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IntroductionThe administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI).MethodsA cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT.ResultsThe study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx.DiscussionThis suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients.

The Regional Pest Control program represents a strategic intervention aimed at optimizing pesticide use in crop production, thereby mitigating the environmental impact of agricultural non-point source pollution from pesticides and fostering the development of high-quality agriculture. This study examines the influence of farmers’ perceived risks on the adoption of the Regional Pest Control program and evaluates its effect on pesticide application across a nationally representative dataset from Heilongjiang, Jiangsu, Anhui, Hubei, and Sichuan provinces. To account for unobserved heterogeneity, an endogenous switching regression model was employed. The findings reveal that farmers’ perceived risks associated with the Regional Pest Control program significantly deter its adoption. Furthermore, the program has been effective not only in reducing the frequency of pesticide applications but also in increasing the usage of pesticides with lower acute toxicity levels. Notably, the impact of the Regional Pest Control program on pesticide application demonstrates considerable variation in accordance with farmers’ risk attitudes.

ObjectiveThis study explores the intricate relationship between social support and eating behaviors in children and adolescents, considering the mediating role of eating self-efficacy and the moderating effects of body mass index (BMI) and weight concern.MethodsData from 1986 primary and secondary school students aged 8 to 17 in Shanghai, China, were analyzed using moderated mediation analysis.ResultsThe results demonstrate a robust positive association between social support and eating self-efficacy, particularly prominent among individuals with low BMI (effect = 0.506, 95% CI [0.376, 0.636]). Moreover, the study highlights that eating behavior is influenced not only by eating self-control (β = −0.054, 95% CI [−0.062, −0.046]) but also by the interaction term between individuals’ perceptions of their body weight (β = −0.0008, 95% CI [−0.0015, −0.0001]).ConclusionEating self-efficacy serves as a mediator in the relationship between social support and eating behavior, modulated by BMI and weight concern. Importantly, high weight concern significantly strengthens the mediating effect of eating self-efficacy on the relationship between social support and eating behavior, regardless of BMI.

ObjectiveRhizosphere microorganisms play crucial roles in the growth and development of plants, disease resistance, and environmental adaptability. As the only wild pepper variety resource in China, domesticated Capsicum frutescens Linn. (Xiaomila) exhibits varying beneficial traits and affects rhizosphere microbial composition compared with its wild counterparts. In this study, we aimed to identify specific rhizosphere microbiome and metabolism patterns established during the domestication process.MethodsThe rhizosphere microbial diversity and composition of domesticated and wild C. frutescens were detected and analyzed by metagenomics. Non-targeted metabolomics were used to explore the differences of metabolites in rhizosphere soil between wild and domesticated C. frutescens.ResultsWe found that the rhizosphere microbial diversity of domesticated variety was significantly different from that of the wild variety, with Massilia being its dominant bacteria. However, the abundance of certain beneficial microbes such as Gemmatimonas, Streptomyces, Rambibacter, and Lysobacter decreased significantly. The main metabolites identified in the wild variety included serylthreonine, deoxyloganic acid, vitamin C, among others. In contrast, those identified in the domesticated group were 4-hydroxy-l-glutamic acid and benzoic acid. Furthermore, the differentially enriched pathways were concentrated in tyrosine and tryptophan biosynthesis, histidine and purine-derived alkaloids biosynthesis, benzoic acid family, two-component system, etc.ConclusionThis study revealed that C. frutescens established specific rhizosphere microbiota and metabolites during domestication, which has important significance for the efficient utilization of beneficial microorganisms in breeding and cultivation practices.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents’ safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

Verticillium wilt, caused by Verticillium dahliae, is a soil-borne disease affecting eggplant. Wild eggplant, recognized as an excellent disease-resistant resource against verticillium wilt, plays a pivotal role in grafting and breeding for disease resistance. However, the underlying resistance mechanisms of wild eggplant remain poorly understood. This study compared two wild eggplant varieties, LC-2 (high resistance) and LC-7 (sensitive) at the phenotypic, transcriptomic, and metabolomic levels to determine the molecular basis of their resistance to verticillium wilt. These two varieties exhibit substantial phenotypic differences in petal color, leaf spines, and fruit traits. Following inoculation with V. dahliae, LC-2 demonstrated significantly higher activities of polyphenol oxidase, superoxide dismutase, peroxidase, phenylalanine ammonia lyase, β-1,3 glucanase, and chitinase than did LC-7. RNA sequencing revealed 4,017 differentially expressed genes (DEGs), with a significant portion implicated in processes associated with disease resistance and growth. These processes encompassed defense responses, cell wall biogenesis, developmental processes, and biosynthesis of spermidine, cinnamic acid, and cutin. A gene co-expression analysis identified 13 transcription factors as hub genes in modules related to plant defense response. Some genes exhibited distinct expression patterns between LC-2 and LC-7, suggesting their crucial roles in responding to infection. Further, metabolome analysis identified 549 differentially accumulated metabolites (DAMs) between LC-2 and LC-7, primarily consisting of compounds such as flavonoids, phenolic acids, lipids, and other metabolites. Integrated transcriptome and metabolome analyses revealed the association of 35 gene–metabolite pairs in modules related to the plant defense response, highlighting the interconnected processes underlying the plant defense response. These findings characterize the molecular basis of LC-2 resistance to verticillium wilt and thus have potential value for future breeding of wilt-resistant eggplant varieties.

Soil microorganisms can be used as one of the important indicators of wetland ecosystem restoration. To study the effects of different restoration stages on soil microbial community composition and diversity in Naolihe Wetland, we employed a “time and space parallel” method. Four restoration stages, namely corn field (Corn), short-term restoration wetland (2 years, ST), long-term restoration wetland (8 years, LT) and natural wetland (>25 years, NW), were selected to represent the restoration time and geographical location in Naolihe Nature Wetland. We investigated the composition and diversity of soil microbial communities in different restoration wetland (from corn fields to natural wetlands) by using 16S rRNA and ITS rRNA gene sequencing. We also performed chemical experiments to measure soil enzyme activity and physicochemical properties at each sampling site. The results showed that soil physicochemical properties and enzyme activities significantly differed with the extension of wetland restoration years (p

Flower color is a classic example of an ecologically important trait under selection in plants. Understanding the genetic mechanisms underlying shifts in flower color can provide key insights into ecological speciation. In this study, we investigated the genetic basis of flower color divergence in Barthea barthei, a shrub tree species exhibiting natural variation in flower color. We assembled a high-quality genome assembly for B. barthei with a contig N50 of 2.39 Mb and a scaffold N50 of 16.21 Mb. The assembly was annotated with 46,430 protein-coding genes and 1,560 non-coding RNAs. Genome synteny analysis revealed two recent tetraploidization events in B. barthei, estimated to have occurred at approximately 17 and 63 million years ago. These tetraploidization events resulted in massive duplicated gene content, with over 70% of genes retained in collinear blocks. Gene family members of the core regulators of the MBW complex were significantly expanded in B. barthei compared to Arabidopsis, suggesting that these duplications may have provided raw genetic material for the evolution of novel regulatory interactions and the diversification of anthocyanin pigmentation. Transcriptome profiling of B. barthei flowers revealed differential expression of 9 transcription factors related to anthocyanin biosynthesis between the two ecotypes. Six of these differentially expressed transcription factors were identified as high-confidence candidates for adaptive evolution based on positive selection signals. This study provides insights into the genetic basis of flower color divergence and the evolutionary mechanisms underlying ecological adaptation in plants.

In the post-genomic era, virus-induced gene silencing (VIGS) has played an important role in research on reverse genetics in plants. Commonly used Agrobacterium-mediated VIGS inoculation methods include stem scratching, leaf infiltration, use of agrodrench, and air-brush spraying. In this study, we developed a root wounding–immersion method in which 1/3 of the plant root (length) was cut and immersed in a tobacco rattle virus (TRV)1:TRV2 mixed solution for 30 min. We optimized the procedure in Nicotiana benthamiana and successfully silenced N. benthamiana, tomato (Solanum lycopersicum), pepper (Capsicum annuum L.), eggplant (Solanum melongena), and Arabidopsis thaliana phytoene desaturase (PDS), and we observed the movement of green fluorescent protein (GFP) from the roots to the stem and leaves. The silencing rate of PDS in N. benthamiana and tomato was 95–100%. In addition, we successfully silenced two disease-resistance genes, SITL5 and SITL6, to decrease disease resistance in tomatoes (CLN2037E). The root wounding–immersion method can be used to inoculate large batches of plants in a short time and with high efficiency, and fresh bacterial infusions can be reused several times. The most important aspect of the root wounding–immersion method is its application to plant species susceptible to root inoculation, as well as its ability to inoculate seedlings from early growth stages. This method offers a means to conduct large-scale functional genome screening in plants.

The Hehuang Valley (HV) is a key development area in the Qinghai Province; understanding changes in the vegetation within this area is of great significance if we are to maintain the ecological quality of this regional environment. Based on the 30 m spatial resolution Normalized difference vegetation index (NDVI) time series dataset, this paper analyzes the spatial and temporal characteristics and evolutionary trends of NDVI in the HV from 2001 to 2020 under the influences of climate change and human activities, by applying Mann-Kendall trend analysis, the Hurst index, and residual analysis. Analysis showed that firstly, high NDVI values (>0.5) were distributed in the low elevation areas of the HV except for towns and cropland, while the low NDVI values (

IntroductionUltraviolet (UV) light is a known trigger of both cutaneous and systemic disease manifestations in lupus patients. Lupus skin has elevated expression of type I interferons (IFNs) that promote increased keratinocyte (KC) death after UV exposure. The mechanisms by which KC cell death is increased by type I IFNs are unknown.MethodsHere, we examine the specific cell death pathways that are activated in KCs by type I IFN priming and UVB exposure using a variety of pharmacological and genetic approaches. Mice that overexpress Ifnk in the epidermis were exposed to UVB light and cell death was measured. RNA-sequencing from IFN-treated KCs was analyzed to identify candidate genes for further analysis that could drive enhanced cell death responses after UVB exposure.ResultsWe identify enhanced activation of caspase-8 dependent apoptosis, but not other cell death pathways, in type I IFN and UVB-exposed KCs. In vivo, overexpression of epidermal Ifnk resulted in increased apoptosis in murine skin after UVB treatment. This increase in KC apoptosis was not dependent on known death ligands but rather dependent on type I IFN-upregulation of interferon regulatory factor 1 (IRF1).DiscussionThese data suggest that enhanced sensitivity to UV light exhibited by lupus patients results from type I IFN priming of KCs that drives IRF1 expression resulting in caspase-8 activation and increased apoptosis after minimal exposures to UVB.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

Exhausted CD8+T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8+T cells, termed Tpex cells, which are characterized as TCF-1+PD-1+CD8+T cells. Elevated Tpex cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating Tpex cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of Tpex cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between Tpex cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for Tpex cell detection using mIHC technology but also confirmed that assessing Tpex cells within the CRC TME could be indicative of patients’ survival. We further uncovered the transcriptional and functional characteristics of Tpex cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.

BackgroundBabesia is a unique apicomplexan parasite that specifically invades and proliferates in red blood cells and can be transmitted via blood transfusion, resulting in transfusion-transmitted babesiosis. However, detecting Babesia in blood before transfusion has not received enough attention, and the risk of transfusing blood containing a low density of Babesia microti (B. microti) is unclear, possibly threatening public health and wellness.PurposeThis study aimed to determine the lower detection limit of B. microti in blood and to evaluate the transmission risk of blood transfusion containing low-density B. microti.MethodsInfected BALB/c mouse models were established by transfusing infected whole blood with different infection rates and densities of B. microti. Microscopic examination, nested Polymerase Chain Reaction (nested PCR), and an enzyme-linked immunosorbent assay (ELISA) were used to evaluate the infection status of the mouse models. Meanwhile, the nested PCR detection limit of B. microti was obtained using pure B. microti DNA samples with serial concentrations and whole blood samples with different densities of B. microti-infected red blood cells. Thereafter, whole mouse blood with a B. microti density lower than that of the nested PCR detection limit and human blood samples infected with B. microti were transfused into healthy mice to assess the transmission risk in mouse models. The infection status of these mice was evaluated through microscopic examination, nested PCR tests, and ELISA.ResultsThe mice inoculated with different densities of B. microti reached the peak infection rate on different days. Overall, the higher the blood B. microti density was, the earlier the peak infection rate was reached. The levels of specific antibodies against B. microti in the blood of the infected mice increased sharply during the first 30 days of infection, reaching a peak level at 60 days post-infection, and maintaining a high level thereafter. The nested PCR detection limits of B. microti DNA and parasite density were 3 fg and 5.48 parasites/μL, respectively. The whole blood containing an extremely low density of B. microti and human blood samples infected with B. microti could infect mice, confirming the transmission risk of transfusing blood with low-density B. microti.ConclusionWhole blood containing extremely low density of B. microti poses a high transmission risk when transfused between mice and mice or human and mice, suggesting that Babesia detection should be considered by governments, hospitals, and disease prevention and control centers as a mandatory test before blood donation or transfusion.

IntroductionT cells are the core of the cellular immunity and play a key role in the regulation of intestinal immune homeostasis. In order to explore the impact Moniezia benedeni (M. benedeni) infection on distributions of CD3+ T cells in the small intestine of the sheep.MethodsIn this study, sheep pET-28a-CD3 recombinant plasmid were constructed and expressed in BL21 receptor cells, then the rabbit anti-sheep CD3 polyclonal antibody was prepared through recombinant protein inducing. The M. benedeni-infected sheep (infection group, n = 6) and healthy sheep (control group, n = 6) were selected, and the distributions of CD3+ T cells in intestinal laminae propria (LP) and mucous epitheliums were observed and analyzed systematically.ResultsThe results showed that the rabbit anti-sheep CD3 polyclonal antibody had good potency and specificity. In the effector area of small intestine, a large number of CD3+ T cells were mainly diffusely distributed in the intestinal LP as well as in the mucous epitheliums, and the densities of intestinal LP from duodenum to jejunum to ileum were 6.01 cells/104 μm2, 7.01 cells/104 μm2 and 6.43 cells/104 μm2, respectively. Their distribution densities in mucous epitheliums were 6.71 cells/104 μm2, 7.93 cells/104 μm2 and 7.21 cells/104 μm2, respectively; in the infected group, the distributions of CD3+ T cells were similar to that of the control group, and the densities in each intestinal segment were all significantly increased (p

Alzheimer’s disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as “tauopathies”, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.

Microgrid has been extensively applied in the modern power system as a supplementary mode for the distributed energy resources. The microgrid with wind energy is usually vulnerable to the intermittence and uncertainty of the wind energy. To increase the robustness of the microgrid, the energy storage system (ESS) is necessary to compensate the power imbalance between the power supply and the load. To further maximize the economic efficiency of the system, the system level control for the microgrid is desired to be optimized when it is integrated with the utility grid. Aiming at the aforementioned problem, this paper comprehensively analyzes the power flow of a typical loop microgrid. A transformer-based wind power prediction (WPP) algorithm is proposed and compared with recurrent neural networks algorithm. With the historical weather data, it can accurately predict the 24 h average wind energy. Based on the predicted wind energy and the time-of-use (TOU) electricity price, a day-ahead daily cycling profile of the ESS with particle swarm optimization algorithm is introduced. It comprehensively considers the system capacity constraints and the battery degree of health. The functionality of the proposed energy management strategy is validated from three levels. First, WPP is conducted with the proposed algorithm and the true historical weather data. It has validated the accuracy of the transformer algorithm in prediction of the hourly level wind energy. Second, with the predicted wind energy, a case study is given to validate the day-ahead daily cycling profile. A typical 1 MVA microgrid is utilized as the simulation model to validate performance of the daily cycling optimization algorithm. The case study results show that the ESS daily cycling can effectively reduce the daily energy expense and help to shave the peak power demand in the grid.

BackgroundThe gut microbiota (GM) is believed to be closely associated with symptomatic carotid atherosclerosis (SCAS), yet more evidence is needed to substantiate the significant role of GM in SCAS. This study, based on the detection of bacterial DNA in carotid plaques, explores the characteristics of GM in SCAS patients with plaque bacterial genetic material positivity, aiming to provide a reference for subsequent research.MethodsWe enrolled 27 healthy individuals (NHF group) and 23 SCAS patients (PFBS group). We utilized 16S rDNA V3-V4 region gene sequencing to analyze the microbiota in fecal samples from both groups, as well as in plaque samples from the carotid bifurcation extending to the origin of the internal carotid artery in all patients.ResultsOur results indicate significant differences in the gut microbiota (GM) between SCAS patients and healthy individuals. The detection rate of bacterial DNA in plaque samples was approximately 26%. Compared to patients with negative plaques (PRSOPWNP group), those with positive plaques (PRSOPWPP group) exhibited significant alterations in their GM, particularly an upregulation of 11 bacterial genera (such as Klebsiella and Streptococcus) in the gut, which were also present in the plaques. In terms of microbial gene function prediction, pathways such as Fluorobenzoate degradation were significantly upregulated in the GM of patients with positive plaques.ConclusionIn summary, our study is the first to identify significant alterations in the gut microbiota of patients with positive plaques, providing crucial microbial evidence for further exploration of the pathogenesis of SCAS.

A wide variety of small-amplitude waves widely exist in the ionosphere and have significant effects on the evolution of equatorial plasma bubbles. In this paper, we simulated equatorial plasma bubbles (EPB) seeded by vertical neutral wind perturbations with wavelengths of 125 km and 250 km, and compared the morphology characteristics of plasma bubble structures with those under random noise perturbations in the background density. The numerical results showed that both vertical winds and random background noise perturbations can contribute to the growth of plasma bubbles, and the perturbations under additional random background noise can promote the growth of the plasma bubble structures faster. Additionally, several processes of the nonlinear behavior of bifurcated EPB structures, including bifurcation, pinching, and small-scale turbulent structures, were successfully obtained. Our simulation captured supersonic flows within the low-density plasma structures characterized by vertical velocities of about 1.5 km/s, which is consistent with experimental studies found in the literature.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor, particularly in children, and its clinical manifestations vary. When the tumor is small, it may be asymptomatic; however, with larger tumors, patients may present with symptoms such as recurring pneumonia, atelectasis, persistent cough, chest pain, and even hemoptysis. PMEC appears as an exophytic intrabronchial mass. This study aims to report on the clinical manifestations, imaging findings, treatment approaches, and prognosis of two children diagnosed with PMEC at our hospital between January 2018 and December 2022. The age of onset for both children was 9 years, and the masses were located in the right upper lobe bronchi. Following surgical treatment, both patients showed a good prognosis. In addition, we conducted a comprehensive review of the relevant literature to enhance the overall understanding of PMEC.

Introduction: Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R/R AML and MS patients.Methods: Ten patients with R/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety.Results: All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia.Conclusion: The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.

ObjectiveCerebral white matter hyperintensity can lead to cerebral small vessel disease, MRI images in the brain are used to assess the degree of pathological changes in white matter regions. In this paper, we propose a framework for automatic 3D segmentation of brain white matter hyperintensity based on MRI images to address the problems of low accuracy and segmentation inhomogeneity in 3D segmentation. We explored correlation analyses of cognitive assessment parameters and multiple comparison analyses to investigate differences in brain white matter hyperintensity volume among three cognitive states, Dementia, MCI and NCI. The study explored the correlation between cognitive assessment coefficients and brain white matter hyperintensity volume.MethodsThis paper proposes an automatic 3D segmentation framework for white matter hyperintensity using a deep multi-mapping encoder-decoder structure. The method introduces a 3D residual mapping structure for the encoder and decoder. Multi-layer Cross-connected Residual Mapping Module (MCRCM) is proposed in the encoding stage to enhance the expressiveness of model and perception of detailed features. Spatial Attention Weighted Enhanced Supervision Module (SAWESM) is proposed in the decoding stage to adjust the supervision strategy through a spatial attention weighting mechanism. This helps guide the decoder to perform feature reconstruction and detail recovery more effectively.ResultExperimental data was obtained from a privately owned independent brain white matter dataset. The results of the automatic 3D segmentation framework showed a higher segmentation accuracy compared to nnunet and nnunet-resnet, with a p-value of

Vacuum preloading coupled with prefabricated vertical drains (PVDs) has been widely used to improve the property of the dredged slurry. However, the effect of PVD layout on slurry consolidation characteristics remains poorly understood. This study conducted two vacuum preloading model tests—with single and dual PVDs. Particle image velocimetry (PIV) was used to directly observe the slurry displacements and strain paths. The test results revealed that the slurry consolidation characteristics were similar under different PVD layouts in the early stage of vacuum preloading. However, in the mid-stage, the effect of dual PVDs led to a significant reduction and increased dispersion of the slurry horizontal displacement. This, in turn, resulted in a thinner clogging zone and a subsequent decrease in vacuum pressure loss. Consequently, the slurry near the PVDs experienced an extended period of consolidation deformation. During the later stage, the single PVD model test exhibited a distinct zone of both vertical and horizontal compression in the slurry, while under dual PVDs, the slurry primarily underwent vertical compression and horizontal extension. The study also provided the relationship between the clogging zone thickness and time, which provided a reference for theoretical consolidation calculations.

ObjectiveTo evaluate the prognostic value of common clinical inflammatory and nutritional indicators before treatment in patients with non-small cell lung cancer in the real world.MethodA total of 5,239 patients with pathologically confirmed non-small cell lung cancer from 2011 to 2018 in the Affiliated Cancer Hospital of Xinjiang Medical University were selected. Their inflammatory and nutritional indicators (RDW, PDW, NLR, LMR, NMR, PLR, SII, PNI, TP, ALB, CYRFA21-1, CEA, CA125, NSE, α1-globulin, α2-globulin, β1-globulin, β2-globulin, and γ-globulin) before treatment were collected. From the total number, 1,049 patients were randomly sampled (18 to 20% of patients each year) and used as the validation set; the remaining 4,190 patients were used as the training set. According to the eighth edition of the guidelines for the diagnosis, treatment, and stage risk stratification of lung cancer, the patients were divided into four groups: stage I/II operable, stage III operable, stage III inoperable, and stage IV. We used the X-tile software to intercept and classify the cut-off values of each index in the validation set. Univariate and multivariate Cox proportional-hazard regression were used to screen the independent risk factors affecting the prognosis of non-small cell lung cancer and establish a prognostic model for 1, 3, and 5 years. The validation set was used to verify its performance. Finally, the Kaplan–Meier curve was used to assess the survival rate, and the corresponding nomogram was established for clinical use.ResultsAfter screening, no effective indicators were found in the stage I/II operable group. RDW and CA125 were effective indicators for the stage III operable group (cut-off values were 14.1 and 9.21, respectively, compared with the low-value group; univariate HR was 2.145 and 1.612, and multivariate HR was 1.491 and 1.691, respectively). CYRFA21-1 and CA125 were effective prognostic indicators for the stage III inoperable group (cut-off values were 10.62 and 44.10, respectively, compared with the low-value group; univariate HR was 1.744 and 1.342, and multivariate HR was 1.284 and 1.304, respectively). CYRFA21-1, CA125, NLR, and α1-globulin were effective indicators of prognosis in stage IV (cut-off values were 3.07, 69.60, 4.08, and 5.30, respectively, compared with the low-value group; univariate HR was 1.713, 1.339, 1.388, and 1.539; and multivariate HR was 1.407, 1.119, 1.191, and 1.110, respectively). The model was constructed with the best validation power in stage IV patients (C-index = 0.733, 0.749, and 0.75 at 1, 3, and 5 years, respectively).ConclusionFor patients with stage III and IV non-small cell lung cancer, some inflammatory markers, serum tumor markers, and nutritional indicators are independent prognostic factors. Combined with the general data of patients, the constructed prognostic evaluation model has the best efficacy in patients with stage IV and can be widely used in clinical practice.

IntroductionTo compare the accuracy of Artificial Intelligent Breast Ultrasound (AIBUS) with hand-held breast ultrasound (HHUS) in asymptomatic women and to offer recommendations for screening in regions with limited medical resources.Methods852 participants who underwent both HHUS and AIBUS were enrolled between December 2020 and June 2021. Two radiologists, who were unaware of the HHUS results, reviewed the AIBUS data and scored the image quality on a separate workstation. Breast imaging reporting and data system (BI-RADS) final recall assessment, breast density category, quantified lesion features, and examination time were evaluated for both devices. The statistical analysis included McNemar’s test, paired t-test, and Wilcoxon test. The kappa coefficient and consistency rate were calculated in different subgroups.ResultsSubjective satisfaction with AIBUS image quality reached 70%. Moderate agreements were found between AIBUS with good quality images and HHUS for the BI-RADS final recall assessment (κ = 0.47, consistency rate = 73.9%) and breast density category (κ = 0.50, consistency rate = 74.8%). The lesions measured by AIBUS were statistically smaller and deeper than those measured by HHUS (P < 0.001), though they were not significant in clinical diagnosis (all < 3 mm). The total time required for the AIBUS examination and image interpretation was 1.03 (95% CI (0.57, 1.50)) minutes shorter than that of HHUS per case.ConclusionModerate agreement was obtained for the description of the BI-RADS final recall assessment and breast density category. With image quality comparable to that of HHUS, AIBUS was superior for the efficiency of primary screening.

IntroductionGastric cancer is a highly heterogeneous malignant tumor of the digestive system. Anti-HER2 treatment can inhibit downstream signaling pathways and improve clinical treatment and outcomes in patients with HER2 protein overexpression. Currently, two standard methods for evaluating HER2 expression status are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). However, these low-throughput assays often produce discordant or equivocal results.MethodsIn this study, we presented a new HER2 protein detection method based on mass spectrometry selected reaction monitoring (MS-SRM) and validated the method. We conducted a retrospective study on 118 formalin-fixed paraffin-embedded (FFPE) tissues from patients with advanced gastric adenocarcinoma in northern China, and we compared the MS-SRM results with those from IHC and correlated them with FISH. ResultsWe established and validated the upper and lower detection limits (300-700 amol/μg) for abnormal HER2 protein expression in advanced gastric cancer. We also found that, among samples with mixed Lauren subtypes, those with a high level of HER2 expression had typical intestinal type features in pathology. DiscussionThis study demonstrated that the MS-SRM method can overcome the limitations and deficiencies of IHC, directly quantify the expression of HER2 protein in tumor cells and be used as a supplement to IHC. It has the potential to be used as a companion diagnosis for new drugs used to treat advanced gastric cancer. Large-scale clinical validation is required.

Landscape ecological risk reflects the impact of human activities or natural hazards on landscape patterns, functions, and processes in a region. The scientific assessment of its evolutionary trends can play an essential role in maintaining and improving regional human wellbeing. This study focused on the Fuchunjiang River Basin in the suburbs of Hangzhou, a large city in China with a high degree of landscape heterogeneity and rapid economic growth. Based on land use data from 1990 to 2020, an ecological risk assessment model and geodetector tools were combined to study the spatiotemporal variation characteristics and influencing factors of landscape ecological risk in the basin. The results showed the following: (1) from 1990 to 2020, the landscape pattern of various land use types showed a general trend of an increasing degree of agglomeration and decreasing loss index; (2) the spatial distribution pattern of landscape ecological risk was “high in the northwest and low in the southeast.” From basin to township scales, landscape ecological risk showed a decreasing trend on long time scales, although the changes were relatively drastic in short time periods; (3) GDP, human interference, area of urban and rural residential land, area of arable land transferred in, and area of arable land transferred out were the dominant influencing factors of landscape ecological risk; (4) the coupling between landscape ecological risk and GDP in 2020 exhibited an inverted “U” shaped relationship, indicating that the environmental Kuznets curve (EKC) may have the same applicability in the ecological risk management; (5) according to the main functions of different risk agglomerations, targeted ecological risk management strategies were proposed. In short, this study carried out the landscape ecological risk assessment at the township scale for the first time, quantitatively analyzed the relationship between economic development and ecological risk, and proposed targeted risk prevention strategies, which are instructive for other basin areas that are experiencing rapid urbanization in the world.

Establishing plantation forests significantly increases the carbon (C) storage of terrestrial ecosystems. However, how vegetation types affect the ecosystem C sequestration capacity is not completely clear. Here, a slash pine plantation (SPP), a Schima superba plantation (SSP), and a Masson pine plantation (MPP), which have been planted for 30 years, were selected in subtropical China. The C storage and distribution patterns of plant, litter, and soil were investigated and calculated. The ecosystem C density was 17.7, 21.6, and 15.3 kg m–2 for SPP, SSP, and MPP, respectively. Ecosystem C stocks were mainly contributed by tree aboveground (39.9–46.0%) and soil C stocks (41.6–44.2%). The ecosystem C density of SSP was higher than that of SPP and MPP, and significant differences were found among three plantations for both aboveground and underground C densities. The aboveground and underground ecosystem C storage of SSP was 27.4 and 53.4% higher than that of MPP, respectively. Meanwhile, root C storage of MPP was lower than that of SPP and SSP, while soil C storage of MPP was lower than that of SSP. In the understory layer, SPP had the highest C density, followed by MPP, and there was a significant difference in C density among three plantations. However, no significant difference was found for the ecosystem C distribution among three plantations. Our results show that vegetation types significantly affect C storage but not C distribution in forest ecosystems and establishing the broad-leaved plantation has the highest ecosystem C storage in the subtropics. This study provides a theoretical basis for us to choose appropriate forest management measures.

Parry-Romberg syndrome (PRS) combined with hemimasticatory spasm (HMS) is a rare craniofacial disorder characterized by unilateral facial tissue atrophy with paroxysmal involuntary contractions of the jaw-closing muscles. Although a majority believe that this is a result of demyelination changes from the effect of the facial involvement of PRS on the trigeminal nerve motor branches, the mechanism of PRS is presently unclear. Moreover, the therapeutic effects of existing drugs that target PRS have not been satisfactory. For intolerable spasms of the masticatory muscles, botulinum toxin injection may temporarily relieve the symptoms of spasms. We report a case of HMS secondary to PRS that was treated via a partial resection of the trigeminal nerve motor branch under intraoperative neurophysiological monitoring.

This paper takes insurers' intervention as the entry point, and sets insurers' intervention, separation of two rights and firms' technological innovation in a specific context to study the transmission mechanism and economic consequences using panal model. The results show that there is a positive relationship between insurers' intervention and firm's technological innovation, and the degree of separation of two rights has a negative moderating effect on the relationship between insurers' intervention and technological innovation, and this effect is more obvious in the sample of state-owned enterprises. Therefore, the state should formulate relevant policies to guide the equity investment behavior of insurance companies so as to improve the operational efficiency of market resources.

Background and objectivesCerebral revascularization surgery is the mainstay of treatment for moyamoya syndrome (MMS) today, and intraoperative determination of the patency of the revascularized vessel is a critical factor in the success of the procedure. Currently, major imaging modalities include intraoperative indocyanine green (ICG) videoangiography (ICG-VA), digital subtraction angiography (DSA), and vascular ultrasound Doppler. Infrared thermography is a modern imaging modality with non-contact devices for the acquisition and analysis of thermal data. We aimed to investigate the feasibility and advantages of infrared thermography in determining anastomotic patency during MMS surgery.MethodsIndocyanine green videoangiography and infrared thermography were performed simultaneously in 21 patients with MMS who underwent bypass surgery. The detection result of vessel patency was compared, and the feasibility and advantages of infrared thermography were assessed.ResultsThe patency of the anastomosis was accurately determined in 21 patients using either ICG angiography or infrared thermography. In 20 patients, the results of infrared thermography showed that the vascular anastomosis was unobstructed, and there was an agreement with the subsequent results of ICG-VA. In one patient, we suspected inadequate patency after testing the anastomosis with infrared thermography, and the results of ICG-VA evaluation of the anastomosis confirmed that there was indeed an anastomotic obstruction.ConclusionCompared with ICG-VA, infrared thermography might offer an alternative non-invasive, contrast-free option in assessing anastomosis patency compared with ICG-VA, and it is likely to become more widely used in the clinic in the near future.

It is well-known that CD226 serves as a critical activating receptor on various immune cells, such as lymphocytes and monocytes, and it is suggested to promote anti-tumor immunity in the tumor microenvironment (TME). Herein, we showed a crucial regulatory role of CD226 in CD8+T cell-mediated anti-tumor response in TME of human gastric cancer (GC). Specifically, the increased CD226 expression in cancer tissues was significantly associated with better clinical outcomes in GC patients. Moreover, the increased infiltrating CD226+CD8+T cells and the increased ratio of infiltrating CD226+CD8+T cells in CD8+T subpopulation within cancer tissues could also be valuable prognostic predictors for GC patients. Mechanically, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis revealed that the chromatin accessibility of CD226 in CD4+ and CD8+TILs was significantly higher than that in CD8+T cells in normal tissues. Further analysis showed that CD8+TILs highly expressed immune checkpoint molecules, such as TIGIT, LAG3, and HAVCR2, which means CD8+TILs are more exhausted. In addition, our multi-color immunohistochemical staining (mIHC) revealed that GC patients with higher frequency of IFN-γ+CD226+CD8+TILs showed poorer prognosis. Combined with the single-cell transcriptome sequencing (scRNA-seq) data analysis, we found that the expressions of IFN-γ and TIGIT in CD8+TILs were significantly and positively correlated. The expression of TIGIT in IFN-γ+CD226+CD8+TILs was higher, while that in IFN-γ-CD226+CD8+TILs was significantly lower. The correlation analysis showed that the expression of CD226 was positively correlated with the score of effector T cells but negatively correlated with that of immunosuppressive factors, such as Tregs and tumor-associated macrophages (TAMs). Collectively, we showed that the frequency of CD226+CD8+TILs was an excellent prognostic predictor for GC patients. Our findings provided insights into the interaction pattern between co-stimulatory receptor CD226 and tumor cells as well as the infiltrating immune cells in the TME in GC.

Introduction: Chronic kidney disease (CKD) can lead to significant elevation of 1-deoxysphingolipids (1-deoxySL). The increase of 1-deoxySL in turn can result in mitochondrial damage and oxidative stress, which can cause further progression of CKD.Methods: This study assessed the therapeutic effect of Astragaloside IV (AST) against 1-deoxySL-induced cytotoxicity in vitro and in rats with CKD. HK-2 cells were exposed to 1-deoxysphinganine (doxSA) or doxSA + AST. doxSA-induced mitochondrial dysfunction and oxidative stress were evaluated by immunostaining, real-time PCR, oxidative stress sensor, and transmission electron microscopy. The potential effects of AST on kidney damage were evaluated in a rat 5/6 nephrectomy (5/6 Nx) model of CKD.Results: The findings of in vitro experiments showed that doxSA induced mitochondrial damage, oxidative stress, and apoptosis. AST markedly reduced the level of mitochondrial reactive oxygen species, lowered apoptosis, and improved mitochondrial function. In addition, exposure to AST significantly induced the phosphorylation of p62 and the nuclear translocation of Nrf2 as well as its downstream anti-oxidant genes. p62 knock-down fully abolished Nrf2 nuclear translocation in cells after AST treatment. However, p62 knock-down did not affect TBHQ-induced Nrf2 nuclear translocation, indicating that AST can ameliorate doxSA-induced oxidative stress through modulation of p62 phosphorylation and Nrf2 nuclear translocation.Conclusion: The findings indicate that AST can activate Nrf2 antioxidant pathway in a p62 dependent manner. The anti-oxidative stress effect and the further mitochondrial protective effect of AST represent a promising therapeutic strategy for the progression of CKD.

Aiming at the unreliability of historical data for short-term load forecasting caused by the sudden change of power grid load under emergencies, a short-term load prediction method adopting transfer learning is studied. The proposed transfer learning method combines the attention mechanism (AM) with the long short-term memory network coupled with input and forgetting gates (CIF-LSTM) to construct the AM-CIF-LSTM short-term load prediction model. First, the variational modal decomposition (VMD) method is used to extract the trend component and certain periodic high-frequency components of the load datasets of the scene to be predicted and similar scenes. Subsequently, the AM-encoder/decoder learning model is established based on the trend component, and the AM learnable parameters are trained and transferred to the AM-CIF-LSTM model. Furthermore, inspired by the idea of classified forecasting, the load trend component and periodic high-frequency components under the required prediction scene are predicted by AM-CIF-LSTM and deep recursive neural network (DRNN), respectively. Finally, the load forecasting results are superimposed to obtain the load forecasting value. The experimental results demonstrate that the proposed method outperformed the existing methods in multiple accuracy indicators and could predict the rapid change trend of load in the case of insufficient data accurately and stably.

Childhood emotional neglect (CEN) has a relatively high incidence rate and substantially adverse effects. Many studies have found that CEN is closely related to emotion regulation and depression symptoms. Besides, the functional activity of the prefrontal lobe may also be related to them. However, the relationships between the above variables have not been thoroughly studied. This study recruited two groups of college students, namely, those with primary CEN (neglect group) and those without childhood trauma (control group), to explore the relationships among CEN, adulthood emotion regulation, depressive symptoms, and prefrontal resting functional connections. The methods used in this study included the Childhood Trauma Questionnaire (CTQ), Emotion Regulation Questionnaire (ERQ), Beck Depression Inventory-II (BDI-II) and resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared with the control group, the neglect group utilized the reappraisal strategy less frequently and displayed more depressive symptoms. The prefrontal functional connections with other brain regions in the neglect group were more robust than those in the control group using less stringent multiple correction standards. Across the two groups, the functional connection strength between the right orbitofrontal gyrus and the right middle frontal gyrus significantly negatively correlated with the ERQ reappraisal score and positively correlated with the BDI-II total score; the ERQ reappraisal score wholly mediated the relationship between the functional connection strength and the BDI-II total score. It suggests that primary CEN may closely correlate with more depressive symptoms in adulthood. Furthermore, the more robust spontaneous activity of the prefrontal lobe may also be closely associated with more depressive symptoms by utilizing a reappraisal strategy less frequently.

BackgroundTo investigate the association between insufficient maternal gestational weight gain (GWG) during dietary treatment, and neonatal complications of small-for-gestational-age (SGA) infants born to mothers with Gestational diabetes mellitus (GDM).MethodsA retrospective case-control study was conducted, involving 1,651 infants born to mothers with GDM. The prevalence of a perinatal outcome and maternal GWG were compared among SGA, adequate- (AGA), and large-for-gestational-age (LGA); association with birth weight and GWG was identified using Pearson's correlation analysis; binary logistic regression was performed to determine the odds ratio (OR) associated with SGA.ResultsIn total, 343 SGA, 1025 AGA, and 283 LGA infants met inclusion criteria. The frequency of SGA infants who were siblings (41.7 vs. 4.3 vs. 1.9%) and composite of complications (19.2 vs. 12.0 vs. 11.7%) were higher in SGA infants than in those in AGA or LGA infants group (both P < 0.01). GWG and pre-partum BMI were lower among the SGA mothers with GDM group (11.7 ± 4.5 kg, 25.2 ± 3.1 kg/m2) than AGA (12.3 ± 4.6 kg, 26.3 ± 3.4 kg/m2) or LGA (14.0 ± 5.1 kg, 28.7 ± 3.9 kg/m2) mothers with GDM group. Binary logistic regression showed that siblings who were SGA (AOR 18.06, 95% CI [10.83–30.13]) and preeclampsia (AOR 3.12, 95% CI [1.34–7.30]) were associated with SGA, but not GWG below guidelines (P > 0.05). The risk of SGA (25.7 vs. 19.1 vs. 14.2%) and FGR (15.3 vs. 10.9 vs. 7.8%) was higher in GWG below guidelines group than those in GWG above and within guidelines group, the risk of low Apgar score (6.4 vs. 3.0 vs. 2.8%) was higher in GWG above guidelines group than that in GWG below and within guidelines group (P < 0.05).ConclusionOur findings demonstrated that GWG above and below guidelines, compared with GWG within guidelines, had a higher risk of adverse infant outcomes. Our findings also suggested that GWG below guidelines did not increase the risk for SGA, though SGA infants had more adverse outcomes among neonates born to mothers with GDM.

Vehicle load is an important factor for the fatigue damage of the orthotropic steel decks. The traffic vehicles for port highway in China are mainly multi-axle container trucks, which show different characteristics from conventional highways. Based on the multi-period traffic flow data collected by weight-in-motion system of a bridge over the sea in Zhejiang, China, this study has investigated the traffic load characteristics of the port highway bridge. Eight typical vehicles of fatigue load spectrum are classified according to the number of axles and wheelbase. The distribution characteristics of the gross vehicle weight (GVW) and axle weights of typical vehicles are analyzed by lane. Depended on the equivalent fatigue damage principle, the vehicle load spectrum for fatigue evaluation of the port highway bridges is established. The results show that the average proportion of the trucks (weighing greater than 3 tons) in the total traffic flow is 73.2%, and trucks with more than four-axle accounted for 89.0%. Heavy vehicles are mainly concentrated on the outer lanes, and the probability of vehicles driving in the heavy lane increases with the increase of gross vehicle weight. The maximum equivalent gross vehicle weight is 62.5 tons, which appeared in V7 in the exiting island direction. The simplified fatigue vehicle model in the heavy lane for Chinese port highway bridges is proposed, based on the six-axle vehicle which contributed the most fatigue damage. The proposed fatigue load model can better represent the actual traffic load level of port highway bridges in China.

Sedimentation is an important mechanism to mitigate the shrinking of tidal flat and to restore its ecological function by means of sand or mud nourishment. To explore the sedimentation of cohesive sediments, a seabed tripod observation system was deployed at the subtidal region of the Hengsha Shoal adjacent to the turbidity maximum zone of the Yangtze Estuary for 11 days. The results showed that the fine sediment with the median grain size around 8 mm occupied the whole water column. The seabed was in relative equilibrium state with the fluctuation of bed level smaller than 16 mm during the moderate wind condition while the seabed experienced a rapid erosion of 38mm and a successive intensive accretion of 68mm during the process of wind wave and swell. The bottom hydrodynamic at 0.3mab during the bed accretion was stronger than that during the bed erosion. The deposition process of cohesive sediments can be better described by the simultaneous deposition paradigm than that by the exclusive deposition paradigm according to the direct data-model comparison of the bed level changes, especially during the impact of fluid mud. Three possible reasons for the better performance of the simultaneous deposition paradigm were proposed. The first possibility is that the fine suspended sediments do maintain a continuous contact with the sediment bed since the direct bed level changes during our observation period has been well reproduced by the simultaneous deposition paradigm. The second possibility is the SSC-induced turbulence damping which facilitates the fine sediment settling in the form of cohesive sediment flocs, indicating the settling of sediments can’t be judged by the critical shear stress for deposition just based on the single particle grain size. The last possibility is the fluid mud-induced overestimated bed shear stress by using turbulent velocity fluctuation above the fluid mud-water interface, which produces excess sediment erosion waiting to be compensated by the simultaneous deposition paradigm. For practical modeling purposes, modeling under the simultaneous deposition paradigm can give satisfactory results for the sedimentation of cohesive sediment especially during the impact of wave or swell.

BackgroundThe enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model.MethodsIn this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining.ResultsEA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters.ConclusionOur results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.

IntroductionCastor bean or ricin-induced intoxication or terror events have threatened public security and social safety. Potential resources or materials include beans, raw extraction products, crude toxins, and purified ricin. The traceability of the origins of castor beans is thus essential for forensic and anti-terror investigations. As a new imaging technique with label-free, rapid, and high throughput features, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been gradually stressed in plant research. However, sample preparation approaches for plant tissues still face severe challenges, especially for some lipid-rich, water-rich, or fragile tissues. Proper tissue washing procedures would be pivotal, but little information is known until now.MethodsFor castor beans containing plenty of lipids that were fragile when handled, we developed a comprehensive tissue pretreatment protocol. Eight washing procedures aimed at removing lipids were discussed in detail. We then constructed a robust MALDI-MSI method to enhance the detection sensitivity of RCBs in castor beans.Results and DiscussionA modified six-step washing procedure was chosen as the most critical parameter regarding the MSI visualization of peptides. The method was further applied to visualize and quantify the defense peptides, Ricinus communis biomarkers (RCBs) in castor bean tissue sections from nine different geographic sources from China, Pakistan, and Ethiopia. Multivariate statistical models, including deep learning network, revealed a valuable classification clue concerning nationality and altitude.

IntroductionGlutamine is characterized as the nutrient required in tumor cells. The study based on glutamine metabolism aimed to develop a new predictive factor for pan-cancer prognostic and therapeutic analyses and to explore the mechanisms underlying the development of cancer.MethodsThe RNA-sequence data retrieved from TCGA, ICGC, GEO, and CGGA databases were applied to train and further validate our signature. Single-cell RNA transcriptome data from GEO were used to investigate the correlation between glutamine metabolism and cell cycle progression. A series of bioinformatics and machine learning approaches were applied to accomplish the statistical analyses in this study.ResultsAs an individual risk factor, our signature could predict the overall survival (OS) and immunotherapy responses of patients in the pan-cancer analysis. The nomogram model combined several clinicopathological features, provided the GMscore, a readable measurement to clinically predict the probability of OS and improve the predictive capacity of GMscore. While analyzing the correlations between glutamine metabolism and malignant features of the tumor, we observed that the accumulation of TP53 inactivation might underlie glutamine metabolism with cell cycle progression in cancer. Supposedly, CAD and its upstream genes in glutamine metabolism would be potential targets in the therapy of patients with IDH-mutated glioma. Immune infiltration and sensitivity to anti-cancer drugs have been confirmed in the high-risk group.DiscussionIn summary, glutamine metabolism is significant to the clinical outcomes of patients with pan-cancer and is tightly associated with several hallmarks of a malignant tumor.

Schistosomiasis is a zoonotic parasitic disease caused by schistosome infection that severely threatens human health. Therapy relies mainly on single drug treatment with praziquantel. Therefore, there is an urgent need to develop alternative medicines. The glutamate neurotransmitter in helminths is involved in many physiological functions by interacting with various cell-surface receptors. However, the roles and detailed regulatory mechanisms of the metabotropic glutamate receptor (mGluR) in the growth and development of Schistosoma japonicum remain poorly understood. In this study, we identified two putative mGluRs in S. japonicum and named them SjGRM7 (Sjc_001309, similar to GRM7) and SjGRM (Sjc_001163, similar to mGluR). Further validation using a calcium mobilization assay showed that SjGRM7 and SjGRM are glutamate-specific. The results of in situ hybridization showed that SjGRM is mainly located in the nerves of both males and gonads of females, and SjGRM7 is principally found in the nerves and gonads of males and females. In a RNA interference experiment, the results showed that SjGRM7 knockdown by double-stranded RNA (dsRNA) in S. japonicum caused edema, chassis detachment, and separation of paired worms in vitro. Furthermore, dsRNA interference of SjGRM7 could significantly affect the development and egg production of male and female worms in vivo and alleviate the host liver granulomas and fibrosis. Finally, we examined the molecular mechanisms underlying the regulatory function of mGluR using RNA sequencing. The data suggest that SjGRM7 propagates its signals through the G protein-coupled receptor signaling pathway to promote nervous system development in S. japonicum. In conclusion, SjGRM7 is a potential target for anti-schistosomiasis. This study enables future research on the mechanisms of action of Schistosomiasis japonica drugs.

Bone metastatic breast cancer has severely threatened the survival and life quality of patients. Due to the suboptimal efficacy of anti-metastatic chemotherapeutic drugs and the complicated bone marrow microenvironments, effective treatment of metastatic breast cancer remains challenging for traditional clinical approaches. In this work, we developed a mesoporous nanoplatform (m-CuS-PEG) with the co-loading of CuS nanodots and a chemotherapeutic drug cisplatin for the combined photothermal-chemotherapy of bone-metastasized breast cancer. The CuS nanodots were decorated onto mesoporous silica (m-SiO2) surface with dendritic mesoporous channels, into which the cisplatin was accommodated. The carboxyl-terminated poly (ethylene glycol) (PEG) was further functionalized onto the surface to obtain the functional nanoplatform m-CuS-PEG. The drug release of the loaded cisplatin exhibited pH- and thermal-dual responsive manner. The attached CuS nanodots rendered the mesoporous nanoplatform with high photothermal conversion ability. Upon irradiation with a near-infrared laser in the second near-infrared (NIR-II) window, m-CuS-PEG dispersions exhibited rapid temperature elevation and high photostability. The results revealed that m-CuS-PEG had excellent biocompatibility. The cisplatin-loaded m-CuS-PEG not only showed superior cancer cell-killing effects, but also significantly inhibit the growth of metastatic tumors. The tumor-induced bone destruction was also dramatically attenuated by the mesoporous nanoplatform-mediated combined therapy. Overall, the developed functional nanoplatform integrates photothermal therapy and efficient chemotherapeutic drug delivery to offer an alternative approach for combating breast cancer bone metastasis.

BackgroundConversion therapy is feasible in patients with oncologically unresectable hepatocellular carcinoma (HCC). However, it is challenging to prospectively identify patients who are more likely to achieve successful conversion before initiating systemic therapy, either alone or combined with locoregional therapy.MethodsCriteria for identifying potentially resectable patients with initially oncologically unresectable HCC before treatment with lenvatinib plus an anti-PD-1 antibody were proposed based on real-world evidence. Multivariate Firth logistic regression was used to validate the proposed criteria in a retrospective cohort of consecutive patients with advanced HCC, who received combination therapy with lenvatinib plus an anti-PD-1 antibody between September 2018 and September 2021.ResultsThe proposed criteria were as follows: (1) Eastern Cooperative Oncology Group performance status of 0 or 1; (2) Child-Pugh class A; (3) intrahepatic tumors confined to one lobe (left, right, or middle lobe), or present in one lobe alongside a single tumor with diameter ≤5 cm or up to three tumors each with diameter ≤3 cm in the remaining lobes, with R0 resection achievable by hemihepatectomy, alone or combined with locoregional therapy to the remaining lobes during surgery; and (4) no portal vein tumor thrombus involving the contralateral liver lobe or reaching the superior mesenteric vein, no hepatic vein tumor thrombus involving more than two major hepatic vein branches on the tumor side, and no tumor thrombus of the inferior vena cava reaching the atrium. Firth logistic regression confirmed the criteria were an independent predictor of surgery following conversion therapy with lenvatinib plus an anti-PD-1 antibody.ConclusionsThis study proposed and validated criteria for identifying patients with initially oncologically unresectable HCC who are potentially resectable when treated with combination therapy with lenvatinib plus an anti-PD-1 antibody. The proposed criteria could help standardize conversion therapy studies in advanced HCC.

Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent. we show that EA dose-dependently stimulates GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. In addition, EA induces L-cells to secrete peptide YY (PYY). EA induces a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) or Gαq ablates EA-stimulated increase of [Ca2+]i and GLP-1 secretion. In vivo, a single dose of EA acutely stimulates GLP-1 and PYY secretion in mice, accompanied with an improved glucose tolerance and insulin levels. Oral administration of EA at a dose of 50 mg/kg/day for 2 weeks normalized the fasting blood glucose and restored glucose tolerance in high-fat diet-induced obese (DIO) mice to levels that were comparable to chow-fed mice. In addition, EA suppresses appetite, reduces food intake, promotes weight loss, and reverses perturbated metabolic variables in obese mice. These results suggest that EA could be a dual-action agent as an alternative or adjuvant treatment for both T2D and obesity.

BackgroundErectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied.Materials and methodsData on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results.ResultsA total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all P < 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all P < 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results.ConclusionIncreasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.

With the success of chimeric antigen receptor-modified (CAR) T-cell therapy for relapsed/refractory (r/r) B-cell malignancies, severe complications after CAR T-cell infusion have emerged as nonnegligible prognosis-related factors. However, the prognosis of patients with CAR T-cell-related hyperferritinaemia (HFA) is unclear. We report the efficacy and safety of CAR T-cell therapy in 16 r/r B-cell malignancy patients with CAR T-cell-related HFA. The rates of serum ferritin levels above 10,000 ng/ml during CAR T-cell therapy were 6.2% and 14.3% in B-cell non-Hodgkin’s lymphoma (B-NHL) and acute B lymphocyte leukemia (B-ALL), respectively. These patients were characterized by an extremely high tumor burden and a high rate of extranodal involvement. In lymphoma, the complete remission (CR) rate was 37.5% (3/8), which was lower than that in the control group with the lowest value of ferritin (CR was 87.5% (7/8), P=0.0406), and it could also be seen that the OS of the control group (1-year OS rate 100%) had a better trend than HFA group (1-year OS rate 50%). In the B-ALL patients, the OS of the control group (1-year OS rate 100%) was higher than HFA group (1-year OS rate 45%, P=0.0189), although there was no significant difference in CR rate. High-grade CRS (≥3) occurred in 56.25% of the patients, and the mortality rate was 56.25%, which was significantly higher than control group (12.5% and 12.5%, P=0.009). The peak serum ferritin level in the patients who died of CRS was significantly higher than others (P=0.0168). Regardless of whether the CAR T-related MAS diagnostic criteria were met, there was no significant difference in ORR and OS in HFA group, however patients with MAS showed a higher rate of high-grade CRS. Interestingly, in our study, glucocorticoid intervention in HFA group showed little impact on expansion of CAR-T cells, whether compared with control group or compared within HFA group by dividing patients into high and low dosage subgroups based on the median dose of glucocorticoid. High mortality was observed in patients with CAR T-cell-related HFA. Early glucocorticoid intervention might be worth trying to improve the safety of CAR T therapy in these patients.