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In this article, we study eigenvalues λ\lambda and their associated eigenvectors xx of the adjacency matrices AA of balanced signed graphs. Balanced signed graphs were first introduced and studied by Harary to handle a problem in social psychology. Harary showed in 1953 that a signed graph is balanced if and only if its vertex set VV can be divided into two sets (either of which may be empty), XX and YY, so that each edge between the sets is negative and each within a set is positive. Based on this fundamental theorem for the balanced signed graphs, vertices of a balanced signed graph can be labeled in a way so that its adjacency matrix is well structured. Using this special structure, we find algebraically all eigenvalues and their associated eigenvectors of the adjacency matrix AA of a given balanced signed graph. We present in this study eigenpairs (λ,x)\left(\lambda ,x) of adjacency matrices of balanced signed graphs with some special structures.

Uveitis, a complex ocular disorder with numerous etiologies, can result from infection, autoimmune, and various physicochemical and mechanical injury factors. The treatment of this disease is difficult, and failure to receive timely and effective treatment can often lead to blindness. With the deepening of people's understanding of uveitis and its related mechanisms, various new sustained-release drug delivery systems for uveitis have been studied. However, due to the existence of various anatomical and physiological barriers in the eye, there are multiple obstacles to the sustained release treatment of uveitis. In this paper, the main research results in this field in recent years are reviewed, and the innovations and limitations of various new sustained-release drug delivery systems are discussed in order to provide new ideas for the sustained-release drug delivery treatment of uveitis in the future. These new sustained-release drug delivery systems will help to completely change the traditional treatment mode of uveitis with side effects and poor compliance in the future, bringing longer targeted sustained release and less toxic reactions.

[Objective] In order to explore the impact of uranium on algae growth and photosynthesis, and to screen new ecological risk assessment indicators for uranium pollution in water bodies based on photosynthesis. [Methods] This experiment used different concentrations of uranium (0, 0.5, 1, 5, 10, 20 mg/ L U6+ ) to treat two types of microalgae, chlorella (Chlorella vulgaris) and Huanglong chlorella, from different environments. The relative growth rate, photosynthetic oxygen release rate, chlorophyll content, and chlorophyll fluorescence kinetic parameters were measured on the 3rd, 5th, 7th, 10th, and 14th days after treatment. [Results] (1) Low concentration uranium (0.5 mg/L) treatment significantly promoted the growth and photosynthetic efficiency of the two types of microalgae, where the relative growth rate, photosynthetic oxygen release rate, maximum photochemical quantum yield (Fv/Fm) of photosystem Ⅱ, actual photochemical quantum yield Y (Ⅱ), and relative electron transfer rate (rETR) of the two microalgae were significantly higher than the control. However, high concentration uranium treatment (5 -20 mg/L) significantly inhibited the growth and photosynthesis of the two types of chlorella. (2) Huanglong chlorella was more sensitive to uranium treatment than chlorella, and its growth and photosynthesis were significantly inhibited at 1mg/L, and it could be used as an bioindicator for monitoring of uranium pollution in water bodies. (3) Regression analysis showed that under different concentrations of uranium treatment, the response speed of chlorophyll fluorescence parameters Y (Ⅱ) and rETR was faster than the changes in relative growth rate, photosynthetic oxygen release rate, chlorophyll content, and Fv/Fm, which could be used as sensitive indicators for ecological risk assessment of uranium pollution in water bodies. [Conclusion] Uranium exhibits a concentration effect on the growth and photosynthesis of chlorella, where low concentrations promote growth while high concentrations inhibit growth. Huanglong chlorella is more sensitive to uranium pollution. Therefore, the combination of Huanglong chlorella and chlorophyll fluorescence kinetic parameters Y (Ⅱ) and rETR can be applied for the ecological risk assessment of uranium pollution in water bodies.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

Objective To explore the effect of diet coke combined with chlorhexidine gargle in oral care of tracheal intubation patients in Neurology ICU.Methods From October 2019 to October 2022, 110 patients with tracheal intubation who were admitted to the Neurology Intensive Care Unit of Huai'an First People's Hospital were selected as the research object. The patients were randomly divided into control group and observation group (n=55, each). The control group received routine oral care (wiping with saline cotton balls). In the observation group, the diet coke combined with chlorhexidine gargle was used for negative pressure washing. The incidence of ventilator-associated pneumonia (VAP), improved Beck oral score, mechanical ventilation time, and ICU hospitalization time between two groups were compared after implementing oral care. Results After implementing oral care, the incidence of VAP in the intervention group was lower than that in the control group [9.09%（5/55） vs 32.73%(18/55), χ=9.29, P＜0.05]. Compared with the control group, the observation group had lower Beck oral score (P＜0.05), ICU hospitalization time [(7.71±0.66) d vs (12.00±0.72) d, P＜0.05], and mechanical ventilation time[(5.82±0.77) d vs (8.36±0.73) d, P＜0.05]. Conclusion Diet coke combined with chlorhexidine mouthwash under negative pressure can improve oral hygiene, reduce the incidence of VAP, and shorten the hospital stay and mechanical ventilation time in ICU.

Intravascular large B-cell lymphoma, known for its diverse organ involvement, presents significant diagnostic challenges, particularly when it affects the kidneys. This report highlights a rare case of primary renal intravascular large B-cell lymphoma in a 60-year-old male patient, who presented with persistent fever and renal dysfunction. The case underscores the intricacy of diagnosis and the efficacy of personalized treatment. Following the identification of primary renal intravascular large B-cell lymphoma, a modified R-CHOP regimen was administered, resulting in notable amelioration of symptoms and renal function following the initial treatment cycle. The patient achieved sustained complete remission without any complications after completing five subsequent R-CHOP cycles and two additional cycles of rituximab monotherapy, as confirmed by recent assessments. He is currently under regular follow-up for ongoing monitoring and improvement. This case adds to the limited yet expanding pool of knowledge concerning intravascular large B-cell lymphoma, emphasizing the necessity for personalized therapeutic strategies in atypical presentations. It also highlights the importance of early detection and customized intervention in managing rare lymphoma subtypes with unique organ involvement.

This paper applies the EVA-based bonus incentive model and the EVA-based stock option incentive model to the executive compensation incentive system of multinational enterprise D and calculates the EVA amount by combining the profitability of multinational enterprise D and compares it with the net profit amount of the enterprise to obtain the difference between the two. In order to further investigate the relationship between the EVA amount and the net profit of multinational enterprises, the correlation hypothesis between executive compensation and the management of accrued surplus and the management of actual surplus is carried out, respectively. The countermeasures for the management of executive compensation in multinational enterprises under the background of the internationalization of the RMB are proposed according to the establishment of the research hypothesis. Executive compensation and accrued surplus management are negatively correlated, as shown by regression analysis, and an increase in the former will have a significant inhibitory impact on accrued surplus management behavior. There is a positive correlation between executive compensation and natural surplus management, and the significance level is 5%. This means that the increase in executive compensation has a promotion effect on natural surplus management.

Objective To investigate the effects of lycopene (Lyc) on hippocampal inflammation, social deficits and repetitive stereotyped behaviors in BTBR T+ Itpr3tf/J autistic mice (BTBR, a mouse strain showing lower sociability as a model for autism spectrum disorder). Methods Adult male C57BL/6J (C57) and BTBR mice aged 7-8 weeks were randomly divided into (n=8): C57+Veh group, C57+Lyc group, BTBR+Veh group and BTBR+Lyc group. The mice from the C57+Lyc group and BTBR+Lyc group were given 20 mg/kg Lyc by gavage once a day for 7 d, and those of the C57+Veh group and BTBR+Veh mice were given equal volume of corn oil. Then three-chamber social test, male-female reciprocal social interactions, self-grooming, marble buying, open field test, object recognition test, nest building, and Y-maze test were conducted in these mice. Immediately after the behavioral tests, the mice were sacrificed and their brain samples were harvested for RT-qPCR and Western blotting. Results Behavioral results showed that in the three-chamber social test, the mice of the BTBR+Veh group spent longer time in the chamber with the object, showing much curiosity about the object (P < 0.05), while the mice after Lyc treatment showed a preference for strange mice (P < 0.05). In the self-grooming and marble burying behavior test, the BTBR+Veh group showed markedly increased repeated stereotyped behaviors than the C57+Veh group mice (P < 0.05), which could be alleviated by Lyc treatment (P < 0.05). The hippocampal expression of NLRP3 at mRNA and protein levels (P < 0.05), and the mRNA levels of IL-1β, IL-18, IL-6, NF-κB, and TNF-α were significantly increased in the BTBR+Veh group mice when compared with the C57+Veh group mice, and Lyc treatment obviously reversed above changes (P < 0.05). Conclusion Lyc treatment improves three-chamber social deficits and repetitive stereotyped behaviors in BTBR mice by reducing NLRP3 inflammasome in the hippocampus of BTBR mice.

To evaluate the effect of family psychosocial intervention on the mental health and family function of caregivers of children with cancer.

The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx273, Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx83;dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration.

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.

At present, there is a lack of reliable prediction index for sudden unexpected death in epilepsy (SUDEP), which poses a great threat to the lives of patients with epilepsy. With the deepening of research, it has been found that postictal generalized electroencephalography suppression (PGES) occurs in EEG monitoring after seizure, especially generalized tonic⁃clonic seizure (GTCS). Since then, PGES has attracted much attention as a possible EEG marker of SUDEP. Combined with the study of the pathophysiological mechanism, related factors of PGES phenomenon, and this paper further analyzes the relationship between the occurrence of PGES and SUDEP.

Abstract An enriched environment (EE) is a promising strategy for protecting the intestinal mucosal barrier and regulating the brain-gut axis, but the optimal EE intervention duration is unknown. Here, different EE intervention durations were applied to assess the optimal intervention duration in rats with colorectal cancer. We used a rat model of 1, 2-dimethylhydrazine-induced colorectal cancer. The rats were housed in an EE for 0, 2, 4, 8 weeks and 8-week blank group. The intestinal mucosa and serum TNF-α, IL-6, IL-10, ATP, CRF, and occludin levels and bacterial translocation (BT) were measured, and the intestinal mucosa morphology was evaluated. In 8 weeks, the effect of tumor on intestinal mucosal barrier was not obvious and the EE had a greater impact on it. Eight weeks of EE was more beneficial to the intestinal mucosal mechanical barrier than 2 or 4 weeks of intervention. A significant difference in BT was found between the 4- and 8-week groups. Overall, the analysis of inflammatory factor regulation revealed that the two blank groups exhibited the worst effect, and the intervention effect at 8 weeks was better than that at 2 and 4 weeks. CRF at 4 weeks was higher than that at 8-week blank group. The effect of 8-week intervention duration on the intestinal mucosal barrier was generally better than that of 2- and 4-week durations and intervention within 4 weeks can help to stabilize and promote the secretion of brain gut peptide, but the effect of different intervention durations on the brain-gut peptide levels was not obvious. In the future, we can further explore the molecular biological mechanism of the effect of different EE intervention durations on the intestinal mucosal barrier and analyze the effect of an EE on other brain-gut peptides.

Objective To investigate the effects of Chaihu Oral Liquid (CHOL) on the neurogenesis in hippocampal dentate gyrus (DG) and short-term memory defects in BTBR T+ Itpr3tf/J (BTBR) autism model mice. Methods Healthy adult male C57BL/6J(C57) mice (7~8 weeks old, 24.72±1.35 g) and BTBR mice (7~ 8 weeks old, 27.7±1.42 g) were randomly divided into groups as follows (n=4 in each group): C57 control, C57 drug treatment, BTBR control, and BTBR drug treatment. Mice in the treatment groups were given CHOL solution gavage (10 μL/g) once a day for 7 consecutive days, while those of the control group received equal volume of normal saline. Daily changes of body weight were recorded. After the last administration, hair grooming, bead embedding, new object recognition and open field experiments were conducted on the next day and lasted for 4 d. Finally, the samples of mice brain tissue were harvested, and immunofluorescence staining was performed to detect the NeuN, DCX, SOX2/GFAP labeled nerve cells in hippocampal DG. Results Behavioral results suggested that mice in the BTBR control group showed a more obvious preference for old objects in the new object recognition experiment (P < 0.01), as compared with the C57 control group, while the new object recognition index was significantly improved in the BTBR drug treatment group (P < 0.05). Moreover, the BTBR control group presented more repetitive behavior and longer movement distance than the C57 control during the hair grooming, bead embedding and open field experiments, as well as higher body weight (P < 0.05), whereas the BTBR treatment group had no significant changes in comparison with the BTBR control regarding these aspects. There were no notable differences between the C57 control and C57 treatment groups in terms of new object recognition index, repetitive behavior, motor ability and body weight. Immunofluorescence staining results indicated that the numbers of NeuN labeled mature neurons and DCX labeled newborn neurons in hippocampal DG were greatly decreased in the BTBR control group, so as the number of SOX/GFAP labeled neural progenitor cells (P < 0.01), while the number of neurocytes was remarkably increased in the BTBR drug treatment group (P < 0.05). There were no significant differences in the numbers of NeuN, DCX and SOX2/GFAP labeled neurocytes between the C57 control and the C57 treatment groups. Conclusion CHOL promotes the generation of hippocampal DG nerve progenitor cells, new and mature neurons in adult BTBR mice, and improves the short-term learning and memory dysfunction.

Migraine is one of the most common primary headaches, but its pathogenesis remains unclear. Recent studies have found that the onset of migraine may be a response to the imbalance of brain energy metabolism and oxidative stress, suggesting that migraine may be a metabolic disease of brain related to mitochondrial dysfunction. This study uses the migraine trigger and mitigating factors, biological markers, genetic research and evidence⁃based treatment as the breakthrough point, to explore the pathogenesis of migraine brain energy metabolism, and explores the mechanism of brain energy metabolism and other associated with migraine mechanism, in order to provide a new strategy for the treatment of migraine and promote the development of the individual and precise treatment of migraine.

The R&D (Research & Development) process of mobile application can be regarded as a complex system engineering that needs to take into account a variety of influencing elements, such as customer’s demands, engineering measures and business goals etc., as well as their interplay. A novel decision support platform is proposed to assist project managers in determining the optimal technical measures with implementation degrees and resource allocation scheme. Specially, the HDQ (House of Development Quality) is designed to collect essential data and information as well as reflect correlations among elements, which can effectively connect isolated information islands. Through the transform of HDQ, a multi-objective programming model is constructed to meet customers’ overall demands and specific requirements. A combination of specified technical measures and resource allocation can be obtained under ideal conditions. Additionally, the extended model considering resource substitution is designed to realize further improvement by effectively utilizing the surplus resource in the above optimal condition, demonstrating the advantage of proper managerial arrangement and resource deployment. Finally, the R&D case of family financial management application is conducted to illustrate the effectiveness of the suggested method, which offers a new perspective on mobile application R&D project management.

Objective To investigate the autonomic nervous dysfunction in patients with Alzheimer's disease (AD) and its relationship with cognitive function. Methods A total of 160 AD patients were enrolled in Shanghai Jinshan Zhongren Aged Care Hospital from July 2020 to June 2021. Min⁃Mental State Examination (MMSE), Montreal Cognitive Assessment⁃Basic (MoCA⁃B) and Scale for Outcomes in Parkinson's Disease⁃Autonomic (SCOPA⁃AUT) were used to assess the cognitive and autonomic nervous function of AD patients, and the occurrence of orthostatic hypotension (OH) in AD were evaluated with the lying and standing blood pressure testing. Spearman rank correlation analysis was used to analyze the correlation between autonomic nervous function and cognitive function. Results Compared with the mild AD group, the scores of MMSE, MoCA⁃B and their subitems were lower (P=0.000, for all), and SCOPA⁃AUT score (P=0.000) and its subitem of digestive system (P=0.000), urinary system (P=0.000) and body temperature (P=0.001) were increased in the severe AD group. The incidence of OH was 32.22% (29/90). Spearman rank correlation analysis showed that the SCOPA⁃AUT sore (rs=⁃2.980, P=0.000; rs=⁃3.580, P=0.000) and its subitem of digestive system (rs=⁃2.730, P=0.000; rs=⁃3.160, P=0.000), urinary system (rs=⁃3.000, P=0.000; rs=⁃3.240, P=0.000) and body temperature (rs=⁃0.244, P=0.005; rs=⁃3.270, P=0.000) were negatively correlated with MMSE and MoCA⁃B scores. Conclusions The autonomic nervous dysfunction and its subitem of digestive system, urinary system and body temperature were significant correlated with the cognitive impairment in AD patients. However, there is a lower incidence of OH in AD.

Abstract Background Trisomy 8 positivity myelodysplastic syndrome with Behçet's disease is rare. Isolated trisomy 8 is a frequent cytogenetic abnormality in the MDS, but the characteristic of trisomy 8 and the association between trisomy 8 positivity myelodysplastic syndrome and Behçet's disease is unclear. Case presentation Here, we reported a 63‐year‐old man, who presented with fever, abdominal pain and hematochezia. Imaging studies revealed bowel wall thickening and mural hyperenhancement of terminal ileum and cecum. Colonoscopy found multiple round ulcers in terminal ileum, ileocecal valve and multiple yellow dotted pseudomembranous attachments throughout the colon. Capsule endoscopy also revealed multiple irregular ulcers in lower ileum. Serum C-reactive protein levels and fecal calprotectin were abnormally high. The clostridium difficile toxin A and B was positive. However, the patient's intestinal ulcers did not resolve after two weeks course of vancomycin. Considered that the patient was diagnosed as MDS-RAEB2 with a karyotype of 47 XX, + 8. And detailed inquiry of medical history revealed epifolliculitis and frequently recurrent oral ulcers 2 months before admission. A diagnosis of trisomy 8 positivity MDS with BD was made. Then he received glucocorticoid along with the 5th course of azacytidine. The follow-up endoscopy showed significantly improved intestinal ulcer 2 months after treatment. we report a rare disease and provide the diagnose and treatment ideas. Conclusions We highlight the challenges and the process of thinking about of the diagnosis. This may provide a new idea for the diagnosis of intestinal ulcers.

ABSTRACT Avibacterium paragallinarum is the etiological agent of infectious coryza, an acute respiratory disease of chickens that is globally distributed and causes serious economic losses for chicken production. A. paragallinarum is a Gram-negative bacterium that releases outer membrane vesicles (OMVs). In this study, a comparative genomic analysis of A. paragallinarum isolate P4chr1 and its OMVs was carried out, and the ability to transfer antibiotic resistance genes (ARGs) via the OMVs was studied. Sequencing and data analyses demonstrated that the genomic size of A. paragallinarum P4chr1 was approximately 2.77 Mb with a 25 kb tolerance island that covered six types of antibiotics and 11 ARGs. The genomic size of its OMVs was approximately 2.69 Mb, covering 97% of the genomic length and almost all the gene sequences of P4chr1. Purified and DNase-treated A. paragallinarum P4chr1 OMVs were cocultured with the antibiotic-sensitive A. paragallinarum Modesto strain on an antibiotic (chloramphenicol, erythromycin, tetracycline, or streptomycin)-containing plate, and the corresponding ARGs were detected in the colonies grown on the plates. However, using an antimicrobial susceptibility test, we found that ARGs delivered by OMVs were not persistent but only appeared transiently on the antibiotic-containing plates. Antibiotic resistance and ARGs were lost by the second bacterial passage. IMPORTANCE The functions and roles of OMVs on ARG and virulent gene transfer and dissemination have been reported in numerous Gram-negative bacteria. However, the role of OMVs in mediating antibiotic resistance in A. paragallinarum has not been reported. This study is the first report to compare the genomic characteristics of OMVs with its parent A. paragallinarum strain and to study A. paragallinarum ARG transfer via OMVs. This work has provided useful data for further studies focusing on nonplasmid ARG transfer mediated by A. paragallinarum OMVs.

Objective: To investigate the effect and mechanism of linarin (LA) in an experimental dry eye model Methods: LA or vehicle was applied in two dry eye models: an in vitro hyperosmotic stress model and an in vivo desiccating stress (DS) murine model. The viability of human corneal epithelial cells (HCECs) was measured using a cell counting kit (CCK-8). Tear secretion was assessed using the phenol red cotton test. The tear break-up time (TBUT) was recorded using 0.1% liquid fluorescein sodium. Corneal epithelial permeability was evaluated through Oregon green dextran (OGD) staining. Conjunctival goblet cells were counted using periodic acid-Schiff (PAS) staining. Terminal deoxynucleotidyl transfer dUTP nick-end labeling (TUNEL) staining was used to quantify apoptotic cells in both models. The expression of Ki-67 was measured in HCECs in the cell model while that of matrix metalloproteinase (MMP)-3 and -9 was measured in the murine model through immunofluorescence staining. Real-time quantitative PCR (RT-qPCR) was performed to assess the expression of MMP-3 and MMP-9 in the corneal epithelium and NLRP3, ASC, Caspase-1, interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α in the conjunctiva. The protein expression levels of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the conjunctiva were assessed via Western blot Results: In the in vitro model, treatment of HCECs with LA showed no toxicity, increased proliferation, and reduced apoptosis. In the murine model, compared to the control, LA significantly increased tear production and TBUT, improved OGD staining, and increased the number of goblet cells. Topical treatment of LA to mice provided decreased expression of MMP-3, MMP-9, TNF-α, and apoptotic corneal epithelium. Topical administration of LA also suppressed the NLRP3 inflammasome in the dry eye disease (DED) murine model by decreasing the expression of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the conjunctiva. Conclusion: Our findings support the safety and efficacy of LA in the treatment of DED. LA alleviated corneal epithelial damage and suppressed NLRP3 inflammasome-mediated immunity in the conjunctiva in a murine model of DED.

Abstract Chronic myelomonocytic leukemia (CMML) is a rare disease of elderly people characterized by the presence of sustained peripheral blood monocytosis, overlapping features of myeloproliferation, and myelodysplasia. We present a large retrospective study of 156 CMML patients in China. Mean age at diagnosis was 68 years old (range 23‐91). According to the CMML‐specific prognostic scoring system (CPSS), 10 patients (8.3%) were low risk, 27 patients (22.5%) were intermediate‐1 risk, 72 patients (60%) were intermediate‐2 risk, and 11 patients (9.2%) were high risk. A total of 90 patients (57.7%) received hypomethylating agents (HMAs) treatment, 19 patients (12.2%) received chemotherapy and 47 patients (30.1%) received the best supportive care. Seventeen patients (10.9%) underwent allogeneic hematopoietic stem cell transplantation (allo‐SCT) after HMAs treatment or chemotherapy. With a median follow‐up of 35.3 months, overall response rate (ORR) was 69.5% in the HMAs ± chemotherapy group, 79.5% in the HMAs monotherapy group, 60.0% in the HMAs + chemotherapy group, and 37.5% in the chemotherapy group. HMAs monotherapy group had prolonged OS compared with the chemotherapy group (23.57 months vs. 11.73 months; p = 0.035). Patients who achieved ORR had prolonged OS (25.83 months vs. 8.00 months; p

Abstract Purpose To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS). Methods A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS‐related mutations sequencing. Results 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and

The diagnosis of a concurrent infection of Avibacterium paragallinarum and fowl adenovirus (FAdV) in an infectious coryza–like outbreak in the outskirt of Beijing is reported. The primary signs of the infection were acute respiratory signs, a drop in egg production, and the presence of hydropericardium–hepatitis syndrome–like gross lesions. Laboratory examination confirmed the presence of A. paragallinarum by bacterial isolation and a species-specific PCR test. In addition, conventional serotyping identified the isolates as Page serovar A. Fowl adenovirus was isolated from chicken liver specimen and identified by hexon gene amplification. In addition, histopathologic analysis and transmission electron microscopy examination further confirmed the presence of the virus. Both hexon gene sequencing and phylogenetic analysis defined the viral isolate as FAdV-4. The pathogenic role of A. paragallinarum and FAdV was evaluated by experimental infection of specific-pathogen-free chickens. The challenge trial showed that combined A. paragallinarum and FAdV infection resulted in more severe clinical signs than that by FAdV infection alone. The concurrent infection caused 50% mortality compared with 40% mortality by FAdV infection alone and zero mortality by A. paragallinarum infection alone. To our knowledge, this is the first report of A. paragallinarum coinfection with FAdV. The case implies that concurrent infections with these 2 agents do occur and more attention should be given to the potential of multiple agents during disease diagnosis and treatment.

The continuity and homogeneity of sandstone uranium deposits are inherent characteristics that affect in situ leaching performance indexes and have important guiding effects on the optimization of mining design. In this work, we propose a spatial information entropy calculation method based on a convex hull search strategy to quantitatively evaluate the geological characteristics of uranium deposits. We use the 3-D block model of sandstone-hosted uranium deposits as hard data. First, we use the Alpha-Shapes algorithm to calculate the convex hull of the space area where various types of unit blocks are located. Second, we formulate a suitable multi-point configuration based on the convex hull size. Then, we use the multi-point density function. Scanning the convex hull point cloud establishes a probability density function to calculate the local information entropy of various sub-regions. Finally, the local spatial information entropy is aggregated using addition and multiplication to obtain the joint spatial information entropy of the entire evaluation area. A series of parameter sensitivity and performance analysis experiments prove the stability of the method and the accuracy of the quantitative and homogeneous evaluations of the complex geological conditions. In order to solve the problem of the difference between the designed production capacity and actual production capacity of a uranium deposit, we use a new method to evaluate the homogeneity and continuity of the lithology and grade of the deposit. The new method and evaluation conclusions can be used for the automation and understanding of future engineering optimization processes.

Canine mammary tumors (CMTs) have histopathological, epidemiologic and clinical characteristics similar to those in humans and are known to be one of the best models for human breast cancer (HBC). This research aimed to describe a newly established canine cell line, CMT-1026. Tumor samples were collected from a female dog exhibiting clinical mammary neoplasm, and the adherent cells were cultured. Both the histology and immunohistochemistry (IHC) of tumor samples were estimated. Cell growth, ultrastructural, cytological and immunocytochemistry (ICC) features of CMT-1026 were examined. CMT-1026 cells were inoculated into 10 female BALB/c nude mice to evaluate oncogenicity and metastatic ability. Hematoxylin-eosin (H.E.) staining of the tumors revealed an epithelial morphology. Electron microscopy was used to detect histological and cytological of smears, and ultrathin sections showed that CMT-1026 cells were polygonal and characterized by atypia and high mitotic index in the tumor, with prominent nucleoli and multinucleated cells. IHC characterization of CMT-1026 indicated ER-, PR-, HER-2, p63+, CK5/6+, and α-SMA+ epithelial cells. ICC characterization of CMT-1026 showed high expression of Claudin-1, Delta-catenin, SOX-2, and KI-67. At 2 weeks after inoculation of the CMT-1026 cells, phyma was found in 100% of the mice. The xenograft cancers showed conservation of the original H.E. features of the female dog cancer. In conclusion, CMT-1026 may be a model of canine mammary cancer that can be used in research on the pathogenesis of both CMT and HBC.

Avibacterium paragallinarum, the causative agent of infectious coryza, is known to release outer membrane vesicles (OMVs). In the present study, we investigated the composition, bioactivities, and functional properties of the OMVs of A. paragallinarum. Following extraction and purification, the OMVs were observed to be spherical in shape, with diameters ranging from 20 to 300 nm. The vesicles contained endotoxin as well as genomic DNA. The molecular weights of the OMV-contained protein fragments were mostly concentrated at 65 and 15 kDa. The components of the OMV proteins were mainly various functional enzymes (e.g., ATP-dependent RNA helicase), structural components (e.g., streptomycin B receptor and membrane protein), and some hypothetical proteins with unknown functions. The expression levels of inflammation-related factors, such as interleukin (IL)-2, IL-6, IL-1β, IL-10, and inducible nitric oxide synthase (iNOs), were significantly upregulated in chicken macrophage cells HD11 incubated with OMVs. Serum IgG antibodies were measured after two intramuscular injections of an OMV-based vaccine into specific pathogen-free (SPF) chickens. The vaccinated chickens were then challenged by A. paragallinarum of homologous and heterologous serovars. It was noted that the vaccinated chickens produced immunoglobulin G (IgG) antibodies against A. paragallinarum. The OMVs conferred an acceptable level of protection (70%), defined as an absence of colonization and of clinical signs, against the homologous strain (serovar A), while the cross-protection against heterologous challenge with serovars B and C was much weaker. However, the OMVS did provide significant protection against clinical signs for all three serovars. Overall, this study laid a foundation for further unraveling the functional roles of OMVs released by A. paragallinarum.

Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25–8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

The construction of “Double First Class” opens a new journey of building a Powerful Country in Higher Education. As an important part of higher education, private colleges and universities also undertake the important mission of talent training. The construction level of the teaching staff of private colleges and universities directly affects the smooth implementation of the national “double first-class” construction. The number of private universities in Shandong ranks among the top in the country. Taking Shandong Province as an example, this paper conducts a research on the construction of the teaching staff of private universities from the aspects of the current situation, problems encountered, problem analysis and countermeasures of the teaching staff of private universities.

Regulatory T cells (Treg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Treg cells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a new Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.

Abstract Patients with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndromes have a poor prognosis marked by an increased resistance to chemotherapy. An urgent need exists for adjuvant treatments that can enhance or replace current therapeutic options. Here we show the potential of LB100, a small-molecule protein phosphatase 2 A (PP2A) inhibitor, as a monotherapy and chemosensitizing agent for sAML using an in-vitro and in-vivo approach. We demonstrate that LB100 decreases cell viability through caspase activation and G2/M cell-cycle arrest. LB100 enhances daunorubicin (DNR) cytotoxicity resulting in decreased xenograft volumes and improved overall survival. LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3′ untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. Our research highlights the therapeutic potential of LB100, and provides new insights into the mechanism of LB100 chemosensitization.

Although cytarabine has been widely considered as one of the chemotherapy drugs for high-risk myelodysplastic syndromes (MDS), the overall response rate is only approximately 20-30%. Nuclear factor erythroid 2-related factor 2 (NRF2, also called NFE2L2) has been shown to play a pivotal role in preventing cancer cells from being affected by chemotherapy. However, it is not yet known whether NRF2 can be used as a prognostic biomarker in MDS, or whether elevated NRF2 levels are associated with cytarabine resistance. Here, we found that NRF2 expression levels in bone marrow from high-risk patients exceeded that of low-risk MDS patients. Importantly, high NRF2 levels are correlated with inferior outcomes in MDS patients (n=137). Downregulation of NRF2 by the inhibitor Luteolin, or lentiviral shRNA knockdown, enhanced the chemotherapeutic efficacy of cytarabine, while MDS cells treated by NRF2 agonist Sulforaphane showed increased resistance to cytarabine. More importantly, pharmacological inhibition of NRF2 could sensitize primary high-risk MDS cells to cytarabine treatment. Mechanistically, downregulation of dual specificity protein phosphatase 1, an NRF2 direct target gene, could abrogate cytarabine resistance in NRF2 elevated MDS cells. Silencing NRF2 or dual specificity protein phosphatase 1 also significantly sensitized cytarabine treatment and inhibited tumors in MDS cells transplanted mouse models in vivo. Our study suggests that targeting NRF2 in combination with conventional chemotherapy could pave the way for future therapy for high-risk MDS.