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Ethnopharmacological Relevance: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear., Aim of the Study: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism., Materials and Methods: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases., Results: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone., Conclusion: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammasomes play important roles in resisting infections caused by various pathogens. HSV-1 is a highly contagious virus among humans. The process by which HSV-1 particles bud from the nucleus is unique to herpes viruses, but the specific mechanism is still unclear. Here, we screened genes involved in HSV-1 replication. We found that TET3 plays an essential role in HSV-1 infection. TET3 recognizes the UL proteins of HSV-1 and, upon activation, can directly bind to caspase-1 to activate an ASC-independent inflammasome in the nucleus. The subsequent cleavage of GSDMD in the nucleus is crucial for the budding of HSV-1 particles from the nucleus. Inhibiting the perforation ability of GSDMD on the nuclear membrane can significantly reduce the maturation and spread of HSV-1. Our results may provide a new approach for the treatment of HSV-1 in the future., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Background: Hearing loss and lifestyle factors have been associated with cognitive impairment. We aimed to explore the joint association of combined healthy lifestyle factors and hearing loss with cognitive impairment, which has been scarcely studied., Methods: This baseline study used data from the CHOICE-Cohort study (Chinese Hearing Solution for Improvement of Cognition in Elders). Hearing loss was assessed by the better-ear pure-tone average. A composite healthy lifestyle score was built based on never smoking, never drinking, regular physical activity, and a balanced diet. Cognitive impairment was diagnosed by the Mini-Mental State Examination score of less than 24., Results: We included 17 057 participants aged 60 years or older in China (mean age 69.8 [standard deviation 6.2] years, 55.7% female). Among the participants, 48.3% (n = 8 234) had mild hearing loss, and 25.8% (n = 4 395) had moderate or greater hearing loss. The proportion of participants with healthy lifestyle scores of 0-1, 2, 3, and 4 was 14.9% (n = 2 539), 29.3% (n = 5 000), 37.4% (n = 6 386), and 18.4% (n = 3 132), respectively. About 29.6% (n = 5 057) participants had cognitive impairment. When compared to those with normal hearing and healthy lifestyle (scores of 3-4), participants with hearing loss plus unhealthy lifestyle (scores of 0-2) exhibited approximately twofold increased risk of cognitive impairment (odds ratio [OR] = 1.92, 95% confidence interval [CI] 1.70-2.18). Conversely, the risk was greatly attenuated by adherence to healthy lifestyle in individuals with hearing loss (OR = 1.57, 95% CI 1.40-1.76)., Conclusions: Our findings demonstrated adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment among participants with hearing loss., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (M.tb) and responsible for millions of deaths worldwide each year. It has a complex pathogenesis that primarily affects the lungs but can also impact systemic organs. In recent years, single-cell sequencing technology has been utilized to characterize the composition and proportion of immune cell subpopulations associated with the pathogenesis of TB disease since it has a high resolution that surpasses conventional techniques. This paper reviews the current use of single-cell sequencing technologies in TB research and their application in analysing specimens from various sources of TB, primarily peripheral blood and lung specimens. The focus is on how these technologies can reveal dynamic changes in immune cell subpopulations, genes and proteins during disease progression after M.tb infection. Based on the current findings, single-cell sequencing has significant potential clinical value in the field of TB research. Next, we will focus on the real-world applications of the potential targets identified through single-cell sequencing for diagnostics, therapeutics and the development of effective vaccines., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1β, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown., Objective: This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics., Methods: Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites., Results: Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect., Conclusion: PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application., Competing Interests: The authors have no conflicts of interest in this work., (© 2024 Bai et al.)

Gastric cancer (GC) is one of the most lethal malignancies worldwide. Despite extensive efforts to develop novel therapeutic targets, effective drugs for GC remain limited. Recent studies have indicated that Lipocalin (LCN)2 abnormalities significantly impact GC progression; however, its regulatory network remains unclear. Our study investigates the functional role and regulatory mechanism of action of LCN2 in GC progression. We observed a positive correlation between LCN2 expression, lower GC grade, and better prognosis in patients with GC. LCN2 overexpression suppressed GC proliferation and metastasis both in vitro and in vivo. Transcriptome sequencing identified secreted protein acidic and rich in cysteine (SPARC) as a pivotal downstream target of LCN2. Mechanistically, c-Jun acted as a transcription factor inducing SPARC expression, and LCN2 downregulated SPARC by inhibiting the JNK/c-Jun pathway. Moreover, LCN2 bound to its receptor, 24p3R, via autocrine signaling, which directly inhibited JNK phosphorylation and then inhibited the JNK/c-Jun pathway. Finally, analysis of clinical data demonstrated that SPARC expression correlated negatively with lower GC grade and better prognosis, and that LCN2 expression correlated negatively with p-JNK, c-Jun, and SPARC expression in GC. These findings suggest that the LCN2/24p3R/JNK/c-Jun/SPARC axis is crucial in the malignant progression of GC, offering novel prognostic markers and therapeutic targets., (© 2024. The Author(s).)

Actin stabilizers that are capable of interfering with actin cytoskeleton dynamics play an important role in chemical biology. Rhizopodin, a novel actin stabilizer, affects the actin cytoskeleton at nanomolar concentrations and exhibits potent antiproliferative activities against a range of tumor cell lines with IC 50 values in the low nanomolar range. Herein, we report the total synthesis of rhizopodin based on a late-stage oxazole ring formation strategy, whose success demonstrates the feasibility of late-stage oxazole ring formation in the synthesis of complex oxazole containing natural products. Other features of the synthesis include a Nagao aldol reaction, a Suzuki coupling, a Yamaguchi esterification, a modified Robinson-Gabriel synthesis of the oxazoles, and a bidirectional Ba(OH) 2 -mediated Horner-Wadsworth-Emmons (HWE) reaction.

Background: Several studies have upheld the advantages of blood collection using via central venous access device (CVAD); the procedure has a high success rate and avoids painful repeated punctures. Some studies have suggested that via central venous access device (CVAD) blood collection is preferable for acute and critical care, oncology, and pediatric patients. However, there is no consensus on or standardization of this approach., Purpose: To explore the facilitators of and barriers factors of evidence-based decision-making in CVAD blood collection in clinical practice., Methods: This was a qualitative study guided by phenomenological research. A purposive sampling method was used to select 13 clinical nurses from two public hospitals in China to conduct semi-structured personal interviews. The interview outline was designed based on a literature review and the i-PARIHS theoretical framework, and information was organized and analyzed using the Colaizzi 7-step analysis method., Results: Two themes and seven sub-themes were derived from the analysis of interview data. Facilitating factors: (1) nurses' trust the evidence-based nursing decisions; (2) low rate of operational complications; (3) high success rate of blood collection; (4) nurses' sense of professional benefit; Hindering factors: (1) preparation of operational materials and time-consuming operation; (2) nursing interruptions; (3) patients' economic factors. The interview data showed that CVAD blood collection is suitable for critically ill patients, children, patients with poor venous conditions and poor cooperation., Conclusion: This study provides guidance for advancing the clinical application of evidence-based CVAD blood collection. Evidence-based nursing culture, operational advantages, and nurses' sense of professional benefit were effective facilitators of the evidence-based practice. Researchers need to optimize the operating materials and methods, and comprehensively consider multiple factors to promote the better application of evidence., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited., Methods: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism., Results: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA., Conclusion: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury)., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The laboratory standard MRSA strain WHO-2 and clinical isolate S1 were used to establish a pneumonia infection model. The results showed that methicillin increased the expression of Hla and PVL protein at subminimum inhibitory concentration, while artesunate decreased the secretion of Hla and PVL protein. Artesunate alone reduced hemolysin expression and reversed methicillin-induced increases in Hla and PVL proteins. In addition, the study found that the combination of artesunate and methicillin had the best therapeutic effect, with survival rates of 70 % and 40 % at seven days, respectively (corresponding to the WHO-2 and S1 strains). The combination treatment was able to reduce cell mortality, showing a 65 % and 46 % reduction in cell mortality, respectively. The study also found that the combination therapy decreased the expression of alpha-hemolysin and pantone valentin leukin in the culture medium and significantly reduced the activation of NF-kB. This is caused by a significant decrease in the expression of inflammatory factors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Long-term use of rhubarb (RH) can cause adverse gastrointestinal reactions (such as diarrhea), whereas RH steaming with wine (PRH) can alleviate RH-induced diarrhea. However, the potential material basis and mechanisms by which wine steaming alleviates diarrhea caused by RH remain unclear., Purpose: To reveal the potential material basis and underlying mechanisms of wine steaming in alleviating diarrhea caused by RH from the perspective of small intestinal flora and immune function., Methods: The major anthraquinone/anthrone components were detected using high-performance liquid chromatography (HPLC). Constipation model mice were replicated using loperamide hydrochloride and were administered RH and PRH for six consecutive weeks. Histopathological observation (duodenum, jejunum, and ileum) was performed using hematoxylin-eosin (HE) staining, and the serum levels of inflammatory cytokines, immunoglobulin G (IgG), and immunoglobulin A (IgA) were examined. CD4 + , CD8 + , and Treg cells counts in peripheral blood were determined using flow cytometry; The protein expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) was determined using immunohistochemistry (IHC) and western blot (WB). The small intestine contents and feces were analyzed by 16 S rRNA sequencing and the contents of short chain fatty acids (SCFAs) in feces were determined using gas chromatography-mass spectrometry (GC-MS). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the blood absorption compounds and endogenous metabolites., Results: The levels of the major anthraquinone/anthrone components were decreased in PRH. RH and PRH both increased the wet fecal weight at 12 h (WFW-12) and fecal water rate (FWR), alleviated the dry and black fecal morphology, and relieved small intestine injuries in the second week. In the fourth week, although RH and PRH alleviated the abnormal levels of indicators in the model mice (fecal water rate, immune cells percentage, and TLR4/NF-κB expression), minor small intestinal damage was observed. Compared to that at the fourth week, RH and PRH increased the levels of WFW-12, FWR, inflammatory cytokines, and TLR4/NF-κB expression, and decreased the levels of IgG/IgA and immune cells with extended administration (sixth week). Further, damage to the small intestine worsened (severe ileal damage) and different degrees of loose stools were observed in RH- and PRH-administered mice in the sixth week. Compared with those in the control group, the levels of WFW-12, FWR, inflammatory cytokines, TLR4/NF-κB expression, IgG/IgA, and immune cell percentage were significantly different in the RH-H and PRH-H mice at the sixth week (except for CD8 + in PRH-H). Further, RH and PRH disturbed the gut microbiota (GM) (Lactobacillus and Dubosiella decreased, Aerococcus and Corynebacterium increased) and obviously reduced the content of SCFAs (acetic acid, butyric acid, and isobutyric acid). However, almost all the results indicated a lower impact of PRH than that of RH. Metabolic pathways mainly involved in glycerophospholipid metabolism were identified along with a total of 21 blood absorption components, including anthraquinones, anthrones, flavanols, and tannins. The correlation analysis showed a positive correlation of pathogenic bacteria (Aerococcus and Corynebacterium) with inflammatory cytokines, TLR4/NF-κB, LysoPC(20:0/0:0), and PE (16:0/20:4(8Z,11Z,14Z,17Z)) and a negative correlation with immune cells and SCFAs (acetic acid and isobutyric acid); however, the opposite results were observed for beneficial bacteria (Lactobacillus and Dubosiella)., Conclusion: Overall, PRH can alleviate RH-induced diarrhea by recovering the GM imbalance and abnormal levels of GM-mediated SCFAs, alleviating the decrease in cellular immune function and abnormal expression of TLR4/NF-κB, thereby suppressing the release of inflammatory factors, possibly, through its lower content of anthraquinones. This study explored for the first time the processing mechanism of wine steaming in alleviating RH-induced diarrhea from the aspects of small intestinal flora and small intestinal immune function., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

A new sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for nine fasciolicides (closantel, rafoxanide, oxyclozanide, niclosamide, nitroxinil, ioxynil, 4-nitro-3-(trifluoromethyl)phenol, salicylanilide, and triclabendazole) and three metabolite residues (ketotriclabnedazole, triclabendazole sulfone, and triclabendazole sulfoxide) in milk and infant formula was established. The samples were extracted and purified through solid-phase extraction and analyzed using LC-MS/MS. The proposed method demonstrated high accuracy (the average recoveries ranged from 70.5 % to 107.4 %) and high sensitivity (the limits of quantification ranged from 1.0 to 25.0 µg/kg). This method was successfully applied to determine nine fasciolicides and three metabolite residues in 45 milk and infant formula, providing technical support for the safety and quality evaluation of dairy products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13 + ) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

Polygonatum kingianum Collett & Hemsl., is one of the most important traditional Chinese medicines in China. The purpose of this study is to investigate the relationship between herb quality and microbial-soil variables, while also examining the composition and structure of the rhizosphere microbial community in Polygonatum kingianum, the ultimate goal is to provide a scientific approach to enhancing the quality of P. kingianum. Illumina NovaSeq technology unlocks comprehensive genetic variation and biological functionality through high-throughput sequencing. And in this study it was used to analyze the rhizosphere microbial communities in the soils of five P. kingianum planting areas. Conventional techniques were used to measure the organic elements, pH, and organic matter content. The active ingredient content of P. kingianum was identified by High Performance Liquid Chromatography (HPLC) and Colorimetry. A total of 12,715 bacterial and 5487 fungal Operational Taxonomic Units (OTU) were obtained and taxonomically categorized into 81 and 7 different phyla. Proteobacteria, Bacteroidetes, and Acidobacteriae were the dominant bacterial phyla Ascomycota and Basidiomycota were the dominat fungal phyla. The key predictors for bacterial community structure included hydrolysable nitrogen and available potassium, while for altering fungal community structure, soil organic carbon content (OCC), total nitrogen content (TNC), and total potassium content (TPOC) were the main influencing factors. Bryobacter and Candidatus Solibacter may indirectly increase the polysaccharide content of P. kingianum, and can be developed as potential Plant Growth Promoting Rhizobacteria (PGPR). This study has confirmed the differences in the soil and microorganisms of different origins of P. kingianum, and their close association with its active ingredients. And it also broadens the idea of studying the link between plants and microorganisms., (© 2024. The Author(s).)

Background: After acute treatment, patients with schizophrenia return to their original living environment for further rehabilitation, which not only determines the quality of life of the patients and their families but also has an important impact on society. However, patients often find it difficult to adapt to changes in the environment when they are discharged from the hospital. This may be related to the incompleteness of China's mental health service system, as many services for schizophrenia patients are only in the treatment stage. In China, schizophrenia is traditionally associated with poor moral quality, and patients find it difficult to obtain support. Many patients have trouble reintegrating into the community after treatment. Schizophrenic multifamily teams gather families affected by the same illness and pain together to promote healing together in an environment that allows mutual sharing, understanding and transparency, maximizes the use of family resources for support, improves discharge readiness, and better deals with post-discharge recovery., Methods: The multifamily group intervention method was used to improve the motivation of the patients' family motivation as well as the discharge readiness and self-efficacy of the patient., Results: After the intervention, the motivation of the family and discharge readiness of the patient were improved compared with that of the baseline period; however, the improvement was not significant. The self-efficacy of the patients was significantly improved (P=0.042)., Conclusions: In the discharge preparation of schizophrenia patients, multifamily teams can be used to help patients and their families share resources, enhance support and prepare for discharge. Patients will have better support following discharge for recovery in the community. Additional consideration should be given to the impact of the environment on patient services, and the evaluation of the service process is key to continuously improving the service effect., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liu et al.)

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C 18 H 15 ClN 2 O 2 S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 6 O 2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 5 FO 2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 5 NO 4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B.

Background: Despite widespread application of minimally invasive video-assisted thoracic surgery (VATS), postoperative pain following this procedure is still a constant clinical challenge. Serratus anterior plane (SAP) block is one of the regional analgesic techniques with promising outcomes. However, due to the limited duration of action, optimal analgesia is often not achieved with a single injection. We tested whether in patients who have been subjected to routine SAP block under preoperative anesthesia, the addition of a second SAP block 24 hours after surgery, improves quality of recovery, lowers postoperative opioid consumption, and reduces the prevalence of chronic pain., Methods: The present study is a single institutional, prospective, randomized, triple-blinded, placebo-controlled study. Ninety patients undergoing VATS from January 2022 to April 2022 were randomized at 1:1 ratio to receive ultrasound-guided second SAP block with 15 mL 0.375% ropivacaine (SAP block group) or 15 mL normal saline (control group) 24 hours after both groups received routine SAP block with 15 mL 0.375% ropivacaine. The primary outcome was quality of patient recovery, measured using 40-item quality of recovery questionnaire (QoR-40) at postoperative day 2 (POD 2). Secondary outcomes included: postoperative pain scores at rest, postoperative opioid consumptions, number of times that patient controlled analgesia (PCA) pump button was pressed, perioperative complications and adverse effects, prevalence of chronic pain at 2 nd and 3 rd month postoperatively, and length of hospital stay (LOS)., Results: A total of 83 patients completed the study: 43 patients in SAP block group and 40 patients in the control group. The global QoR-40 scores on POD 2 and POD 3 were significantly higher among SAP block group patients (180.07±11.34, 182.09±8.20) compared with the control group (172.18±6.15, 177.50±6.94) (P=0.01, P=0.008) respectively. Postoperative pain scores, opioid consumptions and incidence of postoperative nausea and vomiting were significantly lower among patients in SAP block group versus control group. There were no statistically significant differences in perioperative complications and LOS between the two groups. The prevalence of chronic pain at the 2 nd and 3 rd month postoperatively for patients in SAP block group and control group was 16.3%, 14%, and 32.5%, 27.5% respectively., Conclusions: In patients undergoing VATS, application of ultrasound-guided second SAP block 24 hours after surgery improved postoperative quality of life, reduced opioid consumption and related side effects, and lowered the prevalence of chronic pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-982/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further., Case Presentation: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR., Conclusions: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied., (© 2024. The Author(s).)

Pure carbon materials with magnetic properties have attracted considerable research interest due to their advantages over traditional magnetic materials. Nevertheless, such materials are exceedingly rare. Disrupting the Kekulé valence structures in carbon materials potentially leads to the emergence of magnetism. In this study, using first principles calculations, we developed a range of pure carbon allotropes derived from the smallest fullerene C 20 which potentially disrupts the Kekulé valence structures after polymerization. The results indicate that some of the allotropes disrupting the Kekulé valence structures exhibit intrinsic antiferromagnetic ordering, and the magnetism originates from the presence of isolated three-fold coordinated C atoms. The other allotropes adhering to the Kekulé valence structures show non-magnetism with all three-fold coordinated C atoms forming dimers. In all magnetic polymers, magnetism arises from unpaired electrons on the isolated three-fold coordinated carbon atoms, with magnetic moments of about 0.40 μ B at these sites. The adsorption of dopant atoms can significantly alter the magnetic properties of polymers, for instance, the C 20 -71 polymer with Immm symmetry undergoes a transition from non-magnetic to anti-magnetic ordering upon adsorption of hydrogen atoms. Electronic calculations indicate that these polymers display a range of electronic properties, encompassing both metallic and semiconducting characteristics. Notably, certain magnetic phases exhibit superhard properties, with the hardness value exceeding 40 GPa. This study presents a potential method for designing magnetic carbon materials. Specifically, certain compounds address the gap in magnetic superhard materials composed of light elements, and can be utilized in the field of spintronics where traditional superhard materials are unsuitable.

Photocatalytic technology is widely regarded as an important way to utilize solar energy and achieve carbon neutrality, which has attracted considerable attentions in various fields over the past decades. Metal halide perovskites (MHPs) are recognized as "superstar" materials due to their exceptional photoelectric properties, readily accessible and tunable structure, which made them intensively studied in solar cells, light-emitting diodes, and solar energy conversion fields. Since 2018, increased attention has been focused on applying the MHPs as a heterogeneous visible light photocatalyst in catalyzing organic synthesis reactions. In this review, we present an overview of photocatalytic technology and principles of heterogeneous photocatalysis before delving into the structural characteristics, stability, and classifications of MHPs. We then focus on recent developments of MHPs in photocatalyzing various organic synthesis reactions, such as oxidation, cyclization, C-C coupling etc., based on their classifications and reported reaction types. Finally, we discuss the main limitations and prospects regarding the application of metal halide perovskites in organic synthesis., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

Competing Interests: Declaration of competing interest None.

Background & Aims: The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy., Methods: Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications., Results: Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group., Conclusion: The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications., Competing Interests: Wenbin Zou and Wan Kuang are co-first authors for this study. The authors declare that they have no conflicts of interest in this work., (© 2024 Zou et al.)

Veronica anagallis-aquatica L. and Veronica undulata Wall. are widely used ethnomedicinal plants in China. The two species have different clinical efficacies, while their extremely similar morphology and unclear interspecific relationship make it difficult to accurately identify them, leading to increased instances of mixed usage. This article reports on the complete chloroplast genomes sequence of these two species and their related Veronica species to conduct a comparative genomics analysis and phylogenetic construction. The results showed that the chloroplast (cp) genomes of Veronica exhibited typical circular quadripartite structures, with total lengths of 149,386 to 152,319 base pairs (bp), and GC content of 37.9 to 38.1%, and the number of genes was between 129-134. The total number of simple sequence repeats (SSRs) in V. anagallis-aquatica and V. undulata is 37 and 36, while V. arvensis had the highest total number of 56, predominantly characterized by A/T single bases. The vast majority of long repeat sequence types are forward repeats and palindromic repeats. Selective Ka/Ks values showed that three genes were under positive selection. Sequence differences often occur in the non-coding regions of the large single-copy region (LSC) and small single-copy region (SSC), with the lowest sequence variation in the inverted repeat regions (IR). Seven highly variable regions (trnT-GGU-psbD, rps8-rpl16, trnQ-UUG, trnN-GUU-ndhF, petL, ycf3, and ycf1) were detected, which may be potential molecular markers for identifying V. anagallis-aquatica and V. undulata. The phylogenetic tree indicates that there is a close genetic relationship between the genera Veronica and Neopicrorhiza, and V. anagallis-aquatica and V. undulata are sister groups. The molecular clock analysis results indicate that the divergence time of Veronica may occur at ∼ 9.09 Ma, and the divergence time of these two species occurs at ∼ 0.48 Ma. It is speculated that climate change may be the cause of Veronica species diversity and promote the radiation of the genus. The chloroplast genome data of nine Veronica specie provides important insights into the characteristics and evolution of the chloroplast genome of this genus, as well as the phylogenetic relationships of the genus Veronica., (© 2024. The Author(s).)

Background: The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood., Methods: This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration., Results: Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment., Conclusions: The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value., (© 2024. The Author(s).)

Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery., Methods/design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO 2 max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay., Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers., Trial Registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759)., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results., (© 2024. The Author(s).)

The scarcity of superhard materials with magnetism or a narrow band gap, despite their potential applications in various fields, makes it desirable to design such materials. Here, a series of C 1+ x N 1- x compounds are theoretically designed by replacing different numbers of nitrogen atoms with carbon atoms in the synthesized C 1 N 1 compound. The results indicate that the compounds C 5 N 3 and C 7 N 1 possess both superhardness and antiferromagnetic ordering due to the introduction of low-coordinated carbon atoms. The hardness of the two compounds is about 40.3 and 54.5 GPa, respectively. The magnetism in both compounds is attributed to the unpaired electrons in low-coordinated carbon atoms, and the magnetic moments are 0.42 and 0.39 μ B , respectively. Interestingly, the magnetism in C 5 N 3 remains unaffected by the external pressure used in this study, whereas C 7 N 1 becomes nonmagnetic when the pressure exceeds ∼80 GPa. Electronic calculations reveal that both compounds behave as indirect band gap semiconductors, with narrow energy gaps of about 0.30 and 0.20 eV, respectively. Additionally, the other two compounds, C 6 N 2 -I and C 6 N 2 -III, exhibit nonmagnetic ordering and possess hardness values of 52.6 and 35.0 GPa, respectively. C 6 N 2 -I behaves as a semiconductor with an energy gap of 0.79 eV, and C 6 N 2 -III shows metallic behavior. Notably, the energy gaps of C 5 N 3 and C 6 N 2 -I remain nearly constant under arbitrary pressure due to their porous and superhard structure. These compounds fill the gap in magnetic or narrow band gap superhard materials, and they can be used in the spintronic or optoelectronic fields where conventional superhard materials are not suitable.

Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy., (© 2024. The Author(s).)

Persistent type (T) 2 airway inflammation plays an important role in the development of severe asthma. However, the molecular mechanisms leading to T2 severe asthma have yet to be fully clarified. Human normal lung epithelial cells (BEAS-2B cells) were transfected with LINC00158/BCL11B plasmid/small interfering RNA (siRNA). Levels of epithelial-mesenchymal transition (EMT)-related markers were measured using real-time qPCR (RT-qPCR) and western blot. A dual luciferase reporter assay was used to validate the targeting relationship between LINC00158 and BCL11B. The effects of LINC00158-lentivirus vector-mediated overexpression and dexamethasone on ovalbumin (OVA)/lipopolysaccharide (LPS)-induced severe asthma were investigated in mice in vivo. Our study showed that overexpression of LINC00158/BCL11B inhibited the levels of EMT-related proteins, apoptosis, and promoted the proliferation of BEAS-2B cells. BCL11B was a direct target of LINC00158. And LINC00158 targeted BCL11B to regulate EMT, apoptosis, and cell proliferation of BEAS-2B cells. Compared with severe asthma mice, LINC00158 overexpression alleviated OVA/LPS-induced airway hyperresponsiveness and airway inflammation, including reductions in T helper 2 cells factors in lung tissue and BALF, serum total- and OVA-specific IgE, inflammatory cell infiltration, and goblet cells hyperplasia. In addition, LINC00158 overexpression alleviated airway remodeling, including reduced plasma TGF-β1 and collagen fiber deposition, as well as suppression of EMT. Additionally, overexpression of LINC00158 enhanced the therapeutic effect of dexamethasone in severe asthmatic mice models. LINC00158 regulates BEAS-2B cell biological function by targeting BCL11B. LINC00158 ameliorates T2 severe asthma in vivo and provides new insights into the clinical treatment of severe asthma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The discovery of novel and highly effective P-gp inhibitors is considered to be an effective strategy for overcoming tumor drug resistance. In this paper, a phenotypic screening via a self-constructed synthetic methodology-based library identified a new class of tricyclic spiroindole derivatives with excellent tumor multidrug resistance reversal activity. A stereospecific compound OY-103-B with the best reversal activity was obtained based on a detailed structure-activity relationship study, metabolic stability optimization and chiral resolution. For the VCR-resistant Eca109 cell line (Eca109/VCR), co-administration of 5.0 μM OY-103-B resulted in a reversal fold of up to 727.2, superior to the typical third-generation P-gp inhibitor tariquidar. Moreover, the compound inhibited the proliferation of Eca109/VCR cells in a concentration-dependent manner in plate cloning and flow cytometry. Furthermore, fluorescence substrate accumulation assay and chemotherapeutic drug reversal activity tests demonstrated that OY-103-B reversed tumor drug resistance via P-gp inhibition. In conclusion, this study provides a novel skeleton that inspires the design of new P-gp inhibitors, laying the foundation for the treatment of drug-resistant tumors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mi, Liu, Chen, Qian, Zhu, Zhang, Liang, Wang and Ta.)

To explore the of Qufeng Tongqiao Prescription in the treatment of cerebral ischemia-reperfusion (CIR) and associated molecular network mechanism. Venny diagram, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis, protein-protein interaction (PPI), hub genes mining, molecular docking, combined with animal experiments and Nissl stain were performed to determine the molecular network mechanism of Qufeng Tongqiao Prescription for CIR treatment. Fifty three intersecting genes between Qufeng Tongqiao Prescription and cerebral ischemia reperfusion were acquired from Venny analysis. GO analysis showed that the main biological process (BP) was response to lipopolysaccharide, and the main cell localization (CC) process was membrane raft, while the most important molecular function (MF) process is Cytokine receptor binding. Moreover, AGE-RAGE signaling pathway in diabetic complications is the most important signaling pathway in KEGG pathway. Through molecular docking, it was found that Astragalus membranaceus was docked with MAPK14, IL4, FOS, IL6, and JUN; pueraria membranaceus was directly docked with JUN and IL4; Acorus acorus was linked to JUN and MAPK14; Ganoderma ganoderma and human were involved in JUN docking, and Ligusticum chuanqi and pueraria could not be docked with MAPK14, respectively. The results of animal experiments showed that Qufeng Tongqiao Prescription significantly improved behavioral performance and reduced the number of neuronal deaths in rats subjected to CIR, and molecular mechanisms are associated with FOS, IL-6, IL4, JUN, and MAPK14, of there, IL-6, as a vital candidator, which has been confirmed by immunostaining detection. Together, Qufeng Tongqiao Prescription has positive therapeutic effect on CIR, and the underlying mechanism is involved MAPK14, FOS, IL4, and JUN network, while IL-6 may be as a vital target., (© 2024 John Wiley & Sons Ltd.)

Interactions between astrocytes and microglia play an important role in the regeneration and repair of traumatic brain injury (TBI), and exosomes are involved in cell-cell interactions. A TBI model was constructed in rats. Brain extract (Ext) was isolated 1 d after TBI. Astrocyte-derived exosomes were obtained by coculturing Ext with primary astrocytes, and the morphology of exosomes was observed by electron microscopy. The isolated exosomes were cocultured with microglia to observe phenotypic changes in M1 and M2 markers. Aberrant RNA expression was detected in necrotic brain tissue and edematous brain tissue. The role of miR-148a-3p in regulating microglial phenotype was explored by knocking down or overexpressing miR-148a-3p. Finally, the effect of miR-148a-3p on TBI was studied in a rat TBI model. Astrocyte-derived exosomes stimulated by Ext promoted the transition of microglia from the M1 phenotype to the M2 phenotype. MiR-148a-3p was highly expressed in TBI. Transfecting miR-148a-3p promoted the transition of microglia from the M1 phenotype to the M2 phenotype and inhibited the lipopolysaccharide-induced inflammatory response in pre-microglia. In a rat TBI model, miR-148a-3p significantly improved the modified neurological severity score and attenuated brain injury, which promoted the transition of microglia from the M1 phenotype to the M2 phenotype. MiR-148a-3p alleviated TBI by inhibiting the nuclear factor κB pathway. Astrocyte-derived exosomal miR-148a-3p regulates the microglial phenotype, inhibits neuroinflammation, and restores neurological function in TBI. These results provide new potential targets for the treatment of TBI., (Copyright © 2024 Qian et al.)

Hot exciton organic light-emitting diode (OLED) emitters can balance the high performance of a device and reduce efficiency roll-off by fast reverse intersystem crossing from high-lying triplets (hRISC). In this study, an excited-state intramolecular proton transfer (ESIPT) fluorophore of 2-(benzo[d]thiazol-2-yl)-4-(pyren-1-yl)phenol (PyHBT) with the typical characteristic properties of a hot exciton is developed. With high efficiency of utilization of the exciton (91%), its yellow OLED exhibited high external quantum efficiency (EQE) of 5.6%, current efficiency (CE) of 16.8 cd A -1 , and power efficiency (PE) of 17.3 lm W -1 . The performance of the yellow emissive "hot exciton" ESIPT fluorophores is among the highest recorded. Due to the large Stokes shift of the ESIPT emitter, non-energy-transferred high-performance white OLEDs (WOLEDs) are developed, which are reproducible and highly efficient. This is possible because of the independent harvesting of most of the triplets in both complementary-color emitters without the interference of energy transfer. The PyHBT-based WOLEDs exhibit a maximum EQE of 14.3% and CE of 41.1 cd A -1 , which facilitates the high-yield mass production of inexpensive WOLEDs., (© 2023 Wiley-VCH GmbH.)

The pulsed electric field (PEF) of μs duration can induce electroporation by causing permanent damage to the membrane, leading to cell death. The microbe was treated by a homemade PEF generator instrument. The sterilization effect of PEF on the Rhizoctonia solani was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM), and the leakage of the intracellular contents was measured with a conductometer and an ultraviolet spectrophotometer. The increases in the electrical conductivity and the optical density (OD) value indicated that the cell membrane was damaged, and the intracellular contents overflowed. As a result, according to our experimental conditions, the optimum condition was the high-pulsed electric voltage of 26 kV, and the treatment time was 4 min. It could be concluded that the PEF could damage the cell membrane, and the ratio of electroporation reached 100%, which provides a new method of killing R. solani efficiently., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Autophagy exerts a vital role in the progression of lung squamous cell carcinoma (LUSC). Ubiquitin-specific peptidase 31 (USP31) has recently been found to be involved in the development of a variety of cancers. However, whether USP31 modulates autophagy in LUSC remains unclear., Methods: This study revealed that high levels of USP31 were discovered in LUSC tissue samples employing the Gene Expression Profiling Interactive Analysis (GEPIA) database, quantitative real- time PCR (qRT-PCR), and Western blot analysis. Cell proliferation was tested via cell counting kit 8 (CCK-8) as well as colony formation, demonstrating that USP31-stable knockdown reduced cell viability., Results: Immunofluorescence analysis illustrated that USP31 knockdown blocked the occurrence of LUSC autophagy. Meanwhile, USP31 has been shown to stabilize the expression of E2F transcription factor 1 (E2F1) through the proteasome pathway. Furthermore, overexpressed E2F1 effectively eliminated the effect of USP31 knockdown on LUSC cell proliferation and autophagy., Conclusion: In summary, this investigation proved that USP31 promoted LUSC cell growth and autophagy, at least in part by stabilizing E2F1 expression, which provided a potential therapeutic gene for the treatment of LUSC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins. Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs. However, it was found ANGPTL3 inhibitors were also effective in reducing low-density lipoprotein cholesterol (LDL-C) and they were studied in patients with homozygous familial hypercholesterolaemia (FH). Evinacumab targets ANGPTL3 and reduced LDL-C by about 50% in patients with homozygous FH and it has been approved for that indication. The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies. ApoC3 can be inhibited by the ASO volanesorsen, which reduced triglycerides by >70% in patients with FCS and it was approved for FCS in Europe but not in the United States because of concerns about thrombocytopaenia. Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. ARO-APOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies., Competing Interests: Conflict of Interest: Brian Tomlinson is the editor of Journal of LIpid and Atherosclerosis. However, he was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Korean Society of Lipid and Atherosclerosis.)

Introduction: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent clinical or subclinical allergic symptom of diseases of the upper and lower respiratory tract. This study is the first to explore the expression profiles of mRNA, lncRNA, and circRNA in CARAS using RNA sequencing, which may provide insight into the mechanisms underlying CARAS., Material and Methods: Whole blood samples from nine participants (three CARAS patients, three AR patients, and three normal control participants) were subjected to perform RNA sequencing, followed by identification of differentially expressed lncRNAs (DElncRNAs), circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Then, lncRNA/circRNA-mRNA regulatory pairs were constructed, followed by functional analysis, immune infiltration analysis, drug prediction, and expression validation with RT-qPCR and ELISA., Results: The results showed that 61 DEmRNAs, 23 DElncRNAs and 3 DEcircRNAs may be related to the occurrence and development of CARAS. KRT8 may be implicated in the development of AR into CARAS. Three immunity-related mRNAs (IDO1, CYSLTR2, and TEC) and two hypoxia-related mRNAs (TKTL1 and VLDLR) were associated with the occurrence and development of CARAS. TEC may be considered a drug target for Dasatinib in treating CARAS. Several lncRNA/circRNA-mRNA regulatory pairs were identified in CARAS, including LINC00452/MIR4280HG/hsa&#95;circ&#95;0007272/hsa&#95;circ&#95;0070934-CLC, HEATR6-DT/LINC00639/LINC01783/hsa&#95;circ&#95;0008903-TEC, RP11-71L14.3-IDO1/SMPD3, RP11-178F10.2-IDO1/HRH4, and hsa&#95;circ&#95;0008903-CYSLTR2, which may indicate potential regulatory effects of lncRNAs/circRNAs in CARAS. Dysregulated levels of immune cell infiltration may be closely related to CARAS., Conclusion: The regulating effect of lncRNA/circRNA-immunity/hypoxia-related mRNA regulatory pairs may be involved in the occurrence and development of CARAS., Competing Interests: The authors report no conflict of interest., (© 2023 Mao et al.)

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5's function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5's demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer., (© 2023. The Author(s).)

Previous studies have proved that exposure to extreme temperature in specific windows of pregnancy could cause some complications, such as pregnancy induced hypertension (PIH) and gestational diabetes mellitus (GDM), but differences in the effect of extreme temperature on the 2 complications are rarely studied. We carried a retrospective study on the impact of temperature on GDM/PIH in different trimesters based on data from a maternal and child health center in Beijing, China. Ambient temperatures (°C) were obtained from the China Meteorological Administration from January 1st, 2013 to May 15th, 2018. We use distributed lag non-linear models (DLNMs) combined with logistic regression to calculate the lag exposure-response relationships between the temperature and GDM/PIH from 1st to 24th/20th weeks of pregnancy. In both first and second trimesters, the risk of GDM was increased in summer with high temperatures; in second trimester, the risk of GDM increased in winter with low temperatures. In first half of pregnancy, risk of PIH was decreased in winter with low temperatures. These findings can provide the guideline for preventing the GDM and PIH induced by extreme temperature during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)