Crystallization-Induced Dimerization and Solution-Phase Bond Dissociation of Stable Dibenzoolympicenyl Radicals.

Crystallization of organic materials can lead to different assembly structure with different reactivity, but this phenomenon is rarely observed for delocalized hydrocarbon radicals. This report introduces a crystallization-induced radical-radical coupling reaction, which employs a series of stable nonplanar organic π-radicals as reactants. Six stable radical congeners are synthesized, resulting in radical-radical coupling at the allenyl radical site during crystallization to produce close-shell dimers. This coupling reaction is absent in the solution phase, which highlights the importance of preorganization in the lattice. Remarkably, the attempts of cocrystallization of different congeners yielded homocoupling products instead of cross-coupling products. In specific cases, two distinct polymorphs are observed and their reactivity is different according to the distance of the reaction sites. Theoretical calculations indicate that the transition from a metastable preorganized monomer to a dimer is barrierless and spontaneous. The dimer could regenerate free radicals by heating or photoirradiation in the solution phase. This discovery may lead to controllable molecular switches.

Comparative safety analysis of lacosamide and perampanel in epilepsy management: insights from FAERS database.

Background: Epilepsy is a chronic neurological condition requiring effective management with minimal adverse effects. Lacosamide (LCM) and Perampanel (PER), two promising treatments, have distinct profiles that merit comparative analysis to guide clinical decision-making. Methods: This study utilizes a pharmacovigilance analysis of adverse events reported in the FDA Adverse Event Reporting System database from Q1 2009 to Q3 2023. Employing disproportionality and Bayesian analyses, we assessed and compared the AE signals associated with LCM and PER to elucidate their safety profiles in epilepsy treatment. Results: The analysis included 12,576 AE reports for LCM and 2,703 for PER, highlighting a higher incidence of psychiatric disorders, including aggression with LCM, and a notable association of PER with psychiatric disorders such as psychotic disorders and dizziness. LCM showed a relatively safe profile during pregnancy, whereas PER's data suggested caution due to reported cases of suicidal ideation and attempts. Conclusion: This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of LCM and PER in clinical practice, providing valuable insights for personalized epilepsy management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events.

Effects of Bushen Huayu Decoction combined with entecavir on liver function and hepatic fibrosis in patients with compensated cirrhosis.

OBJECTIVE: To analyze the effect of Bushen Huayu Decoction combined with entecavir on alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (Alb) in patients with hepatitis cirrhosis. METHODS: A retrospective study was conducted on 102 patients with compensated hepatitis cirrhosis treated at the No. 2 Hospital of Baoding from February 2020 to April 2023. These patients were divided into two groups based on different treatment modalities: a control group treated with entecavir (n=51) and an observation group treated with Bushen Huayu decoction plus entecavir (n=51). The Traditional Chinese Medicine (TCM) syndrome scores, level of liver function indicators, and liver fibrosis symptoms were compared between the two groups before treatment and after 2 weeks and 4 weeks of treatment. RESULTS: Before treatment, the two groups differed insignificantly in liver fibrosis indicators (HA, IV-C, and PCIII), liver function indices (ALT, AST, TBil, and Alb) and TCM syndrome scores (all P>0.05). After 2 weeks and 4 weeks of treatment, HA, IV-C, and PCIII in both groups decreased. Those in the observation group were significantly lower than those in the control group (P<0.05). The levels ALT, AST, and TBil decreased significantly in both groups. The level of Alb increased significantly, and the alterations in the observation group was more prominent compared with those in the control group (all P<0.05). The scores of TCM syndromes across various aspects all decreased significantly. The scores in the observation group were significantly lower than those of control group (P<0.05). CONCLUSION: The combined treatment of Bushen Huayu Decoction and entecavir is helpful to improve the TCM symptoms, reduce the levels of ALT, AST, and TBil, increase the level of Alb, improve the state of liver fibrosis, and promote the recovery of liver function in patients with compensatory hepatitis cirrhosis.

Air bag-embedded MIL-101(Fe) metal-organic frameworks for an amplified tumor microenvironment activation loop through strategic delivery of iron ions and lentinan.

Background: Iron-based nanocarriers have demonstrated potential in redirecting tumor associated macrophages (TAMs) polarization towards the M1 phenotype, critical for activating the tumor microenvironment (TME) in triple negative breast cancer (TNBC). However, their real-world effectiveness is curtailed by insufficient Fe2+/3+ exposure and the absence of suitable synergists in tumors. Methods: We introduce an air bag-embedded iron-based MIL-101 metal-organic frameworks (MOFMIL-101(Fe)) for igniting the TME in TNBC through bubble-driven tumoral codelivery of Fe2+/3+ and lentinan. This system, named HM/Ef/LNT-MOFMIL-101(Fe), features nano-sized MOFMIL-101(Fe) as the core, embedded NaHCO3 as a pH-triggered air bag, electrostatically-adsorbed lentinan forming the inner shell, and a shield shell with 4T1&red blood cell hybrid membrane. Results: HM/Ef/LNT-MOFMIL-101(Fe) can mitigate non-specific capture in the bloodstream but respond to the acidic tumor milieu, rapidly generating a burst of CO2 bubbles to disassemble MOFMIL-101(Fe). Upon entering tumors, lentinan-induced interferon-γ (IFN-γ) enable Fe2+/3+ facilitating an enhanced ferroptosis and Fenton-like reaction, pushing TAMs towards M1 polarization via the "IFN-γ-ferroptosis-ROS-Caspase-3" pathway. Moreover, HM/Ef/LNT-MOFMIL-101(Fe) increases the infiltration of T lymphocytes and decreases regulatory T cells. These cascading immune responses synergistically foster a loop of amplified TME activation based on TAMs M1 polarization, showcasing notable advancements in anticancer effectiveness and promise for various combination therapies. Conclusion: This study utilizes an "embedded air-bag" strategy to achieve strategic codelivery of Fe2+/3+ and lentinan, providing a new tool for engineering the TME.

Efficacy and safety of autologous platelet-rich plasma in anal fistula: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to determine the efficacy and safety of autologous PRP in anal fistula. METHODS: The search was done in electronic databases such as; PubMed, Scopus, Google Scholar, Embase, and Cochrane Library. The outcomes investigated in this study were the rate of improvement, the rate of recurrence, and the rate of fecal incontinence. RESULTS: Cure, incontinence, and recurrence rates were 68% (95% CI, .60-.76), 27% (95% CI, .12-.46), and 18% (95% CI, .12-.26), respectively. The pooled improvement ratio in patients treated with PRP compared to control group was 1.35 times, which was statistically significant (pooled OR=1.35, 95% CI, 1.14-1.60, P<001). The pooled recurrence ratio in patients treated with PRP compared to control group was 1.17, which was not statistically significant (pooled OR=1.17, 95% CI, 0.44-3.11). DISCUSSION: Platelet-rich plasma is an effective method of healing people with anal fistula.

Nondestructive flash cathode recycling.

Effective recycling of end-of-life Li-ion batteries (LIBs) is essential due to continuous accumulation of battery waste and gradual depletion of battery metal resources. The present closed-loop solutions include destructive conversion to metal compounds, by destroying the entire three-dimensional morphology of the cathode through continuous thermal treatment or harsh wet extraction methods, and direct regeneration by lithium replenishment. Here, we report a solvent- and water-free flash Joule heating (FJH) method combined with magnetic separation to restore fresh cathodes from waste cathodes, followed by solid-state relithiation. The entire process is called flash recycling. This FJH method exhibits the merits of milliseconds of duration and high battery metal recovery yields of ~98%. After FJH, the cathodes reveal intact core structures with hierarchical features, implying the feasibility of their reconstituting into new cathodes. Relithiated cathodes are further used in LIBs, and show good electrochemical performance, comparable to new commercial counterparts. Life-cycle-analysis highlights that flash recycling has higher environmental and economic benefits over traditional destructive recycling processes.

Cytomegalovirus pneumonia with intermittent pulmonary hemorrhage leading to asphyxia death: a case report and literature review.

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.

Removal and assessment of cadmium contamination based on the toxic responds of a soil ciliate Colpoda sp.

Bioremediation of cadmium (Cd) pollution, a recognized low-carbon green environmental protection technology, is significantly enhanced by the discovery of Cd-tolerant microorganisms and their underlying tolerance mechanisms. This study presents Colpoda sp., a soil ciliate with widespread distribution, as a novel bioindicator and bioremediator for Cd contamination. With a 24 h-LC50 of 5.39 mg l-1 and an IC50 of 24.85 µg l-1 in Cd-contaminated water, Colpoda sp. achieves a maximum bioaccumulation factor (BAF) of 3.58 and a Cd removal rate of 32.98 ± 0.74 % within 96 h. The toxic responses of Colpoda sp. to Cd stress were assessed through cytological observation with transmission electron microscopy (TEM), oxidative stress kinase activity, and analysis of Cd-metallothionein (Cd-MTs) and the cd-mt gene via qRT-PCR. The integrated biomarker response index version 2 (IBRv2) and structural equation models (SEM) were utilized to analyze key factors and mechanisms, revealing that the up-regulation of Cd-MTs and cd-mt expression, rather than the oxidative stress system, is the primary determinant of Cd accumulation and tolerance in Colpoda sp. The ciliate's ability to maintain growth under 24.85 µg l-1 Cd stress and its capacity to absorb and accumulate Cd particles from water into cells are pivotal for bioremediation. A new mathematical formula and regression equations based on Colpoda sp.'s response parameters have been established to evaluate environmental Cd removal levels and design remediation schemes for contaminated sites. These findings provide a novel bioremediation and monitoring pathway for Cd remobilization and accumulation in soil and water, potentially revolutionizing the governance of Cd pollution.

Polymeric piezoelectric accelerometers with high sensitivity, broad bandwidth, and low noise density for organic electronics and wearable microsystems.

Piezoelectric accelerometers excel in vibration sensing. In the emerging trend of fully organic electronic microsystems, polymeric piezoelectric accelerometers can be used as vital front-end components to capture dynamic signals, such as vocal vibrations in wearable speaking assistants for those with speaking difficulties. However, high-performance polymeric piezoelectric accelerometers suitable for such applications are rare. Piezoelectric organic compounds such as PVDF have inferior properties to their inorganic counterparts such as PZT. Consequently, most existing polymeric piezoelectric accelerometers have very unbalanced performance metrics. They often sacrifice resonance frequency and bandwidth for a flat-band sensitivity comparable to those of PZT-based accelerometers, leading to increased noise density and limited application potentials. In this study, a new polymeric piezoelectric accelerometer design to overcome the material limitations of PVDF is introduced. This new design aims to simultaneously achieve high sensitivity, broad bandwidth, and low noise. Five samples were manufactured and characterized, demonstrating an average sensitivity of 29.45 pC/g within a ± 10 g input range, a 5% flat band of 160 Hz, and an in-band noise density of 1.4 µg/Hz. These results surpass those of many PZT-based piezoelectric accelerometers, showing the feasibility of achieving comprehensively high performance in polymeric piezoelectric accelerometers to increase their potential in novel applications such as organic microsystems.

Exploring the novel antioxidant peptides in low-salt dry-cured ham: Preparation, purification, identification and molecular docking.

Dry-cured ham is important source of bioactive peptides. In this study, the antioxidant activities of peptides and components from low and fully salted dry-cured hams were compared by peptidomics. And novel antioxidant peptides were identified and characterized. The results showed that the peptides (<3 KDa) extracted from low-salt dry-cured ham had higher antioxidant activity. Therefore, the antioxidant peptides in low-salt dry-cured ham were further characterized and the mechanism of their antioxidant activity was investigated. From the five candidate peptides selected, we found DWPDARGIWHND (DD12) to be highly stable, non-sensitizing, and non-toxic with the highest free radical scavenging activity. Molecular docking predicted that DD12 interacted with Keap1 through hydrogen-bond formation and hydrophobic interactions, suggesting that DD12 had good cellular antioxidant activity. DD12 peptide can bind to DPPH• and ABTS•+, resulting in strong free radical scavenging activity. Our findings support the development and application of natural antioxidant peptides in dry-cured ham.

m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis.

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.

M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages.

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.

A novel long-tailed myovirus represents a new T4-like cyanophage cluster.

Cyanophages affect the abundance, diversity, metabolism, and evolution of picocyanobacteria in marine ecosystems. Here we report an estuarine Synechococcus phage, S-CREM2, which represents a novel viral genus and leads to the establishment of a new T4-like cyanophage clade named cluster C. S-CREM2 possesses the longest tail (~418 nm) among isolated cyanomyoviruses and encodes six tail-related proteins that are exclusively homologous to those predicted in the cluster C cyanophages. Furthermore, S-CREM2 may carry three regulatory proteins in the virion, which may play a crucial role in optimizing the host intracellular environment for viral replication at the initial stage of infection. The cluster C cyanophages lack auxiliary metabolic genes (AMGs) that are commonly found in cyanophages of the T4-like clusters A and B and encode unique AMGs like an S-type phycobilin lyase gene. A variation in the composition of tRNA and cis-regulatory RNA genes was observed between the marine and freshwater phage strains in cluster C, reflecting their different modes of coping with hosts and habitats. The cluster C cyanophages are widespread in estuarine and coastal regions and exhibit equivalent or even higher relative abundance compared to those of clusters A and B cyanophages in certain estuarine regions. The isolation of cyanophage S-CREM2 provides new insights into the phage-host interactions mediated by both newly discovered AMGs and virion-associated proteins and emphasizes the ecological significance of cluster C cyanophages in estuarine environments.

Regulation of the pleiotropic transcriptional regulator CodY on the conversion of branched-chain amino acids into branched-chain aldehydes in Lactococcus lactis.

IMPORTANCE: Branched-chain aldehydes are the primary compounds that contribute to the nutty flavor in cheddar cheese. Lactococcus lactis, which is often applied as primary starter culture, is a significant contributor to the nutty flavor of cheddar cheese due to its ability of conversion of BCAAs into branched-chain aldehydes. In the present study, we found that the regulatory role of CodY is crucial for the conversion. CodY acts as a pleiotropic transcriptional regulator via binding to various regulatory regions of key genes. The results presented valuable knowledge into the role of CodY on the regulation and biosynthetic pathway of branched-chain amino acids and the related aldehydes. Furthermore, it provided new insight for increasing the nutty flavor produced during the manufacture and ripening of cheese.

Asymmetric formal C-C bond insertion into aldehydes via copper-catalyzed diyne cyclization.

The formal C-C bond insertion into aldehydes is an attractive methodology for the assembly of homologated carbonyl compounds. However, the homologation of aldehydes has been limited to diazo approach and the enantioselective reaction was rarely developed. Herein, we report an asymmetric formal C-C bond insertion into aldehydes through diyne cyclization strategy. In the presence of Cu(I)/SaBOX catalyst, this method leads to the efficient construction of versatile axially chiral naphthylpyrroles in moderate to excellent yields with good to excellent enantioselectivities. This protocol represents a rare example of asymmetric formal C-C bond insertion into aldehydes using non-diazo approach. The combined experimental and computational mechanistic studies reveal the reaction mechanism, origin of regioselectivity and stereoselectivity. Notably, the chiral phosphine ligand derived from synthesized axially chiral skeleton was proven to be applicable to asymmetric catalysis.

A polymeric piezoelectric MEMS accelerometer with high sensitivity, low noise density, and an innovative manufacturing approach.

The piezoelectric coupling principle is widely used (along with capacitive coupling and piezoresistive coupling) for MEMS accelerometers. Piezoelectric MEMS accelerometers are used primarily for vibration monitoring. Polymer piezoelectric MEMS accelerometers offer the merits of heavy-metal-free structure material and simple microfabrication flow. More importantly, polymeric piezoelectric MEMS accelerometers may be the basis of novel applications, such as fully organic inertial sensing microsystems using polymer sensors and organic integrated circuits. This paper presents a novel polymer piezoelectric MEMS accelerometer design using PVDF films. A simple and rapid microfabrication flow based on laser micromachining of thin films and 3D stereolithography was developed to fabricate three samples of this design. During proof-of-concept experiments, the design achieved a sensitivity of 21.82 pC/g (equivalent open-circuit voltage sensitivity: 126.32 mV/g), a 5% flat band of 58.5 Hz, and a noise density of 6.02 µg/√Hz. Thus, this design rivals state-of-the-art PZT-based counterparts in charge sensitivity and noise density, and it surpasses the performance capabilities of several commercial MEMS accelerometers. Moreover, this design has a 10-times smaller device area and a 4-times larger flat band than previous state-of-the-art organic piezoelectric MEMS accelerometers. These experimentally validated performance metrics demonstrate the promising application potential of the polymeric piezoelectric MEMS accelerometer design presented in this article.

BRISC is required for optimal activation of NF-κB in Kupffer cells induced by LPS and contributes to acute liver injury.

BRISC (BRCC3 isopeptidase complex) is a deubiquitinating enzyme that has been linked with inflammatory processes, but its role in liver diseases and the underlying mechanism are unknown. Here, we investigated the pathophysiological role of BRISC in acute liver failure using a mice model induced by D-galactosamine (D-GalN) plus lipopolysaccharide (LPS). We found that the expression of BRISC components was dramatically increased in kupffer cells (KCs) upon LPS treatment in vitro or by the injection of LPS in D-GalN-sensitized mice. D-GalN plus LPS-induced liver damage and mortality in global BRISC-null mice were markedly attenuated, which was accompanied by impaired hepatocyte death and hepatic inflammation response. Constantly, treatment with thiolutin, a potent BRISC inhibitor, remarkably alleviated D-GalN/LPS-induced liver injury in mice. By using bone marrow-reconstituted chimeric mice and cell-specific BRISC-deficient mice, we demonstrated that KCs are the key effector cells responsible for protection against D-GalN/LPS-induced liver injury in BRISC-deficient mice. Mechanistically, we found that hepatic and circulating levels of TNF-α, IL-6, MCP-1, and IL-1ß, as well as TNF-α- and MCP-1-producing KCs, in BRISC-deleted mice were dramatically decreased as early as 1 h after D-GalN/LPS challenge, which occurred prior to the elevation of the liver injury markers. Moreover, LPS-induced proinflammatory cytokines production in KCs was significantly diminished by BRISC deficiency in vitro, which was accompanied by potently attenuated NF-κB activation. Restoration of NF-κB activation by two small molecular activators of NF-κB p65 effectively reversed the suppression of cytokines production in ABRO1-deficient KCs by LPS. In conclusion, BRISC is required for optimal activation of NF-κB-mediated proinflammatory cytokines production in LPS-treated KCs and contributes to acute liver injury. This study opens the possibility to develop new strategies for the inhibition of KCs-driven inflammation in liver diseases.

Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.