Hyaluronic Acid-Modified Spherical MgO2/Pd Nanocomposites Exhibit Superior Antitumor Effect through Tumor Microenvironment-Responsive Ferroptosis Induction and Photothermal Therapy.

Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (•OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant •OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.

Mitigation of ammonia and hydrogen sulfide emissions during aerobic composting of laying hen waste through NaOH-modified biochar.

The impact of NaOH-modified biochar on the release of NH3 and H2S from laying hens' manure was examined for 44 days, using a small-scale simulated aerobic composting system. The findings revealed that the NaOH-modified biochar reduced NH3 and H2S emissions by 40.63% and 77.78%, respectively, compared to the control group. Moreover, the emissions of H2S were significantly lower than those of the unmodified biochar group (p < 0.05). The increased specific surface area and microporous structure of the biochar, as well as the higher content of alkaline and oxygenated functional groups, were found to facilitate the adsorption of NH3 and H2S. This enhanced adsorption capability was the primary reason for the significant reduction in NH3 emissions. Furthermore, during the high-temperature phase of composting, there was a notable alteration in the microbial community. The abundance of Limnochordaceae, Savagea, and IMCC26207 increased significantly which aided in the conversion of H2S to stable sulfate. These microorganisms also influenced the abundance of functional genes involved in sulfur metabolism, thereby inhibiting cysteine synthesis, along with the decomposition and conversion of sulfate to sulfite. This led to a significant decrease in H2S emissions. This study provides valuable data for the selection of deodorizers in the composting process of egg-laying hens. The results have significant implications for the application of NaOH-modified biochar for odor reduction in aerobic composting processes.

Time-Series Field Phenotyping of Soybean Growth Analysis by Combining Multimodal Deep Learning and Dynamic Modeling.

The rate of soybean canopy establishment largely determines photoperiodic sensitivity, subsequently influencing yield potential. However, assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming. High-throughput phenotyping methods based on unmanned aerial vehicle (UAV) systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes. In this study, high-resolution and time-series raw data from field soybean populations were collected using UAVs. The RGB (red, green, and blue) and infrared images are used as inputs to construct the multimodal image segmentation model-the RGB & Infrared Feature Fusion Segmentation Network (RIFSeg-Net). Subsequently, the segment anything model was employed to extract complete individual leaves from the segmentation results obtained from RIFSeg-Net. These leaf aspect ratios facilitated the accurate categorization of soybean populations into 2 distinct varieties: oval leaf type variety and lanceolate leaf type variety. Finally, dynamic modeling was conducted to identify 5 phenotypic traits associated with the canopy development rate that differed substantially among the classified soybean varieties. The results showed that the developed multimodal image segmentation model RIFSeg-Net for extracting soybean canopy cover from UAV images outperformed traditional deep learning image segmentation networks (precision = 0.94, recall = 0.93, F1-score = 0.93). The proposed method has high practical value in the field of germplasm resource identification. This approach could lead to the use of a practical tool for further genotypic differentiation analysis and the selection of target genes.

Short-, long-read metagenome and virome reveal the profile of phage-mediated ARGs in anoxic-oxic processes for swine wastewater treatment.

Phages are among the most widely spread viruses, but their profiles and the antibiotic resistance genes (ARGs) they carry in swine wastewater remain underexplored. The present study investigated the distribution characteristics of phages and their ARG risk in anoxic/oxic (A/O) wastewater treatment processes of swine farms using short- and long-read metagenome and virome. The results demonstrated that the virome could extract more phage sequences than the total metagenome; thus, it was more suited for studying phages in wastewater settings. Intriguingly, phages had significantly lower abundance of ARG than ARGs harbored by total microorganisms (P < 0.01). Eleven ARGs co-occurred with phages and bacteria (R > 0.6 and P < 0.05), with Siphoviridae being the phage co-occurring with the most ARGs (5). Horizontal gene transfer (HGT) events were observed between Proteobacteria and the major phyla except for Bacteroidota. Furthermore, there were prophage sequences and ARGs on the same contig in bacterial MAGs. These data strongly demonstrate that phages promote horizontal transfer of ARG between bacterial hosts in A/O processes for swine wastewater treatment. Therefore, the risk of phage-mediated horizontal transfer of ARGs cannot be overlooked despite the low abundance of phage ARGs (pARG).

Pleosmaranes A-R, Isopimarane and 20-nor Isopimarane Diterpenoids with Anti-inflammatory Activities from the Mangrove Endophytic Fungus Pleosporales sp. HNQQJ-1.

Pleosmaranes A-R (1-18), 18 new isopimarane-type diterpenoids, together with four known analogs (19-22), were isolated from the mangrove endophytic fungus Pleosporales sp. HNQQJ-1. Their structures and absolute configurations were established by analysis of their spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-9 possess an unusual aromatic B ring and a 20-nor-isopimarane skeleton. Compounds 15-17 contain a unique 2-oxabicyclo[2.2.2]octane moiety. Compound 18 features an unexpected 2-oxabicyclo[3.2.1]octane moiety. Compounds 8 and 12 exhibited a moderate inhibitory effect against LPS-induced NO production, with IC50 values of 19 and 25 µM, respectively.

Multi-replicas integrity checking scheme with supporting probability audit for cloud-based IoT.

Nowadays, more people are choosing to use cloud storage services to save space and reduce costs. To enhance the durability and persistence, users opt to store important data in the form of multiple copies on cloud servers. However, outsourcing data in the cloud means that it is not directly under the control of users, raising concerns about security and integrity. Recent research has found that most existing multicopy integrity verification schemes can correctly perform integrity verification even when multiple copies are stored on the same Cloud Service Provider (CSP), which clearly deviates from the initial intention of users wanting to store files on multiple CSPs. With these considerations in mind, this paper proposes a scheme for synchronizing the integrity verification of copies, specifically focusing on strongly privacy Internet of Things (IoT) electronic health record (EHR) data. First, the paper addresses the issues present in existing multicopy integrity verification schemes. The scheme incorporates the entity Cloud Service Manager (CSM) to assist in the model construction, and each replica file is accompanied with its corresponding homomorphic verification tag. To handle scenarios where replica files stored on multiple CSPs cannot provide audit proof on time due to objective reasons, the paper introduces a novel approach called probability audit. By incorporating a probability audit, the scheme ensures that replica files are indeed stored on different CSPs and guarantees the normal execution of the public auditing phase. The scheme utilizes identity-based encryption (IBE) for the detailed design, avoiding the additional overhead caused by dealing with complex certificate issues. The proposed scheme can withstand forgery attack, replace attack, and replay attack, demonstrating strong security. The performance analysis demonstrates the feasibility and effectiveness of the scheme.

In Situ Understanding of the Effect of Manure on the Availability of Sulfonamide Antibiotics in Soils Using DGT.

In this study, the effects of manure on the availability of sulfonamide antibiotics (SAs) in soils were explored in situ by the Diffusive gradients in thin films (DGT) technique. Five antibiotics, including sulfadiazine (SDZ), sulfamethoxazole (SMX), sulfamethazine (SMZ), sulfachloropyridazine (SCP), and sulfadimethoxine (SDM), were selected as target compounds. Results showed that the manure application to soil could reduce the antibiotic availability indicated by DGT. DGT measurement (CDGT) showed good correlations with the soil solution concentrations (Cd). Manure application can suppress the fluxes of SAs from the soil to the soil solution. Using the DGT-induced soil/sediment flux model (DIFS), the labile pool size (Kdl), the rate constants (k1, k-1) of adsorption and desorption and response time (Tc) of SAs in soils were obtained. The addition of manure increased extractable fraction, labile pool size (Kdl) and k1 but decreased k-1. Together with the nonlinear relationship between DGT fluxes and the reciprocal of diffusive layer thickness (Δg), these findings suggested that the release of SAs from soil particles into the soil solution is thermodynamically and kinetically limited, and the manure application could enhance this limitation. This study offers insight into antibiotic availability in soils caused by manure application.

Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus Phomopsis sp. QYM-13.

Six previously undescribed cytosporone derivatives (phomotones A-E (1-5) and phomotone F (13)), two new spiro-alkanol phombistenes A-B (14-15), and seven known analogs (6-12) were isolated from the mangrove endophytic fungus Phomopsis sp. QYM-13. The structures of these compounds were elucidated using spectroscopic data analysis, electronic circular dichroism (ECD), and 13C NMR calculations. Compound 14 features an unprecedented 1,6-dioxaspiro[4.5]decane ring system. All isolates were evaluated for their inhibitory effect on nitric oxide (NO) in LPS-induced RAW264.7 cells. The results showed that compounds 1, 6, 8, and 11 exhibited potent bioactivities by comparing with positive control. Then, compound 1 displayed the anti-inflammatory effect by inhibiting the MAPK/NF-κB signaling pathways. Molecular docking further revealed the possible mechanism of compound 1 interaction with ERK protein.

SGN-YOLO: Detecting Wood Defects with Improved YOLOv5 Based on Semi-Global Network.

Object detection based on wood defects involves using bounding boxes to label defects in the surface image of the wood. This step is crucial before the transformation of wood products. Due to the small size and diverse shape of wood defects, most previous object detection models are unable to filter out critical features effectively. Consequently, they have faced challenges in generating adequate contextual information to detect defects accurately. In this paper, we proposed a YOLOv5 model based on a Semi-Global Network (SGN) to detect wood defects. Unlike previous models, firstly, a lightweight SGN is introduced in the backbone to model the global context, which can improve the accuracy and reduce the complexity of the network at the same time; the backbone is embedded with the Extended Efficient Layer Aggregation Network (E-ELAN), which continuously enhances the learning ability of the network; and finally, the Efficient Intersection and Merger (EIOU) loss is used to solve the problems of slow convergence speed and inaccurate regression results. Experimental results on public wood defect datasets demonstrated that our approach outperformed existing target detection models. The mAP value was 86.4%, a 3.1% improvement over the baseline network model, a 7.1% improvement over SSD, and a 13.6% improvement over Faster R-CNN. These results show the effectiveness of our proposed methodology.

Pet cats may shape the antibiotic resistome of their owner's gut and living environment.

BACKGROUND: Companion animals can contribute to the physical and mental health of people and often live in very close association with their owners. However, the antibiotic resistome carried by companion animals and the impact they have on their owners and living environment remain unclear. In this study, we compared the ARG profiles of cats, humans, and their living environments using metagenomic analysis to identify the core ARGs in the cat and human gut and explore the potential impact of cats on ARGs in the human gut through the environment. RESULTS: Results showed that the abundance of ARGs in the cat gut was significantly higher than that in the human gut (P < 0.0001), with aminoglycoside and tetracycline resistance genes being the dominant ARGs in the cat gut. There was no significant difference in the abundance of total ARGs in the guts of cat owners and non-owners (P > 0.05). However, the abundance of aminoglycoside resistance genes including APH(2'')-IIa and AAC(6')-Im was significantly higher in cat owners than that in non-cat owners (P < 0.001). Also, ARG abundance was positively correlated with the frequency of cat activity in the living environment. Enterobacteriaceae was the dominant ARG host co-occurring in the cat gut, human gut, and living environment. CONCLUSIONS: Our results show that cats may shape the living environment resistome and thus the composition of some ARGs in the human gut, highlighting the importance of companion animal environment health. Video Abstract.

Metabolites isolated from the mangrove endophytic fungus Didymella sp. CYSK-4 and their cytotoxic activities.

Two new 12- or 13- membered-ring macrocyclic alkaloids ascomylactam D and E (1 & 2), and a pair of new enantiomer (+)- and (-)- didymetone (3) were purified from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures and absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, ECD and 13C NMR calculations. Compound 2 exhibited significant cytotoxicity against human A549 and KYSE 150 cancer cell lines with IC50 values of 2.8 µM and 5.9 µM, respectively.

Remote data possession checking scheme with supporting efficient group user authority management for shared cloud data.

Under the shared big data environment, the existing shared data auditing schemes rarely consider the authorization management of group users. Thus, in this paper, we propose a novel remote shared data checking possession scheme that support group authority management. To implement group user rights management, we firstly introduce a trusted entity group manager. To assist the group manager in authorization management, we formalize a new algebraic structure operator named authorization invisible authenticator (AIA). Meanwhile, we provide a basic AIA scheme for general security scenarios and a standard AIA scheme suitable for high-level security scenarios respectively. The standard AIA scheme can fully meet the needs of the group manager to safely perform rights management work. It is composed of the User Information Table (UIT) and the basic AIA scheme, which has higher security and is applicable to a wider range of scenarios. By distributing AIA through the standard AIA scheme, the group manager can easily carry out authority management, including enrolling, revoking, updating. After solving the problem of authorization management, the detailed design of the scheme based on identity-based encryption (IBE) is given. Furthermore, the security analysis and performance evaluation demonstrate that the scheme is safe and feasible.

Factors that influence family-focused practice in Chinese mental health workers: A cross-sectional survey.

INTRODUCTION: Family-focused practice has become an emerging paradigm in mental health services. However, little is known about family-focused practice and associated factors in Chinese mental health workers. AIM: To examine family-focused practice and associated factors in Chinese mental health workers. METHOD: A cross-sectional survey was conducted in a convenience sample of mental health workers (n = 515) in Beijing, China. The Family-Focused Mental Health Practice Questionnaire was used to measure family-focused practice, as well as worker, workplace and client factors that might influence family-focused practice. Multiple linear regression analysis was performed to investigate the factors associated with family-focused practice. RESULTS: On average, the participants exhibited a moderate level of engagement in family-focused practice. The factors that most significantly influenced family-focused practice in Chinese mental health workers were skill and knowledge, worker confidence and time and workload. Moreover, psychiatrists were found to engage more in family-focused practice than psychiatric nurses, and community mental health workers were more active in family-focused practice than hospital-based ones. DISCUSSION: This study provided important data concerning family-focused practice and associated factors in Chinese mental health workers. IMPLICATIONS FOR PRACTICE: The varying level of Chinese mental health workers to engage in family-focused practice has advocacy, training, research and organizational implications for mental health services in China and elsewhere.

Limitations of gene editing assessments in human preimplantation embryos.

Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.

Reducing light exposure enhances the circadian rhythm of the biological clock through interactions with the gut microbiota.

Light mainly synergistically regulates the central biological clock system. In farming, long-term light exposure may induce metabolic disorders and increase the load on the liver in laying hens. In contrast, intermittent photoperiods can reduce light exposure and increase rest time to improve the health of laying hens. The circadian rhythms of gut microbes are essential for the health of the host. However, the circadian rhythms of gut microbes and how those microbes interact with the host under intermittent photoperiods are not clear. We used laying hens as a model to evaluate the circadian rhythms of gut microbes and biological clock genes under different intermittent photoperiods. Intermittent photoperiod 1 (IP1, 16 [3 h -L/1 h -D]: 8 D) enhanced the circadian rhythms of cBmal1, cBmal2, cCry1, and cCry2 in the hypothalamus and increased the expression of cClock, cBmal1, and cCry2 in the liver and seven clock genes in the cecal wall. The intermittent photoperiod also significantly altered the composition and metabolic function of the cecal microbiota via the melatonin pathway. The concentrations of short-chain fatty acids (SCFAs) and the abundance of SCFA-producing genera such as Odoribacter significantly increased under the IP1 treatment and might have further fed back into and strengthened the peripheral and central rhythms by activating the SCFA receptor gene pathway in cecal wall. These findings clarify the mediation mechanisms for the circadian rhythms of the central circadian clock and highlight the role of intermittent photoperiod-induced regulation of the interaction between the host clock and the cecal microbial community.

Glucocorticoids Improve the Pregnancy Rate and Outcome in Women With Unexplained Positive Autoantibodies: A Systematic Review and Meta-Analysis.

The effect of glucocorticoid therapy on women with unexplained positive autoantibodies is under debate. This systemic review and meta-analysis were performed to evaluate whether glucocorticoid administration can improve the pregnancy outcome of this population. Relevant publications were searched from databases, and a total of seven prospective and retrospective cohort studies that investigated the effects of glucocorticoid administration on women with unexplained positive autoantibodies, were included. The outcomes of our systematic review and meta-analysis were measured in terms of risk ratios (RR) with 95% confidence intervals (CI) using fixed or random effect models. We found that glucocorticoid treatment improved the clinical pregnancy rate (RR 2.19, 95% CI 1.64-2.92) and live birth rate (RR 1.92, 95% CI 1.17-3.16), especially when glucocorticoid administration was started before pregnancy (clinical pregnancy rate: RR 2.30, 95% CI 1.58-3.34; live birth rate: RR 2.30, 95% CI 1.58-3.34). However, no effect of glucocorticoids on the miscarriage rate was found (RR 0.75, 95% CI 0.55-1.02) regardless of the time of drug administration. Our systematic review and meta-analysis support the rational use of glucocorticoids in women with unexplained positive autoantibodies. Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD42019124442].

Diversified Polyketides With Anti-inflammatory Activities From Mangrove Endophytic Fungus Daldinia eschscholtzii KBJYZ-1.

In total, five new polyketide derivatives: eschscholin B (2), dalditone A and B (3 and 4), (1R, 4R)-5-methoxy-1,2,3,4-tetrahydronaphthalene-1,4-dio (5), and daldilene A (6), together with 10 known as analogs (1, 7-15) were isolated from the mangrove endophytic fungus Daldinia eschscholtzii KBJYZ-1. Their structures and absolute configurations were established by extensive analysis of NMR and HRESIMS spectra data combined with ECD calculations and the reported literature. Compounds 2 and 6 showed significant cell-based anti-inflammatory activities with IC50 values of 19.3 and 12.9 µM, respectively. In addition, western blot results suggested that compound 2 effectively inhibits the expression of iNOS and COX-2 in LPS-induced RAW264.7 cells. Further molecular biology work revealed the potential mechanism of 2 exerts anti-inflammatory function by inactivating the MAPK and NF-κB signaling pathways.

Metagenomic assembly reveals the circadian oscillations of the microbiome and antibiotic resistance genes in a model of laying hens.

The increasing risks of antibiotic resistance genes (ARGs) in livestock feces have attracted global attention. However, how the rhythmic activity of ARGs changes in fecal microbiota remains largely unclear. In our study, we collected 52 fresh fecal samples every 6 h over 72 h from laying hens and characterized circadian oscillations of bacteria and ARGs using an approach based on assembled metagenome shotgun sequencing. We found that 14% of commensal bacterial taxonomic units fluctuated over 24 h. A total of 33 out of 281 ARGs and 17 of 574 mobile genetic elements (MGEs) featured rhythmic patterns in feces. lnuC and ANT(6)H-lb were the two most abundant ARGs with circadian oscillation identified from feces, and they increased during the day and decreased at night. Acetate, butyrate, propionate, and 78 out of 392 MetaCyc pathways relating to short-chain fatty acid (SCFA) metabolism featured circadian oscillations. Assessment of the above ARG-other element connections revealed that 17 ARGs presented strong correlations with 7 MGEs, and 2 SCFAs (acetate and propanoate) and bacterial species in feces. Structural equation model (SEM) analysis showed that ARGs were directly affected by microbial ß-diversity and MGEs. These results showed a comprehensive map of ARGs over 24 h and revealed circadian oscillations of ARGs, which are influenced by key bacterial species, MGEs, and metabolites. Together, our findings advance comprehension of circadian oscillations of ARGs in the fecal microbiota and provide a reference for ARGs control and management.

Towards efficient verifiable multi-keyword search over encrypted data based on blockchain.

Searchable symmetric encryption (SSE) provides an effective way to search encrypted data stored on untrusted servers. When the server is not trusted, it is indispensable to verify the results returned by it. However, the existing SSE schemes either lack fairness in the verification of search results, or do not support the verification of multiple keywords. To address this, we designed a multi-keyword verifiable searchable symmetric encryption scheme based on blockchain, which provides an efficient multi-keyword search and fair verification of search results. We utilized bitmap to build a search index in order to improve search efficiency, and used blockchain to ensure fair verification of search results. The bitmap and hash function are combined to realize lightweight multi-keyword search result verification, compared with the existing verification schemes using public key cryptography primitives, our scheme reduces the verification time and improves the verification efficiency. In addition, our scheme supports the dynamic update of files and realizes the forward security in update. Finally, formal security analysis proves that our scheme is secure against Chosen-Keyword Attacks (CKA), experimental analysis demonstrations that our scheme is efficient and viable in practice.

Metabolites With Cytotoxic Activities From the Mangrove Endophytic Fungus Fusarium sp. 2ST2.

Two new 3-decalinoyltetramic acid derivatives with peroxide bridge fusarisetins E (1) and F (2), one new chromone fusarimone A (5), two new benzofurans fusarifurans A (9) and B (10), three new isocoumarins fusarimarins A-C (11-13), as well as five known analogues 3, 4, 6-8 and 14 were isolated from mangrove endophytic fungus Fusarium sp. 2ST2. Their structures and absolute configurations were established by spectroscopic analysis, density functional theory-gauge invariant atomic orbital NMR calculation with DP4+ statistical analysis, and electronic circular dichroism calculation. Compounds 1 and 2 showed significant cytotoxicity against human A549 cell lines with IC50 values of 8.7 and 4.3 µM, respectively.