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Abstract The spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we distinguished several sentinel animal species and genera for monitoring the re-emergence of COVID-19 or the new outbreak of COVID-19-like disease. We analyzed SARS-CoV-2 genomic data from human and nonhuman mammals in the taxonomic hierarchies of species, genus, family and order of their host. We find that SARS-CoV-2 carried by domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) cluster closely to human-origin viruses and show no differences in the majority of amino acids, but have the most positively selected sites and should be monitored to prevent the re-emergence of COVID-19 caused by novel variants of SARS-CoV-2. Viruses from the genera Panthera (especially lion (Panthera leo)), Manis and Rhinolophus differ significantly from human-origin viruses, and long-term surveillance should be undertaken to prevent the future COVID-19-like outbreaks. Investigation of the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein may be necessary to predict the novel animal SARS-CoV-2 variants.

Abstract Background Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson’s disease (PD) is hardly extensively researched. Methods A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. Results Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P

Random flaps are frequently employed in treating substantial skin abnormalities and in surgical tissue-rebuilding interventions. The random flap technique provides flaps of specific dimensions and contours to fit the surgical incision. However, blood supply deficiency and subsequent ischemia-reperfusion injury can cause severe oxidative stress and apoptosis, eventually leading to distal necrosis, which limits the clinical application of the flap. Quercetin (QUE) is primarily found in the glycoside form in many plant parts, such as stem bark, flowers, leaves, buds, seeds, and fruits. Cellular, animal, and clinical studies have demonstrated the antioxidant, anti-apoptosis, anti-inflammatory, and activation of autophagy properties of QUE. In previous studies, high doses of QUE effectively suppressed the survival of human umbilical vein endothelial cells (HUVECs) stimulated by hydrogen peroxide. However, different concentration gradients of QUE on HUVECs revealed a significant protective effect at a concentration of 10 mM. The protective impact of QUE on HUVECs was evaluated using scratch tests, CCK-8 assays, and EDU assays. Simultaneously, a mouse model of random skin flap was created, and the impact of QUE on skin flap survival was examined by intragastric injection. The QUE group showed a significantly larger survival area of the random flap and higher blood flow intensity compared to the control group. Furthermore, the beneficial effects of QUE were reversed by the autophagy inhibitor 3-MA. Therefore, autophagy plays a significant role in the therapeutic benefits of QUE on flap survival.

Transglutaminase (TGase) can catalyze the crosslinking within or between protein molecules, improving the structural and functional properties of proteins. It has been widely used in artificial meat, yogurt products, flour products and other foods. In this study, a high yield TGase strain was screened from fermented soybean, and it was identified as the Bacillus amyloliquefaciens XCT-09. Then, the transglutaminase (X9Tgl) from XCT-09 was expressed in Escherichia coli BL21(DE3), and the enzyme activity of purified X9Tgl reached 5.73 U/mg. Subsequently, the catalytic mechanism of X9Tgl was elucidated, and the X9Tgl contained the active center of E115, C116 and E187, as well as the substrate binding sites W149 and F69. Furthermore, this study characterized the enzymatic properties of X9Tgl, and the optimal catalytic temperature and pH were 60 °C and 6, respectively. Moreover, X9Tgl exhibited stronger thermal stability and pH tolerance than STG, and it was not inhibited by the majority of metal ions. This study successfully identified a X9Tgl with high thermal stability, and pH tolerance, which provided a potential TGase resource for application in the food and medicine fields.

ObjectiveThis study aimed to assess the efficacy and safety of QiMing granules (QM) in the treatment of patients with diabetic retinopathy (DR).MethodsWe systematically searched multiple databases, including Pubmed, Embase, Web of Science, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database. Randomized controlled trials (RCTs) of QM in the treatment of DR were collected, and the search time limit was from the establishment of the database to 27 March 2024. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. The risk of bias in the included studies was assessed using the Risk of Bias Assessment tool for randomized controlled trials of Cochrane Collaboration 2.0 (RoB 2.0). The main outcomes were the overall efficacy, visual acuity, retinal circulation time, macular thickness. The secondary outcomes were the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1c). The adverse events was considered the safety outcome. Review Manager 5.4.1 and Stata 15.1 were used for meta-analysis. Data were pooled by random-effects or fixed-effects model to obtain the mean difference (MD), risk ratio (RR), and 95% confidence interval (CI).ResultsA total of 33 RCTs involving 3,042 patients were included in this study. Overall, we demonstrated that QM had a significant clinical effect on DR. QM alone was superior to conventional treatment (CT) in terms of overall efficacy [RR = 1.45, 95% CI: (1.34, 1.58), p < 0.00001, moderate certainty], retinal circulation time [MD = −0.56, 95% CI: (−1.01, −0.12), p = 0.01] and macular thickness [MD = −11.99, 95% CI: (−23.15, −0.83), p = 0.04]. QM plus CT was superior to CT in terms of overall efficacy [RR = 1.29, 95% CI: (1.24, 1.33), p < 0.00001], visual acuity [MD = 0.14, 95% CI: (0.11, 0.17), p < 0.00001], macular thickness [MD = −14.70, 95% CI: (−21.56, −7.83), p < 0.0001], TG [MD = −0.20, 95% CI: (−0.33, −0.08), p = 0.001, moderate certainty], TC [MD = −0.57, 95% CI: (−1.06, −0.07), p = 0.02], and LDL-C [MD = −0.36, 95% CI: (−0.70, −0.03), p = 0.03]. In terms of safety, the incidence of adverse events in the experimental group was less than that in the control group. The results of the GRADE evidence quality evaluation showed that the evidence quality of outcome indicators was mostly low.ConclusionQM can effectively improve overall efficacy, visual acuity, macular thickness, retinal circulation time, and reduce the levels of TG, TC, and LDL-C. However, due to the limited number of studies included, a small sample size, and a lack of high-quality literature, the possibility of publication bias cannot be excluded. Moreover, biases are present due to differences in study design, such as the absence of placebo use in the control group and a predominant use of combined intervention designs in the control group, along with deficiencies in allocation concealment and blinding methods. Therefore, more multi-center, large-sample, and rigorously designed studies are needed to substantiate this conclusion.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023465165.

Summary: Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18–65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin −10% (2.69%; 95% CI −4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (−3.25; 95% CI −5.56, −0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP

Summary: Understanding the specific movements of bacteria isolated from human feces can serve as a novel diagnostic and therapeutic tool for inflammatory bowel disease. Here, we present a protocol for a microbial swarming assay and to isolate the bacteria responsible for swarming activity. We describe steps for identifying bacteria using MALDI-TOF mass spectrometry and whole-genome sequencing. We then detail procedures for validating findings by observing the same swarming phenotype upon reperforming the swarming assay.For complete details on the use and execution of this protocol, please refer to De et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Objective This study was designed to investigate the regulatory effects of kinesin family member (KIF) 23 on anaplastic thyroid cancer (ATC) cell viability and migration and the underlying mechanism. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the levels of KIF23 in ATC cells. Besides, the effects of KIF23 and sirtuin (SIRT) 7 on the viability and migration of ATC cells were detected using cell counting kit-8, transwell and wound healing assays. The interaction between SIRT7 and KIF23 was evaluated by co-immunoprecipitation (Co-IP) assay. The succinylation (succ) of KIF23 was analyzed by western blot. Results The KIF23 expression was upregulated in ATC cells. Silencing of KIF23 suppressed the viability and migration of 8505C and BCPAP cells. The KIF23-succ level was decreased in ATC cells. SIRT7 interacted with KIF23 to inhibit the succinylation of KIF23 at K537 site in human embryonic kidney (HEK)-293T cells. Overexpression of SIRT7 enhanced the protein stability of KIF23 in HEK-293T cells. Besides, overexpression of KIF23 promoted the viability and migration of 8505C and BCPAP cells, which was partly blocked by silenced SIRT7. Conclusions SIRT7 promoted the proliferation and migration of ATC cells by regulating the desuccinylation of KIF23.

Highlights Compared with the traditional single-atom catalysts (SACs), the Mg SACs with axial displacement is accurately fabricated on the functional carbon nanotubes. The electronic spin polarization modulates the spin density of MgPc, facilitating the LiPSs conversion kinetics in Li-S batteries. The MgPc@FCNT achieves ultra-low capacity decay rate under the high sulfur loading.

Torreya grandis is a characteristic rare economic tree species in subtropical mountainous areas. The nut has a variety of bioactive compounds, such as polyphenols and vitamins. However, the carotenoids compositions and its regulatory mechanisms underlying carotenoid biosynthesis in kernels remain unknown. Here, the major carotenoids in the kernel were analyzed. The result showed that lutein and β-carotene were the predominant carotenoids in the kernel, while low levels of α-carotenoid and zeaxanthin were detected. Lutein and β-carotene were decreased during the maturation of kernel. Expression analysis by RNA-seq and qRT-PCR indicated that the expressions of TgCYP97A3 and TgLCYB were also reduced during the maturation of kernel. The contents of lutein or β-carotene were obviously increased in tobacco transiently overexpressing TgCYP97A3 or TgLCYB. Moreover, DPPH radical scavenging activity and FRAP were also significantly enhanced. In addition, several MYB and WRKY transcription factors TgMYBS3, TgMYB48 and TgWRKY11 were identified to positively regulate the TgCYP97A3 expression, while TgMYB48, TgWRKY2 and TgWRKY11 could upregulate the TgLCYB expression. The illustration of carotenoids biosynthesis and its molecular mechanism in kernels not only provides a basis for understanding carotenoids biosynthesis in kernels, but also enables the use of molecular biotechnology to develop new health products rich in carotenoids based on T. grandis nuts.

Abstract Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA–miRNA–mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration.

Titanium dioxide (TiO2) is widely employed in the catalytic degradation of wastewater, owing to its robust stability, superior photocatalytic efficiency, and cost-effectiveness. Nonetheless, isolating the fine particulate photocatalysts from the solution post-reaction poses a significant challenge in practical photocatalytic processes. Furthermore, these particles have a tendency to agglomerate into larger clusters, which diminishes their stability. To address this issue, the present study has developed Al2O3–SiO2–TiO2 composite semiconductor porous ceramics and has systematically explored the influence of Al2O3 and SiO2 on the structure and properties of TiO2 porous ceramics. The findings reveal that the incorporation of Al2O3 augments the open porosity of the ceramics and inhibits the aggregation of TiO2, thereby increasing the catalytic site and improving the light absorption capacity. On the other hand, the addition of SiO2 enhances the bending strength of the ceramics and inhibits the conversion of anatase to rutile, thereby further enhancing its photocatalytic activity. Consequently, at an optimal composition of 55 wt.% Al2O3, 40 wt.% TiO2, and 5 wt.% SiO2, the resulting porous ceramics exhibit a methylene blue removal rate of 91.50%, and even after undergoing five cycles of testing, their catalytic efficiency remains approximately 83.82%. These outcomes underscore the exceptional photocatalytic degradation efficiency, recyclability, and reusability of the Al2O3–SiO2–TiO2 porous ceramics, suggesting their substantial potential for application in the treatment of dye wastewater, especially for the removal of methylene blue.

Abstract Dopant‐free hole transport layers (HTLs) are crucial in enhancing perovskite solar cells (pero‐SCs). Nevertheless, conventional processing of these HTL materials involves using toxic solvents, which gives rise to substantial environmental concerns and renders them unsuitable for large‐scale industrial production. Consequently, there is a pressing need to develop dopant‐free HTL materials processed using green solvents to facilitate the production of high‐performance pero‐SCs. Recently, several strategies have been developed to simultaneously improve the solubility of these materials and regulate molecular stacking for high hole mobility. In this review, a comprehensive overview of the methodologies utilized in developing dopant‐free HTL materials processed from green solvents is provided. First, the study provides a brief overview of fundamental information about green solvents and Hansen solubility parameters, which can serve as a guideline for the molecular design of optimal HTL materials. Second, the intrinsic relationships between molecular structure, solubility in green solvents, molecular stacking, and device performance are discussed. Finally, conclusions and perspectives are presented along with the rational design of highly efficient, stable, and green solvent‐processable dopant‐free HTL materials.

China is facing tremendous pressure to reduce carbon emissions. This paper investigates the impact of financial technology (fintech) on carbon emissions reduction across Chinese provincial regions using annual data from 2011 to 2021. To comprehensively reflect the development level of fintech, we utilize web crawler technology and word frequency analysis to create new variables for measuring the technology level and innovation capability, with fintech-related keywords sourced from the Baidu index. Subsequently, we construct a fintech index for each province in China. Given the heterogeneous relationship between fintech and carbon emissions reduction, we employ an innovative sparse support vector quantile regression to explore the impact of fintech on carbon emissions reduction at different quantile levels. This method employs an Lp-norm regularization term to identify the key variables influencing carbon emission reduction. The empirical results indicate that fintech significantly reduces carbon emissions in all Chinese provincial regions. Furthermore, the positive effects of fintech on carbon emissions reduction are much stronger in high-carbon provinces than in low-carbon provinces. Consequently, it is imperative for policy-makers and practitioners to focus on increasing investment in digital infrastructure and enhancing digital services, particularly in Shanxi, Hebei, Henan, Shaanxi, Ningxia, and Xinjiang provinces. The mechanism analysis reveals that fintech contributes to carbon emission reduction by promoting industrial structure upgrading in more economically developed provinces, while its mediating role is absent in less developed provinces.

Purpose: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). Methods: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. Results: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. Conclusions: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.

Positron Emission Tomography (PET) is a powerful medical imaging technique widely used for detection and monitoring of disease. However, PET imaging can be adversely affected by patient motion, leading to degraded image quality and diagnostic capability. Hence, motion gating schemes have been developed to monitor various motion sources including head motion, respiratory motion, and cardiac motion. The approaches for these techniques have commonly come in the form of hardware-driven gating and data-driven gating, where the distinguishing aspect is the use of external hardware to make motion measurements vs. deriving these measures from the data itself. The implementation of these techniques helps correct for motion artifacts and improves tracer uptake measurements. With the great impact that these methods have on the diagnostic and quantitative quality of PET images, much research has been performed in this area, and this paper outlines the various approaches that have been developed as applied to whole-body PET imaging.

Abstract Purpose To investigate the value of ultrasound and serum marker tests in detecting lateral lymph node metastasis in medullary thyroid cancer (MTC). Methods Data of 105 patients diagnosed with MTC and admitted to the Department of General Surgery in Peking Union Medical College Hospital from June 2010 to August 2020 were collected and retrospectively analyzed. Results Ultrasound examination alone had a sensitivity of 89.36% and a specificity of 70.69%. For surveillance of postoperative carcinoembryonic antigen and calcitonin, cut‐off values of 7.115 ng/mL and 13.185 pg/mL, respectively, were shown to discriminate the presence of cervical lymph node metastasis. Combining ultrasound and postoperative serum levels of both carcinoembryonic antigen and calcitonin as serial tests increased the specificity to 91.38% and 87.93%, with a sensitivity of 95.45%. Multivariate logistic analysis identified the following risk factors for lateral lymph node metastasis in MTC: suspicious lymph nodes detected by ultrasound and postoperative calcitonin above 13.185 pg/mL. Conclusion The combination of ultrasound and serological tests achieved higher sensitivity and specificity to identify MTC cases with potential occult lateral cervical lymph node metastasis compared with single tests.

Abstract Background Microglial polarization is one of the most promising therapeutic targets for multiple central nervous system (CNS) disorders, including ischemic stroke. However, detailed transcriptional alteration of microglia following cerebral ischemic stroke remains largely unclear. Methods Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 60 min in mice. Single-cell RNA sequencing (scRNA-seq) was performed using ischemic brain tissues from tMCAO and sham mice 3 days after surgery. Ch25h −/− mice were used to investigate the role of specific microglia subcluster on post-stroke infarct volume and neuroinflammation. Results We identified a relatively homeostatic subcluster with enhanced antigen processing and three “ischemic stroke associated microglia” (ISAM): MKI67+, CH25H+ and OASL+ subclusters. We found the MKI67+ subcluster undergo proliferation and differentiation into CH25H+ and OASL+ subclusters. CH25H+ microglia was a critical subcluster of ISAM that exhibited increased phagocytosis and neuroprotective property after stroke. Ch25h −/− mice developed significantly increased infarct volume following ischemic stroke compared to Ch25h +/−. Meanwhile, the OASL+ subcluster accumulated in the ischemic brain and was associated with the evolving of neuroinflammation after stroke, which was further aggravated in the aged mice brain. Conclusions Our data reveal previously unrecognized roles of the newly defined CH25H+ and OASL+ microglia subclusters following ischemic stroke, with novel insights for precise microglia modulation towards stroke therapy.

Duodenal cancer (DC) has complex subtypes and undergoes complicated morphological changes throughout progression, so understanding the molecular basis is crucial. Here, the authors perform a proteogenomics analysis of 156 DCs, revealing molecular subtypes as well as the roles of smoking, AARS1 and PARP1.

Abstract The nuts of Torreya grandis are abundant in flavonoids, providing potential antioxidant activity. Considering that T. grandis can yield nuts for hundreds or thousands of years, effects of tree age on flavonoids and antioxidant activity of T. grandis nuts were targeted in this study for the first time. Results revealed that antioxidant activity and total flavonoid contents in 100‐ and 1000‐years‐old T. grandis nuts were much higher compared to 10‐years‐old T. grandis. The content of 19 flavonoids showed significant correlations with antioxidant activity in 100‐ and 1000‐years‐old trees using metabolites profiling. Transcriptome and coexpression analysis indicated that seven genes were associated with aged‐related flavonoids biosynthesis. Further analysis showed that abscisic acid and gibberellin might regulate the age‐related differential flavonoids accumulation. Our study provides a novel viewpoint that aged T. grandis is likely to present a better source of natural antioxidants and has yet to be examined in other tree models.

The progression of oesophageal squamous cell carcinoma (ESCC) from early to advanced stages requires comprehensive molecular characterisation. Here, the authors perform a proteogenomics analysis of ESCC patient samples across nine histopathological stages and three phases, identifying key alterations and paths for progression.

Torreya grandis is a gymnosperm species that produces edible seeds with high level of sciadonic acid (SCA). Here, the authors assemble the genome of this species, preform methylone analysis of seeds at different developmental stages, and reveal two key genes involved in SCA biosynthesis.

In this paper, a numerical investigation is performed to study the broadband noise of a fan stage with wavy trailing-edge blades. A study of the wavelength and ratio of amplitude to wavelength (H/L) is conducted to better understand the noise reduction effect of wavy trailing-edge blades. A rotor–stator interaction broadband noise prediction method based on the result of a Reynolds-averaged Navier–Stokes equation is used. The results show that all wavy trailing-edge configurations reduce the sound power level of the fan stage. The noise reduction effect of H20L10 is the best among all the wavy trailing-edge configurations, and the sound power level is reduced by 2.4 dB at 1000 Hz. When the H/L remains unchanged, the noise reduction effect of the wavy trailing-edge configuration increases with the increase in wavelength. When the wavelength remains unchanged, the noise reduction effect of the wavy trailing-edge configuration with an H/L of 2 is the best. The use of wavy trailing-edge configurations reduces the turbulent kinetic energy and turbulent integral length scale upstream of the stator by changing the wake of the rotor, thereby reducing the rotor–stator interaction broadband noise of the fan stage.

Future UHBR (Ultra-High Bypass-Ratio) engines might cause serious ‘turbine noise storms’ but, at present, turbine noise prediction capability is lacking. The large turning angle of the turbine blade is the first major factor deserving special attention. The RANS (Reynold Averaged Navier–Stokes equation)-informed (here called RI) method and LINSUB (the bound vorticity 2D model LINearized SUBsonic flow in cascade), developed to predict fan broadband noise, coupled with a two-flat-plates (here called TP) assumption for the turbine blade, is applied here, and one autonomous rapid RI-TP model for predicting turbine wake interaction broadband noise has been developed. Firstly, taking the single axial turbine test rig NPU-Turb as the object, both the experimental data and the DDES/AA (delayed Detached Eddy Simulation/Acoustic Analogy) hybrid model have been used to validate the RI-TP model. High consistency in the medium and high frequencies among the three designed and off-designed rotation speeds indicates that the RI-TP model has the ability to predict turbine broadband noise rapidly. And compared with the original RANS-informed method, with one thin-flat-plate assumption on the blade, the RI-TP model can enhance the PWL (sound power level) in almost the whole spectral range below 10 KHz, which, in turn, is closer to the experimental data and the DDES/AA prediction results. The PWL trend with a ‘dividing point’ position is also studied. The spectrum would move up or down if the location is away from true value. In addition, the extraction location for turbulence as an input for the RI-TP model is negligible. In the future, multi-stage characteristics and the blade thickness effect should be further considered when predicting turbine noise.

To investigate the deformation characteristics of shield tunnel linings under ground surcharge, finite element software was employed to create a detailed three-dimensional model of the staggered assembly of the shield tunnel lining. This model includes components such as precast concrete segments, reinforcements, and joints (comprising bent bolts, washers, and bolt sleeves). Additionally, the model accounts for interface frictions between segments and the interactions between different rings. The reliability of the numerical model was verified based on the results of a full-scale model test. Additionally, the model accounts for interface frictions between segments and the interactions between different rings. Changes in tunnel convergence, joint tensioning, bolt stresses, reinforcement stresses, and concrete crack development were systematically analyzed. The results indicate the following: (1) the deformation mode of the lining structure under ground surcharge resembles a “transverse ellipse”. Joints located near the haunch opened along the outer arc, while those near the vault and bottom opened along the inner arc. The restraining effect of the bolts on joints opening in the inner arc was greater than that on the outer arc. Notably, when the opening of the inner arc reached 4.9 mm, the bolt stress escalated to the yield strength of 640 Mpa. (2) Under larger loads, the lining structure’s joints are susceptible to greater deformation, resulting in the tensile yielding of local reinforcement within these joints. (3) Cracks predominantly occur near the haunch, vault, and bottom of the lining structure, with the central angle of crack distribution ranging between 70° and 85°.

In recent years, the detection of offshore pile foundations has received wide attention in engineering. Compared with traditional methods, the O-cell test has unique advantages in offshore pile foundation detection. To study the load transfer characteristics of the O-cell method for pile testing in coastal soft soil foundation, this paper established the pile–soil numerical model to simulate the O-cell and traditional testing processes. The finite element method and equal displacement method are combined to calculate the conversion coefficient and ultimate bearing capacity, and the distribution forms of axial force, side friction resistance, and tip resistance are discussed. The research results show that the O-cell test method and the traditional method have different load transfer forms. By introducing the equal displacement method into the O-cell pile–soil model, the error between the equivalent conversion ultimate bearing capacity and the calculation result of the surcharge method is less than 0.5%, and the O-cell conversion coefficient can be accurately calculated.

Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.

BackgroundCardioneuroablation (CNA) is recognized as a promising therapeutic option for adults with severe symptomatic bradycardia caused by excessive vagal tone. However, no pediatric cases have been reported to date. Therefore, the aim of this study is to evaluate the feasibility and efficacy of CNA in children.MethodsA 12-year-old male patient was hospitalized with symptoms of fatigue, palpitations, and syncope for more than 2 months, and was definitively diagnosed with functional sinoatrial node dysfunction by using a 12-lead electrocardiogram, 24-h Holter monitoring, loading dose of atropine test (0.04 mg/kg), and treadmill exercise test. Simultaneously, whole-exome sequencing was performed on the child and his core family members. After completing the preoperative examination and signing the informed consent form, the child underwent CNA therapy.ResultsFirst, the electroanatomic structures of both atria were mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram–guided CNA methods. Then, the local fractionated intracardiac electrograms of each cardiac ganglionated plexus (GP), including the GP between the aortic root and the medial wall of the superior vena cava, the GP between the posterior wall of the coronary sinus ostium and the left atrium, the GP between the anterior antrum of the right superior pulmonary vein and the superior vena cava, the GP in the superolateral area around the root of the left superior pulmonary vein, the GP around the root of the right inferior pulmonary vein, and the GP around the root of the left inferior pulmonary vein, were used as targets for ablation at a power of 30 W with an ablation index of 350–400. At a 6-month follow-up, the child's heart rhythm saw a complete restoration to sinus rhythm and clinical symptoms disappeared.ConclusionThe first application of CNA in a child with symptomatic sinus bradycardia was achieved with better clinical outcomes. CNA can be carried out cautiously in children under suitable indications.

Background: PD-1 inhibitor and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). The present study aimed to evaluate the efficacy of PD-1 inhibitors plus different dose intensity neoadjuvant chemotherapy in the treatment of locally advanced ESCC. Methods: Patients with locally advanced but resectable thoracic ESCC, staged as T3 or T4a, N0–3, and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes), were enrolled in this study. The eligible patients received tislelizumab plus different dose intensity chemotherapy for a 21-day cycle with repeated 2–4 cycles before surgery. The primary endpoints are pathological complete response (pCR) and major pathological response (MPR), and the secondary endpoints are objective response rate (ORR), disease control rate (DCR), and disease-free survival (DFS). Results: From November 2019 to February 2022, 122 cases received at least two cycles neoadjuvant chemoimmunotherapy and were evaluated by imaging examination. Subsequently, 99 patients underwent surgery and were evaluated by pathological evaluation. According to chemotherapy dose intensity, the patients were divided into three cohorts: cohort 1 (

Mutation of SERPINC1 is related to the incidence of Inherited antithrombin (AT) deficiency. In this study, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with a mutation of SERPINC1 c.236G>A (p.R79H). The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Besides, it has a normal female karyotype and could differentiate into all three germ layers in vitro.

Abstract Background Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration. Methods The characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up. Results The proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P

Abstract Background This study aimed to investigate the effect of aging on glucose metabolism improvement after Roux-en-Y gastric bypass (RYGB) in rat models with type 2 diabetes mellitus (T2DM). Methods Twenty aged Goto-Kakizaki rats were randomly assigned into RYGB-A group and sham RYGB (SR-A) group, and 10 adult Goto-Kakizaki rats also accept RYGB procedures (RYGB-Y). Glucose metabolism, resting energy expenditure (REE), glucagon-like peptide-1 (GLP-1) and total bile acid level were measured. Results RYGB could significantly improve glucose metabolism in aged diabetic rats. The fasting blood glucose level in the RYGB-A group decreased from 15.8 ± 1.1 mmol/l before surgery to 12.3 ± 1.5 mmol/l 16 weeks after surgery (P

Abstract Background To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes. Methods The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture. Results Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839–29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804–36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183–42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018–0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029). Conclusions Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.

Abstract Background Gamma-glutamyl transpeptidase to platelet ratio (GPR) and gamma-glutamyl transpeptidase to lymphocyte ratio (GLR) are assumed to be prognostic factors in liver fibrosis, cirrhosis and hepatocellular carcinoma. However, the reference values of GPR and GLR were not known. Objectives The study aimed to investigate the reference ranges of GPR and GLR in Chinese Han population in Chaoshan region in South China. Methods A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. 2400 healthy adults aged 20~79 years were included. GPR and GLR were determined. Results Of 2400 healthy adults, 1200 men and 1200 women were included. The median GPR and GLR for men were 0.22 and 11.28, for women were 0.18 and 7.86, respectively. The 95% reference range of GPR in normal male and female are 0.09~0.54 and 0.08~0.55, GLR are 4.55~29.64 and 3.52~23.08, respectively. The male had a higher GPR at age 20~49 than the female while the GPR at age 60~79 was higher in the female than in the male. The GPR was affected by age, decreased with aging in male and increased in female. The GLR was higher in the male than in the female and varied with aging in the female but not in the male. Conclusion The study provides reference data on GPR and GLR from different age and sex groups in South China. GPR and GLR varied with age and sex.

The upregulation of 4-hydroxyphenylpyruvate dioxygenase (HPPD) can protect plants from adverse abiotic stress. Therefore, studying the changes of HPPD under abiotic stress is extremely valuable. In this study, we employed a rational molecular design strategy to prepare an HPPD-responsive fluorescent probe consisting of a pyrene fluorophore, a linker and a benquitrione skeleton recognition moiety that functions via an aggregation–disaggregation sensing mechanism. As predicted, this probe exhibited an obvious turn-on fluorescence response towards HPPD. In addition, in vivo imaging demonstrated the excellent capability of this probe to track HPPD in Arabidopsis thaliana, and the dynamic changes in HPPD were monitored under different stress degrees of high temperature and Cadmium (II) ion (Cd2+) stress. This work provides an efficient design strategy for acquiring a noninvasive HPPD fluorescence probe, which could evaluate the degree of stress and be further employed for exploring the stress resistance mechanism in plants.

In response to the unprecedented global healthcare crisis of the COVID-19 pandemic, the scientific community has joined forces to tackle the challenges and prepare for future pandemics. Multiple modalities of data have been investigated to understand the nature of COVID-19. In this paper, MIDRC investigators present an overview of the state-of-the-art development of multimodal machine learning for COVID-19 and model assessment considerations for future studies. We begin with a discussion of the lessons learned from radiogenomic studies for cancer diagnosis. We then summarize the multi-modality COVID-19 data investigated in the literature including symptoms and other clinical data, laboratory tests, imaging, pathology, physiology, and other omics data. Publicly available multimodal COVID-19 data provided by MIDRC and other sources are summarized. After an overview of machine learning developments using multimodal data for COVID-19, we present our perspectives on the future development of multimodal machine learning models for COVID-19.

Maritime transportation is vital for the movement of cargo between different continents and distant locations but can be disrupted by the frequent occurrence of pirate attacks. Based on the pirate attacks from July 1994 to December 2019, a spatial analysis of pirate attacks using a Geographic Information System (GIS) was conducted in the present study using the data available for tankers, dry bulk carriers, container vessels, general cargo vessels, and tugs. The adoption of the kernel density analysis was intended to identify the spatial pattern of global pirate attacks. The research results demonstrated that the pirate attacks showed a clustering pattern and were mostly associated with areas experiencing economic depression, a high unemployment rate, and social unrest. Accordingly, spatiotemporal hot spot analysis was carried out to recognize the changing directions of cold spots and hot spots over a period of time. The waters off Somalia, the Strait of Malacca, the Philippines, the Bay of Bengal, the Gulf of Guinea, and the northwest of South America were found to be the common locations of pirate attacks. The cold and hot spots of pirate attacks on the three key vessel types, including tankers, dry bulk carriers, and container vessels, were found to be similar. When considering the same area, the trends of cold and hot spots of different vessel types being attacked were substantially different. This study can provide a useful guideline for the International Maritime Organization and other relevant organizations in the world to design and implement targeted strategies to combat and mitigate pirate attacks. Additionally, the introduction of a GIS may help to envision the spatial and temporal distribution of pirate attacks and to explore the characteristics of pirate behaviors at sea and the patterns of piracy.

Torreya grandis is native Chinese tree species of economic significance, renowned for its long lifespan and the rich nutritional value of its nuts. In this study, we analyzed the morphological characteristics, metabolites, associated gene expressions, and regulatory mechanism in nuts from young (10 years old) and old (1000 years old) T. grandis trees. We observed that the length, width, and weight of nuts from older trees were considerably greater than those from younger trees. Metabolomic analysis revealed that the concentrations of 18 amino acids and derivatives (including histidine and serine) in nuts from older trees were markedly higher than those in nuts from younger trees. Transcriptome and metabolomic correlation analysis identified 16 genes, including TgPK (pyruvate kinase), TgGAPDH (glyceraldehyde 3-phosphate dehydrogenase), and others, which exhibit higher expression levels in older trees compared to younger trees, as confirmed by qRT-PCR. These genes are associated with the biosynthesis of histidine, glutamic acid, tryptophan, and serine. Transient expression of TgPK in tobacco led to increased pyruvate kinase activity and amino acid content (histidine, tryptophan, and serine). Additionally, dual-luciferase assays and yeast one-hybrid results demonstrated that TgWRKY21 positively regulates TgPK expression by directly binding to the TgPK promoter. These findings not only demonstrate the nutritional differences between nuts from young and old trees but also offer fresh insights into the development of nutritional sources and functional components based on nuts from old trees, enriching our understanding of the potential benefits of utilizing nuts from older trees.

In vertebrates, bony fishes possess not only innate immune cells but also T and B cells that are equivalent to those in mammals. However, the precise sub-cluster of immune cells in teleost fish remains largely unknown. Herein, we developed a dynamic bacterial infection model in turbot (Scophthalmus maximus) and created a fish immune cell landscape (FICL) for a primary lymphoid organ (head kidney), a secondary lymphoid organ (spleen), and barrier tissues (gills and posterior intestine). Moreover, through comprehensive characterization of the expression profiles of 16 clusters, including dendritic cells-like (DCs-like), macrophages (MΦs), neutrophils, NK cells, as well as 12 sub-clusters of T and B cells, we found that CD8+ CTLs, CD4−CD8− T, Th17 and ILC3-2 like cells possess a bifunctional role associated with cytotoxicity and immunoregulation during bacterial infection. To our knowledge, these results could provide a useful resource for a better understanding of immune cells in teleost fish and could act as a comprehensive knowledge base for assessing the evolutionary mechanism of adaptive immunity in vertebrates.

Abstract Background We aimed to investigate changes of bile acids and resting energy expenditure (REE) in patients with type 2 diabetes mellitus (T2DM) after laparoscopic cholecystectomy (LC) and the role in metabolic homeostasis. Methods From December 2019 to December 2021, a total of 77 T2DM patients with gallbladder polyps were included in our study. Among them, 40 patients who underwent LC were enrolled into the cholecystectomy group, and 37 patients who did not undergo LC were enrolled into the control group. Preoperative and 6-months postoperative demographic data, body weight, food intake, effects on diabetes control, and biomedical variables were recorded and compared. Results The mean level of total bile acids (TBA) was higher than that in the control group (P = 0.033) and increased significantly after LC compared to baseline (P = 0.029). The REE level in the cholecystectomy group was higher than that in the control group (P = 0.032) and increased compared to the baseline (P = 0.011). The utilization of carbohydrates increased significantly after LC (P

BackgroundIntracorporeal anastomosis (IA) is a difficult but popular anastomotic approach for reconstruction of digestive tract after laparoscopic right hemicolectomy, which may reduce some limitations faced during extracorporeal anastomosis (EA).MethodsA retrospective review of 78 patients who underwent laparoscopic right hemicolectomy by a veteran surgeon in a high-volume public tertiary hospital, including 50 patients with IA and 28 patients with EA. The intraoperative-related factors and short-term results of the two anastomotic approaches were compared.ResultsThere was no significant difference in demographics and clinical characteristics between the two groups (P>0.05). The intraoperative blood loss was less (P=0.010) and the incision length was shorter (P

Executing code containing side-channel vulnerabilities exhibits different non-functional behaviors related to inputs.Attackers can obtain these behaviors by leveraging micro architecture side-channel attacks and then analyze the pattern between the behaviors and the inputs to access sensitive data.Vulnerability repairing at the software layer brings low overheads to a program’s execution.Besides, it does not require modifying hardware or system, which enables fast patching and widespread deployment.It becomes the mainstream strategy applied to the current cryptographic implementations.However, existing solutions are deeply bound to the program’s implementation and requires manual intervention.This brings challenge to implement and is not versatile enough.A general patching method was proposed for side-channel vulnerabilities that combined dynamic obfuscated execution with hardware atomic transaction.To hide the real accesses of the side-channel vulnerabilities of a program, the proposed method inserted dynamic confusing accesses into the vulnerabilities.To avoid an attacker using fine-grained side-channel attack to distinguish the real access and the confusing access, both of them were encapsulated as transactions and they were guaranteed to be uninterrupted during the running period.In addition, a prototype system called SC-Patcher was implemented based on the LLVM compiler.Various optimization strategies were supported, including secure springboard and transaction aggregation, to further improve system security and performance.Experimental results show that the proposed method makes it impossible for an attacker to restore accurate sensitive data through side-channel attack, and it also brings almost no additional performance overhead to the program.

Text classification is a machine learning technique employed to assign a given text to predefined categories, facilitating the automatic analysis and processing of textual data. However, an important problem is that the number of new text categories is growing faster than that of human annotation data, which makes many new categories of text data lack a lot of annotation data. As a result, the conventional deep neural network is forced to over-fit, which damages the application in the real world. As a solution to this problem, academics recommend addressing data scarcity through few-shot learning. One of the efficient methods is prompt-tuning, which transforms the input text into a mask prediction problem featuring [MASK]. By utilizing descriptors, the model maps output words to labels, enabling accurate prediction. Nevertheless, the previous prompt-based adaption approaches often relied on manually produced verbalizers or a single label to represent the entire label vocabulary, which makes the mapping granularity low, resulting in words not being accurately mapped to their label. To address these issues, we propose to enhance the verbalizer and construct the refined external knowledge into a prompt-tuning (REKP) model. We employ the external knowledge bases to increase the mapping space of tagged terms and design three refinement methods to remove noise data. We conduct comprehensive experiments on four benchmark datasets, namely AG’s News, Yahoo, IMDB, and Amazon. The results demonstrate that REKP can outperform the state-of-the-art baselines in terms of Micro-F1 on knowledge-enhanced text classification. In addition, we conduct an ablation study to ascertain the functionality of each module in our model, revealing that the refinement module significantly contributes to enhancing classification accuracy.

This paper proposes a distributed coordination scheme for connected vehicles, including automated vehicles (AVs) and manual vehicles (MVs), at signal-free intersections. The cooperation issue of vehicles at an intersection is formulated into a multi-objective optimization problem that aims to eliminate conflicts and improve traffic mobility and fuel economy. For this purpose, the future trajectories of AVs and MVs are predicted by the respective car-following models, and are shared with neighboring vehicles in conflict relationships. The proposed scheme optimizes the sum of the performance of AVs within the cooperative zone in a prediction horizon. A distributed optimization algorithm in the receding horizon is presented to obtain the local optimal solutions, and is tested in simulations with different demand levels and penetration rates of AVs. The results show that the proposed scheme reduces travel time by 29.7–45.5% and 34.5–49.2%, and decreases fuel consumption by 27.6–35.3% and 21.6–29.9% under 70–100% penetration rates of AVs, compared to the no-control operation and fixed-time signal control strategy. In addition, a comparison simulation with the strategy of jointly optimizing the vehicle trajectory and signal timing is conducted to evaluate the relative merits of the proposed scheme.

Purpose: To characterize the magnetic resonance imaging features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). Materials and Methods: Thirty-four patients with 38 histologically confirmed LELCCs were enrolled retrospectively from January 2014 to August 2022. We evaluated the clinical features, histologic findings, and imaging manifestations on dynamic enhanced MRI. Results: 74% (25/34) of the cases were associated with EBV infection. Moreover, patients infected with EBV exhibited a lower level of Ki-67 proliferation. The serum CA199 level was elevated in 10 patients. The median tumor diameter was 2.8 cm (range, 1.1–8.7 cm). Most tumors were well-defined with a smooth or lobulated margin and showed peripheral hyperintensity and central hypointensity on T2-weighted imaging (T2WI). T2 hyperintense foci were recognized in 8 patients. In the dynamic enhanced MRI, 21 tumors demonstrated Type A enhancement pattern (rim enhancement), 10 demonstrated Type B (rapid wash-in and wash-out), and seven demonstrated Type C (rapid wash-in without wash-out). Capsular enhancement in PVP or DP was found in 22 tumors. A few patients had satellite lesions, portal vein thrombosis, bile duct dilatation, and distal metastasis. Lymph node metastases were discovered pathologically in 11 patients. Conclusions: MRI findings of LELCC vary and are non-specific. While a majority of LELCCs exhibit typical features of intrahepatic cholangiocarcinoma (iCCA), unique findings like T2 hyperintense foci or capsular enhancement could suggest LELCC. EBV infection and elevated tumor markers can aid in differentiation. However, given the mimics of some cases of liver hypervascular lesions, histological examination remains essential for definitive diagnosis.

In this study, a refined numerical model for segmental lining of a shield tunnel, which contains detailed models of reinforcement and connecting bolts, is established using finite element software. The model is first validated by the results from a full-scale model test. Then, based on the load-structure method, this numerical model is adopted to investigate the internal force distribution and the transverse deformation characteristics of the shield tunnel when it is subject to local soil loosening. The influence of loosening position, loosening range, and loosening extent on the mechanical response is extensively studied through comprehensive numerical analyses. The results show that the main influence of local soil loosening on the ring is to disturb the force balance and change the constraint conditions, thus changing the deformation pattern and force state. After the loosening occurs, the bending moment of the ring in the loosening range increases and the axial force decreases. The vertical convergence of the ring is the largest and the equivalent stiffness of the ring is the smallest when the local soil loosened at the haunch and the loosening range α is 90°. The vertical convergence of the ring increases with increasing of the loosening extent, and the equivalent stiffness decreases linearly with increasing of the loosening extent. The results can enhance our understanding of mechanical behaviors of segmental lining associated soil loosening, and will show a possible way for detecting soil loosening based on the measured deformation and internal forces.

Abstract Background Tumor-associated macrophages (TAMs) are closely related to unfavorable prognosis of patients with clear cell renal cell carcinoma (ccRCC). However, the important molecules in the interaction between ccRCC and TAMs are unclear. Methods TCGA-KIRC gene expression data of tumor tissues and normal tissues adjacent to tumor were compared to identify differentially expressed genes in ccRCC. TAMs related genes were discovered by analyzing the correlation between these differentially expressed genes and common macrophage biomarkers. Gene set enrichment analysis was performed to predict functions of TAMs related gene. The findings were further validated using RNA sequencing data obtained from the CheckMate 025 study and immunohistochemical analysis of samples from 350 patients with ccRCC. Kaplan–Meier survival curve, Cox regression analysis and Harrell’s concordance index analysis were used to determine the prognostic significance. Results In this study, we applied bioinformatic analysis to explore TAMs related differentially expressed genes in ccRCC and identified 5 genes strongly correlated with all selected macrophage biomarkers: STAC3, LGALS9, TREM2, FCER1G, and PILRA. Among them, FCER1G was abundantly expressed in tumor tissues and showed prognostic importance in patients with ccRCC who received treatment with Nivolumab; however, it did not exhibit prognostic value in those treated with Everolimus. We also discovered that high expression levels of FCER1G are related to T cell suppression. Moreover, combination of FCER1G and macrophage biomarker CD68 can improve the prognostic stratification of patients with ccRCC from TCGA-KIRC. Based on the immunohistochemical analysis of samples from patients with ccRCC, we further validated that FCER1G and CD68 are both highly expressed in tumor tissue and correlate with each other. Higher expression of CD68 or FCER1G in ccRCC tissue indicates shorter overall survival and progression-free survival; patients with high expression of both CD68 and FCER1G have the worst outcome. Combining CD68 and FCER1G facilitates the screening of patients with a worse prognosis from the same TNM stage group. Conclusions High expression of FCER1G in ccRCC is closely related to TAMs infiltration and suppression of T cell activation and proliferation. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC.

Torreya grandis is a characteristic rare economic tree species in subtropical mountainous areas. The kernels of T. grandis have rich content of organic acids, and malate is the predominant organic acid in T. grandis kernels. However, the contents, biosynthesis/metabolism pathway and transcriptional regulation of malate in developing T. grandis kernels remain completely unknown. Here, the organic acid composition in developing T. grandis kernels was first analyzed. The results showed that the content of malate was increased during the maturation T. grandis kernels. A malate synthase (TgMLS) gene might be involved in the accumulation of malate based on transcriptome data, gene expression and enzyme activity analysis. Transient expression of TgMLS in tobacco resulted in the high malate synthase activity and malate content. Furthermore, a basic helix-loop-helix transcription factor (bHLH), TgbHLH87 was identified to positively regulate the TgMLS expression via directly binding the TgMLS promoter. Our finding contributes to mechanism underlying malate accumulation in T. grandis kernels.

Ginseng is an international herb that has been used for thousands of years. Two species most commonly applied and investigated in the ginseng family are Asian ginseng and American ginseng. The number of randomized controlled clinical trials (RCTs) has conspicuously increased, driven by the rapid development of ginseng. However, the reporting of RCT items of ginseng is deficient because of different trial designs and reporting formats, which is a challenge for researchers who are looking for the data with high quality and reliability. Thus, this study focused on providing an extensive analysis of these two species and examined the quality of the RCTs, based on the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ninety-one RCTs conducted from 1980 to 2019 that were related to Asian ginseng and American ginseng used singly met our inclusion criteria. We found that the reporting quality of the two species has improved during the past 40 years. Publication date and sample size were significantly associated with the reporting quality. Rigorous RCTs designed for the species of ginseng are warranted, which can shed light on product research and development of ginseng in the future.

Abstract Background Intestinal pseudo-obstruction (IPO) accompanied by hepatobiliary dilatation and ureterohydronephrosis is extremely rare in systemic lupus erythematosus (SLE). This triad is also called visceral muscle dysmotility syndrome (VMDS). Only 9 cases have been reported in the literature. Here, we report a rare case of VMDS with mechanical intestinal obstruction that was clinically relieved by surgery. Case presentation This report refers to a 31-year-old woman with SLE and gastrointestinal symptoms presented as abdominal pain, nausea and stoppage of the passage of flatus or stool without obvious reasons. The patient suffered from severe abdominal distension because of massive flatulence. Contrast-enhanced computed tomography (CT) of the abdomen performed in our hospital showed localized stenosis of the bowel, ureterohydronephrosis, and biliary tract dilatation. Endoscopy showed a stenotic segment located in the sigmoid colon. The colon biopsy samples suggested that the stenosis was caused by inflammatory tissues. Biochemical investigations showed hypoalbuminemia, electrolyte disturbance and decreased C3. Antinuclear antibody was positive. After careful assessment, transverse colostomy was performed for this patient. Gastrointestinal symptoms were clinically relieved after the surgery. Conclusion To the best of our knowledge, no VMDS patients have presented with mechanical ileus before. This case is the first documented occurrence of SLE with VMDS and mechanical intestinal obstruction symptoms relieved by surgery. Due to the low incidence of this condition, no standard treatment regimen has been established. However, surgical treatment offers significant benefit in specific situations.