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Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.

The BRCA2 tumor suppressor protects genome integrity by promoting homologous recombination-based repair of DNA breaks, stability of stalled DNA replication forks and DNA damage-induced cell cycle checkpoints. BRCA2 deficient cells display the radio-resistant DNA synthesis (RDS) phenotype, however the mechanism has remained elusive. Here we show that cells without BRCA2 are unable to sufficiently restrain DNA replication fork progression after DNA damage, and the underrestrained fork progression is due primarily to Primase-Polymerase (PRIMPOL)-mediated repriming of DNA synthesis downstream of lesions, leaving behind single-stranded DNA gaps. Moreover, we find that BRCA2 associates with the essential DNA replication factor MCM10 and this association suppresses PRIMPOL-mediated repriming and ssDNA gap formation, while having no impact on the stability of stalled replication forks. Our findings establish an important function for BRCA2, provide insights into replication fork control during the DNA damage response, and may have implications in tumor suppression and therapy response. Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

Previous studies have suggested that von Willebrand Factor (VWF) may be implicated in the pathogenesis of Alzheimer's disease (AD). However, the association between plasma VWF levels and cognitive decline and neurodegeneration in older adults without dementia remains unclear. We investigated the cross-sectional and longitudinal associations between plasma von Willebrand Factor (VWF) levels and cognitive decline, as measured by the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), as well as the volumes of six brain regions: the hippocampus, entorhinal cortex, middle temporal gyrus, fusiform gyrus, ventricles, and whole brain. Linear mixed-effects models were used to assess the association between plasma VWF levels and longitudinal changes in cognitive function and neuroimaging markers over time. The study cohort consisted of 340 older adults without dementia at baseline. We observed that lower plasma VWF levels were associated with a faster rate of cognitive decline (MMSE: coefficient = 0.204, 95% CIs = [0.030, 0.378], -value = 0.021; CDR-SB: coefficient = -0.268, 95% CIs = [-0.374, -0.163], -value <0.001). Additionally, lower plasma VWF levels were linked to a more rapid reduction in the volumes of the hippocampus (coefficient = 0.016, 95% CIs = [0.004, 0.027], -value = 0.009), entorhinal cortex (coefficient = 0.031, 95% CIs = [0.014, 0.048], -value <0.001), and fusiform gyrus (coefficient = 0.047, 95% CIs = [0.008, 0.085], -value = 0.017), as well as a faster enlargement of the ventricles (coefficient = -0.380, 95% CIs = [-0.558, -0.203], -value <0.001). However, no significant relationships were observed between plasma VWF levels and changes in the volumes of the middle temporal gyrus or the whole brain (all -values > 0.05). Our findings may contribute to the growing body of knowledge on the vascular contributions to cognitive function and may help identify potential biomarkers for the early detection and intervention of AD.

Polarization response of artificially structured nano-antennas can be exploited to design innovative optical components, also dubbed “vectorial metasurfaces”, for the modulation of phase, amplitude, and polarization with subwavelength spatial resolution. Recent efforts in conceiving Jones matrix formalism led to the advancement of vectorial metasurfaces to independently manipulate any arbitrary phase function of orthogonal polarization states. Here, we are taking advantages of this formalism to design and experimentally validate the performance of CMOS compatible Jones matrix metasurfaces monolithically integrated with standard VCSELs for on-chip spin-decoupling and phase shaping. Our approach enables accessing the optical spin states of VCSELs in an ultra-compact way with previously unattainable phase controllability. By exploiting spin states as a new degree of freedom for laser wavefront engineering, our platform is capable of operating and reading-out the spin-momentum of lasers associated with injected spin carriers, which would potentially play a pivotal role for the development of emerging spin-optoelectronic devices. Here the authors harness the on-chip integration of Jones matrix metasurfaces to demonstrate an ultra-compact approach to access and manipulate the optical spin states of vertical cavity surface-emitting lasers (VCSELs) with previously unattainable phase controllability.

Chemokines and their receptors have been reported to drive immune cells into tumours or to be directly involved in the promotion or inhibition of the development of tumours. However, their expression in regional lymph node (LN) tissues in melanoma patients remains unknown. The present study investigated the relationship between the expression of mRNA of chemokines and their receptors and clinicopathology of the regional LN tissues of skin cutaneous melanoma (SKCM) patients available in The Cancer Genome Atlas. The relationship between chemokines and their receptors and the composition of immune cells within the tumour was analysed. In SKCM regional LN tissues, the high expression of 32 types of chemokines and receptors, namely CCL2, 4‐5, 7‐8, 13, 22‐25, CCR1‐9, CXCL9‐13, 16, CXCR3, 5, 6, XCL1‐2 and XCR1 in LN was associated with favourable patient prognosis. Conversely, high expression of CXCL17 was an indicator of poor prognosis. The expression of mRNA for CXCL9‐11, 13, CXCR3, 6, CCL2, 4, 5, 7, 8, 25, CCR1, 2, 5, and XCL1, 2 in regional LN tissues was positively correlated with the fraction of CD8‐positive T cells and M1 macrophages, and was negatively correlated with M0 macrophages. CCR4, 6‐9, CCL13, 22, 23 and XCR1 were positively correlated with the fraction of memory B cells and naive T cells, and negatively correlated with M0 macrophages and resting mast cells, suggesting that chemokines and their receptors may affect the prognosis of patients by guiding immune cells into the tumour microenvironment to eliminate tumour cells.

We aimed to examine the association of CSF tumor necrosis factor-alpha (TNFα) with conversion from mild cognitive impairment (MCI) to dementia. At baseline, there were a total of 129 participants with MCI in this study. The association of CSF TNFα levels with the incidence of dementia were evaluated using Cox proportional hazards regression analysis adjusted for potential confounders. Individuals were categorized into groups based on the CSF TNFα tertiles. Compared to the low group (the reference group), the intermediate group progressed more rapidly to dementia [HR (95% CI) = 2.2 (1.15–4.1); p = 0.016] after adjusting for other covariates. However, the high group did not progress faster than the low group [HR (95% CI) = 1.5 (0.79–2.8); p = 0.214]. Our study suggested a potential non-relationship between CSF TNFα levels and the risk of development of dementia among MCI older people.

The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the ‘Warburg Effect’, is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786‐O and SN12C cells. Based on the RNA‐seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT–mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786‐O and SN12C cells. Notably, knockdown of PB1 activates AKT–mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT–mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.

The precise spatial organization of cells into functional tissues represents a fundamental challenge in biology and regenerative medicine. Conventional methods for directing cell assembly often lack the specificity, reproducibility, and dynamic control necessary to mimic native tissue architectures. This review explores the emerging use of DNA as a programmable and biocompatible strategy to engineer cell–cell interactions and construct hierarchically ordered tissue models. We first introduce the properties of various DNA toolbox and their strategies for cell modification and assembly. Importantly, we highlight the latest research advances in DNA-encoded cell spheroids, layered tissues, and organoids. Finally, we summarize current challenges and future directions in DNA-programmed assembly.

Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

Trans -resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo . Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.