Screening of Optimal Konjac Glucomannan-Protein Composite Gel Formulations to Mimic the Texture and Appearance of Tripe.

This study aimed to develop a product that closely replicates the texture and appearance of tripe. The effect of three different proteins (soy protein isolate (SPI), pea protein isolate (PPI), and whey protein isolate (WPI)) at different protein levels and processing conditions (heating (90 °C, 1 h) followed by cooling (4 °C, 12 h) and heating (90 °C, 1h) followed by freezing (-18 °C, 12 h)) of konjac glucomannan (KGM) was analyzed. The optimal formulations for simulating tripe were screened by examining their similarity to real tripe in terms of texture, color, and sensory experience. The screened formulations were also subjected to a preliminary mechanistic investigation. The results show that all three proteins improved the gel's textural properties to varying degrees. At the same concentration, the hardness and chewiness of the KGM/WPI composite gel were significantly higher than those of the other two KGM/protein composite gels, among which the composite gel obtained by adding 8% WPI and 5% KGM heating-frozen (FWK4) had the greatest hardness and chewiness of 4338.07 g and 2313.76, respectively, and the springiness differences in all of the composite gels were small. In addition, the addition of protein increased the whiteness of the hybrid gels, with WPI having the most significant effect on the whiteness of the composite gels (whiteness increased from 30.25 to 62.80 as the concentration of WPI increased from 0 to 10%). Freezing increased composite gel hardness and chewiness, but reduced gel springiness and whiteness. Cluster analysis showed that the composite gel obtained by heating-cooling 8% WPI and 5% KGM (WK4) was very similar to the real tripe in terms of chewiness and whiteness, and WK4 had the highest sensory scores for color, tissue morphology, tactile sensation, taste, and odor. The acceptability score in terms of tissue morphology reached 4.3. Meanwhile, the characterization results of WK4 indicate the presence of large junction areas in the gel network. Fourier transform infrared spectroscopy (FTIR) analysis, X-ray diffraction, and intermolecular force contributions indicated that the incorporation of WPI promoted integral interactions, and that hydrophobic interactions and disulfide bonding played a key role in the WK4 composite gel system. Moreover, scanning electron microscopy (SEM) also showed that the combination of WPI and konjac glucan resulted in a more compact gel structure. This study is informative for the development of the field of bionic tripe processing.

Methylglyoxal induces endothelial cell apoptosis and coronary microvascular dysfunction through regulating AR-cPLA2 signaling.

OBJECTIVE: Since diabetic patients with coronary microvascular dysfunction (CMD) exhibit high cardiac mortality and women have higher prevalence of non-obstructive coronary artery disease than men, we tried to expand the limited understanding about the etiology and the sex difference of diabetic CMD. APPROACH AND RESULTS: Accumulated methylglyoxal (MGO) due to diabetes promotes vascular damage and it was used for mimicking diabetic status. Flow cytometry analysis and isometric tension measurement were performed to evaluate coronary artery endothelial injury. MGO induced apoptosis of coronary endothelial cells, accompanied by downregulation of androgen receptor (AR). Lentivirus-mediated stable expression of AR in coronary endothelial cells increased anti-apoptotic Bcl-2 expression and attenuated MGO-induced cell apoptosis. cPLA2 activation was the downstream of AR downregulation by MGO treatment. Moreover, MGO also activated cPLA2 rapidly to impair endothelium-dependent vasodilation of coronary arteries from mice. Reactive oxygen species (ROS) overproduction was demonstrated to account for MGO-mediated cPLA2 activation and endothelial dysfunction. Importantly, AR blockade increased endothelial ROS production whereas AR activation protected coronary artery endothelial vasodilatory function from the MGO-induced injury. Although galectin-3 upregulation was confirmed by siRNA knockdown in endothelial cells not to participate in MGO-induced endothelial apoptosis, pharmacological inhibitor of galectin-3 further enhanced MGO-triggered ROS generation and coronary artery endothelial impairment. CONCLUSIONS: Our data proposed the AR downregulation-ROS overproduction-cPLA2 activation pathway as one of the mechanisms underlying diabetic CMD and postulated a possible reason for the sex difference of CMD-related angina. Meanwhile, MGO-induced galectin-3 activation played a compensatory role against coronary endothelial dysfunction.

Hydrogen Sulfide Delivery System Based on Salting-Out Effect for Enhancing Synergistic Photothermal and Photodynamic Cancer Therapies.

The simultaneous application of photothermal therapy (PTT) and photodynamic therapy (PDT) offers substantial advantages in cancer treatment. However, their synergistic anticancer efficacy is often limited by tumor hypoxia, and thermotolerance induced by high expression of heat shock proteins (HSP). Fortunately, hydrogen sulfide (H2S), known for its direct cytotoxic effect on tumor cells, has been recognized for its ability to enhance PTT and PDT. The effectiveness of H2S in these therapies is challenged by its low loading efficiency, poor stability, and short diffusion distance. To address these issues, a nanoscale emulsion drop template created through the salting-out effect is employed to construct a robust H2S delivery system. Polydopamine (PDA), chosen for its interfacial polymerization tendency and excellent photothermal conversion rate, is utilized as a carrier for the H2S donor (ADT) and Zinc phthalocyanine (ZnPc) to fabricate a novel nanomedicine termed APZ NPs. The temperature-responsive APZ NPs are designed to release H2S during the PTT process. Elevated H2S levels promoted vasodilation, thereby enhancing the enhanced permeability and retention effect (EPR) of APZ NPs within solid tumors. This strategy effectively alleviated tumor hypoxia by disrupting the mitochondrial respiratory chain and mitigated tumor cell heat tolerance by inhibiting HSP expression.

Experimental study of the biological properties of nmHA-SiO2 fiber materials prepared by electrospinning technology.

To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO2 fiber material and its efficacy in guided bone regeneration. ① The cytotoxicity of the nmHA-SiO2 fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. ② Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO2, implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO2 membrane or Hai'ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. ① The nmHA-SiO2 fiber material has suitable biocompatibility. ② The nmHA-SiO2 fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits.

Homologous polydopamine ameliorates haemolysis of melittin for enhancing its anticancer efficacy.

Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL-polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.

Enhanced AHL-mediated quorum sensing accelerates the start-up of biofilm reactors by elevating the fitness of fast-growing bacteria in sludge and biofilm communities.

Quorum sensing (QS)-based manipulations emerge as a promising solution for biofilm reactors to overcome challenges from inefficient biofilm formation and lengthy start-ups. However, the ecological mechanisms underlying how QS regulates microbial behaviors and community assembly remain elusive. Herein, by introducing different levels of N-acyl-homoserine lactones, we manipulated the strength of QS during the start-up of moving bed biofilm reactors and compared the dynamics of bacterial communities. We found that enhanced QS elevated the fitness of fast-growing bacteria with high ribosomal RNA operon (rrn) copy numbers in their genomes in both the sludge and biofilm communities. This led to notably increased extracellular substance production, as evidenced by strong positive correlations between community-level rrn copy numbers and extracellular proteins and polysaccharides (Pearson's r = 0.529-0.830, P < 0.001). Network analyses demonstrated that enhanced QS significantly promoted the ecological interactions among taxa, particularly cooperative interactions. Bacterial taxa with higher network degrees were more strongly correlated with extracellular substances, suggesting their crucial roles as public goods in regulating bacterial interactions and shaping network structures. However, the assembly of more cooperative communities in QS-enhanced reactors came at the cost of decreased network stability and modularity. Null model and dissimilarity-overlap curve analysis revealed that enhanced QS strengthened stochastic processes in community assembly and rendered the universal population dynamics more convergent. Additionally, these shaping effects were consistent for both the sludge and biofilm communities, underpinning the planktonic-to-biofilm transition. This work highlights that QS manipulations efficiently drive community assembly and confer specialized functional traits to communities by recruiting taxa with specific life strategies and regulating interspecific interactions. These ecological insights deepen our understanding of the rules governing microbial societies and provide guidance for managing engineering ecosystems.

GLYR1 transcriptionally regulates PER3 expression to promote the proliferation and migration of multiple myeloma.

Period circadian regulator 3 (PER3) functions as a tumor suppressor in various cancers. However, the role of PER3 in multiple myeloma (MM) has not been reported yet. Through this study, we aimed to investigate the potential role of PER3 in MM and the underlying mechanisms. RT-qPCR and western blotting were used to determine the mRNA and protein expression levels of PER3. Glyoxylate reductase 1 homolog (GLYR1) was predicted to be a transcription factor of PER3. The binding sites of GLYR1 on the promoter region of PER3 were analyzed using UCSC and confirmed using luciferase and chromatin immunoprecipitation assays. Viability, apoptosis, and metathesis were determined using CCK-8, colony formation, TUNEL, and transwell assays. We found that PER3 expression decreased in MM. Low PER3 levels may predict poor survival rates; PER3 overexpression suppresses the viability and migration of MM cells and promotes apoptosis. Moreover, GLYR1 transcriptionally activates PER3, and the knockdown of PER3 alleviates the effects of GLYR1 and induces its malignant behavior in MM cells. To conclude, GLYR1 upregulates PER3 and suppresses the aggressive behavior of MM cells, suggesting that GLYR1/PER3 signaling may be a potential therapeutic target for MM.

Construction of microgravity biological knowledge graph and its applications in anti-osteoporosis drug prediction.

Microgravity in the space environment can potentially have various negative effects on the human body, one of which is bone loss. Given the increasing frequency of human space activities, there is an urgent need to identify effective anti-osteoporosis drugs for the microgravity environment. Traditional microgravity experiments conducted in space suffer from limitations such as time-consuming procedures, high costs, and small sample sizes. In recent years, the in-silico drug discovery method has emerged as a promising strategy due to the advancements in bioinformatics and computer technology. In this study, we first collected a total of 184,915 literature articles related to microgravity and bone loss. We employed a combination of dependency path extraction and clustering techniques to extract data from the text. Afterwards, we conducted data cleaning and standardization to integrate data from several sources, including The Global Network of Biomedical Relationships (GNBR), Curated Drug-Drug Interactions Database (DDInter), Search Tool for Interacting Chemicals (STITCH), DrugBank, and Traditional Chinese Medicines Integrated Database (TCMID). Through this integration process, we constructed the Microgravity Biology Knowledge Graph (MBKG) consisting of 134,796 biological entities and 3,395,273 triplets. Subsequently, the TransE model was utilized to perform knowledge graph embedding. By calculating the distances between entities in the model space, the model successfully predicted potential drugs for treating osteoporosis and microgravity-induced bone loss. The results indicate that out of the top 10 ranked western medicines, 7 have been approved for the treatment of osteoporosis. Additionally, among the top 10 ranked traditional Chinese medicines, 5 have scientific literature supporting their effectiveness in treating bone loss. Among the top 20 predicted medicines for microgravity-induced bone loss, 15 have been studied in microgravity or simulated microgravity environments, while the remaining 5 are also applicable for treating osteoporosis. This research highlights the potential application of MBKG in the field of space drug discovery.

Metagenomics reveals the influence of small microplastics on microbial communities in coastal sediments.

The ecological impact of microplastics (MPs) in coastal environments has been widely studied. However, the influence of small microplastics in the actual environment is often overlooked due to measurement challenges. In this study, Hangzhou Bay (HZB), China, was selected as our study area. High-throughput metagenomic sequencing and micro-Raman spectrometry were employed to analyze the microbial communities and microplastics of coastal sediment samples, respectively. We aimed to explore the ecological impact of MPs with small sizes (≤ 100 µm) in real coastal sediment environments. Our results revealed that as microplastic size decreased, the environmental behavior of MPs underwent alterations. In the coastal sediments, no significant correlations were observed between the detected MPs and the whole microbial communities, but small MPs posed potential hazards to eukaryotic communities. Moreover, these small MPs were more prone to microbial degradation and significantly affected carbon metabolism in the habitat. This study is the first to reveal the comprehensive impact of small MPs on microbial communities in a real coastal sediment environment.

Moderate anthropogenic disturbance stimulates versatile microbial taxa contributing to denitrification and aromatic compound degradation.

Wastewater treatment plants (WWTPs) effluent often contains a significant amount of residual organic pollutants and nutrients, causing disturbance to the coastal effluent receiving areas (ERA). Microbial communities in coastal ERA sediments may benefit from the coexistence of organic pollutants and nutrients, promoting the emergence of versatile taxa that are capable of eliminating these substances simultaneously. However, the identification and exploration of versatile taxa in natural environments under anthropogenic disturbances remain largely uncharted territory. In this study, we specifically focused on the versatile taxa coupled by the degradation of aromatic compounds (ACs) and denitrification, using Hangzhou Bay in China as our study area. We explored how WWTPs effluent disturbance would affect the versatile taxa, and particularly examined the role of disturbance intensity in shaping their composition. Intriguingly, we found that versatile taxa were mainly derived from denitrifiers like Pseudomonas, suggesting the fulfilled potential of denitrifiers regarding ACs degradation. We also discovered that moderate disturbance stimulated the diversity of versatile taxa, resulting in strengthened functional redundancy. Through correlation network analysis, we further demonstrated that moderate disturbance enhanced the community-level cooperation. Thus, moderate disturbance serves as a catalyst for versatile taxa to maintain community function, making them more resilient to effluent disturbances. Additionally, we identified COD and NO3--N concentrations as significant environmental factors influencing the versatile taxa. Overall, our findings reveal the role of effluent disturbances in the promotion of versatile taxa, and highlight moderate disturbance can foster more robust versatile taxa that are better equipped to handle effluent disturbances.

PWL1, a G-type lectin receptor-like kinase, positively regulates leaf senescence and heat tolerance but negatively regulates resistance to Xanthomonas oryzae in rice.

Plant leaf senescence, caused by multiple internal and environmental factors, has an important impact on agricultural production. The lectin receptor-like kinase (LecRLK) family members participate in plant development and responses to biotic and abiotic stresses, but their roles in regulating leaf senescence remain elusive. Here, we identify and characterize a rice premature withered leaf 1 (pwl1) mutant, which exhibits premature leaf senescence throughout the plant life cycle. The pwl1 mutant displayed withered and whitish leaf tips, decreased chlorophyll content, and accelerated chloroplast degradation. Map-based cloning revealed an amino acid substitution (Gly412Arg) in LOC_Os03g62180 (PWL1) was responsible for the phenotypes of pwl1. The expression of PWL1 was detected in all tissues, but predominantly in tillering and mature leaves. PWL1 encodes a G-type LecRLK with active kinase and autophosphorylation activities. PWL1 is localized to the plasma membrane and can self-associate, mainly mediated by the plasminogen-apple-nematode (PAN) domain. Substitution of the PAN domain significantly diminished the self-interaction of PWL1. Moreover, the pwl1 mutant showed enhanced reactive oxygen species (ROS) accumulation, cell death, and severe DNA fragmentation. RNA sequencing analysis revealed that PWL1 was involved in the regulation of multiple biological processes, like carbon metabolism, ribosome, and peroxisome pathways. Meanwhile, interfering of biological processes induced by the PWL1 mutation also enhanced heat sensitivity and resistance to bacterial blight and bacterial leaf streak with excessive accumulation of ROS and impaired chloroplast development in rice. Natural variation analysis indicated more variations in indica varieties, and the vast majority of japonica varieties harbour the PWL1Hap1 allele. Together, our results suggest that PWL1, a member of LecRLKs, exerts multiple roles in regulating plant growth and development, heat-tolerance, and resistance to bacterial pathogens.

Rna M6 a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis.

N6-methyladenosine (m6 A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m6 A-sequencing and RNA-sequencing, this work reports that upon beige adipocytes activation, glycolytic genes undergo major events of m6 A modification and transcriptional activation. Genetic ablation of m6 A writer Mettl3 in fat tissues reveals that Mettl3 deficiency in mature beige adipocytes leads to suppressed glycolytic capability and thermogenesis, as well as reduced preadipocytes proliferation via glycolytic product lactate. In addition, specific modulation of Mettl3 in beige fat via AAV delivery demonstrates consistently Mettl3's role in glucose metabolism, thermogenesis, and beige fat hyperplasia. Mechanistically, Mettl3 and m6 A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes. Overall, these findings highlight the significance of m6 A on fat biology and systemic energy homeostasis.

Current development of biosensing technologies towards diagnosis of mental diseases.

The biosensor is an instrument that converts the concentration of biomarkers into electrical signals for detection. Biosensing technology is non-invasive, lightweight, automated, and biocompatible in nature. These features have significantly advanced medical diagnosis, particularly in the diagnosis of mental disorder in recent years. The traditional method of diagnosing mental disorders is time-intensive, expensive, and subject to individual interpretation. It involves a combination of the clinical experience by the psychiatrist and the physical symptoms and self-reported scales provided by the patient. Biosensors on the other hand can objectively and continually detect disease states by monitoring abnormal data in biomarkers. Hence, this paper reviews the application of biosensors in the detection of mental diseases, and the diagnostic methods are divided into five sub-themes of biosensors based on vision, EEG signal, EOG signal, and multi-signal. A prospective application in clinical diagnosis is also discussed.

A systematic analysis of genotype-phenotype associations with PLA2G6.

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP). OBJECTIVES: To determine the genotype-phenotype association in PLAN. METHODS: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2ß" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment. RESULTS: The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025). CONCLUSIONS: LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.

Wastewater treatment plant effluent discharge decreases bacterial community diversity and network complexity in urbanized coastal sediment.

The wastewater treatment plant (WWTP) effluent discharge affects the microorganisms in the receiving water bodies. Despite the ecological significance of microbial communities in pollutant degradation and element cycling, how the community diversity is affected by effluent remains obscure. Here, we compared the sediment bacterial communities exposed to different intensities of WWTP effluent discharge in Hangzhou Bay, China: i) a severely polluted area that receives effluent from an industrial WWTP, ii) a moderately polluted area that receives effluent from a municipal WWTP, and iii) less affected area that inner the bay. We found that the sediment bacterial diversity decreased dramatically with pollution levels of inorganic nutrients, heavy metals, and organic halogens. Microbial community assembly model analysis revealed increased environmental selection and decreased species migration rate in the severely polluted area, resulting in high phylogenetic clustering of the bacterial communities. The ecological networks were less complex in the two WWTP effluent receiving areas than in the inner bay area, as suggested by the smaller network size and lower modularity. Fewer negative network associations were detected in the severely (6.7%) and moderately (8.3%) polluted areas than in the less affected area (16.7%), indicating more collaborative inter-species behaviors are required under stressful environmental conditions. Overall, our results reveal the fundamental impacts of WWTP effluents on the ecological processes shaping coastal microbial communities and point to the potential adverse effects of diversity loss on ecosystem functions.

Industrial effluents boosted antibiotic resistome risk in coastal environments.

Wastewater treatment plants (WWTPs) have been regarded as an important source of antibiotic resistance genes (ARGs) in environment, but out of municipal domestic WWTPs, few evidences show how environment is affected by industrial WWTPs. Here we chose Hangzhou Bay (HZB), China as our study area, where land-based municipal and industrial WWTPs discharged their effluent into the bay for decades. We adopted high-throughput metagenomic sequencing to examine the antibiotic resistome of the WWTP effluent and coastal sediment samples. And we proposed a conceptual framework for the assessment of antibiotic resistome risk, and a new bioinformatic pipeline for the evaluation of the potential horizontal gene transfer (HGT) frequency. Our results revealed that the diversity and abundance of ARGs in the WWTP's effluent were significantly higher than those in the sediment. Furthermore, the antibiotic resistome in the effluent-receiving area (ERA) showed significant difference from that in HZB. For the first time, we identified that industrial WWTP effluent boosted antibiotic resistome risk in coastal sediment. The crucial evidences included: 1) the proportion of ARGs derived from WWTP activated sludge (WA) was higher (14.3 %) and two high-risky polymyxin resistance genes (mcr-4 and mcr-5) were enriched in the industrial effluent receiving area; 2) the HGT potential was higher between resistant microbiome of the industrial effluent and its ERA sediment; and 3) the highest resistome risk was determined in the industrial effluent, and some biocide resistance genes located on high-risky contigs were related to long-term stress of industrial chemicals. These findings highlight the important effects of industrial activities on the development of environmental antimicrobial resistance.

Sodium humate based double network hydrogel for Cu and Pb removal.

Sodium humate (SH) is one of the derivatives humic substances, which can be utilized for heavy metal removal from water due to its containing plenty of functional groups. In this study, a double network hydrogel SH/polyacrylamide (SH/PAM) was synthesized by a simple free-radical polymerization and used for Cu2+ and Pb2+ removal from water. The adsorption process can be well described by Langmuir-Freundlich model, indicating that both physical and chemical adsorption were involved. X-ray photoelectron spectroscopy (XPS) characterization demonstrated that complexation was the main mechanism for the adsorption. Two-dimensional correlation analysis of FTIR (2D-FTIR-COS) results showed that the variation order of functional groups during Cu2+ and Pb2+ adsorption in the following order: COOH ≈ -CO > -OH > C-O and -COOH ≈ C-O > -CO > -OH, respectively. According to the density functional theory (DFT) calculation results, the O atom of SH in the COO- was the main adsorption site. Meanwhile, the adsorption energy of Pb2+ was more negative than that of Cu2+ and the orbital hybridization between O atom of SH and Pb2+ was denser than that of Cu2+, which suggested that SH/PAM had a stronger combining capacity for Pb2+ than Cu2+. Therefore, the adsorption capacity for Pb2+ was larger than Cu2+. Moreover, the removal efficiencies are 30.2% for Al, 98.79% for Cu, 99.0% for Fe, 17.2% for Mn, 93.4% for Pb, and 62.4% for Zn in actual acid mine drainage using 6 g L-1 adsorbent. Collectively, this study not only provided a new adsorbent for heavy metal removal but also explicated the mechanism of heavy metal removal by SH from molecule and electron perspective, which is helpful for the application of SH in the environmental field.

Oxygen-evolving hollow polydopamine alleviates tumour hypoxia for enhancing photodynamic therapy in cancer treatment.

Hypoxia, a characteristic hallmark of solid tumours, restricts the therapeutic effect of photodynamic therapy (PDT) for cancer treatment. To address this issue, a facile and nanosized oxygen (O2) bubble template is established by mixing oxygenated water and water-soluble solvents for guiding hollow polydopamine (HPDA) synthesis, and O2 is encapsulated in the cavity of HPDA. HPDA with abundant catechol is designed as a carrier for zinc phthalocyanine (ZnPc, a boronic acid modified photosensitizer) via borate ester bonds to fabricate nanomedicine (denoted as HZNPs). The in vitro and in vivo results indicate that O2-evolving HZNPs could alleviate tumour hypoxia and enhance PDT-anticancer efficiency. Melanin-like HPDA with a photothermal conversion rate (η) of 38.2% shows excellent synergistic photothermal therapy (PTT) efficiency in cancer treatment.

CD169+ subcapsular sinus macrophage-derived microvesicles are associated with light zone follicular dendritic cells.

Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined. In this study, we unexpectedly observed an accumulation of CD169+ subcapsular sinus macrophage (SSM)-derived microvesicles (MVs) in the B-cell zone, which were tightly associated with the FDC network. Interestingly, a selective deposition of CD169+ MVs was detected in both GC LZ FDCs in secondary follicles and on predetermined LZ FDCs in primary follicles. The ablation of CD169+ MVs, resulting from SSM depletion, resulted in significantly decreased expression of LZ-related genes in FDCs. In addition, we found that CD169+ MVs could colocalize with fluorescently tagged antigen-containing immune complexes (ICs), supporting a possible role of CD169+ MVs in transporting antigens to the FDC network. Thus, our data reveal intimate crosstalk between FDCs and SSMs located outside B-cell follicles via SSM-released MVs, providing a novel perspective on the mechanisms underlying the regulation of FDC maturation and polarization.

WATER-SOAKED SPOT1 Controls Chloroplast Development and Leaf Senescence via Regulating Reactive Oxygen Species Homeostasis in Rice.

Transmembrane kinases (TMKs) play important roles in plant growth and signaling cascades of phytohormones. However, its function in the regulation of early leaf senescence (ELS) of plants remains unknown. Here, we report the molecular cloning and functional characterization of the WATER-SOAKED SPOT1 gene which encodes a protein belongs to the TMK family and controls chloroplast development and leaf senescence in rice (Oryza sativa L.). The water-soaked spot1 (oswss1) mutant displays water-soaked spots which subsequently developed into necrotic symptoms at the tillering stage. Moreover, oswss1 exhibits slightly rolled leaves with irregular epidermal cells, decreased chlorophyll contents, and defective stomata and chloroplasts as compared with the wild type. Map-based cloning revealed that OsWSS1 encodes transmembrane kinase TMK1. Genetic complementary experiments verified that a Leu396Pro amino acid substitution, residing in the highly conserved region of leucine-rich repeat (LRR) domain, was responsible for the phenotypes of oswss1. OsWSS1 was constitutively expressed in all tissues and its encoded protein is localized to the plasma membrane. Mutation of OsWSS1 led to hyper-accumulation of reactive oxygen species (ROS), more severe DNA fragmentation, and cell death than that of the wild-type control. In addition, we found that the expression of senescence-associated genes (SAGs) was significantly higher, while the expression of genes associated with chloroplast development and photosynthesis was significantly downregulated in oswss1 as compared with the wild type. Taken together, our results demonstrated that OsWSS1, a member of TMKs, plays a vital role in the regulation of ROS homeostasis, chloroplast development, and leaf senescence in rice.