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Abstract In order to evaluate the beneficiation plant environment in a more scientific and reasonable way, this paper took the workshop environment of the beneficiation plant as the research object. This paper divided the beneficiation plant into 7 evaluation units according to its functions. The evaluation indices are dust, noise, light environment, microclimate, benzene, toluene and xylene. This paper combines the G1 method and the entropy weight method to evaluate the weight of each evaluation index, the element extension model of the concentrator working environment is established by the element analysis method, and the matter element analysis method is used to establish an evaluation index system of a beneficiation plant in East China. The results show that the evaluation level of the breaking workshop and the auxiliary facilities are unqualified, the auxiliary facility is qualified, the culling workshop, culled yard and accessory building are medium, the screening workshop and grinding workshop are good.

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Abstract The weakening of circular tunnels is a global problem that has not been resolved satisfactorily. In the tunnelling process, surrounding rock of circular-tunnel performs a process of “excavating → weakening → continuous excavating → weakening strengthens”. Different rates of excavation affect the stress adjustment of the surrounding rock, and also have an impact on the weakening of a circular-tunnel. An instability failure test was conducted on a circular-tunnel with varying vertical loading rates. The loading rate was utilized as a representative measure for the excavation rate on the site. The results showed that the weakening process of a circular-tunnel can be divided into four distinct phases, hydrostatic pressure (E1), particle ejection (E2), flake stripping (E3), and instability (E4). The ordering of these phases is E3 > E4 > E1 > E2. In the weakening process of a circular-tunnel, the root cause is the original stress level, while the essential factor is the engineering disturbance. A faster vertical loading rate leads to greater stress adjustment, higher strain energy accumulation, and an increased probability of circular-tunnel instability. The presence of a quiet period of AE events in the middle and later phases of flake stripping is a precursory characteristic of circular-tunnel instability. This study has both theoretical and practical significance in terms of revealing the mechanism of circular-tunnel instability and achieving a reasonable arrangement of the circular-tunnel support process.

Abstract Objectives Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. Methods We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves. Results There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI−lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI−lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. Conclusion 18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

Key Clinical Message In addition to post‐transplant lymphoproliferative disorders, it is necessary to be alert to the drug‐resistant bacteria or fungal infection, especially Talaromyces marneffei, in kidney transplant patients who have failed antibiotic treatment and whose PET‐CT indicates high metabolic mass in the transplanted kidney with a large number of other organs and lymph nodes. Abstract Talaromyces marneffei (TM) is a rare pathogenic fungus that primarily affects individuals with compromised immune systems. Post‐transplant lymphoproliferative disorders (PTLD) are serious complications that can occur after solid organ and cell transplantation. Both TM infection and PTLD can invade the monocyte–macrophage system and often manifest as extranodal masses. This case report describes a kidney transplant patient who presented with symptoms of frequent, urgent, and painful urination over 6 months. Pulmonary CT scans revealed multiple nodules, and PET‐CT demonstrated enlarged lymph nodes in the lungs and the transplanted kidney. The clinical manifestations closely mimicked those of PTLD. The confirmation of TM was achieved through pathogen metagenomic next‐generation sequencing and renal biopsy. Unfortunately, despite receiving treatment with antifungal agents, anti‐infective therapy, the patient's condition did not respond favorably, ultimately resulting in their unfortunate demise due to COVID‐19.

Vascular smooth muscle cells (VSMCs) are integral to the pathophysiology of cardiovascular diseases (CVDs). Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in epigenetic regulation of VSMCs gene expression. Emerging researches suggest that EZH2 has a dual role in VSMCs, contingent on the pathological context of specific CVDs. This mini-review synthesizes the current knowledge on the mechanisms by which EZH2 regulates VSMC proliferation, migration and survival in the context of CVDs. The goal is to underscore the potential of EZH2 as a therapeutic target for CVDs treatment. Modulating EZH2 and its associated epigenetic pathways in VSMCs could potentially ameliorate vascular remodeling, a key factor in the progression of many CVDs. Despite the promising outlook, further investigation is warranted to elucidate the epigenetic mechanisms mediated by EZH2 in VSMCs, which may pave the way for novel epigenetic therapies for conditions such as atherosclerosis and hypertension.

PurposeThe objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among individuals diagnosed with Type 2 diabetes mellitus (T2DM) across different cognitive states. Moreover, the study sought to explore the potential association between aberrant FCD/FC patterns and clinical or cognitive variables.MethodsA total of 211 participants were recruited for this study, consisting of 75 healthy controls (HCs), 89 T2DM patients with normal cognitive function (DMCN), and 47 T2DM patients with mild cognitive impairment (DMCI). The study employed FCD analysis to pinpoint brain regions exhibiting significant FCD alterations. Subsequently, these regions showing abnormal FCD served as seeds for FC analysis. Exploratory partial correlations were conducted to explore the relationship between clinical biochemical indicators, neuropsychological test scores, and altered FCD or FC.ResultsThe FCD analysis revealed an increased trend in global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD) within the bilateral supramarginal gyrus (SMG) among individuals with DMCN. Additionally, significant lFCD alterations were observed in the right inferior frontal gyrus and left precuneus when comparing DMCN to HCs and DMCI.ConclusionWhen comparing individuals with T2DM and healthy controls (HCs), it was revealed that DMCN exhibited significant improvements in FCD. This suggests that the brain may employ specific compensatory mechanisms to maintain normal cognitive function at this stage. Our findings provide a novel perspective on the neural mechanisms involved in cognitive decline associated with T2DM.

PPM1A is a member of the serine/threonine protein phosphatase family. It can bind to a variety of proteins to dephosphorylate them, and extensively regulates many life activities such as cell growth, cell stress, immune response, and tumor formation. Here we constructed a human induced pluripotent stem cell (hiPSC) line with knockout of PPM1A using CRISPR/Cas9-mediated gene targeting. This cell line exhibits normal karyotype, pluripotency, and trilineage differentiation potential, which could provide a useful cellular resource for exploring the mechanism of PPM1A in regulating downstream signaling pathways and explore the application of PPM1A in anti-tumor and anti-infection.

Abstract Background Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear. Case presentation Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma. Conclusion This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes.

Abstract Water and mud inrush caused by fault is a geological disaster characterized by high frequency and huge destructiveness. It is important to study the evolutionary laws of water inrush in fault fracture zones with various filling types. The effect of filling gradation on the mesoscopic structure and seepage characteristics of fault fracture zones was investigated. The law of water inrush evolution and water inrush characteristics of fault-fractured zones with different filling gradations and strong zoning filling characteristics were studied. The results showed that for the larger Talbot gradation indices, the mass of water inrush and the fractal dimension of the lost particles were larger, the peak water pressure and the mass of the lost particles were smaller, and the duration of the initial impermeability stage was shorter for the same loading water pressure. For the fault fracture zones with strong zoning filling characteristics, the peak water pressure, the mass of water surges, and the mass of lost particles were larger, the fractal dimension of the lost particles was smaller, and the duration of the initial impermeability stage was shorter for the fracture zones with larger filling gradation were used as the initial impermeability zones. Furthermore, with larger filling gradation, we observed a greater proportion of large pores, a larger equivalent throat radius, higher pore connectivity, and coordination numbers. Filling gradation and confining pressure greatly affected the permeability of the fault. The permeability decreased by 98.71% when the Talbot gradation indices decreased from 1.25 to 0.6, and decreased by 58.4% when the confining pressure increased from 5 MPa to 15 MPa.

This study examines the issues of privacy protection, data security, and query efficiency in blockchain-based electronic medical record (EMR) sharing. It proposes a secure storage and sharing scheme for EMR based on Hyperledger Fabric and the InterPlanetary File System (IPFS). To mitigate the privacy risks of data mining that could reveal patient identities, we establish an attribution channel in Hyperledger Fabric to store EMR ownership information and a data channel to store the storage location, digest, and usage records of medical data. Encrypted medical data are stored in the IPFS. To improve query efficiency in the blockchain, we integrate queryable medical data attributes into a composite key for conditional queries, avoiding complex data filtering processes. Additionally, we use a zero-knowledge proof combined with smart contracts for decentralized identity verification, eliminating reliance on third-party centralized verification services and enhancing system security. We also integrate AES and proxy re-encryption techniques to ensure data security during sharing. This scheme provides a more secure, efficient, and privacy-preserving approach for EMR systems, with significant practical implications and broad application potential.

Orf virus (ORFV), a typical member of the genus Parapoxvirus, Poxvirus family, causes a contagious pustular dermatitis in sheep, goats, and humans. Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm, which is a viral factor essential to poxvirus replication. Due to its vital role in viral life, vRNAP has emerged as one of the potential drug targets. In the present study, we investigated the antiviral effect of genistein against ORFV infection. We provided evidence that genistein exerted antiviral effect through blocking viral genome DNA transcription/replication and viral protein synthesis and reducing viral progeny, which were dosedependently decreased in genistein-treated cells. Furthermore, we identified that genistein interacted with the vRNAP RPO30 protein by CETSA, molecular modeling and Fluorescence quenching, a novel antiviral target for ORFV. By blocking vRNAP RPO30 protein using antibody against RPO30, we confirmed that the inhibitory effect exerted by genistein against ORFV infection is mediated through the interaction with RPO30. In conclusion, we demonstrate that genistein effectively inhibits ORFV transcription in host cells by targeting vRNAP RPO30, which might be a promising drug candidate against poxvirus infection.

Retaining wall is essential for stopes mining in two steps, for it can prevent the instability and collapse of backfill. In this study, taking the retaining wall of backfilled stope as the research object, a stability analysis method of retaining wall based on the close coupling of catastrophe theory and numerical analysis was proposed. First, by extracting the unit failure rate of the retaining wall from the numerical simulation results and fitting it with the mining depth, the functional expression between them was established. Second, the function relation was transformed into the normal form according to catastrophe theory, and the instability criterion of retaining wall was deduced. Furthermore, an effort was made to analyze the changing law of the state of retaining wall and calculate the critical span of stope, under different thickness conditions. On this basis, the application test of retaining wall was carried out by using this method. The results show that with the thickness decreasing, the values of splitting variables a and b show a reverse trend, which leads to the discriminant of instability criterion decreasing and turning from positive to negative, resulting in the collapse. Meanwhile, in order to ensure the stability, the wider the span of the stope, the thicker the retaining wall is required, and conversely, the thicker the retaining wall, the higher the adaptability to the span of stope. In addition, it can be found from the application test that instability was bound to occur with a thickness of 3 m, but the retaining wall with a thickness of 4 m maintained stable, which tended to be consistent with the analysis. Therefore, the stability analysis method proposed in this study provides a way to accurately evaluate the stability of the retaining wall and calculate the critical thickness of that, and its application value is expected to be further explored.

NSD2 is a histone methyltransferase (HMT) and is involved in the epigenetic regulation of hematopoiesis and hematological cancers. To understand and illustrate the precise roles of NSD2 in hematopoietic development, here we constructed a human embryonic stem cell (hESC) line with knockout of NSD2 using CRISPR/Cas9-mediated gene targeting. The cell line maintained typical stem cell morphology and normal karyotype. Furthermore, the pluripotency of the cell line was evidenced by high expression level of pluripotency genes and differentiation potential into three germ layers. The cell line provides a good model for studying roles of NSD2 in embryonic development, especially hematopoiesis.

Abstract Orf virus (ORFV) is the causative agent of contagious ecthyma, which is an important zoonotic pathogen with a widespread distribution affecting sheep, goats and humans. Our previous research showed that autophagy can be induced in host cells by ORFV infection. However, the exact mechanism of ORFV-induced autophagy remains unknown. In this study, we investigated the underlying mechanisms of autophagy induced by ORFV in OFTu cells and the impact of autophagy on ORFV replication. By using specific autophagy inhibitors and activators, Western blotting, immunofluorescence and transmission electron microscopy imaging, we confirmed that ORFV infection triggered intracellular autophagosome accumulation and the activation of autophagic flux. Moreover, ORFV-induced autophagic activity was found to rely on an increase in the phosphorylation of tuberous sclerosis complex 2 (TSC2) and a decrease in the phosphorylation of mammalian target of rapamycin (mTOR), which is mediated by the suppression of the PI3K/AKT/mTOR signalling pathway and activation of the ERK1/2/mTOR signalling pathway. Furthermore, we investigated the role of mTOR-mediated autophagy during ORFV replication using pharmacological agents and demonstrated that ORFV-induced autophagy correlated positively with viral replication. Taken together, our data reveal the pathways of ORFV-induced autophagy and the impact of autophagy on ORFV replication, providing new insights into ORFV pathogenesis.

China's “demographic dividend” has gradually disappeared since 2013, but the problem of human capital mismatch prevails in various industries and sectors, and improving human capital mismatch and optimizing the allocation of human capital has become an important measure for high-quality economic development. This study uses panel data at the provincial level in the Yangtze River Delta region from 2012 to 2021 and employs spatial econometric models to quantitatively analyze the index of human capital mismatch, the impact mechanism, and spatial interaction effects in strategic emerging industries. The results show that the spatial agglomeration and dependence of human capital mismatch decreased in the Yangtze River Delta region, and the index of human capital mismatch in strategic emerging industries is generally insufficient. The shortage of talent supply within industries is particularly severe in high-end equipment manufacturing and biotechnology industries. Second, fiscal subsidies have exacerbated human capital mismatches in both local and neighboring areas, with significant spatial spillover effects. Urbanization has exacerbated local human capital mismatches but has improved the degree of human capital mismatch in neighboring areas. The index of industrial structural adjustment is generally conducive to alleviating human capital mismatches. Distorted markets and financial levels have accelerated human capital mismatches by distorting the efficiency of human capital allocation. Third, regional heterogeneity significantly influences the spatial interaction effects of human capital mismatches. This study contributes to improving the situation of human capital mismatch in strategic emerging industries in the Yangtze River Delta and provides theoretical and policy recommendations for local governments.

Long-term stability and stable efficiency are essential for large-area fabrication of perovskite solar cells. Here, the authors achieve in situ anion-fixation and undercoordinated-Pb passivation using amidino-based ligand, realizing maximum power conversion efficiency of 25.3% with T95 over 500 h.

Oncolytic viruses are able to target tumours and thought to induce apoptosis while remodelling the tumour immune microenvironment. Here authors show in an oncolytic parapoxvirus ovis model that pyroptosis, a highly immunogenic Gasdermin-E-dependent cell death mechanism, is the dominant cell death pathway during virotherapy.

Lactiplantibacillus plantarum, a typical ecological species against pathogens, used due to its bacteriocin yield in fermented foods, was proven to have the capacity to lower cholesterol. In this study, using L. plantarum ATCC8014 as the control, L. plantarum WLPL21 and ZDY04 were probed with whole-genome sequencing to ascertain their potential ability to lower cholesterol and yield bacteriocins, as well as to further evaluate their survival capacity in vitro. Our results showed 386 transport-system genes in both L. plantarum WLPL21 and ZDY04. Correspondingly, the in vitro results showed that L. plantarum WLPL21 and ZDY04 could remove cholesterol at 49.23% and 41.97%, respectively, which is 1.89 and 1.61 times that of L. plantarum ATCC8014. The survival rates of L. plantarum WLPL21 and ZDY04 in 1% H2O2, pH 3.0, and 0.3% bile salt were higher than those of L. plantarum ATCC8014. Our results exhibited a complete gene cluster for bacteriocin production encoded by L. plantarum WLPL21 and ZDY04, including plnJKR, plnPQAB, plnEFI, plnSUVWY, and plnJK; and plnMN, plnPQA and plnEFI, respectively, compared with only plnEF in L. plantarum ATCC8014. The present study suggests that the combination of genomic analysis with in vitro evaluations might be useful for exploring the potential functions of probiotics.

In order to meet the increasing pollutants discharge standard, the selective catalytic reduction (SCR) module in the diesel engine after-treatment system is an important means to reduce nitrogen oxide (NOx) emissions. SCR systems are prone to urea crystallization at lower temperatures, especially during the cold-start conditions of diesel engines. In this study, we use the diesel engine after-treatment system test bench to obtain the boundary parameter of the simulation modules, and the urea crystallization risk assessment model of the diesel SCR system is established. Comparing the computational fluid dynamics (CFD) results with the test bench results, it is shown that the predicted urea film distribution of the assessment model is in good agreement with the experimental results. In order to clarify the various factors that affect the urea crystallization risk, this paper conducts a simulation analysis on a nozzle and mixer structure and operating parameters. The CFD results indicate that the increase in urea spray time will increase the maximum urea film thickness on the SCR system mixer surface. Exhaust temperature is the most important influencing factor. When the diesel engine exhaust temperature increases from 190 °C to 300 °C, the maximum urea film thickness decreases by 32 and the urea film mass accumulation decreases by 5%. Exhaust flow has a small impact on urea crystallization risk. When the exhaust flow increases from 300 kg/h to 600 kg/h, the maximum urea film thickness decreases by 39% and the urea film mass accumulation decreases by about 1%. In addition, urea spray rate, nozzle numbers, spray angle, and spray cone angle are also factors that affect urea crystallization risk.

Abstract Background It is vital to distinguish between inflammatory and malignant lymphadenopathy in human immunodeficiency virus (HIV) infected individuals. The purpose of our study was to differentiate the variations in the clinical characteristics of HIV patients, and apply 18F-FDG PET/CT parameters for distinguishing of malignant lymphoma and inflammatory lymphadenopathy in such patients. Methods This retrospective cross-sectional study included 59 consecutive HIV-infected patients who underwent whole-body 18F-FDG PET/CT. Of these patients, 37 had biopsy-proven HIV-associated lymphoma, and 22 with HIV-associated inflammatory lymphadenopathy were used as controls. The determined parameters were the maximum of standard uptake value (SUVmax), SUVmax of only lymph nodes (SUVLN), the most FDG-avid lesion-to-liver SUVmax ratio (SURmax), laboratory examinations and demographics. The optimal cut-off of 18F-FDG PET/CT value was analyzed by receiver operating characteristic curve (ROC). Results Considering the clinical records, the Karnofsky Performance Status (KPS) scores in patients with inflammatory lymphadenopathy were obviously higher than those in patients with malignant lymphoma (P = 0.015), whereas lymphocyte counts and lactate dehydrogenase (LDH) were obviously lower (P = 0.014 and 0.010, respectively). For the 18F-FDG PET/CT imaging, extra-lymphatic lesions, especially digestive tract and Waldeyer’s ring, occurred more frequently in malignant lymphoma than inflammatory lymphadenopathy. Furthermore, the SURmax and SUVLN in malignant lymphoma were markedly higher than those in inflammatory lymphadenopathy (P = 0.000 and 0.000, respectively). The cut-off point of 3.1 for SURmax had higher specificity (91.9%) and relatively reasonable sensitivity (68.2%) and the cut-off point of 8.0 for the SUVLN had high specificity (89.2%) and relatively reasonable sensitivity (63.6%). Conclusion Our study identified the distinctive characteristics of the clinical manifestations, the SURmax, SUVLN and detectability of extra-lymphatic lesions on 18F-FDG PET, and thus provides a new basis for distinguishing of malignant lymphoma from inflammatory lymphadenopathy in HIV-infected patients.

Abstract Background Nonocclusive mesenteric ischemia (NOMI) is defined as acute intestinal ischemia because of decreased blood flow in mesenteric vessels. Only a few cases of NOMI that occur secondary to aortic dissection (AD) have been reported, resulting in the lack of sufficient knowledge of diagnosis and treatment. Case presentation We aimed to report a case of NOMI caused by type B Aortic Dissection. A 26-year-old male patient was transferred to our hospital with the diagnose of NOMI and aortic dissection in April 2018. The abdominal computed tomography (CT) assists the diagnosis of paralytic intestinal obstruction, intestinal wall pneumatosis, and perforation. Emergency laparotomy revealed that the bowel wall supplied by the superior mesenteric artery (SMA) was pale with the palpable but weak pulsation of the parietal artery. The small intestine was extremely dilated with a paper-thin, fragile wall that was ruptured easily and could not be sutured. In this case, extensive resection and segmental drainage were done. Postoperatively, the digestive tract was reconstructed. However, the patient suffered from iron deficiency anemia and short bowel syndrome eight months later, and unfortunately died from long-term complications. Conclusion Aortic dissection leads to continuous decrease in blood pressure and blood flow to the SMA, considering as a predisposing factor for NOMI. During the treatment, extensive resection and segmental drainage are the optimal surgical strategy, which can make benefit in emergencies especially.

PurposeThis study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.MethodsThis study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants’ serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.ResultsThe levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.ConclusionT2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.

We report an uncommon case of ipsilateral comminuted distal radius and comminuted radial head fractures with posterolateral elbow dislocation. A 51-year-old female had a fall that resulted in a comminuted distal radius fracture with an ipsilateral comminuted radial head fracture and posterolateral dislocation of the elbow. Clinical evaluation revealed that her left elbow was posteriorly dislocated and her left wrist was deformed. Plain radiographs showed an intraarticular fracture of the distal end of the radius and a comminuted radial head fracture with a proximally migrated radius. Magnetic resonance imaging (MRI) also showed lateral ulnar collateral ligament injuries. We addressed her distal radius with an anatomical locking plate and then treated her comminution radial head fracture with a radial head replacement. Postoperative radiographs showed a good reduction. The Cooney score was 90 at one year postoperatively.

Contagious ecthyma (Orf), an acute and highly contagious zoonosis, is prevalent worldwide. Orf is caused by Orf virus (ORFV), which mainly infects sheep/goats and humans. Therefore, effective and safe vaccination strategies for Orf prevention are needed. Although immunization with single-type Orf vaccines has been tested, heterologous prime-boost strategies still need to be studied. In the present study, ORFV B2L and F1L were selected as immunogens, based on which DNA, subunit and adenovirus vaccine candidates were generated. Of note, heterologous immunization strategies using DNA prime-protein boost and DNA prime-adenovirus boost in mice were performed, with single-type vaccines as controls. We have found that the DNA prime-protein boost strategy induces stronger humoral and cellular immune responses than DNA prime-adenovirus boost strategy in mice, which was confirmed by the changes in specific antibodies, lymphocyte proliferation and cytokine expression. Importantly, this observation was also confirmed when these heterologous immunization strategies were performed in sheep. In summary, by comparing the two immune strategies, we found that DNA prime-protein boost strategy can induce a better immune response, which provides a new attempt for exploring Orf immunization strategy.

ABSTRACT Porcine hemagglutinating encephalomyelitis virus (PHEV) is a member of the family Coronaviridae, genus Betacoronavirus, and subgenus Embecovirus that causes neurological disorders, vomiting and wasting disease (VWD), or influenza-like illness (ILI) in pigs. Exosomes regulate nearby or distant cells as a means of intercellular communication; however, whether they are involved in the transmission of viral reference materials during PHEV infection is unknown. Here, we collected exosomes derived from PHEV-infected neural cells (PHEV-exos) and validated their morphological, structural, and content characteristics. High-resolution mass spectrometry indicated that PHEV-exos carry a variety of cargoes, including host innate immunity sensors and viral ingredients. Furthermore, transwell analysis revealed that viral ingredients, such as proteins and RNA fragments, could be encapsulated in the exosomes of multivesicular bodies (MVBs) to nonpermissive microglia. Inhibition of exosome secretion could suppress PHEV infection. Therefore, we concluded that the mode of infectious transmission of PHEV is likely through a mixture of virus-modified exosomes and virions and that exosomal export acts as a host strategy to induce an innate response in replicating nonpermissive bystander cells free of immune system recognition. IMPORTANCE The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a large number of deaths worldwide. Clinical neurological complications have occurred in some cases; however, knowledge of the natural history of coronavirus in the central nervous system (CNS) is thus far limited. PHEV is a typical neurotropic betacoronavirus (β-CoV) that propagates via neural circuits in the host CNS after peripheral incubation rather than through the bloodstream. It is therefore a good prototype pathogen to investigate the neuropathological pathogenesis of acute human coronavirus infection. In this study, we demonstrate a new association between host vesicle-based secretion and PHEV infection, showing that multivesicular-derived exosomes are one of the modes of infectious transmission and that they mediate the transfer of immunostimulatory cargo to uninfected neuroimmune cells. These findings provide novel insights into the treatment and monitoring of neurological consequences associated with β-CoV, similar to those associated with SARS-CoV-2.

BackgroundOur study aimed to construct and validate prognostic nomograms for predicting survival for patients with Nonfunctional Pancreatic neuroendocrine tumor (NF-pNET).MethodsThis retrospective study included 1824 patients diagnosed with NF-pNET in the Surveillance, Epidemiology and End Results database between 2004 and 2016. Randomization divided the patients into training (n = 1278) and validation (n = 546) cohorts. Prognostic factors were determined using Cox regression analyses, nomograms based on AJCC 7th and 8th staging system were constructed separately. The prediction models were validated using internal validation and external validation.ResultsAge, year of diagnosis, primary tumor site, grade, 7th or 8th TNM stage, surgery, tumor size were determined as prognostic indicator to construct two nomograms. Harrell's concordance index (C-index) of two nomograms exhibited a clinical predictive ability of 0.828 (95%CI, 0.808~0.849) vs 0.828 (95% CI, 0.808~0.849) in the internal verification. The c-index in the external validation was 0.812 (95%CI, 0.778~0.864) vs 0.814 (95% CI, 0.779~0.848). The predictive power of the two nomograms is comparable.ConclusionsOur nomogram may be a effective tool for predicting overall survival in patients with NF-pNET. The AJCC 8th-edition system provides discrimination similar to that of the 7th-edition system.

IntroductionType 2 diabetes mellitus (T2DM) can accelerate cognitive decline and even dementia so that the underlying mechanism deserves further exploration. In the resting state, brain function is still changing dynamically. At present, it is still unknown whether the dynamic functional connectivity (dFC) between various brain regions is in a stable state. It is necessary to interpret brain changes from a new perspective, that is, the stability of brain architecture.MethodsIn this study, we used a fixed dynamic time scale to explore the stability of dynamic functional architecture in T2DM, then the dynamic effective connectivity (dEC) was used to further explain how information flows through dynamically fluctuating brain architecture in T2DM.ResultTwo brain regions with decreased stability were found including the right supra-marginal gyrus (SMG) and the right median cingulate gyrus (MCG) in T2DM subjects. The dEC variation has increased between the left inferior frontal gyrus (IFG) and the right MCG. The direction of causal flow is from the right MCG to the left IFG.ConclusionThe combination of stability and dEC can not only show the stability of dynamic functional architecture in brain but also reflect the fluidity of brain information, which is an innovative and interesting attempt in the field of neuroimaging. The changes of dynamic architecture in T2DM patients may present an innovative perspective and explanation for their cognitive decline.

Initially described as an ancient and highly conserved catabolic biofunction, autophagy plays a significant role in disease pathogenesis and progression. As the bioactive ingredient of Salvia miltiorrhiza, tanshinone has recently shown profound effects in alleviating and treating various diseases by regulating autophagy. However, compared to the remarkable achievements in the known pharmacological effects of this traditional Chinese medicine, there is a lack of a concise and comprehensive review deciphering the mechanism by which tanshinone regulates autophagy for medicinal research. In this context, we concisely review the advances of tanshinone in regulating autophagy for medicinal research, including human cancer, the nervous system, and cardiovascular diseases. The pharmacological effects of tanshinone targeting autophagy involve the regulation of autophagy-related proteins, such as Beclin-1, LC3-II, P62, ULK1, Bax, ATG3, ATG5, ATG7, ATG9, and ATG12; the regulation of the PI3K/Akt/mTOR, MEK/ERK/mTOR, Beclin-1-related, and AMPK-related signaling pathways; the accumulation of reactive oxygen species (ROS); and the activation of AMPK. Notably, we found that tanshinone played a dual role in human cancers in an autophagic manner, which may provide a new avenue for potential clinical application. In brief, these findings on autophagic tanshinone and its derivatives provide a new clue for expediting medicinal research related to tanshinone compounds and autophagy.

ObjectiveThis study aims to explore the changes in the structure, perfusion, and function of the bilateral hippocampus in type 2 diabetes mellitus (T2DM) applying multimodal MRI methods, hoping to provide reliable neuroimaging evidence for the diagnosis of hippocampus-related brain injury in T2DM.MethodsWe recruited 30 T2DM patients and 45 healthy controls (HCs), on which we performed 3D T1-weighted images, resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) sequences, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, fractional ALFF (fALFF) value, coherence-based regional homogeneity (Cohe-ReHo) value, and degree centrality (DC) values of the bilateral hippocampus.ResultsIn the T2DM group, the bilateral hippocampal volumes and the CBF value of the right hippocampus were lower than those in the HCs, while the ALFF value, fALFF value, and Cohe-ReHo value of the bilateral hippocampus were higher than those in the HCs. Correlation analysis showed that fasting blood glucose (FBG) was negatively correlated with the residuals of left hippocampal volume (r = −0.407, P = 0.025) and right hippocampal volume (r = −0.420, P = 0.021). The residual of the auditory-verbal learning test (AVLT) (immediate) score was positively correlated with the residual of right hippocampal volume (r = 0.369, P = 0.045).ConclusionThis study indicated that the volume and perfusion of the hippocampus are decreased in T2DM patients that related to chronic hyperglycemia. Local spontaneous neural activity and coordination are increased in the hippocampus of T2DM patients, possibly as an adaptive compensation for cognitive decline.

IntroductionInfluenza A viruses (IAVs) are important pathogens of respiratory infections, causing not only seasonal influenza but also influenza pandemics and posing a global threat to public health. IAVs infection spreads rapidly, widely, and across species, causing huge losses, especially zoonotic IAVs infections that are more harmful. Fast and sensitive detection of IAVs is critical for controlling the spread of this disease.MethodsHere, a real-time reverse transcription recombinase-aided amplification (real-time RT-RAA) assay targeting conserved positions in the matrix protein gene (M gene) of IAVs, is successfully established to detect IAVs. The assay can be completed within 20 min at 42°C.ResultsThe sensitivity of the real-time RT-RAA assay was 142 copies per reaction at 95% probability, which was comparable to the sensitivity of the RT-qPCR assay. The specificity assay showed that the real-time RT-RAA assay was specific to IAVs, and there was no cross-reactivity with other important viruses. In addition, 100%concordance between the real-time RT-RAA and RT-qPCR assays was achieved after testing 120 clinical specimens.DiscussionThe results suggested that the real-time RT-RAA assay we developed was a specific, sensitive and reliable diagnostic tool for the rapid detection of IAVs.

Orf virus (ORFV) causes highly contagious vesiculoulcerative pustular and skin lesions in ruminants like sheep. Developing ORFV-based recombinant vaccine is a potential way to combat Orf disease. Although ORFV could propagate in some kinds of primary cells, the proliferative capacity of primary cells is limited. Therefore, establishing immortalized stable cell line is an effective and affordable way for the production of live ORFV vaccine. In the present study, we introduced a telomerase reverse transcriptase (TERT) gene-expressing cassette into primary ovine fetal turbinate (OFTu) cells, then selected and expanded the cells, which was considered as immortalized OFTu cell line. Our results showed that TERT introduction has successfully expended the lifespan of OFTu cell line over 80 passages, without changing the cellular morphology, affecting chromosomes karyotype and inducing the cellular tumorigenic ability. Immortalized OFTu cell line-derived ORFV has caused similar levels of cytopathic effects (CPE), viral titers and viral particles when compared with the ORFV from primary OFTu cell. Importantly, immortalized OFTu cell line was suitable for generating gene-modified ORFV recombinant through homologous recombination, and for the amplification of ORFV recombinant. In summary, an immortalized OFTu cell line was established and characterized, which could be a powerful tool for preparing ORFV recombinant vaccines.

Currently, it is believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne virus, and virus-containing aerosol particles have been found concurrent with the onset of COVID-19, which may contribute to the noncontact transmission of SARS-CoV-2. Exploring agents to block SARS-CoV-2 transmission is of great importance to prevent the COVID-19 pandemic. In this study, we found that inactivated Parapoxvirus ovis (iORFV), a kind of immunomodulator, could compress the proportion of small particle aerosols exhaled by Syrian golden hamsters. Notably, the concentration of SARS-CoV-2 RNA-containing aerosol particles was significantly reduced by iORFV in the early stages after viral inoculation. Importantly, smaller aerosol particles (

Abstract In the field of public opinion analysis, sentiment analysis is an important basic research branch. Previous studies have successfully proved that the advanced transformer pre‐training model can be applied to this scenario in Uyghur and other low‐resource language scenarios. However, the majority of these studies are based on the traditional language anchor point and rely on the pre‐training model's cross‐lingual understanding ability. The Senti‐eXLM model proposed in this paper employs a method that allows for adaptively expanding the model's knowledge domain and dynamically adjusting the model for Uyghur language in order to improve the language's understanding and representation capability, thereby increasing the accuracy of text emotion analysis. Experiments on publicly available data sets demonstrate that when compared to the original model, the model's emotion classification accuracy is improved by 6.17%, the training convergence speed is increased by 27%, and the average reasoning time is increased by only 11%.

Abstract Innate radioresistance substantially limits the effectiveness of radiotherapy for colorectal cancer (CRC); thus, a strategy to enhance the radiosensitivity of CRC is urgently needed. Herein, we reported that ankyrin repeat and KH domain containing 1 (ANKHD1) serves as a key regulator of radioresistance in CRC. ANKHD1 was highly expressed in CRC tissues and was highly correlated with Yes-associated protein 1 (YAP1) in CRC. Our results first revealed that ANKHD1 knockdown could increase the radiosensitivity of CRC by regulating DNA-damage repair, both in vitro and in vivo. Furthermore, the interactive regulation between ANKHD1 or YAP1 and lncRNA MALAT1 was revealed by RIP and RNA pull-down assays. Moreover, our results also demonstrated that MALAT1 silencing can radiosensitize CRC cells to IR through YAP1/AKT axis, similar to ANKHD1 silencing. Taken together, we report a feedback loop of ANKHD1/MALAT1/YAP1 that synergistically promotes the transcriptional coactivation of YAP1 and in turn enhances the radioresistance of CRC by regulating DNA-damage repair, probably via the YAP1/AKT axis. Our results suggested that targeting the YAP1/AKT axis downstream of ANKHD1/MALAT1/YAP1 may enhance the radiosensitivity of CRC.

The stability of the filling roof—as an important bearing unit in the stope of the access stope in the filling mining method—is of great significance to guarantee the safe and efficient production of the mine. Arrangement of the mining approach in downward cemented filling stope is the key factor affecting the stability of the filling body roof. Based on a combination of laboratory tests, theoretical analysis, and numerical simulation, the influence of different mining approach arrangements on the stability of the filling body roof is analyzed. The weak filling surface is formed between adjacent mining paths. The mechanical strength of the weak filling surface is significantly reduced by laboratory experiments. The relationship between the distribution of the weak filling surface, azimuth angle, and the stability of the filling roof is further studied by numerical simulation. The results show that, when the upper and lower layered mining approaches are arranged vertically or nearly vertically, the areas of stress concentration and the plastic zone in the numerical simulation results are the smallest, and the stability of the filler roof is the best.

Probiotics are prospective for the prevention and treatment of cardiovascular diseases. Until now, systematic studies on the amelioration of hypercholesterolemia have been rare in terms of (cholesterol metabolism and transportation, reshaping of gut microbiota, as well as yielding SCFAs) intervention with lactic acid bacteria (LAB). In this study, strains of Lactiplantibacillus plantarum, WLPL21, WLPL72, and ZDY04, from fermented food and two combinations (Enterococcus faecium WEFA23 with L. plantarum WLPL21 and WLPL72) were compared for their effect on hypercholesterolemia. Comprehensively, with regard to the above aspects, L. plantarum WLPL21 showed the best mitigatory effect among all groups, which was revealed by decreasing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, upregulated cholesterol metabolism (Cyp27a1, Cyp7b1, Cyp7a1, and Cyp8b1) levels in the liver, cholesterol transportation (Abca1, Abcg5, and Abcg8) in the ileum or liver, and downregulated Npc1l1. Moreover, it reshaped the constitution of gut microbiota; specifically, the ratio of Firmicutes to Bacteroidetes (F/B) was downregulated; the relative abundance of Allobaculum, Blautia, and Lactobacillus was upregulated by 7.48–14.82-fold; and that of Lachnoclostridium and Desulfovibrio was then downregulated by 69.95% and 60.66%, respectively. In conclusion, L. plantarum WLPL21 improved cholesterol metabolism and transportation, as well as the abundance of gut microbiota, for alleviating high-cholesterol-diet-induced hypercholesterolemia.

Abstract Background It has been reported the prognostic value of MTV in predicting the disease prognosis of peripheral T-cell lymphoma (PTCL) through pre-treatment PET/CT imaging. However, these are limited data on pretreatment evaluation and prognosis assessments of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). This study aimed to determine the prognostic values of pre-treatment and mid-treatment total metabolic tumor volume (MTV), total lesion glycolysis (TLG), and Deauville 5-Point Scale (D-5PS) in accessing the prognosis of PTCL-NOS. Methods A retrospective analysis was conducted in 31 patients with pathologically diagnosed PTCL-NOS. These patients have undergone positron emission PET/CT scanning before and during chemotherapy. Follow-ups were also done to investigate the 2-year progression-free survival (PFS) and Overall Survival (OS) of these patients. During $${}^{18}$$ 18 F-fluorodeoxyglucose ( $${}^{18}$$ 18 F-FDG) PET/CT scans, the MTV and TLG were recorded. Meanwhile, $$\bigtriangleup$$ △ MTV and $$\bigtriangleup$$ △ TLG were calculated. Furthermore, the receiver operating characteristic (ROC) curve was employed to classify and to define the threshold values. On the other hand, the mid-chemotherapy assessment and staging of these 31 patients were done by utilizing D-5PS. Subsequently, based on the D-5PS scores obtained, these patients were grouped into two categories: a group of patients with a score of

In this study, uniaxial and triaxial compression acoustic emission (AE) tests were implemented to investigate the AE effect and failure characteristics of sandstone under different confining pressures (σ3). The evolution of AE parameters in the rock failure process and fracture fractal dimension characteristics after failure were analyzed. The results revealed that the activity of the AE signal is strongly related to σ3. The evolution of the Ib value can be divided into the I-fluctuation, II-stability, and III-decrease stages. In the first stage, the Ib value of the AE was relatively high, and the AE energy was low. Then, the Ib value tended to be stable; however, the fluctuation amplitude decreased, and the AE energy rapidly increased. In the stage of decrease, the AE energy sharply increased before the load approached the peak value, and the Ib value significantly decreased and dropped to the lowest point before the peak value. As σ3 increased, the rock’s failure mode changed from tensile failure to shear failure and became more coordinated. As the confining pressure increased, the shape dimension decreased, and the order degree of rock failure increased. The confining pressure exerted a certain control effect on the rock failure.

The root and rhizome of Salvia miltiorrhiza (Danshen in short) is a well-known herbal medicine used to treat cardiovascular diseases in the world. In China, the roots and rhizomes of several other Salvia species (Non-Danshen in short) are also used as this medicine in traditional folk medicine by local herbalists. Differences have been reported in these medicines originating from different sources, and their quality variation needs to be clearly investigated for effective clinical application. This study presented a comprehensive quality evaluation and monitoring for Danshen from 27 sampling sites and Non-Danshen from other 5 Salvia species based on a high-performance liquid chromatography-diode array detector (HPLC-DAD) and near-infrared (NIR), with the combination of chemometric models. The results showed that cryptotanshinone, tanshinone IIA, tanshinone I, salvianolic acid B, salvianic acid A sodium, dihydrotanshinone I, and rosmarinic acid in these medicines from different sources exhibited great variations. Referring to the standards in Chinese Pharmacopoeia (CP), European Pharmacopeia (EP), and United States Pharmacopeia (USP), Non-Danshen from S. brachyloma, S. castanea, S. trijuga, S. bowleyana, and S. przewalskii were assessed as unqualified, and Danshen in the Shandong Province had the best quality due to the high qualified rate. Based on random forest (RF) and partial least-squares discriminant analysis (PLS-DA), NIR technique could successfully monitor the quality of these medicines by discriminating the species and regions with the accuracies of 100.00 and 99.60%, respectively. Additionally, modified partial least-squares regression (MPLSR) models were successfully constructed to investigate the feasibility of NIR fingerprints for the prediction of the quality indicators in these medicines. The optimized models obtained the best results for the total of tanshinone IIA, tanshinone I, and cryptotanshinone (TTC), tanshinone IIA, and salvianolic acid B, with the relative prediction deviation (RPD) of 4.08, 3.92, and 2.46, respectively. In summary, this study demonstrated that HPLC-DAD and NIR techniques can complement each other and could be simultaneously applied for evaluating and monitoring the quality of Danshen medicines.

Cytomegalovirus (CMV) infection remains a frequent complication after hematopoietic stem cell transplantation (HSCT) and causes significant morbidity and mortality in transplantation recipients. In this review, we highlight the role of major risk factors that are associated with the incidence of CMV infection. Advances in immunosurveillance may predict CMV infection, allowing early interventions to prevent severe infection. Furthermore, numerous therapeutic strategies against CMV infection after HSCT are summarized. A comprehensive understanding of the current situation of CMV treatment may provide a hint for clinical practice and even promote the development of novel strategies for precision medicine.

Abstract Background Histological transformation (HT) of follicular lymphoma to a more aggressive lymphoma is a serious event affecting patients’ outcomes. To date, no strong clinical HT predictors present at diagnosis have yet been identified. The fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is highlighted as a non-invasive diagnostic tool for the detection of HT, but its ability to predict HT at early stage of disease has not been clear. Therefore, this study investigated the predictive values of the pre-transformation standardized uptake value (SUVmax) for the risk of transformation in FL. Methods This retrospective study involved 219 patients with FL between June 2008 and October 2019 who had undergone 18F-FDG PET/CT scan. One hundred and thirty-two, 64, and 78 patients underwent PET at baseline (PETbaseline), interim (PETinterim) and end-of-induction therapy (PETend), respectively. Qualitative assessment was performed using the 5-point Deauville scale. Statistical analysis was done using Cox regression models, receiver operating characteristic (ROC) analysis, and Kaplan–Meir survival curves. Results Of the 219 patients included, 128 had low-grade FL (grade 1–2) and 91 had high-grade FL (grade 3a). HT eventually occurred in 30 patients. The median time to HT was 13.6 months. Among clinical indicators, advance pathological grade was shown as the most significant predictor of HT (HR = 4.561, 95% CI 1.604–12.965). We further assessed the relationship between PET and HT risk in FL. Univariate Cox regression determined that SUVbaseline and SUVend were significant predictors for HT, while neither SUVinterim nor qualitative assessment of Deauville score has predictive value for HT. Due to the noticeable impact of high pathological grade on the HT risk, we conducted the subgroup analysis in patients with low/high pathological grade, and found SUVbaseline could still predict HT risk in both low-grade and high-grade subgroups. Multivariate analysis adjusted by FLIPI2 score showed the SUVbaseline (HR 1.065, 95% CI 1.020–1.111) and SUVend (HR 1.261, 95% CI 1.076–1.478) remained as significant predictors independently of the FLIPI2 score. According to the cut-off determined from the ROC analysis, increased SUVbaseline with a cutoff value of 14.3 and higher SUVend with a cutoff value of 7.3 were highly predictive of a shorter time to HT. Conclusions In follicular lymphoma, quantitative assessment used SUVmax at the pre-treatment and end-of-treatment PET/CT scan may be helpful for early screen out patients at high risk of transformation and guide treatment decisions.

ObjectiveWe performed a pan-cancer analysis to explore the potential mechanisms of FAT4 in 33 different tumors.MethodsIn this study, we selected 33 types of cancers based on the datasets of TCGA (the cancer genome atlas). We analyzed the expression of FAT4 in tumor and normal tissues. Meanwhile, we analyzed the expression levels of FAT4 in tissues from tumors of different stages. Kaplan-Meier survival analysis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), immune infiltration analysis, Gene set enrichment analysis (GSEA), and FAT4-related gene enrichment analysis were performed.ResultsFAT4 expression in most tumor tissues was lower than in corresponding control tissues. FAT4 expression was different in different stages of bladder cancer (BLCA), kidney clear cell carcinoma (KIRC), and breast cancer (BRCA). In addition, the expression level of FAT4 in different types of tumors has an important impact on the prognosis of patients. FAT4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. We observed a statistically positive correlation between cancer-associated fibroblasts and FAT4 expression in most tumors. GSEA of BLCA indicated that low FAT4 expression groups were mainly enriched in calcium signaling pathway and chemokine signaling pathway. GSEA analysis of KIRC suggested low FAT4 expression groups were mainly involved in olfactory transduction and oxidative phosphorylation. Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the role of FAT4 in the pathogenesis of cancer may be related to human papillomavirus infection, Hippo signaling pathway, PI3K–Akt signaling pathway, etc. Gene Ontology (GO) enrichment analysis further showed that most of these genes were related to the pathways or cell biology, such as peptidyl–tyrosine phosphorylation, cell junction assembly, protein tyrosine kinase activity, etc.ConclusionOur study summarized and analyzed the antitumor effect of FAT4 in different tumors comprehensively, which aided in understanding the role of FAT4 in tumorigenesis from the perspective of clinical tumor samples. Pan-cancer analysis showed that FAT4 to be novel biomarkers for various cancers prognosis.

Under seismic action, the stock of phosphogypsum (PG) affects the security risk significantly, so it is crucial to study the dynamic characteristics of PG. In this article, unidirectional and bidirectional vibration tests on typical PG in Yunnan under different consolidation-confining pressure and vibration conditions were carried out using a dynamic triaxial apparatus that can be used for bidirectional vibration. The results show that the pore pressure growth of PG under both unidirectional and bidirectional vibrations has obvious stages and can be fitted by the BiDoseResp function. The dynamic strength of PG does not increase monotonically with the increase in consolidation-confining pressure and dynamic stress under the same cyclic stress ratio (CSR) but varies under a specific critical condition. The dynamic strength of PG decreases significantly with the increase in CSR under unidirectional and bidirectional vibrations. The number of vibrations required for liquefaction by bidirectional vibrations is much larger than that by unidirectional vibrations under the same CSR conditions, and the specimens have significant softening characteristics after liquefaction by bidirectional vibrations. The study results can provide theoretical references for studying the dynamic stability of PG reservoirs under seismic action.

Pseudorabies (PR) is a serious disease affecting the pig industry in China, and it is very important to understand the epidemiology of pseudorabies virus (PRV). In the present study, 693 clinical samples were collected from Bartha-K61 vaccinated pigs with symptoms of suspected PRV infection between January 2017 and December 2018. All cases were referred for full clinical autopsy with detailed examination of histopathological examination, virus isolation and genetic evolution analysis of the PRV glycoprotein E (gE) gene. In addition, PRV gE antibodies in 3,449 serum samples were detected by the enzyme-linked immunosorbent assay (ELISA). The clinical data revealed that abortion and stillbirth are the most frequent appearances in pregnant sows of those cases. Histopathological examination exhibited a variety of pathological lesions, such as lobar pneumonia, hepatitis, lymphadenitis, nephritis, and typical nonsuppurative encephalitis. A total of 248 cases tested positive for the PRV gE gene. 11 PRV variants were isolated and confirmed by gE gene sequencing and phylogenetic analysis. These strains had 97.1%-100.0% nucleotide homology with the PRV reference strains. Notably, the isolated strains were highly homologous and clustered in the same branch as HSD-1/2019, which caused human acute encephalitis. Serological tests showed that the positive rate of PRV gE antibody in the 3449 serum samples collected from the Hebei Province was 46.27%. In conclusion, PRV variant strains Are high prevalence in the Hebei Province, which not only causes huge economic losses to the breeding industry but also potentially poses a threat to public health.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.

Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan in vivo, and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1β, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.

Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant treatment with sintilimab (3 mg/kg for cases 1 patient) grade 3 treatment-related adverse events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4–5 AEs were observed. Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.

Orf is an important zoonotic disease caused by the Orf virus (ORFV) which can cause contagious pustular dermatitis in goats and sheep. Orf is widespread in most sheep-raising countries in the world, causing huge economic losses. Although diagnostic methods for ORFV infection already exist, it is still necessary to develop a time-saving, labor-saving, specific, low-cost and visual diagnostic method for rapid detection of ORFV in the field and application in grassroots laboratories. This study establishes a DNA extraction–free, real-time, visual recombinase–aided amplification (RAA) method for the rapid detection of ORFV. This method is specific to ORFV and does not cross-react with other common DNA viruses. The detection limits of the real-time RAA and visual judgment of the RAA assay at 95% probability were 13 and 21 copies per reaction for ORFV, respectively. Compared with qPCR, the sensitivity and specificity of the real-time RAA assay were 100%, and those of the visual RAA assay were 92.31% and 100.0%, respectively. The DNA extraction–free visual detection method of RAA established in this study can meet the needs of rapid onsite detection and grassroots laboratories and has important reference value and significance for the early diagnosis of diseased animals.