Optimal distributed time-varying formation control for second-order multiagent systems: LQR-based method.

The optimal leaderless and leader-following time-varying formation (TVF) control problems for second-order multiagent systems (MASs) are investigated, where two optimal TVF control protocols are proposed to achieve the desired formations as well as minimize the comprehensive optimization function that contain the cooperative performance index and the control energy index. For leaderless case, the optimal formation control problem is reformulated as an infinite-time state regulator problem by employing the state space decomposition method, which is subject to specified constraints on energy and performance indices, and the analytic criterion for optimal TVF achievability is subsequently proposed. Then, the results of optimal leaderless TVF control are extended to the leader-following case with switching topologies, where the main challenge is changed to find the optimal controller rather than the optimal gain matrix, and the optimal value of the comprehensive index is accurately determined. Finally, two simulation cases are proposed to validate the effectiveness of the theoretical results, and comparisons with previous works are presented to expound the optimality of the proposed formation control method.

Serum metabolomic profile of myasthenia gravis and potential values as biomarkers in disease monitoring.

OBJECTIVE: Serum metabolites from 19 myasthenia gravis (MG) patients and 15 normal controls were analyzed via untargeted metabolomics, including 6 pre/post-treatment paired MG patients, to assess the value of serum metabolites as biomarkers in monitoring MG. METHOD: Differential metabolites between MG patients and normal controls were identified through liquid and gas chromatography-mass spectrometry simultaneously. Principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify the differential metabolites. Candidate metabolites and pathways associated with MG were selected through a random forest machine learning model. RESULT: A total of 310 differential metabolites were identified with a threshold of variable projected importance > 1 and P value < 0.05. Among these, 158 metabolites were upregulated and 152 were downregulated. The random forest machine learning model selected 5 metabolites as potential biomarkers associated with MG: lignoceric acid (AUC=0.944), uridine diphosphate-N-acetylglucosamine (AUC=0.951), arachidonic acid (AUC=0.951), beta-glycerophosphoric acid (AUC=0.933), and L-Asparagine (AUC=0.877). Further analysis using 6 paired MG patients pre- and post-immunosuppression treatment revealed 25 upregulated and 6 downregulated metabolites in post-treatment serum, which might be relevant to disease intervention. The significance remains elusive due to the limited number of patients. CONCLUSION: A subset of differential metabolites was identified in the serum of MG patients, some of which changed with immunosuppressive therapy. Small molecule metabolites may serve as valuable biomarkers for disease monitoring in MG.

Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris.

INTRODUCTION: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods: Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. FINDINGS: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). INTERPRETATION: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

Synthesis of Hexabenzocoronene-cored Graphdiyne Nanosheets through Dehydrogenative Coupling on Au(111) Surface.

Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize 𝜋-conjugated carbon nanostructures with atomic precision. However, this protocol has rarely been utilized to fabricate structurally defined carbon nanosheets composed of sp- and sp2-hybridized carbon atoms. Here, we present the synthesis of butadiyne-linked hexabenzocoronenes (HBCs) on Au(111) surfaces as core-expanded graphdiynes. The reaction started from hexa(4-ethylphenyl)benzene, which undergoes dehydrogenation toward hexa(4-vinylphenyl)benzene, followed by planarization to hexabenzocoronene, coupling between the vinyl groups, and further dehydrogenation. In addition to butadiyne linkages, benzene groups were also found as another type of linker. The reaction sequences were monitored by scanning tunneling microscopy and bond-resolved non-contact atomic force microscopy, which disclose the structures of intermediates and final products. In combination with density functional theory simulations, the key steps from ethyl substituents to butadiyne and benzene linkers were elucidated. This is a new on-surface synthesis of core-expanded graphdiynes with unprecedented electronic properties.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

Elucidating trauma-related and disease-related regional cortical activity in post-traumatic stress disorder.

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder-related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.

Paenalcaligenes faecalis sp. nov., a novel species of the family Alcaligenaceae isolated from chicken faeces.

A Gram-negative, motile, rod-shaped aerobic and alkalogenic bacterium, designated as strain YLCF04T, was isolated from chicken faeces. Its growth was optimal at 28 °C (range, 10-40 °C), pH 8 (range, pH 6-9) and in 1 % (w/v) NaCl (range, 0-10 %). It was classified to the genus Paenalcaligenes and was most closely related to Paenalcaligenes hominis CCUG 53761AT (97.5 % similarity) based on 16S rRNA gene sequence analysis. Average nucleotide identity and digital DNA-DNA hybridization values between YLCF04T and P. hominis CCUG 53761AT were 76.3 and 18.2 %, respectively. Strain YLCF04T has a genome size of 2.7 Mb with DNA G+C content of 46.3 mol%. Based on its phylogenetic, genomic, phenotypic and biochemical characteristics, strain YLCF04T represents a novel species of the genus Paenalcaligenes, for which the name Paenalcaligenes faecalis sp. nov. is proposed. The type strain is YLCF04T (=CCTCC AB 2022359T= KCTC 92789T).

Unraveling the mechanism of thermotolerance by Set302 in Cryptococcus neoformans.

The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity.

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity.

Advances in MXene surface functionalization modification strategies for CO2 reduction.

MXenes, 2D transition metal carbides and nitrides, show great potential in electrocatalytic CO2 reduction reaction (ECO2RR) applications owing to their tunable structure, abundant surface functional groups, large specific surface area and remarkable conductivity. However, the ECO2RR has a complex pathway involving various reaction intermediates. The reaction process yields various products alongside a competitive electrolytic water-splitting reaction. These factors limit the application of MXenes in ECO2RRs. Therefore, this review begins by examining the functionalized modification of MXenes to enhance their catalytic activity and stability via the regulation of interactions between carriers and the catalytic centre. The review firstly covers the synthesis methods and characterisation techniques for functionalized MXenes reported in recent years. Secondly, it presents the methods applied for the functionalized modification of carriers through surface loading of single atoms, clusters, and nanoparticles and construction of composites. These methods regulate the stability, active sites, and metal-carrier electronic interactions. Finally, the article discusses the challenges, opportunities, pressing issues, and future prospects related to MXene-based electrocatalysts.

Rules for dissipationless topotronics.

Topological systems hosting gapless boundary states have attracted huge attention as promising components for next-generation information processing, attributed to their capacity for dissipationless electronics. Nevertheless, recent theoretical and experimental inquiries have revealed the emergence of energy dissipation in precisely quantized electrical transport. Here, we present a criterion for the realization of truly no-dissipation design, characterized as Nin = Ntunl + Nbs, where Nin, Ntunl, and Nbs represent the number of modes participating in injecting, tunneling, and backscattering processes, respectively. The key lies in matching the number of injecting, tunneling, and backscattering modes, ensuring the equilibrium among all engaged modes inside the device. Among all the topological materials, we advocate for the indispensability of Chern insulators exhibiting higher Chern numbers to achieve functional devices and uphold the no-dissipation rule simultaneously. Furthermore, we design the topological current divider and collector, evading dissipation upon fulfilling the established criterion. Our work paves the path for developing the prospective topotronics.

Abnormal sleep patterns are associated with depressive symptoms in Chinese community-dwelling older adults.

OBJECTIVE: Depression is an important public health issue among older adults, often associated with their sleep-related problems. We aimed to investigate the association between sleep-related problems and depressive symptoms among Chinese community-dwelling older adults. METHODS: This cross-sectional study utilized self-reported data from 2896 participants (aged ≥60 years) from Shanghai, China. Nocturnal sleep duration and difficulty initiating sleep (DIS) symptoms were obtained through face-to-face questionnaires. Nocturnal sleep duration was categorized as 'short' (<7 h), 'normal' (7-8 h), and 'long' (>8 h). Subsequently, the 3 groups were further divided into 6 groups based on the presence of DIS, and the combined sleep behaviors were termed 'sleep patterns'. Logistic regression was conducted to assess the association of sleep variables and sleep patterns with the risk of depressive symptoms. RESULTS: Compared to the reference group, 'short sleep duration' and DIS symptoms were associated with depressive symptoms (with odds ratios (OR) of 1.50 and 1.79, respectively, with 95% confidence intervals (CI) of 1.14-1.97 and 1.39-2.31). When compared to 'normal sleep duration without DIS', both 'short sleep duration with DIS' (OR = 2.60, 95% CI: 1.81-3.72) and 'normal sleep duration with DIS' (OR = 1.60, 95% CI: 1.03-2.49) were statistically associated with depressive symptoms in adjusted regression models. CONCLUSION: Short sleep duration and DIS symptoms were found to be associated with depressive symptoms. Combining DIS symptoms with sleep duration, DIS was identified as a risk factor for elevated depressive symptoms in individuals with short and normal sleep durations. In managing depressive symptoms, it is imperative to thoroughly evaluate insomnia and nighttime sleep, which can provide valuable insights for nursing and medical policy.

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Comparisons of pharmacokinetics and tissue distribution of six major bioactive components of the herbal pair Alpinia officinarum-Cyperus rotundus in normal and primary dysmenorrhea rats.

The Liangfu formula, as described in 'Liangfang Jiye', is well-known for its efficacy in treating stomach pain, abdominal pain, and dysmenorrhea. This research aimed to investigate the pharmacokinetics and tissue distribution of 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone (DPHA), Galangin, Kaempferide, 5-Hydroxy-1,7-diphenyl-3-heptanone (DPHC), α-Cyperone, and Nootkatone in vivo using an LC-MS/MS method. The method successfully separated the six active components and internal standards (Chrysin and Yakuchinone-A) on an XB-C18 column with a mobile phase of 0.2 ‰ formic acid water-acetonitrile. It demonstrated good linearity with a correlation coefficient (r2) ≥ 0.9911 and a lower limit of quantification (LLOQ) of 5-80 ng/mL for the different components. Precision, accuracy, matrix effects, and recovery rates were within acceptable ranges. Pharmacokinetic analysis revealed significant differences in parameters between primary dysmenorrhea (PD) and normal rats (especially AUC, Tmax, and CLz/F). Tissue distribution showed that the six active components of the herbal pair Alpinia officinarum Hance-Cyperus rotundus L. (HPAC) extract was primarily distributed in the liver, lung, and kidney. This study offers valuable insights into the potential mechanisms of action and drug development for treating PD.

Interplay between Wnt signaling molecules and exosomal miRNAs in breast cancer (Review).

Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial­mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.

A complete review on the oxygen-containing functional groups of biochar: Formation mechanisms, detection methods, engineering, and applications.

Biochar is a porous carbon material generated by the thermal treatment of biomass under anaerobic or anoxic conditions with wealthy Oxygen-containing functional groups (OCFGs). To date, OCFGs of biochar have been extensively studied for their significant utility in pollutant removal, catalysis, capacitive applications, etc. This review adopted a whole system philosophy and systematically summarizes up-to-date knowledge of formation, detection methods, engineering, and application for OCFGs. The formation mechanisms and detection methods of OCFGs, as well as the relationships between OCFGs and pyrolysis conditions (such as feedstocks, temperature, atmosphere, and heating rate), were discussed in detail. The review also summarized strategies and mechanisms for the oxidation of biochar to afford OCFGs, with the performances and mechanisms of OCFGs in the various application fields (environmental remediation, catalytic biorefinery, and electrode material) being highlighted. In the end, the future research direction of biochar OCFGs was put forward.

Hydroxyapatite Nanoparticles Promote the Development of Bone Microtissues for Accelerated Bone Regeneration by Activating the FAK/Akt Pathway.

Scaffold-free bone microtissues differentiated from mesenchymal stem cell (MSC) spheroids offer great potential for bottom-up bone tissue engineering as a direct supply of cells and osteogenic signals. Many biomaterials or biomolecules have been incorporated into bone microtissues to enhance their osteogenic abilities, but these materials are far from clinical approval. Here, we aimed to incorporate hydroxyapatite (HAP) nanoparticles, an essential component of bone matrix, into MSC spheroids to instruct their osteogenic differentiation into bone microtissues and further self-organization into bone organoids with a trabecular structure. Furthermore, the biological interaction between HAP nanoparticles and MSCs and the potential molecular mechanisms in the bone development of MSC spheroids were investigated by both in vitro and in vivo studies. As a result, improved cell viability and osteogenic abilities were observed for the MSC spheroids incorporated with HAP nanoparticles at a concentration of 30 µg/mL. HAP nanoparticles could promote the sequential expression of osteogenic markers (Runx2, Osterix, Sclerostin), promote the expression of bone matrix proteins (OPN, OCN, and Collagen I), promote the mineralization of the bone matrix, and thus promote the bone development of MSC spheroids. The differentiated bone microtissues could further self-organize into linear, lamellar, and spatial bone organoids with trabecular structures. More importantly, adding FAK or Akt inhibitors could decrease the level of HAP-induced osteogenic differentiation of bone microtissues. Finally, excellent new bone regeneration was achieved after injecting bone microtissues into cranial bone defect models, which could also be eliminated by the Akt inhibitor. In conclusion, HAP nanoparticles could promote the development of bone microtissues by promoting the osteogenic differentiation of MSCs and the formation and mineralization of the bone matrix via the FAK/Akt pathway. The bone microtissues could act as individual ossification centers and self-organize into macroscale bone organoids, and in this meaning, the bone microtissues could be called microscale bone organoids. Furthermore, the bone microtissues revealed excellent clinical perspectives for injectable cellular therapies for bone defects.

Automated machine learning-aided prediction and interpretation of gaseous by-products from the hydrothermal liquefaction of biomass.

Hydrothermal liquefaction (HTL) is a thermochemical conversion technology that produces bio-oil from wet biomass without drying. However, by-product gases will inevitably be produced, and their formation is unclear. Therefore, an automated machine learning (AutoML) approach, automatically training without human intervention, was used to aid in predicting gaseous production and interpreting the formation mechanisms of four gases (CO2, CH4, CO, and H2). Specifically, four accurate optimal single-target models based on AutoML were developed with elemental compositions and HTL conditions as inputs for four gases. Herein, the gradient boosting machine (GBM) performed excellently with train R2 ≥ 0.99 and test R2 ≥ 0.80. Then, the screened GBM algorithm-based ML multi-target models (maximum average test R2 = 0.89 and RMSE = 0.39) were built to predict four gases simultaneously. Results indicated that biomass carbon, solid content, pressure, and biomass hydrogen were the top four factors for gas production from HTL of biomass. This study proposed an AutoML-aided prediction and interpretation framework, which could provide new insight for rapid prediction and revelation of gaseous compositions from the HTL process.

SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

Wnt/ß-catenin signaling inhibits oxidative stress-induced ferroptosis to improve interstitial cystitis/bladder pain syndrome by reducing NF-κB.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder syndrome of unknown etiology. Reactive oxygen species (ROS) plays a major role in ferroptosis and bladder dysfunction of IC/BPS, while the role of ferroptosis in IC/BPS progression is still unclear. This study aims to investigate the role and mechanism of ROS-induced ferroptosis in IC/BPS using cell and rat model. METHODS: We collected IC/BPS patient bladder tissue samples and established a LPS-induced IC/BPS rat model (LRM). The level of oxidative stress and ferroptosis in IC/BPS patients and LRM rats was analyzed. Function and regulatory mechanism of ferroptosis in IC/BPS were explored by in vitro and in vivo experiments. RESULTS: The patients with IC/BPS showed mast cells and inflammatory cells infiltration in bladder epithelial tissues. Expression of NRF2 was up-regulated, and GPX4 was decreased in IC/BPS patients compared with normal tissues. IC model cells underwent oxidative stress, which induced ferroptosis. These above results were validated in LRM rat models, and inhibition of ferroptosis ameliorated bladder dysfunction in LRM rats. Wnt/ß-catenin signaling was deactivated in IC/BPS patients and animals, and activation of Wnt/ß-catenin signaling reduced cellular free radical production, thereby inhibited ferroptosis in IC model cells. Mechanistically, the Wnt/ß-catenin signaling pathway inhibited oxidative stress-induced ferroptosis by down-regulating NF-κB, thus contributing to recover IC/BPS both in vitro and in vivo. CONCLUSIONS: We demonstrate for the first time that oxidative stress-induced ferroptosis plays an important role in the pathology of IC/BPS. Mechanistically, the Wnt/ß-catenin signaling suppressed oxidative stress-induced ferroptosis by down-regulating NF-κB to improve bladder injury in IC/BPS.