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

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

Interactome Analysis of ClpX Reveals Its Regulatory Role in Metabolism and Photosynthesis in Cyanobacteria.

Protein homeostasis is essential for cyanobacteria to maintain proper cellular function under adverse and fluctuating conditions. The AAA+ superfamily of proteolytic complexes in cyanobacteria plays a critical role in this process, including ClpXP, which comprises a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. Despite the physiological effects of ClpX on growth and photosynthesis, its potential substrates and underlying mechanisms in cyanobacteria remain unknown. In this study, we employed a streptavidin-biotin affinity pull-down assay coupled with label-free proteome quantitation to analyze the interactome of ClpX in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis). We identified 503 proteins as potential ClpX-binding targets, many of which had novel interactions. These ClpX-binding targets were found to be involved in various biological processes, with particular enrichment in metabolic processes and photosynthesis. Using protein-protein docking, GST pull-down, and biolayer interferometry assays, we confirmed the direct association of ClpX with the photosynthetic proteins, ferredoxin-NADP+ oxidoreductase (FNR) and phycocyanin subunit (CpcA). Subsequent functional investigations revealed that ClpX participates in the maintenance of FNR homeostasis and functionality in Synechocystis grown under different light conditions. Overall, our study provides a comprehensive understanding of the extensive functions regulated by ClpX in cyanobacteria to maintain protein homeostasis and adapt to environmental challenges.

CK1α deficiency impairs mouse uterine adenogenesis by inducing epithelial cell apoptosis through GSK3ß pathway and inhibiting Foxa2 expression through p53 pathway†.

Uterine glands and their secretions are crucial for conceptus survival and implantation in rodents and humans. In mice, the development of uterine gland known as adenogenesis occurs after birth, whereas the adenogenesis in humans initiates from fetal life and completed at puberty. Uterine adenogenesis involves dynamic epithelial cell proliferation, differentiation, and apoptosis. However, it is largely unexplored about the mechanisms governing adenogenesis. CK1α plays important roles in regulating cell division, differentiation, and death, but it is unknown whether CK1α affects adenogenesis. In the current study, uterus-specific CK1α knockout female mice (Csnk1a1d/d) were infertile resulted from lack of uterine glands. Subsequent analysis revealed that CK1α deletion induced massive apoptosis in uterine epithelium by activating GSK3ß, which was confirmed by injections of GSK3ß inhibitor SB216763 to Csnk1a1d/d females, and the co-treatment of SB216763 and CK1 inhibitor d4476 on cultured epithelial cells. Another important finding was that our results revealed CK1α deficiency activated p53, which then blocked the expression of Foxa2, an important factor for glandular epithelium development and function. This was confirmed by that Foxa2 expression level was elevated in p53 inhibitor pifithrin-α injected Csnk1a1d/d mouse uterus and in vitro dual-luciferase reporter assay between p53 and Foxa2. Collectively, these studies reveal that CK1α is a novel factor regulating uterine adenogenesis by inhibiting epithelial cell apoptosis through GSK3ß pathway and regulating Foxa2 expression through p53 pathway. Uncovering the mechanisms of uterine adenogenesis is expected to improve pregnancy success in humans and other mammals.

Enhancement and suppression of nonsequential double ionization by spatially inhomogeneous fields.

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

Observation of the possible magnetic correction above the Curie temperature in Cr2Si2Te6 single crystals.

Intrinsic magnetic semiconductors hold great promise in the fields of fundamental magnetization and spintronics. One such semiconductor is Cr2Si2Ti6 (CST), a quasi two-dimensional (2D) magnetic semiconductor with potential applications in future magnetic devices. However, the origin of ferromagnetism in CST remains a mystery. To investigate this, ac/dc susceptibility and electronic spin resonance (ESR) measurements were conducted. Based on ac susceptibility scaling, the critical temperature (TC) for the ferromagnetic (FM) to paramagnetic (PM) phase transition was found to be ∼32.5 K, with a critical exponent of δ = 6.7 from the critical isotherm, ß + γ = 1.72 from the temperature dependence of the crossover line, and γ = 1.43 from the temperature dependence of susceptibility along the same line. All critical exponents were found to be consistent with the dc magnetization scaling method. However, above and below TC, the origin of magnetism cannot be explained by a single theory. To explore the origin of abnormal magnetic critical behavior, ESR measurements were performed. Below T* ∼ 130 K, the ESR measurements revealed that the resonance field width (ΔH) tends to increase and decrease for the applied magnetic field H parallel and perpendicular to the c axis, respectively, indicating the onset of magnetic interaction even in the PM state. Meanwhile, the deviation from Curie-Weiss behavior below T* also confirmed the occurrence of magnetic correlation above the TC in CST. These observations suggest that the competition and cooperation among the direct and indirect interactions, the structural distortion and the van der Waals interaction at high temperature should be considered to investigate the origin of anomalous magnetism in CST. The present results provide valuable insights into the nature of ferromagnetism in 2D magnetic semiconductors.

Evaluating imaging repeatability of fully self-service fundus photography within a community-based eye disease screening setting.

PURPOSE: This study aimed to investigate the imaging repeatability of self-service fundus photography compared to traditional fundus photography performed by experienced operators. DESIGN: Prospective cross-sectional study. METHODS: In a community-based eye diseases screening site, we recruited 65 eyes (65 participants) from the resident population of Shanghai, China. All participants were devoid of cataract or any other conditions that could potentially compromise the quality of fundus imaging. Participants were categorized into fully self-service fundus photography or traditional fundus photography group. Image quantitative analysis software was used to extract clinically relevant indicators from the fundus images. Finally, a statistical analysis was performed to depict the imaging repeatability of fully self-service fundus photography. RESULTS: There was no statistical difference in the absolute differences, or the extents of variation of the indicators between the two groups. The extents of variation of all the measurement indicators, with the exception of the optic cup area, were below 10% in both groups. The Bland-Altman plots and multivariate analysis results were consistent with results mentioned above. CONCLUSIONS: The image repeatability of fully self-service fundus photography is comparable to that of traditional fundus photography performed by professionals, demonstrating promise in large-scale eye disease screening programs.

Defective nitrogen doped carbon material derived from nano-ZIF-8 for enhanced in-situ H2O2 generation and tetracycline hydrochloride degradation in electro-Fenton system.

Tetracycline hydrochloride (TC) accumulates in large quantities in the water environment, causing a serious threat to human health and ecological environment safety. This research focused on developing cost-effective catalysts with high 2e- selectivity for electro-Fenton (EF) technology, a green pollution treatment method. Defective nitrogen-doped porous carbon (d-NPC) was prepared using the metal-organic framework as the precursor to achieve in-situ H2O2 production and self-decomposition into high activity ·OH for degradation of TC combined with Co2+/Co3+. The d-NPC produced 172.1 mg L-1 H2O2 within 120 min, and could degrade 96.4% of TC in EF system. The self-doped defects and graphite-nitrogen in d-NPC improved the oxygen reduction performance and increased the H2O2 yield, while pyridine nitrogen could catalyze H2O2 to generate ·OH. The possible pathway of TC degradation was also proposed. In this study, defective carbon materials were prepared by ball milling, which provided a new strategy for efficient in-situ H2O2 production and the degradation of pollutants.

Bimetallic iron-nickel phosphide as efficient peroxymonosulfate activator for tetracycline hydrochloride degradation: Performance and mechanism.

Sulfate radical-based advanced oxidation processes with (SR-AOPs) are widely employed to degrade organic pollutants due to their high efficiency, cost-effectiveness and safety. In this study, a highly active and stable FeNiP was successfully prepared by reduction and heat treatment. FeNiP exhibited high performance of peroxymonosulfate (PMS) activation for tetracycline hydrochloride (TC) removal. Over a wide pH range, an impressive TC degaradation efficiency 97.86% was achieved within 60 min employing 0.1 g/L FeNiP and 0.2 g/L PMS at room temperature. Both free radicals of SO4·-, ·OH, ·O2- and non-free radicals of 1O2 participated the TC degradation in the FeNiP/PMS system. The PMS activation ability was greatly enhanced by the cycling between Ni and Fe bimetal, and the active site regeneration was achieved due to the existence of the negatively charged Pn-. Moreover, the FeNiP/PMS system exhibited substantial TC degradation levels in both simulated real-world disturbance scenarios and practical water tests. Cycling experiments further affirmed the robust stability of FeNiP catalyst, demonstrating sustained degradation efficiency of approximately 80% even after four cycles. These findings illuminate its promising potential across natural water bodies, presenting an innovative catalyst construction approach for PMS activation in the degradation of antibiotic pollutants.

Dynamic evolution and spatial difference of public health service supply in economically developed provinces of China: typical evidence from Guangdong Province.

OBJECTIVE: The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. METHODS: This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. RESULTS: Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. CONCLUSION: The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.

Total shoulder arthroplasty in patients with factor V Leiden.

BACKGROUND: Anatomic and reverse total shoulder arthroplasty (TSA) are effective treatment options for end-stage glenohumeral osteoarthritis. However, consideration for pre-existing conditions must be taken into account. Factor V Leiden (FVL), the most common inherited thrombophilia, is one such condition that predisposes to a prothrombotic state and may affect perioperative and longer-term outcomes following TSA. METHODS: Adult patients undergoing primary TSA for osteoarthritis indication were identified in the 2010 through October 2021 PearlDiver M157 database. Patients with or without FVL were matched at a 1:4 ratio based on age, sex, and Elixhauser Comorbidity Index. Ninety-day adverse events and 5-year revision rates were assessed and compared with multivariable logistic regression and rank-log tests, respectively. Finally, the relative use and bleeding/clotting outcomes were assessed based on venous thromboembolic (VTE) prophylactic agents used, with categories defined as (1) warfarin, heparin, or direct oral anticoagulant (DOAC) or (2) aspirin/no prescription found. RESULTS: Of 104,258 TSA patients, FVL was identified for 283 (0.27%). Based on matching, 1081 patients without FVL and 272 patients with FVL were selected. Multivariable analyses demonstrated that those with FVL displayed independently greater odds ratios (ORs) of deep vein thrombosis (DVT, OR = 9.50, P < .0001), pulmonary embolism (PE, OR = 10.10, P < .0001), and pneumonia (OR = 2.43, P = .0019). Further, these events contributed to the increased odds of aggregated minor (OR = 1.95, P = .0001), serious (OR = 6.38, P < .0001), and all (OR = 3.51, P < .0001) adverse events. All other individual 90-day adverse events, as well as 5-year revision rates, were not different between the study groups. When compared to matched patients without FVL on the same anticoagulant agents, FVL patients on warfarin, heparin, or DOAC agents demonstrated lesser odds of 90-day DVT and PE (OR = 4.25, P < .0001, and OR = 2.54, P = .0065) than those on aspirin/no prescription found (OR = 7.64 and OR = 21.95, P < .0001 for both). Interestingly, those on VTE prophylactic agents were not at greater odds of bleeding complications (hematoma or transfusion). DISCUSSION AND CONCLUSIONS: TSA patients with FVL present a difficult challenge to shoulder reconstruction surgeons. The current study highlights the strong risk of VTE that was reduced but still significantly elevated for those with stronger classes of VTE chemoprophylaxis. Acknowledging this risk is important for surgical planning and patient counseling, but also noted was the reassurance of similar 5-year revision rates for those with vs. without FVL.

RFID Adaptive Parallel Response Collision Tree Algorithm Based on Lock-Bit.

This paper proposes the Lock-Position-Based RFID Adaptive Parallel Collision Tree (LAPCT) algorithm to address the issues of excessive time slots required in the identification process of collision tree algorithms for multiple tags and the high communication complexity between the reader and multiple tags. The LAPCT algorithm adopts a single-query multiple-response mechanism and dynamically divides the response sub-cycle numbers in the identification cycle based on an adaptive strategy. It uses Manchester encoding to lock collision positions and generate a common query prefix, effectively reducing the number of reader queries. This reduction in queries decreases the total number of required time slots and transmitted bits during the reader-tag communication process, thereby improving the efficiency of multiple tag recognition. Theoretical and simulation experiments demonstrate that compared to similar algorithms, the LAPCT algorithm achieves a maximum reduction of 37% in total time slots required, a maximum improvement of 30% in recognition efficiency, and a maximum reduction of 90% in communication complexity. Furthermore, with an increase in the number of tags, the performance advantages of the LAPCT algorithm become more pronounced, making it suitable for large-scale tag scenarios.

A new multivariate index for ecological security assessment in the China-Myanmar border region.

The coordination of development efforts and ecological conservation in China's border regions is a significant challenge due to the overlap of biodiversity hotspots, ecologically fragile zones, and impoverished areas. Achieving the harmonious integration of ecological preservation and economic development relies on the fundamental assessment of ecological security (ES). However, comprehensive assessments of ES in border regions remain limited. This study introduces a new index, the multivariate ecological security index (MESI), which integrates ecosystem vigor, organization, elasticity, services and risk. Here, the MESI was utilized to assess the temporal and spatial changes in ES and its associated impact factors in the China-Myanmar border region (CMBR) from 2000 to 2020. The MESI provides a clear representation of the actual ES status in the CMBR, exhibiting a significant correlation with the eco-environmental quality index (EEQI; p < 0.01). The ES status exhibited notable spatial heterogeneity in the CMBR, consisting primarily of both relatively safe and safe levels, which accounted for approximately 85% of the total area. From 2000 to 2020, the CMBR experienced a gradual improvement in ES status, with the area experiencing an increase in the ES level accounting for 23.41% of the total area, which exceeded the proportion of the area experiencing a decrease in the ES level (4.71%). The combined impact of multiple factors exerted a greater influence on ES than did individual factors alone. Notably, human factors increasingly influenced the ES status during the study period. The results of this study provide valuable insights for ecological preservation and sustainable management in the CMBR, and the MESI can be extended to assess the ES of other regions.

Effect of fire and post-fire management on soil microbial communities in a lower subtropical forest ecosystem after a mountain fire.

Wildfires and post-fire management exert profound effects on soil properties and microbial communities in forest ecosystems. Understanding microbial community recovery from fire and what the best post-fire management should be is very important but needs to be sufficiently studied. In light of these gaps in our understanding, this study aimed to assess the short-term effects of wildfire and post-fire management on both bacteria and fungi community composition, diversity, structure, and co-occurrence networks, and to identify the principal determinants of soil processes influencing the restoration of these communities. Specifically, we investigated soil bacterial and fungal community composition, diversity, structure, and co-occurrence networks in lower subtropical forests during a short-term (<3 years) post-fire recovery period at four main sites in Guangdong Province, southern China. Our results revealed significant effects of wildfires on fungal community composition, diversity, and co-occurrence patterns. Network analysis indicated reduced bacterial network complexity and connectivity post-fire, while the same features were enhanced in fungal networks. However, post-fire management effects on microbial communities were negligible. Bacterial diversity correlated positively with soil microbial biomass nitrogen, soil organic carbon, and soil total nitrogen. Conversely, based on the best random forest model, fungal community dynamics were negatively linked to nitrate-nitrogen and soil water content. Spearman's correlation analysis suggested positive associations between bacterial networks and soil factors, whereas fungal networks exhibited predominantly negative associations. This study elucidates the pivotal role of post-fire management in shaping ecological outcomes. Additionally, it accentuates the discernible distinctions between bacterial and fungal responses to fire throughout a short-term recovery period. These findings contribute novel insights that bear significance in evaluating the efficacy of environmental management strategies.

mTORC1-GLUT1-mediated glucose metabolism drives hyperactivation of B cells in primary Sjogren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by B cell hyperactivation and hypergrammaglobulinemia. Currently, the role of metabolic pathways in the B cells of pSS patients is poorly defined. Here, we showed that upon cytosine phosphate-guanine (CpG)/sCD40L/IL-4 stimulation, B cells proportionally increased glycolysis and oxygen consumption, and compared with B cells from healthy controls (HCs), B cells from pSS patients exhibited higher glycolysis capacity and maximal oxidative respiration (OXPHOS). We also found that glucose transporter 1 (GLUT1) expression in B cells from pSS patients was significantly higher than that in B cells from HCs. Treatment with 2-deoxy-d-glucose (2-DG) inhibited the activation of B cells in pSS patients. Both 2-DG and Metformin inhibited the proliferation, formation of plasma/plasmablasts and decreased the IgG and IgM levels in the supernatants of B cells from pSS patients. Furthermore, inhibition of mTORC1 by rapamycin had an effect similar to that of 2-DG, suppressing B cell activation, proliferation and antibody production. Taken together, we demonstrated that B cells from pSS patients are more metabolically active than those from HCs and suggested that the mTORC1-GLUT1 glycolysis pathways were the major drivers of B cell hyperactivation and autoantibody production in pSS patients.

Localized Alkaline Environment via In Situ Electrostatic Confinement for Enhanced CO2-to-Ethylene Conversion in Neutral Medium.

Electrocatalytic CO2 reduction reaction (CO2RR) is one of the most promising routes to facilitate carbon neutrality. An alkaline electrolyte is typically needed to promote the production of valuable multi-carbon molecules (such as ethylene). However, the reaction between CO2 and OH- consumes a significant quantity of CO2/alkali and causes the rapid decay of CO2RR selectivity and stability. Here, we design a catalyst-electrolyte interface with an effective electrostatic confinement of in situ generated OH- to improve ethylene electrosynthesis from CO2 in neutral medium. In situ Raman measurements indicate the direct correlation between ethylene selectivity and the intensities of surface Cu-CO and Cu-OH species, suggesting the promoted C-C coupling with the surface enrichment of OH-. Thus, we report a CO2-to-ethylene Faradaic efficiency (FE) of 70% and a partial current density of 350 mA cm-2 at -0.89 V vs the reversible hydrogen electrode. Furthermore, the system demonstrated a 50 h stable operation at 300 mA cm-2 with an average ethylene FE of ∼68%. This study offers a universal strategy to tune the reaction micro-environment, and a significantly improved ethylene FE of 64.5% was obtained even in acidic electrolytes (pH = 2).

Unconventional Bilateral Compressive Strained Ni-Ir Interface Synergistically Accelerates Alkaline Hydrogen Oxidation.

The alkaline hydrogen oxidation reaction (HOR) involves the coupling of adsorbed hydrogen (Had) and hydroxyl (OHad) species and is thus orders of magnitude slower than that in acid media. According to the Sabatier principle, developing electrocatalysts with appropriate binding energy for both intermediates is vital to accelerating the HOR though it is still challenging. Herein, we propose an unconventional bilateral compressive strained Ni-Ir interface (Ni-Ir(BCS)) as efficient synergistic HOR sites. Density functional theory (DFT) simulations reveal that the bilateral compressive strain effect leads to the appropriate adsorption for both Had and OHad, enabling their coupling thermodynamically spontaneous and kinetically preferential. Such Ni-Ir(BCS) is experimentally achieved by embedding sub-nanometer Ir clusters in graphene-loaded high-density Ni nanocrystals (Ni-Ir(BCS)/G). As predicted, it exhibits a HOR mass activity of 7.95 and 2.88 times those of commercial Ir/C and Pt/C together with much enhanced CO tolerance, respectively, ranking among the most active state-of-the-art HOR catalysts. These results provide new insights into the rational design of advanced electrocatalysts involving coordinated adsorption and activation of multiple reactants.

Cascade-Activated AIEgen-Peptide Probe for Noninvasively Monitoring Chymotrypsin-like Activity of Proteasomes in Cancer Cells.

Noninvasive monitoring of chymotrypsin-like (ChT-L) activity of proteasomes is of great significance for the diagnosis and prognosis of various cancers. However, commercially available proteasome probes usually lack adequate cancer-cell selectivity. To noninvasively monitor ChT-L activity of proteasomes in living cells, we rationally designed a cascade-activated AIEgen-peptide probe (abbreviated as TPE-1p), which self-assembled in aqueous solution to exhibit bright fluorescence in response to sequential treatment of alkaline phosphatase (ALP) and ChT-L. Transmission electron microscopy, enzymatic kinetics, and in vitro fluorescence experiments validated that TPE-1p was efficiently dephosphorylated by ALP to generate TPE-1, which was recognized by ChT-L in the proteasome, and transformed to form nanofibers with strong fluorescence signals. Cell imaging experiments revealed that bright blue fluorescence was observed in TPE-1p-treated HeLa cells, whereas NIH3T3 and HepG2 cells showed less fluorescence at the same condition. The enhanced fluorescence signals in HeLa cells were attributed to the high activities of endogenous ALP and ChT-L. Moreover, TPE-1p was utilized to noninvasively assess the inhibition efficiency of a ChT-L inhibitor (bortezomib, abbreviated as Btz) in HeLa cells. Significant correlation was found between the fluorescence signals of TPE and the viabilities of Btz-treated cells in concentration ranges from 0 to 1 µM, indicating that TPE-1p could be employed to predict the activity of ChT-L inhibitors. The design of the cascade-activated AIEgen-peptide probe provides a viable approach for noninvasively monitoring the ChT-L activity of proteasomes in living cells, which facilitates high-throughput screening of ChT-L inhibitors in cancer therapy.

A Dual-Responsive Morphologically-Adaptable Nanoplatform for Targeted Delivery of Activatable Photosensitizers in Precision Photodynamic Therapy.

Photodynamic therapy (PDT) is an effective approach for treating melanoma. However, the photosensitizers employed in PDT can accumulate in healthy tissues, potentially causing harm to normal cells and resulting in side effects such as heightened photosensitivity. To address this, an activatable photosensitizer (PSD) by linking PpIX with a fluorescence quencher using a disulfide bond is designed. PSD responded to endogenous GSH, showing high selectivity for A375 cells. To enhance PSD's bioavailability and anticancer efficacy, an enzyme-responsive nanoplatform based on a lonidamine-derived self-assembling peptide is developed. Initially, PSD and the peptide self-assembled into nanoparticles, displaying potent tumor targeting of PSD in vivo. Upon cell uptake, these nanoparticles specifically responded to elevated cathepsin B, causing nanoparticle disintegration and releasing PSD and lonidamine prodrug (LND-1). PSD is selectively activated by GSH for cancer-specific fluorescence imaging and precision PDT, while LND-1 targeted mitochondria, forming a fibrous lonidamine depot in situ and intensifying photosensitizer's cytotoxicity through ROS generation, mitochondrial dysfunction, and DNA damage. Notably, intravenous administration of LND-1-PEG@PSD with light irradiation significantly suppressed A375-xenografted mouse tumor growth, with minimal systemic toxicity. Together, the synergy of activatable photosensitizer and enzyme-responsive nanoplatform elevates PDT precision and diminishes side effects, showcasing significant potential in the realm of cancer nanomedicine.

Comparative cytogenetic analysis of diploid and triploid pacific abalone, Haliotis discus hannai.

Cytogenetic analysis of triploid Haliotis discus hannai larvae (produced by chemical treatment) and its diploids were performed. The results showed that triploid H. discus hannai had a chromosome number of 3n = 54, consisting of 30 metacentric (m) and 24 submetacentric (sm) chromosomes, while the diploids had a chromosome number of 2n = 36, consisting of 20 metacentric (m) and 16 submetacentric (sm) chromosomes. Notably, both triploids and diploids displayed variation in the number of NORs and/or their diameter. The average number of NORs was significantly higher in triploids than in diploids (P < 0.05), while there was no significant difference in the average diameter of NORs between the two groups (P > 0.05). Additionally, 5S rDNA localization to 3 submetacentric chromosomes was observed in triploids, compared to 2 submetacentric chromosomes in diploids. The number of 18S rDNA sites displayed positional conservancy and quantitative variability in both diploids and triploids. Specifically, 18S rDNA was found at the end of the chromosome in both groups, with triploids exhibiting a significantly higher number of loci than diploids (P < 0.01). This study provides valuable insights into the cytogenetic characteristics of triploid H. discus hannai, which could facilitate further research on the stability of the chromosome set in this species.

Comparison of the relative efficacy of ß-lactam/ß-lactamase inhibitors and carbapenems in the treatment of complicated urinary tract infections caused by ceftriaxone-non-susceptible Enterobacterales: a multicentre retrospective observational cohort study.

BACKGROUND: Treating complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales represents a significant clinical challenge. The present study was thus developed to explore the relative efficacy of ß-lactam/ß-lactamase inhibitors (BLBLIs) and carbapenems for the treatment of hospitalized patients suffering from cUTIs caused by BLBLI-susceptible ceftriaxone-non-susceptible Enterobacterales. METHODS: Data from 557 patients from four Chinese teaching hospitals diagnosed with cUTIs caused by ceftriaxone-non-susceptible Enterobacterales from January 2017 to May 2022 were retrospectively assessed. RESULT: The 30 day rate of treatment failure, defined by unresolved symptoms or mortality, was 10.4% (58/557). Independent predictors of 30 day treatment failure included immunocompromised status, bacteraemia, septic shock, lack of infection source control and appropriate empirical treatment. When data were controlled for potential confounding variables, BLBLI treatment exhibited a comparable risk of 14 day (OR 1.61, 95% CI 0.86-3.00, P = 0.133) and 30 day treatment failure (OR 1.45, 95% CI 0.66-3.15, P = 0.354) relative to carbapenem treatment for the overall cohort of patients. In contrast, BLBLI treatment in immunocompromised patients was associated with an elevated risk of both 14 day (OR 3.18, 95% CI 1.43-7.10, P = 0.005) and 30 day treatment failure (OR 3.06, 95% CI 1.07-8.80, P = 0.038) relative to carbapenem treatment. CONCLUSIONS: These results suggested that carbapenem treatment may be superior to BLBLI treatment for immunocompromised patients suffering from cUTIs caused by ceftriaxone-non-susceptible Enterobacterales species. However, these results will need to be validated in appropriately constructed randomized controlled trials to ensure appropriate patient treatment.