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Abstract Introduction Treatment of multiple myeloma (MM) has been transformed by novel therapies, including CD38 monoclonal antibodies (mAbs), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), resulting in increasing numbers of patients who are triple-class exposed (TCE; exposed to ≥ 1 drug in each class). Many patients are penta-exposed (PE; ≥ 2 IMiDs, ≥ 2 PIs, and a CD38 mAb), some are triple-class refractory (TCR), and some are PE and TCR (PE-TCR). Data on real-world outcomes in elderly patients with MM across this spectrum of exposure are limited. Methods Data from the Medicare Chronic Conditions Warehouse Database from November 2006–December 2020 were used to examine cohorts of TCE, TCR, PE, and PE-TCR patients. Outcomes were assessed from the start of the index line of therapy (LOT), defined as the first LOT after becoming TCE or PE. Results A total of 2830 TCE, 1371 TCR, 1121 PE, and 774 PE-TCR patients were identified. Pomalidomide was the most frequently used medication for the index LOT in all cohorts (32.6% [PE-TCR] to 43.3% [TCR]). The most frequently used regimens for the index LOT were pomalidomide plus daratumumab for TCE (17.2%) and PE (7.0%), pomalidomide plus carfilzomib for TCR (10.3%), and pomalidomide plus elotuzumab for PE-TCR (7.4%). Median time to discontinuation (TTD) ranged from 4.2 (PE-TCR) to 6.9 (TCE) months, and overall survival (OS) ranged from 13.0 (TCR) to 15.9 (PE) months. Healthcare resource utilization (HRU) was lowest for TCE and highest for PE-TCR patients. Mean monthly healthcare costs (HCC) ranged from $23,091 (TCE) to $24,412 (PE-TCR). MM medications represented 66.2% (PE-TCR) to 72.8% (TCE) of costs. Conclusions In this study across a spectrum of Medicare TCE patients, there was heterogeneity in treatment regimens, suggesting no standard of care. TTD and OS were short, and HRU and HCC were high. These results underscore the potential for new therapies in this population.

Abstract Background Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women’s ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. Methods We retrospectively analysed data from patients aged 20–40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. Results With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of ‘exclusive breastfeeding’ was 5.1 months, and the mean duration of ‘any breastfeeding’ was 8.8 months. The rate of ‘ever breastfeeding’ is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. Conclusions There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.

Purpose: Pathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms. Methods: Genes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-β1 (TGF-β1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ. Results: Through network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-β1/Smad pathway. Conclusion: Resveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB in vivo and may be considered a novel therapeutic strategy.

Abstract Clinical studies have shown that there may be a certain relationship between pathological changes of the myodural bridge complex (MDBC) and chronic headaches of unknown cause. But there is still a lack of experimental evidence to explain the possible mechanism. This study aims to further confirm this relationship between MDBC and chronic headaches and explore its potential occurrence mechanism in rats. Bleomycin (BLM) or phosphate-buffered saline (PBS) was injected into the myodural bridge fibers of rats to establish the hyperplastic model of MDBC. After 4 weeks, the occurrence of headaches in rats was evaluated through behavioral scores. The immunohistochemistry staining method was applied to observe the expression levels of headache-related neurotransmitters in the brain. Masson trichrome staining results showed that the number of collagen fibers of MDBC was increased in the BLM group compared to those of the other two groups. It revealed hyperplastic changes of MDBC. The behavioral scores of the BLM group were significantly higher than those of the PBS group and the blank control group. Meanwhile, expression levels of CGRP and 5-HT in the headache-related nuclei of the brain were increased in the BLM group. The current study further confirms the view that there is a relationship between pathological changes of MDBC and chronic headaches of unknown cause. This study may provide anatomical and physiological explanations for the pathogenesis of some chronic headaches of unknown cause.

Soil microorganisms play an important role in regulating and contributing to carbon cycling processes in grassland ecosystems. Soil salinization is one of the major problems causing soil degradation, and its effects on carbon cycle immobilization-related functional genes in soil microorganisms remain unknown. Therefore, we took Songnen salinization grassland as the research object, selected grasslands with different salinization levels, and explored the diversity of soil microorganisms and functional genes related to carbon cycling in Songnen grassland with different salinization levels through metagenomic technology. The results showed that with the increase of salinity, the relative abundance of Ascomycetes increased, while the relative abundance of Proteus and Firmicutes decreased. In addition, the relative abundance of functional genes related to carbon cycling fixation has also decreased. As the degree of soil salinization increases, the relative abundance of glycoside hydrolases (GH)130 family significantly increases, while the relative abundance of soil carbohydrate enzymes belonging to GH3 and GH55 families significantly decreases. Using structural equation modeling (SEM), it was found that soil pH and conductivity (EC) have a significant impact on soil microbial diversity and functional genes related to carbon cycling fixation. The increase in soil pH directly reduces the Shannon diversity of soil microbial diversity and functional genes related to carbon cycling fixation. Therefore, it can be concluded that the intensification of grassland salinization reduces the diversity of bacteria and fungi, and affects the diversity of functional genes related to carbon cycling fixation by reducing the total diversity of bacteria. The increase in salinity has a negative feedback effect on grassland soil carbon cycling. This study provides a theoretical framework for grassland soil carbon sequestration and degradation restoration.

Background The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population.Methods RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4–6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform.Results Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity.Conclusions Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients.Trial registration number ChiCTR2100045104.

Abstract Background Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients. Methods Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI). Results Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P

BackgroundThere is increased demand for high spatial resolution in domestic and international nano-imaging experimental stations utilizing synchrotron radiation. Nano or nanoradian level positioning accuracy and stability are necessary for focusing mirrors or monochromators on the beamlines.PurposeThis study aims to design and optimize a redundant parallel flexible hinge rotating device to meet this demand.MethodsFirst of all, the kinematics of the flexible mechanism were initially analyzed, and the virtual displacement principle was employed to derive the overall static rotational stiffness of the mechanism. Then, the characteristics of the mechanism, as well as the impact of hinge parameters on stiffness, were investigated. Subsequently, the dynamic model of the mechanism was built by employing the Lagrange equation, and the natural frequency in the motion direction was deduced. Finally, an optimization model was developed for the static and dynamic dual purpose mechanism design, solved through a genetic algorithm accounting for nonlinear constraints. In addition, the first four resonance frequencies and vibration modes of the flexible mechanism were examined using a finite element method for modal analysis followed by the creation and assembly of a high-precision flexible hinge mechanism along with a rotary adjustment device for experimental testing.ResultsTest results indicate that the flexible angular displacement adjustment mechanism achieves a rotation angle of 0.668° and bidirectional repeatability of ±8.91 nrad during fine-tuning. In addition, the angle resolution of 15 nrad and stability of 2.72 nrad (root mean square value) are achieved over a 30 min test in the frequency range of 1~500 Hz. The first natural frequency of the mechanism is approximately 295 Hz, which aligns with the theoretical calculations and finite element analysis results.ConclusionsThe effectiveness and reliability of the optimized flexible mechanism in achieving nanoradian level high-precision angular displacement adjustment is confirmed by this study.

Pheromones play an important role in mate choice in insects, and pheromone synthesis pathways are potential targets for the control of harmful insects, among which desaturation is of great significance in pheromone structural diversity. However, little is known about the desaturase genes regulating pheromone synthesis in Coleoptera. In this study, taking the internationally significant pest Anoplophora glabripennis as a research object, we identified 6 AglaFAD genes, all of which were mapped to the endoplasmic reticulum and shared a highly similar distribution of conserved domains. A phylogenetic analysis showed that AglaFAD1–2 and AglaFAD3–6 exerted desaturation at different positions of the acyl chain, respectively. In regard to the expression levels of these six AglaFADs in both sexes, six tissues and three developmental stages were analyzed by qPCR. Combined with the chemical composition of the female pheromones that have been identified, two candidate genes, AglaFAD2 and AglaFAD5, which are specifically expressed in females, were screened, showing higher expression levels before mating and significantly decreasing after mating. It is speculated that they may be involved in the biosynthesis of contact pheromones in females. These results provide a basis for detailed functional studies of candidate genes in insect pheromone synthesis.

Abstract Background A totally implanted venous access port (TIVAP) in the upper arm is a safe and cost-effective vascular access device and is widely used in breast cancer patients. Traditional tunnelling technique increases the operation time and has an unsatisfied cosmetic effect, so we explored the feasibility, cosmetic effect and complications of an upper arm port with a novel incision in this retrospective study. Methods We reviewed 489 cases of totally implantable venous access port implantation in the upper arm with two types of incisions in our centre from 1 January 2018 to 30 January 2022. The patients were divided into two different incision groups including the puncture site incision group (n = 282) and the conventional tunnelling group (n = 207). The comparison of the results was collected between the two groups, and contributing factors were analyzed for major complications. Results A total of 489 patients were successfully implanted with arm ports using the puncture site incision technique (n = 282, 57.7%) and conventional tunnelling technique (n = 207, 42.3%). The average operation time of the two types of incisions was 36.5 ± 15 min in the puncture site incision group and 55 ± 18.1 min in the tunnel needle group (P < 0.05). In terms of complications, 33 catheter-related complications occurred (6.4%), including 9 cases of infection, 15 cases of catheter-related thrombosis and 7 cases of skin exposure. Fourteen patients in the puncture site incision group developed complications compared with 17 in the traditional incision group. There were no significant differences between the two groups in terms of overall complication events (5.0% and 8.2%, P = 0.145) while the same result was found in each complication event. Weight, total cholesterol and diabetes were found to be associated with device-related infections in the univariate Cox proportional hazard regression models. Diabetes was found to be associated with device-related infections in multivariate analysis while hypertension was associated with thrombosis. Conclusions The puncture site incision method is a novel technique with a better cosmetic appearance and less operation time than the traditional tunnelling technique, providing a comparable overall rate of complications. It offers a preferable choice for clinicians when dealing with different situations of patients. It is worthy of being used and promoted for patients requiring the totally implanted venous access port in the upper arm.

Abstract Background Alimentary tract malignancies (ATM) caused nearly one-third of all tumor-related death. Cuproptosis is a newly identified cell death pattern. The role of cuproptosis-associated lncRNAs in ATM is unknown. Method Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify prognostic lncRNAs by Cox regression and LASSO. Then a predictive nomogram was constructed based on seven prognostic lncRNAs. In addition, the prognostic potential of the seven-lncRNA signature was verified via survival analysis, the receiver operating characteristic (ROC) curve, calibration curve, and clinicopathologic characteristics correlation analysis. Furthermore, we explored the associations between the signature risk score and immune landscape, and somatic gene mutation. Results We identified 1211 cuproptosis-related lncRNAs and seven survival-related lncRNAs. Patients were categorized into high-risk and low-risk groups with significantly different prognoses. ROC and calibration curve confirmed the good prediction capability of the risk model and nomogram. Somatic mutations between the two groups were compared. We also found that patients in the two groups responded differently to immune checkpoint inhibitors and immunotherapy. Conclusion The proposed novel seven lncRNAs nomogram could predict prognosis and guide treatment of ATM. Further research was required to validate the nomogram.

Membrane materials were widely used in guided tissue regeneration (GTR) to prevent fibroblast invasion and form a confined area for preferentially growing of osteoblast. A novel collagen-hyaluronate composite gradient membrane was prepared by Tilapia (Oreochromis mossambicus) skin collagen and sodium hyaluronate for potential GTR applications and their bioactivities were investigated by cellular viability. SEM results indicated the membrane showed a dense outer and a porous inner surface for effectively guiding the growth of bone tissue. Physicochemical and biosafety experiments showed the tensile strength of membrane was 466.57 ± 44.31 KPa and contact angle was 74.11°, and the membrane showed perfect biocompatibility and cytocompatibility as well, which met the requirements of GTR material. Cell morphology revealed that the membrane could facilitate the adherence and proliferation of fibroblast and osteoblast. The results of qRT-PCR and ELISA demonstrated that the membrane could effectively activate TGF-β/Smad pathway in fibroblast, and promote the expressions of TGF-β1, FN1 and VEGF. Remarkably, RUNX2 was stimulated in BMP2 pathway by the membrane to regulate osteoblast differentiation. In summary, the collagen-hyaluronate composite gradient membrane not only fulfills the prerequisites for use as a GTR material but also demonstrates substantial potential for practical applications in the field.

Abstract Background The purpose of this research was to construct a novel predictive nomogram to identify specific stage IB gastric adenocarcinoma (GAC) populations who could benefit from postoperative adjuvant chemotherapy (ACT). Method Between 2004 and 2015, 1889 stage IB GAC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) program database. Then Kaplan–Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were implemented. Finally, the predictive nomograms were constructed. The methods of area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to validate the clinical effectiveness of the models. Results Of these patients, 708 cases underwent ACT, while the other 1181 patients didn’t receive ACT. After PSM, the patients in the ACT group presented a longer median overall survival (133 vs. 85 months, p = 0.0087). Among the ACT group, 194 (36.0%) patients achieving more prolonged overall survival than 85 months were regarded as the beneficiary population. Then the logistic regression analyses were performed, and age, gender, marital status, primary site, tumor size, and regional nodes examined were included as predicting factors to construct the nomogram. The AUC value was 0.725 in the training cohort and 0.739 in the validation cohort, which demonstrated good discrimination. And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. Furthermore, the prognostic nomogram predicting 1-, 3-, and 5-year cancer-specific survival presented good predictive ability. Conclusion The benefit nomogram could guide clinicians in decision-making and selecting optimal candidates for ACT among stage IB GAC patients. And the prognostic nomogram presented great prediction ability for these patients.

Abstract Membranous nephropathy is the main cause of nephrotic syndrome, which has an insidious onset and may progress to end-stage renal disease with a high mortality rate, such as renal failure and uremia. At present, the diagnosis of membranous nephropathy mainly relies on the clinical manifestations of patients and pathological examination of kidney biopsy, which are expensive, time-consuming, and have certain chance and other disadvantages. Therefore, there is an urgent need to find a rapid, accurate and non-invasive diagnostic technique for the diagnosis of membranous nephropathy. In this study, Raman spectra of serum and urine were combined with deep learning methods to diagnose membranous nephropathy. After baseline correction and smoothing of the data, Gaussian white noise of different decibels was added to the training set for data amplification, and the amplified data were imported into ResNet, AlexNet and GoogleNet models to obtain the evaluation results of the models for membranous nephropathy. The experimental results showed that the three deep learning models achieved an accuracy of 1 for the classification of serum data of patients with membranous nephropathy and control group, and the discrimination of urine data was above 0.85, among which AlexNet was the best classification model for both samples. The above experimental results illustrate the great potential of serum- and urine-based Raman spectroscopy combined with deep learning methods for rapid and accurate identification of patients with membranous nephropathy.

Immobilizing organocatalysts onto helical polymers can facilitate catalyst recycling and boost enantioselectivity. Here, the authors prepare achiral organoiodine-functionalized single left- and right-handed helical polyisocyanides from the same monomers and demonstrate their use in three asymmetric oxidations.

Leaf color mutants are ideal materials for studying chlorophyll metabolism, chloroplast development, and photosynthesis in plants. We discovered a novel eggplant (Solanum melongena L.) mutant yl20 (yellow leaf 20) that exhibits yellow leaves. In this study, we compared the leaves of the mutant yl20 and wild type (WT) plants for cytological, physiological, and transcriptomic analyses. The results showed that the mutant yl20 exhibits abnormal chloroplast ultrastructure, reduced chlorophyll and carotenoid contents, and lower photosynthetic efficiency compared to the WT. Transcriptome data indicated 3267 and 478 differentially expressed genes (DEGs) between WT and yl20 lines in the cotyledon and euphylla stages, respectively, where most DEGs were downregulated in the yl20. Gene Ontology (GO) analysis revealed the “plastid-encoded plastid RNA polymerase complex” and the “chloroplast-related” terms were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the significantly enriched DEGs were involved in flavone and flavonol biosynthesis, porphyrin and chlorophyll metabolism, etc. We speculated that these DEGs involved in significant terms were closely related to the leaf color development of the mutant yl20. Our results provide a possible explanation for the altered phenotype of leaf color mutants in eggplant and lay a theoretical foundation for plant breeding.

Traditional methods for surface pretreatment of carbon fibers often rely on the use of precious metals like palladium and silver as activators to enhance surface reactivity through redox reactions, achieving metallization. However, such approaches are costly and economically inefficient. This study employed a cost-effective copper (Cu)-nickel (Ni) colloid mixture as an activator and investigated its effectiveness in enhancing surface reactivity. Meanwhile, it examined the influence of various parameters, such as pH value, reducing agent (formaldehyde (HCHO) concentration, temperature, and deposition duration, on the morphology and structure of copper-electrodeposited carbon fibers. To characterize the treated samples, scanning electron microscope (SEM) and x-ray photoelectron spectrometer (XPS) were adopted, shedding light on the mechanism underlying copper electrodeposition on the carbon fiber surface. The results indicate that Cu-Ni colloid mixture activation exhibits significant improvements. The optimal conditions for uniform and smooth copper electrodeposition on the carbon fiber surface identified as follows: a pH value of 13.5, a HCHO concentration of 15 ml L ^−1 , a temperature of 50 °C, and a deposition duration of 5 min. Consequently, these results represent a cost-effective alternative to traditional precious metal-based activation methods, with promising applications in surface pretreatment for carbon fibers.

Due to the use of strapdown seeker in small missiles, a small field of view angle is required to ensure effective tracking and strike of the target during the final interception. Based on the tracking strategy of dragonfly chasing targets, a composite guidance law is studied. In the initial guidance section, the parallax angle is controlled by the sliding mode control law to adjust the missile to the tail following attitude. The final guidance section used the motion camouflage guidance law with the focus at infinity for target tracking,and between the initial guidance and the final guidance. The second-order smooth interface law is used for the transition. The simulation results show that compared with the traditional proportional guidance law, the required overload of the missile in the final guidance is small,and the target is closer to the center of the field of view, which can reduce the missile in the final guidance. The overload and the field of view of the seeker can be used to effectively improve the attack accuracy.

BackgroundIntracranial metastasis that failed standard systematic treatment is common in advanced non-small cell lung cancer (NSCLC), contributing significantly to morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with whole-brain radiotherapy (WBRT) for NSCLC with brain metastases (BMs) that progressed or developed after at least one line of prior treatment and compare the outcomes with that of the contemporary institutional control.MethodsNSCLC patients with multiple BMs that progressed or developed after at least one line of prior systematic treatment and treated with WBRT subsequently between 2019 and 2021 were selected retrospectively for analysis. Based on whether concurrent anlotinib had been used in combination with WBRT, the cases were divided into the anlotinib group and control group. The primary endpoints were intracranial progression-free survival (iPFS) and safety.ResultsA total of 76 patients met the inclusion criteria of the study. Of the 76 patients, 34 received concurrent WBRT and anlotinib followed by anlotinib maintenance and 42 were treated with WBRT alone or in combination with other systemic agents at the physicians’ discretion. The median follow-up for the entire cohort was 21 months. The median iPFS for the anlotinib and control group was 6.7 months (95% CI, 4.6–9.9) and 5.3 months (95% CI, 4.0–6.5), respectively (log-rank P = 0.04). There was no difference in overall survival between the two groups (log-rank P = 0.38). In the anlotinib group, treatment-related adverse events were reported in 15 patients (44.1%), with acute or late grade 3–5 adverse events identified in 14.7% of patients (n = 5).ConclusionsWBRT plus anlotinib, as a convenient chemo-free regimen, may represent an overall safe and effective procedure in advanced NSCLC with multiple BMs that progressed or developed after standard systematic treatment.

Background: Gastric cancer (GC) is the fifth leading cancer in the world, and there is a high mortality rate in China. Exploring the relationship between the prognosis of GC and the expression of related genes is helpful to further understand the common characteristics of the occurrence and development of GC and provide a new method for the identification of early GC, so as to provide the best therapeutic targets. Methods: Vascular endothelial growth factor (VEGF) and markers of epithelial-mesenchymal transition (EMT) were investigated immunohistochemically using tumor samples obtained from 196 GC tissues and adjacent tumor tissues. The correlation of the expression level with histopathologic features and survival was investigated. Results: Here, we show that VEGF and EMT markers expression were significantly correlated with depth of tumor invasion and GC stage ( P

The evolvement and development of antibiotic resistance in microorganisms may be influenced by metals; however, it is still unclear how cadmium (Cd) and copper (Cu) combined affect the distribution and presence of antibiotic-resistance genes (ARGs) in rhizosphere soil. The aims of this research were to (1) compare the distribution patterns of bacterial communities and ARGs in response to the effects of Cd and Cu both separately and combined; (2) explore the possible mechanisms underlying the variation in soil bacterial communities and ARGs in addition to the combined effects of Cd, Cu, and various environmental variables (nutrients, pH, etc.); and (3) provide a reference for assessing the risks of metals (Cd and Cu) and ARGs. The findings showed that the multidrug resistance genes acrA and acrB and the transposon gene intI-1 were present in high relative abundance in bacterial communities. Cadmium and Cu had a substantial interaction effect on the abundance of acrA, whereas Cu had a notable main effect on the abundance of intI-1. According to the network analysis, the strong links between bacterial taxa and specific ARGs revealed that most ARGs were hosted by Proteobacteria, Actinobacteria, and Bacteroidetes. According to structural equation modeling, Cd had a larger effect on ARGs than Cu. Compared to previous analyses of ARGs, bacterial community diversity had little effect on ARGs in this study. Overall, the results may have important consequences for determining the possible hazard of soil metals and extend the understanding of how Cd and Cu co-select ARGs in rhizosphere soils.

Abstract Background The stromal antigen 3 (STAG3) gene encodes an adhesion complex subunit that can regulate sister chromatid cohesion during cell division. Chromosome instability caused by STAG3 gene mutation may potentially promote tumor progression, but the effect of STAG3 on hepatocellular carcinoma (HCC) and the related molecular mechanism are not reported in the literature. The mechanism of the occurrence and development of HCC is not adequately understood. Therefore, the biological role of STAG3 in HCC remains to be studied, and whether STAG3 might be a sensitive therapeutic target in HCC remains to be determined. Methods The expression and clinical significance of STAG3 in HCC tissues and cell lines were determined by RT–qPCR and immunohistochemistry analyses. The biological functions of STAG3 in HCC were determined through in vitro and in vivo cell function tests. The molecular mechanism of STAG3 in HCC cells was then investigated by western blot assay. Results The mRNA expression of STAG3 was lower in most HCC cells than in normal cells. Subsequently, an immunohistochemical analysis of STAG3 was performed with 126 samples, and lower STAG3 expression was associated with worse overall survival in HCC patients. Moreover, cytofunctional tests revealed that the lentivirus-mediated overexpression of STAG3 in HCC cells inhibited cell proliferation, migration, and invasion; promoted apoptosis; induced G1/S phase arrest in vitro; and inhibited tumor growth in vivo. Furthermore, studies of the molecular mechanism suggested that the overexpression of STAG3 increased Smad3 expression and decreased CDK4, CDK6, cyclin D1, CXCR4 and RhoA expression. Conclusion STAG3 exhibits anticancer effects against HCC, and these effects involve the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways. STAG3 is a tumor-suppressor gene that may serve as a potential target for molecular therapy, which provides a new idea for the treatment of HCC.

In order to optimize the steam distillation extraction process of essential oil from Citrus reticulata Blanco cv. Manau Gan, fresh peel samples were used as materials, and ultrasonic assisted treatment was adopted. On the basis of optimized distillation equipment and single factor tests, Box-Behnken experiment was used to design for ultrasonic temperature, ultrasonic power and ultrasonic time. The essential oils were analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that the extraction effect of Clevenger distillation apparatus was better than the other three distillation devices. The optimal oil extraction process was obtained by response surface analysis: ultrasonic temperature 33 ℃, ultrasonic power 80 W, ultrasonic time 32 min. Under the optimal conditions, the extraction yield of essential oil reached 2.50%±0.02%. Twenty-nine compounds were identified by gas chromatography-mass spectrometry (GC-MS), accounted for 99.16% of the total volatiles, including alkenes (mainly D-limonene, content up to 88.35%), alcohols (mainly Linalool 0.18%), aldehydes (mainly Octanal 0.17%), et al. This research technique could be used for the extraction of essential oil from Citrus reticulata Blanco cv. Manau Gan.

Objective： The fatty acid composition and content of three kinds of Dendrobium were studied in order to provide reference for the development of dendrobium efficacy. Methods： The fatty acids compositions of Dendrobium nobile, Dendrobium officinale and Dendrobium chrysotoxum from different regions were systematically quantified by gas chromatography-mass spectrometry （GC-MS）, and a series of Odd-carbon fatty acids （OCFA） containing 15~23 carbons were found in all dendrobiums. Results： The results showed that the OCFA accounted for more than 8% of the total fatty acids. The relative abundances of OCFA from high to low were C15:0, C17:0, C23:0, C19:0 and C21:0. C15:0/C17:0 （C15:0 and C17:0 relative abundance ratios） in D. nobile and D. officinale were less than 1.6 and more than 1.8, respectively. It was concluded that orchids contain a series of OCFA as one of the features in this family plants. Conclusion： The existence of OCFA in Dendrobium may be related to their drug activities.

Objective LncRNA PART1 has been confirmed related to multiple cancer bioactivities mediated with vascular endothelial growth factor signaling. Nevertheless, the role of LncRNA PART1 in esophageal cancer induced angiogenesis remains unclear. The present work focused on assessing LncRNA PART1 effects on esophageal cancer–induced angiogenesis and exploring possible mechanisms. Methods Western blot and immunofluorescence were conducted for identifying EC9706 exosomes. MiR-302a-3p and LncRNA PART1 levels were assessed by real-time quantitative polymerase chain reaction. Cell Counting Kit-8, EdU, wound healing, transwell, and tubule information were adopted for detecting human umbilical vein endothelial cell viability, proliferation, migration, invasion, and tubule information, respectively. Starbase software and dual-luciferase reporter were conducted for predicting and judging the expression interrelation of LncRNA PART1 and its potential target-miR-302a-3p. The same methods were carried out for verifying the inhibiting influences of miR-302a-3p upregulation and its potential target-cell division cycle 25 A. Results LncRNA PART1 levels were upregulated and related to the overall survival of patients in esophageal cancer. EC9706-Exos accelerated human umbilical vein endothelial cell proliferation, migration, invasion, and tubule formation via LncRNA PART1. LncRNA PART1 served as a sponge of miR-302a-3p, then miR-302a-3p targeted cell division cycle 25 A, and EC9706-Exos accelerated human umbilical vein endothelial cell angiogenesis via LncRNA PART1/ miR-302a-3p/cell division cycle 25 A axis. Conclusion EC9706-Exos accelerates human umbilical vein endothelial cell angiogenesis via LncRNA PART1/miR-302a-3p/ cell division cycle 25 A axis, indicating EC9706-Exos may act as a promoter of angiogenesis. Our research will contribute to clarify the mechanism of tumor angiogenesis.

PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Background This study aimed to develop a novel predictive nomogram to identify specific stage IB non-small cell lung cancer (NSCLC) populations who could benefit from adjuvant chemotherapy (ACT). Method Stage IB NSCLC patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the ACT and non-ACT groups. Then the methods of Kaplan-Meier analysis, propensity score matching (PSM), Least absolute shrink and selection operator (LASSO) regression, and multivariate logistic regression analyses were implemented. Finally, the predictive nomogram was constructed and validated. Results 9055 stage IB NSCLC patients were enrolled from the SEER database while 47 patients from Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University were identified as the external validation cohort. Of these patients, 1334 cases underwent ACT while the other 7721 patients didn’t receive ACT. After PSM, the patients in the ACT group presented longer median overall survival (100 vs 82 months, P < .001). Among the ACT group, 482 (49.6%) patients achieving more prolonged overall survival than 82 months were regarded as the beneficiary population. Then the LASSO regression and multivariate logistic regression analyses were implemented. Finally, 8 predictors were selected for model construction, including age, gender, marital status, laterality, pathology, tumor size, regional nodes examined, and tumor size. The predictive nomogram demonstrated good discrimination in the training cohort (AUC = .781), internal validation cohort (AUC = .772), and external validation cohort (AUC = .851). And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. Conclusion The practical nomogram could guide treatment decision-making and select optimal ACT candidates among stage IB NSCLC patients.

Abstract Background Pleural invasion (PL) has been regarded as an unfavorable prognostic factor for non-small cell lung cancer (NSCLC). But there was no agreement on the optimal surgical extent in NSCLC patients with PL. We aimed to compare the survival outcomes of lobectomy and sub-lobectomy in these patients. Method 2717 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the lobectomy and sub-lobectomy groups. The propensity score matching (PSM) and competing risk analysis were implemented. Then the predictive nomogram was constructed and validated. Results 2230 Patients received lobectomy while the other 487 patients underwent sub-lobectomy. After 1:1 PSM, the cumulative incidence of cancer-specific death (CSD) was lower in the lobectomy group compared with the sub-lobectomy group (1-year: 12% vs. 15%; 3-year: 30% vs. 37%, 5-year: 34% vs. 45%, P = 0.04). According to the subgroup analysis, the patients who underwent lobectomy suffered lower CSD in the N0–1 stage, adenocarcinoma, and PL-2 cohort (p

Abstract Background This study aimed to investigate the potential effect of adjuvant chemotherapy in patients diagnosed with stage IB gastric adenocarcinoma (GAC). Method A total of 1727 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and divided into the chemotherapy and no-chemotherapy groups. Then, the methods of Kaplan-Meier analysis, propensity score matching (PSM), and competing risk analysis were implemented. Results After PSM, no significant difference was found in the chemotherapy and no-chemotherapy groups in overall survival (OS) (p=0.4) and cancer-specific survival (CSS) (p=0.12) in survival curves. The competing risk analysis presented that the 5-year cumulative incidence of cancer-specific death (CSD) was significantly lower in patients receiving chemotherapy (11.5% vs. 20.8%, p=0.007), while no significant discrepancy was observed in other causes of death (OCD) in both groups (10.6% vs. 10.9%, p=0.474). Multivariable competing risks regression models presented a significant correlation between chemotherapy and CSD (HR, 0.51; 95%CI, 0.31–0.82; p=0.007). Conclusion The stage IB GAC patients can benefit from adjuvant chemotherapy based on this competing risk analysis.

Introduction: The optimal route and dosing regimen of tranexamic acid (TXA) in primary total knee arthroplasty (TKA) remains unclear. This study aims to explore if there was a synergistic effect of intravenous (IV) and topical TXA on blood loss and risk of complications. Materials and methods: From Jan 2019 to June 2021, medical records of patients aged 65 years or older who underwent primary unilateral TKA for primary osteoarthritis were retrospectively reviewed. The included patients were divided into 3 groups according to the methods of TXA application: Intravenous (IV) group, topical group, or combined group. Propensity-score match was used to reduce the bias and imbalance of confounding variables. The primary outcome was total blood loss. Results: The total blood loss, hidden blood loss, and the reduction of Hb concentration in the combined group were significantly lower than in the IV group and topical group (all P < .01). There is no significant difference in the transfusion rate, length of hospital stay, and incidence of thromboembolic events (both P > .05). Conclusions: Combined administration of IV and topical TXA is the most effective approach to decrease blood loss and postoperative Hb drop in the treatment of TKA without increasing any risk of complications.

Diazoacetate polymerizations using inexpensive catalysts has been a long-standing challenge to achieve. Here the authors report a Ni(II) catalyst that can promote living polymerization of various diazoacetates, yielding well-defined carbon–carbon main chain polymers, polycarbenes.

Due to the characteristics of limited resources and dynamic topology, wireless sensor networks (WSNs) are facing two major problems: security and energy consumption. Nowadays, the trust based solutions are feasible to cope with different bad behaviors of nodes, but there still exist a variety of attacks, high energy consumption and communication congestion between nodes. Therefore, this paper proposes a new trust based secure and energy efficient routing protocol (TBSEER) to solve these problems. TBSEER calculates the comprehensive trust value through adaptive direct trust value, indirect trust value and energy trust value, which can be resistant to black hole, selective forwarding, sinkhole and hello flood attacks. Moreover, the adaptive penalty mechanism and volatilization factor are used to fast identify the malicious nodes. In addition, the nodes only need to calculate the direct trust value, and the indirect trust value is obtained by the Sink, so as to further reduce the energy consumption caused by iterative calculations. Finally, the cluster heads find the safest multi-hop routes based on the comprehensive trust value, which can actively avoid wormhole attack. The simulation results show that the proposed TBSEER reduces network energy consumption, speeds up the identification of malicious nodes, as well as resists all common attacks.

Abstract Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide and is accompanied by low diagnosis and survival rates. The molecular mechanism of GC must be elucidated to improve treatment strategies. Recent research has shown that the expression of myelin and lymphocyte (MAL) protein is reduced in a variety of adenocarcinomas and has the function of suppressing tumor growth. However, the mechanism by which MAL regulates the epithelial-mesenchymal transition (EMT) in GC remains unclear. Here, we showed that MAL expression was downregulated in specimens from patients with GC and was negatively correlated with the clinical stage. Gain- and loss-of function assays showed that interference with MAL significantly increased tumor cell proliferation, metastasis, invasion and the EMT. Overexpression of MAL significantly inhibited the malignant behavior of GC cells. Moreover, MAL suppressed the malignant behavior of GC cells by inhibiting STAT3 phosphorylation in vitro and in vivo. Our data indicate that MAL suppresses the malignant behavior of GC cells via the STAT3/EMT axis. This study also provides insights into the pathophysiological process of GC and a reference for diagnosis and treatment.

Background and Aims: To quantify the indirect burden of cyclic vomiting syndrome (CVS), we assessed work-related productivity loss in patients with CVS and caregivers using large-sized databases in the United States. Methods: Patients aged 18–64 years with full-time employment in MarketScan Commercial and Health and Productivity Management Databases were selected if they had ≥1 inpatient or ≥2 outpatient claims for CVS between 2008 and 2018 and continuous enrollment of ≥6 months before and ≥3 months after the initial CVS diagnosis. CVS caregivers were adults with full-time employment and also having dependent(s) with CVS. Propensity scores via multivariable regressions were used to match patients with CVS and their caregivers to non-CVS controls. Productivity loss was assessed by short-term disability (STD) and absenteeism (ABS) days, and the associated costs were also calculated. Differences between the matched cohorts were regarded as the burden attributable to CVS. Results: Patients with CVS had longer annualized STD (21.1 vs 7.0, P < .001) and ABS days (26.4 vs 22.8, P < .05) than their matched controls. CVS caregivers had more annualized STD (3.9 vs 2.6, P < .001) and ABS days (20.9 vs 19.5, P < .05) than controls. Productivity loss costs for STD or ABS days were greater for patients with CVS and caregivers. Annualized health-care resource utilization (inpatient, emergency room, outpatient) was 5.2–6.0 times higher in patients with CVS (P < .001). Conclusion: CVS is associated with higher productivity loss due to STD/ABS and, therefore, greater indirect costs for patients and caregivers. Further research is needed to assess the full societal burden of CVS. More effective interventions may reduce the disease burden.

BACKGROUND AND AIMS: This study aimed to estimate the extent of US health care resource use (HRU) and direct cost burden of cyclic vomiting syndrome (CVS). Methods: We selected patients in the MarketScan Commercial and Medicare Supplemental databases with ≥1 inpatient (IP) or ≥2 outpatient (OP) claims for CVS between October 1, 2015 and June 30, 2019, and continuous insurance enrollment for ≥12 months before (baseline) and ≥3 months after first CVS diagnosis (index). Using propensity scores based on baseline characteristics, each patient with CVS was matched to ∼3 non-CVS controls. We annualized HRU and costs to accommodate varying follow-up periods. Multivariable regressions further balanced CVS and non-CVS groups, and differences in HRU and costs between the matched cohorts were compared to quantify the direct cost burden of CVS. Results: Patients with CVS incurred significantly higher average annualized HRU, with the largest differences in emergency room (1.9 vs 0.4) visits and hospital IP (0.9 vs 0.1) stays (P < .001). Patients with CVS had significantly higher annual total health care costs ($57,140 vs $14,912), with IP spending as the primary driver ($28,522 vs $3250) of the cost difference (all P < .001). After multivariable regression adjustments, total health care costs remained 4.1 times higher for patients with CVS relative to non-CVS controls, with IP costs 12.3 times higher, emergency room costs 5.8 times higher, OP visit costs 2.9 times higher, and OP pharmacy costs 1.5 times higher (all P < .001). Conclusion: Newly diagnosed patients with CVS have greater health care utilization and higher costs than matched non-CVS counterparts, suggesting substantial economic burden of CVS on the US health care system.

In the research of heterogeneous wireless sensor networks, clustering is one of the most commonly used energy-saving methods. However, existing clustering methods face challenges when applied to heterogeneous wireless sensor networks, such as energy balance, node heterogeneity, algorithm efficiency, and more. Among these challenges, a well-designed clustering approach can lead to extended node lifetimes. Efficient selection of cluster heads is crucial for achieving optimal clustering. In this paper, we propose an Enhanced Pelican Optimization Algorithm for Cluster Head Selection (EPOA-CHS) to address these issues and enhance cluster head selection for optimal clustering. This method combines the Levy flight process with the traditional POA algorithm, which not only improves the optimization level of the algorithm, but also ensures the selection of the optimal cluster head. The logistic-sine chaotic mapping method is used in the population initialization, and the appropriate cluster head is selected through the new fitness function. Finally, we utilized MATLAB to simulate 100 sensor nodes within a configured area of 100 × 100 m2. These nodes were categorized into four heterogeneous scenarios: m=0,α=0, m=0.1,α=2, m=0.2,α=3, and m=0.3,α=1.5. We conducted verification for four aspects: total residual energy, network survival time, number of surviving nodes, and network throughput, across all protocols. Extensive experimental research ultimately indicates that the EPOA-CHS method outperforms the SEP, DEEC, Z-SEP, and PSO-ECSM protocols in these aspects.

Minimal change disease (MCD) is one of the common causes of idiopathic nephrotic syndrome (INS), accounting for 10–20% of INS in adults. Glucocorticoids are the most commonly used and effective drugs in the treatment of MCD, but there is still a proportion of adult patients with MCD who are characterized by glucocorticoid resistance, glucocorticoid dependence, and frequent relapse, which are defined as refractory nephrotic syndrome. Glucocorticoid combination with immunosuppressants is frequently used in patients with refractory nephrotic syndrome, and patients concerned about adverse effects caused by long-term high-dose glucocorticoid therapy. Recent studies have suggested that Rituximab (RTX), a chimeric monoclonal antibody targeted against the pan-B-cell marker CD20, combined with a small or medium dose of glucocorticoid has a beneficial effect with less adverse effects on adult patients with refractory MCD. β-thalassemia is an inherited hemoglobulin disorder caused by the mutation of genes that encode β-globin and results in ineffective erythropoiesis. We here report a case of an adult patient with refractory MCD complicated with β-thalassemia minor accompanied by autoimmune hemolytic anemia (AIHA). MCD relapsed several times despite treatment using glucocorticoid combined with or without different immunosuppressive agent regimens. The β-thalassemia minor was caused by heterozygosity for a 4-base deletion mutation [codons 41/42 (−TTCT) BETA0] of the β-globin gene. After the administration of RTX, MCD achieved clinical complete remission, and the anemia due to mild β-thalassemia recovered to normal as well. The disease situation remained stable during 36 months of follow-up. These findings suggest that RTX may contribute to the improvement of refractory MCD and anemia in β-thalassemia minor accompanied by AIHA.

Inferior vena cava (IVC) filters are used to prevent pulmonary embolism in patients with deep vein thrombosis for whom anticoagulation is unresponsive. The head is a necessary structure for an Inferior vena cava filter (IVCF) in clinic use. At present, there are various head configurations for IVCFs. However, the effect of head pattern on the hemodynamics of IVCF is still a matter of unclear. In this study, computational fluid dynamics is used to simulate non-Newtonian blood flows around four IVCFs with different heads inside an IVC model, in which the Denali filter with a solid and hooked head is employed as a prototype, and three virtual variants are reconstructed either with a no-hook head or with a through-hole head for comparison. The simulation results show that the through-hole head can effectively avoid the recirculation region and weaken the blood flow stasis closely downstream the IVCF head. The shape change of the filter head has no significant effect on the blood flow acceleration inside the IVCF cone as well as little influence on the wall shear stress (WSS) distribution on the filter wire surface and IVC wall. The structure pattern of filter head greatly affects the flow resistance of its own. However, the flow drag of filter head only occupies a small proportion of the total resistance of IVCF. Therefore, to reduce the flow resistance of an IVCF should optimize its whole structure.

Objective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms.Methods: Our study included three gene expression datasets of IgA nephropathy (GSE37460, GSE73953, GSE93798). Differential expression of RBPs between IgA nephropathy and normal samples was analyzed via limma, and hub RBPs were determined through MCODE. Afterwards, three machine learning algorithms (LASSO, SVM-RFE, random forest) were integrated to determine characteristic RBPs, which were verified in the Nephroseq database. Immune cell infiltrations were estimated through CIBERSORT. Utilizing ConsensusClusterPlus, IgA nephropathy were classified based on hub RBPs. The potential upstream miRNAs were predicted.Results: Among 388 RBPs with differential expression, 43 hub RBPs were determined. After integration of three machine learning algorithms, three characteristic RBPs were finally identified (DDX27, RCL1, and TFB2M). All of them were down-regulated in IgA nephropathy than normal specimens, with the excellent diagnostic efficacy. Additionally, they were significantly linked to immune cell infiltrations, immune checkpoints, and pyroptosis-relevant genes. Based on hub RBPs, IgA nephropathy was stably classified as two subtypes (cluster 1 and 2). Cluster 1 exhibited the relatively high expression of pyroptosis-relevant genes and characteristic RBPs. MiR-501-3p, miR-760, miR-502-3p, miR-1224-5p, and miR-107 were potential upstream miRNAs of hub RBPs.Conclusion: Collectively, our findings determine three characteristic RBPs in IgA nephropathy and two RBPs-based subtypes, and thus provide a certain basis for further research on the diagnosis and pathogenesis of IgA nephropathy.

Bat groups have a high degree of species diversity, and the taxonomic status and phylogenetic relationships among bat species have always been research hotspots. Due to the fact that morphological characteristics do not always reflect the evolutionary relationships among species, mitochondrial DNA has been widely used in the study of species relationships due to its maternal inheritance pattern. Myotis aurascens has been suggested as a possible synonym for M. davidii. However, the status of this classification has been controversial. In this study, the morphological and molecular characteristics of a M. aurascens captured from Inner Mongolia, China, were analyzed to determine its taxonomic status. In terms of morphological features, the body weight was 6.33 g, the head and body length were 45.10 mm, the forearm length was 35.87 mm, and the tragus length was 7.51 mm. These values all fell within the species signature data range. Nucleotide skew analysis of the protein-coding genes (PCGs) suggested that only five PCGs (ND1, ND2, COX2, ATP8, and ND4) showed AT-skew value within the mitogenome of M. aurascens. Except for ND6, the GC-skew values of the other PCGs were negative, reflecting the preference for C and T bases compared to G and A bases. Molecular phylogenetic analyses based on mitochondrial PCGs indicated that M. aurascens was a distinct species from M. davidii and phylogenetically closer to M. ikonnikovi, M. alcathoe, and M. mystacinus. Genetic distance analysis also showed that M. aurascens and M. davidii were distantly related. Therefore, the integrated analysis demonstrated that M. aurascens should be considered a distinct species rather than a synonym of M. davidii. Our study could provide a reference for enriching species diversity and research on conservation in China.

Faced with the scarcity of water resources and irrational fertilizer use, it is critical to supply plants with water and fertilizer in a coordinated pattern to improve yield with high water use efficiency (WUE). One such method, alternate partial root-zone irrigation (APRI), has been practiced worldwide, but there is limited information on the performance of different irrigation regimes and nitrogen (N) rates under APRI. The objectives of this study were to investigate the effects of varying irrigation regimes and N rates on shoot growth, grain yield and WUE of maize (Zea mays L.) grown under APRI in the Hexi Corridor area of Northwest China in 2014 and 2015. The three N rates were 100, 200 and 300 kg N ha−1, designated N1, N2 and N3, respectively. The three irrigation regimes of 45–50%, 60–65% and 75–80% field capacity (FC) throughout the maize growing season, designated W1, W2 and W3, respectively, were applied in combination with each N rate. The results showed that W2 and W3 significantly increased the plant height, stem diameter, crop growth rate, chlorophyll SPAD value, net photosynthetic rate (Pn), biomass, grain yield, ears per ha, kernels per cob, 1 000-kernel weight, harvest index, evapotranspiration and leaf area index (LAI) compared to W1 at each N rate. The N2 and N3 treatments increased those parameters compared to N1 in each irrigation treatment. Increasing the N rate from the N2 to N3 resulted in increased biomass and grain yield under W3 while it had no impact on those under the W1 and W2 treatments. The W3N3 and W2N2 and W2N3 treatments achieved the greatest and the second-greatest biomass and grain yield, respectively. Increasing the N rate significantly enhanced the maximum LAI (LAI at the silking stage) and Pn under W3, suggesting that the interaction of irrigation and fertilizer N management can effectively improve leaf growth and development, and consequently provide high biomass and grain yield of maize. The W2N2, W2N3 and W3N3 treatments attained the greatest WUE among all the treatments. Thus, either 60–65% FC coupled with 200–300 kg N ha−1 or 75–80% FC coupled with 300 kg N ha−1 is proposed as a better pattern of irrigation and nitrogen application with positive regulative effects on grain yield and WUE of maize under APRI in the Hexi Corridor area of Northwest China and other regions with similar environments. These results can provide a basis for in-depth understanding of the mechanisms of grain yield and WUE to supply levels of water and nitrogen.

Abstract Objective Our study examined the association between molecular features and clinical results of pancreatic ductal adenocarcinoma (PDAC) patients, aiming to explore the genomic determinants of the recurrence and prognosis of PDAC after surgical removal. Methods This retrospective study analyzed 181 PDAC patients who received pancreatectomy and adjuvant chemotherapy, with 67 patients in the training set. An internal validation set of 48 patients and an external validation set of 66 patients were used to validate the result. Comprehensive genomic profiling was performed on formalin‐fixed paraffin‐embedded (FFPE) tumor specimens to determine genomic features using the designed cancer‐related gene panel based on next‐generation sequencing (NGS). Results Significant differences were identified between the late recurrence (LR) group and early recurrence (ER) group in tumor copy number instability (CNI) levels. Next, the utility of low CNI (the middle and lowest tertile) with regard to predicting LR was confirmed in the training, internal, and external validation sets. Further univariate and multivariate analyses revealed that CNI was an independent predictive and prognostic biomarker, and had higher predictive accuracy for LR than CA19‐9 level, pathological stage, tumor size, and age. In addition, CNI combined with lymph node (LN) metastasis status could provide a more accurate model for predicting LR of PDAC. Conclusion We discovered and validated the association between CNI and clinical outcome in 181 patients with resectable PDAC, demonstrating the utility of lower tumor CNI levels as biomarkers of postoperative LR and favorable prognosis. Moreover, the combination of CNI and LN metastasis status elevated the predictive accuracy and illuminated strategies for patient stratification.

AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low ametropia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P

Abstract Background Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long‐term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites. Methods We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from patients with breast cancer) were collected as controls. By comparing the brain metastases and paired samples of adjacent noncancerous brain tissue from 13 patients, we detected three upregulated and six downregulated genes, representing the malignant properties of cancer cells and increased immune infiltration in the microenvironment. Next, we profiled the immune‐related genes in brain metastases from three primary cancer types. Results A group of genes were significantly overexpressed in the microenvironment of brain metastases from lung cancer, covering the checkpoint pathways, lymphocyte infiltration, and TCR‐coexpression. Especially, immune checkpoint molecules, PD‐L1, PD‐L2, and IDO1 were expressed at higher levels in brain metastases from lung cancer than those from the other two cancer types. Conclusions This study presents an immune landscape of brain metastases from different cancer types. With high RNA expression levels of PD‐1/PD‐L1 axis and immune infiltration in brain metastases, it would be worthwhile to explore the efficacy of immune checkpoint blockade for lung cancer patients with intracranial metastases.

[Retraction]AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low myopia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P

With the development of the Cyber-Physical-Social Systems(CPSS), a large number of multidimensional time series have been generated in today's world, such as: sensor data for industrial equipment operation, vehicle driving data, and cloud server operation and maintenance data and so on. The key task of Cloud-Fog-Edge Computing in managing these systems is how to detect anomalous data in a specific time series to facilitate operator action to solve potential system problems. So multidimensional time series outlier detection become an important direction of CPSS data mining and Cloud-Fog-Edge Computing research, and it has a wide range of applications in industry, finance, medicine and other fields. This paper proposes a framework called Multidimensional time series Outlier detection based on a Time Convolutional Network AutoEncoder (MOTCN-AE), which can detect outliers in time series data, such as identifying equipment failures, dangerous driving behaviors of cars, etc. Specifically, this paper first uses a feature extraction method to transform the original time series into a feature-rich time series. Second, the proposed TCN-AE is used to reconstruct the feature-rich time series data, and the reconstruction error is used to calculate outlier scores. Finally, the MOTCN-AE framework is validated by multiple time series datasets to demonstrate its effectiveness in detecting time series outliers.

Abstract Background Appendiceal inversion with neoplasia in adults is an extremely rare event with a reported incidence of

Abstract Background Formalin-fixed and paraffin-embedded (FFPE) blocks held in clinical laboratories are an invaluable resource for clinical research, especially in the era of personalized medicine. It is important to accurately quantitate gene expression with degraded and small amounts of total RNA from FFPE materials. Results High concordance in transcript quantifications were shown between FF and FFPE samples using the same kit. The gene expression using the TaKaRa kit showed a difference with other kits, which may be due to the different principle of rRNA depletion or the amount of input total RNA. For seriously degraded RNA from FFPE samples, libraries could be constructed with as low as 50 ng of total RNA, although there was residual rRNA in the libraries. Data analysis with HISAT demonstrated that the unique mapping ratio, percentage of exons in unique mapping reads and number of detected genes decreased along with the decreasing quality of input RNA. Conclusions The method of RNA library construction with rRNA depletion can be used for clinical FFPE samples. For degraded and low-input RNA samples, it is still possible to obtain repeatable RNA expression profiling but with a low unique mapping ratio and high residual rRNA.