A novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance.

The eradication of cancer stem cells (CSCs) with drug resistance confers the probability of local tumor control after chemotherapy or targeted therapy. As the main drug resistance marker, ABCG2 is also critical for colorectal cancer (CRC) evolution, in particular cancer stem-like traits expansion. Hitherto, the knowledge about the expression regulation of ABCG2, in particular its upstream transcriptional regulatory mechanisms, remains limited in cancer, including CRC. Here, ABCG2 was found to be markedly up-regulated in CRC CSCs (cCSCs) expansion and chemo-resistant CRC tissues and closely associated with CRC recurrence. Mechanistically, TOX3 was identified as a specific transcriptional factor to drive ABCG2 expression and subsequent cCSCs expansion and chemoresistance by binding to -261 to -141 segments of the ABCG2 promoter region. Moreover, we found that TOX3 recruited WDR5 to promote tri-methylation of H3K4 at the ABCG2 promoter in cCSCs, which further confers stem-like traits and chemoresistance to CRC by co-regulating the transcription of ABCG2. In line with this observation, TOX3, WDR5, and ABCG2 showed abnormal activation in chemo-resistant tumor tissues of in situ CRC mouse model and clinical investigation further demonstrated the comprehensive assessment of TOX3, WDR5, and ABCG2 could be a more efficient strategy for survival prediction of CRC patients with recurrence or metastasis. Thus, our study found that TOX3-WDR5/ABCG2 signaling axis plays a critical role in regulating CRC stem-like traits and chemoresistance, and a combination of chemotherapy with WDR5 inhibitors may induce synthetic lethality in ABCG2-deregulated tumors.

Selective Vulnerability of GABAergic Inhibitory Interneurons to Bilirubin Neurotoxicity in the Neonatal Brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here we report that bilirubin (BIL)-dependent cell death in auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated current (Ih), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca2+-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, Ih and death, compromising audition at young adult stage in HCN1+/+, but not in HCN1-/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca2+ overload, neuronal death and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.Significance Statement This study demonstrated that bilirubin preferentially targets GABAergic interneurons where it facilitates not only gating of HCN1 channels but also targeting of intracellular HCN1 to plasma membrane in calcium-dependent manner, resulting in neuronal hyperexcitability, injury and sensory dysfunction. These findings implicate HCN1 channel not only as a potential driver for auditory abnormalities in neonatal patients with bilirubin encephalopathy, but also potential intervention target for clinical management of neurological impairments associated with severe jaundice. Selective vulnerability of interneurons to neurotoxicity may be of general significance for understanding other forms of brain injury.

Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development.

Metabolites such as crotonyl-CoA and lactyl-CoA influence gene expression by covalently modifying histones, known as histone lysine crotonylation (Kcr) and lysine lactylation (Kla). However, the existence patterns, dynamic changes, biological functions and associations of these modifications with histone lysine acetylation and gene expression during mammalian development remain largely unknown. Here, we find that histone Kcr and Kla are widely distributed in the brain and undergo global changes during neural development. By profiling the genome-wide dynamics of H3K9ac, H3K9cr and H3K18la in combination with ATAC and RNA sequencing, we reveal that these marks are tightly correlated with chromatin state and gene expression, and extensively involved in transcriptome remodeling to promote cell-fate transitions in the developing telencephalon. Importantly, we demonstrate that global Kcr and Kla levels are not the consequence of transcription and identify the histone deacetylases (HDACs) 1-3 as novel 'erasers' of H3K18la. Using P19 cells as an induced neural differentiation system, we find that HDAC1-3 inhibition by MS-275 pre-activates neuronal transcriptional programs by stimulating multiple histone lysine acylations simultaneously. These findings suggest that histone Kcr and Kla play crucial roles in the epigenetic regulation of neural development.

PdMo bimetallene for oxygen reduction catalysis.

The efficient interconversion of chemicals and electricity through electrocatalytic processes is central to many renewable-energy initiatives. The sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER)1-4 has long posed one of the biggest challenges in this field, and electrocatalysts based on expensive platinum-group metals are often required to improve the activity and durability of these reactions. The use of alloying5-7, surface strain8-11 and optimized coordination environments12 has resulted in platinum-based nanocrystals that enable very high ORR activities in acidic media; however, improving the activity of this reaction in alkaline environments remains challenging because of the difficulty in achieving optimized oxygen binding strength on platinum-group metals in the presence of hydroxide. Here we show that PdMo bimetallene-a palladium-molybdenum alloy in the form of a highly curved and sub-nanometre-thick metal nanosheet-is an efficient and stable electrocatalyst for the ORR and the OER in alkaline electrolytes, and shows promising performance as a cathode in Zn-air and Li-air batteries. The thin-sheet structure of PdMo bimetallene enables a large electrochemically active surface area (138.7 square metres per gram of palladium) as well as high atomic utilization, resulting in a mass activity towards the ORR of 16.37 amperes per milligram of palladium at 0.9 volts versus the reversible hydrogen electrode in alkaline electrolytes. This mass activity is 78 times and 327 times higher than those of commercial Pt/C and Pd/C catalysts, respectively, and shows little decay after 30,000 potential cycles. Density functional theory calculations reveal that the alloying effect, the strain effect due to the curved geometry, and the quantum size effect due to the thinness of the sheets tune the electronic structure of the system for optimized oxygen binding. Given the properties and the structure-activity relationships of PdMo metallene, we suggest that other metallene materials could show great promise in energy electrocatalysis.

The herbicide bensulfuron-methyl inhibits rice seedling development by blocking calcium ion flux in the OsCNGC12 channel.

Identification of translocator protein-related genes involved in bensulfuron-methyl (BSM) uptake and transport in rice could facilitate the development of herbicide-tolerant cultivars by inactivating them. This study found that the OsCNGC12 mutants not only reduced BSM uptake but also compromised the Ca2 ⁺ efflux caused by BSM in the roots, regulating dynamic equilibrium of Ca2 ⁺ inside the cell and conferring non-target-site tolerance to BSM.

Mycorrhizal Types Regulate Tree Spatial Associations in Temperate Forests: Ectomycorrhizal Trees Might Favour Species Coexistence.

In temperate mixed forests, dominant ectomycorrhizal (EM) tree species usually coexist with diverse arbuscular mycorrhizal (AM) understorey tree species. Here, we investigated the spatial associations between AM and EM trees in two > 20 ha temperate forest mega-plots to better understand the observed 'EM-dominant versus AM-diverse' coexistence. Overall, we found that positive spatial associations (e.g., facilitation) were mostly related to EM trees, while negative spatial associations (e.g., inhibition) were mainly related to AM trees. Because adult EM trees tended to facilitate surrounding AM and EM saplings and other EM adults in these two forests, facilitation hotspots that stabilize AM-EM tree coexistence should be centred around EM tree species rather than around AM tree species. Together, we propose a novel EM-stabilization mechanism, which emphasises how, despite some species-specific variation, EM tree species foster 'EM-dominant versus AM-diverse' coexistence in temperate mixed forests by facilitating other trees.

Capsaicin mitigates ventilator-induced lung injury by suppressing ferroptosis and maintaining mitochondrial redox homeostasis through SIRT3-dependent mechanisms.

BACKGROUND: Ventilator-induced lung injury (VILI) is one of the severe complications in the clinic concerning mechanical ventilation (MV). Capsaicin (CAP) has anti-inflammatory and inhibitory effects on oxidative stress, which is a significant element causing cellular ferroptosis. Nevertheless, the specific role and potential mechanistic pathways through which CAP modulates ferroptosis in VILI remain elusive. METHODS: VILI was established in vivo, and the pulmonary epithelial cell injury model induced by circulation stretching (CS) was established in vitro. Both mice and cells were pretreated with CAP. Transmission electron microscopy, ELISA, Western blot, immunofluorescence, RT-PCR, fluorescent probes, and other experimental methods were used to clarify the relationship between iron death and VILI in alveolar epithelial cells, and whether capsaicin alleviates VILI by inhibiting iron death and its specific mechanism. RESULTS: Ferroptosis was involved in VILI by utilizing in vivo models. CAP inhibited ferroptosis and alleviated VILI's lung damage and inflammation, and this protective effect of CAP was dependent on maintaining mitochondrial redox system through SITR3 signaling. In the CS-caused lung epithelial cell injury models, CAP reduced pathological CS-caused ferroptosis and cell injury. Knockdown SIRT3 reversed the role of CAP on the maintaining mitochondria dysfunction under pathological CS and eliminated its subsequent advantageous impacts for ferroptosis against overstretching cells. CONCLUSION: The outcomes showed that CAP alleviated ferroptosis in VILI via improving the activity of SITR3 to suppressing mitochondrial oxidative damage and maintaining mitochondrial redox homeostasis, illustrating its possibility as a novel therapeutic goal for VILI.

Prognostic significance of the novel immunonutritional marker of cholesterol-to-lymphocyte ratio in patients with non-metastatic breast cancer.

BACKGROUND: Although there is a strong correlation between the novel cholesterol-to-lymphocyte ratio (CLR) and tumor survival, its prognostic significance in breast cancer (BC) is unknown. After analyzing the relationship between CLR and the overall survival (OS) of patients with BC, we created a predictive model. METHODS: Following retrospective enrollment, 1316 patients with BC were randomized into two cohorts: validation (n = 392) and training (n = 924). Distinct factors within the training dataset were identified for OS by univariate and multivariate Cox analyses; two-tailed P-value < 0.05 were considered to indicate statistical significance. On this premise, we developed novel signals for survival prediction and utilized the calibration curve, receiver operating characteristic curves, and concordance index (C-index) to validate their efficacy across both datasets. RESULTS: Patients with BC were categorized into two categories with differing prognoses based on the CLR score [hazard ratio = 0.492; 95% confidence interval (CI): 0.286-0.846, P = 0.009]. A prediction nomogram was created based on multivariate analysis, which showed that N stage, postoperative pathological categorization, and CLR score were all independently correlated with OS. In the training [C-index = 0.831 (95% CI: 0.788-0.874)] and validation [C-index = 0.775 (95% CI: 0.694-0.856)] cohorts, the nomogram demonstrated favorable performance in predicting OS. In both the training and validation cohorts, it outperformed the traditional staging system [C-index = 0.702 (95% CI: 0.623-0.782)] and [C-index = 0.709 (95% CI: 0.570-0.847)]. The accurate prediction by the signature was further demonstrated by the time-dependent receiver operating characteristic curves. CONCLUSIONS: The novel immunonutritional marker CLR could function as a simplified, cost-effective, easily accessible, non-invasive, and readily promotive prognostic indicator for patients with early-stage BC and demonstrates superior predictive power than the traditional staging system.

A quinoline-2-thione derivative as a novel chemotherapy drug candidate displays anti-tumor activity in vitro and in vivo.

Ovarian cancer is the fifth most prevalent cancer in women. Chemotherapy is a major treatment option for patients with advanced ovarian cancer (OC). Quinoline-2-thione and its derivatives are potential candidates for tumor therapy. In this study, we investigated the anticancer activity of the quinoline-2-thione derivative KA3D against ovarian cancer. The effect of KA3D on the viability of ovarian cancer cells was evaluated using MTT assay, and its effects on apoptosis and the cell cycle were detected using flow cytometry. Western blotting was performed to identify apoptosis-and cell cycle-related proteins altered by KA3D treatment. A xenograft model was used to verify the inhibitory effect of KA3D in vivo. H&E staining, biochemical indicator detection, and blood cell counts were used to observe the toxicity and side effects of KA3D. KA3D treatment impeded cell viability, induced apoptosis, and impeded the G2 phase of the cell cycle in ovarian cancer cells. Mechanistically, we found that KA3D enhanced the expression of proapoptotic molecules such as BAX and Caspase 3, while antiapoptotic proteins such as BCL2 were inhibited. The G0/G1 phase-related protein cyclin D1 was reduced and the G2 phase-related protein cyclin B1 was upregulated. In vivo, KA3D displayed potent anticancer activity, with no apparent toxicity in BABLC/c nude mice bearing SKOV3 cells. KA3D demonstrated remarkable chemotherapeutic drug efficacy in terms of significant cancer suppression in vitro and in vivo with low toxicity.

Prevalence and progression of pneumonia in immunocompetent adults with varicella.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Disturbance history, neighborhood crowding and soil conditions jointly shape tree growth in temperate forests.

Understanding how different mechanisms act and interact in shaping communities and ecosystems is essential to better predict their future with global change. Disturbance legacy, abiotic conditions, and biotic interactions can simultaneously influence tree growth, but it remains unclear what are their relative contributions and whether they have additive or interactive effects. We examined the separate and joint effects of disturbance intensity, soil conditions, and neighborhood crowding on tree growth in 10 temperate forests in northeast China. We found that disturbance was the strongest driver of tree growth, followed by neighbors and soil. Specifically, trees grew slower with decreasing initial disturbance intensity, but with increasing neighborhood crowding, soil pH and soil total phosphorus. Interestingly, the decrease in tree growth with increasing soil pH and soil phosphorus was steeper with high initial disturbance intensity. Testing the role of species traits, we showed that fast-growing species exhibited greater maximum tree size, but lower wood density and specific leaf area. Species with lower wood density grew faster with increasing initial disturbance intensity, while species with higher specific leaf area suffered less from neighbors in areas with high initial disturbance intensity. Our study suggests that accounting for both individual and interactive effects of multiple drivers is crucial to better predict forest dynamics.

Embryological characteristics and clinical outcomes of oocytes with different degrees of abnormal zona pellucida during assisted reproductive treatment.

Abnormalities in the zona pellucida (ZP) adversely affect oocyte maturation, embryo development and pregnancy outcomes. However, the assessment of severity is challenging. To evaluate the effects of different degrees of ZP abnormalities on embryo development and clinical outcomes, in total, 590 retrieval cycles were scored and divided into four categories (control, mild, moderate and severe) based on three parameters: perivitelline space, percentage of immature oocytes and percentage of oocytes with abnormal morphology. As the severity of abnormal ZP increased, both the number of retrieved oocytes and mature oocytes decreased. The fertilization rate did not differ significantly among groups. The rates of embryo cleavage and day-3 high-quality embryos in the mild group and the moderate group did not vary significantly between the two groups but were significantly higher than those in the severe group. The blastulation rates of the abnormal ZP groups were similar; however, they were lower than those of the control group. Moreover, the cycle cancellation rate of the severe abnormal ZP group was as high as 66.20%, which was significantly higher than that of the other three groups. Although the rates of cumulative clinical pregnancy and live births were lower than those in the control group, they were comparable among the abnormal ZP groups. There were no differences in the neonatal outcomes of the different groups. Together, ZP abnormalities show various degrees of severity, and in all patients regardless of the degree of ZP abnormalities who achieve available embryos, there will be an opportunity to eventually give birth.

The clinical application of affected-embryo-based SNP haplotype analysis for patients with de novo pathogenic mutations in PGT-M cycles.

PURPOSE: In preimplantation genetic testing for monogenic/single gene disorders (PGT-M) cycles, direct detection of the pathogenic mutation combined with indirect haplotype analysis are recommended to achieve accurate diagnosis. However, it poses a challenge to conduct haplotype analysis for patients carried de novo pathogenetic mutations or without no identified haplotype in families. Herein, the strategy of affected-embryo-based haplotype analysis was implemented in clinical practice to provide a convenient, economical and effective way for such patients. MATERIALS AND METHODS: Eight cases with de novo mutations were recruited. Six cases found the embryo-proband from biopsied blastocysts, and two case (case5 and 6) found them from developmental arrested embryos. A total of thirty-seven biopsied blastocysts from eight PGT-M cycles were performed direct detection and affected-embryo-based single nucleotide polymorphism (SNP) haplotype analyses. RESULTS: Till now, five cases (case 1, 2, 3, 7, 8) had delivered healthy babies and one case (case6) achieved successful ongoing pregnancy. We reported for the first time to find proband from developmental arrested embryos to complete haplotype analyses when no carriers were found in biopsied ones in clinical practice. CONCLUSION: Our study further proves and expands the application of the double-checking strategy based on affected-embryo proband and allows patients with de novo mutations or lack positive family members to benefit from the strategy.

A tumor-associated macrophages related model for predicting biochemical recurrence and tumor immune environment in prostate cancer.

OBJECTIVE: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa). METHODS: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis. RESULTS: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified. CONCLUSIONS: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa.

Determinants of tree population temporal stability in a temperate mixed forest over a gradient of nitrogen addition.

Nitrogen (N) deposition is a significant threat to the functioning of forests and negatively impacts the delivery of forest goods and services. Contemporary management approaches seek to adapt forests to such N-deposition stressors, but to date how plant populations in natural forests respond to N deposition and what factors determine the contrasting responses among populations are still unclear. Here, we investigated the impact of N-addition (control: 0 kg ha-1 yr-1; low: 25 kg ha-1 yr-1; medium: 50 kg ha-1 yr-1; high: 75 kg ha-1 ha yr-1) on tree population temporal stability and how initial tree size, mycorrhizal type, and leaf N content (LNC; as a surrogate for functional trait composition) mediate tree population responses to N-addition in a Korean pine and mixed broadleaved dominated temperate forest in northern China. We quantified tree species population temporal stability as the ratio of mean to standard deviation of the year-by-year stem increments recorded in individual trees from 2015 to 2022 experimental period. The results showed different temporal stabilities of tree species among four N-addition levels, with the highest population stability observed within the high N-addition plots. Furthermore, initial tree size had significantly (p < 0.001) positive effects on population temporal stability. The effect of LNC and initial tree size were also contingent on the level of N applied. Specifically, increase in tree population LNC reduced population temporal stability in all plots where N was added. Our results imply that retention of large-sized trees and species with resource-conservative strategies (e.g., low LNC) could enhance forest stability under N deposition.

Analysis of pollutant dispersion patterns in rivers under different rainfall based on an integrated water-land model.

In the context of rapid urban expansion, the interaction between humanity and nature has become more prominent. Urban land and rivers often exist as distinct entities with limited material exchange. However, during rainfall, these two systems interconnect, resulting in the transfer of land-derived pollutants into rivers. Such transfer significantly increases river pollutant levels, adversely affecting water quality. Therefore, developing a water quality simulation and prediction model is crucial. This model should effectively illustrate pollutant movement and dispersion during rain events. This study proposes a comprehensive model that merges the Storm Water Management Model (SWMM) with the Environmental Fluid Dynamics Code (EFDC). This integrated model assesses the spread and dispersion of pollutants, including Ammonia Nitrogen (NH3-N), Total Phosphorus (TP), Total Nitrogen (TN), and Chemical Oxygen Demand (COD), within urban water cycles for various rainfall conditions, thus offering critical theoretical support for managing the water environment. The application of this model under different rainfall intensities (light, moderate and heavy) provides vital insights. During light rainfall, the river's natural purification process can sustain surface water quality at Class IV. Moderate rainfall causes accumulation of pollutants, reducing water quality to Class V. Conversely, heavy rainfall rapidly increases pollutant concentrations due to higher inflow, pushing the river to a degraded Class V status, which is beyond its natural purification capacity, necessitating engineering solutions to reattain Class IV quality. Furthermore, pollutant accumulation in downstream river sections is more influenced by flow rate than by rainfall intensity. In summary, the SWMM-EFDC integrated model proves highly effective in predicting river water quality, thereby significantly aiding urban water pollution control.

Differentiation of closely-related species within Acinetobacter baumannii-calcoaceticus complex via Raman spectroscopy: a comparative machine learning analysis.

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Multi-Time-Scale Optimal Scheduling Strategy for Marine Renewable Energy Based on Deep Reinforcement Learning Algorithm.

Surrounded by the Shandong Peninsula, the Bohai Sea and Yellow Sea possess vast marine energy resources. An analysis of actual meteorological data from these regions indicates significant seasonality and intra-day uncertainty in wind and photovoltaic power generation. The challenge of scheduling to leverage the complementary characteristics of various renewable energy sources for maintaining grid stability is substantial. In response, we have integrated wave energy with offshore photovoltaic and wind power generation and propose a day-ahead and intra-day multi-time-scale rolling optimization scheduling strategy for the complementary dispatch of these three energy sources. Using real meteorological data from this maritime area, we employed a CNN-LSTM neural network to predict the power generation and load demand of the area on both day-ahead 24 h and intra-day 1 h time scales, with the DDPG algorithm applied for refined electricity management through rolling optimization scheduling of the forecast data. Simulation results demonstrate that the proposed strategy effectively meets load demands through complementary scheduling of wave power, wind power, and photovoltaic power generation based on the climatic characteristics of the Bohai and Yellow Sea regions, reducing the negative impacts of the seasonality and intra-day uncertainty of these three energy sources on the grid. Additionally, compared to the day-ahead scheduling strategy alone, the day-ahead and intra-day rolling optimization scheduling strategy achieved a reduction in system costs by 16.1% and 22% for a typical winter day and a typical summer day, respectively.