Bacillus phage phi18-2 is a novel temperate virus with an unintegrated genome present in the cytoplasm of lysogenic cells as a linear phage-plasmid.

Bacillus subtilis is a Gram-positive bacterium that is widely used in fermentation and in the pharmaceutical industry. Phage contamination occasionally occurs in various fermentation processes and causes significant economic loss. Here, we report the isolation and characterization of a temperate B. subtilis phage, termed phi18-2, from spore powder manufactured in a fermentation plant. Transmission electron microscopy showed that phi18-2 has a symmetrical polyhedral head and a long noncontractile tail. Receptor analysis showed that phi18-2 recognizes wall teichoic acid (WTA) for infection. The phage virions have a linear double-stranded DNA genome of 64,467 bp with identical direct repeat sequences of 309 bp at each end of the genome. In lysogenic cells, the phage genome was found to be present in the cytoplasm without integration into the host cell chromosome, and possibly as a linear phage-plasmid with unmodified ends. Our data may provide some insight into the molecular basis of the unique lysogenic cycle of phage phi18-2.

Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens.

Antimicrobial resistance is a major threat for public health. Plasmids play a critical role in the spread of antimicrobial resistance via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic resistance genes (ARGs). Here, we track ARG recruitment and assembly in clinically relevant plasmids by combining a systematic analysis of 2420 complete plasmid genomes and experimental validation. Results showed that ARG transfer across plasmids is prevalent, and 87% ARGs were observed to potentially transfer among various plasmids among 8229 plasmid-borne ARGs. Interestingly, recruitment and assembly of ARGs occur mostly among compatible plasmids within the same bacterial cell, with over 88% of ARG transfers occurring between compatible plasmids. Integron and insertion sequences drive the ongoing ARG acquisition by plasmids, especially in which IS26 facilitates 63.1% of ARG transfer events among plasmids. In vitro experiment validated the important role of IS26 involved in transferring gentamicin resistance gene aacC1 between compatible plasmids. Network analysis showed four beta-lactam genes (blaTEM-1, blaNDM-4, blaKPC-2, and blaSHV-1) shuffling among 1029 plasmids and 45 clinical pathogens, suggesting that clinically alarming ARGs transferred accelerate the propagation of antibiotic resistance in clinical pathogens. ARGs in plasmids are also able to transmit across clinical and environmental boundaries, in terms of the high-sequence similarities of plasmid-borne ARGs between clinical and environmental plasmids. This study demonstrated that inter-plasmid ARG transfer is a universal mechanism for plasmid to recruit various ARGs, thus advancing our understanding of the emergence of multidrug-resistant plasmids.

Thymoma negatively affects the neurological outcome of myasthenia gravis after thymectomy: a propensity score matching study.

BACKGROUND: Thymoma and myasthenia gravis (MG) interact with each other. This study aimed to evaluate the effects of thymoma on neurological outcome of MG patients after thymectomy using the propensity score matching (PSM) method. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Clinical and follow-up data were collected. Statistical analysis was performed using SPSS 23.0 software. PSM was performed to eliminate selection bias. RESULTS: A total of 456 patients were included in this study. Thymoma was present in 138 (30.3%) patients. The median follow-up time was 72 (range, 12-135) months. At the last follow-up, a lower proportion of thymomatous MG patients achieved complete stable remission (CSR) compared with non-thymomatous MG patients (P = 0.011), and the effective rate [CSR + pharmatologic remission (PR) + minimal manifestations (MM)] of thymomatous MG patients was also lower (P = 0.037). Considering time to CSR, Kaplan-Meier analysis showed thymomatous MG patients had lower cumulative CSR rate than non-thymomatous MG patients (log-rank, P = 0.019). After PSM, 105 pairs of patients were matched successfully. For the matched patients, thymomatous MG patients had a lower CSR rate and a lower effective rate (P = 0.002, 0.039, respectively), and K-M analysis still showed thymomatous MG patients had lower cumulative CSR rate (log-rank, P = 0.048). Multivariate Cox analysis demonstrated that thymoma (HR: 0.592, 95% CI 0.389-0.900, P = 0.014), older age at the time of surgery (HR: 0.971, 95% CI 0.953-0.990, P = 0.003), and preoperative course of MG > 12 months (HR: 0.474, 95% CI 0.317-0.708, P = 0.000) were negative predictive factors for CSR. CONCLUSIONS: Thymoma had a negative effect on the neurological outcome of MG after thymectomy. MG patients with old age and a preoperative course of longer than one year had a lower probability of achieving CSR.

Microvascular permeability and texture analysis of bone marrow in diabetic rabbits with critical limb ischemia based on dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Early on in the development of diabetes, skeletal muscles can exhibit microarchitectural changes that can be detected using texture analysis (TA) based on volume transfer constant (Ktrans ) maps. Nevertheless, there have been few studies and thus we evaluated microvascular permeability and the TA of the bone marrow in diabetics with critical limb ischemia (CLI). METHODS: Eighteen male rabbits were randomly assigned equally into an operation group with hindlimb ischemia and diabetes, a sham-operated group with diabetes only, and a control group. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was performed on all rabbits at predetermined intervals (1, 5, 10, 15, 20, and 25 days post-surgery). The pharmacokinetic model was used to generate the permeability parameters, while the textural parameters were derived from the Ktrans map. Data analysis methods included the independent sample t-test, Mann-Whitney U test, repeated-measures analysis of variance, and Pearson correlation tests. RESULTS: The Ktrans values reached a minimum on day 1 after ischemia induction, then gradually recovered, but remained lower than those of the sham-operated group. The volume fraction only showed a significant difference between the operation group and the sham-operated group on day 5 post-surgery, but not in the extravascular extracellular space volume fraction at all time points. A significantly reduced Ktrans on day 1, a decreased number of bone trabeculae (Tb.N), and the area of bone trabeculae (Tb.Ar), and an increased microvessel density on day 25 in the operation group compared with the sham-operated group were observed. At each time point, there was a discernible difference between the two groups in the mean value, mean of positive pixels, and sumAverage . CONCLUSIONS: The early stages of diabetic bone marrow with CLI can be evaluated by DCE-MRI for microvascular permeability. Texture analysis based on DCE-MRI could act as an imaging discriminator and new radiological analysis tool for critical limb ischemia in diabetes mellitus.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Psychrophilic phage phiGM22-3 efficiently controls Pseudomonas fluorescens contamination in cold-stored milk.

Pseudomonas fluorescens is a common spoilage causing microbe found in milk. Antibiotic preservatives may cause emergence of multidrug resistance, posing food safety related risks to public health. Phage treatment may be used as an alternative to antibiotics in controlling P. fluorescens contaminations. Here we reported that P. fluorescens phage phiGM22-3 reproduced rapidly over a broad temperature range of 4 through 30°C, and the optimum growth of phiGM22-3 occurred at 10°C, indicating that it was a psychrophilic virus. Genome analysis revealed that phiGM22-3 has a genome of 42,662 bp with an identical terminal direct repeat sequence of 328 bp and encodes 58 predicted proteins. Evidence revealed that phiGM22-3 recognized lipopolysaccharides (LPS) as receptor for infection. Additionally, two phage mutants phiMX2 and phiMX8 with different host ranges were identified in the phiGM22-3 population. Phage killing efficiency of P. fluorescens cells artificially inoculated in milk was evaluated. Phage phiGM22-3 and the cocktails containing phiMX2 and phiMX8 can lyse almost 100% bacterial cells at 4°C within 24 h. Taken together, our data indicated that the psychrophilic virus phiGM22-3 and its two mutants can efficiently inhibit bacteria growth at 4°C, showing a great potential to be used as alternatives to conventional antibiotics against P. fluorescens in refrigerated foods.

TMEM16A deficiency in alveolar type 2 epithelial cells protected against endoplasmic reticulum stress-induced ferroptosis during acute lung injury.

Transmembrane protein 16A (TMEM16A) is one of the members of the ten-member family of "transmembrane protein 16", playing critical roles in infection and solid organ injury. Acute lung injury (ALI) is a devastating disease which could be triggered by sepsis, trauma, and ischemia reperfusion. However, molecular mechanisms contributing to ALI are poorly understood at presently. In this study, we investigated the role of TMEM16A in sepsis-induced ALI using TMEM16A-deficient mice. Sepsis-induced ALI model was established by intratracheal injection of lipopolysaccharide (LPS). Our results showed that LPS stimulation significantly upregulated the expression levels of TMEM16A in lung tissues and in alveolar epithelial type II (AT2) cells. Knockout of TMEM16A in AT2 cells significantly improved pulmonary function and alleviated lung pathological injury in LPS-treated mice. Meanwhile, TMEM16A deficiency also inhibited endoplasmic reticulum (ER) stress and ferroptosis in AT2 cells from LPS-treated mice. In vitro experiments further demonstrated that ER stress and ferroptosis were inhibited after TMEM16A was knocked out. Furthermore, we used ER stress inducer thapsigargin to induce ER stress in TMEM16A-null AT2 cells and found that the induction of ER stress abolished the inhibition of ferroptosis by TMEM16A deficiency in LPS-treated AT2 cells. Finally, we disclosed that pharmacological inhibition of TMEM16A by shikonin also showed similar therapeutic effect on LPS-induced ALI in vivo. In conclusion, TMEM16A deficiency in AT2 cells could alleviate sepsis-induced ALI by decreasing ER stress-induced ferroptosis during ALI.

Glofitamab monotherapy induces high complete response rates and manageable safety in Chinese patients with heavily pretreated relapsed or refractory diffuse large B-cell lymphoma.

Not available.

Systematic analysis of histone acetylation regulators across human cancers.

BACKGROUND: Histone acetylation (HA) is an important and common epigenetic pathway, which could be hijacked by tumor cells during carcinogenesis and cancer progression. However, the important role of HA across human cancers remains elusive. METHODS: In this study, we performed a comprehensive analysis at multiple levels, aiming to systematically describe the molecular characteristics and clinical relevance of HA regulators in more than 10000 tumor samples representing 33 cancer types. RESULTS: We found a highly heterogeneous genetic alteration landscape of HA regulators across different human cancer types. CNV alteration may be one of the major mechanisms leading to the expression perturbations in HA regulators. Furthermore, expression perturbations of HA regulators correlated with the activity of multiple hallmark oncogenic pathways. HA regulators were found to be potentially useful for the prognostic stratification of kidney renal clear cell carcinoma (KIRC). Additionally, we identified HDAC3 as a potential oncogene in lung adenocarcinoma (LUAD). CONCLUSION: Overall, our results highlights the importance of HA regulators in cancer development, which may contribute to the development of clinical strategies for cancer treatment.

HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury.

Activated inflammation and pyroptosis in macrophage are closely associated with acute lung injury (ALI). Histone deacetylase 3 (HDAC3) serves as an important enzyme that could repress gene expression by mediating chromatin remodeling. In this study, we found that HDAC3 was highly expressed in lung tissues of lipopolysaccharide (LPS)-treated mice. Lung tissues from macrophage HDAC3-deficient mice stimulated with LPS showed alleviative lung pathological injury and inflammatory response. HDAC3 silencing significantly blocked the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in LPS-induced macrophage. LPS could recruit HDAC3 and H3K9Ac to the miR-4767 gene promoter, which repressed the expression of miR-4767 to promote the expression of cGAS. Taken together, our findings demonstrated that HDAC3 played a pivotal role in mediating pyroptosis in macrophage and ALI by activating cGAS/STING pathway through its histone deacetylation function. Targeting HDAC3 in macrophage may provide a new therapeutic target for the prevention of LPS-induced ALI.

Eriocitrin attenuates sepsis-induced acute lung injury in mice by regulating MKP1/MAPK pathway mediated-glycolysis.

Metabolic reprogramming has been shown to aggravate sepsis-induced acute lung injury. In particular, enhanced glycolysis is closely associated with inflammation and oxidative stress. Eriocitrin (ERI) is a natural flavonoid found in citrus fruit that exhibits various pharmacological activities, with antioxidant, anti-inflammatory, anti-diabetic, and anti-tumor properties. However, the role of ERI in lung injury is not well understood. We established a septic mouse model of acute lung injury (ALI) using lipopolysaccharide (LPS) for induction. Primary peritoneal macrophages were isolated to verify the relevant molecular mechanism. Tissues were assessed for lung pathology, pro-inflammatory cytokines, markers of oxidative stress, and protein and mRNA expression levels. In vivo experiments showed that ERI effectively alleviated LPS-induced pathological injury, suppress the inflammatory response (TNF-α, IL-1ß, IL-6 levels) and decreased oxidative stress (MDA, ROS) in murine lung tissue. In vitro, ERI increased the resistance of LPS-treated cells to excessive inflammation and oxidative stress by inhibiting the enhancement of glycolysis (indicated by expression levels of HIF-1α, HK2, LDHA, PFKFB3, and PKM2). Specifically, the beneficial effects of ERI following LPS-induced lung injury occurred through promoting the expression of MKP1, which mediates the inactivation of the MAPK pathway to inhibit enhanced glycolysis. These results demonstrate that ERI has a protective effect on sepsis-induced ALI by regulating MKP1/MAPK pathway mediated-glycolysis. Hence, ERI is a promising candidate against ALI via inhibiting glycolysis.

Variants of a putative baseplate wedge protein extend the host range of Pseudomonas phage K8.

BACKGROUND: Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins. RESULTS: Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life. CONCLUSION: Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors. Video Abstract.

Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center.

BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.

Analysis of influencing factors of postoperative myasthenic crisis in 564 patients with myasthenia gravis in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period. METHODS: A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymoma/thymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded. RESULTS: Osserman-stages IIB + III + IV (odds ratio [OR] 16.091, 95% confidence interval [CI] 5.170-50.076, p value < 0.001), the dosage of pyridostigmine bromide more than 240 mg (OR 6.462, 95% CI 3.110-13.427, p value < 0.001), ASA score 2 and 3 (OR 3.203, 95% CI 1.461-7.020, p value = 0.004), low diffusion lung capacity for carbon monoxide (DLCO%) (OR 0.981, 95% CI 0.963-1.000 p value = 0.049), and blood loss greater than 1000 ml (OR 16.590, 95% CI 1.911-144.011, p value = 0.011) were independent risk factors for myasthenic crisis. CONCLUSIONS: Patients with poor Osserman stages, higher preoperative dosage of pyridostigmine bromide, higher ASA score, poor pulmonary function (low DLCO%), and more intraoperative bleeding should be highly vigilant for the occurrence of postoperative myasthenic crisis.

Analysis of influencing factors of perioperative myasthenic crisis in 387 myasthenia gravis patients without thymoma in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in non-thymoma myasthenia gravis (MG) patients during perioperative period. METHODS: We retrospectively analyzed a total of 387 non-thymoma MG patients who underwent extended thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from February 2011 to December 2021, recorded ASA score, Osserman classification, preoperative course, pyridostigmine dosage, operation method, operation time, and intraoperative blood loss, then analyzed the factors associated with postoperative myasthenic crisis by univariate and multivariate logistic regression. RESULTS: Osserman classification IIB + III + IV (P < 0.001), history of myasthenic crisis (P = 0.013), pyridostigmine dosage greater than 240 (P < 0.001), ASA score 2 and 3 (P = 0.001) are independent risk factors for myasthenic crisis. CONCLUSION: Patients with poor Osserman classification, history of myasthenic crisis before surgery, larger preoperative dosage of pyridostigmine, and higher ASA scores should be highly alert to the occurrence of postoperative myasthenic crisis.

Surgical safety analysis and clinical experience sharing of myasthenia gravis patients aged 65 and over.

BACKGROUND: To evaluate the surgical safety in myasthenia gravis (MG) patients aged 65 and over. METHODS: A total of 564 patients with MG who underwent surgery in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were included in the study and divided into two groups taking the age of 65 as the boundary. Perioperative data of patients were recorded and statistically analyzed. RESULTS: Compared with young patients, FEV1, FEV1% and MVV in lung function of elderly MG patients were worse (p < 0.001, p < 0.001, p = 0.002). Postoperative drainage time was longer (p < 0.001), combined with more drainage volume (p = 0.002). The American Society of Anesthesiologists (ASA) score of elderly MG patients was higher (p < 0.001). Complications were more likely to occur (p = 0.008) after surgery and Clavien-Dindo classification (CDC) of postoperative complications was also higher (p = 0.003). Meanwhile, postoperative myasthenic crisis (POMC) was more likely to occur (p = 0.038). Logistic regression showed that lower DLCO% (p = 0.049) was an independent risk factor for postoperative complications. CONCLUSIONS: Surgical indications should be considered in each elderly MG patient on an individual basis. Moreover, most elderly MG patients safely survive the perioperative period and benefit from surgery through individualized consideration.

Bacillus subtilis phage phi18: genomic analysis and receptor identification.

Bacillus subtilis strains play a pivotal role in the fermentation industry. B. subtilis phages can cause severe damage by infecting bacterial cells used in industrial fermentation processes. In this work, we isolated and characterized a Bacillus subtilis-infecting phage, termed phi18. Transmission electron microscopy revealed that phage phi18 particles have typical myovirus morphology, with an icosahedral head connected to a contractile tail. Genomic analysis revealed that the phage genome is a linear double-stranded DNA molecule of 147,298 bp with terminal redundancy of 14,434 bp, and 226 protein coding genes and four tRNA genes were predicted in the genome. Phage-resistant mutants were selected from a mariner transposon-insertion library of B. subtilis 168 in which two bacterial genes, tagE and pgcA, which are required for the glycosylation of wall teichoic acid (WTA), were found to be disrupted, suggesting that WTA is the receptor for phage phi18. Comparative genomic analysis showed that phage phi18 is a new member of the genus Okubovirus of the family Herelleviridae. Finally, general characteristics of the phage-resistant mutants, including biofilm formation, growth, and sporulation, were examined. The results showed that the phage-resistant mutants grew as rapidly as the parental strain B. subtilis 168 at 42 °C, suggesting that these phage-resistant mutants may be used as starters in fermentation processes.

Single-cell RNA sequencing analysis revealed cellular and molecular immune profiles in lung squamous cell carcinoma.

Although breakthroughs have been made in the treatment of non-small cell lung cancer, there are only a few choices for advanced-stage or recurrent lung squamous cell carcinoma (LUSC) patients. In our study, we identified 7 major cell types in thedepicted the immunolandscape of LUSC microenvironment using single-cell RNA sequencing. We found that an immunosuppressive receptor, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), was highly expressed by regulatory T cells (Tregs) and exhausted CD8+T cells, suggesting that upregulation of TIGIT might promote an immunosuppressive microenvironment and inhibit the cytotoxic ability of CD8+T cells. We also identified tumor-associated neutrophil (TAN), characterized by CXCR2, CSF3R and CXCL8, in the tumor region, and TANs upregulated the expression of interleukin 1 receptor antagonist (IL1RN) which suggested that TAN might exert an immunosuppressive role via expressing IL1RN. Furthermore, the number of SPP1+ macrophages(SPP1+M) significantly increased in tumor microenvirnment, which was correlated with the poor survival of patients. Additionally, regulatory networks based on SPP1+M revealed that the disparities of several ligand-receptor pairs existed between tumor and normal tissues. Among these pairs, SPP1-CD44 showed the most interactions between SPP1+M and other cell types. Our results provided deep insight into the immune landscape of LUSC and an essential resource for drug discovery in the future.

Clinical characteristics of myasthenia gravis (MG) patients developing other autoimmune diseases after thymectomy from one single center cohort.

BACKGROUND: Myasthenia gravis (MG) patients are reported to have a high risk of other autoimmune diseases (ADs), and thymectomy may increase the risk further. A cohort of MG patients in which thymectomy was performed were investigated to analyze the prevalence, types and features of the new onset ADs. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Patients with a postoperative follow-up period shorter than a year or incomplete clinical records were excluded. Clinical and follow-up data were collected. Statistical analyses were performed using SPSS version 22.0. RESULTS: A total of 445 patients were included in this study. The median follow-up period was 72 months (range, 12-135 months). A total of 63 (14.2%) MG patients had concurrent ADs. The incidence rate was higher than the background prevalence of population (5%), and also higher than that of a former Chinese MG cohort (11.6%). A total of 47 patients (10.6%) were diagnosed with ADs before thymectomy, and 19 (4.3%) developed a new AD after thymectomy. The most common types of new onset ADs after thymectomy were Hashimoto's thyroiditis and rheumatoid arthritis (RA), which were different from those before thymectomy (hyperthyroidism and Hashimoto's thyroiditis). The incidence rate of new onset RA (1.35%) was higher than the frequency of RA before thymectomy (0.45%), and also higher than the incidence rate in a Chinese MG cohort (0.5%). There was a higher proportion of female patients (p = 0.026) with postoperative ADs. A younger age at operation may increase the risk of nonthymoma MG patients (p = 0.040) developing ADs. The postoperative treatment effect of MG was similar between patients with and without new onset ADs (p > 0.05). CONCLUSIONS: We observed a higher incidence rate of autoimmune diseases, especially rheumatoid arthritis, in MG patients after thymectomy. The most common types of ADs after thymectomy were different from those before thymectomy. New onset ADs tended to occur in female and young nonthymoma MG patients. The postoperative effect of MG was not related with the new occurrence of ADs.

Phage phiZ98: A novel tri-segmented dsRNA cystovirus for controlling Pseudomonas strains with defective lipopolysaccharides in foods.

Many Pseudomonas phages recognize lipopolysaccharides (LPS) as the receptor for infection. LPS defective mutants are often recovered from phage treatments, possibly causing the failure of phage applications. In this work, we isolated a lytic Pseudomonas phage, phiZ98, that can specifically lyse LPS defective strains of the genus Pseudomonas. Transmission electron microscopy (TEM) showed that phiZ98 particles were enveloped in a layer of membrane-like structure. Genomic analysis revealed that the phage has a genome of tri-segmented double-stranded RNA molecules of 6627 bp, 3769 bp, and 3075 bp, respectively. The results indicated that phage phiZ98 was the nineth member of the genus Cystovirus. The phiZ98 genome encoded 12 putative proteins with predicted functions and 15 hypothetical proteins. Mass spectrum analysis further identified 11 proteins present in the virions. Antibacterial activity assays showed that phage phiZ98 significantly inhibited cell growth, reduced biofilm formation, and removed mature biofilm. Moreover, phage phiZ98 can significantly control the growth of the host bacterial cells in sterilized milk or canned corned beef. In combination with phage K8 which used LPS as the receptor, phiZ98 can significantly reduce the phage-resistant mutants generated from the K8 treatment in milk. Taken together, the dsRNA phage phiZ98 could be an effective scavenger in removing phage-resistant mutants with defective LPS in cocktail applications.