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Shigella is one of the main food-borne pathogens, and its low infectious dose and serious hazard have attracted people's attention. Therefore, it is essential to develop rapid, sensitive and efficient methods for the detection of Shigella and to ensure food quality and safety. Methods for detecting Shigella can be divided into three categories: traditional culture methods, immunological methods and molecular biology methods. Many studies have made various improvements in order to make the detection technology more practical in sample detection. This article reviews recent methods for the detection of Shigella, including improved traditional methods, immunological methods, molecular biology methods, as well as new and emerging detection methods. The application scope and progress of these methods are highlighted to provide a reference for the selection of detection methods for Shigella.

Abstract Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p

This paper develops a multisensor data fusion-based deep learning algorithm to locate and classify faults in a leader-following multiagent system. First, sequences of one-dimensional data collected from multiple sensors of followers are fused into a two-dimensional image. Then, the image is employed to train a convolution neural network with a batch normalisation layer. The trained network can locate and classify three typical fault types: the actuator limitation fault, the sensor failure and the communication failure. Moreover, faults can exist in both leaders and followers, and the faults in leaders can be identified through data from followers, indicating that the developed deep learning fault diagnosis is distributed. The effectiveness of the deep learning-based fault diagnosis algorithm is demonstrated via Quanser Servo 2 rotating inverted pendulums with a leader-follower protocol. From the experimental results, the fault classification accuracy can reach 98.9%.

Sustainability and environmental consciousness directed attention toward research and innovation in the field of natural fiber composites. Baobab (Adansonia digitata L.) is tropical tree of the silk-cotton family that is native to Africa. The aim of this study is to pore over the use of baobab bast fibers as potential reinforcement in polymer composites. The baobab bast fibers were extracted from the bark of baobab tree in Sudan. Fibers were investigated by chemical analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and single fiber tensile test. Further, the density and relative humidity of fibers were determined.The cellulose, hemicellulose, lignin, ash, and moisture contents present in the fiber are 60.70%, 21.98%, 5.91%, 5.32%, 13%, respectively. The fiber has a density of 1.1041 g/cm3. FTIR spectra for cellulose and nanocellulose confirms absorption bands characteristic of pure celluloses at 3330, 2919, 1640, 1028. Scanning electron micrographs showed roughening of the fiber surface and crack-like lines indicate fiber clusters being held together. The baobab fiber possessed a crystallinity index of 48.01% with thermal stability up to 250°C. The results revealed that baobab fiber can be utilized as reinforcement in polymer composites.

Due to the diversity and variability of Chinese syntax and semantics, accurately identifying and distinguishing individual emotions from online texts is challenging. To overcome this limitation, we incorporate a new source of individual sentiment, emojis, which contain thousands of graphic symbols and are increasingly being used for expressing emotion in online conversations. We examined popular sentiment analysis algorithms, including rule-based and classification algorithms, to evaluate the impact of supplementing emojis as additional features to improve the algorithm performance. Emojis were also translated into corresponding sentiment words when constructing features for comparison with those directly generated from emoji label words. In addition, considering different functions of emojis in texts, we classified all posts in the dataset by their emoji usage and examined the changes in algorithm performance. We found that emojis are effective as expanding features for improving the accuracy of sentiment analysis algorithms, and the algorithm performance can be further increased by taking different emoji usages into consideration. In this study, we developed an improved emoji-embedding model based on Bi-LSTM (namely, CEmo-LSTM), which achieves the highest accuracy (around 0.95) when analyzing online Chinese texts. We applied the CEmo-LSTM algorithm to a large dataset collected from Weibo from December 1, 2019 to March 20, 2020 to understand the sentiment evolution of online users during the COVID-19 pandemic. We found that the pandemic remarkably impacted individual sentiments and caused more passive emotions (e.g., horror and sadness). Our novel emoji-embedding algorithm creatively combined emojis as well as emoji usage with the sentiment analysis model and can handle emotion mining tasks more effectively and efficiently.

Abstract Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a Ca2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating Ca2+ influx and phosphorylation of phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1–Ca2+–PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.

Immunochromatographic assay (ICA) plays an important role in in vitro diagnostics because of its simpleness, convenience, fastness, sensitivity, accuracy, and low cost. The employment of magnetic nanoparticles (MNPs), possessing both excellent optical properties and magnetic separation functions, can effectively promote the performances of ICA. In this study, an ICA based on MNPs (MNP–ICA) has been successfully developed for the sensitive detection of carcinoembryonic antigen (CEA). The magnetic probes were prepared by covalently conjugating carboxylated MNPs with the specific monoclonal antibody against CEA, which were not only employed to enrich and extract CEA from serum samples under an external magnetic field but also used as a signal output with its inherent optical property. Under the optimal parameters, the limit of detection (LOD) for qualitative detection with naked eyes was 1.0 ng/mL, and the quantitative detection could be realized with the help of a portable optical reader, indicating that the ratio of optical signal intensity correlated well with CEA concentration ranging from 1.0 ng/mL to 64.0 ng/mL (R2 = 0.9997). Additionally, method comparison demonstrated that the magnetic probes were beneficial for sensitivity improvement due to the matrix effect reduction after magnetic separation, and the MNP–ICA is eight times higher sensitive than ICA based on colloidal gold nanoparticles. The developed MNP–ICA will provide sensitive, convenient, and efficient technical support for biomarkers rapid screening in cancer diagnosis and prognosis.

Twisted graphene multilayers are highly tunable flatband systems for developing new phases of matter. Thus far, while orbital ferromagnetism has been observed in valley-polarized phases, the long-range orders of other correlated phases as well as the quantum phase transitions between different orders mostly remain unknown. Here, we report an observation of Coulomb-interaction-driven first-order quantum phase transitions and ferromagnetism in twisted double bilayer graphene (TDBG). At zero magnetic field, the transitions are revealed in a series of steplike abrupt resistance jumps with a prominent hysteresis loop when either the displacement field (D) or the carrier density (n) is tuned across a symmetry-breaking boundary near half filling, indicating a formation of ordered domains. It is worth noting that the good tunability and switching of these states give rise to a memory performance with a large on/off ratio. Moreover, when both spin and valley play the roles at finite magnetic field, we observe abundant first-order quantum phase transitions among normal metallic states from the charge-neutral point, orbital ferromagnetic states from quarter filling, and spin-polarized states from half filling. We interpret these first-order phase transitions in the picture of phase separations and spin-domain percolations driven by multifield tunable Coulomb interactions, in agreement with the Lifshitz transition and the Hartree-Fock calculations. The observed multifield tunable domain structure and its hysteresis resembles the characteristics of multiferroics, revealing intriguing magnetoelectric properties. Our result enriches the correlated phase diagram in TDBG for discovering novel exotic phases and quantum phase transitions, and it will benefit other twisted moiré systems as well.

The healthy growth of infants during early life is associated with lifelong consequences. Breastfeeding has positive impacts on reducing obesity risk, which is likely due to the varied components of breast milk, such as N-acetylneuraminic acid (Neu5Ac). However, the effect of breast milk Neu5Ac on infant growth has not been well studied. In this study, targeted metabolomic and metagenomic analyses were performed to illustrate the association between breast milk Neu5Ac and infant growth. Results demonstrated that Neu5Ac was significantly abundant in breast milk from infants with low obesity risk in two independent Chinese cohorts. Neu5Ac from breast milk altered infant gut microbiota and bile acid metabolism, resulting in a distinct fecal bile acid profile in the high-Neu5Ac group, which was characterized by reduced levels of primary bile acids and elevated levels of secondary bile acids. Taurodeoxycholic acid 3-sulfate and taurochenodeoxycholic acid 3-sulfate were correlated with high breast milk Neu5Ac and low obesity risk in infants, and their associations with healthy growth were reproduced in mice colonized with infant-derived microbiota. Parabacteroides might be linked to bile acid metabolism and act as a mediator between Neu5Ac and infant growth. These results showed the gut microbiota-dependent crosstalk between breast milk Neu5Ac and infant growth.

The prediction of high-speed traffic flow around the city is affected by multiple factors, which have certain particularity and difficulty. This study devised an asymmetric Bayesian optimization extreme gradient boosting (BO-XGBoost) model based on Bayesian optimization for the spatiotemporal and multigranularity prediction of high-speed traffic flow around a city. First, a traffic flow dataset for a ring expressway was constructed, and the data features were processed based on the original data. The data were then visualized, and their spatiotemporal distribution exhibited characteristics such as randomness, continuity, periodicity, and rising fluctuations. Secondly, a feature matrix was constructed monthly for the dataset, and the BO-XGBoost model was used for traffic flow prediction. The proposed model BO-XGBoost was compared with the symmetric model bidirectional long short-term memory and integrated models (random forest, extreme gradient boosting, and categorical boosting) that directly input temporal data. The R-squared (R2) of the BO XGBoost model for predicting TF and PCU reached 0.90 and 0.87, respectively, with an average absolute percentage error of 2.88% and 3.12%, respectively. Thus, the proposed model achieved an accurate prediction of high-speed traffic flow around the province, providing a theoretical basis and data support for the development of central-city planning.

Understanding of the potential leaching of plastic particles, particularly nanoplastics (NPs), from food packaging is crucial in assessing the safety of the packaging materials. Therefore, the objective of this study was to investigate potential exposure risks by simulating the release of NPs from various plastic packaging materials, including polypropylene (PP), general casting polypropylene (GCPP) or metalized casting polypropylene (MCPP), polyethylene (PE), polyethylene terephthalate (PET), and polyphenylene sulfone (PPSU), under corresponding food consumption scenarios. Surface-enhanced Raman scattering (SERS) and scanning electron microscopy (SEM) were utilized to identify and characterize the NPs leached from plastic packaging. The presence of separated NPs was observed in PP groups subjected to 100 °C hot water, GCPP plastic sterilized at a high temperature (121 °C), and PE plastic soaked in 100 °C hot water, exhibited a distorted morphology and susceptibility to aggregation. The findings suggest that the frequent consumption of takeaway food, hot beverages served in disposable paper cups, and foods packaged with GCPP materials may elevate the risk of ingestion of NPs. This reminds us that food packaging can serve as an important avenue for human exposure to NPs, and the results can offer valuable insights for food safety management and the development of food packaging materials.

The traditional centralized power trading model suffers from high maintenance costs, low processing efficiency and unsynchronized information, and it cannot adapt to the high-frequency and small-dollar distributed energy trading scenario. To address the above issues, we propose Trust-DETM, a model for the implementation of distributed energy trading based on a trusted execution environment. First, we introduce a reputation metric mechanism and propose a transaction matching algorithm based on the reputation metric to achieve the accurate matching of transaction objects. Secondly, as the distributed energy trading model lacks an effective trust mechanism, we propose a commitment scheme based on smart contracts and a trusted execution environment to solve the trust problem between producers and consumers. Finally, we conduct a comprehensive experimental evaluation of the efficiency of Trust-DETM. Through comparative experiments, we find that Trust-DETM achieves trade matching and trusted execution in a lower simultaneous running time than comparable distributed trading models.

Abstract Heterotopic ossification (HO) represents a common problem after tendon injury with no effective treatment yet being developed. Tenomodulin (Tnmd), the best-known mature marker for tendon lineage cells, has important effects in tendon tissue aging and function. We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd −/− ) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd − /− tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd −/− tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd −/ − tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd −/− tendons and this, together with augmented HO, resulted in diminished running capacity of Tnmd −/− mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.

Abstract Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

TiAl alloys are difficult to obtain high density through traditional pressing and sintering process. Sn is a promising liquid-phase sintering addition for TiAl alloys; however, the further studies have elaborated that the liquid phase sintering of Sn is limited due to poor wettability between TiAl and melt Sn. Based on it, this study adopts Sn–Al powder addition instead of pure Sn powder. The results describe that a small amount of active Al enhanced the wettability of the Sn droplets to the TiAl matrix, thereby further promoting the liquid phase sintering effect of the addition of Sn. The sample sintered at 1320–1350 °C has a density excess of 95%, near γ or duplex microstructure with small proportion of lamellar colonies. Through subsequent non-encapsulation HIP, the fine-grained structure is maintained at the same time to reach full density, which enables the as-sintered samples to obtain moderate tensile properties at room temperatures (UST = 520 ± 5 MPa, YS = 401 ± 7 MPa, EL = 1.33 ± 0.1).

Abstract. Background:. Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. Methods:. Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log–log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. Results:. The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by −54.81% (interquartile range, −65.50% to −43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%–0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. Conclusions:. Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.

While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (P ​< 0.01) to 0.86 (P ​< 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC.

Vaccination is one of the most vigorous ways to intervene in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cases of autoimmune hepatitis (AIH) after coronavirus disease (COVID-19) vaccination have been increasingly reported. Twenty-seven cases of AIH are summarized in this study, providing emerging evidence of autoimmune reactions in response to various COVID-19 vaccines, including in patients with special disease backgrounds such as primary sclerosing cholangitis (PSC), liver transplantation, and previous hepatitis C virus (HCV) treatment. Molecular mimicry, adjuvants, epitope spreading, bystander activation, X chromosome, and sceptical hepatotropism of SARS-CoV-2 may account for, to some extent, such autoimmune phenomena. Immunosuppressive corticosteroids perform well with or without azathioprine in such post-COVID-19-vaccination AIH. However, determination of the exact mechanism and establishment of causality require further confirmation.

The heat transfer characteristics of the wall formed by the aluminum extrusion and multi insulation material layers are studied experimentally and numerically. The experimental results show that the equivalent thermal conductivity of the wall does not depend on the temperature difference and its position regarding to the gravity direction. These results indicate that the roles of the natural convection and the radiation heat transfer in the aluminum extrusion are very weak, which are confirmed by the numerical results. The numerical results show that the aluminum extrusion formed by the aluminum tape with thickness less than 5% of the wall thickness transfers more than 99% of the total heat transferred through the combined layer. As resulting, a more uniform temperature distribution is obtained on the surface in contact with the air in the aluminum extrusion. The results suggest that the natural convection and heat radiation in the combined layer can be safely ignored.

Most of the leakage faults in hydraulic pipeline systems occur in the pipe joint. The research on the high-pressure sealing and reliability of the pipe joint is very important in the application of civil aircraft parts. On the basis of studying the characteristics of pressure pulsating fluid, this paper explores the influence of a high pressure pulsating fluid on the sealing performance of flameless extruded pipe joints and analyzes the influence of the internal fluid pulsating amplitude and fluid under different pressures on the contact stress distribution of the sealing surface of the pipe joint. The results show that with the increase in flow pulsation amplitude from 0.5% to 5%, the amplitude of contact stress on the sealing surface decreases with creep time, which makes the sealing performance better. However, the effective working time of the joint as a whole decreases from 2000 to 194 h. The high-stress area of the contact surface expands as the fluid pressure increases, and the high internal fluid pressure obviously improves the sealing effectiveness and reliability of the pipe joint. In addition, the influence of fluid pulsation amplitude on the leakage rate of the joint is much greater than that of the fluid pressure.

Response resistance to the immune checkpoint blockade (ICB) immunotherapy remains a major clinical challenge that may be overcome through the rational combination of ICB and specific targeted therapeutics. One emerging combination strategy is based on sensitizing ICB-refractory tumors with antagonists of 90kD heat shock protein (Hsp90) that target all four isoforms. However, pan-Hsp90 inhibitors are limited by the modest efficacy, on-target and off-tumor toxicities, and induction of the heat shock response (HSR) that overrides the effect of Hsp90 inhibition. Recently, we developed Hsp90β-selective inhibitors that were cytotoxic to cancer cells but did not induce HSR in vitro. Here, we report that the Hsp90β inhibitor NDNB1182 downregulated CDK4 (an Hsp90β-dependent client protein) and induced the expression of endogenous retroviral elements and interferon-stimulated genes. In syngeneic mouse models of prostate cancer and breast cancer, NDNB1182 significantly augmented the efficacy of ICB therapy. Furthermore, NDNB1182 showed superior tolerability to the pan-Hsp90 inhibitor Ganetespib in mice. Our findings provide evidence that Hsp90β inhibition is a potentially effective and safe regimen to combine with ICB to treat immunotherapy-refractory solid tumors.

BackgroundPostpartum hemorrhage (PPH) is one of the leading causes of maternal mortality. Promptly recovering blood loss is critical for PPH. Intraoperative cell salvage (ICS) is a method to collect and process red blood cells (RBCs) from the blood lost during surgery and transfuse them to the patient’s circulation during or immediately after surgery. Its effectiveness in reducing the demand for allogeneic blood transfusion has been proven, but its effectiveness and safety as a sole treatment for PPH during Cesarean sections are unclear. This is particularly important for patients who cannot or do not want to accept allogeneic blood transfusion.Materials and methodsIn this prospective randomized controlled study, patients with high risks of PPH were randomized into the ICS group or the control group, receiving ICS or allogeneic RBC transfusion if their hemoglobin level was less than 80 g/L during operation. Data collected include clinical examination, blood cell count, hemoglobin level, coagulation function, and plasma levels of fetal hemoglobin, tissue factor, and alpha-fetoprotein before and after fetal delivery and 0, 2, and 12 h after treatment. Adverse events were recorded.ResultsA total of 130 patients were enrolled, aged 33 ± 1 years with a mean gestation period of 37 ± 1 week. The most common cause of Cesarean section was placenta previa, followed by twin pregnancy, scarred uterus, preeclampsia, placental abruption, fetal distress, and placenta accreta spectrum. Bleeding amount was similar between the two groups. The ICS group, compared to controls, had more efficient increases in levels of hemoglobin, RBC, and hematocrit (all p < 0.05). Coagulation function was maintained in the ICS group but reduced in controls 24 h after transfusion, indicated by significantly reduced fibrinogen level and prolonged prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (aPTT) (all p < 0.05). There was a transient but significant decrease in plasma tissue factor and alpha-fetoprotein levels and an increase in plasma fetal hemoglobin level with ICS treatment in the postpartum period. No adverse event occurred with ICS intervention.ConclusionICS is an effective and safe intervention for patients with a high risk of PPH during elective or emergency Cesarean section. It can effectively clear tissue factors and alpha-fetoprotein but not fetal hemoglobin.

IntroductionParathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most common target organ for distant metastases of PC, but no guidelines are available for the diagnosis and treatment of liver metastases. In this study, we attempted to summarize the characteristics of the diagnosis and treatment of liver metastases based on our patients and other cases reported in the literature.Materials and methodsThe files of all patients diagnosed with PC with liver metastases summarized at our center between 2000 and 2022 were reviewed, and three datasets from Medline, Web of Science, and Embase were systematically searched to identify relevant articles.ResultsThree patients with liver metastases from our center and 11 patients from the literature were included in the study. All patients had pHPT with borderline remission of hypercalcemia after each operation. A total of 71.4% of the patients’ liver lesions were found by abdominal CT scans, while 35.7% were found by MRI, PET-CT, and fine-needle aspiration biopsy (FNAB), which were also helpful for diagnosis. Eight of nine patients (88.9%) who underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial embolization (TAE) were alive, and only one postoperative patient died after a follow-up of 60 months.ConclusionsPC is a rare malignant tumor prone to recurrence and metastasis, and postoperative reviews should be carried out routinely. Abnormally elevated parathyroid hormone (PTH) and serum calcium can indicate recurrence or metastasis. Enhanced CT and MRI can provide valuable support for the diagnosis of liver metastases, but whether [18F]FDG-PET-CT, [18F]FCH-PET-CT, or [11C]choline-PET-CT can be used as a diagnostic basis requires further study. Resection of liver metastases, segmental hepatectomy, or RFA can significantly improve patients’ symptoms.

Carboxyl compounds have a significant influence on the flavor of Chinese Baijiu. However, because of the structural diversity and low concentration, the deep profiling of carboxyl compounds in Chinese Baijiu is still challenging. In this work, a systematic method for comprehensive analysis of carboxyl compounds in Chinese Baijiu was established. After derivatized under optimized conditions, 197 p-dimethylaminophenacyl bromide-derived carboxylic compounds were annotated by multidimensional information including accurate mass, predicted tR, in-silico MS/MS, and diagnostic ions for the first time. In addition, 48 of the 197 carboxyl compounds were positively identified, and three of them were newly identified in Chinese Baijiu. Moreover, we found the number and the concentration of carboxyl compounds in sauce-flavor Baijiu were more abundant than in strong-flavor Baijiu. This work provides a novel method for the analysis of carboxyl compounds in Baijiu and other complex samples.

Strategy evaluation and optimization in response to troubling urban issues has become a challenging issue due to increasing social uncertainty, unreliable predictions, and poor decision-making. To address this problem, we propose a universal computational experiment framework with a fine-grained artificial society that is integrated with data-based models. The purpose of the framework is to evaluate the consequences of various combinations of strategies geared towards reaching a Pareto optimum with regards to efficacy versus costs. As an example, by modeling coronavirus 2019 mitigation, we show that Pareto frontier nations could achieve better economic growth and more effective epidemic control through the analysis of real-world data. Our work suggests that a nation’s intervention strategy could be optimized based on the measures adopted by Pareto frontier nations through large-scale computational experiments. Our solution has been validated for epidemic control, and it can be generalized to other urban issues as well.

Phthalates are a class of environmental endocrine disruptors. Previous studies have demonstrated that phthalate exposure can affect thyroid function; however, limited studies have assessed the associations between phthalate exposure and thyroid function, especially thyroid autoimmunity in pregnant women during the first trimester. We recruited participants from a cohort of pregnant women in Beijing, China, and collected urine samples to measure ten phthalate metabolites, serum samples to measure free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) during the first trimester. We included 325 pregnant women without thyroid diseases or dysfunction in this study. Associations between phthalate metabolites and thyroid function parameters were assessed with the Bayesian kernel machine regression (BKMR) model, multiple linear regression model, and restricted cubic spline. In the BKMR model analysis, compared to the 50th percentile, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels when phthalate metabolites were at or below the 40th percentile. Stratifying by body mass index, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels in normal weight women when phthalate metabolites were at or below the 45th percentile. However, total urinary phthalate metabolites levels were positively associated with serum TPOAb levels in underweight women when phthalate metabolites were at or below the 30th percentile. In restricted cubic spline analysis, L-shaped nonlinear associations of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), di-(2-ethylhexyl) phthalate (ΣDEHP), and inverted S-shaped nonlinear association of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with TPOAb were observed. In conclusion, our findings suggest that phthalate exposure may affect thyroid autoimmunity in underweight pregnant women during early pregnancy, and the potential effects of phthalate exposure on thyroid autoimmunity may be nonlinear.

Supraglacial lakes and rivers dominate the storage and transport of meltwater on the southwest Greenland Ice Sheet (GrIS) surface. Despite functioning as interconnected hydrologic networks, supraglacial lakes and rivers are commonly studied as independent features, resulting in an incomplete understanding of their collective impact on meltwater storage and routing. We use Landsat 8 satellite imagery to assess the seasonal evolution of supraglacial lakes and rivers on the southwest GrIS during the 2015 melt season. Remotely sensed meltwater areas and volumes are compared with surface runoff simulations from three climate models (MERRA-2, MAR 3.6 and RACMO 2.3), and with in situ observations of proglacial discharge in the Watson River. We find: (1) at elevations >1600 m, 21% of supraglacial lakes and 28% of supraglacial rivers drain into moulins, signifying the presence of high-elevation surface-to-bed meltwater connections even during a colder-than-average melt season; (2) while supraglacial lakes dominate instantaneous surface meltwater storage, supraglacial rivers dominate total surface meltwater area and discharge; (3) the combined surface area of supraglacial lakes and rivers is strongly correlated with modeled surface runoff; and (4) of the three models examined here, MERRA-2 runoff yields the highest overall correlation with observed proglacial discharge in the Watson River.

Abstract Background Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. Methods The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. Results Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. Conclusions The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.

Patients with rheumatoid arthritis are commonly stratified by ACPA serology, with positivity being associated with more severe disease and joint destruction. Here the authors present a single cell RNA sequencing resource comparing peripheral blood and synovial tissue cells from patients with ACPA+ versus ACPA- rheumatoid arthritis.

The progression from biliary tract intraepithelial neoplasia (BilIN) to gallbladder carcinoma (GBC) remains unclear. Here the authors use genomics to analyze coexisting GBC lesions, low-grade and high-grade BilINs, revealing two distinct evolutionary paths for GBC development.

Here, the authors use mobile telecom data to study communication in family networks after a natural disaster, and find that the structural configuration of families’ social tie sharing predicted their post-disaster communications dynamics.

Climate change affects parasitic plants and their hosts on distributions. However, little is known about how parasites and their hosts shift in distribution, and niche overlap in response to global change remains unclear to date. Here, the potential distribution and habitat suitability of four endangered holoparasites and their primary hosts in northern China were predicted using MaxEnt based on occurrence records and bioclimatic variables. The results indicated that (1) Temperature annual range (Bio7) and Precipitation of driest quarter (Bio17) were identified as the common key climatic factors influencing distribution (percentage contribution > 10%) for Cynomorium songaricum vs. Nitraria sibirica (i.e., parasite vs. host); Temperature seasonality (Bio4) and Precipitation of driest month (Bio14) for Boschniakia rossica vs. Alnus mandshurica; Bio4 for Cistanche deserticola vs. Haloxylon ammodendron; Precipitation of warmest quarter (Bio18) for Cistanche mongolica vs. Tamarix ramosissima. Accordingly, different parasite-host pairs share to varying degree the common climatic factors. (2) Currently, these holoparasites had small suitable habitats (i.e., moderately and highly) (0.97–3.77%), with few highly suitable habitats (0.19–0.81%). Under future scenarios, their suitable habitats would change to some extent; their distribution shifts fell into two categories: growing type (Boschniakia rossica and Cistanche mongolica) and fluctuating type (Cynomorium songaricum and Cistanche deserticola). In contrast, the hosts’ current suitable habitats (1.42–13.43%) varied greatly, with highly restricted suitable habitats (0.18–1.00%). Under future scenarios, their suitable habitats presented different trends: growing type (Nitraria sibirica), declining type (Haloxylon ammodendron) and fluctuating type (the other hosts). (3) The niche overlaps between parasites and hosts differed significantly in the future, which can be grouped into two categories: growing type (Boschniakia rossica vs. Alnus mandshurica, Cistanche mongolica vs. Tamarix ramosissima), and fluctuating type (the others). Such niche overlap asynchronies may result in severe spatial limitations of parasites under future climate conditions. Our findings indicate that climate factors restricting parasites and hosts’ distributions, niche overlaps between them, together with parasitic species identity, may jointly influence the suitable habitats of parasitic plants. Therefore, it is necessary to take into account the threatened holoparasites themselves in conjunction with their suitable habitats and the parasite-host association when developing conservation planning in the future.

IntroductionHyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.MethodsClinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle–Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2).ResultsForty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%–15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P 2 (OR = 2.38, P

Abstract Optical response of crystalline solids is to a large extent driven by excitations that promote electrons among individual bands. This allows one to apply optical and magneto‐optical methods to determine experimentally the energy band gap —a fundamental property crucial to our understanding of any solid—with a great precision. Here it is shown that such conventional methods, applied with great success to many materials in the past, do not work in topological Dirac semimetals with a dispersive nodal line. There, the optically deduced band gap depends on how the magnetic field is oriented with respect to the crystal axes. Such highly unusual behavior is explained in terms of band‐gap renormalization driven by Lorentz boosts which results from the Lorentz‐covariant form of the Dirac Hamiltonian relevant for the nodal line at low energies.

It has been reported that DNA-Organic hybrid amphiphiles in aqueous solution could self-assemble into various morphologies including micelles, fibers and vesicles, where the hydrophobic parts intend to aggregate to avoid touching with water and the hydrophilic DNA are exposed at the shell. The regulation of their self-assembling morphologies and sizes usually needs to change the molecular inner structure, or assembling conditions and methods. Hence, it is a huge challenging to obtain aggregate with single variable of morphology or size. Inspired by the diversity of cell membrane morphologies in living organisms, a novel Frame-Guided Assembly (FGA) strategy is firstly proposed. The amphiphiles are guided to assemble along the leading hydrophobic groups (LHGs) anchored on the frame and finally form morphologies with certain shape and uniform size in accordance with the predesigned frame. It has been successfully applied to direct self-assembly behaviors of amphiphiles, including DNA and Dendron hybrids, DNA and Polymer hybrids and small molecules lipids. This strategy breaks the limits of traditional assembly method, and makes it possible to prepare aggregates with programmed geometry and size, and lays foundation for the application in the life science and potentially solves the issues of nano assemblies and cellular uptake mechanism.

ABSTRACT When exposed to adverse conditions, many bacterial pathogens, including Vibrio cholerae, can adapt to the environment by entering the viable but nonculturable (VBNC) state. Cells in this state cannot grow on conventional media but still survive. The VBNC state is a significant threat to aquatic safety and public health due to the enhanced ability of the bacteria to remain in the environment and escape from monitoring. Detecting and quantifying VBNC cells and distinguishing them from nonviable cells is necessary for microbiological studies and pathogen monitoring. Cell staining and microscopy are used for the observation of VBNC cells, but it is difficult to quantify VBNC cells accurately. In this study, we developed droplet digital PCR (ddPCR) with a chromosomal single-copy gene as an internal reference combined with Propidium monoazide (PMA) treatment to enumerate VBNC cells of V. cholerae. In this method, bacterial cells, but not extracted chromosomal DNA, were used directly to form oil-enveloped droplets in the ddPCR procedure. One bacterial cell possesses one copy of the chromosome. Thus, enumeration of a single-copy gene on the chromosome can be used to count VBNC cells. ddPCR showed greater accuracy and sensitivity than qPCR. This study showed that the oil-enveloped bacterial method can reduce the number of steps needed and improve the accuracy of VBNC cells quantification and has the potential to be extended to quantify bacterial VBNC cells and assess pathogen survival in the environment. IMPORTANCE The viable but nonculturable (VBNC) state of bacteria represents an important life state for their survival in adverse environments. The VBNC cells of the pathogenic bacteria in the environment and food will be a potential threat to public health because these pathogens cannot be found by the detection of culture. We developed a sensitive molecular method to detect and enumerate the VBNC cells of V. cholerae, which can distinguish the VBNC and dead cells, and count the VBNC cells in the sample without the step of DNA extraction from cells. It can be used to improve the sensitivity of pathogen detection in the surveillance, risk assessment of environment and food contamination, and outbreak warning. The accurate identification and numeration of VBNC cells will also facilitate the microbiological and genetic studies on the development, adaptation, resuscitation, and elimination of the VBNC state.

ObjectiveTo explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody presentation.MethodsWe retrospectively analyzed 1280 consecutive patients with idiopathic inflammatory myopathy (IIM). Individuals with anti-MDA5 and anti-ARS antibodies (anti-MDA5+/ARS+) were compared to anti-MDA5-/ARS+ and anti-MDA5+/ARS- control individuals based on clinical, pulmonary radiological characteristics, treatment, and follow-up information.ResultsSix individuals (0.47%) presented with anti-MDA5+/ARS+; of these, 2 (33.3%) were anti-PL-12+, 2 (33.3%) were anti-Jo-1+, 1 (16.7%) was anti-EJ+, and 1 (16.7%) was anti-PL-7+. Hallmark cutaneous manifestations, including Gottron’s sign (100%), heliotrope rash (50%), mechanic’s hand (66.7%), and skin ulcers (16.7%) were common. Anti-MDA5+/ARS+ patients tended to have higher ferritin levels (p = 0.038) than anti-MDA5-/ARS+ group, and higher CD4+ T-cell counts (p = 0.032) compared to the anti-MDA5+/ARS- group. Radiologically, NSIP with OP overlap was predominant (60%). Consolidation (60%), ground-glass attenuation (GGA) (80%), traction bronchiectasis (80%), and intralobular reticulation (100%) were common in anti-MDA5+/ARS+ individuals. All were diagnosed with ILD and 50% were categorized as RPILD. All patients received glucocorticoids combined with one or more immunosuppressants. Most (83.3%) had a good prognosis following treatment, but there was no difference in the survival rate between the three subgroups.ConclusionPresentation with anti-MDA5+/ARS+ DM was rare. The clinical and radiological characteristics of anti-MDA5+/ARS+ DM combined the features of anti-MDA5+ and anti-ARS+ individuals. Individuals with anti-MDA5+/ARS+ antibodies may respond well to glucocorticoid therapy; glucocorticoids combined with one or more immunosuppressants may be considered a basic treatment approach.

ABSTRACT The genetic features of foodborne Salmonella have changed in recent years as multidrug-resistant (MDR) strains have become prevalent among various serovars. The recent expansion of MDR Salmonella enterica serovar Indiana sequence type 17 (ST17) poses an increasing threat to global public health, as 24.3% (61/251) of S. Indiana isolates in this study exhibited resistance to three clinically important antimicrobial agents: fluoroquinolones (ciprofloxacin), extended-spectrum β-lactams (cephalosporin), and macrolides (azithromycin). Both the evolutionary histories and antimicrobial resistance (AMR) profiles of this serovar remain to be described. Bioinformatic analysis revealed multiple lineages have coexisted and spread throughout China. Specifically, emergence of a predominant lineage appears to be associated with accumulated various substitutions in the chromosomal quinolone resistance-determining regions (GyrA S83F D87N and ParC T57S S80R) (141 [56.2%]), as well as acquisition of an extended-spectrum β-lactamase (ESBL)-producing IncHI2 plasmid that has subsequently undergone extensive rearrangement and an IncX1 plasmid that contains mph(A), conferring resistance to azithromycin. Several other evolutionary events influencing the trajectory of this drug-resistant serovar were also identified, including sporadic acquisitions of blaCTX-M-carrying plasmids, along with chromosomal integration of blaCTX-M within subclusters. Most human isolates reside in clusters containing isolates from animals, mainly from chickens, indicating the close relationship of human isolates with those from food animals. These data demonstrate that MDR S. Indiana ST17 is already widespread and capable of acquiring resistance traits against the clinical important antimicrobial agents, suggesting it should be considered a high-risk global MDR pathogen. The complexity of its evolutionary history has implications for AMR surveillance, epidemiological analysis, and control of emerging clinical lineages. IMPORTANCE The emergence and worldwide spread of AMR Salmonella constitute great public health concerns. S. enterica serovar Indiana is a typical MDR serovar characterized by sporadic reports. However, comprehensive population genomics studies have not been performed on this serovar. This study provides a detailed and comprehensive insight into the rapid evolution of AMR in this important Salmonella serovar in the past 15 years in eight provinces of China. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, the persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance determinants that occur at all genetic levels (genes, genetic contexts, plasmids, and host strains). There are different mechanisms of antimicrobial resistance in S. enterica serovar Indiana from those of other serovars. This study sheds light on the formation of MDR S. enterica serovar Indiana with chickens as its potential reservoirs and paves the way to curb its further expansion among food animals.

PurposeThe study evaluated the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for differentiating hepatocellular carcinoma (HCC) from primary liver cancer in patients with liver cirrhosis based on the updated 2019 WHO classification.Materials and MethodsFrom 2016 to 2021, 300 patients with surgically confirmed primary liver cancer (PLC) and liver cirrhosis based on the updated 2019 WHO classification were eligible for this retrospective study (100 cases in each of three groups including HCC, ICC, and cHCC-CCA). Two radiologists were blinded to the final diagnosis and independently assigned an LI-RADS category to each liver nodule. The diagnostic performances of the LR-5 category (definitely HCC), and the LR-M category (probably or definitely malignant, but not specific for HCC) were calculated in overall and small observations (

There is no denying that there is ample evidence of numerous factors that influence language learners' success. Recently, there is a critical call to embrace positive psychology that is more open and appreciative of the positive influences in learning English as a foreign language (EFL). Set against this burgeoning area of study in language learning, this paper puts forward the findings of a study that aimed to examine the mediating roles of grit and foreign language enjoyment in the relationship between growth mindset and English language performance. The study employed a correlational research design involving 388 EFL students from one university in China. The data were collected through a questionnaire and an English language performance test. Using the structural equation modeling, this study found that the association between growth mindset and English language performance was partially mediated by grit and foreign language enjoyment. This indicates that students with a growth mindset tend to possess a higher level of grit as well as experience more enjoyment in learning English, which consequently can lead to students becoming more successful language learners. These findings provide significant implications for language teachers, educational material developers, and school administrators in China to embrace the affective domain postulated by positive psychology.

Resistant starch appears to have promising effects on hypertension, cardiovascular and enteric illness. The influence of resistant starch on intestinal physiological function has drawn great attention. In this study, we first analyzed the physicochemical characteristics, including the crystalline properties, amylose content, and anti-digestibility among different types of buckwheat-resistant starch. The influence of resistant starch on the physiological functions of the mouse intestinal system, contained defecation, and intestinal microbes were also evaluated. The results showed that the crystalline mold of buckwheat-resistant starch changed from A to B + V after acid hydrolysis treatment (AHT) and autoclaving enzymatic debranching treatment (AEDT). The amylose content in AEDT was higher than in AHT and raw buckwheat. Moreover, the anti-digestibility of AEDT was also stronger than that in AHT and raw buckwheat. The buckwheat-resistant starch can promote bowel intestinal tract movement. The quantity of intestinal microbe was regulated by buckwheat-resistant starch. Our research demonstrates an effective preparation method for improving the quality of buckwheat-resistant starch and found that buckwheat-resistant starch has the role of adjusting the distribution of the intestinal flora and maintaining the health of the body.

Phase-sensitive optical time-domain reflectometry (φOTDR) is a technology for distributed vibration sensing, where vibration amplitudes are determined by recovering the phase of the backscattered light. Measurement noise induces phase errors, which degrades sensing performance. The phase errors, using a differentiation and cross-multiplication (DCM) algorithm, are investigated theoretically and experimentally in a φOTDR system based on a phase retrieval configuration consisting of an imbalanced Mach–Zehnder interferometer (IMZI) and a 3 × 3 coupler. Analysis shows that phase error is highly dependent on the AC component of the obtained signal, essentially being inversely proportional to the product of the power of the light backscattered from two locations. An analytical expression was derived to estimate the phase error and was confirmed by experiment. When applied to the same measurement data, the error is found to be slightly smaller than that obtained using in-phase/quadrature (I/Q) demodulation. The error, however, increases for longer measurement times.

Background: Short-term outcomes of laparoscopic hepatectomy of central-located liver lesions (LHCL) compared with traditional open hepatectomy of central-located liver lesions (OHCL) remain unclear. The aim of this study was to explore the safety and efficacy of LHCL. Methods: A retrospective analysis was performed on 262 patients who underwent hepatectomies involving resections of liver segment II, IV or VIII from January 2015 to June 2021 in two institutions. Patients in the LHCL group were matched in a 1:2 ratio to patients in the OHCL group. Results: After propensity score-matched (PSM) analysis, 61 patients remained in the LHCL group and 122 patients were in the OHCL group. What needs to be mentioned is that although not significant, patients in the OHCL group had increased lesion size (4.3 vs. 3.6 cm, p = 0.052), number (single/multiple, 84.8%/15.2% vs. 93.4%/6.6%, p = 0.097), and number of liver segments involved (one/two/three, 47.3%/42.0%/10.7% vs. 57.4%36.1%/10.7%, p = 0.393). To ensure surgical safety, fewer patients in the LHCL group underwent vascular exclusion than those in the OHCL group (p = 0.004). In addition, LHCL was associated with lower blood loss (p = 0.001) and transfusion requirement (p = 0.004). In terms of short-term outcomes, the LHCL group had significantly lower levels of peak ALT (p < 0.001), peak DBIL (p = 0.042), peak PT (p = 0.012), and higher levels of bottom ALB (p = 0.049). Moreover, the LHCL group demonstrated quicker postoperative recovery, which was represented by shorter time to first flatus, time to oral intake, time to drain off, and hospital stay (all p < 0.001). Importantly, the LHCL group had a significantly reduced occurrence of postoperative complications (p < 0.001) and similar R0 resection rates (p = 0.678) when compared to the OHCL group. Conclusion: LHCL is associated with increased safety and better perioperative outcomes and thus could be recommended for patients with central space-occupying liver lesions when appropriately selecting the surgical procedure according to the total tumor burden and carefully handled by experienced surgeons. From the experience of our center, LHCL could be performed to solitary lesion involving liver segment IV/V/VIII,

Direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) is a promising tool for high-throughput metabolomics analysis. However, metabolite assignment is limited by the inadequate mass accuracy and chemical space of the metabolome database. Here, a serum metabolome characterization method was proposed to make full use of the potential of DI-nESI-HRMS. Different from the widely used database search approach, unambiguous formula assignments were achieved by a reaction network combined with mass accuracy and isotopic patterns filter. To provide enough initial known nodes, an initial network was directly constructed by known metabolite formulas. Then experimental formula candidates were screened by the predefined reaction with the network. The effects of sources and scales of networks on assignment performance were investigated. Further, a scoring rule for filtering unambiguous formula candidates was proposed. The developed approach was validated by a pooled serum sample spiked with reference standards. The coverage and accuracy rates for the spiked standards were 98.9% and 93.6%, respectively. A total of 1958 monoisotopic features were assigned with unique formula candidates for the pooled serum, which is twice more than the database search. Finally, a case study of serum metabolomics in diabetes was carried out using the developed method.

Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural, mechanical, and biological properties. In this study, six types of composite lattice structures with different strut radius that consist of simple cubic (structure A), body-centered cubic (structure B), and edge-centered cubic (structure C) unit cells are designed. The designed structures are firstly simulated and analysed by the finite element (FE) method. Commercially pure Ti (CP–Ti) lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting (SLM), and the dimensions, microtopography, and mechanical properties are characterised. The results show that among the six types of composite lattice structures, combined BA, CA, and CB structures exhibit smaller maximum von-Mises stress, indicating that these structures have higher strength. Based on the fitting curves of stress/specific surface area versus strut radius, the optimized strut radius of BA, CA, and CB structures is 0.28, 0.23, and 0.30 mm respectively. Their corresponding compressive yield strength and compressive modulus are 42.28, 30.11, and 176.96 MPa, and 4.13, 2.16, and 7.84 GPa, respectively. The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone, which makes it a potential candidate for subchondral bone restorations.

Abstract Background The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic. Results We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model. Conclusions Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.

Abstract Background Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown. Methods Analysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging. Results Our results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1β, IL-6 and the proinflammatory DAM subset gene CD44. Conclusion The present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.

Abstract A safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 μm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.