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Background: To evaluate the clinical effectiveness of lateral cervical region (LCR) lymphadenectomy as a preventative procedure for stage CN0 papillary thyroid cancer (PTC).Methods: From December 2019 to October 2021, 108 patients with CN0 stage PTC hospitalized to our general surgery department were recruited. After analysis, the clinical data of these patients were separated into two groups: 57 cases were in the Surgical + lymphatic dissection group and 51 instances were in the surgical group. Total thyroidectomy with central node dissection (TTCD) was carried out on the surgical group, whereas intraoperative ultrasound (IOUS) for prophylactic LCR lymph nodes dissection was carried out on the basis of TTCD in the Surgical + lymphatic dissection group. The postoperative complications, cervical lymph node metastases and recurrent reoperation were analyzed in both groups.Results: In the Surgical + lymphatic dissection group, the rate of lymph node metastasis (LNM) identified by IOUS in the LCR of PTC was 29.82% (17/57). In the central group with >2 lymph node metastases compared to the central group with < 2 lymph node metastases, the rate of LCR LNM was considerably greater (20% vs. 43%). Between the two groups, there was no statistically significant difference in the frequency of postoperative complications (P > 0.05). At the 1-year postoperative follow-up, the recurrence rate in the surgical group was 13.73%, whereas there was no recurrence in the Surgical + lymphatic dissection group.Conclusions: The recurrence/reoperation rate of PTC in individuals with stage CN0 can be decreased by IOUS guided prophylactic lymph node dissection in the LCR.

Objectives The present study aimed to investigate the effect and mechanism of angiotensin II–induced ferroptosis in vascular endothelial cells. Methods In vitro, HUVECs were treated with AngII, AT1/2 R antagonist, P53 inhibitor, or their combinations. MDA and intracellular iron content were evaluated using an ELISA assay. The expression of ALOX12, P53, P21, and SLC7A11 were determined by western blotting in HUVECs and then confirmed through RT-PCR. Results As the concentration of Ang II (0, 0.1,1,10,100, and 1000uM for 48 h) increased, the level of MDA and intracellular iron content increased in HUVECs. Compared with the single AngII group, ALOX12, p53, MDA, and intracellular iron content in AT1/2R antagonist group decreased significantly. In pifithrin-α hydrobromide-treated, ALOX12, P21,MDA, and intracellular iron content decreased significantly as compared to the single AngII group. Similarly, the effect of combined use of blockers is stronger than that of blockers alone. Conclusions AngII can induce ferroptosis of vascular endothelial cells. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of p53-ALOX12.

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in the treatment landscape of non-small cell lung cancer (NSCLC). Despite the promising long-term survival outcomes and optimization of pathological complete response (cPR) demonstrated by various studies such as Impower010 and Checkmate-816, the effectiveness of neoadjuvant immunotherapy in advanced resectable NSCLC remains a subject of debate. Although previous research has explored the connection between the efficacy of neoadjuvant therapy and surgical-related safety, limited studies have specifically investigated the surgical-related safety of neoadjuvant immunotherapy. Therefore, our study aims to assess the efficacy and surgical-related safety of neoadjuvant immunotherapy in advanced resectable non-small cell lung cancer.MethodWe conducted a retrospective study on a cohort of 93 patients with stage IIIA-IIIC NSCLC who underwent neoadjuvant therapy and surgical resection. Among them, 53 patients received neoadjuvant immunotherapy, 18 patients underwent neoadjuvant chemotherapy while the remaining 22 underwent neoadjuvant targeted therapy. The patients were separated into further groups according to their pathological type. Data analyses were performed using Mann-Whitney U test, chi-square test.ResultsAll patients were categorized into six distinct groups. Notably, the neoadjuvant immunotherapy squamous carcinoma group exhibited a favorable edge over the neoadjuvant targeted squamous carcinoma group concerning the duration of drainage tube indwelling and the extent of lymph node dissection. Furthermore, the neoadjuvant immunotherapy adenocarcinoma group outperformed neoadjuvant targeted therapy adenocarcinoma counterpart in terms of achieving complete pathological response (cPR). Simultaneously, the neoadjuvant immunotherapy adenocarcinoma group surpassed the neoadjuvant chemotherapy adenocarcinoma group in the incidence of hydrothorax. Nevertheless, no statistically significant disparities were noted between the neoadjuvant immunotherapy squamous carcinoma group and the neoadjuvant chemotherapy carcinoma group.ConclusionRegarding surgical outcomes, neoadjuvant immunotherapy conferred notable advantages compared to conventional neoadjuvant chemotherapy and neoadjuvant targeted therapy for patients diagnosed with adenocarcinoma. In the case of squamous carcinoma, neoadjuvant immunotherapy exhibited superiority over neoadjuvant targeted therapy, although additional evidence is required to conclusively establish its precedence over neoadjuvant chemotherapy.

Background: Intrauterine adhesions (IUAs) are a common illness of the uterine cavity. Endometrial fibrosis is the main pathological feature. In addition to a high recurrence rate, patients with severe IUAs have a low pregnancy rate. However, there are few effective treatments for IUAs. This study aims to confirm the influence of apoptotic bodies of bone marrow mesenchymal stem cells (BMSCs) on endometrial stromal cell fibrosis by mediating the Wnt/β-catenin signaling pathway and to provide new insight for the clinical treatment of IUAs. Methods: Human endometrial stromal cells (HESCs) were used to establish an IUA cell model by treatment with TGF-β1, and a rat IUA model was established by the double injury method. Apoptosis of BMSCs was detected by TUNEL assays, and cell morphology was observed by the CM-DiI tracer. The morphology of apoptotic vacuoles and apoptotic bodies (ABs) was detected by TEM. We used Western blotting to detect the expression of histone H3.3, histone H2B, C3b, cyclin D1, C1QC, α-SMA, COL1A1, COL5A2, FN, CTGF, Wnt2b, c-MYC, CK-18 and VIM. The expression levels of α-SMA, COL1A1, COL5A2, FN and CTGF were detected by RT‒qPCR. The expression levels of α-SMA, COL1A1, FN and CTGF were detected by immunofluorescence. Immunohistochemistry was used to detect the expression of TGF-β, CK-18 and VIM. Flow cytometry, cell scratch assays, CCK-8 assays, and H & E and Masson staining were used to detect the cell cycle, cell migration, cell proliferation, and endometrial pathology, respectively. Results: We found that ultraviolet light (UV) irradiation induced apoptosis of BMSCs and increased the production of ABs. TGF-β1 treatment can induce HESCs to form extracellular matrix (ECM), and aggravate cell fibrosis, and adding ABs or FH535, an inhibitor of the Wnt/β-catenin signaling pathway, can inhibit TGF-β1-induced HESC fibrosis. However, the inhibitory effect of ABs on TGF-β1-induced fibrosis of HESCs was attenuated by the addition of LiCl. In the Wnt/β-catenin signaling pathway, LiCl is an activator after coculture with TGF-β1. In vivo, IUA-induced narrowing of the uterine cavity was accompanied by intrauterine adhesions, increased deposition of collagen fibers, upregulation of TGF-β1, VIM, α-SMA, COL1A1 and COL5A2, and downregulation of CK-18. These changes in expression were reversed after treatment with ABs or FH535. When ABs and LiCl were added at the same time, the inhibitory effect of ABs on IUA fibrosis was weakened. Conclusion: BMSC-derived ABs inhibit the fibrosis of HESCs by inhibiting the Wnt/β-catenin signaling pathway. These results provide a new direction for the clinical treatment of IUAs.

T cells are among the most potent anti-tumor cells that are found in humans. Our study sought to develop a reliable signature incorporating T cell marker genes (TMGs) for predicting the prognosis and therapy responsiveness of head and neck squamous cell carcinoma (HNSCC) patients. We downloaded scRNA-seq data from the GSE181919 to identify TMGs. Subsequently, we devised a 12 TMG signature in the TCGA HNSCC cohort by using LASSO analysis. Patients with high-risk scores were shown to experience unfavorable progression-free survival, disease-specific survival, and overall survival, which was validated in the GSE65858 cohort. Additionally, the nomogram integrated risk score and clinical features are more suitable for clinical application. The enrichment analyses of both pathways and functions showed that high- and low-risk patients had functionally related distinctions. Furthermore, analysis of the immunological landscape confirmed that the low-risk patients had a larger percentage of infiltrating immune cells as well as a higher incidence rate of immune-related events. In the meantime, a greater IPS score and expression of immune checkpoint genes suggested significantly favorable responsiveness to immunotherapy in low-risk patients. On the other hand, the high-risk patients had a greater degree of sensitivity to the chemotherapy agents, which included paclitaxel, gemcitabine, docetaxel, and cisplatin. Our finding revealed that this TMG signature independently functioned as a prognostic marker and guided individualized immunotherapy and chemotherapy selection for patients with HNSCC.

The accurate simulation of anisotropic media is critical in seismic imaging and inversion. In recent years, some scholars have dedicated efforts to the study of precise elastic waves in anisotropic media; however, it is easy to separate P-wave and S-wave from elastic wave fields in isotropic media but difficult to separate them in anisotropic media. To address this issue, others have proposed pseudo-pure-wave equations based on the theory of wave-mode separation, but shear wave interference still exists. Therefore, we derived the first-order pure quasi-P-wave equation with no shear wave component in orthorhombic anisotropic media (ORT) which is common in the Earth’s crust and has very important research value. The presence of a pseudodifferential operator in the equation poses a challenge for solving. In order to solve the pure wave equation, we decomposed the original pseudodifferential operator into an elliptic differential operator and a scalar operator, both of which are easily solvable. In addition, we extended the equation from ORT media to tilted ORT (TORT) media. The example results indicate that our pure quasi-P-wave equation can yield a more stable and accurate P-wave field. The pure wave equation we propose can be applied in reverse time migration (RTM), the least squares RTM (LSRTM), and even the full waveform inversion (FWI).

In agriculture, diphenyl ether herbicides are a broad-spectrum family of pesticides mainly used to control annual weeds in agriculture. Although diphenyl ether herbicides have a long-lasting effect in weed control, they can also be harmful to succeeding crops, as well as to the water and soil environment. Residual herbicides can also harm a large number of non-target organisms, leading to the death of pest predators and other beneficial organisms. Therefore, it is of great significance to control and remediate the contamination caused by diphenyl ether herbicide residues for the sake of environmental, nutritional, and biological safety. This review provides an overview of the techniques used for remediating diphenyl ether herbicide contamination, including biological, physical, and chemical remediation. Among these techniques, bioremediation, particularly microbial biodegradation technology, is extensively employed. The mechanisms and influencing factors of different remediation techniques in eliminating diphenyl ether herbicide contamination are discussed, together with a prospect for future development directions. This review serves as a scientific reference for the efficient remediation of residual contamination from diphenyl ether herbicides.

Abstract Background Exosomal long non‐coding RNA (lncRNA) has been shown to be potential biomarker for cancer diagnosis and follow up. However, little is known about its application in esophageal squamous cell carcinoma (ESCC) detection. Here, we sought to develop a novel diagnostic model based on serum exosomal lncRNAs to improve ESCC screening efficiency. Methods A multiphase, case‐control study was conducted among 140 ESCC patients and 140 healthy controls. Microarray screening was performed to acquire differentially expressed exosomal lncRNAs in the discovery phase. The diagnostic model Index I was constructed based on a panel of three lncRNAs using logistic regression in the training phase, and were confirmed in a subsequent validation phase. A receiver operating characteristic (ROC) curve was generated to calculate the diagnostic value. The effects of the selected lncRNAs level on ESCC mortality were evaluated using a Cox hazard regression model and Kaplan‐Meier curve analysis, and the expression level with clinicopathological features was also calculated. Finally, we explored the oncogenic potential of candidate lncRNA RASSF8‐AS1 in vitro and by target mRNA sequencing. Results Index I was able to discriminate ESCC patients from healthy controls, and showed superiority to classic tumor biomarkers. Moreover, serum levels of the exosomal lncRNAs correlated with clinicopathological features and prognosis. The in vitro assays showed that RASSF8‐AS1 played an oncogenic role in ESCC. Target mRNA scanning results suggested involvement of RASSF8‐AS1 in tumor immunity and metabolism. Conclusion The newly identified serum exosomal lncRNAs could be used as new biomarkers for ESCC, and showed oncogenic potential in ESCC.

Abstract Background Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) binding sites can affect the interactions between miRNAs and target genes, which is related to cancer susceptibility and tumorigenesis. However, the association between SNPs located in miR-17-92 cluster binding sites and ESCC risk remains unclear. Therefore, we aimed to explore the relationship between polymorphisms in miR-17-92 cluster binding sites and ESCC susceptibility. Methods Six SNPs in the binding sites of miR-17-92 cluster were selected using bioinformatics databases, and their association with ESCC risk was investigated in a case-control study (including 488 cases and 512 controls) based on the population from high incidence areas of ESCC in China. We evaluated the SNP-SNP and SNP-smoking interactions using generalized multifactor dimensionality reduction (GMDR). Moreover, the expression of the miR-17-92 cluster and its target genes was determined in ESCC and adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was conducted to verify the effect of SNPs on the binding affinity between miRNAs and target genes. Results We found that the SNP rs1804506 C > T had a significant association with the decreased ESCC risk. The SNP rs1804506 T allele was associated with a significantly decreased risk of ESCC in the additive model (OR = 0.817, 95% CI = 0.681–0.981, P = 0.030). The rs1804506 T allele had more striking effects on reducing ESCC risk in older individuals, female or non-smoker subgroups. We also found a significant interaction effect between rs1366600 and smoking by GMDR methods (P = 0.011). Additionally, the expression levels of miR-19a-3p and TGFBR3 were significantly downregulated in ESCC tissues compared with normal tissues, and the carriers of rs1804506 TT genotype had lower expression level of TGFBR3 than those of rs1804506 CC/CT genotype. Following dual-luciferase reporter assay showed that the rs1804506 T allele reduced the binding of miR-19a-3p and TGFBR3 3′-UTR. Conclusions Our findings suggest that the rs1804506 polymorphism in miR-17-92 cluster binding sites contributes to the susceptibility of ESCC, which might provide new clues and scientific evidence for the etiology and biomarkers for the prevention and treatment of ESCC.

Abstract Background Pyroptosis plays an essential function in carcinogenesis and the antitumor immune response. Herein, we constructed a pyroptosis‐related long noncoding RNA (prLncRNA) signature to predict therapeutic effects and outcomes for head and neck squamous cell carcinoma (HNSCC) patients. Methods Patients obtained from the TCGA‐HNSC project were divided randomly into the training as well as the validation sets at a ratio of 7:3. A novel prognostic prLncRNA signature was constructed from the results of the training set using the least absolute shrinkage and selection operation. The medium value was used as the basis for categorizing all HNSCC patients into a low‐ or high‐risk cohort. Cox regression and Kaplan–Meier (KM) survival analyses were executed to estimate the prognostic value. We also evaluated the functional enrichment, tumor microenvironment, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between the high‐ and low‐risk cohorts. Results Nineteen prognostic prlncRNAs were identified to establish the prognostic signature. Multivariate Cox regression and KM survival analyses confirmed that this prlncRNA signature might serve as an independent prognostic indicator of patient survival, which was subsequently confirmed using a validating dataset. Multiple ROC curves indicated the prlncRNA signature presented a more predictive power than clinicopathological factors (age, sex, tumor grade, and tumor stage). GO, KEGG, and GSEA enrichment analysis disclosed several immune‐related pathways which appeared to be enhanced in the low‐risk cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithms indicated considerable differences in the tumor microenvironment and immune cell infiltration in the low‐ and high‐risk cohorts. Furthermore, the low‐risk cohort was predicted to achieve a better response to immunotherapeutic drugs, while in contrast, the high‐risk cohort would be more sensitive to chemotherapy drugs. Conclusions Our findings robustly demonstrate that our constructed prlncRNA signature could serve as an efficient indicator of prognosis, immunotherapy response, and chemosensitivity for HNSCC patients.

Abstract Objectives Esophageal cancer is a high-mortality disease. Esophagectomy is the most effective method to treat esophageal cancer, accompanied with a high incidence of post-operation complications. The anastomosis has a close connection to many severe post-operation complications. However, it remains controversial about the choice of intrathoracic anastomosis (IA) or cervical anastomosis (CA). The study was conducted to compare the clinical outcomes between the two approaches. Methods We searched databases for both randomized controlled trials (RCTs) and cohort studies comparing post-operation outcomes between IA and CA. Primary outcomes were the incidences of anastomotic leakage and mortality. Secondary outcomes were the incidences of anastomotic stenosis, pneumonia and re-operation. Results Twenty studies with a total of 7,479 patients (CA group: n = 3,183; IA group: n = 4296) were included. The results indicated that CA group had a higher incidence of anastomotic leakage than IA group (odds ratio [OR] = 2.05, 95% confidence intervals [CI] = 1.61–2.60, I2 = 53.31%, P

Abstract Cluster of differentiation 31 (CD31), phalloidin and alpha smooth muscle actin (α-SMA) have been widely applied to label the cerebral blood vessels in the past years. Although CD31 is mainly used as endothelial marker in determining the cerebral capillaries, it seems likely that its labeling efficiency is closely correlated with the antibodies from the polyclonal or monoclonal one, as well as the conditions of blood vessels. In order to test this phenomenon, we compared the labeling characteristics of goat polyclonal anti-CD31 (gP-CD31) and mouse monoclonal anti-CD31 (mM-CD31) with those of phalloidin and α-SMA on the rat brain in health and ischemia/reperfusion (I/R) with the middle cerebral artery occlusion. By multiple immunofluorescence staining, it was found that gP-CD31 labeling expressed extensively on the cerebral capillaries forming the vascular networks on the normal and ischemic regions, but mM-CD31 labeling mainly presented on the capillaries in the ischemic region. In contrast to the vascular labeling with gP-CD31, phalloidin and α-SMA were mainly expressed on the wall of cortical penetrating arteries, and less on that of capillaries. By three-dimensional reconstruction analysis, it was clearly shown that gP-CD31 labeling was mainly located on the lumen side of vascular wall and was surrounded by phalloidin labeling and α-SMA labeling. These results indicate that gP-CD31 is more sensitive than mM-CD31 for labeling the cerebral vasculature, and is highly compatible with phalloidin and α-SMA for evaluating the cerebral vascular networks under the physiological and pathological conditions.

In circular shield tunnels bearing high inner pressure or rectangular shaped shield tunnels, as the axial force at the segmental lining decreases, the bolt load at the segmental joint increases. It is essential to adopt high-stiffness segmental joints to improve the bearing capacity and control the deformation at the joint position. When designing high-stiffness segmental joints, the selection of ductile-iron joint panel is crucial. In this study, two types of segmental joints with different joint panels were fabricated, and the effects of joint panel stiffness on the mechanical properties of segmental joints were analyzed through full-scale sagging and hogging bending tests. The results showed that the failure mode of high-stiffness segmental joint was similar to that of large eccentric compression section. According to the difference of panel stiffness, the failure modes can be specified into two types. If the stiffness is sufficient, the joint failure occurs due to the yielding of bolts; otherwise, it occurs due to the large deformation of ductile-iron joint panels. As for the design requirement of segmental joint, the stiffness of joint panel should be sufficient, i.e., the opening and failure of the joints are finally induced by the bolt deformation. Otherwise, before the plastic deformation of the bolts, the large deformation of the joint panels will occur under a bending-moment-dominant load, and the bearing capacity of the joints will greatly decrease.

The operation of a liquid metal battery involves multiple physical fields, such as electrochemical reaction, mass transfer, heat transfer, fluid flow, magnetic field, etc. It is of great significance to closely couple these physical phenomena. Flow is an important phenomenon in liquid metal batteries, and its generation mechanism is also diverse. Flow can be triggered by temperature fields, electromagnetic fields, or concentration fields. In this work, we firstly established a multi-field coupled model for Li‖Bi liquid metal battery. Through this model, we compared and analyzed the various flow types in the molten salt and the positive electrode, and further discussed the effects of flow on mass transfer and electrochemical performance.

Abstract Background Tiger bone, which had been one of the most famous traditional Chinese medicine for 2000 years, was originate from the skeleton of Panthera tigris L., and had the actions of anti-inflammatory, analgesic, immune-regulatory and promoting healing of bone fracture, and was used for the treatment of osteoporosis and rheumatoid arthritis. Jin-Tian-Ge (JTG), the artificial tiger bone powder, were prepared from skeletons of several farmed animals to substitute the natural tiger bone, and has been used for the treatment of osteoporosis in clinical practice. However, the characteristic and mechanism of action of JTG for the therapy of osteoporosis need to be further evidenced by using modern pharmacological methods. The aim of this work is to investigate the bone-protective effects of JTG, and explore the possible underlying mechanism. Methods Ovariectomy (OVX) rats were orally administrated JTG or estradiol valerate (EV) for 12 weeks. We investigated the pharmacodynamic effects of JTG on anti-bone loss in OVX rats, and also investigated the role of JTG in promoting osteogenesis and inhibiting osteoclast differentiation. Results JTG increased the bone mineral density (BMD), improved the bone microarchitecture and biomechanical properties in ovariectomized rast, whereas reversed the bone high turnover in OVX rats as evidenced by serum biochemical markers in OVX rats. JTG increased osteogenic differentiation of BMSCs in vitro, and up-regulated the expression of the key proteins of BMP and Wnt/β-catenin pathways. JTG also inhibited the osteoclastogenesis of BMM as evidenced by the alteration of the TRAP activity, F-actin construction and the expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, Cathepsin K (Ctsk) and matrix metallopeptidase 9 (MMP9) of OCs induced with RANKL and LPS, reduced the expression and phosphorylation of NF-κB in OCs. Conclusions JTG prevented bone loss in OVX rats and increased osteogenic differentiation of BMSCs through regulation of the BMP and Wnt/β-catenin pathway, inhibited osteoclastogenesis by suppressing the NF-κB pathway, suggesting that JTG had the potentials for prevention and treatment of osteoporosis by modulating formation and differentiation of osteoblast and osteoclast.

We propose a legal Unmanned Aerial Vehicle (UAV) surveillance system to perform passive surveillance or active jamming while in the presence of a suspicious relay or source, where a UAV works in half-duplex mode and the relay/source deploys artificial noise to prevent monitoring. Three schemes are considered for a Multiple-Input Multiple-Output (MIMO) UAV: surveilling followed by jamming; jamming followed by surveilling; and two-stage surveilling. For each scheme, a closed-form expression of surveilling non-outage probability is derived, and surveilling performance under different system configurations is analyzed. Monte Carlo (MC) simulation validates derivation correctness.

The bone tumour microenvironment plays an essential role in multiple myeloma (MM) development. Here, the authors show that bone collagen degradation provides glycine to support MM progression through glutathione and purine synthesis.

Abstract Objective To investigate the analgesic effect and rehabilitation quality of patients undergoing thoracoscopic wedge resection of the lung under erector spinae plane (ESP) block with dexmedetomidine combined with the same dose and different concentrations of ropivacaine. Methods Seventy patients undergoing thoracoscopic wedge resection were randomly divided into groups A (n = 35) and B (n = 35). To perform ESP block, the groups were administered dexmedetomidine (0.5 μg/kg) combined with 30 mL of 0.33% ropivacaine or 20 mL of 0.5% ropivacaine, respectively, half an hour before general anesthesia induction. We compared the onset time of anesthesia, the block level, and the duration of the block between the two groups. The number of compressions of the analgesic pump within 24 h and 48 h postoperatively and the time of the first compression were noted. The visual analog scale (VAS) scores of static and cough at 0.5 h, 6 h, 12 h, 24 h, and 48 h postoperatively were noted. Furthermore, the 40-item quality of recovery questionnaire (QoR-40) score was recorded at 24 h postoperatively. In addition, we noted the time taken to get out of the bed for the first time, the length of hospital stay, analgesia satisfaction, and the occurrence of related adverse reactions and complications within 48 h postoperatively. Results The range of ESP block was wider in Group A than in Group B (P

The amination of C(sp3)–H bonds is an appealing and challenging task in organic synthesis. Here, by using an electrogenerated sulfate radical an HAT agent, the authors report a practical Ritter-type amination of C(sp3)–H bonds.

High-specific-energy batteries with long-lifespan are the development aspiration for energy storage applications. Metal electrodes with high specific capacity and low reduction potential are potential candidates for next-generation high-specific-energy batteries. Nevertheless, the stability of the metal electrode batteries is constantly suffered from the unstable interface issue during the plating/stripping process, such as dendrite formation, dynamic evolution of solid electrolyte interphase, and other accompanied side reactions. To solve these challenges, numerous researches have been intensively studied based on the interfacial engineering of metal electrodes, including electrode configuration optimization, interfacial chemistry regulation and solid–solid interface construction, and the recent progress is elaborately introduced in this paper. Nevertheless, the dendrite issues cannot be entirely prohibited in solid metal electrodes, which motivate the search for potential alternatives. Liquid-metal electrodes with completely reversible structural changes and high mass transfer rate are rendered as an effective approach to solve the dendrite problem. Therefore, the development of liquid metal electrode batteries is reviewed in this paper, in which the interfacial issues are explicated and some commendable achievements are summarized. In the end, the implementation of interfacial engineering and the development roadmap of the metal electrode batteries are prospected.

Abstract Background Homologous recombination deficiency (HRD) is a molecular biomarker for administrating PARP inhibitor (PARPi) or platinum-based (Pt) chemotherapy. The most well-studied mechanism of causing HRD is pathogenic BRCA1/2 mutations, while HRD phenotype is also present in patients without BRCA1/2 alterations, suggesting other unknown factors. Methods The targeted next-generation sequencing (GeneseeqPrime® HRD) was used to evaluate the HRD scores of 199 patients (Cohort I). In Cohort II, a total of 85 Pt-chemotherapy-treated high-grade serous ovarian cancer (HGSOC) patients were included for investigating the role of HRD score in predicting treatment efficacy. The concurrent genomic features analyzed along HRD score evaluation were studied in a third cohort with 416 solid tumor patients (Cohort III). Results An HRD score ≥ 38 was predefined as HRD-positive by analyzing Cohort I (range: 0–107). Over 95% of the BRCA1/2-deficient cases of Cohort I were HRD-positive under this threshold. In Cohort II, Pt-sensitive patients have significantly higher HRD scores than Pt-resistant patients (median: 54 vs. 34, p = 0.031) and a significantly longer PFS was observed in HRD-positive patients (median: 548 vs. 343 days, p = 0.003). Furthermore, TP53, NCOR1, and PTK2 alterations were enriched in HRD-positive patients. In Cohort III, impaired homologous recombination repair pathway was more frequently observed in HRD-positive patients without BRCA1/2 pathogenic mutations. The alteration enrichment of TP53, NCOR1, and PTK2 observed in Cohort II was also validated by the ovarian subgroup in Cohort III. Conclusions Using an in-house HRD evaluation method, our findings show that overall HRR gene mutations account for a significant part of HRD in the absence of BRCA1/2 aberrations, and suggest that HRD positive status might be a predictive biomarker of Pt-chemotherapy.

Abstract Backgrounds High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax − AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). Methods In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid–base variables. Cox regression model and Kaplan Meier curve were applied to predict patients’ 90-day overall survival (OS). Results A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11–1.39, p

Abstract Background Periacetabular malignant tumor seriously endangers the life and health of patients. Hemipelvic replacement provides a good method for patients who want complete resection of the tumor while retaining or restoring the function of the affected limb. Objective To investigate the performance and clinical application of the new adjustable modular hemipelvic prosthesis and to compare the effects of three kinds of hemipelvic prosthesis. Methods In this study, 23 patients, with an average age of 44.6 years (21–75 years), were collected, who received hemipelvic replacement with new adjustable, modular, and screw-rod system hemipelvic prosthesis. Preoperative preparation was conducted on them, and operative complications were recorded. Postoperative functional follow-up was performed regularly. Results The average operation time was 319 min (170–480 min), and the average blood loss was 2813 ml (1000 mL-8000 ml). The incidence of complications was 47.8%, and type A (wound-related complications) had the highest incidence (34.8%). Postoperative dislocation occurred in 3 cases (13.0%), and no dislocation occurred in the new adjustable modular hemipelvic prosthesis group. The average MSTS score of the patients was 18.6 (10–23), and the average Harris score was 73.7 (53–87). Conclusions The new adjustable modular hemipelvic prosthesis has the feasibility of reconstruction and good functional outcome, making it ideal for periacetabular tumors. Furthermore, preoperative tumor-feeding artery embolization and abdominal aortic balloon implantation may be an effective choice to reduce intraoperative blood loss and facilitate the operation of tumor resection.

In order to avoid frequent replacement of fixtures to the robot due to the clamping of disc type workpieces of various varieties and sizes on automated production lines， and improve the stability and safety of robot clamping， a self-locking under-actuated gripper is designed and optimized. The structure design of the gripper is completed based on the under-actuated principle， and the feasibility of structural self-locking and enveloping clamping is ensured through the analysis of the clamping configuration and clamping process. According to the principle of virtual work and the vector closed equation of the linkage mechanism， a static modeling under the adaptive gripping state of the gripper is constructed. A structural parameter optimization model is established according to the balance of the clamping force of each gripper knuckle， and a genetic algorithm is introduced to realize the parameter optimization. Numerical test results show that， compared with the empirical method and the Fmincon algorithm， the target value error optimized by the genetic algorithm is reduced by 70% and 62.5%， and the maximum deviation of the gripper's clamping force is reduced by 78.3% and 61.4% respectively， which verifies the superiority of the genetic optimization design of the proposed under-actuated gripper， and satisfies the stable clamping requirement of the clamper through the balance of the knuckle forces.

In this paper, expanded graphite was prepared by chemical oxidation system with hydrogen peroxide as oxidant and concentrated sulfuric acid as intercalation agent. Expanded graphite was obtained by microwave expansion. The effects of the amount of hydrogen peroxide and concentrated sulfuric acid on the morphology and specific surface area of expanded graphite were systematically studied. It was found that the expanded graphite retained the structural characteristics of natural small flake graphite and had wormlike surface morphology, The maximum expansion volume was 291.39 ml/g and the specific surface area was 55.62 m2/g. Small flake expanded graphite was used as anode material of lithium ion battery to assemble button battery and its electrochemical performance was tested which showed good lithium removal/intercalation capacity and good cycling performance.

Abstract Genetically-encoded biosensors based on a single fluorescent protein are widely used to visualize analyte levels or enzymatic activities in cells, though usually to monitor relative changes rather than absolute values. We report photochromism-enabled absolute quantification (PEAQ) biosensing, a method that leverages the photochromic properties of biosensors to provide an absolute measure of the analyte concentration or activity. We develop proof-of-concept photochromic variants of the popular GCaMP family of Ca2+ biosensors, and show that these can be used to resolve dynamic changes in the absolute Ca2+ concentration in live cells. We also develop intermittent quantification, a technique that combines absolute aquisitions with fast fluorescence acquisitions to deliver fast but fully quantitative measurements. We also show how the photochromism-based measurements can be expanded to situations where the absolute illumination intensities are unknown. In principle, PEAQ biosensing can be applied to other biosensors with photochromic properties, thereby expanding the possibilities for fully quantitative measurements in complex and dynamic systems.

ObjectiveInflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis.MethodsDifferentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model.ResultsACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls.ConclusionsThe reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.

Sensitivity to the temporal properties of auditory patterns tends to be poorer in older listeners, and this has been hypothesized to be one factor contributing to their poorer speech understanding. This study examined sensitivity to speech rhythms in young and older normal-hearing subjects, using a task designed to measure the effect of speech rhythmic context on the detection of changes in the timing of word onsets in spoken sentences. A temporal-shift detection paradigm was used in which listeners were presented with an intact sentence followed by two versions of the sentence in which a portion of speech was replaced with a silent gap: one with correct gap timing (the same duration as the missing speech) and one with altered gap timing (shorter or longer than the duration of the missing speech), resulting in an early or late resumption of the sentence after the gap. The sentences were presented with either an intact rhythm or an altered rhythm preceding the silent gap. Listeners judged which sentence had the altered gap timing, and thresholds for the detection of deviations from the correct timing were calculated separately for shortened and lengthened gaps. Both young and older listeners demonstrated lower thresholds in the intact rhythm condition than in the altered rhythm conditions. However, shortened gaps led to lower thresholds than lengthened gaps for the young listeners, while older listeners were not sensitive to the direction of the change in timing. These results show that both young and older listeners rely on speech rhythms to generate temporal expectancies for upcoming speech events. However, the absence of lower thresholds for shortened gaps among the older listeners indicates a change in speech-timing expectancies with age. A further examination of individual differences within the older group revealed that those with better rhythm-discrimination abilities (from a separate study) tended to show the same heightened sensitivity to early events observed with the young listeners.

Abstract Directed greybox fuzzing (DGF) is an effective method to detect vulnerabilities of the specified target code. Nevertheless, there are three main issues in the existing DGFs. First, the target vulnerable code of the DGFs needs to be manually selected, which is tedious. Second, DGFs mainly leverage distance information as feedback, which neglects the unequal roles of different code snippets in reaching the targets. Third, most of the existing DGFs need the source code of the test programs, which is not available for binary programs. In this paper, we propose a vulnerability-oriented directed binary fuzzing framework named VDFuzz, which automatically identifies the targets and leverages dynamic information to guide the fuzzing. In specific, VDFuzz consists of two components, a target identifier and a directed fuzzer. The target identifier is designed based on a neural-network, which can automatically locate the target code areas that are similar to the known vulnerabilities. Considering the inequality of code snippets in reaching the given target, the directed fuzzer assigns different weights to basic blocks and takes the weights as feedback to generate test cases to reach the target code. Experimental results demonstrate that VDFuzz outperformed the state-of-the-art fuzzers and was effective in vulnerability detection of real-world programs.

Abstract Background & aims Sarcopenia is associated with poor clinical outcomes of patients who underwent esophagectomy. The current diagnostic criteria for sarcopenia are complex and laborious. We aimed to employ the simple and economic indicator sarcopenia index (SI = creatinine/cystatin C ×100) to screen for sarcopenia and to evaluate its prognostic value in patients with esophageal cancer (EC). Methods Older participants in the National health and nutrition examination survey (NHANES) database (1999–2002) were divided into three groups according to tertiles of the SI value to explore the feasibility of SI in the diagnosis of sarcopenia. Restricted cubic spline (RCS) was utilized to show the non-linear relationship between all-cause mortality and SI. Patients with EC admitted to Jinling Hospital were enrolled to validate the efficacy and prognostic value of SI. Cut-off values of SI were determined using receiver operating characteristic curves. Multivariable logistic analyses and Cox analyses were used to identify the independent factors of postoperative complications and long-term survival, respectively. Results A total of 989 participants were identified from the NHANES database. SI showed the diagnostic value of sarcopenia (tertile 1 vs. tertile 3: odds ratio [OR]=3.67, 95% confidence interval [CI]: 1.52–8.87, p=0.004; tertile 2 vs. tertile 3: OR=1.79, 95% CI: 0.75–4.28, p=0.191) adjusted for race, gender, and body mass index (BMI). Individuals with SI ≤ 68 had a poorer overall survival (OS) (hazard ratio [HR]=2.14, 95% CI: 1.71–2.68, p

Abstract Background Uncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand’s disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction. Case presentation This paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department. Conclusion Mild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals’ attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.

Abstract Background In recent years, preoperative nutrition has received great attention, especially for patients who received surgical reconstruction of the digestive tract such as esophagectomy. Preoperative nutrition therapy was reported to accelerate the patient's postoperative recovery. In addition, immune suppression, nausea, and vomiting may lead to poor immune and nutritional status of patients with esophageal cancer who underwent neoadjuvant chemotherapy (NAC), which is not conducive to surgery. Therefore, preoperative nutritional treatment is necessary for patients with esophageal cancer who underwent NAC. Method Patients with esophageal cancer who received NAC at Nanjing Jinling Hospital from January 2018 to September 2020 were retrospectively identified. Patients were divided into enteral immunonutrition (EIN) group (those who received a conventional diet and immunonutrition supplement, Peptisorb, Nutricia, 500 mL/day * 7 via oral intake), and control group (those who only received a conventional diet were divided into). The primary outcomes were immune and nutritional indicators changes, including immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin G (IgG), and albumin (ALB), which were measured at preoperative day (PRD) 7, PRD-1, postoperative day (POD) 1 and POD-7. The secondary outcomes were postoperative complications, adverse reactions, and length of hospital stay. Results A total of 124 eligible patients were included in the study, with 21 patients in EIN group. After 1:2 matching, significant difference in baseline characteristics between the two groups was not observed (EIN: n = 21, Control group: n = 42). Compared with the control group, the IgA is significantly increased in the EIN group at POD-7 (p = 0.017). However, we observed that the IgM level in the control group was significantly higher than those in the EIN group at POD-7 (p = 0.007). The incidence of pneumonia and total complications in the EIN group were significantly lower than those in control group (p = 0.024, p = 0.028, respectively). There is no significant difference in ALB and adverse reactions between two groups (p = 0.303, p = 0.108, respectively). Conclusion Immunonutritional supplement after NAC is an effective strategy to improve the postoperative immune status of esophageal cancer patients and could reduce the incidence of infectious complication. More well-designed prospective studies are needed to verify and update our finding.

Stem cell-derived exosomes (SC-EXO) was an emerging therapeutic agent in regenerative medicine. Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction (ED) treatment. However, high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection. In this study, a Polydopamine nanoparticles (PDNPs) incorporated poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PDNPs-PELA) thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes (EXO). The hydrogels exhibited sol-gel transition at body temperature. Moreover, the in-situ polymerization of PDNPs using poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PELA) block copolymer as a template was found to be more stable dispersion in the gel system. After being encapsulated into the hydrogel, EXO shows sustained release behavior within two weeks. In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons, increase of the cavity's pressure, thereby restoring the erectile function. In particular, since the PDNPs in thermosensitive gels have excellent photoacoustic performance, the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging. These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.

Program-wide binary code diffing is widely used in the binary analysis field, such as vulnerability detection. Mature tools, including BinDiff and TurboDiff, make program-wide diffing using rigorous comparison basis that varies across versions, optimization levels and architectures, leading to a relatively inaccurate comparison result. In this paper, we propose a program-wide binary diffing method based on neural network model that can make diffing across versions, optimization levels and architectures. We analyze the target comparison files in four different granularities, and implement the diffing by both top down process and bottom up process according to the granularities. The top down process aims to narrow the comparison scope, selecting the candidate functions that are likely to be similar according to the call relationship. Neural network model is applied in the bottom up process to vectorize the semantic features of candidate functions into matrices, and calculate the similarity score to obtain the corresponding relationship between functions to be compared. The bottom up process improves the comparison accuracy, while the top down process guarantees efficiency. We have implemented a prototype PBDiff and verified its better performance compared with state-of-the-art BinDiff, Asm2vec and TurboDiff. The effectiveness of PBDiff is further illustrated through the case study of diffing and vulnerability detection in real-world firmware files.

Nitrogen deficiency can cause floral abortion during reproductive development of rice. Here the authors show that when nitrogen is limited, rice plants require the ETFβ protein, which is involved in branched chain amino acid catabolism, to promote nitrogen reutilization and support the initiation of meiosis.

The mouse model of multiple cerebral infarctions, established by injecting fluorescent microspheres into the common carotid artery, is a recent development in animal models of cerebral ischemia. To investigate its effectiveness, mouse models of cerebral infarction were created by injecting fluorescent microspheres, 45–53 µm in diameter, into the common carotid artery. Six hours after modeling, fluorescent microspheres were observed directly through a fluorescence stereomicroscope, both on the brain surface and in brain sections. Changes in blood vessels, neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry. The microspheres were distributed mainly in the cerebral cortex, striatum and hippocampus ipsilateral to the side of injection. Microinfarcts were found in the brain regions where the fluorescent microspheres were present. Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia. These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts. This model is an effective, additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions. This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences (approval No. D2021-03-16-1) on March 16, 2021.

Pericytes, as the mural cells surrounding the microvasculature, play a critical role in the regulation of microcirculation; however, how these cells respond to ischemic stroke remains unclear. To determine the temporal alterations in pericytes after ischemia/reperfusion, we used the 1-hour middle cerebral artery occlusion model, which was examined at 2, 12, and 24 hours after reperfusion. Our results showed that in the reperfused regions, the cerebral blood flow decreased and the infarct volume increased with time. Furthermore, the pericytes in the infarct regions contracted and acted on the vascular endothelial cells within 24 hours after reperfusion. These effects may result in incomplete microcirculation reperfusion and a gradual worsening trend with time in the acute phase. These findings provide strong evidence for explaining the “no-reflow” phenomenon that occurs after recanalization in clinical practice.

Resistant starch (RS) is beneficial for humans, especially for the diabetes. Raw potato had a great deal of RS, while most of which become digestible after gelatinization. Thus, few RS will be retained in potatoes after regular cooking. To preserve RS in cooked potatoes as much as possible, microwave heating before (MFD) and after freeze-drying (FDM) were conducted with three different potatoes. After MFD, the RS content in potatoes was lower than 7% and the RDS content was higher than 45% for three potatoes. However, RS in potatoes treated with FDM was still as high as 40%, similar to that in the raw potatoes. Meantime, FDM caused less browning, produced a certain level of pyrazines, benzeneacetaldehyde and other flavor compounds, endowing cooked potatoes special baked flavor. Freeze-drying before microwave heating is a valuable way to reserve RS in cooked potatoes, which could also be used to reserve high RS content in crisp, chips, and other processed potatoes.

Abstract Background Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease. Methods We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40–69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram. Results We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: “Healthy”, “Western”, “Lower consumers-combination”, “Medium consumers-combination” and “Higher consumers-combination” patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into “Asymptomatic”, “Mild symptoms” and “Overt symptoms” classes based on health-related symptoms reported by the participants. Compared to the “Healthy” pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the “Asymptomatic”. The nomograms reflect the good predictive ability of the model. Conclusion Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

GPAT enzymes (glycerol-3-phosphate 1-O-acyltransferase, EC 2.3.1.15) catalyze the initial and rate-limiting step of plant glycerolipid biosynthesis for membrane homeostasis and lipid accumulation, yet little research has been done on peanuts. By reverse genetics and bioinformatics analyses, we have characterized an AhGPAT9 isozyme, of which the homologous product is isolated from cultivated peanut. QRT-PCR assay revealed a spatio-temporal expression pattern that the transcripts of AhGPAT9 accumulating in various peanut tissues are highly expressed during seed development, followed by leaves. Green fluorescent protein tagging of AhGPAT9 confirmed its subcellular accumulation in the endoplasmic reticulum. Compared with the wild type control, overexpressed AhGPAT9 delayed the bolting stage of transgenic Arabidopsis, reduced the number of siliques, and increased the seed weight as well as seed area, suggesting the possibility of participating in plant growth and development. Meanwhile, the mean seed oil content from five overexpression lines increased by about 18.73%. The two lines with the largest increases in seed oil content showed a decrease in palmitic acid (C16:0) and eicosenic acid (C20:1) by 17.35% and 8.33%, respectively, and an increase in linolenic acid (C18:3) and eicosatrienoic acid (C20:3) by 14.91% and 15.94%, respectively. In addition, overexpressed AhGPAT9 had no significant effect on leaf lipid content of transgenic plants. Taken together, these results suggest that AhGPAT9 is critical for the biosynthesis of storage lipids, which contributes to the goal of modifying peanut seeds for improved oil content and fatty acid composition.

ObjectiveSplenectomy is a vital treatment method for hypersplenism with portal hypertension. However, portal venous system thrombosis (PVST) is a serious problem after splenectomy. Therefore, constructing an effective visual risk prediction model is important for preventing, diagnosing, and treating early PVST in hepatolenticular degeneration (HLD) surgical patients.MethodsBetween January 2016 and December 2021, 309 HLD patients were selected. The data were split into a development set (215 cases from January 2016 to December 2019) and a validation set (94 cases from January 2019 to December 2021). Patients’ clinical characteristics and laboratory examinations were obtained from electronic medical record system, and PVST was diagnosed using Doppler ultrasound. Univariate and multivariate logistic regression analyses were used to establish the prediction model by variables filtered by LASSO regression, and a nomogram was drawn. The area under the curve (AUC) of receiver operating characteristic (ROC) curve and Hosmer–Lemeshow goodness-of-fit test were used to evaluate the differentiation and calibration of the model. Clinical net benefit was evaluated by using decision curve analysis (DCA). The 36-month survival of PVST was studied as well.ResultsSeven predictive variables were screened out using LASSO regression analysis, including grade, POD14D-dimer (Postoperative day 14 D-dimer), POD7PLT (Postoperative day 7 platelet), PVD (portal vein diameter), PVV (portal vein velocity), PVF (portal vein flow), and SVD (splenic vein diameter). Multivariate logistic regression analysis revealed that all seven predictive variables had predictive values (P < 0.05). According to the prediction variables, the diagnosis model and predictive nomogram of PVST cases were constructed. The AUC under the ROC curve obtained from the prediction model was 0.812 (95% CI: 0.756–0.869) in the development set and 0.839 (95% CI: 0.756–0.921) in the validation set. Hosmer–Lemeshow goodness-of-fit test fitted well (P = 0.858 for development set; P = 0.137 for validation set). The nomogram model was found to be clinically useful by DCA. The 36-month survival rate of three sites of PVST was significantly different from that of one (P = 0.047) and two sites (P = 0.023).ConclusionThe proposed nomogram-based prediction model can predict postoperative PVST. Meanwhile, an earlier intervention should be performed on three sites of PVST.

BackgroundsTrimodal therapy (neoadjuvant chemoradiotherapy followed by esophagectomy) for locally advanced esophageal squamous cell carcinoma (ESCC) is associated with a significant survival benefit. Modified Ryan score is an effective tool to evaluated the tumor regression grade (TRG) after neoadjuvant therapy. The aim of this study was to evaluate the prognostic value of TRG for overall survival (OS) and disease-free survival (DFS) in ESCC patients undergoing neoadjuvant chemoradiation.MethodsThe study retrospectively reviewed 523 ESCC patients who underwent neoadjuvant chemoradiotherapy and radical esophagectomy at Jinling Hospital from January 2014 to July 2020. Kaplan–Meier curves with log-rank test and Cox regression model were used to evaluate the prognostic factor of TRG based on modified Ryan scoring system on OS and DFS.ResultsAfter application of inclusion and exclusion criteria, 494 patients with ESCC following neoadjuvant chemoradiotherapy and radical esophagectomy were available for analysis. The TRG scores are significantly associated with smoke history (p = 0.02), lymphovascular invasion (LVI) and/or peripheral nerve invasion (PNI) (p

ObjectivesThe causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).MethodsIn this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.ResultsMR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn’t support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger).ConclusionsOur findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.

This study aims to investigate the factors and consequences of gas deflagration accidents in metro shield tunnels based on on-site investigation and numerical analysis. We built a numerical model and detection process for an underground shield tunnel subjected to an internal explosion from an actual accident. The tunnel geometry under consideration is the same as that used for the metro line. Concerning the limitations of research on the failure and recovery mechanism of shield segmental linings under the action of internal explosion load, an explosion accident of a shield segmental lining under construction caused by the shield tunneling machine destroying natural gas pipelines was discussed, in which the structure failure characteristics during the explosion and the structure repair method after the explosion were investigated. An interval repair scheme was proposed, which provides experience for the treatment of similar engineering accidents. To investigate the gas explosion within the tunnel during the accident, the finite element software Ansys LS-DYNA with the arbitrary Lagrangian–Eulerian (ALE) technique was employed to simulate the explosion scenario. Dynamic analyses were carried out to reproduce the blast scenario. The stress distribution within the segmental lining as well as the lining’s deformation were calculated. The potential applications of the treatment and planning of comparable engineering mishaps were discussed in the study.

A novel Non-Isolated-Pentagon-Rule (non-IPR) isomer of thorium-based endohedral mono-metallofullerenes (mono-EMFs), Th@C1(17418)-C76, was successfully synthesized and characterized using MALDI-TOF mass spectroscopy, single-crystal X-ray diffraction, UV-vis-NIR spectroscopy, and Raman spectroscopy. The molecular structure of this non-IPR isomer was determined unambiguously as Th@C1(17418)-C76 using a single-crystal X-ray diffraction analysis. The crystallographic results further revealed that the optimal Th site resided at the intersection of two adjacent pentagons, similar to that of U@C1(17418)-C76. Additionally, the UV-vis-NIR spectra of Th@C1(17418)-C76 exhibited distinct differences compared to the previously reported U@C1(17418)-C76, highlighting the distinctive electronic structure of actinium-based endohedral metallofullerenes (EMFs). The Raman spectrum of Th@C1(17418)-C76 exhibited similarities to that previously reported for thorium-based EMFs, indicating the analogous strong metal–cage interactions of thorium-based EMFs.

Abstract Background and Aim Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Methods Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results In this GWAS, we found that two SNPs were associated with HCC at P

Abstract Backgrounds As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understanding of the genetic etiology of OA. Methods Six participants (3 OA and 3 controls) were recruited and serum samples were assayed through RNA sequencing (RNA-seq). And, RNA-seq dataset was analysed to identify genes, pathways and regulatory networks dysregulated in OA. The overlapped differentially expressed microRNAs (DEMs) were further screened in combination with the microarray dataset GSE143514. The expression levels of candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) based on the GEO dataset (GSE114007). Results Serum samples were sequenced interrogating 382 miRNAs. After screening of independent samples and GEO database, the two comparison datasets shared 19 overlapped candidate micRNAs. Of these, 9 up-regulated DEMs and 10 down-regulated DEMs were detected, respectively. There were 236 target genes for up-regulated DEMs and 400 target genes for those down-regulated DEMs. For up-regulated DEMs, the top 10 hub genes were KRAS, NRAS, CDC42, GDNF, SOS1, PIK3R3, GSK3B, IRS2, GNG12, and PRKCA; for down-regulated DEMs, the top 10 hub genes were NR3C1, PPARGC1A, SUMO1, MEF2C, FOXO3, PPP1CB, MAP2K1, RARA, RHOC, CDC23, and CREB3L2. Mir-584-5p-KRAS, mir-183-5p-NRAS, mir-4435-PIK3R3, and mir-4435-SOS1 were identified as four potential regulatory pathways by integrated analysis. Conclusions We have integrated differential expression data to reveal putative genes and detected four potential miRNA-target gene pathways through bioinformatics analysis that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.