The Impact of High Intensity Focused Ultrasound (HIFU) on Tumor-Specific Immune Responses of Prostate Cancer.

High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for prostate cancer. It utilizes focused acoustic energy to achieve localized thermal ablation, while also potentially exerting immunomodulatory effects. This review aims to elucidate the mechanisms underlying how HIFU influences tumor-specific immune responses in prostate cancer. These mechanisms include the release of tumor-associated antigens and damage-associated molecular patterns, the activation of innate immune cells, the facilitation of antigen presentation to adaptive immune cells, the enhancement of activation and proliferation of tumor-specific cytotoxic T lymphocytes, and the attenuation of the immunosuppressive tumor microenvironment by reducing the activity of regulatory T cells and myeloid-derived suppressor cells. Both preclinical investigations and emerging clinical data in prostate cancer models highlight HIFU's potential to modulate the immune system, as evidenced by increased infiltration of effector immune cells, elevated levels of pro-inflammatory cytokines, and improved responsiveness to immune checkpoint inhibitors. HIFU induces immunogenic cell death, leading to the release of tumor antigens and danger signals that activate dendritic cells and facilitate cross-presentation to cytotoxic T cells. Additionally, FUS ablation reduces immunosuppressive cells and increases infiltration of CD8+ T cells into the tumor, reshaping the tumor microenvironment. By priming the immune system while overcoming immunosuppression, combining FUS with other immunotherapies like checkpoint inhibitors and cancer vaccines holds promise for synergistic anti-tumor effects. Despite challenges in optimizing parameters and identifying suitable patients, FUS represents a novel frontier by modulating the tumor microenvironment and enhancing anti-tumor immunity through a non-invasive approach.

Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real-world study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs. METHODS: Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD). RESULTS: A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications. CONCLUSIONS: Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.

The prevalence and risk factors of work-related musculoskeletal disorders among nurses in China: A systematic review and meta-analysis.

BACKGROUND: Work-related musculoskeletal disorders significantly impact the job performance and quality of life of nursing personnel in China, necessitating an understanding of their prevalence and risk factors to enhance occupational health and improve medical safety. OBJECTIVE: To systematically evaluate the prevalence and risk factors of work-related musculoskeletal disorders among clinical nurses in China. DESIGN: Systematic literature review and meta-analysis. METHODS: A computerized search was conducted on databases, including the China Knowledge Resource Integrated Database, Wanfang Database, China Biomedical Literature Database, Weipu Database, Embase, PubMed, Web of Science, the Cochrane Library, and CINAHL, covering studies from inception to February 28, 2024, addressing the risk factors for work-related musculoskeletal disorders among clinical nursing professionals in China. The meta-analysis was performed using Review Manager 5.4 and Stata 14 software. RESULTS: The analysis included 23 articles, involving a total of 21,042 cases, and revealed a prevalence rate of 79 % (95 % CI: 73 %-84 %) for work-related musculoskeletal disorders among clinical nursing staff in China. Subgroup analysis revealed that the prevalence of work-related musculoskeletal disorders was highest among those with length of service >15 years, at 87 %; the 31-40 age group had a higher prevalence than other age groups, at 85 %; female nurses exhibited a prevalence rate of 80 %, surpassing male nurses at 77 %, while surgical nurses had a higher prevalence rate (83 %) than those in other departments. The most affected body parts were the neck (58 %), waist (57 %), shoulders (49 %), and back (35 %). Identified risk factors for work-related musculoskeletal disorders among clinical nurses in China included age >35 years (OR = 1.69, 95 % CI: 1.16-2.45), length of service ≥10 years (OR = 3.30, 95 % CI: 1.84-5.92), marital status (married) (OR = 2.19, 95 % CI: 1.91-2.50), heavy workload (OR = 2.46, 95 % CI: 1.25-4.83), weekly work hours >40 h (OR = 1.50, 95 % CI: 1.34-1.67), daily work hours >8 h (OR = 1.71, 95 % CI: 1.32-2.21), strong sense of work fatigue (OR = 1.47, 95 % CI: 1.22-1.76), and high night shift frequency (OR = 1.81, 95 % CI: 1.62-2.02). Regular physical exercise was found to be a protective factor (OR = 0.68, 95 % CI: 0.56-0.82). CONCLUSION: The overall prevalence of work-related musculoskeletal disorders among clinical nursing staff in China was 79 %. Age >35 years, length of service ≥10 years, marital status (married), heavy workload, weekly work hours >40 h, daily work hours >8 h, strong sense of work fatigue, and night shift frequency were identified as risk factors. Nursing administrators and staff can take proactive measures against the aforementioned factors to reduce the risk of illness and ensure the safety of medical care. REGISTRATION: PROSPERO: CRD42023479433.

Histology and transcriptomic analysis reveal the inflammation and affected pathways under 2-methylisoborneol (2-MIB) exposure on grass carp.

2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.

Complete genome analysis of copper resistant bacteria Pseudoalteromonas sp. CuT4-3 isolated from a deep-sea hydrothermal vent.

Pseudoalteromonas sp. CuT4-3, a copper resistant bacterium, was isolated from deep-sea hydrothermal sulfides on the Southwest Indian Ridge (SWIR), is an aerobic, mesophilic and rod-shaped bacterium belonging to the family Pseudoalteromonadaceae (class Gammaproteobacteria, order Alteromonadales). In this study, we present the complete genome sequence of strain CuT4-3, which consists of a single circular chromosome comprising 3,660,538 nucleotides with 41.05% G + C content and two circular plasmids comprising 792,064 nucleotides with 40.36% G + C content and 65,436 nucleotides with 41.50% G + C content. In total, 4078 protein coding genes, 105 tRNA genes, and 25 rRNA genes were obtained. Genomic analysis of strain CuT4-3 identified numerous genes related to heavy metal resistance (especially copper) and EPS production. The genome of strain CuT4-3 will be helpful for further understanding of its adaptive strategies, particularly its ability to resist heavy metal, in the deep-sea hydrothermal vent environment.

Multi-Mode Damage and Fracture Mechanisms of Thin-Walled Tubular Parts with Cross Inner Ribs Manufactured via Flow Forming.

In order to study the multi-mode damage and fracture mechanisms of thin-walled tubular parts with cross inner ribs (longitudinal and transverse inner ribs, LTIRs), the Gurson-Tvergaard-Needleman (GTN) model was modified with a newly proposed stress state function. Thus, tension damage and shear damage were unified by the new stress state function, which was asymmetric with respect to stress triaxiality. Tension damage dominated the modification, which coupled with the shear damage variable, ensured the optimal prediction of fractures of thin-walled tubular parts with LTIRs by the modified GTN model. This included fractures occurring at the non-rib zone (NRZ), the longitudinal rib (LIR) and the interface between the transverse rib (TIR) and the NRZ. Among them, the stripping of material from the outer surface of the tubular part was mainly caused by the shearing of built-up material in front of the rollers under a large wall thickness reduction (ΔT). Shear and tension deformation were the causes of fractures occurring at the NRZ, while axial tension under a large TIR interval (l) mainly resulted in fractures on LIRs. Fractures at the interface between the TIR and NRZ were due to the shearing applied by rib grooves and radial tension during the formation of ribs. This study can provide guidance for the manufacturing of high-performance aluminum alloy thin-walled tubular components with complex inner ribs.

Correlation Between the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated with Hashimoto's Thyroiditis, BRAF V600E Gene Mutation, and RET Gene Rearrangement.

OBJECTIVE: To analyse the expression of BRAF V600E protein and RET gene rearrangement in papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT) and to explore its clinical and pathological significance. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology, East China Normal University (Wuhu No. 2 People's Hospital), Wuhu, China, from January 2019 to July 2022. METHODOLOGY: The study population of 150 patients who underwent central lymph node dissection. They were divided into two groups: the PTC group (76/150, 50.7%) and the PTC with HC group (74/150, 49.3%). The expression of BRAF V600E protein was detected using immunohistochemistry, and the RET gene rearrangement status was detected using fluorescence in situ hybridisation. The detection results and clinical pathological characteristics were statistically analysed. RESULTS: Compared with the PTC group, the prevalence rate of female PTC in HT group was significantly higher than that of the male group, the rate of lymph node metastasis was lower, and the proportion of tumour diameter ≤ 1cm was higher (p < 0.05). However, no significant difference in patient age and multifocality was found between the two groups (p > 0.05). The BRAF V600E positive rate in the PTC combined with HT group (48.6%) was lower than in the PTC group (73.7%), and the RET gene rearrangement positive rate was higher than in the PTC group (p < 0.05). The expression of BRAF V600E protein in PTC combined with HT is correlated with multifocality (p < 0.05), and there is a correlation between RET gene rearrangement and the gender of the patient in the PTC group (p < 0.05). CONCLUSION: There is a lower rate of BRAF V600E protein positivity in PTC combined with HT patients, as well as a higher rate of RET gene rearrangements positive in PTC combined with HT patients. There is a correlation between multifocality and BRAF V600E protein expression. KEY WORDS: Papillary thyroid carcinoma, Hashimoto's thyroiditis, BRAF V600E protein, RET gene rearrangement.

4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

Dithiocarbonate-Protected Au25 Nanorods of a Chiral D5 Configuration and NIR-II Phosphorescence.

Innovative surface-protecting ligands are in constant demand due to their crucial role in shaping the configuration, property, and application of gold nanoclusters. Here, the unprecedented O-ethyl dithiocarbonate (DTX)-stabilized atomically precise gold nanoclusters, [Au25(PPh3)10(DTX)5Cl2]2+ (Au25DTX-Cl) and [Au25(PPh3)10(DTX)5Br2]2+ (Au25DTX-Br), were synthesized and structurally characterized. The introduction of bidentate DTX ligands not only endowed the gold nanocluster with unique staggered Au25 nanorod configurations but also generated the symmetry breaking from the D5d geometry of the Au25 kernels to the chiral D5 configuration of the Au25 molecules. The chirality of Au25 nanorods was notably revealed through single-crystal X-ray diffraction, and chiral separation was induced by employing chiral DTX ligands. The staggered configurations of Au25 nanorods, as opposed to eclipsed ones, were responsible for the large red shift in the emission wavelengths, giving rise to a promising near-infrared II (NIR-II, >1000 nm) phosphorescence. Furthermore, their performances in photocatalytic sulfide oxidation and electrocatalytic hydrogen evolution reactions have been examined, and it has been demonstrated that the outstanding catalytic activity of gold nanoclusters is highly related to their stability.

Supertwisted Chiral Gyroid Mesophase in Chiral Rod-Like Compounds.

Among the intriguing bicontinuous self-assembled structures, the gyroid cubic is the most ubiquitous. It is found in block and star polymers, surfactants with or without solvent, in thermotropic liquid crystals with end- or side-chains, and in biosystems providing structural color and modelling cell mitosis. It contains two interpenetrating networks of opposite chirality and is thus achiral if, as usual, the content of the two nets is the same. However, we now find that this is not the case for strongly chiral compounds. While achiral molecules follow the opposite twists of nets 1 and 2, molecules with a chiral center in their rod-like core fail to follow the 70° twist between junctions in net 2 and instead wind against it by -110° to still match the junction orientation. The metastable chiral gyroid is a high-entropy high-heat-capacity mesophase. The homochirality of its nets makes the CD signal of the thienofluorenone compounds close to that in the stable I23 phase with 3 isochiral nets.

An Outbreak of Serogroup Y Meningococcal Meningitis in a Private Secondary Vocational School - Guangzhou City, Guangdong Province, China, 2023.

What is already known about this topic?: The inclusion of meningococcal vaccines in the National Immunization Program (NIP) over several years has significantly reduced the incidence of meningococcal meningitis in China to historic lows. Worldwide, there has been a diversification of meningococcal serogroups, leading to a shift in dominant serogroups in China from serogroup A to serogroups C and B, accompanied by a rise in reports of serogroups Y and W. What is added by this report?: An outbreak of serogroup Y Neisseria meningitidis (Nm) in a secondary vocational school involved a single confirmed severe case and 24 individuals with laboratory-confirmed Nm carriage. Epidemiological investigation revealed that the outbreak was localized to the classroom of the confirmed case. Prolonged close contact within a confined space was identified as a significant risk factor for Nm transmission. The genotype sequence identified was type 1655 (ST-1655), which is categorized under clonal complex 23 (CC-23) and bears resemblance to 8 previously confirmed cases of serogroup Y meningococcal meningitis within Guangdong Province. This suggests that serogroup Y infections continue to sporadically emerge and have become prevalent strains. What are the implications for public health practice?: This outbreak underscores the critical need to enhance surveillance of meningococcal serogroups and population carrier, and advocate for vaccination with MenY-containing vaccines.

COMP promotes pancreatic fibrosis by activating pancreatic stellate cells through CD36-ERK/AKT signaling pathways.

BACKGROUND: Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. METHODS: ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. RESULTS: ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-ß1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. CONCLUSION: In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.

Pirfenidone alleviates chronic pancreatitis via suppressing the activation of pancreatic stellate cells and the M1 polarization of macrophages.

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.

GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

Experimental Investigation of Current Intensity and Feed Speed in Electrically Assisted Necking and Thickening of 5A02 Aluminum Alloy Tubes.

In order to further explore the forming limits of thin-wall tube necking and thickening, and obtain sufficient thickness of the tube in the thickening area, local electric pulse-assisted forming experiments were carried out to study the effects of current intensity and feed speed on the necking and thickening forming of thin-wall tube. The experimental results show that with the increase in current intensity, the temperature in the forming area of the tube increases, and the forming load for necking and thickening decreases. However, with the increase in feed speed, the overall forming load for necking and thickening increases in general, and the smaller feed speed is more conducive to forming. Taking into account the forming efficiency and electrode loss, the corresponding forming process window is obtained for the manufacturing of good parts. That is, during the necking stage, the current intensity shall not be less than 300 A, and the feed speed shall not exceed 10 mm/min. During the thickening stage, the current intensity should not be less than 1400 A, and the feed speed should not exceed 1 mm/min. The target part is finally formed, with an average wall thickness of 5.984 mm in the thickening zone and a thickening rate of 303.2%.

A Facile Surface Modification Scheme for Medical-Grade Titanium and Polypropylene Using a Novel Mussel-Inspired Biomimetic Polymer with Cationic Quaternary Ammonium Functionalities for Antibacterial Application.

Medical device-associated infection remains a critical problem in the healthcare setting. Different clinical- or device-related methods have been attempted to reduce the infection rate. Among these approaches, creating a surface with bactericidal cationic functionality has been proposed. To do so, a sophisticated multi-step chemical procedure would be needed. Instead, a simple immersion approach was utilized in this investigation to render the titanium and polypropylene surface with the quaternary ammonium functionality by using a mussel-inspired novel lab-synthesized biomimetic catechol-terminated polymer, PQA-C8. The chemical oxidants, CuSO4/H2O2, as well as dopamine, were added into the novel PQA-C8 polymer immersion solution for one-step surface modification. Additionally, a two-step immersion scheme, in which the polypropylene substrate was first immersed in the dopamine solution and then in the PQA-C8 solution, was also attempted. Surface analysis results indicated the surface characteristics of the modified substrates were affected by the immersion solution formulation as well as the procedure utilized. The antibacterial assay has shown the titanium substrates modified by the one-step dopamine + PQA-C8 mixtures with the oxidants added and the polypropylene modified by the two-step scheme exhibited bacterial reduction percentages greater than 90% against both Gram-positive S. aureus and Gram-negative E. coli and these antibacterial substrates were non-cytotoxic.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Mechanism of color change in Antarctic krill oil during storage.

Antarctic krill oil (AKO) is reddish-orange in color but undergoes changes during storage. To investigate the color deterioration and potential mechanisms involved, the changes in color, endogenous components (astaxanthin, fatty acids, and phospholipids), and reaction products (aldehydes, α-dicarbonyl compounds, and pyrroles) of AKO upon storage were determined. Although the visual color of AKO tended to darken upon storage, the colorimetric analysis and ultraviolet-visible spectrum analysis both indicated a fading in red and yellow due to the oxidative degradation of astaxanthin. During storage of AKO, lipid oxidation led to the formation of carbonyl compounds such as aldehydes and α-dicarbonyls. In addition, phosphatidylethanolamines (PEs) exhibited a faster loss rate than phosphatidylcholines. Moreover, hydrophobic pyrroles, the Maillard-like reaction products associated with primary amine groups in PEs accumulated. Therefore, it is suggested that the Maillard-like reaction between PEs and carbonyl compounds formed by lipid oxidation contributed to color darkening of AKO during storage.

Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis.

Metastasis is the main culprit of cancer-related death and account for the poor prognosis of hepatocellular carcinoma. Although platelets have been shown to accelerate tumor cell metastasis, the exact mechanism remained to be fully understood. Here, we found that high blood platelet counts and increased tumor tissue ADAM10 expression indicated the poor prognosis of HCC patients. Meanwhile, blood platelet count has positive correlation with tumor tissue ADAM10 expression. In vitro, we revealed that platelet increased ADAM10 expression in tumor cell through TLR4/NF-κB signaling pathway. ADAM10 catalyzed the shedding of CX3CL1 which bound to CX3CR1 receptor, followed by inducing epithelial to mesenchymal transition and activating RhoA signaling in cancer cells. Moreover, knockdown HCC cell TLR4 (Tlr4) or inhibition of ADAM10 prevented platelet-increased tumor cell migration, invasion and endothelial permeability. In vivo, we further verified in mice lung metastatic model that platelet accelerated tumor metastasis via cancer cell TLR4/ADAM10/CX3CL1 axis. Overall, our study provides new insights into the underlying mechanism of platelet-induced HCC metastasis. Therefore, targeting the TLR4/ADAM10/CX3CL1 axis in cancer cells hold promise for the inhibition of platelet-promoted lung metastasis of HCC.

Caproicibacterium argilliputei sp. nov., a novel caproic acid producing anaerobic bacterium isolated from pit clay.

An anaerobic, Gram-positive, rod-shaped, motile and spore-forming bacterium, designated strain ZCY20-5T, was isolated from pit clay of Chinese strong-aroma type Baijiu (Chinese liquor). Phylogenetic analyses based on 16S rRNA gene and genome sequences showed that strain ZCY20-5T belonged to the genus Caproicibacterium, family Oscillospiracheae, but it showed low similarity to the type species Caproicibacterium amylolyticum LBM18003T (98.00 %) and Caproicibacterium lactatifermentans LBM19010T (95.67 %). In anaerobic yeast extract medium, growth was observed at 20-45 °C (optimum, 35-40 °C), at pH 4.0-9.0 (optimum, pH 6.5-7.0) and with 0.0-2.0 % NaCl (w/v). The predominant fatty acids were C16 : 0, C14 : 0, C13 3-OH and C16 3-OH, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, three phospholipids of unknown structure containing glucosamine and two unidentified phospholipids. Strain ZCY20-5T exhibited an 81.32 % pairwise average nucleotide identity value, a 78.98 % average amino acid identity value and a 22.30 % digital DNA-DNA hybridization value compared to its closest relative C. amylolyticum LBM18003T. Based on morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, strain ZCY20-5T represents a novel species of Caproicibacterium, and the type strain is ZCY20-5T (=MCCC 1A19399T=KCTC 25590T).