GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors.

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.

Metagenomic analysis of a thermophilic bacterial consortium and its use in the bioremediation of a petroleum-contaminated soil.

Biodegradation is difficult at high temperatures due to the limited capacity of microorganisms to survive and function outside their optimum temperature range. Here, a thermophilic petroleum-degrading consortium was enriched from compost at a temperature of 55 °C. 16S rDNA and metagenomic techniques were used to analyze the composition of the consortium and the mechanisms of degradation. The consortium degraded 17000 mg total petroleum hydrocarbons (TPHs) L-1 with a degradation efficiency of 81.5% in 14 days. The consortium utilized a range of substrates such as n-hexadecane, n-docosane, naphthalene and pyrene and grew well over a wide range of pH (4-10) and salinity (0-90 g L-1). The hydrocarbon-degrading extremophilic consortium contained, inter alia, (relative abundance > 1%) Caldibacillus, Geobacillus, Mycolicibacterium, Bacillus, Chelatococcus, and Aeribacillus spp. Metagenomic analysis was conducted to discover the degradation and environmental tolerance functional genes of the consortium. Two alkane hydroxylase genes, alkB and ladA, were found. A microcosm study shows that the consortium promoted the bioremediation of soil TPHs. The results indicate that the consortium may be a good candidate for the high-temperature bioremediation of petroleum-contaminated soils.

Polydopamine Synergizes with Quercetin Nanosystem to Reshape the Perifollicular Microenvironment for Accelerating Hair Regrowth in Androgenetic Alopecia.

Accumulated reactive oxygen species (ROS) and their resultant vascular dysfunction in androgenic alopecia (AGA) hinder hair follicle survival and cause permanent hair loss. However, safe and effective strategies to rescue hair follicle viability to enhance AGA therapeutic efficiency remain challenging. Herein, we fabricated a quercetin-encapsulated (Que) and polydopamine-integrated (PDA@QLipo) nanosystem that can reshape the perifollicular microenvironment to initial hair follicle regeneration for AGA treatment. Both the ROS scavenging and angiogenesis promotion abilities of PDA@QLipo were demonstrated. In vivo assays revealed that PDA@QLipo administrated with roller-microneedles successfully rejuvenated the "poor" perifollicular microenvironment, thereby promoting cell proliferation, accelerating hair follicle renewal, and facilitating hair follicle recovery. Moreover, PDA@QLipo achieved a higher hair regeneration coverage of 92.5% in the AGA mouse model than minoxidil (87.8%), even when dosed less frequently. The nanosystem creates a regenerative microenvironment by scavenging ROS and augmenting neovascularity for hair regrowth, presenting a promising approach for AGA clinical treatment.

Vacancy-Defect Ternary Topological Insulators Bi2Se2Te Encapsulated in Mesoporous Carbon Spheres for High Performance Sodium Ion Batteries and Hybrid Capacitors.

Ternary topological insulators have attracted worldwide attention because of their broad application prospects in fields such as magnetism, optics, electronics, and quantum computing. However, their potential and electrochemical mechanisms in sodium ion batteries (SIBs) and hybrid capacitors (SIHCs) have not been fully studied. Herein, a composite material comprising vacancy-defects ternary topological insulator Bi2Se2Te encapsulated in mesoporous carbon spheres (Bi2Se2Te@C) is designed. Bi2Se2Te with ample vacancy-defects has a wide interlayer spacing to enable frequent insertion/extraction of Na+ and boost reaction kinetics within the electrode. Meanwhile, the Bi2Se2Te@C with optimized yolk-shell structure can buffer the volume variation without breaking the outer protective carbon shell, ensuring structural stability and integrity. As expected, the Bi2Se2Te@C electrode delivers high reversible capacity and excellent rate capability in half SIB cells. Various electrochemical analyses and theoretical calculations manifest that Bi2Se2Te@C anode confirms the synergistic effect of ternary chalcogenide systems and suitable void space yolk-shell structure. Consequently, the full cells of SIB and SIHC coupled with Bi2Se2Te@C anode exhibit good performance and high energy/power density, indicating its widespread practical applications. This design is expected to offer a reliable strategy for further exploring advanced topological insulators in Na+-based storage systems.

An Underwater Source Location Privacy Protection Scheme Based on Game Theory in a Multi-Attacker Cooperation Scenario.

Ensuring source location privacy is crucial for the security of underwater acoustic sensor networks amid the growing use of marine environmental monitoring. However, the traditional source location privacy scheme overlooks multi-attacker cooperation strategies and also has the problem of high communication overhead. This paper addresses the aforementioned limitations by proposing an underwater source location privacy protection scheme based on game theory under the scenario of multiple cooperating attackers (SLP-MACGT). First, a transformation method of a virtual coordinate system is proposed to conceal the real position of nodes to a certain extent. Second, through using the relay node selection strategy, the diversity of transmission paths is increased, passive attacks by adversaries are resisted, and the privacy of source nodes is protected. Additionally, a secure data transmission technique utilizing fountain codes is employed to resist active attacks by adversaries, ensuring data integrity and enhancing data transmission stability. Finally, Nash equilibrium could be achieved after the multi-round evolutionary game theory of source node and multiple attackers adopting their respective strategies. Simulation experiments and performance evaluation verify the effectiveness and reliability of SLP-MACGT regarding aspects of the packet forwarding success rate, security time, delay and energy consumption: the packet delivery rate average increases by 30%, security time is extended by at least 85%, and the delay is reduced by at least 90% compared with SSLP, PP-LSPP, and MRGSLP.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

Learning Graph Attentions via Replicator Dynamics.

Graph Attention (GA) which aims to learn the attention coefficients for graph edges has achieved impressive performance in GNNs on many graph learning tasks. However, existing GAs are usually learned based on edges' (or connected nodes') features which fail to fully capture the rich structural information of edges. Some recent research attempts to incorporate the structural information into GA learning but how to fully exploit them in GA learning is still a challenging problem. To address this challenge, in this work, we propose to leverage a new Replicator Dynamics model for graph attention learning, termed Graph Replicator Attention (GRA). The core of GRA is our derivation of replicator dynamics based sparse attention diffusion which can explicitly learn context-aware and sparse preserved graph attentions via a simple self-supervised way. Moreover, GRA can be theoretically explained from an energy minimization model. This provides a more theoretical justification for the proposed GRA method. Experiments on several graph learning tasks demonstrate the effectiveness and advantages of the proposed GRA method on ten benchmark datasets.

Risk Factors Asscociated with Hypokalemia during Postanesthesia Recovery and Its Impact on Outcomes in Gynecological Patients: A Propensity Score Matching Study.

OBJECTIVE: This study aimed to explore the risk factors and outcomes of hypokalemia during the recovery period from anesthesia in the gynecological population. METHODS: This retrospective cohort study included 208 patients who underwent gynecological surgery at our institution between January 2021 and March 2022. Data were collected for each patient, including demographics, disease status, surgical data, and clinical information. Preoperative bowel preparation, postoperative gastrointestinal function, and electrolyte levels were compared between the two groups using propensity score matching (PSM). RESULTS: The incidence of hypokalemia (serum potassium level <3.5 mmol/L) during the recovery period from anesthesia was approximately 43.75%. After PSM, oral laxative use (96.4% vs. 82.4%, P=0.005), the number of general enemas (P=0.014), and the rate of ≥2 general enemas (92.9% vs. 77.8%, P=0.004) were identified as risk factors for hypokalemia, which was accompanied by decreased PaCO2 and hypocalcemia. There were no significant differences in postoperative gastrointestinal outcomes, such as the time to first flatus or feces, the I-FEED score (a scoring system was created to evaluate impaired postoperative gastrointestinal function), or postoperative recovery outcomes, between the hypokalemia group and the normal serum potassium group. CONCLUSION: Hypokalemia during postanesthesia recovery period occurred in 43.75% of gynecological patients, which resulted from preoperative mechanical bowel preparation; however, it did not directly affect clinical outcomes, including postoperative gastrointestinal function, postoperative complications, and length of hospital stay.

The structure, self-assembly and dynamics of lipid nanodiscs revealed by computational approaches.

Nanodisc technology is increasingly being used in structural, biochemical and biophysical studies of membrane proteins. The computational approaches have revealed many important features of nanodisc assembly, structures and dynamics. Therefore, we reviewed the application of computational approaches, especially molecular modeling and molecular dyncamics (MD) simulations, to characterize nanodiscs, including the structural models, assembly and disassembly, protocols for modeling, structural properties and dynamics, and protein-lipid interactions in nanodiscs. More amazing computational studies about nanodiscs are looked forward to in the future.

Water-assisted oxidative redispersion of Cu particles through formation of Cu hydroxide at room temperature.

Sintering of active metal species often happens during catalytic reactions, which requires redispersion in a reactive atmosphere at elevated temperatures to recover the activity. Herein, we report a simple method to redisperse sintered Cu catalysts via O2-H2O treatment at room temperature. In-situ spectroscopic characterizations reveal that H2O induces the formation of hydroxylated Cu species in humid O2, pushing surface diffusion of Cu atoms at room temperature. Further, surface OH groups formed on most hydroxylable support surfaces such as γ-Al2O3, SiO2, and CeO2 in the humid atmosphere help to pull the mobile Cu species and enhance Cu redispersion. Both pushing and pulling effects of gaseous H2O promote the structural transformation of Cu aggregates into highly dispersed Cu species at room temperature, which exhibit enhanced activity in reverse water gas shift and preferential oxidation of carbon monoxide reactions. These findings highlight the important role of H2O in the dynamic structure evolution of supported metal nanocatalysts and lay the foundation for the regeneration of sintered catalysts under mild conditions.

Evaluation of Blue Honeysuckle Berries (Lonicera caerulea L.) Dried at Different Temperatures: Basic Quality, Sensory Attributes, Bioactive Compounds, and In Vitro Antioxidant Activity.

This study aims to comprehensively investigate the effects of hot-air dehydration on the quality of blue honeysuckle berries (Lonicera caerulea L.). The results demonstrated that drying with hot air at 40-65 °C for 7-72 h resulted in blue honeysuckle berries with a moisture content of 0.21-1.10 g H2O/g dry weight. Generally, low to medium temperatures (40-55 °C) showed a better effect on the quality than high temperatures (60-65 °C). Specifically, drying at 40 °C exclusively resulted in better retention of cuticular wax, the best sensory appearance, and the highest total phenolic content. Drying at 45 °C and 50 °C resulted in the highest antioxidant capacity and the optimal sensory flavor. Drying at 55 °C led to the highest soluble solid/acid ratio, ascorbic acid concentration, total flavonoid, and total anthocyanin. The work introduces an innovative raw berry product and provides a comprehensive practical and theoretical framework for convective dehydration of blue honeysuckle berries.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons of Rural Population in Northwestern China: Oxidative Stress and Health Risk Assessment.

Polycyclic aromatic hydrocarbon (PAH) exposure is suspected to be linked to oxidative damage. Herein, ten PAH human exposure biomarkers [hydroxylated PAH metabolites (OH-PAHs)] and five oxidative stress biomarkers (OSBs) were detected in urine samples collected from participants living in a rural area (n = 181) in Northwestern China. The median molar concentration of ΣOH-PAHs in urine was 47.0 pmol mL-1. The 2-hydroxynaphthalene (2-OHNap; median: 2.21 ng mL-1) was the dominant OH-PAH. The risk assessment of PAH exposure found that hazard index (HI) values were <1, indicating that the PAH exposure of rural people in Jingyuan would not generate significant cumulative risks. Smokers (median: 0.033) obtained higher HI values than nonsmokers (median: 0.015, p < 0.01), suggesting that smokers face a higher health risk from PAH exposure than nonsmokers. Pearson correlation and multivariate linear regression analysis revealed that ΣOH-PAH concentrations were significant factors in increasing the oxidative damage to deoxyribonucleic acid (DNA) (8-hydroxy-2'-deoxyguanosine, 8-OHdG), ribonucleic acid (RNA) (8-oxo-7,8-dihydroguanine, 8-oxoGua), and protein (o, o'-dityrosine, diY) (p < 0.05). Among all PAH metabolites, only 1-hydroxypyrene (1-OHPyr) could positively affect the expression of all five OSBs (p < 0.05), suggesting that urinary 1-OHPyr might be a reliable biomarker for PAH exposure and a useful indicator for assessing the impacts of PAH exposure on oxidative stress. This study is focused on the relation between PAH exposure and oxidative damage and lays a foundation for the study of the health effect mechanism of PAHs.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis - a single center retrospective case-control study.

OBJECTIVE: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. METHODS: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. RESULTS: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]. CONCLUSION: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Assessment of nomogram model for the prediction of esophageal variceal hemorrhage in hepatitis B-induced hepatic cirrhosis.

BACKGROUND: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in hepatitis B virus (HBV) -induced cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to find EVs for treatment have complications, contraindications, and high costs. We sought to identify the nomogram models (NMs) as alternative predictions for the risk of EV hemorrhage. METHODS: In this case-control study, we retrospectively analyzed 241 HBV-induced liver cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January 2021 to April 2023. We applied univariate analysis and multivariate logistic regression to assess the accuracy of various NMs in EV hemorrhage. The area under the curve (AUC) and calibration curves of the receiver's operating characteristics were used to evaluate the predictive accuracy of the nomogram. Decision curve analysis (DCA) was used to determine the clinically relevant of nomograms. RESULTS: In the prediction group, multivariate logistic regression analysis identified platelet distribution and spleen length as independent risk factors for EVs. We applied NMs as the independent risk factors to predict EVs risk. The NMs fit well with the calibration curve and have good discrimination ability. The AUC and DCA demonstrated that NMs with a good net benefit. The above results were validated in the validation cohort. CONCLUSION: Our non-invasive NMs based on the platelet distribution width and spleen length may be used to predict EV hemorrhage in HBV-induced cirrhotic patients. NMs can help clinicians to increase diagnostic performance leading to improved treatment measures.

Binary-amplifying electrochemiluminescence sensor for sensitive assay of catechol and luteolin based on HKUST-1 derived CuO nanoneedles as a novel luminophore.

Herein, a highly novel and effective electrochemiluminescence (ECL) sensor based on metal-organic framework (MOF, HKUST-1) derived CuO nanoneedles (HKUST-1 derived CuO NNs), gold nanoparticles (AuNPs) and TiO2 was developed for ultrasensitive detection of catechol and luteolin. The HKUST-1 derived CuO NNs were employed as luminophore for the first time, which were successfully fabricated by using HKUST-1 as precursor. The results revealed that the HKUST-1 derived CuO NNs exhibit excellent ECL activity ascribed to its abundant active site and the high specific surface area, thus obviously promoting the separation and transfer of charge and further improving the current density of ECL sensor. To binary-amplify the signal of the ECL sensor, the AuNPs and TiO2 nano-materials with good biocompatibility, great electron transport efficiency and high catalytic activity were used as co-reaction accelerators in the ECL process. Dependent on the above brilliant strategy, the proposed ECL sensor achieved wide linear ranges from 3 × 10-9 - 1 × 10-4 M for catechol and 1 × 10-8 - 2 × 10-4 M for luteolin, with the detection limits of 1.5 × 10-9 M for catechol and 5.3 × 10-9 M for luteolin, respectively. Furthermore, the ECL sensor exhibited outstanding selectivity, repeatability, stability and obtained great feedback on determination of catechol and luteolin in actual samples. The method not only filled a gap in the ECL application of MOF-derived materials but also provided a novel sight for design other highly efficient luminescent materials.

A commercial humic acid inhibits benzo(a)pyrene biodegradation by Paracoccus aminovorans HPD-2.

Benzo(a)pyrene (BaP) is posing serious threats to soil ecosystems and its bioremediation usually limited by environmental factors and microbial activity. Humic acid (HA), a ubiquitous heterogeneous organic matter, which could affect the fate of environmental pollutants. However, the impact of HA on bioremediation of organic contamination remains controversial. In the present study, the biodegradation of BaP by Paracoccus aminovorans HPD-2 with and without HA was explored. Approximately 87.4 % of BaP was biodegraded in the HPD-2 treatment after 5 days of incubation, whereas the addition of HA dramatically reduced BaP biodegradation to 56.0 %. The limited BaP biodegradation in the HA + HPD-2 treatment was probably due to the decrease of BaP bioavailability which induced by the adsorption of HA with unspecific interactions. The excitation-emission matrix (EEM) of fluorescence characteristics showed that strain HPD-2 was responsible for the presence of protein-like substances and the microbial original humic substances in the HPD-2 treatment. Addition of HA would result in the increase of soluble microbial humic-like material, which should ascribe to the biodegradation of BaP and probably utilization of HA. Furthermore, both the growth and survival of strain HPD-2 were inhibited in the HA + HPD-2 treatment, because of the limited available carbon source (i.e. BaP) at the presence of HA. The expression of gene1789 and gene2589 dramatically decreased in the HA + HPD-2 treatment, and this should be responsible for the decrease of BaP biodegradation as well. This study reveals the mechanism that HA affect the BaP biodegradation, and the decrease of biodegradation should ascribe to the interaction of HA and bacterial strain. Thus, the bioremediation strategies of PAHs need to consider the effects of organic matter in environment.

Identification and functional analysis of Toll-like receptor 2 from razor clam Sinonovacula constricta.

Toll-like receptor 2 (TLR2) is a member of TLR family that plays important roles in the innate immune system, such as pathogen recognition and inflammation regulation. In this study, the TLR2 homologue was cloned from razor clam Sinonovacula constricta (denoted as ScTLR2) and its immune function was explored. The full-length cDNA of ScTLR2 comprised 2890 nucleotides with a 5'-UTR of 218 bp, an open reading frame of 2169 bp encoding 722 amino acids and a 3'-UTR of 503 bp. The deduced amino acid of ScTLR2 showed similar structure to TLR2 homologue with a conserved signal peptide, four LRR domains, one LRR-TYP domain, one LRR-CT domain, one transmembrane domain and a conserved TIR domain. ScTLR2 mRNA was detected in all examined tissues with the highest expression in the gill. After Vibrio parahaemolyticus challenge, the mRNA expression of ScTLR2 was significantly induced both in gill and haemocytes. The recombinant ScTLR2-LRR protein could bind all tested PAMPs including LPS, PGN and MAN. Bacterial agglutination assay showed that rScTLR2 could agglutinate the six tested bacteria with a calcium dependent manner. More importantly, ScTLR2 silencing by siRNA transfection could significantly depress the mRNA expression of Myd88, NF-κB, Tollip, IRF1, and IRF8. The survival rate of S. constricta was markedly decreased after V. parahaemolyticus challenge under this condition. Our current study demonstrated that ScTLR2 served as a pattern recognition receptor to induce immune response against invasive pathogen.

Integrated landscape of chicken egg chalaza proteomics.

Chicken egg chalaza (CLZ) is a natural colloidal structure in eggs that exists as an egg yolk stabilizer and is similar in composition to egg white. In this study, the proteome, phosphoproteome, and N-glycoproteome of CLZ were characterized in depth. We hydrolyzed the CLZ proteins and enriched the phosphopeptides and glycopeptides. We identified 45 phosphoproteins and 80 N-glycoproteins, containing 59 phosphosites and 203 N-glycosylation sites, respectively. Typically, the ovalbumin in CLZ was both phosphorylated and N-glycosylated, with 4 phosphosites and 4 N-glycosylation sites. Moreover, we identified 2 N-glycosylated subunits of ovomucin, mucin-5B and mucin-6, with 32 and nine N- glycosylation sites, respectively. Analysis of the phosphorylation and N-glycosylation status of CLZ proteins could provide novel insights into the structural and functional characteristics of CLZ.