Case Report: Mycoplasma pneumoniae-associated acute pancreatitis.

Mycoplasma pneumoniae is the primary pathogen causing community-acquired pneumonia in children, accounting for approximately 10%-40% of cases. It can lead to various extrapulmonary complications, including acute pancreatitis, which has been reported in approximately 30 cases to date. Here, we report a 4-year-old girl who presented with fever, cough, and elevated levels of M. pneumoniae IgM antibodies, followed by the onset of abdominal pain, elevated lipase, and elevated blood and urine amylase. Abdominal CT implied diffuse inflammation of the pancreas. Serum inflammatory cytokines, such as interleukin (IL)-2, IL-6, IL-17A, tumor necrosis factor, and interferon-gamma, were elevated. After excluding other causes, it was determined that M. pneumoniae infection was the cause of her acute pancreatitis. She was treated with macrolides and glucocorticoids and ultimately made a full recovery. Therefore, acute pancreatitis should be included in the differential diagnosis for patients with M. pneumoniae infection who present with abdominal pain. Inflammatory cytokines may play a role in mediating pancreatic damage.

New Sesquiterpenoids from the Mangrove-Derived Fungus Talaromyces sp. as Modulators of Nuclear Receptors.

Four new sesquiterpenoids, talaroterpenes A-D (1-4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1-4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1-4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A-D (1-4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 µM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors.

Liver X receptor α contribution to neuroinflammation and glial cells activation induced by MPTP: Implications for Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder whose etiology remains unknown. The immune system has been implicated in hallmarks of PD including aggregation of α-synuclein and death of dopaminergic neurons in the substantia nigra. As a core regulator of immune response and inflammation, liver X receptors (LXRs) have been shown to have protective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. With two isoforms of LXRs (LXRα and LXRß) expressed in the brain, their roles and distributions in this tissue remain largely unexplored. Here, we used MPTP to mimic symptoms and biomedical changes seen in PD in LXRα-/- and wild-type mice to investigate the role of LXRα in the etiology and progression of PD. We found that MPTP is unable to induce motor deficits, anxiety-like behavior in LXRα-/- mice, which has been seen in WT mice. Gene ontology analysis of RNA sequencing revealed that knockout of LXRα led to enrichment of the process, including immune response and inflammation in the midbrain. In addition, MPTP did not lead to dopaminergic neuron death in the striatum and substantia nigra in LXRα-/- mice, the basal GFAP protein level, and pro-inflammatory cytokines were elevated in LXRα-/- mice. Lastly, the microglia activation and astrogliosis caused by MPTP intoxication we found in WT mice were abolished in LXRα-/- mice. To sum up, we conclude that LXRα is a critical regulator in MPTP intoxication and may play a unique role in astrogliosis seen in the neuroinflammation of PD.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization.

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1-overexpression (Prdx1-OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC0‒t , half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI.

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC-MS method.

N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC-MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs.

Tumorigenic role of Pak4 in ovarian cancer and its correlation with immune infiltration.

BACKGROUND: Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is still not clarified. METHODS: In this study, we used immunohistochemistry to investigate into Pak4 expression in different histological types of ovarian cancer. TIMER, TISCH2, GEPIA, ualcan, KM plotter, GSCA and GeneMANIA were used to identify the prognostic roles and gene regulation networks of Pak4 in ovarian cancer. Immune infiltration levels were investigated using TIMER database. RESULTS: Pak4 was highly expressed in ovarian cancers, regardless of different FIGO stages and histological grades. Single cell sequencing database proved that Pak4 was highly expressed in malignant ovarian cancer cells. Pak4 level was significantly correlated with different histological types of ovarian cancer. Pak4 expression was negatively connected with OS and PFS of ovarian cancer patients. Functions of Pak4 and its interacted genes were mainly involved in protein serine/threonine kinase activity, regulation of actin filament-based process and regulation of cytoskeleton organization. Pak4 level was negatively correlated with immune biomarkers of B cell infiltration (p = 2.39e-05), CD8 + T cell infiltration (p = 1.51e-04), neutrophil (p = 1.74e-06) and dendritic cell (p = 4.41e-08). Close correlation was found between Pak4 expression and T cell exhaustion (p < 0.05). CONCLUSIONS: Our results demonstrated the expression level, gene interaction networks and immune infiltration levels of Pak4 in ovarian cancer. And the results revealed role of Pak4 in tumorigenesis and the possibility to be a potential immunotherapeutic target.

Biogenic sulfur recovery from sulfate-laden antibiotic production wastewater using a single-chamber up-flow bioelectrochemical reactor.

The high-concentration sulfate (SO42-) in the antibiotic production wastewater hinders the anerobic methanogenic process and also proposes possible environmental risk. In this study, a novel single-chamber up-flow anaerobic bioelectrochemical reactor (UBER) was designed to realize simultaneous SO42- removal and elemental sulfur (S0) recovery. With the carbon felt, the cathode was installed underneath and the anode above to meet the different biological niches for sulfate reducing bacteria (SRB) and sulfur oxidizing bacteria (SOB). The bio-anode UBER (B-UBER) demonstrated a much higher average SO42- removal rate (SRR) of 113.2 ± 5.7 mg SO42--S L-1 d-1 coupled with a S0 production rate (SPR) of 54.4 ± 5.8 mg S0-S L-1 d-1 at the optimal voltage of 0.8 V than that in the abio-anode UBER (control reactor) (SRR = 86.6 ± 13.4 mg SO42--S L-1 d-1; SPR = 25.5 ± 9.7 mg S0-S L-1 d-1) under long-term operation. A large amount of biogenic S0 (about 72.2 mg g-1 VSS) was recovered in the B-UBER. The bio-anode, dominated by Thiovirga (SOB genus) and Acinetobacter (electrochemically active bacteria genus), exhibited a higher current density, lower overpotential, and lower internal resistance. C-type cytochromes mainly served as the crucial electron transfer mediator for both direct and indirect electron transfer, so that significantly increasing electron transfer capacity and biogenic S0 recovery. The reaction pathways of the sulfur transformation in the B-UBER were hypothesized that SRB utilized acetate as the main electron donor for SO42- reduction in the cathode zone and SOB transferred electrons to the anode or oxygen to produce biogenic S0 in the anode zone. This study proved a new pathway for biogenic S0 recovery and sulfate removal from sulfate-laden antibiotic production wastewater using a well-designed single-chamber bioelectrochemical reactor.

Efficacy of Targeted Scapular Stabilization Exercise Versus Conventional Exercise for Patients With Shoulder Pain: A Randomized Clinical Trial.

OBJECTIVE: The aim of the study is to investigate the efficacy of targeted scapular stabilization exercise in shoulder pain. DESIGN: This is an evaluator-blinded, multicenter, randomized controlled trial. The scapular stabilization exercise group ( n = 45) received scapular stabilization exercise based on the type of scapular dyskinesis for 6 wks; the conventional exercise group ( n = 45) received pendulum, wall climbing and stick exercises for 6 wks. Constant-Murley score, numerical rating scale, range of motion, type of scapular dyskinesis, lateral scapular sliding test, pectoralis minor index, scapular index, and satisfaction were assessed at baseline, 2-, 4-, and 6-wk treatment as well as a 6-wk follow-up. RESULTS: After a 6-wk intervention, the improvement of Constant-Murley score was greater in the scapular stabilization exercise group than in the conventional exercise group, and improvement continued at the 6-wk follow-up ( F = 15.39, P < 0.001, partial η 2 = 0.17). The results were also significant for numerical rating scale during activity, lateral scapular sliding test, pectoralis minor index, type of scapular dyskinesis, and satisfaction in favor of the scapular stabilization exercise group ( P < 0.05). CONCLUSIONS: Targeted scapular stabilization exercise is an effective intervention program that might be applied to the rehabilitation of shoulder pain.

Discovery of Anti-Hypercholesterolemia Agents Targeting LXRα from Marine Microorganism-Derived Natural Products.

A strategy integrating in silico molecular docking with LXRα and phenotypic assays was adopted to discover anti-hypercholesterolemia agents in a small library containing 205 marine microorganism-derived natural products, collected by our group in recent years. Two fumitremorgin derivatives, 12R,13S-dihydroxyfumitremorgin C (1) and tryprostatin A (3), were identified as potential LXRα agonists, by real-time qPCR and Western blot (WB) analysis, together with a surface plasmon resonance (SPR) assay. The anti-hypercholesterolemic effects of 1 and 3, together with their mechanisms, were investigated in depth using different cell and mouse models, among which the study of LXRα is of crucial importance. Compound 1 or 3 exhibited the capacity to effectively reverse excessive lipid accumulation in a hepatic steatosis cell model and significantly reduce liver damage and blood cholesterol levels in high cholesterol diet (HCD)-fed wild-type mice, whereas those beneficial effects were completely nullified in HCD-fed LXRα-knockout mice. Furthermore, 1 and 3 outperformed common LXRα agonists by suppressing the expression of sterol regulatory element-binding protein 1 (SREBP1) in HCD-fed mice, mitigating lipotoxicity. Thus, this study highlights the discovery of two marine microorganism-derived anti-hypercholesterolemia agents targeting LXRα.

Efficient sulfur atom-doped three-dimensional porous MXene-assisted sodium ion batteries.

Recently, it has been reported that MXene is a promising pseudocapacitive material for energy storage, primarily due to its intercalation mechanism. However, Ti3C2Tx MXenes face challenges, such as inadequate layer spacing and low specific capacity, which greatly hinder their potential as anode materials for sodium storage. In this study, MXene was doped with sulfur to create a three-dimensional porous structure that resulted in an increased layer spacing. The sulfur-doped porous MXene (SPM) demonstrated exceptional performance as sodium ion battery anodes, with a capacity of 335.2 mA h g-1 after 490 cycles at 2 A g-1 and a long-term cycling performance of 256.1 mA h g-1 even after 2480 cycles at 5 A g-1. It is worth noting that the porous structure formed after sulfur-doping exhibits superior sodium storage performance compared to previously reported MXene-based electrodes. This highlights the feasibility of the structural construction strategy, offering an effective solution for energy storage and conversion applications.

A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation.

Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.

Role and mechanism of MiR-542-3p in regulating TLR4 in nonylphenol-induced neuronal cell pyroptosis.

BACKGROUND: This study aimed to investigate the spatial learning/memory and motor abilities of rats and the alteration of miR-542-3p and pyroptosis in the midbrain nigrostriatal area in vivo after nonylphenol (NP) gavage and to explore the mechanism of miR-542-3p regulation of Toll-like receptor 4 (TLR4) in NP-induced pyroptosis in BV2 microglia in vitro. METHODS: In vivo: Thirty-six specific-pathogen-free-grade Sprague-Dawley rats were divided into three equal groups: blank control group (treated with pure corn oil), NP group (treated with NP, 80 mg/kg body weight per day for 90 days), and positive control group [treated with lipopolysaccharide (LPS), 2 mg/kg body weight for 7 days]. In vitro: The first part of the experiment was divided into blank group (control, saline), LPS group [1 µg/ml + 1 mM adenosine triphosphate (ATP)], and NP group (40 µmol/L). The second part was divided into mimics NC (negative control) group, miR-542-3p mimics group, mimics NC + NP group, and miR-542-3p mimics + NP group. RESULTS: In vivo: Behaviorally, the spatial learning/memory and motor abilities of rats after NP exposure declined, as detected via Y-maze, open field, and rotarod tests. Some microglia in the substantia nigra of the NP-treated rats were activated. The downregulation of miR-542-3p was observed in rat brain tissue after NP exposure. The mRNA/protein expression of pyroptosis-related indicators (TLR4), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin-D (GSDMD), cysteinyl aspartate-specific proteinase-1 (caspase-1), and interleukin-1ß (IL-1ß) in the substantia nigra of the midbrain increased after NP exposure. In vitro: ASC fluorescence intensity increased in BV2 cells after NP exposure. The mRNA and/or protein expression of pyroptosis-related indicators (TLR4, NLRP3, GSDMD, caspase-1, and IL-1ß) in BV2 cells was upregulated after NP exposure. The transfection of miR-542-3p mimics inhibited NP-induced ASC expression in BV2 cells. The overexpression of miR-542-3p, followed by NP exposure, significantly reduced TLR4, NLRP3, ASC, caspase-1, and IL-1ß gene and/or protein expression. CONCLUSIONS: This study suggested that NP exposure caused a decline in spatial learning memory and whole-body motor ability in rats. Our study was novel in reporting that the upregulation of miR-542-3p targeting and regulating TLR4 could inhibit NLRP3 inflammatory activation and alleviate NP-induced microglia pyroptosis.

Rapid fluctuations in functional connectivity of cortical networks encode spontaneous behavior.

Experimental work across species has demonstrated that spontaneously generated behaviors are robustly coupled to variations in neural activity within the cerebral cortex. Functional magnetic resonance imaging data suggest that temporal correlations in cortical networks vary across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these data generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior observed in awake animals. Here, we used wide-field mesoscopic calcium imaging to monitor cortical dynamics in awake mice and developed an approach to quantify rapidly time-varying functional connectivity. We show that spontaneous behaviors are represented by fast changes in both the magnitude and correlational structure of cortical network activity. Combining mesoscopic imaging with simultaneous cellular-resolution two-photon microscopy demonstrated that correlations among neighboring neurons and between local and large-scale networks also encode behavior. Finally, the dynamic functional connectivity of mesoscale signals revealed subnetworks not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide new insights into how behavioral information is represented across the neocortex and demonstrate an analytical framework for investigating time-varying functional connectivity in neural networks.

Circ ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 increases the stability of G9a and ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 messenger RNA through recruiting eukaryotic translation initiation factor 4A3, transcriptionally inhibiting PDZ and homeobox protein domain protein 1, and promotes the metastasis of hepatocellular carcinoma.

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.

An off-policy multi-agent stochastic policy gradient algorithm for cooperative continuous control.

Multi-agent reinforcement learning (MARL) algorithms based on trust regions (TR) have achieved significant success in numerous cooperative multi-agent tasks. These algorithms restrain the Kullback-Leibler (KL) divergence (i.e., TR constraint) between the current and new policies to avoid aggressive update steps and improve learning performance. However, the majority of existing TR-based MARL algorithms are on-policy, meaning that they require new data sampled by current policies for training and cannot utilize off-policy (or historical) data, leading to low sample efficiency. This study aims to enhance the data efficiency of TR-based learning methods. To achieve this, an approximation of the original objective function is designed. In addition, it is proven that as long as the update size of the policy (measured by the KL divergence) is restricted, optimizing the designed objective function using historical data can guarantee the monotonic improvement of the original target. Building on the designed objective, a practical off-policy multi-agent stochastic policy gradient algorithm is proposed within the framework of centralized training with decentralized execution (CTDE). Additionally, policy entropy is integrated into the reward to promote exploration, and consequently, improve stability. Comprehensive experiments are conducted on a representative benchmark for multi-agent MuJoCo (MAMuJoCo), which offers a range of challenging tasks in cooperative continuous multi-agent control. The results demonstrate that the proposed algorithm outperforms all other existing algorithms by a significant margin.

Discovery of a novel anti-osteoporotic agent from marine fungus-derived structurally diverse sirenins.

Thirteen new sirenin derivatives named eupenicisirenins C-O (1-13), along with a biosynthetically related known one (14), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data, quantum chemical calculations, and X-ray diffraction. Among them, eupenicisirenin C (1) exhibited the strongest NF-κB inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.

The creative behavior of virtual idol fans: a psychological perspective based on MOA theory.

Breakthroughs in digital technology are accelerating the development and commercialization of virtual idols. They are overturning the traditional one-way communication between idols and fans, turning fans into producers and consumers. Therefore, identifying the motivations for fan creation can regulate and guide the creative behavior of fans and turn their creativity into productivity. This paper took "the factors influencing fans' spontaneous participation in creating virtual idols" as the primary research question, took the Motivation Opportunity Ability (MOA) theory as the research framework, used questionnaires as the primary research method, and combined the relevant research on motivation theory and self-determination theory to explore fans' creative behavior from the psychological perspective in depth. The empirical tests revealed that in the motivation dimension, interest motivation, achievement motivation, social motivation, and utility motivation all positively influenced fans' creative behavior; in the opportunity dimension, fans' perceived cost had a significant negative moderating effect on the influence of interest motivation, social motivation, and utility motivation on fans' creative behavior; fans' perceived community atmosphere was substantial. The moderating effect of knowledge and skills on the capability dimension was insignificant. For the virtual idol industry, the future development of the industry could not only focus on IP image creation and content production but also effectively stimulate fans' creative motivation through the creation of an excellent community atmosphere, the provision of targeted creator services, and the reduction of fans' perceived costs in the creation process.

Pulmonary mucoepidermoid carcinoma in children: two case reports and a review of the literature.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor, particularly in children, and its clinical manifestations vary. When the tumor is small, it may be asymptomatic; however, with larger tumors, patients may present with symptoms such as recurring pneumonia, atelectasis, persistent cough, chest pain, and even hemoptysis. PMEC appears as an exophytic intrabronchial mass. This study aims to report on the clinical manifestations, imaging findings, treatment approaches, and prognosis of two children diagnosed with PMEC at our hospital between January 2018 and December 2022. The age of onset for both children was 9 years, and the masses were located in the right upper lobe bronchi. Following surgical treatment, both patients showed a good prognosis. In addition, we conducted a comprehensive review of the relevant literature to enhance the overall understanding of PMEC.