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Abstract Background Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g. pancreatic cancer, breast cancer, prostate cancer, and colorectal cancer) and promotes cancer cell proliferation, migration, invasion, and differentiation. Moreover, the overexpression of LIF correlates with poor clinicopathological characteristics. Therefore, we hypothesized that LIF could be a promising target for the treatment of cancer. In this work, we developed the antagonist antibody 1G11 against LIF and investigated its anti-tumor mechanism and its therapeutic efficacy in mouse models. Results A series of single-chain variable fragments (scFvs) targeting LIF were screened from a naive human scFv phage library. These scFvs were reconstructed in complete IgG form and produced by the mammalian transient expression system. Among the antibodies, 1G11 exhibited the excellent binding activity to human, cynomolgus monkey and mouse LIF. Functional analysis demonstrated 1G11 could block LIF binding to LIFR and inhibit the intracellular STAT3 phosphorylation signal. Interestingly, 1G11 did not block LIF binding to gp130, another LIF receptor that is involved in forming the receptor complex together with LIFR. In vivo, intraperitoneal administration of 1G11 inhibited tumor growth in CT26 and MC38 models of colorectal cancer. IHC analysis demonstrated that p-STAT3 and Ki67 were decreased in tumor tissue, while c-caspase 3 was increased. Furthermore, 1G11 treatment improves CD3+, CD4 + and CD8 + T cell infiltration in tumor tissue. Conclusions We developed antagonist antibodies targeting LIF/LIFR signaling pathway from a naive human scFv phage library. Antagonist anti-LIF antibody exerts antitumor effects by specifically reducing p-STAT3. Further studies revealed that anti-LIF antibody 1G11 increased immune cell infiltration in tumor tissues.

Abstract Background Colonization of carbapenem-resistant Enterobacterale (CRE) is considered as one of vital preconditions for infection, with corresponding high morbidity and mortality. It is important to construct a reliable prediction model for those CRE carriers with high risk of infection. Methods A retrospective cohort study was conducted in two Chinese tertiary hospitals for patients with CRE colonization from 2011 to 2021. Univariable analysis and the Fine-Gray sub-distribution hazard model were utilized to identify potential predictors for CRE-colonized infection, while death was the competing event. A nomogram was established to predict 30-day and 60-day risk of CRE-colonized infection. Results 879 eligible patients were enrolled in our study and divided into training (n = 761) and validation (n = 118) group, respectively. There were 196 (25.8%) patients suffered from subsequent CRE infection. The median duration of subsequent infection after identification of CRE colonization was 20 (interquartile range [IQR], 14–32) days. Multisite colonization, polymicrobial colonization, catheterization and receiving albumin after colonization, concomitant respiratory diseases, receiving carbapenems and antimicrobial combination therapy before CRE colonization within 90 days were included in final model. Model discrimination and calibration were acceptable for predicting the probability of 60-day CRE-colonized infection in both training (area under the curve [AUC], 74.7) and validation dataset (AUC, 81.1). Decision-curve analysis revealed a significantly better net benefit in current model. Our prediction model is freely available online at https://ken-zheng.shinyapps.io/PredictingModelofCREcolonizedInfection/ . Conclusions Our nomogram has a good predictive performance and could contribute to early identification of CRE carriers with a high-risk of subsequent infection, although external validation would be required.

Purpose The aim of this study was to explore the mechanisms of central brain action in patients with neurogenic underactive bladder (UAB) treated with intravesical electrical stimulation (IVES). Methods We prospectively recruited patients with neurogenic UAB who chose to receive IVES treatment and healthy subjects (HS). At baseline, the following data were obtained: a 72-hour voiding diary; measurements of postvoid residual urine (PVR), voiding efficiency (VE) and first sensation of bladder filling (FS); American Urological Association Symptom Index Quality of Life (AUA-SI-QOL) scores, and functional near-infrared spectroscopy scans of the prefrontal cortex in the voiding stage. All UAB patients were re-evaluated for these indices after completing 4 weeks of IVES. A >50% improvement in PVR was defined as successful IVES treatment. Prefrontal activity was analyzed using the NIRS_KIT software, corrected with the false discovery rate (P

Summary: Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis (5-year survival rate of 30.5% in the United States). Designing cell therapies to target AML is challenging because no single tumor-associated antigen (TAA) is highly expressed on all cancer subpopulations. Furthermore, TAAs are also expressed on healthy cells, leading to toxicity risk. To address these targeting challenges, we engineer natural killer (NK) cells with a multi-input gene circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates. The OR gate kills a range of AML cells from leukemic stem cells to blasts using a bivalent CAR targeting FLT3 and/or CD33. The NOT gate protects healthy hematopoietic stem cells (HSCs) using an inhibitory CAR targeting endomucin, a protective antigen unique to healthy HSCs. NK cells with the combined OR-NOT gene circuit kill multiple AML subtypes and protect primary HSCs, and the circuit also works in vivo.

Background: Considering the therapeutic difficulties and mortality associated with bloodstream infection (BSI), it is essential to investigate other potential factors affecting mortality in critically ill patients with BSI and examine the utility of the quick Pitt bacteremia (qPitt) score to improve the survival rate. Objectives: To improve the predictive accuracy of the qPitt scoring system by evaluating the five current components of qPitt and including other potential factors influencing mortality in critically ill patients with BSI. Design: This was a retrospective cohort study. Methods: Medical information from the Medical Information Mart for Intensive Care IV database was used in this retrospective cohort study. The risk factors associated with mortality were examined using a multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminatory capability of the prediction models. Results: In total, 1240 eligible critically ill patients with BSI were included. After adjustment for age, community-onset BSI, indwelling invasive lines, and Glasgow Coma Scale (GCS) ⩽ 8, acute kidney injury (AKI) was identified as a notable risk factor for 14-day mortality. Except for altered mental status, the four other main components of the original qPitt were significantly associated with 14-day mortality. Hence, we established a modified qPitt (m-qPitt) by adding AKI and replacing altered mental status with GCS ⩽ 8. The AUCs for m-qPitt and qPitt were 0.723 [95% confidence interval (CI): 0.683–0.759] and 0.708 (95% CI: 0.669–0.745) in predicting 14-day mortality, respectively. Moreover, m-qPitt also had acceptable performance and discrimination power [0.700 (95% CI: 0.666–0.732)] in predicting 28-day mortality. Conclusion: AKI significantly influenced the survival of critically ill patients with BSIs. Compared with the original qPitt, our new m-qPitt was proven to have a better predictive performance for mortality in critically ill patients with BSI. Further studies should be conducted to validate the practicality of m-qPitt.

In order to achieve the lightweight goal of urban rail train braking system, friction stir lap welding (FSLW) was used to weld SiCp/ZL101 and ZL101 sheets to prepare a new type of brake disc material. The effects of different tool tilt angles (TTAs) on microstructure and mechanical properties of the welding joints were systematically studied. The TTA had a significant effect on the microstructure and defect formation of the dissimilar FSLW joints. There were tunnel defects under the advancing side at 1° and 2°. Internal defect-free weld structures were formed at 3° and 3.5°. A large number of dislocations caused by plastic deformation remained in the microstructure of the weld region at 1° and 2°, and the transformation of the microstructure of the weld region at 3° and 3.5° was dominated by dynamic recovery and dynamic recrystallization. The distribution of SiC particles in the nugget area was uniform, and the grains were obviously refined. With the increase of the TTA, the average grain size of the nugget area increased, the average size of the SiC particles decreased, and the average hardness of the nugget area increased. The four samples all formed a transition zone with good metallurgical bonding at the welding interface. The shear strength of the welding joints increased first and then decreased with the increase of the TTA. In the absence of welding defects, the shear strength reached the best level of 130.71 MPa at 3°. Both shear and tensile fractures were ductile fractures.

Sentence Boundary Disambiguation (SBD) is crucial for building datasets for tasks such as machine translation, syntactic analysis, and semantic analysis. Currently, most automatic sentence segmentation in Tibetan adopts the methods of rule-based and statistical learning, as well as the combination of the two, which have high requirements on the corpus and the linguistic foundation of the researchers and are more costly to annotate manually. In this study, we explore Tibetan SBD using deep learning technology. Initially, we analyze Tibetan characteristics and various subword techniques, selecting Byte Pair Encoding (BPE) and Sentencepiece (SP) for text segmentation and training the Bidirectional Encoder Representations from Transformers (BERT) pre-trained language model. Secondly, we studied the Tibetan SBD based on different BERT pre-trained language models, which mainly learns the ambiguity of the shad (“།”) in different positions in modern Tibetan texts and determines through the model whether the shad (“།”) in the texts has the function of segmenting sentences. Meanwhile, this study introduces four models, BERT-CNN, BERT-RNN, BERT-RCNN, and BERT-DPCNN, based on the BERT model for performance comparison. Finally, to verify the performance of the pre-trained language models on the SBD task, this study conducts SBD experiments on both the publicly available Tibetan pre-trained language model TiBERT and the multilingual pre-trained language model (Multi-BERT). The experimental results show that the F1 score of the BERT (BPE) model trained in this study reaches 95.32% on 465,669 Tibetan sentences, nearly five percentage points higher than BERT (SP) and Multi-BERT. The SBD method based on pre-trained language models in this study lays the foundation for establishing datasets for the later tasks of Tibetan pre-training, summary extraction, and machine translation.

Purpose To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. Methods Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. Results The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. Conclusions Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation.

Abstract Anti-CD38 monoclonal antibodies (mAbs), daratumumab, and isatuximab have represented a breakthrough in the treatment of multiple myeloma (MM). Recently, CD38-based mAbs were expected to achieve increasing potential beyond MM, which encouraged us to develop new anti-CD38 mAbs to meet clinical needs. In this study, we developed a novel humanized anti-CD38 antibody, FTL004, which exhibited enhanced pro-apoptotic ability and negligible binding to red blood cells (RBCs). FTL004 presented a better ability to induce direct apoptosis independent of Fc-mediated cross-linking against lymphoma and MM cell lines as well as primary myeloma cells derived from MM patients. For instance, FTL004 induced RPMI 8226 cells with 55% early apoptosis cells compared with 20% in the isatuximab-treated group. Of interest, FTL004 showed ignorable binding to CD38 on human RBCs in contrast to tumor cells, even at concentrations up to 30 μg/mL. Furthermore, with an engineered Fc domain, FTL004 displayed stronger antibody-dependent cellular cytotoxicity (ADCC) against CD38+ malignant cells. In vivo MM and non-Hodgkin lymphoma tumor xenograft models showed that FTL004 possessed an effective anti-tumor effect. Cryo-electron microscopy structure resolved two epitope centers of FTL004 on CD38: one of which was unique while the other partly overlapped with that of isatuximab. Taken together, FTL004 distinguishes it from other CD38 targeting mAbs and represents a potential candidate for the treatment of MM and non-Hodgkin lymphoma.

The “do not eat me” signaling pathway is extremely active in tumor cells, providing a means for these cells to elude macrophage phagocytosis and escape immune surveillance. Representative markers of this pathway, such as CD47 and CD24, are highly expressed in numerous tumors. The interaction of SIRPα with CD47 reduces the accumulation of non-myosin ⅡA on the cell membrane. The combination of CD24 and Siglec10 ultimately leads to the recruitment of SHP-1 or SHP-2 to reduce signal transduction. Both of them weaken the ability of macrophages to engulf tumor cells. Blocking the mutual recognition between CD47-SIRPα or CD24-Siglec10 using large molecular proteins or small molecular drugs represents a promising avenue for tumor immunotherapy. Doing so can inhibit signal transduction and enhance macrophage clearance rates of cancer cells. In this paper, we summarize the characteristics of the drugs that affect the “do not eat me” signaling pathway via classical large molecular proteins and small molecule drugs, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways. We expect it will offer insight into the development of new drugs centered on blocking the “do not eat me” signaling pathway.

BackgroundComorbidity is a common phenomenon in the older population; it causes a heavy burden on societies and individuals. However, the relevant evidence, especially in the southwestern region of China, is insufficient.ObjectivesWe aimed to examine current comorbidity characteristics as well as correlations among diseases in individuals aged >60 years.DesignRetrospective study.MethodsWe included records of 2,995 inpatients treated at the Gerontological Department of Sichuan Geriatric Hospital from January 2018 to February 2022. The patients were divided into groups according to sex and age. Diseases were categorised based on the International Classification of Diseases and their Chinese names. We calculated the age-adjusted Charlson Comorbidity Index (ACCI), categorised diseases using the China Health and Retirement Longitudinal Study questionnaire, and visualised comorbidity using web graphs and the Apriori algorithm.ResultsThe ACCI was generally high, and it increased with age. There were significant differences in the frequency of all diseases across age groups, especially in individuals aged ≥90 years. The most common comorbid diseases were liver diseases, stomach or other digestive diseases, and hypertension. Strong correlations between the most common digestive diseases and hypertension were observed.ConclusionOur findings provide insights into the current situation regarding comorbidity and the correlations among diseases in the older population. We expect our findings to inform future research directions as well as policies regarding general clinical practice and public health, especially for medical consortiums.

Abstract Background To assess the inter-observer and intra-observer reliability of the magnetic resonance urography (MRU)—upper urinary tract dilation (UUTD) grading system. Methods A total of 40 patients with a diagnosis of NB were enrolled in this study. The images were assembled in an electronic presentation randomly. The presentations were reviewed and graded by 4 junior and 4 senior urologists. One week later, the images were randomized again and reassessed. The inter-observer reliability was estimated by Kendall’s coefficient of concordance and intra-class correlation coefficient (ICC), and the intra-observer reliability was estimated by weighted Cohen’s kappa. Results The inter-observer reliability strength was excellent for all urologists, with the ICC value of 0.939 (0.908–0.963) and Kendall’s W value of 0.967. The highest agreement was shown in Grade 4 at 92.50%, and the lowest in Grade 2 at 82.14%. All disagreements were within one grade of difference. Moreover, the Intra-observer reliability was excellent, with the weighted kappa value ranging from 0.904 to 0.954. Conclusions The inter-observer and intra-observer reliability of this novel MRU-UUTD grading system is confirmed, providing adequate evidence for broader clinical application.

Abstract Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor “cruise missile”, mesoporous Fe3O4-containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment. Graphical Abstract

Human movement recognition is the use of perceptual technology to collect some of the limb or body movements presented. This practice involves the use of wireless signals, processing, and classification to identify some of the regular movements of the human body. It has a wide range of application prospects, including in intelligent pensions, remote health monitoring, and child supervision. Among the traditional human movement recognition methods, the widely used ones are video image-based recognition technology and Wi-Fi-based recognition technology. However, in some dim and imperfect weather environments, it is not easy to maintain a high performance and recognition rate for human movement recognition using video images. There is the problem of a low recognition degree for Wi-Fi recognition of human movement in the case of a complex environment. Most of the previous research on human movement recognition is based on LiDAR perception technology. LiDAR scanning using a three-dimensional static point cloud can only present the point cloud characteristics of static objects; it struggles to reflect all the characteristics of moving objects. In addition, due to its consideration of privacy and security issues, the dynamic millimeter-wave radar point cloud used in the previous study on the existing problems of human body movement recognition performance is better, with the recognition of human movement characteristics in non-line-of-sight situations as well as better protection of people’s privacy. In this paper, we propose a human motion feature recognition system (PNHM) based on spatiotemporal information of the 3D point cloud of millimeter-wave radar, design a neural network based on the network PointNet++ in order to effectively recognize human motion features, and study four human motions based on the threshold method. The data set of the four movements of the human body at two angles in two experimental environments was constructed. This paper compares four standard mainstream 3D point cloud human action recognition models for the system. The experimental results show that the recognition accuracy of the human body’s when walking upright can reach 94%, the recognition accuracy when moving from squatting to standing can reach 84%, that when moving from standing to sitting can reach 87%, and the recognition accuracy of falling can reach 93%.

Due to their individual advantages, the integration of lexicon information and pre-trained models like BERT has been widely adopted in Chinese sequence labeling tasks. However, given their high demand for training data, efforts have been made to enhance their performance in low-resource scenarios. Currently, certain specialized domains, such as agriculture, the industrial sector, and the metallurgical industry, suffer from a scarcity of data. Consequently, there is a dearth of effective models for entity relationship recognition when faced with limited data availability. Inspired by this, we constructed a suitable small balanced dataset and proposed a based-domain-NER model. Firstly, we construct a domain-specific dictionary based on mine hoist equipment and fault text and generate a dictionary tree to obtain word vector information. Secondly, we use a Lexicon Adapter to obtain the vector information of the domain-specific dictionary feature words matched using the characters and calculate the weights between their word vectors, integrating position encoding to enhance the positional information of the word vectors. Finally, we incorporate word vector information into the feature extraction layer to enhance the boundary information of domain entities and mitigate the semantic loss problem caused via using only character feature representation. Experimental results on a manually annotated dataset of mine hoist fault texts show that this method outperforms BiLSTM, BiLSTM-CRF, BERT, BERT-BiLSTM-CRF, and LEBERT, effectively improving the accuracy of named entity recognition (NER) for mine hoist faults.

Purpose To investigate the video-urodynamic and pelvic floor electrophysiological characteristics in patients with traumatic spinal cord injury (SCI). Methods This retrospective reviewed the clinical records, urodynamic and pelvic floor electrophysiological data of 647 patients with traumatic SCI and out of spinal shock. Patients were classified based on American Spinal Injury Association (ASIA) Impairment Scale and urodynamic findings. Results Of the 647 patients, detrusor overactivity (DO) with or without detrusor sphincter dyssynergia (DSD) was found in 79.5%, 61%, 35.2%, 35%, and 19.2% of patients with cervical, thoracic (T1–9), thoracic (T10–12), lumbar, and conical cauda injury, respectively. Other patients manifested detrusor areflexia (DA). Patients with DO and/or DSD had a longer duration of SCI at each injury level than patients with DA. In suprasacral injury patients with DA, 63.0% (58 of 92) had a normal bulbocavernosus reflex (BCR) response. Compared with patients without bladder sensation (BS), bladder capacity during urine leakage was far higher in those with BS. The manifestation of BCR and somatosensory-evoked potential (SEP) was associated with the level of injury. Conclusions This study showed a significant correlation between the level of SCI and video-urodynamic findings, but clinical examination cannot by predict bladder function; urodynamic testing is also necessary. In addition, the role of BCR and SEP for guiding bladder management is limited. Moreover, BS is important for urinary control in patients with traumatic SCI.

Automatic driving technology refers to equipment such as vehicle-mounted sensors and computers that are used to navigate and control vehicles autonomously by acquiring external environmental information. To achieve automatic driving, vehicles must be able to perceive the surrounding environment and recognize and understand traffic signs, traffic signals, pedestrians, and other traffic participants, as well as accurately plan and control their path. Recognition of traffic signs and signals is an essential part of automatic driving technology, and gesture recognition is a crucial aspect of traffic-signal recognition. This article introduces mm-TPG, a traffic-police gesture recognition system based on a millimeter-wave point cloud. The system uses a 60 GHz frequency-modulated continuous-wave (FMCW) millimeter-wave radar as a sensor to achieve high-precision recognition of traffic-police gestures. Initially, a double-threshold filtering algorithm is used to denoise the millimeter-wave raw data, followed by multi-frame synthesis processing of the generated point cloud data and feature extraction using a ResNet18 network. Finally, gated recurrent units are used for classification to enable the recognition of different traffic-police gestures. Experimental results demonstrate that the mm-TPG system has high accuracy and robustness and can effectively recognize traffic-police gestures in complex environments such as varying lighting and weather conditions, providing strong support for traffic safety.

Aiming at the material selection of the stirring paddle in the mechanical stirring equipment, the corrosion mechanism of four different iron-based material stirring paddles when stirring the ZL101 aluminum alloy melt were studied. Using scanning electron microscopy (SEM), EDS and OM methods, the microstructures and phase compositions of the reaction layers formed by the corrosion of the ZL101 melt in the four iron-based stirring paddles of A3 steel, heat-resistant stainless steel 1.4837, QT5381 and HT300 during the stirring process were analyzed. The experimental results show that the microstructures and phase compositions of the reaction layers of the A3 steel, QT5381, HT300 had certain similarities, and the heat-resistant stainless steel 1.4837 showed greater differences due to the presence of alloy elements such as Cr and Ni. The comparison indicated that due to the presence of flake graphite, the HT300 hindered the corrosion of the aluminum alloy melt on the substrate, which has the best corrosion resistance. Furthermore, the corrosion mechanism of the aluminum alloy melt on different stirring paddles were also analyzed. During the stirring process, the liquid aluminum and iron-based stirring paddle infiltrated, dissolved, and adsorbed each other. Due to the reaction and diffusion of the aluminum and iron atoms, the Fe–Al intermetallic compound layer was gradually formed at the interface of the iron-based material and aluminum melt, and the presence of Si, Cr and other elements leaded to the formation of more complex intermetallic compounds.

The zoonotic protozoa parasites Cryptosporidium spp. and Giardia duodenalis infect a wide range of hosts, including humans. Pigs are reservoir hosts for Cryptosporidium spp. and G. duodenalis, which can transmit cryptosporidiosis and giardiasis to humans and other animals. The current study sought to investigate the infection rates and species/genotypes of Cryptosporidium spp. and G. duodenalis in pigs in Hubei of China. The nested PCR and sequence analyses of the small ribosomal subunit RNA (SSU rRNA) gene for Cryptosporidium spp. and the β-giardin (bg) gene for G. duodenalis was utilized to screen for the infection of those parasites in a total of 826 fresh fecal samples. Both Cryptosporidium spp. and G. duodenalis infection rates were 0.97% (8/826). Of the genotyped positive isolates, 6/8 (75%) were C. scrofarum and 2/8 (25%) were C. suis, while two zoonotic species G. duodenalis assemblage E and assemblage A were also detected in 7/8 (87.5%) isolates and 1/8 (12.5%) isolates, respectively. The findings suggest that both of those parasites in pig in intensive farms of Hubei province, China, pose a potential public health risk.

Babesia microti is an obligate intraerythrocytic protozoan transmitted by an Ixodes tick. Infections caused by protozoa, including Plasmodium yoelii and Toxoplasma gondii, are shown to inhibit tumor development by activating immune responses. Th1 immune response and macrophages not only are essential key factors in Babesia infection control but also play an important role in regulating tumor development. In this study, we investigated the effects of B. microti infection on melanoma in tumor-bearing mice. The results showed that B. microti infection could inhibit the growth of melanoma, significantly enlarge the spleen size (p ≤ 0.0001), and increase the survival period (over 7 days) of tumor-bearing mice. Mouse spleen immune cell analysis revealed that B. microti-infected tumor-bearing mice could increase the number of macrophages and CD4+ T cells, as well as the proportion of CD4+ T cells and M1 macrophages in the tumor. Immunohistochemical assays showed that B. microti infection could inhibit tumor angiogenesis (p ≤ 0.0032). Meanwhile, both B. microti-infected erythrocytes and culture supernatant were observed to significantly (p ≤ 0.0021) induce the mRNA expression of iNOS, IL-6, and TNF-α in macrophages. Moreover, B. microti culture supernatant could also repolarize IL-4-induced M2 macrophages to the M1 type. Overall, B. microti exerted antitumor effects by stimulating the immune system of tumor-bearing mice and inducing the polarization of immunosuppressive M2 macrophages to pro-inflammatory M1 macrophages.

Multiple studies implicate iron accumulation in the substantia nigra in the degeneration of dopaminergic neurons in Parkinson’s disease. Indeed, slowing of iron accumulation in cells has been identified as the key point for delaying and treating Parkinson’s disease. Myricetin reportedly plays an important role in anti-oxidation, anti-apoptosis, anti-inflammation, and iron chelation. However, the mechanism underlying its neuroprotection remains unclear. In the present study, MES23.5 cells were treated with 1 × 10–6 M myricetin for 1 hour, followed by co-treatment with 400 nM rotenone for 24 hours to establish an in vitro cell model of Parkinson’s disease. Our results revealed that myricetin alleviated rotenone-induced decreases in cell viability, suppressed the production of intracellular reactive oxygen species, and restored mitochondrial transmembrane potential. In addition, myricetin significantly suppressed rotenone-induced hepcidin gene transcription and partly relieved rotenone-induced inhibition of ferroportin 1 mRNA and protein levels. Furthermore, myricetin inhibited rotenone-induced phosphorylation of STAT3 and SMAD1 in MES23.5 cells. These findings suggest that myricetin protected rotenone-treated MES23.5 cells by potently inhibiting hepcidin expression to prevent iron accumulation, and this effect was mediated by alteration of STAT3 and SMAD1 signaling pathways.

The ever-increasing integration of power converter-coupled renewable energy sources reduces carbon footprints yet weakens power system inertia due to the retirement of synchronous generators. Inertia shortage makes modern power systems sensitive to frequency variations, thereby leading to undesirable load shedding, cascading failures, or even large-scale blackouts. To address the inertia concern, distributed virtual inertia from grid-tied power converters is emerging as an attractive solution. On top of that, there are upcoming standards of grid-tied power converters, such as PV inverters, that require grid formulation. As such, this paper proposes flexible distributed virtual inertia delivered by grid-forming converters without additional energy storage units. It is revealed that virtual inertia control may possibly cause stability problems. Through the derived state-space model and sensitivity analysis, the mechanism of instability is disclosed. Although droop control may stabilize converters, it inevitably necessitates extra energy storage, and is hence not cost-effective. Instead, a lead compensator, together with its design procedure, is proposed. Finally, simulation and experimental results validate the correctness and effectiveness of the proposed model and compensator. Moreover, the results demonstrate that the proposed grid-forming converters allow significant improvements in inertia and frequency regulation.

Abstract Background Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC. Methods Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. Results In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). Conclusion These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.

Purpose To determine the risk factors predicting upper urinary tract (UUT) damage using a grading system for upper urinary tract dilation (UUTD) and a descriptive system for all urinary tract dysfunction (AUTD) in patients with myelodysplasia. Methods Six hundred thirty-seven patients with myelodysplasia were evaluated at our center from January 2008 to November 2019. Clinical data, ultrasonography, magnetic resonance urography, and video-urodynamics (VUDS) parameters were collected. Univariate and multivariate analyses were used to determine the risk factors predicting UUT damage. Results Three hundred eighty-three males and 254 females were included. The average course of lower urinary tract symptoms (LUTS) was 14.08±7.07 years (range, 3–31 years). The urodynamic diagnoses of all patients were as follows: detrusor overactivity, 26.8%; detrusor underactivity, 6.44%; and acontractile detrusor, 66.72%. UUT damage was determined in 66.56% of the patients. Of the patients, 28.73 % had vesicoureteral reflux (VUR) during filling (bilateral, n=50; unilateral, n=133) on fluoroscopy during VUDS testing. Two hundred thirty-four patients had UUTD (bilateral, n=203; unilateral, n=31). The occurrence of hydronephrosis based on ultrasonography was closely related to ipsilateral VUR (P

In order to achieve the goal of lightening the braking system of urban rail trains, SiCp/ZL101 and ZL101 plates were welded by friction stir lap welding (FSLW) to prepare a new type of brake disc material. The friction and wear properties of the friction-stir-processed composite material were studied at different temperatures (30 °C, 100 °C, 150 °C, 200 °C, 250 °C, 300 °C) to provide a theoretical basis for the evaluation of braking performance. The experimental results showed that the sliding friction processes at each temperature were relatively stable, the friction coefficients did not vary much and the average friction coefficients changed slightly, stabilizing at about 0.4. The wear extent and the depth of wear scars increased with the increase in the temperature, reaching the highest at 150 °C and then began to decrease. At room temperature, the wear forms were mainly oxidative wear and abrasive wear; as the temperature rose, under the cyclic shearing action of the grinding ball, the abrasive debris fell off under the expansion of fatigue cracks and fatigue wear was the main form at this stage. When the temperature reached 200 °C, it began to show the characteristics of adhesive wear; after 250 °C, due to the gradual formation of a mechanical mixed layer containing more SiC particles and oxides on the wear surface, it exhibited high-temperature lubrication characteristics, and the wear extent was equivalent to 35% of the wear extent at normal temperature, indicating that the composite material had good high-temperature friction and wear properties.

To some extent, pore throat structures of the rock can be characterized by NMR T2 distribution and capillary pressure curve. Theoretical analysis showed that NMR T2 distribution of a rock could potentially be used to derive its capillary pressure curve, providing a quick and non-destructive way to obtain the pore structure distribution data of the reservoir. In this study, the capillary pressure curves of typical cores were constructed from nuclear magnetic resonance (NMR) T2 distributions using a piecewise power function method. T2 cutoff values were introduced as piecewise points for the power function. Then the capillary pressure curves constructed with the piecewise power function method and those constructed with the non-piecewise power function method were compared. The results showed that the proposed method had improved precision, with an averaged fitting degree of 0.943 1. Introducing of T2 cutoff values was proven to be useful in constructing NMR capillary curves by the piecewise power function method.

Background/Aims: Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded as a promising radiosensitizer. In this study, we investigated the effect of USMBs on the sensitivity of nasopharyngeal carcinoma (NPC) to radiation. Methods: Human NPC (CNE-2) cells and human umbilical vein endothelial cells (HUVECs) were exposed to radiation (0, 2, and 8 Gy) alone or in combination with USMBs. Cell viability and apoptosis were measured with the MTT assay and flow cytometry, respectively. The angiogenic activity of HUVECs was detected using matrigel tubule formation. The in vitro effects induced by these treatments were confirmed in vivo with xenograft models of CNE-2 cells in nude mice by examining vascular integrity using color Doppler flow imaging and cell survival using immunohistochemistry. Additionally, the in vivo and in vitro expressions of angiotensin II (ANG II) and its receptor (AT1R) were detected by immunohistochemistry and western blotting, respectively. With CNE-2 cells and HUVECs transfected with control, ANG II, or AT1R, perindopril (an inhibitor of angiotensin-converting enzyme) and candesartan (an inhibitor of AT1R) were used to verify the role of ANG II and AT1R in the radiosensitivity of tumor and endothelial cells by USMBs, by determining cell viability and apoptosis and angiogenic activity. Results: In the NPC xenografts, USMBs slightly reduced blood flow and CD34 expression, increased tumor cell death and ANG II and AT1R expression, and significantly enhanced the effects of radiation. With CNE-2 cells and HUVECs, the USMBs further enhanced the inhibition of tumor cell viability and endothelial tubule formation and further enhanced the increase in ANG II and AT1R due to radiation. Furthermore, perindopril and candesartan significantly enhanced the inhibitory effect of radiation and USMBs on tumor cell growth and angiogenesis in vitro. Conclusions: We have demonstrated for the first time that USMB exposure can significantly enhance the destructive effect on NPC of radiation, and this effect might be further increased by ANG II and AT1R inhibition. Our findings suggest that USMBs can be used as a promising sensitizer of radiotherapy to treat NPC, and the clinical effect might be increased by ANG II and AT1R inhibition.

Background/Aim: Bleeding risk among patients with acute or chronic liver disease after invasive procedures is a common concern in clinical practice. This retrospective study aimed to explore whether the presence of coagulopathy increased the risk of major bleeding after invasive procedures in cirrhosis. Patients and Methods: A total of 874 cirrhotic patients underwent invasive procedures. Coagulopathy was defined as international normalized ratio (INR) ≥1.5 and/or platelets (PLTs) ≤50 × 109/L. Severe thrombocytopenia was defined as PLTs ≤ 50 × 109/L. Invasive procedures, major bleeding after invasive procedures, and in-hospital deaths were recorded. Results: In all, 296 patients (33.9%) had coagulopathy. Major bleeding after invasive procedures occurred in 21 patients (2.4%). Major bleeding after invasive procedures was more frequent in patients with coagulopathy than those without coagulopathy (4.1% vs 1.6%, P = 0.023). Major bleeding after invasive procedures was more frequent in patients with severe thrombocytopenia than those without severe thrombocytopenia (4.9% vs 1.6%, P = 0.008). Incidence of major bleeding after invasive procedures was not significantly different between patients with INR ≥ 1.5 and INR < 1.5 (4.5% vs 2.0%, P = 0.065). Patients with INR ≥1.5 had a significantly higher in-hospital mortality than those with INR < 1.5 (6.4% vs 1.3%, P < 0.001). Conclusion: Severe thrombocytopenia significantly increased the risk of major bleeding after invasive procedures in cirrhosis. INR ≥ 1.5 significantly increased in-hospital mortality.

This study investigated the effects of enzymatic deglycosylation following ultrasound pretreatment on structure and immunoreactivity of soybean 7S globulin. Soybean 7S globulin was pretreated by ultrasound (40 kHz, 300 W) and enzymatically deglycosylated by peptide-N-glycosidase F (PNGase F). Changes in structure of processed soybean 7S globulin were characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, reversed-phase high-performance liquid chromatography, ultraviolet absorption spectrum, circular dichroism spectrum, and surface hydrophobicity analysis. Enzyme-linked immunoabsorbent assay was used to evaluate IgE-binding ability. The results showed that the glycan moieties of soybean 7S globulin were effectively removed by PNGase F, which significantly modified protein structures including the secondary and tertiary structures of 7S globulin. Individual enzymatic deglycosylation could reduce IgE-binding capacity of 7S globulin, whereas enzymatic deglycosylation following ultrasound pretreatment enhanced its IgE-binding capacity. In conclusion, soybean 7S globulin treated by single enzymatic deglycosylation can reduce potential allergenicity and may be employed in hypoallergenic food preparation.

The pipeline has historically been the preferred means to transport CO2 due to its low cost for short distances and opportunities for economies of scale. However, interest in vessel-based transport of CO2 is growing. While most of the literature has assumed that CO2 shipping would take place at low pressure (at 7 barg and −46 °C), the issue of identifying best transport conditions, in terms of pressure, temperature, and gas composition, is becoming more relevant as ship-based carbon capture and storage chains move towards implementation. This study focuses on an in-depth comparison of the two primary and relevant transport pressures, 7 and 15 barg, for annual volumes up to 20 MtCO2/year and transport distances up to 2000 km. We also address the impact of a number of key factors on optimal transport conditions, including (a) transport between harbours versus transport to an offshore site, (b) CO2 pressure prior to conditioning, (c) the presence of impurities and of purity constraints, and (d) maximum feasible ship capacities for the 7 and 15 barg options. Overall, we have found that 7 barg shipping is the most cost-efficient option for the combinations of distance and annual volume where transport by ship is the cost-optimal means of transport. Furthermore, 7 barg shipping can enable significant cost reductions (beyond 30%) compared to 15 barg shipping for a wide range of annual volume capacities.

Purpose We investigated the effects of different stimulation frequencies on the inhibition of bladder overactivity by sacral neuromodulation (SNM) in pigs. Methods Implant-driven stimulators were used to stimulate the S3 spinal nerve in 13 pigs. Cystometry was performed by infusing normal saline (NS) or acetic acid (AA). SNM (pulse width, 210 µsec) at frequencies ranging from 5 to 50 Hz was conducted at the intensity threshold at which observable perianal and/or tail movement was induced. Multiple cystometrograms were performed to determine the effects of different frequencies on the micturition reflex. Results AA-induced bladder overactivity significantly reduced the bladder capacity (BC) to 34.4%±4.7% of the NS control level (354.4±35.9 mL) (P0.05), but SNM at 15, 30, and 50 Hz significantly increased the BC to 54.5%±7.1%, 55.2%±6.5%, and 57.2%±6.1% of the NS control level (P0.05). Conclusions This study demonstrated that 15 Hz was an appropriate frequency for SNM and that frequencies higher than 15 Hz did not lead to better surgical outcomes.

There is a growing interest in the security of underwater communication with the increasing demand for undersea exploration. In view of the complex composition and special optical properties of seawater, this paper deals with a performance analysis for continuous-variable quantum key distribution (CVQKD) over an underwater link. In particular, we focus on analyzing the channel transmittance and detection efficiency based on Monte Carlo simulation for different water types, link distances and transceiver parameters. A comparison between the transmittance obtained by simple Beer’s law and Monte Carlo simulation reveals that the transmittance of underwater link may be severely underestimated in the previous underwater CVQKD research. The effect of the receiver aperture and field of view (FOV) on detection efficiency under different water types is further evaluated based on Monte Carlo. Simulation results show that the transmission distance of the underwater CVQKD system obtained by Monte Carlo simulation in pure sea water, clear ocean water and coastal ocean water is larger than that obtained by Beer’s law, while the key rate of the system in all types of water is smaller than that obtained by Beer’s law because the size and FOV of the receiver aperture are taken into account. By considering the practical system parameters, this paper establishes a comprehensive model for evaluating the security of underwater CVQKD systems with different system configurations.

With the rapid development of mobile networks, there are more and more application scenarios that require group communication. For example, in mobile edge computing, group communication can be used to transmit messages to all group members with minimal resources. The group key directly affects the security of the group communication. Most existing group key agreement protocols are often flawed in performance, scalability, forward or backward secrecy, or single node failure. Therefore, this paper proposes a blockchain-based authentication and dynamic group key agreement protocol. With our protocol, each group member only needs to authenticate its left neighbor once to complete the authentication, which improved authentication efficiency. In addition, our protocol guarantees the forward secrecy of group members after joining the group and the backward secrecy of group members after leaving the group. Based on blockchain technology, we solve the problem of single node failure. Furthermore, we use mathematics to prove the correctness and security of our protocol, and the comparison to related protocols shows that our protocol reduces computation and communication costs.

The magnetic properties of the candidate lithium-ion battery cathode materials Li _2 MnSiO _4 have been studied experimentally using static and pulsed high magnetic fields. A field-induced magnetic transition is observed in low temperature region, in which a saturation magnetization is observed above 27 T which confirms that the Mn-ion has a dominant low spin state with a saturated magnetic moment of ∼3.1 μ _B /Mn. With the change of temperature and magnetic field, the Li _2 MnSiO _4 shows a complex magnetic phase transition. Considering to the coupling between spin, charge and orbital, the field-induced magnetic transition may affect the charge-discharge behavior of the cathode material, thus, the study is expected to explore the possibility and stability of the candidate lithium-ion battery cathode materials used in the low temperature and high magnetic field circumstance and its performance degradation.

Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (TZ), a narrow region of metaplastic squamous epithelium that develops at the squamocolumnar junction between the ectocervix and endocervix. It is unclear why the TZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region. We hypothesized that cells cultured from TZ are more susceptible to cellular immortalization, an alteration that contributes to malignant development. We cultured primary epithelial cells from each region of human cervix (ectocervix, endocervix and TZ) and measured susceptibility to immortalization after transfection with the complete HPV-16 genome or infection of HPV16 E6/E7 retroviruses. Cells cultured from each cervical region expressed keratin markers (keratin 14 and 18) that confirmed their region of origin. In contrast to our prediction, cells from TZ were equally susceptible to immortalization as cells from ectocervix or endocervix. Thus, increased susceptibility of the TZ to cervical carcinogenesis is not due to increased frequency of immortalization by HPV-16. We developed a series of HPV16-immortalized cell lines from ectocervix, endocervix and TZ that will enable comparisons of how these cells respond to factors that promote cervical carcinogenesis.

Platelet count to spleen diameter ratio (PSR) was studied extensively as a noninvasive method of diagnosis for varices. The present study aimed to systematically assess the performance of PSR in the diagnosis of varices. PubMed, EMBASE, and article references were searched. The summary receiver operating characteristic curves (AUSROCs), sensitivities, specificities, positive and negative likelihood ratio, and diagnostic odds ratio were calculated. The heterogeneity, quality, and publication bias of studies were evaluated. Subgroup and sensitivity analyses were performed. A total of 49 papers were included. The AUSROCs of PSR for any varices and high-risk varices were 0.8719 and 0.8132, respectively. The summary sensitivities of PSR for any varices and high-risk varices were 0.84 and 0.78, respectively. The summary specificities of PSR for any varices and high-risk varices were 0.78 and 0.67, respectively. The AUSROC of PSR for any varices at the threshold of 909 was 0.8867. The AUSROC of PSR for any varices in viral liver cirrhosis was 0.8675. The overall quality of studies was moderate. Significant heterogeneity and publication bias existed in the study. In conclusion, PSR can be used to identify varices in liver cirrhosis. PSR had a high sensitivity in viral liver cirrhosis.

Background and Aims. A retrospective cross-sectional study was conducted to evaluate the role of hyaluronic acid (HA), laminin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and collagen IV (CIV) in predicting the presence of gastroesophageal varices (GEVs) in patients with liver cirrhosis. Methods. We enrolled 118 patients with liver cirrhosis who underwent the tests for the four serum liver fibrosis markers and upper gastrointestinal endoscopy at the same admissions. The predictive values of the four serum liver fibrosis markers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals (CIs). Results. The prevalence of GEVs was 88% (104/118). The AUROCs for HA, LN, PIIINP, and CIV levels in predicting the presence of GEVs were 0.553 (95% CI: 0.458 to 0.644, P=0.5668), 0.490 (95% CI: 0.397 to 0.584, P=0.9065), 0.622 (95% CI: 0.528 to 0.710, P=0.1099), and 0.560 (95% CI: 0.466 to 0.652, P=0.4909). The PIIINP level at a cut-off value of 31.25 had a sensitivity of 73.1% and a specificity of 57.1%. Conclusions. The present study did not recommend HA, LN, PIIINP, and CIV levels to evaluate the presence of GEVs in liver cirrhosis.