Assembly and comparative analysis of the complete mitochondrial genome of white towel gourd (Luffa cylindrica).

Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the functions of the mitochondrial (mt) genome of Luffa cylindrica. The mt genome of L. cylindrica contained two chromosomes with lengths of 380,879 bp and 67,982 bp, respectively. Seventy-seven genes including 39 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 pseudogene, were identified. About 90.63% of the codons ended with A or U bases, and 98.63% of monomers contained A/T, which contributed to the high A/T content (55.91%) of the complete mt genome. Six genes (ATP8, CCMFC, NAD4, RPL10, RPL5 and RPS4) showed positive selection. Phylogenetic analysis indicates that L. cylindrica is closely related to L. acutangula. The present results provide the mt genome of L. cylindrica, which may facilitate possible genetic variation, evolutionary, and molecular breeding studies of L. cylindrica.

Targeting circadian transcriptional programs in triple negative breast cancer through a cis-regulatory mechanism.

Circadian clock genes are emerging targets in many types of cancer, but their mechanistic contributions to tumor progression are still largely unknown. This makes it challenging to stratify patient populations and develop corresponding treatments. In this work, we show that in breast cancer, the disrupted expression of circadian genes has the potential to serve as biomarkers. We also show that the master circadian transcription factors (TFs) BMAL1 and CLOCK are required for the proliferation of metastatic mesenchymal stem-like (mMSL) triple-negative breast cancer (TNBC) cells. Using currently available small molecule modulators, we found that a stabilizer of cryptochrome 2 (CRY2), the direct repressor of BMAL1 and CLOCK transcriptional activity, synergizes with inhibitors of proteasome, which is required for BMAL1 and CLOCK function, to repress a transcriptional program comprising circadian cycling genes in mMSL TNBC cells. Omics analyses on drug-treated cells implied that this repression of transcription is mediated by the transcription factor binding sites (TFBSs) features in the cis-regulatory elements (CRE) of clock-controlled genes. Through a massive parallel reporter assay, we defined a set of CRE features that are potentially repressed by the specific drug combination. The identification of cis -element enrichment may serve as a new way of defining and targeting tumor types through the modulation of cis -regulatory programs, and ultimately provide a new paradigm of therapy design for cancer types with unclear drivers like TNBC.

Modeling the molecular composition of secondary organic aerosol under highly polluted conditions: A case study in the Yangtze River Delta Region in China.

A near-explicit mechanism, the master chemical mechanism (MCMv3.3.1), coupled with the Community Multiscale Air Quality (CMAQ) model (CMAQ-MCM-SOA), was applied to investigate the characteristics of secondary organic aerosol (SOA) during a pollution event in the Yangtze River Delta (YRD) region in summer 2018. Model performances in predicting explicit volatile organic compounds (VOCs), organic aerosol (OA), secondary organic carbon (SOC), and other related pollutants in Taizhou, as well as ozone (O3) and fine particulate matter (PM2.5) in multiple cities in this region, were evaluated against observations and model predictions by the CMAQ model coupled with a lumped photochemical mechanism (SAPRC07tic, S07). MCM and S07 exhibited similar performances in predicting gaseous species, while MCM better captured the observed PM2.5 and inorganic aerosols. Both models underpredicted OA concentrations. When excluding data during biomass burning events, SOC concentrations were underpredicted by the CMAQ-MCM-SOA model (-28.4 %) and overpredicted by the CMAQ-S07 model (134.4 %), with better agreement with observations in the trend captured by the CMAQ-MCM-SOA model. Dicarbonyl SOA accounted for a significant fraction of total SOA in the YRD, while organic nitrates originating from aromatics were the most abundant species contributing to the SOA formation from gas-particle partitioning. The oxygen-to­carbon ratio (O/C) for SOA and OA were 0.68-0.75 and 0.20-0.65, respectively, indicating a higher oxidation state in the areas influenced by biogenic emissions. Finally, the phase state of SOA was examined by calculating the glass transition temperature (Tg) based on its molecular composition. It was found that semi-solid state characterized SOA in the YRD, which could potentially impact their chemical transformation and lifetimes along with those of their precursors.

Isolation and purification of polysaccharides from Bupleurum marginatum Wall.ex DC and their anti-liver fibrosis activities.

Bupleurum marginatum Wall.ex DC [Apiaceae] (BM)is widely grown in southwestern China, and the whole plant is used as Traditional Chinese Medicine (TCM). Polysaccharides are main natural products in lots of TCM and have been studied for their effects of reducing oxidative stress, anti-inflammation and immune regulation. Herein, we investigated the extraction techniques of Bupleurum marginatum Wall.ex DC polysaccharides (BMP), the identification of their key components, and their ability to inhibit liver fibrosis in both cellular and animal models. Component identification indicated that monosaccharides in BMP mainly consisted of glucose, galactose, mannose, rhamnose, arabinose, and xylose. In vivo analysis revealed that BMP provided significant protective effects on N-Nitroso dimethylamine (NDMA)-induced liver fibrosis rats through reducing hepatomegaly, reducing tissue inflammation, and reducing collagen deposition. BMP also improved the hepatobiliary system and liver metabolism in accord to reduce the serum levels of ALT, AST, ALP, r-GT, and TBIL. In addition, BMP could reduce the level of inflammation and fibrosis through inhibition of IL-1ß and TGF-ß1. Cellular studies showed that the BMP could provide therapeutic effects on lipopolysaccharide (LPS)-induced cellular fibrosis model, and could reduce the level of inflammation and fibrosis by decreasing the level of TGF-ß1, IL-1ß, and TNF-α. Our study demonstrated that BMP may provide a new therapy strategy of liver injury and liver fibrosis.

Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging.

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.

Advanced drive laser system for a high-brightness continuous-wave photocathode electron gun.

In order to enhance the performance of a continuous-wave photocathode electron gun at Peking University, and to achieve electron beams with higher current and brightness, a multifunctional drive laser system named PULSE (Peking University drive Laser System for high-brightness Electron source) has been developed. This innovative system is capable of delivering an average output power of 120 W infrared laser pulse at 81.25 MHz, as well as approximately 13.8 W of green power with reliable stability. The utilization of two stages of photonic crystal fibers plays a crucial role in achieving this output. Additionally, the incorporation of two acousto-optic modulators enables the selection of macro-pulses with varying repetition frequencies and duty cycles, which is essential for effective electron beam diagnosis. Furthermore, the system employs a series of birefringent crystals for temporal pulse shaping, allowing for stacking Gaussian pulses into multiple types of distribution. Overall, the optical schematic and operating performance of PULSE are detailed in this paper.

Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract.

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

The detection methods currently available for protein aggregation in neurological diseases.

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

Tuning the crystallinity of the MnOx catalysts to promote toluene catalytic oxidation.

In this paper, the MnOx catalysts with excellent toluene oxidation performance were prepared by a simple precipitation method. The physicochemical properties of the prepared MnOx catalysts were investigated by XRD, BET, H2-TPR, O2-TPD and XPS. The obtained results revealed that the crystallinity of the prepared MnOx catalysts could be effectively regulated by changing the (NH4)2CO3/Mn(NO3)2 molar ratio, and thus affecting the oxygen vacancy concentration of the prepared MnOx catalysts. The prepared MnOx-4 catalyst with the (NH4)2CO3/Mn(NO3)2 molar ratio of 4.0 had the poor crystallinity and small grain size, which effectively promoted the oxygen defects in the MnOx catalyst to be formed. At the same time, the MnOx-4 catalyst had a large specific surface area, the highest low temperature reducibility and the largest number of oxygen vacancies and surface adsorbed oxygen species, which allowed more surface oxygen species to participate in the redox reaction, and promoted the toluene deep oxidation. Therefore, when the (NH4)2CO3/Mn(NO3)2 molar ratio was 4.0, the prepared MnOx-4 catalyst exhibited an excellent toluene catalytic oxidation performance and robust catalytic stability. What's more, the toluene oxidation conversion on the MnOx-4 catalyst reached 99% at 230°C, and the MnOx-4 catalyst showed excellent resistance to water vapour.

Bilateral Pattern Electroretinogram Abnormalities in Patients with Herpes Zoster Keratitis and Conjunctivitis.

INTRODUCTION: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. METHODS: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. RESULTS: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. CONCLUSIONS: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

Persistent Cytopenia After CD19 CAR T Therapy in Relapsed/Refractory DLBCL Patients Could Be a Predictor of Efficacy and Side Effects.

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.

Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway.

Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain largely elusive. Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo. Mechanistically, HDACi decrease HDAC1 expression and enhance H3K27ac activity. Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/ß-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment.

Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing.

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

A genome-wide spectrum of tandem repeat expansions in 338,963 humans.

The Genome Aggregation Database (gnomAD), widely recognized as the gold-standard reference map of human genetic variation, has largely overlooked tandem repeat (TR) expansions, despite the fact that TRs constitute ∼6% of our genome and are linked to over 50 human diseases. Here, we introduce the TR-gnomAD (https://wlcb.oit.uci.edu/TRgnomAD), a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries (39.5% non-European samples). TR-gnomAD offers critical insights into ancestry-specific disease prevalence using disparities in TR unit number frequencies among ancestries. Moreover, TR-gnomAD is able to differentiate between common, presumably benign TR expansions, which are prevalent in TR-gnomAD, from those potentially pathogenic TR expansions, which are found more frequently in disease groups than within TR-gnomAD. Together, TR-gnomAD is an invaluable resource for researchers and physicians to interpret TR expansions in individuals with genetic diseases.

Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis.

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.

Prognostic Analysis of Lactic Acid Metabolism Genes in Oral Squamous Cell Carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Lactic acid accumulation in the tumour microenvironment (TME) has gained attention for its dual role as an energy source for cancer cells and an activator of signalling pathways crucial to tumour progression. This study aims to reveal the impact of lactate-related genes (LRGs) on the prognosis, TME, and immune characteristics of OSCC, with the ultimate goal of developing a novel prognostic model. METHODS: Unsupervised clustering analysis of LRGs in OSCC patients from The Cancer Genome Atlas database was conducted to evaluate and compare TME, immune features, and clinical characteristics across various lactate subtypes. A refined prognostic model was developed through the application of Cox and Least absolute shrinkage and selection operator (LASSO) regression techniques. External validation sets were then utilised to improve model accuracy, along with a detailed correlation analysis of drug sensitivity. RESULTS: The Cancer Genome Atlas-OSCC patients were categorised into 4 distinct lactate subtypes based on LRGs. Notably, patients in subtype 1 and subtype 2 exhibited the least and most favourable prognoses, respectively. Subtype 1 patients showed elevated expression levels of immune checkpoint genes. Further analysis identified 1086 genes with significant expression differences between cancer and noncancer tissues, as well as between subtype 1 and subtype 2 patients. Selected genes for the prognostic model included ZNF662, CGNL1, VWCE, and ZFP42. The high-risk group defined by this model had a significantly poorer prognosis (P < .0001) and functioned as an independent prognostic factor (P < .001), accurately predicting 1-, 3-, and 5-year survival rates. Additionally, individuals in the high-risk category exhibited heightened sensitivity to chemotherapy drugs such as AZ6102 and Venetoclax. CONCLUSIONS: The predictive model based on the genes ZNF662, CGNL1, VWCE, and ZFP42 can serve as a reliable biomarker, providing accurate prognostic predictions for OSCC patients and potential opportunities for pharmaceutical interventions.

Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of Aspergillus fumigatus.

The hydrophobic layer of Aspergillus conidia, composed of RodA, plays a crucial role in conidia transfer and immune evasion. It self-assembles into hydrophobic rodlets through intramolecular disulfide bonds. However, the secretory process of RodA and its regulatory elements remain unknown. Since protein disulfide isomerase (PDI) is essential for the secretion of many disulfide-bonded proteins, we investigated whether PDI is also involved in RodA secretion and assembly. By gene knockout and phenotypic analysis, we found that Pdi1, one of the four PDI-related proteins of Aspergillus fumigatus, determines the hydrophobicity and integrity of the rodlet layer of the conidia. Preservation of the thioredoxin-active domain of Pdi1 was sufficient to maintain conidial hydrophobicity, suggesting that Pdi1 mediates RodA assembly through its disulfide isomerase activity. In the absence of Pdi1, the disulfide mismatch of RodA in conidia may prevent its delivery from the inner to the outer layer of the cell wall for rodlet assembly. This was demonstrated using a strain expressing a key cysteine-mutated RodA. The dormant conidia of the Pdi1-deficient strain (Δpdi) elicited an immune response, suggesting that the defective conidia surface in the absence of Pdi1 exposes internal immunogenic sources. In conclusion, Pdi1 ensures the correct folding of RodA in the inner layer of conidia, facilitating its secretion into the outer layer of the cell wall and allowing self-assembly of the hydrophobic layer. This study has identified a regulatory element for conidia rodlet assembly.IMPORTANCEAspergillus fumigatus is the major cause of invasive aspergillosis, which is mainly transmitted by the inhalation of conidia. The spread of conidia is largely dependent on their hydrophobicity, which is primarily attributed to the self-assembly of the hydrophobic protein RodA on the cell wall. However, the mechanisms underlying RodA secretion and transport to the outermost layer of the cell wall are still unclear. Our study identified a critical role for Pdi1, a fungal protein disulfide isomerase found in regulating RodA secretion and assembly. Inhibition of Pdi1 prevents the formation of correct S-S bonds in the inner RodA, creating a barrier to RodA delivery and resulting in a defective hydrophobic layer. Our findings provided insight into the formation of the conidial hydrophobic layer and suggested potential drug targets to inhibit A. fumigatus infections by limiting conidial dispersal and altering their immune inertia.

Impact of "blue-green diet" on human health and wellbeing: A systematic review of potential determinants in shaping the effectiveness of blue-green infrastructure (BGI) in urban settings.

Discourses concerning the potential health benefits of blue-green infrastructure (BGI) have gained momentum, highlighting its positive influence on human health and wellbeing. While studies have explored the concept of "Nature Pyramid" and the role of exposure to natural environments in promoting health, the role of water elements remains underexplored. Rooted in this concept, this study proposed a notion of "blue-green diet" as a framework to understand the intricate mechanisms and determinants of optimal blue-green exposure. Understanding the relationship between these determinants and their health-related impacts can facilitate the enhancement of BGI design, leading to greater effectiveness in promoting health and wellbeing and supporting sustainable urban development strategies. To enhance the comprehension of the "blue-green diet", this study conducted a systematic literature review to grasp the underlying mechanisms behind its beneficial effects, focusing on two key determinants of "blue-green diet", which are also derived from the concept of the "Nature Pyramid": (1) the type of BGI and (2) the mode of interaction with and within BGIs. Under the search of BGI's overall health impacts, this study selected 54 journal publications concerning BGI's type and interaction mode from Web of Science and Scopus since 2010. The review revealed significant disparities in the health benefits provided by different types of BGI (in terms of artificial extent and scale) and between active and passive interaction modes. It examines how to balance natural and artificial elements for enhancing the benefits of BGI and discusses the attributes of BGI that encourage diverse and meaningful interaction patterns. These efforts collectively aim to optimize BGI design and planning, increase its capacity to promote health, and extend its benefits to a wider range of individuals. Future research should encompass a broader spectrum of determinants, such as diverse BGI settings, visit frequency and duration, and user's social-cultural backgrounds.

The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA.

Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.