Search

Abstract Background Microtubule polymerization is usually considered as the upstream of apoptotic cell death induced by taxanes, but recently published studies provide more insights into the mechanisms responsible for the antineoplastic effect of taxanes. In this study, we figure out the role of the stress-related PERK/eIF2α axis in tumor cell death upon taxane treatment along with paclitaxel resistance. Methods Utilizing immunoblot assay, the activation status of PERK-eIF2α signaling was detected in a panel of cancer cell lines after the treatment of taxanes. The causal role of PERK-eIF2α signaling in the cancer cell apoptosis induced by taxanes was examined via pharmacological and genetic inhibitions of PERK. The relationship between microtubule polymerization and PERK-eIF2α activation was explored by immunofluorescent and immunoblotting assays. Eventaually, the combined therapeutic effect of paclitaxel (PTX) and CCT020312, a PERK agonist, was investigated in PTX-resistant breast cancer cells in vitro and in vivo. Results PERK-eIF2α axis was dramatically activated by taxanes in several cancer cell types. Pharmacological or genetic inhibition of PERK efficiently impaired taxane-induced apoptotic cell death, independent of the cellular microtubule polymerization status. Moreover, PTX was able to activate the PERK/eIF2α axis in a very low concentration without triggering microtubule polymerization. In PTX-resistant breast cancer cells, the PERK/eIF2α axis was attenuated in comparison with the PTX-sensitive counterparts. Reactivation of the PERK/eIF2α axis in the PTX-resistant breast cancer cells with PERK agonist sensitized them to PTX in vitro. Combination treatment of the xenografted PTX-resistant breast tumors with PERK agonist and PTX validated the synergic effect of PTX and PERK activation in vivo. Conclusion Activation of the PERK/eIF2α axis is a pivotal prerequisite of taxanes to initiate cancer cell apoptosis, which is independent of the well-known microtubule polymerization-dependent manner. Simultaneous activation of PERK-eIF2α signaling would be a promising therapeutic strategy to overcome PTX resistance in breast cancer or other cancers.

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Abstract Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer progression. Epithelial–mesenchymal transition (EMT) is a key feature of metastatic cells. In our pervious study, we found that CD248+CAFs activated M2-polarized macrophages, enhancing the progression of NSCLC. However, it is yet unclear how CD248+CAFs inducing M2-polarized macrophages induce EMT program in NSCLC cells. Herein, we examined CD248 expression from CAFs derived from NSCLC patient tumour tissues. Furthermore, we determined the influence of CD248 knock down CAFs on macrophages polarization. Next, we explored the influences of CD248-harboring CAFs-mediated M2 macrophage polarization to promote NSCLC cells EMT in vitro. We constructed fibroblasts specific CD248 gene knock out mice to examine the significance of CD248-harboring CAFs-induced M2-polarized macrophages to promote NSCLC cells EMT in vivo. Based on our analysis, CD248 is ubiquitously expressed within NSCLC-originating CAFs. CD248+CAFs mediated macrophages polarized to M2 type macrophages. CD248+CAFs induced M2 macrophage polarization to enhance NSCLC cells EMT both in vivo and in vitro. Our findings indicate that CD248-harboring CAFs promote NSCLC cells EMT by regulating M2-polarized macrophages.

Objective In the central Yunnan region, the geological structure is complex and karst formations are prevalent. Sudden water gushing and attenuation of spring flow are among the most difficult problems in tunnel construction. The Mengkuanggou karst water system exhibits a high degree of karst conduitization, with significant differences between karst fissures and karst conduits. Methods This study employs the MODFLOW-CFPv2 dual medium numerical model to simulate the karst water system of Mengkuanggou, providing a detailed description of karst pipeline and diversion tunnel to understand the influence of tunnel construction on groundwater flow and spring flow. Results The results show that (1) The MODFLOW-CFPv2 model can describe the complex geological structure of karst areas, and simulate the dynamic characteristics of the groundwater level and the response characteristics of karst spring flow in the study area. (2) Under the condition of strong discharge, the water inflow per unit length of the tunnel is 164 m3/d·m, with a stable water inflow of 69 m3/d·m, while the Mengkuanggou karst spring flow shows a significant downwards trend. During the simulation period, the average spring flow decreased from 1 578 L/s under natural conditions to 1 098 L/s, an overall decrease of 30.4%, and the peak flow rate decreased from 2 133 L/s to 1 375 L/s, a decrease of 35.5%. The construction of strong discharge conditions will have a significant impact on tunnel construction and the groundwater environment. Under the condition of limited discharge, the maximum water inflow of the tunnel is 39 m3/d·m, and the stable water inflow is 24 m3/d·m. The water inflow of the tunnel is significantly reduced, and the downwards trend of the karst spring flow in Mengkuanggou is also improved to a certain extent. During the simulation period, the average spring flow is reduced to 1 284 L/s, a reduction of 18.6%, and the peak flow is reduced to 1 617 L/s, a decrease of 22.1%. Conclusion The MODFLOW-CFPv2 dual-medium model used in this study accurately describes highly heterogeneous karst water systems with pipelines, karst caves and fissures in karst areas. It can be used to quantitatively evaluate the karst water of Mengkuanggou during Xianglushan Tunnel construction.

Abstract Single cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.

Abstract In this paper, we present a novel Secure Clustering Routing Method based on Blockchain and Swarm Intelligence (BS-SCRM) for Wireless Sensor Networks (WSNs), which serves as a cornerstone in the Internet of Things (IoT) infrastructure. Recognizing the limitations of existing clustering routing methods in addressing security threats, our approach integrates blockchain technology to fortify WSNs against vulnerabilities such as man-in-the-middle attacks. The proposed BS-SCRM method is structured in two phases: (1) an enhanced cluster head (CH) election utilizing an elite strategy-enhanced Whale Optimization Algorithm (WOA) that considers node energy and proximity to the base station, and (2) a secure data on-chain phase where blockchain comes into play, encrypting and validating cluster data to safeguard integrity and prevent tampering. We further tackle the challenge of implementing blockchain in resource-constrained WSNs by assigning distinct roles to devices, i.e., ordinary nodes with data viewing permissions and accounting nodes entrusted with both data viewing and consensus algorithm execution. Extensive simulations confirm that BS-SCRM not only improves clustering quality but also provides a more secure and energy-efficient routing solution compared to contemporary methods. More specifically, simulation results in different scenarios demonstrate that BS-SCRM enhances network lifetime by 24–73% compared to other clustering methods when facing attacks.

Objective To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. Methods LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. Results The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. Conclusion The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

Abstract The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P

Based on varieties, area and distribution of wheat in China, 1 377 newly harvested wheat samples from 12 provinces were collected in 2022. The physio-chemical quality as well as end-use quality evolutions were carried out, and the current quality status of wheat were analyzed. The results showed that the average crude protein content and gluten content of wheat were 13.1% and 29.6%, respectively, and the mean gluten index was 69. Among the rheological parameters of dough, the water absorption of flour was 63.2 mL, and the average stability time was 6.7 min. The mean tensile curve area, elongation and maximum tensile resistance were 75 cm2, 140 mm and 398 EU, respectively. All samples were evaluated for the processing quality of noodles and steamed bread, and samples with strong gluten wheat varieties and wet gluten content ≤25% were evaluated for the processing quality of bread and cake, respectively. The average scores of noodles, steamed bread, bread and cake were 79, 75, 73 and 69 points, respectively. Only 1.7% of the samples met the requirements of “High quality wheat-Strong gluten wheat” (GB/T 17892—1999), while 1.3% of the samples met the requirements of “High quality wheat-Weak gluten wheat” (GB/T 17893—1999). In addition, 44.9%, 31.4% and 2.8% of the samples met the requirements of quality classification, high-quality wheat and high-quality strong gluten wheat in “Quality classification of wheat varieties” (GB/T 17320—2013), respectively, and 56.0% and 3.0% of the samples met the requirements of quality classification and strong gluten hard wheat in “The Grain & Oil Products of China-Wheat” (LS/T 3109—2017), respectively. The results showed that the processing quality of wheat in China was general, and the food quality of steamed food was higher than that of baked food. A few varieties with excellent food processing quality bred were also planted.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.

BackgroundThis study aimed to identify the predictive factors for prolonged length of stay (LOS) in elderly type 2 diabetes mellitus (T2DM) patients suffering from cerebral infarction (CI) and construct a predictive model to effectively utilize hospital resources.MethodsClinical data were retrospectively collected from T2DM patients suffering from CI aged ≥65 years who were admitted to five tertiary hospitals in Southwest China. The least absolute shrinkage and selection operator (LASSO) regression model and multivariable logistic regression analysis were conducted to identify the independent predictors of prolonged LOS. A nomogram was constructed to visualize the model. The discrimination, calibration, and clinical practicality of the model were evaluated according to the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsA total of 13,361 patients were included, comprising 6,023, 2,582, and 4,756 patients in the training, internal validation, and external validation sets, respectively. The results revealed that the ACCI score, OP, PI, analgesics use, antibiotics use, psychotropic drug use, insurance type, and ALB were independent predictors for prolonged LOS. The eight-predictor LASSO logistic regression displayed high prediction ability, with an AUROC of 0.725 (95% confidence interval [CI]: 0.710–0.739), a sensitivity of 0.662 (95% CI: 0.639–0.686), and a specificity of 0.675 (95% CI: 0.661–0.689). The calibration curve (bootstraps = 1,000) showed good calibration. In addition, the DCA and CIC also indicated good clinical practicality. An operation interface on a web page (https://xxmyyz.shinyapps.io/prolonged_los1/) was also established to facilitate clinical use.ConclusionThe developed model can predict the risk of prolonged LOS in elderly T2DM patients diagnosed with CI, enabling clinicians to optimize bed management.

Under resource distribution context, individuals have a strong aversion to unfair treatment not only toward themselves but also toward others. However, there is no clear consensus regarding the commonality and distinction between these two types of unfairness. Moreover, many neuroimaging studies have investigated how people evaluate and respond to unfairness in the abovementioned two contexts, but the consistency of the results remains to be investigated. To resolve these two issues, we sought to summarize existing findings regarding unfairness to self and others and to further elucidate the neural underpinnings related to distinguishing evaluation and response processes through meta-analyses of previous neuroimaging studies. Our results indicated that both types of unfairness consistently activate the affective and conflict-related anterior insula (AI) and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA), but the activations related to unfairness to self appeared stronger than those related to others, suggesting that individuals had negative reactions to both unfairness and a greater aversive response toward unfairness to self. During the evaluation process, unfairness to self activated the bilateral AI, dACC, and right dorsolateral prefrontal cortex (DLPFC), regions associated with unfairness aversion, conflict, and cognitive control, indicating reactive, emotional and automatic responses. In contrast, unfairness to others activated areas associated with theory of mind, the inferior parietal lobule and temporoparietal junction (IPL-TPJ), suggesting that making rational judgments from the perspective of others was needed. During the response, unfairness to self activated the affective-related left AI and striatum, whereas unfairness to others activated cognitive control areas, the left DLPFC and the thalamus. This indicated that the former maintained the traits of automaticity and emotionality, whereas the latter necessitated cognitive control. These findings provide a fine-grained description of the common and distinct neurocognitive mechanisms underlying unfairness to self and unfairness to others. Overall, this study not only validates the inequity aversion model but also provides direct evidence of neural mechanisms for neurobiological models of fairness.

BackgroundSputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.MethodsThis study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.ResultsThe levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).ConclusionThis study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

Background: Qingdu Fang (QDF) is a traditional Chinese herbal formula with remarkable clinical effect in the treatment of HR-HPV, but its mechanism remains unclear. In this study, UPLC-QTOF-MS was used to detect its components, network pharmacology was used to explore the traditional Chinese medicine monomers and their related targets for the treatment of HR-HPV in QDF. Molecular docking and in vitro experiments were performed to verify the results.Methods: QDF constituents and active compounds were identified using UPLC-QTOF-MS analysis. TCMSP and GeneCard databases were used to identify active components, targets, and potential therapeutic targets in HR-HPV. PPI network was constructed using the String database to analyze protein-protein interactions. Cytoscape3.7.2 was used to construct PPI networks, while GO enrichment and KEGG pathway analyses with R. The effect of QDF on H8 cell proliferation was measured using the CCK-8 method, and apoptosis and cell cycle was assessed with flow cytometry. The effects of QDF on PI3K/AKT pathway were detected by Western blotting.Results: A total of 27 compounds were identified on QDF by UPLC-QTOF-MS. Base on Network pharmacology,a total of 254 target genes are involved in the action of QDF on cervical HR-HPV. PPI analysis suggested that TP53, JUN, AKT1, STAT3, TNF and IL6 were potential targets for QDF treatment of HR-HPV. Molecular docking shows that two compounds have strong binding activity with AKT1. CCK-8 and morphological observation have shown that QDF inhibits H8 cell proliferation in a dose-dependent manner. Flow cytometry experiments suggest that QDF induces apoptosis and cell cycle arrest in H8 cells. Western blotting experiments reveal that QDF inhibits the PI3K/AKT signaling pathway.Conclusion: QDF has a multi-faceted therapeutic approach for HR-HPV, targeting inflammation, oxidation, and apoptosis. It induces apoptosis in H8 cells by inhibiting the PI3K/AKT pathway.

Background: Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (PIP5K1A) acts upstream of the Akt regulatory pathway and is abnormally expressed in many types of malignancies. However, the role and mechanism of PIP5K1A in colorectal cancer (CRC) have not yet been reported. In this study, we aimed to determine the association between PIP5K1A and progression of CRC and assess the efficacy and mechanism by which rupatadine targets PIP5K1A. Methods: Firstly, expression and function of PIP5K1A in CRC were investigated by human colon cancer tissue chip analysis and cell proliferation assay. Next, rupatadine was screened by computational screening and cytotoxicity assay and interactions between PIP5K1A and rupatadine assessed by kinase activity detection assay and bio-layer interferometry analysis. Next, rupatadine’s anti-tumor effect was evaluated by in vivo and in vitro pharmacodynamic assays. Finally, rupatadine’s anti-tumor mechanism was explored by quantitative real-time reverse-transcription polymerase chain reaction, western blot, and immunofluorescence. Results: We found that PIP5K1A exerts tumor-promoting effects as a proto-oncogene in CRC and aberrant PIP5K1A expression correlates with CRC malignancy. We also found that rupatadine down-regulates cyclin-dependent kinase 2 and cyclin D1 protein expression by inhibiting the PIP5K1A/Akt/GSK-3β pathway, induces cell cycle arrest, and inhibits CRC cell proliferation in vitro and in vivo. Conclusions: PIP5K1A is a potential drug target for treating CRC. Rupatadine, which targets PIP5K1A, could serve as a new option for treating CRC, its therapeutic mechanism being related to regulation of the Akt/GSK-3β signaling pathway.

Accurate estimation of evapotranspiration (ET) at high spatial resolution is crucial for drought monitoring and water resources management, but currently available remote sensing ET products generally have coarse spatial resolution (≥1000 m). To estimate ET at a high spatial resolution, Landsat images, Global Land Surface Satellite (GLASS), Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological forcing data were integrated, and the surface energy balance (SEBS) model was employed to calculate the 16-day average ET at 30 m resolution for China’s Tarim River Basin, spanning from 2009 to 2018. The results indicated that the average 16-day ET estimates correlated well with ground observations for land and water surfaces (root mean square error (RMSE) for land = 0.92 mm day−1, RMSE for water = 1.63 mm day−1, mean bias for land = 0.3 mm day−1, mean bias for water = 0.52 mm day−1). Cross validation with GLASS, ETMonitor, and Penman-Monteith-Leuning (PML_V2) ET datasets revealed an overall increasing trend for all four products (PML_V2 = 6.277 mm year−1, GLASS = 2.185 mm year−1, ETMonitor = 3.258 mm year−1, SEBS = 1.441 mm year−1), demonstrating good spatial consistency. The consistent increasing pixels were primarily distributed in the northern, southwestern, and southeastern mountainous regions, accounting for 22.8%, while 0.29% of the consistent decreasing pixels were mainly concentrated in the central desert and mountain-front oasis areas. Inconsistent pixels accounted for 76.9%, with 2.34% of the inconsistent decreasing pixels exhibiting a scattered distribution, while 37.28% of the inconsistent increasing pixels were mainly found in the central desert and some oasis areas. Furthermore, SEBS ET trend analysis indicated that the oasis area experienced more pronounced changes than the mountainous and desert areas during the 2009–2018 period. The SEBS ET estimated in this study can provide high-precision data support and a reference for future research on the water resources management.

There are lasting concerns on calvarial development because cranium not only accommodates the growing brain, but also safeguards it from exogenous strikes. In the past decades, most studies attributed the dynamic expansion and remodeling of cranium to the proliferation of osteoprecursors in cranial primordium, and the proliferation of osteoprogenitors at the osteogenic front of cranial suture mesenchyme. Further investigations identified series genes expressed in suture mesenchymal cells as the markers of the progenitors, precursors and postnatal stem cells in cranium. However, similar to many other organs, it is suggested that the reciprocal interactions among different tissues also play essential roles in calvarial development. Actually, there are increasing evidence indicating that dura mater (DM) is indispensable for the calvarial morphogenesis and osteogenesis by secreting multiple growth factors, cytokines and extracellular matrix (ECM). Thus, in this review, we first briefly introduce the development of cranium, suture and DM, and then, comprehensively summarize the latest studies exploring the involvement of ECM in DM and cranium development. Eventually, we discussed the reciprocal interactions between calvarium and DM in calvarial development. Actually, our review provides a novel perspective for cranium development by integrating previous classical researches with a spotlight on the mutual interplay between the developing DM and cranium.

Kokusaginine is an active ingredient alkaloid that has been isolated and extracted from Ruta graveolens L. Some researches have indicated that alkaloids possess anti-inflammatory and antioxidant effects. Nevertheless, the potential nephroprotective effects of kokusaginine on renal fibrosis remain undetermined. This study was conducted to examine the protective effect of kokusaginine on renal fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. Renal fibrosis was induced in male C57BL/6 J mice by feeding with 0.2% adenine-containing food and UUO surgery. Kokusaginine was administered orally simultaneously after the establishment of renal fibrosis. Renal function was measured by serum levels of creatinine and urea nitrogen. Renal pathological changes were assessed by HE staining and Masson staining. Western blotting was employed to detect the expression levels of fibrosis-related proteins in mice and cells. Additionally, network pharmacology analysis and RNA-seq were utilized to predict the pathways through which kokusaginine could exert its anti-fibrotic effects. The treatment with kokusaginine enhanced renal function, alleviated renal histoarchitectural lesions, and mitigated renal fibrosis in the renal fibrosis models. The network pharmacology and RNA-seq enrichment analysis of the KEGG pathway demonstrated that kokusaginine could exert anti-renal fibrosis activity via the PI3K/AKT signaling pathway. And the results were verified in both in vitro and in vivo experiments. In conclusion, our data implied that kokusaginine inhibited the activation of the PI3K/AKT signaling pathway both in vitro and in vivo, and suppressed the formation of renal fibrosis. Thus, the kokusaginine-mediated PI3K/AKT signaling pathway may represent a novel approach for the treatment of renal fibrosis.

Abstract Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with “full house” and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Abstract Background Pathway mutations have been calculated to predict the poor prognosis and immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC). To uncover the unique markers predicting prognosis and immune therapy response, the accurate quantification of pathway mutations are required to evaluate epithelial-mesenchymal transition (EMT) and immune escape. Yet, there is a lack of score to accurately quantify pathway mutations. Material and methods Firstly, we proposed Individualized Weighted Hallmark Gene Set Mutation Burden (IWHMB, https://github.com/YuHongHuang-lab/IWHMB ) which integrated pathway structure information and eliminated the interference of global Tumor Mutation Burden to accurately quantify pathway mutations. Subsequently, to further elucidate the association of IWHMB with EMT and immune escape, support vector machine regression model was used to identify IWHMB-related transcriptomic features (IRG), while Adversarially Regularized Graph Autoencoder (ARVGA) was used to further resolve IRG network features. Finally, Random walk with restart algorithm was used to identify biomarkers for predicting ICI response. Results We quantified the HNSCC pathway mutation signatures and identified pathway mutation subtypes using IWHMB. The IWHMB-related transcriptomic features (IRG) identified by support vector machine regression were divided into 5 communities by ARVGA, among which the Community 1 enriching malignant mesenchymal components promoted EMT dynamically and regulated immune patterns associated with ICI responses. Bridge Hub Gene (BHG) identified by random walk with restart was key to IWHMB in EMT and immune escape, thus, more predictive for ICI response than other 70 public signatures. Conclusion In summary, the novel pathway mutation scoring-IWHMB suggested that the elevated malignancy mediated by pathway mutations is a major cause of poor prognosis and immunotherapy failure in HNSCC, and is capable of identifying novel biomarkers to predict immunotherapy response.

Luojia 3-01 is the world's first intelligent remote sensing satellite, equipped with various imaging modes including video, frame-pushing, and scan-pushing. It boasts submeter level multimode optical imaging capabilities, on-orbit intelligent processing, and real-time intra-satellite and satellite-to-ground data transmission. Throughout the satellite's design and development, we have established the real-time intelligent information service architecture for Luojia 3-01, marking a new paradigm in on-orbit processing and real-time services for intelligent remote sensing satellites. We have proposed the on-orbit real-time processing architecture of Luojia 3-01, addressing the challenges of limited computational and storage resources, particularly in on-orbit processing of vast volumes of remote sensing data, including core algorithmic bottlenecks in “correction-extraction-compression.” A novel intelligent remote sensing satellite system has been developed, featuring multimode imaging, an open platform, intelligent processing, and satellite-to-ground interconnectivity, which significantly reduces the response time of remote sensing services to less than 8 min, thereby shortening the cycle from data acquisition to intelligent information service. This innovation spearheads a technological leap in remote sensing satellite services from data to information, from post-event to real-time, and from professional to widespread public applications, laying a solid foundation for the popularization and commercialization of China's intelligent remote sensing satellites.

Abstract Background The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. Methods A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20−39 years, middle-aged: 40−59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. Results Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. Conclusions In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men’s I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.

Abstract Biochar application is widely studied to mitigate the threats of soil degradation to food security and climate change. However, there are big variations in the effects of biochar application on crops, soils, and the atmosphere during crop production. This study provides a global dataset of biochar application effects on crop yield, soil properties, and greenhouse emissions. The dataset is extracted and integrated from 367 peer-reviewed studies with 891 independent field, laboratory, and incubation experiments across 37 countries. This dataset includes 21 variables before and after biochar application (including soil properties, crop yield, greenhouse gas emissions, etc.) of 2438 items, focusing on two main biochar application types: biochar application alone and combined with fertilizers. Background information on climate conditions, initial soil properties, management practices, and characteristics of biochar sources and production is also contained in the dataset. This dataset facilitates a comprehensive understanding of the impact of biochar application, supports the utilization of agricultural wastes for biochar production, and assists researchers in refining experimental protocols for further studies.

Abstract The present study investigated ultrasound (US) phenotypes reflecting prostate cancer (PCa)‐related genetic mutations. Herein, integration of radiotranscriptomic data, US and contrast‐enhanced ultrasound (CEUS) radiomic images, and RNA sequencing was performed with the aim of significantly improving the accuracy of PCa prognosis. We performed radiotranscriptomic analysis of clinical, imaging, and two genomic (mRNA and microRNA expression) datasets from 48 and 22 men with PCa and benign prostatic hyperplasia (BPH), respectively. Twenty‐three US texture features and four microvascular perfusion features were associated with various patterns of 52 differentially expressed genes related to PCa (p

Abstract Background Interferon-gamma release assay (IGRA) is the main tool for the diagnosis of latent tuberculosis (TB) infection (LTBI). However, the indeterminate results were more frequent in children, and the underlying reasons were largely speculative. We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) with X.DOT-TB (XDOT) for diagnosing LTBI, and to identify the risk factors associated with indeterminate results in children. Methods A retrospective study for children

Covalent organic frameworks (COFs), as an emerging class of porous crystalline materials constructed by covalent links between the building monomers, have gained tremendous attention. Over the past 15 years, COFs have made rapid progress and substantial development in the chemistry and materials fields. However, the synthesis of COFs has been dominated by solvothermal methods for a long time and it usually involves high temperature, high pressure and toxic organic solvents, which created many challenges for environmental considerations. Recently, the exploration of new approaches for facile fabrication of COFs has aroused extensive interest. Hence, in this review, we comprehensively describe the synthetic strategies of COFs from the aspects of nonconventional heating methods and reaction media. In addition, the advantages, limitations and properties of the preparation methods are compared. Finally, we outline the main challenges and development prospects of the synthesis of COFs in the future and propose some possible solutions.

A gas pressure meter-based portable/miniaturized analytical kit was established for rapid and on-site detection of oxalate. Potassium permanganate (KMnO4) and oxalate solution were mixed together in bottle-in-bottle reaction device, a simple oxidation reaction process occurred within 6 min and carbon dioxide (CO2) was generated, inducing the pressure of the sealed bottle changed, which was measured by a portable gas pressure meter. A detectable range of 0.1–6 μmol mL−1 and a detection limit of 0.064 μmol mL−1 were achieved. The proposed analytical method was further used for the analysis of several real samples (spinach, beverages and water samples), with the recoveries of 89–111%. Considering the interferences from the complicated matrix, calcium chloride (CaCl2) was served as a precipitant, oxalate (C2O42−) was precipitated with Ca2+ to form precipitation (CaC2O4), CaC2O4 was then separated from the matrix by centrifuge/filter, eliminating the interferences. It is a rapid, easy-used and interference-free analytical system/device for oxalate on-site and real time analysis.

ABSTRACT: Chicken egg chalaza (CLZ) is a natural colloidal structure in eggs that exists as an egg yolk stabilizer and is similar in composition to egg white. In this study, the proteome, phosphoproteome, and N-glycoproteome of CLZ were characterized in depth. We hydrolyzed the CLZ proteins and enriched the phosphopeptides and glycopeptides. We identified 45 phosphoproteins and 80 N-glycoproteins, containing 59 phosphosites and 203 N-glycosylation sites, respectively. Typically, the ovalbumin in CLZ was both phosphorylated and N-glycosylated, with 4 phosphosites and 4 N-glycosylation sites. Moreover, we identified 2 N-glycosylated subunits of ovomucin, mucin-5B and mucin-6, with 32 and nine N- glycosylation sites, respectively. Analysis of the phosphorylation and N-glycosylation status of CLZ proteins could provide novel insights into the structural and functional characteristics of CLZ.

Objective: The aim of this study was to examine the cervical cancer screening practices among women residing in Lingang New District of Shanghai. Moreover, the study aimed to delve into the characteristics of HPV infection and cervical lesions in older women (≥60 years old), seeking for more effective method for cervical cancer screening. Methods: This is a cross-sectional study enrolled women who were referred to colposcopy and cervical histological examination due to abnormal cytology or HPV tests from Shanghai Sixth People's Hospital between January 2018 and December 2022. Results: A total of 1,931 women (mean age: 41.8 ± 12.5, range: 18–88 years old) were enrolled, 119 individuals aged ≥ 60 and 1732 aged

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment.Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it.Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were “comparative safety/tolerability” (58 times), “comparative effectiveness/efficacy” (56 times), “comparative patient-perceived health/patient reported outcomes” (37 times), “disease severity” (34 times), and “unmet needs” (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were “cost of intervention” (17 times), “comparative other medical costs” (16 times), and “comparative non-medical costs” (18 times). Out of the 10 criteria (18 times) for assessing innovative value, “a novel pharmacological mechanism” was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, “system capacity and appropriate use of intervention” was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, “political/historical/cultural context” was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. “Swing weighting” and “a direct rating scale” were the most frequently used techniques in included articles.Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

Objective Our objective was to investigate the therapeutic mechanism of quercetin in the management of cervical HR-HPV through the integration of network pharmacology and molecular docking techniques.

In this paper, a novel fusion network for automatic modulation classification (AMC) is proposed in underwater acoustic communication, which consists of a Transformer and depth-wise convolution (DWC) network. Transformer breaks the limitation of sequential signal input and establishes the connection between different modulations in a parallel manner. Its attention mechanism can improve the modulation recognition ability by focusing on the key information. DWC is regularly inserted in the Transformer network to constitute a spatial–temporal structure, which can enhance the classification results at lower signal-to-noise ratios (SNRs). The proposed method can obtain more deep features of underwater acoustic signals. The experiment results achieve an average of 92.1% at −4 dB ≤ SNR ≤ 0 dB, which exceed other state-of-the-art neural networks.

Abstract Objective To investigate the relationship between suprasellar extension (SSE) and intracranial infection after endoscopic endonasal transsphenoidal approach (EETA) for pituitary adenoma resection. Methods We retrospectively analyzed 94 patients with suprasellar extended pituitary adenoma admitted to the Department of Neurosurgery of the Affiliated Hospital of Guilin Medical College from January 2018 to December 2021. We measured the preoperative magnetic resonance sagittal SSE and collected clinical data and divided the patients into groups according to the presence of postoperative intracranial infection. The critical value for the SSE was calculated by using a working characteristic curve for the subjects. The risk factors for intracranial infection after EETA resection of pituitary adenomas were analyzed by multivariate regression analysis. Results Among the 94 patients, 12 cases (12.8%) were placed in the infection group and 82 cases (87.2%) in the non-infection group. The cut-off value for the SSE in the sagittal position was 15.6 mm, the sensitivity was 75%, the specificity was 87.8%, and the area under the curve (AUC) was 0.801. The coronary cut-off value for the SSE was 15.8 mm, the sensitivity was 66.7%, the specificity was 79.3%, and the AUC was 0.787. The SSE values in the sagittal and coronal positions were correlated with postoperative intracranial infection (P

Abstract Background Diabetic kidney disease (DKD) has become the largest cause of end-stage kidney disease. Early and accurate detection of DKD is beneficial for patients. The present detection depends on the measurement of albuminuria or the estimated glomerular filtration rate, which is invasive and not optimal; therefore, new detection tools are urgently needed. Meanwhile, a close relationship between diabetic retinopathy and DKD has been reported; thus, we aimed to develop a novel detection algorithm for DKD using artificial intelligence technology based on retinal vascular parameters combined with several easily available clinical parameters in patients with type-2 diabetes. Methods A total of 515 consecutive patients with type-2 diabetes mellitus from Xiangyang Central Hospital were included. Patients were stratified by DKD diagnosis and split randomly into either the training set (70%, N = 360) or the testing set (30%, N = 155) (random seed = 1). Data from the training set were used to develop the machine learning algorithm (MLA), while those from the testing set were used to validate the MLA. Model performances were evaluated. Results The MLA using the random forest classifier presented optimal performance compared with other classifiers. When validated, the accuracy, sensitivity, specificity, F1 score, and AUC for the optimal model were 84.5%(95% CI 83.3–85.7), 84.5%(82.3–86.7), 84.5%(82.7–86.3), 0.845(0.831–0.859), and 0.914(0.903–0.925), respectively. Conclusions A new machine learning algorithm for DKD diagnosis based on fundus images and 8 easily available clinical parameters was developed, which indicated that retinal vascular changes can assist in DKD screening and detection.

To explore the effects of Zoledronic acid (ZA) in the neoadjuvant setting, we conducted a meta-analysis of randomized controlled trials (RCTs) of neoadjuvant therapy with or without ZA in breast cancer (BC). A systematic literature search was carried out by two reviewers independently on the basis of three electronic databases up to February 2022. Six RCTs with a total of 949 patients, comparing neoadjuvant therapy with or without ZA in BC were included. In the total population, adding ZA to the neoadjuvant setting didn’t improved the pathological complete response (pCR) rates (Risk Ratio (RR) = 1.38, 95% CI 0.94–2.03, p = 0.10). However, subgroup analysis revealed that the addition of ZA resulted in an increased pCR rate in postmenopausal women (RR = 2.30, 95% CI 0.93–5.71, p = 0.07) and in patients with triple-negative BC (RR = 2.85, 95% CI 1.01–8.03, p = 0.05), although these results were not statistically significant. Furthermore, the additional ZA did not show benefits on objective response rate, breast-conserving surgery rate or recurrence rate. For mortality, however, the additional ZA resulting in worse outcome compared to the control group (RR = 1.48, 95% CI 1.04–2.10, p = 0.03). Our study suggested that addition of ZA to neoadjuvant therapy didn’t improved the pCR rate. Further investigations are warranted in postmenopausal women and patients with triple-negative BC, since these subgroups might benefit from ZA treatment.

Abstract Background Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC. Methods From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented. Results The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13–104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069–1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053–1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1–1(1–2)] vs. 1[1–2(1–4)] and 1[1–1(1–3)] vs. 1[1–2(1–4)]), shorter cannulation time (205 s [162–283 (66–1,526)] vs. 311 s [243–401 (136–1,223)] and 228 s [193–306 (66–1,669)] vs. 340 s [246–499 (130–944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P

Abstract Background Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown. Methods The effects of MCL on BRG1-induced fibrotic responses and TGF-β1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed. Results BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-β1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-β1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-β1-induced fibrotic responses and blocked TGF-β1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-β1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-β1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-β1-Smad2/3 signaling pathway. Conclusion Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.

Abstract Plasma cleaning is an effective method for removing micro/nanoparticle particles, thus solving the pollution problem of micro/nanoparticle instruments. However, the lack of research on the phase transition evolution law of micro/nanoparticles under the action of plasma affects the popularization and application of this method and is the key factor that affects the cleaning quality. The focus of this study is to analyze this law. Through experimental observation and finite element simulation, the spatial phase transition distribution characteristics of particles and the influence law of laser parameters are analyzed. Moreover, the effect of the particle phase transition on the cleaning process is discussed. The removal threshold and the best removal area of different particles are presented, and a reference and guidance for the follow-up development of laser-plasma shock wave removal technology are provided.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

The consortium blockchain has been widely applied in various fields such as agricultural product traceability, supply chain management, and logistics transportation. As an indispensable component of a consortium blockchain, the consensus algorithm ensures the consistency and trustworthiness of each node in the network. However, existing consensus algorithms in large-scale consortium blockchain scenarios suffer from low system throughput and high latency due to the complexity of communication processes, rendering them impractical for real-world use. To address these issues, this paper proposes a novel consensus algorithm called credit evaluation-based practical Byzantine fault tolerance (CE-PBFT). This algorithm designs a new node credit evaluation model that considers node completion rate, consensus decay, and node behavior. It effectively measures and reflects the specific reliability status of nodes during system operation, thereby enhancing system reliability and security. Additionally, the paper introduces the innovative use of decision tree algorithms to analyze network node behavior and simplifies the existing consensus protocol. Nodes are categorized as excellent, good, ordinary, or poor based on the classification results, and non-Byzantine nodes are dynamically selected accordingly. This greatly improves the overall efficiency of the system. The performance of CE-PBFT is validated through experiments and compared with PBFT, G-PBFT, RBFT, WBFT and PPoR. Experimental results demonstrate that in large-scale consortium scenarios, CE-PBFT significantly improves system throughput, effectively reduces transaction latency and communication overhead, and outperforms the compared protocols.

Conclusions: Our results show that JUN and ATF3 are possibly critical genes in the process of IgAN ferroptosis and may be related with immune cell infiltration.

Objectives: To evaluate the diagnostic value of targeted next generation sequencing (tNGS) in childhood tuberculosis (TB) and compare the accuracy with Xpert MTB/RIF method. Methods: Children aged ≤18 years with symptoms suggestive of TB during July 2021 to December 2022 at Beijing Children's Hospital were included, and the performances of tNGS and Xpert were evaluated. Results: A total of 103 children with suspected TB were recruited, including 72 discharge diagnosis of TB and 31 non-TB cases. The mean age was 7.37 ± 4.77 years, and 62.1 % were male. The most common type of specimens was gastric aspirate (GA) (59, 57.3 %). Among all the 72 TB patients, tNGS showed higher sensitivity than Xpert, but the difference was not significant (34.7 %, 25/72 vs 20.8 %, 15/72; P = 0.063). The specificities of tNGS and Xpert were 87.1 % (27/31) and 96.8 % (30/31), respectively (P = 0.162). Among different types of specimen, the highest sensitivity of tNGS on sputum and pus was observed (80.0 %, 4/5), followed by pleural effusion (50.0 %, 2/4). One rifampin resistance and one protionamide resistance were detected in bacteriologically confirmed TB by tNGS. Conclusion: tNGS had a higher sensitivity but lower specificity compared to Xpert in diagnosis of children TB. tNGS yielded higher sensitivity than Xpert on gastric aspirate and sputum and pus.

Salmonella, especially antimicrobial resistant strains, remains one of the leading causes of foodborne bacterial disease. Retail chicken is a major source of human salmonellosis. Here, we investigated the prevalence, antimicrobial resistance (AMR), and genomic characteristics of Salmonella in 88 out of 360 (24.4%) chilled chicken carcasses, together with 86 Salmonella from humans with diarrhea in Qingdao, China in 2020. The most common serotypes were Enteritidis and Typhimurium (including the serotype I 4,[5],12:i:-) among Salmonella from both chicken and humans. The sequence types were consistent with serotypes, with ST11, ST34 and ST19 the most dominantly identified. Resistance to nalidixic acid, ampicillin, tetracycline and chloramphenicol were the top four detected in Salmonella from both chicken and human sources. High multi-drug resistance (MDR) and resistance to third-generation cephalosporins resistance were found in Salmonella from chicken (53.4%) and humans (75.6%). In total, 149 of 174 (85.6%) Salmonella isolates could be categorized into 60 known SNP clusters, with 8 SNP clusters detected in both sources. Furthermore, high prevalence of plasmid replicons and prophages were observed among the studied isolates. A total of 79 antimicrobial resistant genes (ARGs) were found, with aac(6′)-Iaa, blaTEM-1B, tet(A), aph(6)-Id, aph(3″)-Ib, sul2, floR and qnrS1 being the dominant ARGs. Moreover, nine CTX-M-type ESBL genes and the genes blaNMD-1, mcr-1.1, and mcr-9.1 were detected. The high incidence of MDR Salmonella, especially possessing lots of mobile genetic elements (MGEs) in this study posed a severe risk to food safety and public health, highlighting the importance of improving food hygiene measures to reduce the contamination and transmission of this bacterium. Overall, it is essential to continue monitoring the Salmonella serotypes, implement the necessary prevention and strategic control plans, and conduct an epidemiological surveillance system based on whole-genome sequencing.

AbstractPurpose To analyze the outcomes of radiofrequency ablation (RFA) for isthmus papillary thyroid cancer (PTC) versus PTC originating from the lobes.Methods Patients with solitary low-risk PTC treated with RFA between July 2014 and December 2019 were retrospectively reviewed. This study was approved by our institutional review board. Of the 562 patients, 104 and 458 had PTCs located in the thyroid isthmus and thyroid lobes, respectively. Local tumor progression (LTP), LTP-free survival (LTPFS), changes in tumor volume, and complications were compared between the two groups using propensity-score matching (PSM).Results The isthmic and lobar groups showed no significant differences in LTP (2.9% vs. 3.8%), new PTC (2.9% vs. 2.9%), persistent lesions (0.0% vs. 0.2%), or LTPFS after PSM. Before PSM, the two groups showed significant differences in the volume reduction ratio (VRR) of the ablated tumors at 1, 3, 24, 30, and 48 months after RFA, but no differences between the two groups were observed in tumor volume, VRR, or disappearance rate after PSM (p > .05). One patient in the isthmic group presented with coughing, while another complained of hoarseness. Complications did not differ significantly between the two groups (p > .05).Conclusions The outcomes of RFA for patients with low-risk PTC in the thyroid isthmus and thyroid lobes were similar. Therefore, RFA may serve as an alternative treatment option for patients with low-risk isthmic PTC.

Objective To investigate the role of segmental bioelectrical impedance technique (SBIA) in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis patients.Method We selected the patients at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University and measured the segmental bioelectrical impedance by a German Fresenius body composition analyzer (the Fresenius whole body composition measurement (BCM) machine was used as a segmental machine in this study). An alternating current (5 kHz, 0.05–0.7 mA) was continuously released during the measurement. The released current penetrated the peritoneal cavity on both sides of the body, from which the segmental resistance at a frequency of 5 kHz was obtained from the multifrequency data (R5/Ω). Baseline BIA measurements were initiated after the patient entered the supine position for 5–10 min, then dialysate was instilled into the peritoneal cavity. BIA measurements were performed at 10-min intervals during the retention of dialysate in the abdomen and finally ended when dialysate drainage was complete. Real-time intraperitoneal volume estimated by SBIA (IPVSBIA)and ultrafiltration volume estimated by SBIA(UFVSBIA) was calculated. At the same time, the actual ultrafiltration volume at the end of peritoneal dialysis was weighed and measured (UFVMEA).Results A total of 30 patients were included in the study, 9 patients withdrew from the study due to subjective factors during the measurement process, and 21 patients completed the study. The correlation coefficient R2 of UFVSBIA and UFVMEA was 0.21 (p

Aim Renal artery stenosis (RAS) is an important cause of chronic kidney disease (CKD). The main purpose of this study was to explore the clinical characteristics and predictors of low-grade RAS in female patients with CKD. Methods One hundred and five female CKD patients from Huadong Hospital affiliated with Fudan University who underwent 3 T non-contrast renal artery magnetic resonance angiography (MRA) were analyzed. Basic statistics methods were used in the study, such as independent-sample t test,non-parametric test, binary logistic regression analysis and ROC analysis. Results In this cross-sectional study, there were 50 patients with RAS and 55 without RAS (47.6% versus 52.4%). Binary logistic regression analysis demonstrated that low-level ALB and lymphocyte count, high-level SP, BUN and NLR were independent risk factors for low-grade RAS in female patients with CKD. ROC analysis indicated that eGFR, FeNa and UBCR, ALB, lymphocyte count and NLR had the best predictive value for low-grade RAS, especially eGFR with a sensitivity of 65.50% and specificity of 72.00% and FeNa with a sensitivity of 71.10% and specificity of 72.20% and BUCR with a sensitivity of 71.10% and specificity of 68.10%. Conclusion In female patients with CKD, FeNa, eGFR, ALB, UBCR, lymphocyte count and NLR may be good predictors of low-grade RAS, especially eGFR, FeNa and BUCR.

AbstractObjective To evaluate the long-term efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC).Methods This retrospective study involved 32 patients with pathologically confirmed locally recurrent PTC. The ablation zone was assessed by contrast-enhanced ultrasound (CEUS) after RFA. At baseline, 6 and 12 months and every 6 months or 12 months thereafter, the following results were recorded: recurrence rate, largest diameter, volume, volume reduction rate (VRR) of recurrent lesions, serum thyroglobulin (Tg) level and complications.Results 58 recurrent lesions in 32 patients were successfully ablated with RFA. The mean follow-up time was 73.19 ± 12.68 months (range, 60 to 98 months). At the last follow-up, almost all ablated lesions disappeared completely, and only one lesion showed scar-like changes. Nine (28.13%) patients developed new locally recurrent tumors; they were successfully treated with repeat RFA sessions. No new recurrent lesions were found during the follow-up. The largest diameter and volume of recurrent lesions decreased from 13.71 ± 6.48 mm and 520.43 ± 627.85 mm3 to 0 each at the end of observation period (p

AbstractPurpose Maintaining an optimal thyroid stimulating hormone (TSH) level is important in the postoperative management of papillary thyroid carcinoma (PTC). However, there is little evidence for TSH target levels in patients undergoing radiofrequency ablation (RFA). This study aimed to determine the optimal TSH level for management in low-risk patients who underwent RFA.Methods This retrospective propensity score-matched cohort study included patients with low-risk PTC who underwent RFA from January 2014 to December 2018. The patients were categorized into two groups based on the range of TSH levels: low (≤2 mU/L) and high (>2 mU/L) TSH levels. Local tumor progression and disease-free survival (DFS) were compared between the low TSH and high TSH groups, using propensity score analyses based on patient- and tumor-level characteristics. Univariate analyses were performed to select risk factors for tumor progression.Results Overall, our study included 516 patients with low-risk PTC who underwent RFA with a long-term follow-up of 5-years. During follow-up, the overall incidence rate of local tumor progression was 4.8% (25/516), with no significant difference between the matched groups (7/106 [6.6%] vs. 5/53 [9.4%], p = 0.524). DFS did not differ between the two groups (p = 0.5). Moreover, TSH level was not regarded as a significant predictor of tumor progression after Cox analysis; primary tumor size was the only relevant risk factor.Conclusion This large propensity-matched study revealed no association between TSH levels and tumor progression. Thus, for patients with low-risk PTC who underwent RFA, the optimalTSH level is recommended at the euthyroid range.