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Both of nanoplastics (NPs) and Tetrabromobisphenol A (TBBPA) are organic pollutants widely detected in the environment and organisms. The large specific surface area of NPs makes them ideal vectors for carrying various toxicants, such as organic pollutants, metals, or other nanomaterials, posing potential threats to human health. This study used Caenorhabditis elegans (C. elegans) to investigate the neurodevelopmental toxicity induced by combined exposure of TBBPA and polystyrene NPs. Our results showed that combined exposure caused synergistic inhibitory effects on the survival rate, body length/width, and locomotor ability. Furthermore, the overproduction of reactive oxygen species (ROS), lipofuscin accumulation, and dopaminergic neuronal loss suggested that oxidative stress was involved in induction of neurodevelopmental toxicity in C. elegans. The expressions of Parkinson’s disease related gene (pink-1) and Alzheimer’s disease related gene (hop-1) were significantly increased after combined exposure of TBBPA and polystyrene NPs. Knock out of pink-1 and hop-1 genes alleviated the adverse effects such as growth retardation, locomotion deficits, dopaminergic loss, and oxidative stress induction, indicating that pink-1 and hop-1 genes play an important role in neurodevelopmental toxicity induced by TBBPA and polystyrene NPs. In conclusion, TBBPA and polystyrene NPs had synergistic effect on oxidative stress induction and neurodevelopmental toxicity in C. elegans, which was mediated through increased expressions of pink-1 and hop-1.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from Gardenia jasminoides J. Ellis and has been reported to have protective roles in ischemia-related brain damage. However, the role of GJ-4 in ERS has not been elucidated. We established a VD rat model through bilateral common carotid arteries occlusion (2-VO). The rats were intragastrically administrated with GJ-4 (10, 25, and 50[Formula: see text]mg/kg) and nimodipine (10[Formula: see text]mg/kg). Data from a Morris water maze test showed that GJ-4 could significantly alleviate learning and memory deficits in VD rats. Nissl and cleaved caspase-3 staining revealed that GJ-4 can inhibit apoptosis and thus exert a protective role in the brain of 2-VO rats. Western blot results suggested that GJ-4 significantly reduced ERS-related protein expression and inhibited apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. For in vitro studies, the oxygen-glucose deprivation (OGD) SH-SY5Y model was employed. Western blot and Hoechst 33342/PI double staining were utilized to explore the effects of crocetin, the main active metabolite of GJ-4. Like GJ-4 in vivo, crocetin in vitro also decreased ERS-related protein expression and inhibited the activation of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. Thus, crocetin exerted similar protective roles on OGD challenged SH-SY5Y cells in vitro. In summary, GJ-4 and crocetin reduce the ERS in the brain of VD rats and SY5Y cells subjected to OGD and inhibit neuronal apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP pathway, suggesting that GJ-4 may be useful for the treatment of VD.

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT).Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan-Meier method and log-rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods.From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264-5.566,Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.

A potential consequence of installing a 2 m long pipe offset on a ventilated drainage system in a high-rise buildings is that the water seal could be damaged when the flowrate exceeds the maximum discharge capacity of a drainage system, thereby threatening the indoor health safety. Some high-rise buildings are designed for commercial and residential use to achieve economic and social benefits, so the whole building use and layout changes in the vertical direction. The drainage stack may be designed with an offset between floors to avoid structural obstacles inside the building. The flow direction change could destroy the water seal of sanitary appliances and threaten the health of residents. To better understand the influence of the form of a pipe offset on the drainage capacity, a full-scale experiment was conducted to study the secondary ventilated system with an antireflux H-tube pipe, which was equipped with two guide plates inside to improve the air-water flow pattern and prevent backflow, installed between floor. This study also considered a kind of offset where the offset distance was 2.0 m rather than the S-shaped offset joint, which is more common in commercial and residential complexes. The influence on the discharge capacity of installing an extra antireflux H-tube pipe was compared with normal 90-degree elbow and only one antireflux H-tube pipe above the offset point. The pressure fluctuation and water seal losses under constant discharge rates were adopted as experimental parameters to determine the maximum discharge capacity according to Standard for Capacity Test of Vertical Pipe of the Domestic Residential Drainage System. Results show that the installation of an extra antireflux H-tube pipe can release the air accumulation caused by pipe offset, and the combined installation of a large curvature elbow and an extra antireflux H-tube pipe can effectively improve the discharge capacity. Practical Application: 2 metre long offsets are not unusual in ventilated drainage systems in high-rise buildings, however, designers and builders do not pay sufficient attention to the adverse consequences of the pipe offset. An extra antireflux H-tube pipe can be installed above the offset joint to optimise the drainage system to perform as it would without the offset. In a system with 2 m long pipe offset, installing a large curvature elbow together with an extra antireflux H-tube pipe together provides a better effect.

China has entered a new stage of high-quality economic development, which puts forward in-depth requirements for environmental protection. Companies in heavily polluting industries are required to disclose environmental information. Fulfilling environmental responsibilities and disclosing this information may be either a responsible moral act or an opportunistic act. Taking listed companies in China’s heavily polluting industries from 2009 to 2020 as a sample, this study examines the economic consequences of enterprise environmental information disclosure (EID) from the earnings management (EM) perspective, as an external representation of ‘ethical behaviour’ and ‘opportunism motivations’ of EID and considers the effects of internal management competency and operating environment volatility. Findings include: (1) EID can restrain EM and support the ‘ethical behaviour’ motivation of EID. (2) Compared with the ‘soft disclosure’ of environmental information, the effect of ‘hard disclosure’ on EM is more obvious. (3) Greater management competency can strengthen the EM governance role of EID, while greater environmental uncertainty weakens this mechanism. (4) EID in enterprises in a mature period, state-owned, western regions, or low public environmental concern areas show an inhibitory effect on EM. Furthermore, its moralistic tendencies are more obvious compared with enterprises in growth or recession periods, non-state-owned, eastern regions, and those with high public environmental concerns.

As an attractive immunization approach for chickens, in ovo vaccination can induce a considerable degree of protection by the time of hatching, provide support in closing the window in which birds are susceptible to infection, facilitate fast and uniform vaccine delivery, and reduce labor costs by the use of mechanized injectors. The commercial live Newcastle disease virus (NDV) vaccine strains are not safe for in ovo vaccination and cause the death of chicken embryos.

ABC toxins are pore-forming toxins characterised by the presence of three distinct components assembled into a hetero-oligomeric toxin complex ranging in size from 1.5–2.5 MDa. Most ABC toxins studied to date appear to be insecticidal toxins, although genes predicted to encode for homologous assemblies have also been found in human pathogens. In insects, they are delivered to the midgut either directly via the gastrointestinal tract, or via a nematode symbiont, where they attack the epithelial cells and rapidly trigger widespread cell death. At the molecular level, the homopentameric A subunit is responsible for binding to lipid bilayer membranes and introducing a protein translocation pore, through which a cytotoxic effector — encoded at the C-terminus of the C subunit — is delivered. The B subunit forms a protective cocoon that encapsulates the cytotoxic effector, part of which is contributed by the N-terminus of the C subunit. The latter also includes a protease motif that cleaves the cytotoxic effector, releasing it into the pore lumen. Here, we discuss and review recent studies that begin to explain how ABC toxins selectively target specific cells, establishing host tropism, and how different cytotoxic effectors trigger cell death. These findings allow for a more complete understanding of how ABC toxins function in an in vivo context, which in turn provides a stronger foundation for understanding how they cause disease in invertebrate (and potentially also vertebrate) hosts, and how they might be re-engineered for therapeutic or biotechnological purposes.

Causal inference revealing causal dependencies between variables from empirical data has found applications in multiple sub-fields of scientific research. A quantum perspective of correlations holds the promise of overcoming the limitation by Reichenbach's principle and enabling causal inference with only the observational data. However, it is still not clear how quantum causal inference can provide operational advantages in general cases. Here, we have devised a photonic setup and experimentally realized an algorithm capable of identifying any two-qubit statistical correlations generated by the two basic causal structures under an observational scenario, thus revealing a universal quantum advantage in causal inference over its classical counterpart. We further demonstrate the explainability and stability of our causal discovery method which is widely sought in data processing algorithms. Employing a fully observational approach, our result paves the way for studying quantum causality in general settings.

BackgroundThere is increasing evidence that immunotherapy (programmed cell death-1 (PD-1) inhibitor) combined with chemotherapy is superior to chemotherapy alone in neoadjuvant therapy for patients with previously untreated, unresectable advanced, or metastatic esophageal adenocarcinoma (EAC)/gastric/gastroesophageal junction adenocarcinoma (GEA). However, the results of recent studies have been contradictory. Therefore, the aim of this article is to evaluate the efficacy and safety of PD-1 inhibitors combined with chemotherapy in neoadjuvant therapy through meta-analysis.MethodWe comprehensively reviewed the literature and clinical randomized controlled trials (RCTs) by February 2022 by searching Medical Subject Headings (MeSH) and keywords such as “esophageal adenocarcinoma” or “immunotherapy” in several databases, including the Embase, Cochrane, PubMed, and ClinicalTrials.gov websites. Two authors independently selected studies, extracted data, and assessed the risk of bias and quality of evidence by using standardized Cochrane Methods procedures. The primary outcomes were 1-year overall survival (OS) and 1-year progression-free survival (PFS), estimated by calculating the 95% confidence interval (CI) for the combined odds ratio (OR) and hazard ratio (HR). Secondary outcomes estimated using OR were disease objective response rate (DORR) and incidence of adverse events.ResultsFour RCTs with a total of 3,013 patients researching the efficacy of immunotherapy plus chemotherapy versus chemotherapy alone on gastrointestinal cancer were included in this meta-analysis. The results showed that immune checkpoint inhibitor plus chemotherapy treatment was associated with an increased risk of PFS (HR = 0.76 [95% CI: 0.70–0.83]; p < 0.001), OS (HR = 0.81 [95% CI: 0.74–0.89]; p < 0.001), and DORR (relative ratio (RR) = 1.31 [95% CI: 1.19–1.44]; p < 0.0001) when compared with chemotherapy alone in advanced, unresectable, and metastatic EAC/GEA. However, immunotherapy combined with chemotherapy increased the incidence of adverse reactions such as alanine aminotransferase elevation (OR = 1.55 [95% CI: 1.17–2.07]; p = 0.003) and palmar-plantar erythrodysesthesia (PPE) syndrome (OR = 1.30 [95% CI: 1.05–1.63]; p = 0.02). Nausea (OR = 1.24 [95% CI: 1.07–1.44]; p = 0.005) and white blood cell count decreased (OR = 1.40 [95% CI: 1.13–1.73]; p = 0.002), and so on. Fortunately, toxicities were within acceptable limits. Meanwhile, for patients with a combined positive score (CPS) ≥1, compared with chemotherapy alone, immunotherapy combined with chemotherapy had a better overall survival rate (HR = 0.81 [95% CI: 0.73–0.90]; p = 0.0001).ConclusionOur study shows that immunotherapy plus chemotherapy has an obvious benefit for patients with previously untreated, unresectable advanced, or metastatic EAC/GEA when compared with chemotherapy alone. However, a high risk of adverse reactions may occur during immunotherapy plus chemotherapy, and more studies focusing on the treatment strategies of untreated, unresectable advanced, or metastatic EAC/GEA are warranted.Systematic review registrationwww.crd.york.ac.uk, identifier CRD42022319434.

Sequential weak measurements allow the direct extraction of individual density-matrix elements instead of globally reconstructing the whole density matrix, opening a new avenue for the characterization of quantum systems. Nevertheless, the requirement of multiple coupling for each qudit of quantum systems and the lack of appropriate precision evaluation constraint its applicability extension, especially for multi-qudit quantum systems. Here, we propose a resource-efficient scheme (RES) to directly characterize the density matrix of general multi-qudit systems, which not only optimizes the measurements but also establishes a feasible estimation analysis. In this scheme, an efficient observable of quantum system is constructed such that a single meter state coupled to each qudit is sufficient to extract the corresponding density-matrix element. An appropriate model based on the statistical distribution of errors are used to evaluate the precision and feasibility of the scheme. We experimentally apply the RES to the direct characterization of general single-photon qutrit states and two-photon entangled states. The results show that the RES outperforms the sequential schemes in terms of efficiency and precision in both weak- and strong- coupling scenarios. This work sheds new light on the practical characterization of large-scale quantum systems and investigation of their non-classical properties., 6 pages, 4 figures

In recent years, molecular perovskite energetic materials have attracted more attention because of their simple synthesis processes, high thermal stabilities, excellent performances, and great significance as a design platform for energetic materials. To explore the possibility of the application of molecular perovskite energetic materials in heat-resistant explosives, four silver(I)-based molecular perovskite energetic compounds, (H

Background With the rapid advances of genetic and genomic technologies, the pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) were gradually becoming clear, however, the prognosis of IPF was still poor. This study aimed to systematically explore the ferroptosis-related genes model associated with prognosis in IPF patients. Methods Datasets were collected from the Gene Expression Omnibus (GEO). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to create a multi-gene predicted model from patients with IPF in the Freiburg cohort of the GSE70866 dataset. The Siena cohort and the Leuven cohort were used for validation. Results Nineteen differentially expressed genes (DEGs) between the patients with IPF and control were associated with poor prognosis based on the univariate Cox regression analysis (all P Conclusions These results imply that the 8-ferroptosis-related genes signature in the bronchoalveolar lavage samples might be an effective model to predict the poor prognosis of IPF.

Infectious laryngotracheitis (ILT) and Newcastle disease (ND) are two important avian diseases that have caused huge economic losses to the poultry industry worldwide. Newcastle disease virus (NDV) has been used as a vector in the development of vaccines and gene delivery. In the present study, we generated a thermostable recombinant NDV (rNDV) expressing the glycoprotein gB (gB) of infectious laryngotracheitis virus (ITLV) based on the full-length cDNA clone of the thermostable TS09-C strain. This thermostable rNDV, named rTS-gB, displayed similar thermostability, growth kinetics, and pathogenicity compared with the parental TS09-C virus. The immunization data showed that rTS-gB induced effective ILTV- and NDV-specific antibody responses and conferred immunization protection against ILTV challenge in chickens. The efficacy of rTS-gB in alleviating clinical signs was similar to that of the commercial attenuated ILTV K317 strain. Furthermore, rTS-gB could significantly reduce viral shedding in cloacal and tracheal samples. Our study suggested that the rNDV strain rTS-gB is a thermostable, safe, and highly efficient vaccine candidate against ILT and ND.

Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.

Boron powder is an additive for metalized explosives with great application potential. To improve the energy release ability of boron powder, the composites of RDX and nano-boron (RDX@Nano-B) were prepared by the spray-drying process, and the metalized explosives based on it were designed (named PBX-B1). The detonation heat and explosion pressure of boron-containing explosives PBX-B1 under vacuum and air conditions were measured and analyzed by an internal explosion test. On the other hand, the equilibrium pressure and energy release of the PBX-B1 explosive system after detonation were analyzed and compared with that of an explosive formulation of the same composition (named PBX-B2). Results showed that the detonation heat of PBX-B1 was 7456 J/g in a vacuum environment, which was 34.8% higher than that of RDX (5530 J/g). However, in the air environment, the detonation heat of PBX-B1 increased by 19.2% compared with that in the vacuum environment, and the explosive gas products mainly included N2, NOx, CO, H2O, CH4, HCN, and CO2. The peak pressure and equilibrium pressures of PBX-B1 were 11.2 and 0.42 MPa, which were increased by 155% and 75% compared with the vacuum environment, respectively. It is worth noting that, compared with that of PBX-B2, the released energy in the aerobic combustion stage and equilibrium pressure of PBX-B1 were increased by 49.8% and 10.5%. This study demonstrated the strategy of improving the energy release of boron-containing metalized explosives through the design of an explosive microstructure, which provides important clues for the design of higher-energy metalized explosives.

Background: We aimed to construct and validate the esophageal squamous cell carcinoma (ESCC)-related m6A regulators by means of machine leaning.Methods: We used ESCC RNA-seq data of 66 pairs of ESCC from West China Hospital of Sichuan University and the transcriptome data extracted from The Cancer Genome Atlas (TCGA)-ESCA database to find out the ESCC-related m6A regulators, during which, two machine learning approaches: RF (Random Forest) and SVM (Support Vector Machine) were employed to construct the model of ESCC-related m6A regulators. Calibration curves, clinical decision curves, and clinical impact curves (CIC) were used to evaluate the predictive ability and best-effort ability of the model. Finally, western blot and immunohistochemistry staining were used to assess the expression of prognostic ESCC-related m6A regulators.Results: 2 m6A regulators (YTHDF1 and HNRNPC) were found to be significantly increased in ESCC tissues after screening out through RF machine learning methods from our RNA-seq data and TCGA-ESCA database, respectively, and overlapping the results of the two clusters. A prognostic signature, consisting of YTHDF1 and HNRNPC, was constructed based on our RNA-seq data and validated on TCGA-ESCA database, which can serve as an independent prognostic predictor. Experimental validation including the western and immunohistochemistry staining were further successfully confirmed the results of bioinformatics analysis.Conclusion: We constructed prognostic ESCC-related m6A regulators and validated the model in clinical ESCC cohort as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.

Ethnopharmacological Relevance. The medicinal use of Gastrodia elata BI., a dry tuber of the orchid family, has a long history. Gastrodia elata BI. has the functions of calming the liver, relieving muscle spasms, and dispelling gas. Aim of this Review. To review the traditional uses, botany, phytochemistry, pharmacology, and pharmacokinetics of Gastrodia elata BI. In addition, we discuss the future development and research prospects of this plant in detail. Materials and Methods. This article collects information from relevant documents, including scientific papers, books, and dissertations concerning Gastrodia elata BI. Results. To date, research on Gastrodia elata BI. has identified about 100 active compounds. Many compounds in Gastrodia elata BI. have biological activities, such as sedation and hypnosis, anticonvulsion, improvement of learning and memory, protection of neurons, antidepressive effects, lowering of blood pressure, promotion of angiogenesis, protection of cardiomyocytes, antiplatelet aggregation, anti-inflammatory activity, and amelioration of labor pains. Conclusion. Although many traditional uses of this plant have been confirmed, it is necessary to continue to study the relationship between its structure and function, clarify the mechanisms of pharmacological effects, and explore new clinical applications so as to better delineate the quality control standards for Gastrodia elata BI.

The metal-free energetic material DAP-M4 is a rare room-temperature moisture-stabilized ferroelectric crystal simultaneously exhibiting an exploitable piezoelectricity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

Additional file 1. Table S1: Parameters setup of the wavelengths of the excitation (Ex) lasers and the passbands of the emission (Em) filters of LSCM for inducing and detecting the fluorescence of different biomarkers (kits) for ROS and organelles in cells. Fig. S1: Cell fluorescence images of LSCM for labeled ROS irradiated by Cs-137 with a dose of 6 Gy (magnification: ×20); Fig. S2: Cell fluorescence images of LSCM for labeled activate mitochondria, 48 hours after irradiation of 6 Gy Cs-137 (magnification: ×20); Fig. S3: Cell fluorescence images of LSCM for labeled cytoskeletons, 48 hours after the irradiation of Cs-137 with a dose of 6 Gy (magnification: ×100).

To assess the prognostic significance of immunoglobulin (Ig) paraproteinaemia in mucosa-associated lymphoid tissue (MALT) lymphoma, 218 patients diagnosed with MALT lymphoma were enrolled in this study. Serum Ig paraprotein was detected in 42 of 218 patients (19.3%), mostly IgM-K (15, 35.7%), followed by IgM-L and IgG-L. Advanced age (p = 0.025), poor Eastern Cooperative Oncology Group performance status (p = 0.014), bone marrow involvement (p = 0.019), B symptoms (p = 0.039), advanced disease stage (III-IV) (p 0.0001), elevated serum β2-microglobulin level (p 0.0001), multiple extranodal sites of involvement (p 0.0001), nodal involvement (p 0.0001), systemic therapy (p 0.0001) and higher MALT-lymphoma International Prognostic Index (MALT-IPI) scores (p = 0.001) were significantly associated with the presence of serum Ig paraprotein. Multivariate Cox regression analysis showed that Ig paraproteinaemia was an independent prognostic predictor for inferior progression-free survival (PFS) and overall survival. A new prognostic index based on MALT-IPI and Ig paraproteinaemia, as assessed using receiver operating characteristic curves and the area under the curve statistics, showed better discriminative ability than MALT-IPI in predicting PFS. In conclusion, Ig paraproteinaemia was a promising prognostic predictor for MALT lymphoma. Ig paraproteinaemia together with MALT-IPI might contribute to optimising therapeutic management in clinical practice.

The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity.In vivoevaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.

Lichenysin, an amphiphilic biosurfactant with structural and physicochemical properties similar to surfactin, is produced by Bacillus licheniformis. Its low toxicity, good environmental compatibility, solubilization, foaming, emulsification and detergent activities have led to a wide range of applications in agricultural biocontrol, enhanced oil recovery, foaming agents for cosmetics and detergents for household cleaning products. However, despite the extraordinary surface-active properties and potential applications of lichenysin, the number of wild bacteria found so far is relatively low. Low titers and high costs are the main limiting factors for widespread industrial applications. In this study, a factorial design was used to optimize the composition of the medium for the production of lichenysin by Bacillus licheniformis Ali5. Firstly, the solutions of carbon, nitrogen, amino acids, inorganic salts and trace elements in the medium were evaluated in flasks using a single-factor optimization method. Meanwhile, the operating conditions were optimized in the same way. Afterwards, a partial factorial design was used to investigate the effect of six variables (five medium compositions and inoculum size) on lichenysin production. Based on the results obtained, the concentrations of sucrose and ammonium nitrate and the inoculum size were considered to be important for lichenysin production. Subsequently, a full factorial design was used to optimize these three variables. The optimized medium composition were sucrose 19.8 g/L, NH4NO3 3.9 g/L, K2HPO4·3H2O 4.0 g/L, MgSO4·7H2O 0.6 g/L, FeSO4·7H2O 0.1 g/L, CaCl2 0.01 g/L, NaCl 3.0, trace elements 1.2 mL/L. Finally, the titer of lichenysin after fed-batch fermentation reached 1425.85 mg/L, which was approximately 5.5 times higher than the titer of lichenysin from the original medium. Consequently, the method was further demonstrated to be suitable for lichenysin production.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from

BACKGROUND: We examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic esophageal squamous cell carcinoma (ESCC) patients with negative lymph node. METHODS: We included 1,836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03–117.3 months). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model’s construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P

To investigate the mechanical properties and constitutive equation of pressed CL−20 based aluminized explosives, the stress-strain curves at different strain rates are obtained by quasi-static and dynamic compression tests using universal testing machine and Split Hopkinson Pressure Bars (SHPB), respectively. The results suggest that the quasi-static and dynamic compression process of pressed CL−20 based aluminized explosives can be divided into elastic stage, hardening stage, and strain soften. In the process quasi-static compression, the pressed CL−20 based aluminized explosives have obvious strain rate effects. As the strain rate increases, the elastic modulus and ultimate strength increase, while the critical strain decrease, and the elastic stress basically remains unchanged. Under dynamic compression, strain rate effects are not obvious in the initial stage when the strain is less than 0.01. When the strain is larger than 0.01, there is a significant strain rate effects, causing the elastic stress, elastic modulus and ultimate strength to increase as dynamic loading strain rate increasing. In addition, the constitutive equations under quasi-static and dynamic compression are described by power-exponential hardening model and ZWT model, and the test results of which are in good agreement with the model calculations, indicating that the two model can be used to describe the mechanical properties of a pressed CL−20 based aluminized explosives.

The aim of this project was to promote evidence-based practice in the prevention and management of pressure injury in lung disease patients.Pressure injury is a crucial quality indicator for hospital care of patients. The pressure injury incidence threshold in the chest wards has been exceeding that of the general ward (0.128%), which may extend patients' hospital stay.Clinical audits were performed using the JBI Practical Application of Clinical Evidence System and Getting Research into Practice (GRiP) audit and feedback tool. Twelve audit criteria representing best practice recommendations for preventing and managing pressure injury among lung disease patients were used. A baseline audit was performed to measure the degree of consistency between existing practice and best practice. This project used the GRiP analysis and multiple strategies to develop care protocols for pressure injury prevention and management. A follow-up audit was conducted to measure changes in clinical practice and pressure injury incidence.Postimplementation audit compliance rates improved for the following criteria: skin assessment for identifying pressure injury indications (from 31 to 81%), identification of pressure injury risk score/category (from 19 to 88%), employment of nutritional assessment tools (from 8 to 93%), and provision of information regarding oral nutritional supplements (from 23 to 84%). Furthermore, patients learning the pressure injury care protocols (from 48 to 93%), the receipt of additional skin protection measures, and repositioning of vulnerable areas to relieve pressure increased to 100 and 93%, respectively. After project implementation, the monthly pressure injury incidence decreased markedly from 0.075 to 0.021%.The success factors of this project are attributable to leadership, open communication, multiple learning-by-doing strategies, regular audits, and the promotion of patient and family engagement.