Six transition patterns and seven capture types in different left bundle branch bipolar pacing configurations.

Aims: This study aims to explore the different transition patterns and capture types during two bipolar pacing tests based on the selective left bundle branch (LBB) capture determined by the continuous pacing and recording technique. Methods: In total, 67 patients completed two unipolar and two bipolar pacing tests based on selective LBB capture during screwing-in for left bundle branch pacing (LBBP) using the continuous pacing and recording technique. The electrophysiological characteristics and potential mechanisms of different pacing configurations were further evaluated in this study. Results: We found six transition patterns and derived seven capture types in two bipolar pacing tests according to the analysis of continuous electrocardiogram and electrogram changes. Compared with the conventional configuration of "Tip-Ring+" bipolar pacing, "Ring-Tip+" testing had a lower threshold for simultaneous capture of the LBB and the left and right ventricular septum myocardium (1.57 vs. 2.84 V at 0.5 ms) and was the only configuration to yield the peculiar "LBBP + right ventricular septum pacing (RVSP)" capture type. Conclusions: In this study, we observed for the first time that "Ring-Tip+" bipolar pacing allows for a lower clinically applicable pacing threshold for simultaneous capture of the LBB and left and right ventricular septum myocardium, and the peculiar "LBBP + RVSP" capture type. This may be a more advantageous physiological pacing configuration, warranting further investigation and application in the future. Lay summary: Based on the specific selective LBB capture, we first found six transition patterns and derived seven capture types in two bipolar pacing tests due to the different thresholds of the LBB, left ventricular septal myocardial, and right ventricular septal myocardial. Compared with the conventional configuration of "Tip-Ring+" bipolar pacing, "Ring-Tip+" testing had a lower threshold for simultaneous capture of the LBB and the left and right ventricular septum myocardium (1.57 vs. 2.84 V at 0.5 ms) and was the only configuration to yield the peculiar "LBBP + RVSP" capture type. More pacing strategies should be released and investigated to achieve the best physiological pacing according to the individualized electrophysiological characteristics of patients.

A detailed simulation study on radionuclide dispersion under spent fuel road transportation conditions: Effects of vessel type and coniferous vegetation growth.

Vegetation barriers are an important environmental characteristic of spent fuel road transportation accidents. Spent fuel vessels may be affected by force majeure factors during transportation, which leads to damage to spent fuel assemblies and containers and can cause radionuclides to gradually release from assemblies to vessels to the external environment. In this work, considering the growth periods of coniferous vegetation barriers and vessel type, a radionuclide dispersion model based on computational fluid dynamics (CFD) was established by adding a decay term and a pressure loss term. The simulations showed that, first, compared to the small (Type-II) vessel, the effects of fluid flow around the large vessel (Type-I) have a more significant impact on radionuclide dispersion. The backflow around the Type-I vessel causes leaked radionuclides to disperse towards the vessel, and the larger the vessel is, the more significant the rise of the leaked radionuclide plume tail will be due to the increased negative pressure gradient area. Moreover, the area contaminated exceeding the maximum allowable concentration by radioactivity for the Type-I vessel is reduced gradually with the growth of coniferous vegetation barriers due to the weakening of the backflow effect by growing vegetation. Second, compared to vegetation barriers of 15 years and 23 years, the horizontal distance exceeding the maximum allowable concentration of the leaked 131I dispersion from Type II vessels near vegetation barriers for 12 years is the longest. The older the vegetation barrier is, the shorter the horizontal dispersion range, and the shape of radionuclide dispersion gradually transforms from flat to semicircular with vegetation barrier growth, but this could cause a greater radioactive accumulation effect near the leakage point, and the maximum concentration of leaked 131I reached 0.54 kBq·m-3 for leaked radionuclides from the Type II vessel under vegetation barriers of 23 years. In addition, improvement suggestions based on the proposed method are presented, which will enable the Standards Institutes to apply the research methodologies described herein across various scenarios. ENVIRONMENTAL IMPLICATION: Compared to nonradioative pollutants, radioactive pollutants are intercepted by vegetation barriers and then migrate to the soil through leaves, stems, and roots, which can contaminate the surrounding environment. Considering the effects of vessel type and coniferous vegetation growth, a radionuclide dispersion model based on CFD was established. Suggestions for decontaminating radioactive pollution areas have been proposed based on the simulation results of hypothetical scenarios. The scenario applicability improvements based on the proposed model could assist relevant Standards Institutes to making improving measures.

Optimizing green waste composting with iron-based Fenton-like process.

The presence of refractory lignocellulose presents a significant challenge in green waste (GW) composting. This research applied both a conventional iron-based Fenton-like process (with a Fenton-like reagent composed of 1.0 % Fe3O4 nanoparticles and 1.0 % H2O2) and three modified iron-based Fenton-like processes (with a Fenton-like reagent composed of 1.0 % Fe3O4 nanoparticles and 1.0 % oxalic acid/1.0 % sodium percarbonate/0.5 % Phanerochaete chrysosporium) in GW composting to systematically assess their impacts on lignocellulose degradation during GW composting. The results revealed that iron-based Fenton-like process modified sodium percarbonate exhibited the most significant effects on lignocellulose degradation. Compared with control, degradation rates for lignin, cellulose, and hemicellulose increased by 49.8 %, 39.3 %, and 26.2 % (p < 0.05), respectively. Furthermore, this process enhanced the relative abundance of bacterial communities linked to lignocellulose degradation, particularly Firmicutes and Bacteroidota. These findings offer valuable insights into optimizing GW composting, understanding reactive oxygen species dynamics, and the application of iron-based Fenton-like process.

Homogenizing Energy Landscape for Efficient and Spectrally Stable Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) have attracted enormous attention; however, their unsatisfactory device efficiency and spectral stability still remain great challenges. Unfavorable low-dimensional phase distribution and defects with deeper energy levels usually cause energy disorder, substantially limiting the device's performance. Here, an additive-interface optimization strategy is reported to tackle these issues, thus realizing efficient and spectrally stable blue PeLEDs. A new type of additive-formamidinium tetrafluorosuccinate (FATFSA) is introduced into the quasi-2D mixed halide perovskite accompanied by interface engineering, which effectively impedes the formation of undesired low-dimensional phases with various bandgaps throughout the entire film, thereby boosting energy transfer process for accelerating radiative recombination; this strategy also diminishes the halide vacancies especially chloride-related defects with deep energy level, thus reducing nonradiative energy loss for efficient radiative recombination. Benefitting from homogenized energy landscape throughout the entire perovskite emitting layer, PeLEDs with spectrally-stable blue emission (478 nm) and champion external quantum efficiency (EQE) of 21.9% are realized, which represents a record value among this type of PeLEDs in the pure blue region.

Niacin regulates glucose metabolism and osteogenic differentiation via the SIRT2-C/EBPß-AREG signaling axis.

The pathogenesis of osteoporosis is driven by several mechanisms including the imbalance between osteoblastic bone formation and osteoclastic bone resorption. Currently, the role of Niacin (NA), also known as vitamin B3, in the regulation of osteoblastic differentiation is not fully understood. Data from the NHANES database were employed to investigate the association of NA intake with the prevalence of osteoporosis. Alterations in mRNA and protein levels of genes and proteins involved in osteogenic differentiation were evaluated via techniques including qRT-PCR, protein immunoblotting, Alkaline Phosphatase (ALP) activity analysis, ALP staining, and Alizarin Red staining. Changes in the mouse skeletal system were investigated by organizational analysis and Micro-CT. The results indicated that NA promoted osteogenic differentiation. Co-immunoprecipitation and chromatin immunoprecipitation were performed to explore the underlying mechanisms. It was observed that NA promoted AREG expression by deacetylating C/EBPß via SIRT2, thereby activating the PI3K-AKT signaling pathway. It also enhanced the activity of the pivotal glycolytic enzyme, PFKFB3. This cascade amplified osteoblast glycolysis, facilitating osteoblast differentiation. These findings demonstrate that NA modulates glucose metabolism and influences osteogenic differentiation via the SIRT2-C/EBPß-AREG pathway, suggesting that NA may be a potential therapeutic agent for the management of osteoporosis, and AREG could be a plausible target.

LncSTPred: a predictive model of lncRNA subcellular localization and decipherment of the biological determinants influencing localization.

Introduction: Long non-coding RNAs (lncRNAs) play crucial roles in genetic markers, genome rearrangement, chromatin modifications, and other biological processes. Increasing evidence suggests that lncRNA functions are closely related to their subcellular localization. However, the distribution of lncRNAs in different subcellular localizations is imbalanced. The number of lncRNAs located in the nucleus is more than ten times that in the exosome. Methods: In this study, we propose a new oversampling method to construct a predictive dataset and develop a predictive model called LncSTPred. This model improves the Adaboost algorithm for subcellular localization prediction using 3-mer, 3-RF sequence, and minimum free energy structure features. Results and Discussion: By using our improved Adaboost algorithm, better prediction accuracy for lncRNA subcellular localization was obtained. In addition, we evaluated feature importance by using the F-score and analyzed the influence of highly relevant features on lncRNAs. Our study shows that the ANA features may be a key factor for predicting lncRNA subcellular localization, which correlates with the composition of stems and loops in the secondary structure of lncRNAs.

Thermoplastic PHB-Reinforced Chitosan Piezoelectric Films for Biodegradable Pressure Sensors.

Flexible and wearable pressure sensors have attracted significant attention in the fields of smart medicine and human health monitoring. Nevertheless, the design and fabrication of degradable disposable pressure sensors still face urgent challenges. Herein, we fabricated poly(3-hydroxybutyrate) (PHB)-reinforced chitosan (CS) piezoelectric films for intelligent sensors through a simple, low-cost, and environmentally friendly roll-forming method. The results show that PHB doping successfully increased the effective piezoelectric coefficient of the chitosan-based film from 40.12 to 49.38 pm/V (a 23% increase). Simultaneously, the pressure sensor based on the CS/PHB film exhibited excellent response sensitivity (484 mV/kPa) and a wide linear response range (0-130 kPa), which could be used as haptic sensors and motion monitoring sensors for the fast response to human motion signals. Additionally, the CS/PHB film could be completely degraded within 18 days in a natural soil environment, demonstrating outstanding degradability. Therefore, chitosan-based piezoelectric films with excellent biodegradability and piezoelectric characteristics have been successfully fabricated in this work, which will promote the innovative development of green chitosan-based electronic devices and disposable pressure sensors.

Interfacial Thermal Fluctuations Stabilize Bulk Nanobubbles.

Consensus on bulk nanobubble stability remains elusive, despite accepted indirect evidence for longevity. We develop a nanobubble evolution model by incorporating thermal capillary wave theory that reveals that dense nanobubbles generated by acoustic cavitation tend to shrink and intensify interfacial thermal fluctuations; this significantly reduces surface tension to neutralize enhanced Laplace pressure, and secures their stabilization at a finite size. A stability criterion emerges: thermal fluctuation intensity scales superlinearly with curvature: sqrt[⟨h^{2}⟩]∝(1/R)^{n}, n>1. The model prolongs the time frame for nanobubble contraction to 2 orders of magnitude beyond classical theory estimates, and captures the equilibrium radius (90-215 nm) within the experimental range.

Deciphering the roles of attached and suspended sludges in simultaneous nitrogen and phosphorus removal in an IFAS system based on metagenomic analysis.

Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO3--N reduction, endogenous NO3--N reduction, and endogenous NO2--N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance.

Wnt7B enhances the osteogenic differentiation of lipopolysaccharide-stimulated human periodontal ligament stem cells and inhibits the M1 polarization of macrophages by binding FZD4.

Periodontitis, a common oral disease characterized by the progressive infiltration of bacteria, is a leading cause of adult tooth loss. Periodontal stem cells (PDLSCs) possess good self­renewal and multi­potential differentiation abilities to maintain the integrity of periodontal support structure and repair defects. The present study aimed to analyze the roles of Wnt7B and frizzled4 (FZD4) in the osteogenic differentiation and macrophage polarization during periodontitis using an in vitro cell model. First, Wnt7B expression in the periodontitis­affected gingival tissue of patients and lipopolysaccharide (LPS)­stimulated PDLSCs was assessed using the GSE23586 dataset and western blot analysis, respectively. In Wnt7B­overexpressing PDLSCs exposed to LPS, the capacity of osteogenic differentiation was evaluated by detecting alkaline phosphatase activity, the level of Alizarin Red S staining and the expression of genes related to osteogenic differentiation. Subsequently, conditioned medium from PDLSCs overexpressing Wnt7B was used for M0 macrophage culture. The expression of CD86 and INOS was examined using immunofluorescence staining and western blot analysis. In addition, reverse transcription­quantitative PCR was employed to examine the expression of TNF­α, IL­6 and IL­1ß in macrophages. The binding between Wnt7B and FZD4 was estimated using co­immunoprecipitation. In addition, FZD4 was silenced to perform the rescue experiments to elucidate the regulatory mechanism between Wnt7B and FZD4. The results demonstrated a decreased expression of Wnt7B in periodontitis­affected gingival tissue and in LPS­exposed PDLSCs. Wnt7B overexpression promoted the osteogenic differentiation of LPS­exposed PDLSCs and suppressed the M1 polarization of macrophages. Additionally, Wnt7B bound to FZD4 and upregulated FZD4 expression. FZD4 silencing reversed the effects of Wnt7B overexpression on the osteogenic differentiation in LPS­exposed PDLSCs and the M1 polarization of macrophages. In summary, Wnt7B plays an anti­periodontitis role by binding FZD4 to strengthen the osteogenic differentiation of LPS­stimulated PDLSCs and suppress the M1 polarization of macrophages.

One-dimensional hybrid copper halides with high-efficiency photoluminescence as scintillator.

A new one-dimensional hybrid [APCHA]Cu2I4 was designed and applied as an X-ray scintillator. It exhibits broad-band green emission with a high PLQY of 74.80% and excellent stability. It demonstrates radioluminescence property with a light yield of 28 336 photons MeV-1, detection limit of 41 nGyair s-1, and high spatial limit of 13.95 lp mm-1 in X-ray imaging.

AmTPS6 promotes trehalose biosynthesis to enhance the Cd tolerance in mangrove Avicennia marina.

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.

Soil bacteria and fungi on tropical mountainsides: Joint effects of weathering, climate, and chemical factors.

Contemporary environmental factors such as temperature and pH are generally identified as primary influences on microbial diversity, while the role of geological processes remain understudied. Here, we investigated the diversity and community composition of bacteria and fungi along an elevational gradient of 703 - 4,514 m on Mt. Kilimanjaro, East Africa. We further examined the effects of contemporary environment and geological processes such as weathering on microbial communities and diversities. For community composition, bacteria and fungi showed clear differentiation along elevations and their community dissimilarities increased with elevational distance indicating elevational distance-decay relationships. Multiple variables such as weathering, climate and chemical factors were significantly associated with microbial communities and showed greater effects on bacterial than fungal communities. Specifically, soil pH mainly shaped bacterial communities, while mean annual temperature for fungi, followed by other variables such as weathering processes. For Shannon diversity, bacteria and fungi showed significant hump-shaped elevational patterns with the peak values at 1,857 and 1,436 m, respectively. Shannon diversity was mainly affected by soil weathering accounting for 8.9% of the total variance for bacteria, while jointly by weathering and climate accounted for 14.3% of fungi. For the community uniqueness, represented by local contribution to beta diversity (LCBD), there were U-shaped patterns for both taxonomic groups. LCBD was mainly explained by the joint effects of chemical and climate variables which accounted for 51.1% and 33.4% for bacteria and fungi, respectively. Our results highlight the effects of soil weathering processes on diversity and community composition for bacteria and fungi. Thus, the integration of weathering with contemporary environments could provide new insights into microbial elevational diversity patterns.

The JNK-associated leucine zipper protein exerts a protective effect on renal parenchymal injury by limiting the inflammatory secretome in tubular cells.

JNK-associated leucine zipper protein (JLP) is a newly identified renal endogenous anti-fibrotic factor that is selectively enriched in renal tubular epithelial cells (TECs). The loss of JLP by TECs is a landmark event that heralds the progression of kidney fibrosis. JLP deficiency ensues a series of pathogenetic cellular processes that are conducive to fibrotic injury. Inflammatory injury is functionally relevant in fibrotic kidneys, and TECs play an essential role in fueling inflammation through aberrant secretions. It is speculated that the loss of JLP in TECs is associated with the relentless inflammation during the development of kidney fibrosis. This study examined the alteration of a panel of inflammatory signatures in TECs under kidney fibrotic circumstances using a Jlp gene-modified unilateral ureteral obstruction (UUO) mouse model or cultured HK-2 cells. It was found that a deficiency of JLP in TECs led to a significant increase in the secretion of inflammatory cytokines including interleukin-1ß (IL-1ß), tumor necrosis factor (TNF-α), and monocyte chemotactic protein-1 (MCP-1), overactivation of the nuclear factor (NF)-κB/c-Jun N-terminal kinase (JNK) pathway, as well as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis in response to pro-fibrotic damage. Additionally, the absence of JLP resulted in enhanced macrophage migration and fibroblast activation as paracrine effects elicited by injured TECs. In conclusion, the loss of JLP in TECs catalyses inflammatory injuries in the development of kidney fibrosis.

Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.

BACKGROUND: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. METHODS: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. FINDINGS: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. INTERPRETATION: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. FUNDING: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Effects of plastic aging on biodegradation of polystyrene by Tenebrio molitor larvae: Insights into gut microbiome and bacterial metabolism.

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 µm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae-1·d-1, respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them.

Hyaluronic Acid-Modified Micelles of Azithromycin and Quercetin Against Infections Caused by Methicillin-Resistant Staphylococcus Aureus.

Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA. Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated. Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors. Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.

S. glabra exerts anti-lung cancer effects by inducing ferroptosis and anticancer immunity.

BACKGROUND: Sarcandra glabra (S. glabra), a traditional Chinese medicine (TCM), has demonstrated significant anticancer activity; however, the underlying mechanisms have not yet been fully elucidated. PURPOSE: This study aimed to investigate the effects of S. glabra on lung cancer and to explore its underlying mechanisms. METHODS: The chemical profile of S. glabra was analyzed via ultrahigh-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The effects of S. glabra on the viability, proliferation, apoptosis, migration, and invasion of lung cancer cells were assessed via CCK8, colony formation, flow cytometry, scratch, and Transwell assays. In vivo anticancer activity was evaluated in an LLC mouse model. Proteomic analysis was performed to identify key molecules and pathways in S. glabra-treated LLC cells. The expression of ferroptotic proteins and associated cellular events were examined via western blotting, ROS production, iron accumulation, and lipid peroxidation assays. Immune modulation in tumor-bearing mice was evaluated by detecting immune cells and cytokines in the peripheral blood and tumor tissue. RESULTS: Our analysis quantified 1997 chemical markers in S. glabra aqueous extracts. S. glabra inhibited the viability and proliferation of lung cancer cells and induced cell cycle arrest and apoptosis. Scratch and Transwell assays demonstrated that S. glabra suppressed the migration and invasion of lung cancer cells. Oral administration of S. glabra significantly inhibited tumor growth in LLC tumor-bearing mice. Proteomic analysis revealed that S. glabra upregulated the expression of the HMOX1 protein and activated the ferroptosis pathway. Consistent with these findings, we found that S. glabra triggered ferroptosis in lung cancer cells, as evidenced by the upregulation of HMOX1, downregulation of GPX4 and ferritin light chain proteins, iron accumulation, increased ROS production, and lipid peroxidation. Furthermore, S. glabra demonstrated immunostimulatory properties in LLC tumor-bearing mice, leading to increased populations of immune cells (NK cells) and elevated cytokine levels (IL-2). CONCLUSION: This study is the first to demonstrate that S. glabra induces ferroptosis in lung cancer cells by regulating HMOX1, GPX4, and FTL. These findings provide a robust scientific basis for the clinical application of S. glabra in lung cancer treatment.

High-quality chromosome-level genomic insights into molecular adaptation to low-temperature stress in Madhuca longifolia in southern subtropical China.

BACKGROUND: Madhuca longifolia, the energy-producing and medicinal tropical tree originally from southern India, faces difficulties in adapting to the low temperatures of late autumn and early winter in subtropical southern China, impacting its usability. Therefore, understanding the molecular mechanisms controlling the ability of this species to adapt to environmental challenges is essential for optimising horticulture efforts. Accordingly, this study aimed to elucidate the molecular responses of M. longifolia to low-temperature stress through genomic and transcriptomic analyses to inform strategies for its effective cultivation and utilisation in colder climates. RESULTS: Herein, the high-quality reference genome and genomic assembly for M. longifolia are presented for the first time. Using Illumina sequencing, Hi-C technology, and PacBio HiFi sequencing, we assembled a chromosome-level genome approximately 737.92 Mb in size, investigated its genomic features, and conducted an evolutionary analysis of the genus Madhuca. Additionally, using transcriptome sequencing, we identified 17,941 differentially expressed genes related to low-temperature response. Through bioinformatics analysis of the WRKY gene family, 15 genes crucial for M. longifolia low-temperature resistance were identified. CONCLUSIONS: This research not only lays the groundwork for the successful ecological adaptation and cultivation of M. longifolia in China's southern subtropical regions but also offers valuable insights for the genetic enhancement of cold tolerance in tropical species, contributing to their sustainable horticulture and broader industrial, medicinal, and agricultural use.