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Abstract Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are a group of diseases with marked heterogeneity, including clinical, immunohistochemical, and molecular heterogeneity. The disease remains unspecified in the genetic landscape with only a few sequencing studies to date; however, systematic studies of alimentary canal MALT lymphoma have not been reported. To better understand the genetics of this tumor, targeted sequencing in a group of 31 cases (including 2 esophageal, 2 colonic, 4 small intestinal, and 23 gastric cases) and two cases of lymph node hyperplasiawere performed. We found epigenetic regulation (DNMT3A, KMT2D, KMT2A, EP300, TET2, etc.), signaling pathways (APC, CHD8, TNFAIP3, TNFRSF14, ZAP70, NF1,), and tumor suppressor genes (TP53, BCORL1, FOXO1, ATM, etc.) involved. Moreover, we found MTOR gene mutations in 16% of the cases that made these patients more prone to recurrence and metastasis than those with MTOR wild type genes. More interestingly, ARID2 mutations were detected in 32% of all the cases, and the mutation rate was higher and statistically significant in Helicobacter pylori (Hp)-negative patients in the gastric group. Therefore, this study found that MTOR and ARID2 gene mutations have pathogenic and prognostic implications.

Abstract Background Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis. Case demonstration A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period. Conclusions We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.

Abstract Background Papillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto’s thyroiditis, presenting significant challenges in clinical diagnosis and treatment. Case demonstration A 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis. Conclusions The concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto’s thyroiditis. The patient’s favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases.

Abstract The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome’s biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.

BackgroundMalignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis have been reported. Moreover, primary occurrence in the atrium is extremely rare. The visual appearance of this tumor is similar to that of a common atrial myxoma, which makes it challenging for clinicians and radiologists to diagnose and treat this disease.Case demonstrationAn 18-year-old woman presented with symptoms of chest pain, shortness of breath, cough, and expectoration for 7 days. Echocardiography was performed on the patient, which revealed an atrial mass. Myxoma was one of the differential diagnoses. The tumor was an elliptical mass with tips, and the cut surface was jelly-like, similar to myxoma. After surgery, a pathologic examination of the biopsied tumor confirmed epithelial-type MM. During postoperative follow-up, no recurrence of the tumor was observed.ConclusionsMM originating in the atrium is considered to be extremely rare. Consequently, clinicians can easily misdiagnose atrial MM as a myxoma. Moreover, to confirm the diagnosis, histopathologic biopsy, histomorphological characterization, immunohistochemistry, and molecular genetic testing are required. Therefore, clinical diagnosis and treatment of MM are challenging.

In this study, 17 amino acids were analyzed by amino acid analyzer in 110 honey samples from three different monofloral honeys, i.e.acacia honey, linden honey and rape honey in China, and the honey variety discrimination was performed based on amino acid content combined with chemometrics. The results showed that the content of hydrolyzed amino acids was higher in rape honey than in acacia and linden honey, and the content of 16 amino acids showed significant differences among the honey varieties. The results of principal component analysis (PCA) revealed that the botanical origins of honey samples clustered according to their amino acid content. The results of least squares discriminant analysis (PLS-DA) showed that rape honey could be distinguished from acacia honey and linden honey. Linear discriminant analysis (LDA) showed that the overall discriminant rate of the three honeys was 92.7%, and the discriminant rate of rape honey was 92.3%. This study would provide data support and reference for the classification and identification of rape honey, acacia honey and linden honey.

The transcription factor activating protein 2α (AP2α) is a nuclear transcription factor that specifically binds to DNA and is involved in the regulation of animal embryonic development, cell growth, apoptosis, tumorigenesis, immunity, and other biological processes. In our previous study, the transcription factor AP2α was discovered as a key disease-resistance candidate gene in the yellow drum, Nibea albiflora, in response to a Vibrio harveyi infection through genome-wide association analysis. In the present study, the AP2α gene, which encodes a protein of 424 amino acids, was cloned from a yellow drum. The N-terminal is a trans-activation domain rich in proline and glutamine (P/Q-rich domain), and the middle is a central basic structure (central basic region), which is a highly conserved helix-span-helix motif responsible for DNA binding and protein dimerization. Multiple alignments of amino acid sequences showed that AP2α was highly conserved, with a homology of more than 84.63% among the detected fish, amphibians, birds, and mammals. Quantitative RT-PCR demonstrated that AP2α was widely distributed in the nine tested tissues, with the highest expression in the blood. Moreover, its transcription was significantly activated in the liver, spleen, and head kidney by V. harveyi infection, especially in the liver wherein the transcript level of AP2α reached a peak at 24 h post infection. Subcellular localization by constructing the recombinant eukaryotic expression plasmid pGEFP-AP2α and transfection into HEK293T cells revealed that AP2α was localized in the nucleus. In addition, the soluble GST-AP2α fusion protein was expressed in Escherichia coli BL21. These results demonstrate that AP2α plays an important role in the immune response against V. harveyi in N. albiflora. We provide new insights into the role of AP2α in the innate immunity of teleost fishes and provide a basis for studies on immune mechanisms and disease-resistant breeding in N. albiflora and other marine fish.

Human mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. These cells have been extensively employed in the field of cell-based therapies and regenerative medicine due to their inherent attributes of self-renewal and multipotency. Traditional approaches for assessing hMSCs differentiation capacity have relied heavily on labor-intensive techniques, such as RT-PCR, immunostaining, and Western blot, to identify specific biomarkers. However, these methods are not only time-consuming and economically demanding, but also require the fixation of cells, resulting in the loss of temporal data. Consequently, there is an emerging need for a more efficient and precise approach to predict hMSCs differentiation in live cells, particularly for osteogenic and adipogenic differentiation. In response to this need, we developed innovative approaches that combine live-cell imaging with cutting-edge deep learning techniques, specifically employing a convolutional neural network (CNN) to meticulously classify osteogenic and adipogenic differentiation. Specifically, four notable pre-trained CNN models, VGG 19, Inception V3, ResNet 18, and ResNet 50, were developed and tested for identifying adipogenic and osteogenic differentiated cells based on cell morphology changes. We rigorously evaluated the performance of these four models concerning binary and multi-class classification of differentiated cells at various time intervals, focusing on pivotal metrics such as accuracy, the area under the receiver operating characteristic curve (AUC), sensitivity, precision, and F1-score. Among these four different models, ResNet 50 has proven to be the most effective choice with the highest accuracy (0.9572 for binary, 0.9474 for multi-class) and AUC (0.9958 for binary, 0.9836 for multi-class) in both multi-class and binary classification tasks. Although VGG 19 matched the accuracy of ResNet 50 in both tasks, ResNet 50 consistently outperformed it in terms of AUC, underscoring its superior effectiveness in identifying differentiated cells. Overall, our study demonstrated the capability to use a CNN approach to predict stem cell fate based on morphology changes, which will potentially provide insights for the application of cell-based therapy and advance our understanding of regenerative medicine.

Abstract Background Extragonadal germ cell tumours (EGGCTs) originated in Shoulder are extremely rare, with 1 case described in the literature. We report a case of a patient with a primary Right Shoulder mixed EGGCT. Case presentation A 36-year-old male patient was hospitalized for 6 months due to progressive right shoulder swelling accompanied by pain. Subsequently, the right shoulder tumor was removed entirely. Gross pathological examination showed that the size of the tumor mass was about 14 × 10 × 6 cm.Mutations were observed in ENPEP (4q25), ZCCHC11, RREB1 (6p24.3), CKAP4 (12q23.3), and other genes were detected by whole exome sequencing. Histology revealed a mixed EGGCT of the Right Shoulder with immature teratoma and yolk sac tumour. The patient went through 6 cycles of chemotherapy. After 7 months of follow-up, the patient is recurrence. Conclusion The primary MEGCT of the shoulder is an extremely rare condition. However, the recurrence and metastasis rates are high. Therefore, further research is necessary to determine this rare disease’s genetic and clinical characteristics to develop an effective treatment plan.

Abstract Background CD20-negative diffuse large B-cell lymphoma is a very rare and heterogeneous invasive cancer characterized by chemical resistance and poor prognosis. Primary CD20-negative diffuse large B-cell lymphoma of the central nervous system is even rarer, presenting great challenges in pathological diagnosis and clinical treatment. Case presentation We report a case of primary CD20-negative diffuse large B-cell lymphoma of the CNS in a 54-year-old woman admitted to the hospital with a headache lasting more than 10 days. CT and MRI scans showed right temporal lobe lymphoma. Microscopically, large infiltrating lymphoid cells that induced brain tissue damage were observed. Immunohistochemistry showed that the tumor cells were CD79a+, PAX-5+, MUM1+, and CD20-. The patient was diagnosed with lymphoma and transferred to an oncology hospital for chemotherapy. However, because the disease progressed rapidly, the patient died only after two rounds of chemotherapy. Conclusions To the best of our knowledge, this is one of the first reported cases of unclassifiable CD20-negative diffuse large B-cell lymphoma located in the CNS. This case report aims to deepen the understanding of clinicopathological features of this type of lymphoma and expand the scope of this disease.

Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces, the global regulation based on epigenetic modification is not well explored. N4-methylcytosine (m4C), an abundant epigenetic marker in Actinomycetes’ genome, but its regulatory mechanism remains unclear. In this study, we identify a m4C methyltransferase (SroLm3) in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism. Notably, three BGCs in ΔsroLm3 strain exhibited decreased expression compared to wild type. In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production. In summary, we characterized a m4C methyltransferase, revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment, and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation. Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.

Abstract Introduction Russell body inflammation of the digestive tract (RBIDT) is a rare chronic inflammation of the digestive tract mucosa that commonly presents as Russell body gastritis (RBG). This disease is usually associated with Helicobacter pylori (HP) infection. However, it can also occur in individuals without HP infection and with specific immune profiles, as seen in HIV and hepatitis C infections. The aetiology and pathogenesis of this disease remain controversial. Given the rarity of the disease and the diversity of the immunophenotypes, there is a high probability of misdiagnosis. Case presentation A male patient with RBG and HP infection was included in this study. The case of RBG with an unusual morphology of Mott cells that mimics stamped ring cells.Endoscopy performed during the follow-up revealed regression of the lesion 1 week after anti-HP treatment. Conclusions A case of RBG with a high likelihood of misdiagnosis of signet ring cell carcinoma (SRC) has been reported in this study along with a review of the relevant literature and an overview of RBIDT.

Abstract Background Mucormycosis is a rare but serious opportunistic fungal infection that occurs in immunocompromised individuals, especially those with diabetic ketoacidosis. Presently, early diagnosis of the disease remains a challenge for clinicians. Case presentation The patient, a 68-year-old woman with type 2 diabetes mellitus, was admitted with paroxic sharp pain in the left upper abdomen. CT imaging revealed a patchy hypodense shadow of the spleen with wedge-shaped changes. The patient was not considered early for fungal infection. The diagnosis of spleen mucormycosis was not confirmed until pathological biopsy after splenectomy. After surgery, blood glucose level was controlled, acidosis was corrected, and antifungal therapy was effective. Conclusions We report here, for the first time ever, a case of isolated splenic mucormycosis secondary to diabetic ketoacidosis that was diagnosed and treated with antifungal drugs and splenectomy. Following splenectomy, the presence of splenic mucormycosis was confirmed when characteristic mycelia were observed in a tissue biopsy. As the location of any fungal infection is extremely relevant for treatment options and prognoses, early diagnosis and clinical intervention can greatly affect outcomes and prognoses for patients.

Abstract Background Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

BackgroundThe worldwide dissemination of K. pneumoniae isolates is a significant public health concern, as these organisms possess a unique capacity to acquire genetic elements encoding both resistance and hypervirulence. This study aims to investigate the epidemiological, resistance, and virulence characteristics of K. pneumoniae isolates that carry both virulence plasmids and blaOXA-48-like genes in a tertiary hospital in China.MethodsA total of 217 clinical isolates of carbapenem-resistant K. pneumoniae (CRKP) were collected between April 2020 and March 2022. The antimicrobial susceptibility test was conducted to evaluate the drug resistance profile. All isolates were screened for the presence of genes encoding carbapenemases (blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48-like), ESBLs genes (blaCTX-M, blaSHV, blaTEM), and virulence plasmid pLVPK-borne genes (rmpA, rmpA2, iucA, iroB, and peg344) using polymerase chain reaction (PCR) amplification. Clonal lineages were assigned using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The plasmid incompatibility groups were identified using PCR-based replicon typing (PBRT). The transferability of carbapenemase-encoding plasmids and pLVPK-like virulence plasmids was assessed via conjugation. The plasmid location of rmpA2 was determined using S1-Pulsed Field Gel Electrophoresis (S1-PFGE) and southern blotting hybridization. The virulence potential of the isolates was assessed using the string test, capsular serotyping, serum killing assay and a Galleria mellonella larval infection model.ResultsOf the 217 CRKP clinical isolates collected, 23% were identified as carrying blaOXA-48-like genes. All blaOXA-48-like isolates exhibited resistance to commonly used clinical antimicrobial agents, except for ceftazidime/avibactam, colistin, tigecycline, trimethoprim-sulfamethOXAzole, polymyxin B, and nitrofurantoin. The main common OXA-48-like carbapenemase enzymes were found to be blaOXA-181 and blaOXA-232. MLST and PFGE fingerprinting analysis revealed clonal transmission and plasmid transmission. OXA-48-like producing CRKP isolates mainly clustered in K64 ST11 and K47 ST15. Results of the string Test, serum killing assay (in vitro) and Galleria mellonella infection model (in vivo) indicated hypervirulence. PBRT showed that the blaOXA-181 and blaOXA-232 producing hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) were mainly carried on ColE-type, IncF, and IncX3. Eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (blaKPC, blaOXA-181 or OXA-232, and blaNDM-1). Moreover, Southern blotting hybridization revealed that all eight isolates had a pLVPK-like virulent plasmid (138.9–216.9 kb) with an uneven number and size of plasmid.ConclusionIn our investigation, we have observed the emergence of hv-CRKP carrying blaOXA-48-like genes, which identified two genetic relationships: clonal transmission and plasmid transmission. PBRT analysis showed that these genes were mainly carried on ColE-type, IncF, and IncX3 plasmids. These isolates have been shown to be hypervirulent in vitro and in vivo. Additionally, eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (blaKPC, blaOXA-181 or OXA-232, and blaNDM-1) and carrying a pLVPK-like virulent plasmid. Hence, our findings highlight the need for further investigation and active surveillance of hypervirulent OXA-48-like producing Hv-CRKP isolates to control their transmission.

Microbial communities are essential components of aquatic ecosystems and are widely employed for the detection, protection, and restoration of water ecosystems. The polyurethane foam unit (PFU) method, an effective and widely used environmental monitoring technique, has been improved with the eDNA-PFU method, offering efficiency, rapidity, and standardization advantages. This research aimed to explore the colonization process of microbial communities within PFUs using eDNA-PFU technology. To achieve this, we conducted ten-day monitoring and sequencing of microbial communities within PFUs in a stable and controlled artificial aquatic ecosystem, comparing them with water environmental samples (eDNA samples). Results showed 1065 genera in eDNA-PFU and 1059 in eDNA, with eDNA-PFU detecting 99.95% of eDNA-identified species. Additionally, the diversity indices of bacteria and eukaryotes in both methods showed similar trends over time in the colonization process; however, relative abundance differed. We further analyzed the colonization dynamics of microbes in eDNA-PFU and identified four clusters with varying colonization speeds. Notably, we found differences in colonization rates between bacteria and eukaryotes. Furthermore, the Molecular Ecological Networks (MEN) showed that the network in eDNA-PFU was more modular, forming a unique microbial community differentiated from the aquatic environment. In conclusion, this study, using eDNA-PFU, comprehensively explored microbial colonization and interrelationships in a controlled mesocosm system, providing foundational data and reference standards for its application in aquatic ecosystem monitoring and beyond.

In order to obtain an accurate finite element model of a steel arch bridge, a first-order modal finite element model updating method is proposed by using the measured first-order modal data of the bridge. Using the measured acceleration time history data under random excitation and the first-order mode updating method, the stiffness matrix of the finite element model is updated, and the first-order frequencies and first-order mode shapes before and after updating of the model are compared and analyzed. The state space method is used to compare and analyze the dynamic response and the reliability of the structure before and after the updating of the model. The results show that the difference of the first-order frequencies between the updated finite element model and the measured result is about 0.001, and the difference of the first-order mode shapes is less than 0.197, which meets the needs of engineering. Dynamic response values of the updated structural model are much larger than those of the structural model before updating. The theoretical model is different from the dynamic response of actual structure, so it is necessary to update the theoretical model. The finite element model updating method can provide a reliable analytical way for bridge structural health monitoring, state evaluation, and damage identification.

Uterine adenosarcoma (UA) is an uncommon mixed tumor containing a benign to at most mildly atypical epithelial component and a sarcoma-like stroma, usually a low-grade, stromal component, with rare heterogeneous elements. Currently, tumor etiology is largely unknown. To better understand the gene mutations in UA, next-generation sequencing (NGS) technology analysis was performed. This study showed that two low-grade UAs with heterologous components had ATRX gene frameshift mutation, and one patient had a MED12 missense mutation. Copy number amplification genes were mainly observed on chromosome 12q13–15. In this study, PIK3/AKT/PTEN pathway mutations were found to be common in adenosarcoma. In addition, a rare BCORL1-PRR14L fusion mutation was also identified. These findings provide a basis for future research into these molecular changes in tumorigenesis and targeted therapy.

To provide sufficient lift during takeoff and landing, large aircraft are equipped with complicated high-lift devices. The use of simple flaps coupled with active flow control (AFC) can achieve lift improvement while reducing mechanical structure and weight. The present study focuses on verifying the feasibility and effectiveness of simple flaps combined with sweeping jet flow control. An experimental study on the AFC of flaps, using sweeping jets, was carried out using a NASA SC(2)-0410 supercritical airfoil wind-tunnel model at Re = 2.0 × 105 (with velocity V = 10 m/s). In the experiment, the wing angle of attack (α) ranged from 3 to 18°, and the flap deflection angle (δ) ranged from 0 to 30°; the aerodynamic characteristics and surface pressure characteristics of the wing at typical working conditions were analyzed. Using sweeping jets to control the flow on the flaps, the momentum coefficients (for three actuator groups) of the jet are 0.8%, 3.6%, and 8.2%, respectively, and the maximum lift coefficient was increased by approximately 33%. The influence of the sweeping jet flow rate on the aerodynamic performance of the airfoil is analyzed. There are two main reasons for the lift coefficient increase caused by sweeping jet flow: an extra suction peak near the flap and a suction peak increase near the leading edge area caused by induced flow.

In order to effectively and conveniently identify the damage location and damage degree of structural members under static response, a structural damage identification method based on the force residual vector is proposed. The force residual vector is defined by using the static displacement data and the stiffness matrix of the finite element model structure. The structural element corresponding to the non-zero element of the permutation force residual vector is intelligently determined as the damage element. The damage degree of the damaged unit is calculated from the equilibrium equation, which is established by the global stiffness matrix with only the damaged unit. For example, the identification analysis of damage units of numerical models is carried out for a simply supported beam as a simple structure and a truss as a complex structure based on the proposed method. In El Centro seismic wave, the dynamic responses of the original model and truss damage model are simulated and compared by using state space theory to verify the necessity of damage identification.

In the mechanical analysis of steel structures, whether it is static analysis or dynamic analysis, it is necessary to establish the structural stiffness matrix first. In the process of building the structural stiffness matrix, the same element usually has different node code connection orders, and it has never been argued whether the different connection orders of the same element will have an effect on the building of the stiffness matrix. In this study, the influence of the difference in the node connection order on the construction of the element stiffness matrix is studied. First, the structural element stiffness matrix in the global coordinate system is established when the node connection order is different. It is found that the element stiffness matrix in the global coordinate system is indeed inconsistent for the same element with different connection orders. In this study, the elements of the established element stiffness matrix are extracted into the global stiffness matrix of the structural system based on the law of energy conservation; it is found that the global stiffness matrix finally established by using two different connection relationships is the same. The research results of the example show that in the stress analysis of steel structures, selecting different node connection sequences to establish the structural stiffness matrix will obtain the element stiffness matrix under different global coordinate systems. However, through the aggregation process of the global stiffness matrix of the structural system, the global stiffness matrix obtained is consistent, so the different connection sequences of nodes will not affect the stress analysis of steel structures. The example further analyzes the static stress and dynamic responses of the steel structure. The conclusions of this study provide a reliable theoretical basis for the situation that the order of node connections need not be consistent in the finite element modeling of steel structures and are of reference value for the finite element modeling of steel structures.

Salidroside has been widely used in anti-tumor, cardiovascular, and cerebrovascular protection. However, there are few reports of its use for wound repair. Herein, salidroside inflammation-targeted emulsion gel and non-targeted emulsion gel were developed for wound repair. The inflammation-targeted emulsion gels showed an overall trend of better transdermal penetration and lower potential than non-targeted emulsion gels (−58.7 mV and −1.6 mV, respectively). The apparent improvement of the trauma surface was significant in each administration group. There was a significant difference in the rate of wound healing of the rats between each administration group and the model group at days 7 and 14. Pathological tissue sections showed that inflammatory cells in the epidermis, dermis, and basal layer were significantly reduced, and the granulation tissue was proliferated in the inflammation-targeted emulsion gel group and the non-targeted emulsion gel group. Regarding the expressions of EGF and bFGF, the expressions of bFGF and EGF in the tissues of the inflammation-targeted group at days 7, 14, or 21 were significantly higher than that of the non-targeted emulsion gel group and the model group, both of which were statistically significant compared with the model group (p < 0.05). These results demonstrated that salidroside has the potential as an alternative drug for wound repair.

Hot springs are some of the most special environments on Earth. Many prokaryotic and eukaryotic microbes have been found to live in this environment. The Himalayan geothermal belt (HGB) has numerous hot springs spread across the area. Comprehensive research using molecular techniques to investigate eukaryotic microorganisms is still lacking; investigating the composition and diversity of eukaryotic microorganisms such as protists in the hot spring ecosystems will not only provide critical information on the adaptations of protists to extreme conditions, but could also give valuable contributions to the global knowledge of biogeographic diversity. In this study, we used high-throughput sequencing to illuminate the diversity and composition pattern of protist communities in 41 geothermal springs across the HGB on the Tibetan Plateau. A total of 1238 amplicon sequence variants (ASVs) of protists were identified in the hot springs of the HGB. In general, Cercozoa was the phylum with the highest richness, and Bacillariophyta was the phylum with the highest relative abundance in protists. Based on the occurrence of protist ASVs, most of them are rare. A high variation in protist diversity was found in the hot springs of the HGB. The high variation in protist diversity may be due to the different in environmental conditions of these hot springs. Temperature, salinity, and pH are the most important environmental factors that affect the protist communities in the surface sediments of the hot springs in the HGB. In summary, this study provides the first comprehensive study of the composition and diversity of protists in the hot springs of the HGB and facilitates our understanding of the adaptation of protists in these extreme habitats.

Galectins are proteins that are involved in the innate immune response against pathogenic microorganisms. In the present study, the gene expression pattern of galectin-1 (named as NaGal-1) and its function in mediating the defense response to bacterial attack were investigated. The tertiary structure of NaGal-1 protein consists of homodimers and each subunit has one carbohydrate recognition domain. Quantitative RT-PCR analysis indicated that NaGal-1 was ubiquitously distributed in all the detected tissues and highly expressed in the swim-bladder of Nibea albiflora, and its expression could be upregulated by the pathogenic Vibrio harveyi attack in the brain. Expression of NaGal-1 protein in HEK 293T cells was distributed in the cytoplasm as well as in the nucleus. The recombinant NaGal-1 protein by prokaryotic expression could agglutinate red blood cells from rabbit, Larimichthys crocea, and N. albiflora. The agglutination of N. albiflora red blood cells by the recombinant NaGal-1 protein was inhibited by peptidoglycan, lactose, D-galactose, and lipopolysaccharide in certain concentrations. In addition, the recombinant NaGal-1 protein agglutinated and killed some gram-negative bacteria including Edwardsiella tarda, Escherichia coli, Photobacterium phosphoreum, Aeromonas hydrophila, Pseudomonas aeruginosa, and Aeromonas veronii. These results set the stage for further studies of NaGal-1 protein in the innate immunity of N. albiflora.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and play important roles in many physiological processes. As a representative group of protozoa, ciliates represent the highest stage of eukaryotic cell differentiation and evolution in terms of their reproductive mode, two-state karyotype, and extremely diverse cytogenesis patterns. GPCRs have been poorly reported in ciliates. In this study, we identified 492 GPCRs in 24 ciliates. Using the existing classification system for animals, GPCRs in ciliates can be assigned to four families, including families A, B, E, and F. Most (377 members) belong to family A. The number of GPCRs is extremely different in different ciliates; the Heterotrichea ciliates usually have more GPCRs than other ciliates. Parasitic or symbiotic ciliates usually have only a few GPCRs. Gene/genome duplication events seem to play important roles in the expansion of the GPCR superfamily in ciliates. GPCRs in ciliates displayed seven typical domain organizations. GPCRs in an ortholog group are common and conserved in all ciliates. The gene expression analysis of the members in this conserved ortholog group in the model ciliate, Tetrahymena thermophila, suggested that these GPCRs play important roles in the life cycle of ciliates. In summary, this study provides the first comprehensive genome-wide identification of GPCRs in ciliates, improving our understanding of the evolution and function of GPCR in ciliates.

ObjectiveTo determine if the early response assessments can predict the long-term efficacy of anti-vascular endothelial growth factor (VEGF) treatment for macular edema secondary to retinal vein occlusion (RVO-ME).MethodsA retrospective study of patients with diagnosis of RVO-ME and intravitreal anti-VEGF treatment was conducted. Clinical characteristics including age, gender, disease subtype and disease duration were recorded at baseline. The best corrected visual acuity (BCVA and logMAR), intraocular pressure (IOP), and central macular thickness (CMT) were recorded at baseline, 2 weeks, and every month (months 1–6) after injection. Further, we compared the early response assessments between the cured group (6-month CMT ≤ 250 μm) and the uncured group (6-month CMT > 250 μm).ResultsA total of 164 eyes in 164 patients (77 male and 87 female) were included. At each post-injection time point, both BCVA and CMT are significantly decreased from baseline (all P < 0.001). Spearman’s test showed that 2-week CMT reduction rate after the first injection was negatively correlated with BCVA at 6 months (r = −0.359, P < 0.001). Compared with the uncured group (47 cases), the cured group (117 cases) was younger (59.53 ± 11.68 vs. 65.19 ± 13.10 years old, P < 0.01), had more BRVO patients (76.1% vs. 44.7%, P < 0.01), a shorter disease duration (1.92 ± 2.43 vs. 5.05 ± 4.32 months, P < 0.01), lower baseline CMT (527.09 ± 154.95 vs. 768.96 ± 287.75 μm, P < 0.01), and lower baseline BCVA (0.86 ± 0.44 vs. 1.31 ± 0.51, P < 0.01). At each post-injection time point, the cured group had lower CMT and BCVA values when compared to the uncured group (all P < 0.01), and the 2-week CMT reduction rate was identified as the earliest response time to predict the long-term treatment efficacy. Moreover, ROC curve analysis indicated that a 2-week CMT reduction rate >37% yielded the best cut-off point for predicting the long-term cure of anti-VEGF treatment at 6 months (P < 0.001). Multivariable logistic regression confirmed that the 2-week CMT reduction rate >37% was independently associated with the 6-month cured rate (OR = 9.639, 95% Cl = 1.030–90.227, P = 0.047).ConclusionAge, disease duration, baseline CMT, and baseline BCVA are associated with visual outcomes at 6-month of anti-VEGF treatment for RVO-ME. The “2-week CMT reduction rate >37%” after the first injection is an independent factor to predict better long-term outcomes.

Sauce-flavored Daqu exhibits different colors after being stacked and fermented at high temperatures. Heiqu (black Daqu, BQ) with outstanding functions is difficult to obtain because its formation mechanism is unclear. In this study, we compared the metabolites in different types of Daqu using ultra-high-performance liquid chromatography triple quadrupole mass spectrometry to explore the formation process of BQ. We found that 251 differential metabolites were upregulated in BQ. Metabolic pathway analysis showed that “tyrosine metabolism” was enriched, and most metabolites in this pathway were differential metabolites upregulated in BQ. The tyrosine metabolic pathway is related to enzymatic browning and melanin production. In addition, the high-temperature and high-humidity fermentation environment of sauce-flavored Daqu promoted an increase in the melanoidin content via a typical Maillard reaction; thus, the melanoidin content in BQ was much higher than that in Huangqu and Baiqu. By strengthening the Maillard reaction precursor substances, amino acids, and reducing sugars, the content of Daqu melanoidin increased significantly after simulated fermentation. Therefore, the enzymatic browning product melanin and Maillard reaction product melanoidin are responsible for BQ formation. This study revealed the difference between BQ and other types of Daqu and provides theoretical guidance for controlling the formation of BQ and improving the quality of liquor.

Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia.Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies.Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.

The development of the commercial multi global navigation satellite system (GNSS) dual (multi)-antenna common-clock receiver that uses time-synchronization technology has brought new opportunities for high-precision GNSS-based attitude determination. In this article, for the first time, we present a performance comparison of global positioning system (GPS) L1/Galileo navigation satellite system (Galileo) E1 attitude determination with a common-clock receiver using four different models, i.e., the loosely combined single-differenced (SD-LC) model, the tightly combined single-differenced (SD-TC) model, the loosely combined double-differenced (DD-LC) model, and the tightly combined double-differenced (DD-TC) model. We first introduce the SD-LC, SD-TC, DD-LC, and DD-TC relative positioning models with GPS L1/Galileo E1 observations from a common-clock receiver. Then, we present a performance comparison of the four models in both single-epoch and multi-epoch modes using static data collected with a Trimble BD992 common-clock receiver in terms of the ambiguity dilution of precision (ADOP), the ambiguity resolution (AR) success and failure rates, and the positioning and attitude determination accuracy. In the case of the single-epoch mode, the experimental results revealed that the results of the single-differenced (SD) models were identical to those of double-differenced (DD) models, i.e., the results of SD-LC and SD-TC models were identical to DD-LC and DD-TC models, respectively. Moreover, compared with the loosely combined model (SD-LC/DD-LC), the tightly combined model (SD-TC/DD-TC) delivered a much higher AR success rate and a lower AR failure rate, especially under a high elevation cutoff angle. The AR success rate increased by approximately 35.1% under a 40° elevation cutoff angle, while the AR failure rate decreased by approximately 4.3%. In the case of the multi-epoch mode, the experimental results confirmed the advantages of the tightly combined model over the loosely combined model as well as the SD model over the DD model. Compared with the DD-LC and SD-LC models, the AR success rates of the DD-TC and SD-TC models were improved by approximately 16.7% and 0.6% under a 45° elevation cutoff angle, respectively. The AR failure rates were reduced by approximately 12.4% and 0.3%, respectively. Moreover, compared with the DD-LC and DD-TC models, the AR success rates of the SD-LC and SD-TC models under a 45° elevation cutoff angle were improved by approximately 24.0% and 7.9%, respectively, and the AR failure rates were reduced by approximately 19.9% and 7.8%, respectively. Meanwhile, compared with the DD model, the SD model delivered comparable yaw accuracy and remarkably better pitch accuracy. The pitch accuracy was improved by approximately 65.2–75.0%.

Urban agglomeration is the strategic core area of social–economic high-quality development in the world. However, high-density agglomeration and high-speed expansion have caused dramatic changes in land space, leading to prominent eco-environmental problems and, thus, threatening human well-being. How to solve the contradiction between urban agglomeration land expansion and eco-environment protection has become an urgent scientific problem. In this paper, we constructed a framework of assessing land space change and its eco-environmental effects in the urban agglomeration by using the Geo-informatic Graphic, eco-environmental quality index (EQI), and eco-environmental contribution rate. We then quantitatively analyzed the characteristics of land space transition as well as its eco-environmental effects in the Guanzhong Plain urban Agglomeration (GPUA) based on the land use data in 1990, 2000, 2010 and 2020. The results indicated that from 1990 to 2020, the production space of the GPUA continued to shrink, the living space continued to expand, and the ecological space showed a fluctuating increasing trend. There were significant regional differences in the land space change of the GPUA, with 92.2% of the counties showing a significant contraction in agricultural production space, 93.3% and 91.1% showing a significant expansion in urban and rural living space, and 64.4% showing an increase in woodland ecological space. Agricultural production space is transformed into ecological space and living space, and living space occupies ecological space and agricultural production space, which is the main mode of land space transition in the GPUA. With the continuous expansion of low-quality and high-quality areas of the eco-environment and the continuous contraction of medium-quality areas, the improvement and deterioration of the eco-environmental quality of the GPUA have coexisted, first showing a trend of deterioration and then improvement. The transition of agricultural production space into grassland and woodland ecological space improved the eco-environmental quality, while the transition of grassland ecological space into agricultural production space, and the occupation of agricultural production space by urban and rural living space as well as industrial and mining production space resulted in the deterioration of eco-environmental quality. The findings of this study may provide a theoretical basis for optimizing the allocation of land space resources in ecologically fragile urban agglomeration.

Aluminum (Al) toxicity is the main factor limiting plant growth and the yield of cereal crops in acidic soils. Al-induced oxidative stress could lead to the excessive accumulation of reactive oxygen species (ROS) and aldehydes in plants. Aldehyde dehydrogenase (ALDH) genes, which play an important role in detoxification of aldehydes when exposed to abiotic stress, have been identified in most species. However, little is known about the function of this gene family in the response to Al stress. Here, we identified an ALDH gene in maize, ZmALDH, involved in protection against Al-induced oxidative stress. Al stress up-regulated ZmALDH expression in both the roots and leaves. The expression of ZmALDH only responded to Al toxicity but not to other stresses including low pH and other metals. The heterologous overexpression of ZmALDH in Arabidopsis increased Al tolerance by promoting the ascorbate-glutathione cycle, increasing the transcript levels of antioxidant enzyme genes as well as the activities of their products, reducing MDA, and increasing free proline synthesis. The overexpression of ZmALDH also reduced Al accumulation in roots. Taken together, these findings suggest that ZmALDH participates in Al-induced oxidative stress and Al accumulation in roots, conferring Al tolerance in transgenic Arabidopsis.

In this paper, a new algorithm for extracting the laser fringe center is proposed. Based on a deep learning skeleton extraction network, the laser stripe center can be extracted quickly and accurately. Skeleton extraction is the process of reducing the shape image to its approximate central axis representation while maintaining the image’s topological and geometric shape. Skeleton extraction is an important step in topological and geometric shape analysis. According to the characteristics of the wheelset laser curve dataset, a new skeleton extraction network, a hierarchical skeleton network (LuoNet), is proposed. The proposed architecture has three levels of the encoder–decoder network, and YE Module interconnection is designed between each level of the encoder and decoder network. In the wheelset laser curve dataset, the F1_score can reach 0.714. Compared with the traditional laser curve center extraction algorithm, the proposed LuoNet algorithm has the advantages of short running time, high accuracy, and stable extraction results.

Global navigation satellite system (GNSS)-based attitude determination has been widely applied in a variety of fields due to its high precision, no error accumulation, low power consumption, and low cost. Recently, the emergence of common-clock receivers and construction of GNSS systems have brought new opportunities for high-precision GNSS-based attitude determination. In this contribution, we focus on evaluating the performance of the BeiDou regional navigation satellite system (BDS-2)/BeiDou global navigation satellite system (BDS-3)/Global Positioning System (GPS)/Galileo navigation satellite system (Galileo) attitude determination based on the single-differenced (SD) model with a common-clock receiver. We first investigate the time-varying characteristics of BDS-2/BDS-3/GPS/Galileo line bias (LB) with two different types of common-clock receivers. The results have confirmed that both the phase and code LBs are relatively stable in the time domain once the receivers have started. However, the phase LB is expected to change to an arbitrary value after each restart of the common-clock receivers. For the first time, it is also found that the phase LBs of overlapping frequencies shared by different GNSS systems are identical. Then, we primarily evaluated the performance of BDS-2/BDS-3/GPS/Galileo precise relative positioning and attitude determination based on the SD model with a common-clock receiver, using a static dataset collected at Wuhan. Experimental results demonstrated that, compared with the double-differenced (DD) model, the SD model can deliver a comparable root–mean–square (RMS) error of yaw but a significantly smaller RMS error of pitch, whether for BDS-2, BDS-3, GPS, or Galileo alone or a combination of them. The improvements of pitch accuracy are approximately 20.8–47.5% and 40.7–57.5% with single- and dual-frequency observations, respectively. Additionally, BDS-3 can deliver relatively superior positioning and attitude accuracy with respect to GPS and Galileo, due to its better geometry. The three-dimensional positioning and attitude (including yaw and pitch) accuracy for both the DD and SD models can be remarkably improved by the BDS-2, BDS-3, GPS, and Galileo combination with respect to a single system alone.