility of enhancing lymphatic circulation through deep cervical lymphaticovenular anastomosis as a potential treatment for AD, providing a valuable reference for future therapeutic strategies.

Abstract Complex dynamical behaviors such as bifurcation and chaos exist in H-bridge inverter with RLC load, and these nonlinear behaviors will greatly increase the harmonic content of the output current and reduce the stability and reliability of the system. In this paper, a PI controller is added to widen the stable operation domain of the system. The stroboscopic mapping theory is used to model the system, the nonlinear dynamic behavior of the inverter is investigated by the bifurcation diagram, the folding diagram and the phase trajectory diagram are used for comparative verification, and the TDFC method is introduced to inhibit the chaotic behavior of the inverter, which further improves the stable range of the system operation. The fast-change stability theorem is used to analyze the stability of the system theoretically and verify the correctness of the numerical simulation. Therefore, the conclusions of the study provide a reliable theoretical basis for the design of the inverter system, which has important theoretical significance and practical value.

Abstract The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0–2 years (18.09%, 1054/5,828) and lowest among adults aged 45–64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time.

Abstract Background Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. Results DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). Conclusions Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

This study investigates the correlation between 129Xe ventilation functional MRI and CT-detected pulmonary lesion types. We performed 129Xe ventilation functional MRI and CT scans on a sample of 143 patients, subsequently analyzing the relationship between lung ventilation function at the lobe level and CT lesion types. The findings suggest that the ventilation function from 129Xe MRI was consistent with CT results in the majority of lung lobes (74.6%). The ventilation function impairment of lung correlates with CT lesion types, particularly in instances of mixed diseases and emphysema/bullae, which are more prone to induce lung ventilation dysfunction. Moreover, distinct ventilation patterns are observed among different lesion types. That is, the data from both 129Xe ventilation functional MRI and CT provide complementary insights. The preliminary finding of this study offers data support for evaluating lung ventilation function caused by lung lesions, and provides more references for clinical imaging diagnosis, thereby contributing to the refinement of diagnostic and therapeutic strategies for pulmonary diseases.

From January 31 to February 6 (P1, hereinafter) and from February 19 to February 25, 2024 (P2, hereinafter), China experienced two large-scale and sustained low temperature, rainfall/snowfall, and freezing weather events, which seriously affected the Spring Festival transportation. This paper compared the two events using multi-source observations and ERA5 reanalysis data, with a particular focus on the mechanisms of the differences in precipitation intensity and the phases between rainfall, snowfall, and freezing rain in southern China. The results are as follows. (1) Both events exhibit extreme features in total precipitation and are accompanied by complex phase changes, with the range and the intensity of the freezing rain being the largest since 2009. Compared to P2, the intensity of freezing rain and the snow depth in P1 are greater. However, the range of freezing rain, the precipitation amount, and the convective intensity in P2 are greater. (2) Both the circulation patterns of the two events are affected by the high-altitude trough and low-level cold air. The southwest jet stream in front of the trough and the periphery of the western Pacific subtropical high (WPSH) is stable and significantly stronger than normal, providing sustained and abundant water vapor. The ascent of warm-humid air over a cold cushion and the horizontal convergence of low-level winds are crucial dynamic mechanisms for snowfall and rainfall. Besides, the stable maintenance of the inversion layer and the melting layer is the key to the occurrence of freezing rain and the changes in the precipitation phase. (3) Different mechanisms also exist in the two events. In P1, the air temperature in the freezing layer is between -4~0 ℃ in most areas, which is higher than that in P2 and is more conducive to the formation of freezing rain. In P2, the inversion zone is wide but moves more quickly, with a larger range while weaker freezing rain. In P2, the WPSH is located further northwest, favoring the strengthening and northward shift of the southwest warm-humid jet. Meanwhile, the strong cold wave also leads to a stronger cold cushion. The interaction between the cold and warm airs is conducive to the development of upward movement and the enhancement of precipitation. The longer duration of the melting layer leads to more cloud water content, but the temperature in the freezing layer is lower, which is beneficial for the formation of ice particles or wet snow.

To realize the recycling of iron tailings powder (IP) and desulfurization ash (DA) and reduce the high preparation cost of mine filling cementitious materials (MCs), this article adopts sodium carbonate (SC) as an activator to prepare iron tailings powder-desulfurization ash mine filling cementitious materials (IDMC). The effects of IP content, DA content, SC content, and mirabilite content on the mechanical properties and setting time are experimentally investigated. The micromorphology and phase compositions of the hydration products of IDMC are analyzed and characterized by scanning electron microscopy and X-ray diffraction. The results show that the initial setting time of the IDMC is reduced by 0.87 and 21.83% when the mirabilite content is increased from 0 to 1% and 2%, respectively, and the compressive and flexural strengths of the IDMC are increased by 24.01 and 86.25% when the IP content is increased from 0 to 20%, respectively. The IP not only participates in the hydration reaction but also plays an aggregate filling effect, significantly improving the mechanical properties of the IDMC. The pozzolanic effect is gradually enhanced with the increase of the DA content, and the hydration degree of the IDMC increases. The SC as an activator can moderately reduce the shrinkage rate of the IDMC. Based on the multi-index optimization analysis, the optimal mix proportion of the IDMC is obtained, which provides an effective reference for the preparation of the novel MC.

Three commercial Saccharomyces cerevisiae strains with low, medium, and high H2S-producing capacity were chosen to investigate the effect of yeast assimilable nitrogen (YAN) levels and composition on volatile compounds in a chemically defined medium, specifically high, medium, and low initial YAN levels with varying proportions of DAP or sulfur-containing amino acids (cysteine and methionine). The results revealed that the initial YAN containing a larger proportion of diammonium phosphate resulted in a higher YAN consumption rate during the early stages of fermentation. The yeast strain had a greater effect on the volatiles than the YAN level and composition. Keeping the total YAN constant, a higher proportion of sulfur-containing amino acids resulted in a considerably higher production of 3-methylthiopropanol. The sensory impact of three key volatile sulfur compounds was investigated in a Chardonnay wine matrix, indicating that 3-methylthiopropanol at subthreshold or greater concentrations was effective in enhancing the cantaloupe aroma.

ABSTRACT Biodiversity and ecosystem multifunctionality are currently hot topics in ecological research. However, little is known about the role of multitrophic diversity in regulating various ecosystem functions, which limits our ability to predict the impact of biodiversity loss on human well‐being and ecosystem multifunctionality. In this study, multitrophic diversity was divided into three categories: plant, animal, and microbial communities (i.e., plant diversity, rodent diversity, and bacterial and fungal diversity). Also, 15 ecosystem functions were divided into four categories—water conservation, soil fertility, nutrient cycling and transformation, and community production—to evaluate the significance of biotic and abiotic variables in maintaining ecosystem multifunctionality. Results indicated that species diversity at multiple trophic levels had a greater positive impact on ecosystem multifunctionality than species diversity at a single trophic level. Notably, the specific nature of this relationship depended on the niche breadths of plants, indicating that plants played a key role in linking above and belowground trophic levels. Abiotic factors such as altitude and pH directly acted on ecosystem multifunctionality and could explain changes in ecosystem functions. Overall, our study offers valuable insights into the critical role of multitrophic species diversity in preserving ecosystem multifunctionality within alpine grassland communities, as well as strong support for the importance of biodiversity protection.

Climate warming and human disturbance are supposed to have significantly impacted the alpine grasslands. However, it is still unclear how human activity affects the community composition and niche characteristics in response to warming. We conducted a two-factorial experiment in an alpine meadow, and set up four treatments: warming, mowing, warming with mowing, and control. Based on the investigation of community composition and niche characteristics, we evaluated the impacts of soil carbon, nitrogen, and phosphorus on species niche overlap. The results showed that mowing significantly increased species richness of Grass, Sedge, Forbs and the importance value of Sedge compared to warming (P < 0.05). The niche breadth of species (>50 %) was reduced by warming, but increased under mowing. The niche overlap mainly occurred between Grass and Forbs in warming, while it was evenly distributed among species after mowing, which alleviated the negative effects of warming on interspecific competitiveness. Warming increased the number of species pairs with a niche overlap value >0.9 by 24.15 %, while warming with mowing decreased it by 2.7 %. The number of species pairs with niche overlap was significantly correlated with soil total nitrogen and soil available nitrogen (P < 0.05). In particular, the species pairs with highly competitive showed a greater dependency on soil nitrogen. Our work highlights that moderate utilization and soil nitrogen are two crucial factors influencing the response of community structure in alpine meadows to future climate change. The study provides an important reference for predicting and addressing the impact of global climate change on adaptive management and grassland protection.

ObjectivesObservational studies have identified an association between dried fruit intake and kidney function. However, these studies have limitations such as vulnerability to confounders and reverse causality bias. Therefore, this study aimed to explore the potential causal relationship between dried fruit intake and kidney function.MethodsA two-sample Mendelian randomization (MR) study was conducted using a large-scale genome-wide association study dataset to investigate the causal relationship between dried fruit intake and kidney function markers (blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), cystatin C (CyC), hematuria, microalbuminuria). The main analytical method was inverse variance weighting. In addition, we applied the MR Egger and weighted median to assess the robustness of the results. Finally, Multivariate Mendelian randomization (MVMR) was used to estimate the direct effect of dried fruit intake on kidney function markers.ResultsThe univariate MR analysis showed that increased dried fruit intake was associated with lower kidney function markers, including BUN (β: −0.171, 95% confidence interval (CI): −0.239 to −0.102, p = 1.063 × 10−6), CR (β: −0.205, 95% CI: −0.311 to −0.099, p = 1.455 × 10−4), UA (β = −0.317, 95% CI: −0.384 to −0.249, p = 4.439 × 10−20), and CysC (β = −0.323, 95% CI: −0.384 to −0.249, p = 1.074 × 10−11); however, it was unrelated to hematuria and microalbuminuria. Causality persisted after performing MVMR analysis; however, with the addition of alcohol consumption and smoking as exposure factors, the causality for UA (β = −0.296, 95% CI: −0.523 to −0.068, p = 1.094 × 10−2) and CysC (β = −0.238, 95% CI: −0.465 to −0.011, p = 4.024× 10−2) weakened, while the causality for BUN (β = −0.038, 95% CI: −0.215 to 0.138, p = 6.698 × 10−1) and CR (β = −0.038, 95% CI: −0.431 to 0.046, p = 1.347 × 10−1) disappeared.ConclusionIncreased dried fruit intake was associated with lower kidney function markers (BUN, CR, UA, and CysC) in the absence of smoking and alcohol consumption; however, the causal relationship between dried fruit intake and BUN and CR disappeared in the presence of smoking and alcohol consumption. These results provide a promising avenue for delaying the course of chronic kidney disease.

Litter decomposition is significantly influenced by soil fauna, litter quality, and climate. Effects of soil fauna on litter decomposition are largely dependent on the size classes of the fauna. However, the understanding of how different soil fauna groups affect litter decomposition remains elusive. In this study, we conducted a global meta-analysis of experiments using litterbags with varying mesh sizes to quantify the contributions of mesofauna and macrofauna to litter decomposition by calculating log response ratios. Additionally, we quantitatively assessed how climatic conditions and litter quality influence the effect of these two faunal size classes on litter decomposition. Our findings demonstrated that mesofauna and macrofauna increased litter decomposition by an average of 12.25% and 22.14%, respectively. Furthermore, the relative increase in litter decomposition induced by mesofauna and macrofauna exhibited a significant statistical difference on a global scale. Specifically, in dry and temperate climatics, the effect of soil macrofauna on litter decomposition was significantly greater than that of mesofauna. Climatic conditions, particularly temperature and precipitation, were the primary factors influencing litter decomposition by both mesofauna and macrofauna. In contrast, litter quality significantly influenced decomposition only by macrofauna in dry and tropical climatic conditions. Our findings underscore that the relative increase in litter decomposition rates to mesofauna and macrofauna differed significantly on a global scale and that the climate and litter quality differentially regulate litter decomposition across faunal size classes.

Ultra-short-term wind speed prediction is the key to ensure the implementation effect of wind turbine pitch angle feedforward control, and has an important impact on improving the environmental adaptability of wind turbines. In order to improve the prediction accuracy, an ultra-short-term wind speed prediction method based on an improved combined neural networks was proposed. In this method, BP neural network and long short-term memory (LSTM) neural network, which are suitable for time series prediction and have strong nonlinear learning ability, are selected for weighted combination to eliminate the large error that may exist in a single neural network. At the same time, to improve the combination effect, the differential evolution (DE) algorithm was used to optimize the combination weight. The method was applied to the ultra-short-term wind speed prediction of a wind farm. Compared with the results of single neural network prediction and equal weight combined neural networks prediction, the effectiveness of the proposed method in improving the prediction accuracy was verified.

Abstract Background Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. Methods The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured. Results The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis. Conclusions Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.

Background: Radiotherapy is a major modality for esophageal cancer (ESCA) treatment, yet radioresistance severely hampers its therapeutic efficacy. Ubiquitin-specific peptidase 14 (USP14) is a novel deubiquitinase and can mediate cancer cells’ response to irradiation, although the underlying mechanism remains unclear, including in ESCA. Methods: To evaluate the expression of USP14 in ESCA tissues or cells, we used RNA-Seq, immunoblotting, co-immunoprecipitation (Co-IP), ubiquitination, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence assays in this investigation. Additionally, we used CCK8, cloning, and migration tests to examine the proliferation and migration of ESCA cells. We also used transplantation tumor mouse model to investigate the course of the cancer cell growth. Finally, we looked into the biological processes linked to USP14 using gene set enrichment analysis (GSEA), which was later verified. Results: We observed a significant upregulation of USP14 in human ESCA tissues and cell lines, especially in those with radioresistance. Moreover, USP14 knockdown significantly restrained the proliferation and inhibited the radiation tolerance of ESCC cells. Here, we identified a potential inhibitor of USP14, Degrasyn (DGS), and investigated its regulatory effects on ESCA radioresistance and progression. We found that DGS had marked antiproliferative effects in radiosensitive ESCA cell lines. Notably, a low dose of DGS significantly enhanced the sensitivity of radioresistant ESCA cells to irradiation, as shown by the significantly reduced cell proliferation, migration, and invasion. Furthermore, the combination of DGS and X-ray irradiation strongly induced DNA damage in radioresistant ESCA cell lines by increasing the phosphorylation levels of H2AX (γ-H2AX) and checkpoint kinase 1/ataxia-telangiectasia-mutated-and-Rad3-related kinase (CHK1/ATR) signaling. Animal experiments confirmed the effective role of the DGS and X-ray combined treatment in reducing tumor growth and irradiation tolerance of ESCA in vivo with undetectable toxicity. Importantly, the promotive and malignant biological behaviors of ESCA cells suppressed by the DGS/X-ray combination treatment were almost eliminated by USP14 overexpression, along with the abolished DNA damage process. Mechanistically, we found that USP14 could interact with Yes-associated protein 1 (YAP1) and induce its deubiquitination in radioresistant ESCA cells. Interestingly, we discovered that DGS/X-ray co-therapy significantly reduced the stability of YAP1 and induced its ubiquitination in radioresistant ESCA cells. More importantly, the proliferation, epithelial-mesenchymal tansition (EMT) process, and DNA damage regulated by DGS/X-ray and USP14 knockdown were significantly eliminated when YAP1 was overexpressed in radioresistant ESCA cells. Conclusions: These data revealed the potential role of DGS/X-ray co-therapy in controlling ESCA resistance to radiotherapy by inhibiting the USP14/YAP1 axis, providing a candidate strategy for ESCA treatment.

Spatially explicit, near real time information on surface water dynamics is critical for understanding changes in water resources, and for long-term water security planning. The distribution of surface water across the African continent since 1984 and updated as every new Landsat scene becomes available is presented here, and validated for the continent for the first time. We applied the Water Observations from Space (WOfS) algorithm, developed and well-tested in Australia, to every Landsat scene acquired over Africa since the mid 1980s to provide spatial information on surface water dynamics over the past 30+ years. We assessed the accuracy of WOfS using aerial and satellite imagery. Four regional geospatial organisations, coordinated through the Digital Earth Africa Product Development Task Team, conducted the validation campaign and provided both the regional expertise and experience required for a continental-scale validation effort. We assessed whether the point was wet, dry, or cloud covered, for each of the 12 months in 2018, resulting in 34,800 labelled observations. As waterbodies larger than 100 km2 are easy to identify with Landsat resolution data and can thus boost accuracy, these were masked out. The resulting overall accuracy of the water classification was 82%. WOfS in Africa is expected to be used by ministries and departments of agriculture and water across the continent, by international organisations, academia, and the private sector. A large-scale collaborative effort, which included regional and technical skills spanning two continents was required to create a service that is regionally accurate and is both hosted on, and implemented operationally from, the African continent.

Equitable access to sanitation for all is a goal of sustainable development, notably in rural areas. However, studies including economic, socio-cultural, and other factors that have been conducted to comprehensively assess rural sanitation at the community level in developing countries are limited. This study aimed to investigate the current state of rural environmental sanitation on the community level and to evaluate the characteristics of the diverse sub-clusters. A multidimensional environmental sanitation survey was conducted on 400 communities in Chongqing, China in 2020, and the priority options for improving sub-clusters’ sanitation were explored using cluster analysis. Among all communities, more than 60 % had positive village appearance, 50.50 % had domestic sewage treatment, and the coverage rate of household sanitary toilets was 72.28 %. The average content for lead, cadmium (Cd), and chromium in soil was 26.01, 0.53, and 54.47 mg/kg, respectively. The communities were clustered into 3 groups (I, II, III) based on similar characteristics including basic information, village appearance, water, sanitation, hygiene management, bio-vector control, and soil pollution. The proportion of cluster I, II, and III was 39.25 % (157/400), 31.75 % (127/400), and 29.00 % (116/400), respectively. Each cluster had its sanitation characteristics, and significant differences among the sub-clusters were observed in Cd of soil (p = 0.001), domestic sewage disposal ratio (p

Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.

Abstract Orexin signaling plays a facilitatory role in respiration. Abnormalities in orexin levels correlate with disordered breathing patterns and impaired central respiratory chemoreception. Nucleus tractus solitarii (NTS) neurons expressing the transcription factor Phox2b contribute to the chemoreceptive regulation of respiration. However, the extent to which orexinergic signaling modulates respiratory activity in these Phox2b-expressing NTS neurons remains unclear. In the present study, the injection of orexin A into the NTS significantly increased the firing rate of the phrenic nerve. Further analysis using fluorescence in situ hybridization and immunohistochemistry revealed that orexin 1 receptors (OX1Rs) were primarily located in the ventrolateral subdivision of the NTS and expressed in 25% of Phox2b-expressing neurons. Additionally, electrophysiological recordings showed that exposure to orexin A increased the spontaneous firing rate of Phox2b-expressing neurons. Immunostaining experiments with cFos revealed that the OX1R-residing Phox2b-expressing neurons were activated by an 8% CO2 stimulus. Crucially, OX1R knockdown in these NTS neurons notably blunted the ventilatory response to 8% CO2, alongside an increase in sigh-related apneas. In conclusion, orexinergic signaling in the NTS facilitates breathing through the activation of OX1Rs, which induces the depolarization of Phox2b-expressing neurons. OX1Rs are essential for the involvement of Phox2b-expressing NTS neurons in the hypercapnic ventilatory response.

Objective To investigate the impacts of circular RNA RERE (circRERE) on proliferation, migration and invasion of human multiple myeloma (MM) cell lines by regulating microRNA (miR)-128-3p/serine/threonine protein kinase (WEE1) axis. Methods Normal plasma cells (nPCs) isolated from peripheral blood of healthy subjects and human MM cell lines(U266, RPMI-8226, NCI-H929, LP-1) were cultured. The expressions of circRERE and miR-128-3p were detected by RT-qPCR. The expression of WEE1 was detected by Western blot. After transfection, RPMI-8226 cells were divided into control group (without transfection), sh-circRERE group, sh-NC group, miR-128-3p inhibitor group, inhibitor-NC group, sh-circRERE+inhibitor-NC group and sh-circRERE+miR-128-3p inhibitor group. MTT assay and 5-ethynyl-2'-deoxyuridine (EdU) immunofluorescence staining microscopy were used to detect the proliferation. Migration and invasion were examined by scratch healing experiment as well as Transwell chamber assay. The targeting relationship between miR-128-3p and circRERE or WEE1 was verified though dual-luciferase reporter gene assay. Results Compared with nPCs, the expressions of circRERE and WEE1 in MM cells (RPMI-8226, U266, NCI-H929, LP-1) were increased, and the expression of miR-128-3p was decreased (P＜0.05). Compared with the control group, the proliferation rate, proportion of EdU positive cells, the healing rate of the scratch trauma and the number of invasion of the RPMI-8226 cells in sh-circRERE group were decreased(P＜0.05). However,miR-128-3p inhibitor group showed an opposite result and the difference was statistically significant (P＜0.05). miR-128-3p inhibitor significantly inhibited the effects of sh-circRERE on the proliferation, migration and invasion of RPMI-8226 cells (P＜0.05). Dual luciferase reporter gene experiments showed that circRERE/miR-128-3p and miR-128-3p/WEE1 had a targeting relationship. Conclusions CircRERE may promote proliferation, migration and invasion of RPMI-8226 cells, potentially with a mechanism of regulating miR-128-3p/WEE1 axis.

The current distribution voltage prediction methods have low accuracy and cannot realize more efficient system power allocation. To address this, the study proposes a distributed photovoltaic distribution voltage prediction model based on gradient boosting tree and time convolutional network. The model uses eXtreme gradient boosting for feature selection and time convolutional network and two-layer prediction strategy for voltage prediction. Then, the model is improved and optimized using residual module with bottle sea sheath algorithm. The outcomes indicated that the evaluation results of the model’s prediction intervals coverage probability, prediction interval normalized average width, R-squared, root mean square error, and running time indexes were 97.47%, 0.02, 97.48%, 0.15, and 2.11s, respectively. The research-designed model, when applied to voltage control, can effectively prevent voltage overrun situations. The research-designed voltage prediction model has important practical application value for the prediction and control of photovoltaic distribution voltage in power systems.

Chronic obstructive pulmonary disease (COPD) is one of the major chronic airway diseases, with the highest prevalence among individuals over 60 years old, significantly impacting the health of elderly patients. Both domestic and international COPD prevention and treatment guidelines recommend pulmonary rehabilitation as a complementary and effective adjunct to pharmacological treatment. Pulmonary rehabilitation can significantly improve patients' respiratory function and physical fitness, alleviate symptoms, and reduce hospitalization and mortality rates. However, the specific contents of pulmonary rehabilitation for elderly COPD patients differ depending on the stage of the disease. This expert consensus elaborates on the assessment and treatment contents of pulmonary rehabilitation for elderly COPD patients in the acute exacerbation period, acute exacerbation remission period, and outpatient stable period, aiming to provide guidance for pulmonary rehabilitation treatment at different stages of the disease. This consensus identifies common functional impairments in elderly COPD patients, including respiratory dysfunction, exercise tolerance impairment, psychological issues, swallowing dysfunction and cognitive impairment. It recommends a comprehensive assessment of elderly COPD patients' multifaceted impairments based on the International Classification of Functioning, Disability, and Health (ICF) framework, covering four aspects：body structure, body function (respiratory function, cardiac function, exercise function, psychological and cognitive function, swallowing function, and nutritional factors), activity and participation, and environmental factors. Pulmonary rehabilitation is suitable for all patients exhibiting relevant symptoms and/or those at high risk of acute exacerbations (high-level evidence). As the disease progresses, the rehabilitation team, treatment plan, and treatment location should be adjusted in a timely manner, forming a continuous rehabilitation cycle. Smoking cessation is a crucial intervention to slow down the decline in lung function and the progression of COPD (high-level evidence). Through adequate nutritional support, elderly COPD patients can improve their nutritional status, enhance physical strength and quality of life, better manage the disease, and promote rehabilitation (low to moderate-level evidence). Oxygen therapy is recommended for patients with advanced COPD who remain hypoxemic at rest (low to moderate-level evidence). Some emerging rehabilitation treatments (such as neuromuscular electrical stimulation, acupuncture, and certain traditional Chinese medicines) may have some value for elderly COPD patients (low to moderate-level evidence. This expert consensus divides rehabilitation treatment into three stages：Phase I Pulmonary Rehabilitation, Phase II Pulmonary Rehabilitation, and Phase III Pulmonary Rehabilitation, based on the different stages of elderly COPD patients. It further details the target population, implementation location, rehabilitation content, assessment content, participating disciplines, and rehabilitation goals for each stage, emphasizing the need for clinical respiratory specialists, primary care physicians, rehabilitation physicians/therapists, nurses, nutritionists, psychologists, and social workers to actively coordinate and collaborate throughout the full-cycle rehabilitation process for elderly COPD patients.

Elderly lung cancer is the leading cause of cancer-related deaths worldwide, posing significant challenges to public health. This consensus systematically reviews relevant clinical guidelines and literature both domestically and internationally, integrating recent clinical experiences and research findings. It summarizes new clinical rehabilitation concepts from experts in rehabilitation medicine, respiratory medicine, and nursing regarding elderly lung cancer. The consensus provides detailed discussions on the definition, risk factors, classification, staging, and clinical characteristics of elderly lung cancer, with a focus on functional impairments and their rehabilitation assessment and treatment strategies. Functional impairments encompass multiple aspects, including pulmonary function, cardiac function, exercise capacity, pain, psychological issues, cognition, speech, swallowing, sensory functions, and bowel and bladder dysfunction. The consensus offers comprehensive academic guidance and clinical practice recommendations for rehabilitation professionals across various healthcare settings. It emphasizes that the full-cycle rehabilitation of elderly lung cancer requires multidisciplinary teamwork to ensure seamless integration of clinical care, rehabilitation, and nursing, maximizing patient functional recovery and quality of life. By conducting a comprehensive assessment of patients' overall conditions and formulating personalized rehabilitation treatment plans, effective improvements in functional impairments, symptom relief, and even prolongation of survival can be achieved. Additionally, the consensus outlines the service process for full-cycle rehabilitation of lung cancer, highlighting the interconnectedness of tertiary hospitals, secondary hospitals, community hospitals, and families, as well as the importance of adjusting rehabilitation models based on local circumstances. The promotion and implementation of this consensus aim to provide standardized guidance for the assessment and treatment of full-cycle rehabilitation in elderly lung cancer patients, with the expectation of improving rehabilitation outcomes and quality of life, thereby contributing to the development of elderly lung cancer rehabilitation in China.

Given the strong chattering problem caused by traditional sliding mode control, this paper uses a sliding mode control strategy based on an improved double power exponential reaching law to control the H-bridge inverter. To analyze the working process of the H-bridge inverter system with the improved double power exponential reaching law, a discrete iterative model of the H-bridge inverter system is established based on stroboscopic mapping theory. Then, the bifurcation diagram, folding diagram, and spectral diagram are used to study the nonlinear phenomena of the system under different control parameters, and the stability regions of the control parameters in the system are obtained: the stability region of $k_{1}$ is (0, 0.598], the stability region of $k_{2}$ is (0.26, 0.517], the stability region of k is (0.181, 0.444], the stability region of $\alpha $ is (0.074, 0.89], the stability region of $\beta $ is (1.03, 1.89], and the stability region of $\lambda $ is (0.92, 1.97]. The stable operating range of the system control parameters is analyzed based on the fast-varying stability principle, and the obtained stability range of the control parameters is consistent with the results shown in the bifurcation diagram. Finally, it is found that changes in external parameters such as voltage E, inductance R, and resistance L have an important impact on the performance of the inverter system, and have important theoretical guidance for the optimal design and debugging of H-bridge inverters.

The effects of different concentrations of ε-Poly-lysine (ε-PL: 0.005%, 0.01%, 0.02%, 0.04%, and 0.06%) on the marine fish-egg white protein compound gels, treated with 0.4% TGase induced cross-linking were systematically investigated under low salt and phosphorus-free conditions (0.5% NaCl). The results showed the combination of ε-PL and TGase had a synergistic effect on improving sectional gel properties of composite surimi samples. Wherein the rheological, LF-NMR, and SEM results confirmed that the addition of ε-PL based on 0.4% TGase significantly improved the gel strength (to the highest value: 781.63 g·cm), apparent viscosity, and G 'value of the composite surimi sample, as well as reduced the internal water fluidity of surimi, accompanied by the emergence of a more dense and uniform gel network structure. Notably, ε-PL treatment significantly inhibited fat oxidation in the compound surimi gel and the degree of inhibition was proportional to its addition (decreased from 2.03 to 1.67 mg·kg−1). However, the addition of a small amount (0.005%) or an excessive amount (0.06%) of ε-PL on the gel properties of composite surimi samples witnessed the negative effects of the changes in the internal water distribution state and the cooking loss. To sum up, moderate ε-PL (0.04%) treatment combined with TGase induction can maximize the performance of mixed surimi gel and inhibit fat oxidation. The research results supply a diverse perspective and theoretical basis for the development of 'low salt and no phosphorus' surimi product ingredients.

Abstract Background It is well-known that systemic inflammation plays a crucial role in the pathogenesis and prognosis of acute myocardial infarction (AMI). The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a novel index that is used for the characterization of the severity of systemic inflammation. Recent studies have identified the high SII level as an independent predictor of poor outcomes in patients with AMI. We aimed to investigate the prognostic implications of SII in AMI patients with and without diabetes mellitus (DM). Methods We included 2111 patients with AMI from February 2014 to March 2018. Multivariable Cox regression analyses were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death and cardiovascular (CV) death. Multiple imputation was used for missing covariates. Results Of 2111 patients (mean age: 65.2 ± 12.2 years, 77.5% were males) analyzed, 789 (37.4%) had DM. Generalized additive model analyses showed that as the SII increased, the C-reactive protein and peak TnT elevated while the LVEF declined, and these associations were similar in patients with and without DM. During a median of 2.5 years of follow-up, 210 all-cause deaths and 154 CV deaths occurred. When treating the SII as a continuous variable, a higher log-transformed SII was significantly associated with increased all-cause mortality (HR: 1.57, 95%CI: 1.02–2.43) and CV mortality (HR: 1.85, 95%CI 1.12–3.05), and such an association was also significant in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.90 [1.40–6.01] and 3.28 [1.43–7.57], respectively) while not significant in the nondiabetics (Pinteraction for all-cause death and CV death were 0.019 and 0.049, respectively). Additionally, compared to patients with the lowest tertiles of SII, those with the highest tertiles of SII possessed significantly higher all-cause mortality (HR: 1.82, 95%CI 1.19–2.79) and CV mortality (HR: 1.82, 95%CI 1.19–2.79) after multivariable adjustment, and this relationship remained pronounced in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.00 [1.13–3.55] and 2.09 [1.10–3.98], respectively) but was not observed in the nondiabetics (HRs and 95%CIs for all-cause death and CV death were 1.21 [0.75–1.97] and 1.60 [0.89–2.90], respectively). Our restricted cubic splines analyses indicated a pronounced linear association between SII and mortality only in diabetics. Conclusions In AMI patients with DM, high SII is an independent predictor of poor survival and may be helpful for patient’s risk stratification.

Abstract Background Hospital Examination Reservation System (HERS) was designed for reducing appointment examination waiting time and enhancing patients’ medical satisfaction in China, but implementing HERS would encounter many difficulties. This study would investigate the factors that influence patients’ utilization of HERS through UTAUT2, and provide valuable insights for hospital managements to drive the effective implementation of HERS. It is helpful for improving patients’ medical satisfaction. Methods We conducted a survey through the Sojump platform, targeting patients were who have already used HERS. We collected questionnaire information related to factors behavior intention, performance expectancy, and effort expectancy. Subsequently, we employed a structural equation model to analyze the factors influencing patients’ utilization of HERS. Results A total of 394 valid questionnaires were collected. Habit was the main direct positive factor influencing the behavioral intention of HERS (β = 0.593; 95%CI: 0.072, 1.944; P = 0.002), followed by patient innovation (β = 0.269; 95%CI: 0.002, 0.443; P

As core pieces of equipment in hydropower generation, the operational condition of critical components such as the rotor and thrust bearing is crucial for the stability of hydropower units. The essence of fault diagnosis for hydroelectric generating units is pattern recognition. To achieve high recognition accuracy, it is necessary to maximize the distinguishability of different fault features. However, traditional time–frequency signal processing methods seldom consider this issue during the decomposition process, resulting in low sensitivity of the extracted features to different fault types. To address this issue, this paper proposes a fault feature extraction method for hydroelectric generating units based on Feature Modal Decomposition (FMD) and the Comprehensive Distance Evaluation Index (CDEI). By improving the FMD algorithm, the objective function for selecting modal components during the FMD decomposition process is set as the CDEI, which can measure the sensitivity of fault features, thereby enhancing the distinguishability of the obtained fault features. Next, the Distance Evaluation Index (DEI) is used to measure the sensitivity of the obtained features, and the most sensitive features are selected. Experiments using a rotor test bench and actual signals before and after thrust bearing horizontal adjustment from a hydroelectric generating unit were conducted and compared with related methods. The results show that the proposed method can effectively improve the sensitivity of the obtained fault features and achieve accurate fault diagnosis for hydroelectric generating units.

The oral bioavailability of curcumin is inherently low, which significantly limits its application in food systems. The objective of this study was to evaluate the impact of high-pressure processing on the stability and bioaccessibility of curcumin within an emulsion gel during simulated gastrointestinal transit and to assess its cellular uptake. Our findings suggest that increasing pressure levels and high κ-carrageenan concentrations can enhance the stability of the curcumin delivery system. Elevated κ-CG concentrations were found to retard the action of proteases on dissociating protein molecules from the gel network. The emulsion gel effectively slowed the release of free fatty acids and reduced the curcumin release rate during the gastric phase. Scanning electron microscopy images revealed that higher pressures induced the formation of a more uniform and dense network structure in the gel. While the gel network structures were well-preserved after gastric digestion, they were disrupted into smaller particles following intestinal digestion, with particle size increasing with higher applied pressures. Cytotoxicity assays indicated that the digesta from the intestinal phase was highly toxic to Caco-2 cells. Among the tested samples, the emulsion gel prepared with 1.0% κ-CG at 600 MPa demonstrated the highest curcumin bioavailability, reaching 63.82 ± 7.10%. These findings underscore the potential of HPP-induced emulsion gels as a viable delivery system for enhancing curcumin bioaccessibility and cellular uptake.

Achieving deep-blue light with high color saturation remains a critical challenge in the development of white light-emitting diode (LED) technology, necessitating luminescent materials that excel in efficiency, low toxicity, and stability. Here, we report the synthesis of [N(C2H5)4]2Cu2I4 (TEA2Cu2I4) single crystals (SCs), which exhibit deep-blue photoluminescence (PL) at 450 nm. These crystals are characterized by a significant Stokes shift of 180 nm, a long lifetime of 1.7 μs, and an impressive photoluminescence quantum yield (PLQY) of 96.7% for SCs and 87.2% for polycrystalline films. The zero-dimensional structure is attributed to the proper spacing of triangular inorganic units [Cu2I4]2− by organic cations [N(C2H5)4]+. This structural arrangement facilitates broadband deep-blue light emission with phosphorescent characteristics, as evidenced by temperature-dependent PL and time-resolved photoluminescence (TRPL) measurements. The band gap properties of TEA2Cu2I4 were further elucidated through density functional theory (DFT) computations. Notably, the material exhibited minimal PL intensity degradation after continuous UV irradiation and one month of exposure to ambient conditions. Moreover, the polycrystalline film of TEA2Cu2I4 maintained substantial deep-blue emission even after one year of storage. Utilizing TEA2Cu2I4 thin film, we fabricated an electroluminescent device emitting deep-blue light with high color saturation, featuring CIE coordinates (0.143, 0.076) and a brightness of 90 cd/m2. The exceptional photophysical properties of TEA2Cu2I4 render it a highly promising candidate for optoelectronic applications.

Bolt loosening detection is crucial for ensuring the safe operation of equipment. This paper presents a vision-based real-time detection method that identifies bolt loosening by recognizing anti-loosening line markers at bolt connections. The method employs the YOLOv10-S deep learning model for high-precision, real-time bolt detection, followed by a two-step Fast-SCNN image segmentation technique. This approach effectively isolates the bolt and nut regions, enabling accurate extraction of the anti-loosening line markers. Key intersection points are calculated using ellipse and line fitting techniques, and the loosening angle is determined through spatial projection transformation. The experimental results demonstrate that, for high-resolution images of 2048 × 1024 pixels, the proposed method achieves an average angle detection error of 1.145° with a detection speed of 32 FPS. Compared to traditional methods and other vision-based approaches, this method offers non-contact measurement, real-time detection capabilities, reduced detection error, and general adaptability to various bolt types and configurations, indicating significant application potential.

In this study, the response surface method (RSM) was used to optimize the deproteinization process of polysaccharides from Vitis vinifera L. SuoSuo (VTP). The antioxidant capacities of polysaccharides before and after deproteinization were evaluated. The structure of deproteinized VTP (DVTP), which has relatively strong antioxidant activity, was characterized, and the protective effect of DVTP on H2O2-induced HT22 cell damage was evaluated. The results of the RSM experiment revealed that the ideal parameters for deproteinization included a chloroform/n-butanol ratio (v/v) of 4.6:1, a polysaccharide/Sevage reagent (v/v) ratio of 2:1, a shaking time of 25 min, and five rounds of deproteinization. Preliminary characterization revealed that the DVTP was an acidic heteropolysaccharide composed of seven monosaccharides, among which the molar ratio of galacturonic acid was 40.65. FT-IR and the determination of uronic acid content revealed that DVTP contained abundant uronic acid and that the content was greater than that of VTP. In vitro, the antioxidant activity assay revealed that the hydroxyl radical scavenging capacity and total antioxidant capacity of DVTP were greater than those of VTP. In the range of 0.6~0.8 mg/mL, the DPPH scavenging capacities of VTP and DVTP were greater than that of vitamin C. In addition, cell viability was measured via a CCK-8 assay, which revealed that DVTP had a strong defense effect on H2O2-induced damage to HT22 cells. These findings suggest that DVTP has high antioxidant activity and could be used as a natural antioxidant in functional foods and medicines.

The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits.

Alzheimer's disease (AD) stands as the most prevalent neurodegenerative condition worldwide, and its correlation with microglial function is notably significant. Dl-3-n-butylphthalide (NBP), derived from the seeds of Apium graveolens L. (Chinese celery), has demonstrated the capacity to diminish Aβ levels in the brain tissue of Alzheimer’s transgenic mice. Despite this, its connection to neuroinflammation and microglial phagocytosis, along with the specific molecular mechanism involved, remains undefined. In this study, NBP treatment exhibited a substantial improvement in learning deficits observed in AD transgenic mice (APP/PS1 transgenic mice). Furthermore, NBP treatment significantly mitigated the total cerebral Aβ plaque deposition. This effect was attributed to the heightened presence of activated microglia surrounding Aβ plaques and an increase in microglial phagocytosis of Aβ plaques. Transcriptome sequencing analysis unveiled the potential involvement of the AGE (advanced glycation end products) -RAGE (receptor for AGE) signaling pathway in NBP’s impact on APP/PS1 mice. Subsequent investigation disclosed a reduction in the secretion of AGEs, RAGE, and proinflammatory factors within the hippocampus and cortex of NBP-treated APP/PS1 mice. In summary, NBP alleviates cognitive impairment by augmenting the number of activated microglia around Aβ plaques and ameliorating AGE-RAGE-mediated neuroinflammation. These findings underscore the related mechanism of the crucial neuroprotective roles of microglial phagocytosis and anti-inflammation in NBP treatment for AD, offering a potential therapeutic target for the disease.

Transglutaminase (EC 2.3.2.13, TGase), an enzyme that catalyzes the formation of covalent cross-links between protein or peptide molecules, plays a critical role in commercial food processing, medicine, and textiles. TGase from Streptomyces is the sole commercial enzyme preparation for cross-linking proteins. In this study, we revealed that the SOS response repressor protein LexA in Streptomyces mobaraensis not only triggers morphological development but also enhances TGase synthesis. The absence of lexA significantly diminished TGase production and sporulation. Although LexA does not bind directly to the promoter region of the TGase gene, it indirectly stimulates transcription of the tga gene, which encodes TGase. Furthermore, LexA directly enhances the expression of genes associated with protein synthesis and transcription factors, thus favorably influencing TGase synthesis at both the transcriptional and posttranscriptional levels. Moreover, LexA activates four crucial genes involved in morphological differentiation, promoting spore maturation. Overall, our findings suggest that LexA plays a dual role as a master regulator of the SOS response and a significant contributor to TGase regulation and certain aspects of secondary metabolism, offering insights into the cellular functions of LexA and facilitating the strategic engineering of TGase overproducers.

ObjectiveThis population-based study aims to assess the survival benefits of selective neck dissection (SND) compared to neck observation in patients with T1/T2N0M0 major salivary gland malignancy (MSGC).MethodsWe conducted a retrospective review of T1/T2N0M0 MSGC patients who underwent primary tumor surgical extirpation with or without elective neck dissection in the Surveillance, Epidemiology, and End Results database (SEER) from 2004-2015. The impact of SND and clinical variables on overall survival (OS) and disease-specific survival (DSS) was evaluated using Univariate and Multivariate Cox proportional hazards regression models. Kaplan-Meier survival curves were generated, and survival rates were assessed via the log-rank test.ResultsOf 3778 post-operative T1-T2N0M0 MSGC patients, 2305 underwent elective neck dissection, while 1473 did not. Median follow-up was 106 months. Univariate and Multivariate analysis identified SND as a prognostic factor for OS in all the study population. After stratified analysis, we found that in the poorly high-grade (differentiated and undifferentiated) patients, the survival showed a significant OS and DSS benefit after receiving SND compared with the neck observations [HR for OS (95%CI): 0.571(0.446-0.731), P

ObjectiveThe study aimed to systematically evaluate the relationship between CYP3A5*3 gene polymorphisms and the blood concentration and effectiveness of tacrolimus (TAC) in patients with membranous nephropathy (MN).MethodsPubMed, Cochrane Library, Embase, Web of Science, China Biomedical, China National Knowledge Infrastructure, Wanfang, Vipshop, ReadShow, Clinical Trials Registry, and other databases were searched. Studies on the relationship between CYP3A5*3 gene polymorphism and TAC blood concentration in MN patients were collected, and meta-analysis was performed using Stata 16 software. ResultsA total of eight publications were included in the study, including 498 MN patients. CYP3A5*3 gene polymorphisms are associated with tacrolimus blood levels in patients with MN. The results of the relationship between CYP3A5*3 genotype polymorphisms and tacrolimus blood trough concentrations of the AA + AG genotype were lower than those of the GG genotype at ≤1 month [WMD = −2.08, 95% CI (−2.57, −1.59), p < 0.001] and 1–6 months [WMD = −0.63, 95% CI (−0.98, −0.27), p < 0.001]; however, they were not statistically significant at ≥6 months (p = 0.211). Furthermore, the subgroup analysis revealed that the dose-adjusted concentration of tacrolimus (C0/D) of the AA + AG genotype was lower than that of the GG genotype at ≤1 month [SMD = −1.93, 95% CI (−2.79, −1.08), p < 0.001], 1–6 months [SMD = −2.25, 95% CI (−2.71, −1.79), p < 0.001], and ≥6 months [SMD = −2.36, 95% CI (−2.86, −1.86), p < 0.001]. In addition, there was no statistically significant difference in effectiveness between the two groups at 3, 6, and 12 months of TAC administration (p > 0.05).ConclusionSerum TAC concentrations in MN patients were correlated with CYP3A5*3 genotype polymorphisms. Detection of the CYP3A5*3 genotype before the administration of TAC may provide some clinical value for optimizing the treatment of MN patients.Systematic Review Registration:https://inplasy.com/, identifier [INPLASY202430083].

In October 2017, a small outbreak of echovirus 30 (E30) associated with aseptic meningitis in nine cases occurred at a primary school in the Ningxia Hui Autonomous Region. That year, we observed a significant increase in E30 levels in an acute flaccid paralysis (AFP) case surveillance system. To investigate their phylogenetic relationships, we determined the whole genomic sequences of 12 strains isolated from aseptic meningitis cases, AFP cases, and healthy children. We found that the E30 strains circulating in Ningxia belong to two lineages (H and J). The strains isolated in 2010, 2012, and 2016 belonged to the H lineage. In 2017, a new lineage, J, emerged as the dominant lineage. Phylogenetic trees were constructed based on the whole genome and P1, P2, and P3 regions; clustering with other types of enterovirus species B was found, suggesting that recombination events had occurred. The recombination sites were mainly in regions 2B, 2C, and 3D. This study confirmed that the E30 strains in Ningxia in 2010, 2012, and 2016 had different recombination patterns and were recombined with different enteroviruses. The 2017 epidemic E30 originated from another new lineage with a complex recombination pattern and formed an independent transmission chain in Ningxia.

Abstract. Background:. Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. Methods:. Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration

Strong κ-carrageenan (KC) hydrogels were fabricated via solvent replacement with sorbitol, and the effects of KC mass fraction and solvent replacement on the structural characteristics encapsulation capability of the hydrogels were evaluated. Microstructural observation showed that the 3D network structures of hydrogels exhibited a complete and continuous skeleton. FTIR spectra of KC hydrogels revealed the formation of intermolecular hydrogen bonds after sorbitol replacement. The stability against heating and freeze-thawing of hydrogels was enhanced due to the addition of sorbitol and the rise in KC mass fraction. The hydrogel with 1.5 wt% KC after sorbitol replacement presented the best stability. Frequency sweep tests suggested that storage modulus of the samples were influenced by sorbitol replacement and KC concentration. Swelling tests revealed that the hydrogels after replacement with a higher KC content (1.25, 1.50 wt%) presented higher swelling capacity, and they were more stable in alkaline and acidic solutions. When epigallocatechin gallate (EGCG) was incorporated within the hydrogels, the hydrogels after sorbitol replacement offered higher protection capability. The information obtained in this study indicated that sorbitol replacement strengthened KC hydrogels, and they could act more appropriately as accountable carriers for bioactives.

Abstract To investigate the coupling effect of in situ stress and fluid pore pressure and the propagation law of damaged area during hydraulic fracturing and gas fracturing in heterogeneous fractured reservoirs, according to the effective stress principle and the smooth Rankine stress criterion, this paper establishes a coupled fluid–solid‐damage mathematical model of heterogeneous rock layers and carries out numerical simulations on the characteristic field changes of rock layers under water and nitrogen fracturing. The results show that the continuous injection of nitrogen or water can cause an increase in pore pressure in natural fractures and rock matrices, leading to rock damage and an increase in porosity. Under the same parameters, the damage area and length of the rock mass during nitrogen fracturing are larger than those of hydraulic fracturing, and the changes in pore pressure, permeability, and porosity are consistent with the damage area. The pore pressure near the connected natural fractures is relatively high, resulting in tensile strain; the pore pressure at isolated fractures is relatively low, and some even produce compressive strain. During nitrogen fracturing, the damage evolution is less affected by the in situ stress and the matrix permeability, while hydraulic fracturing is more affected by them. The damage area is the smallest when the horizontal in situ stress is equal. When the initial permeability of the matrix is low, the damaged area mainly follows the natural fractures and is distributed in a strip shape. As the permeability of the matrix increases, the fracturing fluid can enter the matrix, and the damaged area is in the shape of a block.

Codonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography–tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.

Abstract Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Abstract Chronic apical periodontitis is a prevalent oral disease characterized by bone loss, and its underlying mechanisms remain unclear. This study aimed to investigate the role and mechanism of the serine protease GZMA in osteoclasts during chronic apical periodontitis. To address this, we employed crRNA/Cas13d to inhibit GZMA expression and examined its impact on osteoclast behavior. Our findings revealed that GZMA plays a significant role in promoting osteoclast cell proliferation while inhibiting cell apoptosis. Additionally, the inhibition of GZMA led to a notable increase in miR-25-3p expression, which, in turn, downregulated the expression of TGF-β. Consequently, the reduction in TGF-β expression led to a decrease in PAR1 expression within the PARs pathway. These results suggest that GZMA might serve as a promising therapeutic target for the treatment of chronic apical periodontitis. Furthermore, our study highlights the potential of targeting GZMA using crRNA/Cas13d as a valuable approach for future therapeutic interventions.

AIM: To evaluate the damage to optic nerve by detecting the morphological and functional changes of optic nerve in patients with acute primary angle-closure glaucoma.METHODS: The correlation among the positive rates of fundus photography, visual field examination, optical coherence tomography(OCT)scan of the optic nerve, and pattern visual evoked potentials(P-VEP)were analyzed in 28 patients with acute primary angle-closure glaucoma affecting.RESULTS: Among 28 eyes of 28 patients, optic nerve images were obtained in 25 eyes(89%), optic disc color in 25 eyes: there were 9 normal eyes and 16 eyes with congestion and edema, without pallor; C/D: < 0.6 in 5 eyes, > 0.6 in 1 eye, and indistinguishable in 19 eyes; disk edge: 6 eyes were normal, and 19 eyes could not be distinguished.Optic nerve images could not be obtained in 3 eyes(11%). Visual field examination: 9 eyes(32%)were normal, 2 eyes(7%)had visual field damage, 8 eyes(29%)had no reference value due to cataract visual field examination, 2 eyes(7%)had false positive rate ≥15%, and 7 eyes(25%)could not cooperate with the examination. The retinal nerve fiber layer thickness around optic disc was measured by OCT in 26 eyes(93%), of which the thickness of nerve fiber layer was normal in 24 eyes and local thinning in 2 eyes. Severe opacification of refractive stroma could not be measured in 2 eyes(7%). PVEP showed that the peak of P100 was normal in 18 eyes(64%)and prolonged in 10 eyes(36%). The amplitude of P100 wave was normal in 11 eyes(39%)and decreased in 17 eyes(61%).CONCLUSION: After a major acute attack of primary angle-closure glaucoma, the optic nerve does not exhibit typical glaucomatous damage but may present with optic disc congestion and edema. Therefore, a comprehensive evaluation combining subjective and objective examination methods is necessary for optic nerve assessment, and currently, no more precise assessment method is available.