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Pu Yang,1 Tian Wang,1 Yu-Jun He,2 Sheng-Yong Su3,4 1The First School of Clinical Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Faculty of Acupuncture-Moxibustion and Tuina, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 3Department of Acupuncture-Moxibustion, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Sheng-Yong Su, Email ssy21008@126.comBackground: Chronic pain (CP) as a long-lasting stressor can often cause mood disorders, such as depression or anxiety. The comorbidity of CP and mood disorders poses challenges for treatment and increases healthcare costs. Acupuncture has emerged as a widely utilized approach to alleviate both CP and mood disorders. However, there is a lack of well-established bibliometric analyses in this area of research. Therefore, this study aimed to identify the current hotspots and research trends regarding the use of acupuncture for treating CP-related depression or anxiety.Methods: We searched the Web of Science Core Collection spanning from 2003 to 2023 to identify relevant literature about the use of acupuncture for treating CP-related depression or anxiety. Bibliometric and visualization analyses were performed using CiteSpace 5.7.R5 and Vosviewer 1.6.19 software.Results: A total of 254 articles published between 2003 and 2023 were included, revealing an upward trajectory with some fluctuations in publication numbers over the past two decades. China and the Beijing University of Chinese Medicine were the most productive country and institution in this field. Fang JQ and Vickers AJ ascended as the most prolific and influential authors, respectively. Trials was the journal with the highest number of publications, while Pain and BMJ-British Medical Journal exhibited the highest citation and centrality, respectively. “Acupuncture”, “depression”, and “chronic pain” were the top three keywords. The hotspots in this domain encompass types of chronic pain that predispose to negative mood, including fibromyalgia, irritable bowel syndrome (IBS), and neuropathic pain. Randomized controlled trials (RCTs), mechanisms, and evidence-based evaluations are the main research directions.Conclusion: This study uses bibliometric techniques to analyze the research hotspots and forefronts of acupuncture as a therapeutic approach for CP-related depression or anxiety. Our objective is to provide researchers with valuable references and identify research focal points for future investigations.Keywords: acupuncture, chronic pain, depression, anxiety, citespace, VOSviewer, bibliometric analysis

Cheng-Qiong Luo,1–3,* Lei Xing,1–3,* Peng-Fei Cui,1 Jian-Bin Qiao,1 Yu-Jing He,1 Bao-An Chen,4 Liang Jin,1,2,5 Hu-Lin Jiang1–3 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, 2Jiangsu Key Laboratory of Drug Screening, 3Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, 4Department of Hematology, The Affiliated Zhongda Hospital of Southeast University, 5School of Life Science and Technology, China Pharmaceutical University, Nanjing, China *These authors contributed equally to this work Background: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur. Materials and methods: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was –0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle. Conclusion: The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells. Keywords: coordination, curcumin, phenylboronic acid, stimuli-responsive, hydrogen peroxide

Background: Chemotherapeutic drugs used to treat cancer may cause nausea and emesis by inducing the release of 5-hydroxytryptamine (5-HT) in the small intestine. Blockage of 5-HT[3] receptors in the small intestine by 5-HT[3]-receptor antagonists might prevent the nausea and vomiting associated with chemotherapy for cancer.Objective: The aim of this study was to compare the efficacy and tolerability of the selective 5-HT[3] antagonists ramosetron (0.1-mg intraoral disintegrator preparation) and granisetron hydrochloride (2-mg standard tablet) in the treatment of acute chemotherapy-induced digestive disturbances.Methods: Male and female Chinese cancer patients aged 16 to 74 years were eligible for this multicenter, randomized, single-blind, crossover, comparison study. Patients were randomized to 1 of 2 treatment groups. Group 1 received 1-time administration of ramosetron 0.1 mg orally without water, followed by a 2-week washout period after which they received granisetron 2 mg orally with water. Group 2 received granisetron 2 mg orally with water, followed by a 2-week washout period after which they received ramosetron 0.1 mg orally without water. Each study drug was administered 1 time, 1 hour before infusion of the chemotherapeutic agent. For the efficacy assessment, response data were recorded every 6 hours for a total of 24 hours after the start of chemorecorded continuously over 24 hours.Results: A total of 73 patients (46 males, 27 females; mean age, 49.6 years [range, 17-70 years]) were enrolled. Group 1 comprised 37 patients; group 2, 36 patients. Data from 62 (84.9%) patients were used in the efficacy assessment; data from 70 (95.9%) patients were used in the tolerability assessment. The ability of ramosetron to prevent emesis, nausea, and anorexia was similar to that of granisetron during the 0-to-6-hour and 0-to-24-hour periods following administration of cisplatin or doxorubicin chemotherapy. The tolerability of ramosetron was similar to that of granisetron; AEs were generally mild and transient.Conclusions: In this study, both the intraoral disintegrator formulation of ramosetron and the standard tablet formulation of granisetron were clinically useful for preventing chemotherapy-induced digestive disturbances in cancer patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role of ITFG2, a protein highly expressed in cardiac tissues, in myocardial ischemic injury and its potential interactions with NEDD4-2. An in vivo myocardial infarction (MI) model was induced in mice via left anterior descending artery ligation, and ITFG2 expression was modulated using adeno-associated virus AAV9 vectors. Echocardiography was used to assess cardiac function, and primary mouse cardiomyocytes were cultured and subjected to hypoxia. ITFG2 expression was found to be significantly reduced following MI and in hypoxia-treated neonatal cardiomyocytes. Overexpression of ITFG2 improved cardiac contractility, reduced apoptosis, and stabilized calcium levels by inhibiting NEDD4-2-mediated ubiquitination of SERCA2a. Conversely, ITFG2 knockdown exacerbated calcium overload and cardiac dysfunction. Mechanistically, ITFG2 binds to NEDD4-2, decreasing its interaction with SERCA2a and preventing SERCA2a degradation. These findings suggest that ITFG2 acts as a critical inhibitor of NEDD4-2, preserving SERCA2a function and maintaining calcium homeostasis in cardiomyocytes under ischemic conditions. Therefore, ITFG2 may represent a potential therapeutic target for preventing myocardial ischemic injury and improving outcomes in MI patients., 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. Published by Elsevier Inc.)

A novel substrate-regulated [4+1] annulation of α-imidoyl sulfoxonium ylides with diazoketones under catalyst-free conditions is described. The reaction proceeds through a coupling of sulfoxonium ylides and in situ-generated ketenes to form the key reactive zwitterionic intermediates, followed by selective formation of C-C or C-O bonds to achieve five-membered ring systems. The cascade reaction permits the direct synthesis of synthetically useful 2-indanones and 3(2 H )-furanones, which expands the reaction pattern of sulfoxonium ylides in annulation transformation.

Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish ( Danio rerio ) were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 μg/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPARα. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPARα activation may be an important molecular initiating event for PFHxS.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial., Case Summary: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared., Conclusion: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe 3 O 4 @CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe 3 O 4 @CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe 3 O 4 @CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 μg L -1 ), low limits of detection (0.5-1.0 μg L -1 ), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe 3 O 4 @CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples., 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.)

Purpose: To investigate the feasibility and effect of free latissimus dorsi myocutaneous flap in the reconstruction of giant head and neck defects., Methods: Free latissimus dorsi myocutaneous flap on the cadaver was simulated dissected, and measured by Image-Pro Plus 6.0 to assess the feasibility of repairing giant head and neck defects. Between May 2011 and September 2022, seven patients with giant head and neck defects of different causes repaired with the latissimus dorsi myocutaneous flap were retrospectively analyzed., Results: The diameter of the initiating thoracodorsal artery was (4.03±0.56) mm, and the mean lengths of the arteriolar and venous pedicles of the latissimus dorsi myocutaneous flaps obtained from human specimens were (85.5±10.5) mm and (104±4.2) mm, respectively. Among 7 patients, 5 cases had scalp defects, the remaining 2 cases had neck defects. There were no substantial postoperative problems in the donor site, and all seven latissimus dorsi myocutaneous flaps were successfully transplanted., Conclusions: For the treatment of considerable head and neck deformities, the latissimus dorsi myocutaneous flap is an optimal muscle flap due to its abundance of tissue, enough length of vascular pedicles, and sufficient venous drainage.

Silicon (Si) stands out as a promising high-capacity anode material for high-energy Li-ion batteries. However, a drastic volume change of Si during cycling leads to the electrode structure collapse and interfacial stability degradation. Herein, a multifunctional quasisolid gel polymer electrolyte (QSGPE) is designed, which is synthesized through the in situ polymerization of methylene bis(acrylamide) with silica-nanoresin composed of nanosilica and a trifunctional cross-linker in cells, leading to the creation of a "breathing" three-dimensional elastic Li-ion conducting framework that seamlessly integrates an electrode, a binder, and an electrolyte. The silicon particles within the anode are encapsulated by buffering the QSGPE after cross-linking polymerization, which synergistically interacts with the existing PAA binder to reinforce the electrode structure and stabilize the interface. In addition, the formation of the LiF- and Li 3 N-rich SEI layer further improves the interfacial property. The QSGPE demonstrates a wide electrochemical window until 5.5 V, good flame retardancy, high ionic conductivity (1.13 × 10 -3 S cm -1 ), and a Li + transference number of 0.649. The advanced QSGPE and cell design endow both nano- and submicrosized silicon (smSi) anodes with high initial Coulombic efficiencies over 88.0% and impressive cycling stability up to 600 cycles at 1 A g -1 . Furthermore, the NCM811//Si cell achieves capacity retention of ca. 82% after 100 cycles at 0.5 A g -1 . This work provides an effective strategy for extending the cycling life of the Si anode and constructing an integrated cell structure by in situ polymerization of the quasisolid gel polymer electrolyte.

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B ( p -IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro . Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment., Competing Interests: 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., (© 2024 The Authors.)

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.

Objectives: To explore the rules of acupoint selection in the treatment of metabolic-associated fatty liver disease (MAFLD) with acupuncture and moxibustion by using data mining technology., Methods: The clinical research literature on acupuncture treatment of MAFLD was collected from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine from their inception to November 20, 2022. According to our inclusion and exclusion criteria, the literature was independently screened and re-screened by two research members, and the screened results were checked, followed by establishing an acupoint prescription database using Excel 2019. Descriptive statistics of acupoints applied frequency, involved meridians, locations and specific acupoints were perpormed. Then, SPSS Modeler18.0 software was used to conduct analysis about association rules, and the SPSS Statistics 26.0 software was used to perform cluster analysis on high-frequency acupoints, exploring the characteristics and rules of acupoint selection and combination in the treatment of MAFLD., Results: Totally, 178 papers were collected, containing 130 acupoints, with a total application frequency of 1 305. The top five acupoints are Zusanli (ST36), Fenglong (ST40), Ganshu (BL18), Taichong (LR3) and Sanyinjiao (SP6). The commonly involved meridians are the Stomach Meridian of Foot Yangming, Bladder Meridian of Foot Taiyang, and Spleen Meridian of Foot Taiyin. The employed acupoints are mostly located in the lower limbs and abdomen, and the five Shu acupoints and crossing acupoints are in the majority. The association rule analysis of high frequency acupoints indicated that of the 16 qualified acupoint groups, the top 5 with close correlation degrees are ST36 and ST40, ST36 and LR3, ST36 and SP6, ST40 and LR3 and ST36, ST36 and SP6 and ST40. Further, 3 effective clusters were obtained by cluster analysis., Conclusions: Acupuncture and moxibustion treatment of MAFLD follows the therapeutic principles of soothing the liver, invigorating the spleen, tonifying the kidney, and resolving phlegm and removing dampness. The core acupoint group is ST36, ST40 and LR3, and the combination of acupoints is based on syndrome differentiation. These results may provide a useful reference for clinical practice.

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector ( Laodelphax striatellus ) by regulating the target gene, zinc finger protein 708 ( LsZN708 ), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts., Competing Interests: Competing interests statement:The authors declare no competing interest.

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 μg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 μM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 μM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A one-pot synthesis afforded a magnetic, crosslinked polymer adsorbent (m-P6) with a variety of functional groups to realize simultaneous adsorption of Cd 2+ , Pb 2+ , Hg 2+ , and As 3+ . The material was characterized by TEM-EDS, XRD, FT-IR, VSM, and XPS. Kinetic and isothermal analyses suggested mainly chemisorption processes of heavy metal ions that form multiple layers on heterogeneous surfaces. Theoretical adsorption capacities calculated by a pseudo-2nd-order kinetic model and the Sips isothermal model were 282.88 mg/g for Cd 2+ , 326.18 mg/g for Pb 2+ , 117.85 mg/g for Hg 2+ , and 320.29 mg/g for As 3+ . m-P6 not only can efficiently adsorb divalent heavy metals (Cd 2+ , Pb 2+ , Hg 2+ ), but also demonstrate a process of adsorption-driven catalytic oxidation by single-electron transfer (SET) from As 3+ to As 5+ . In application, in addition to adsorption in water, m-P6 is capable of minimizing matrix interference, and extracting trace heavy metals in a complex environment (cereal) through easy operations for improving the detection accuracy, as well as it is potential for application in detection of trace heavy metals in foodstuffs. m-P6 can be readily regenerated and efficiently recycled for 5 cycles using eluent E12 and dilute acid., 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.)

Background: Metabolism dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease. Few MAFLD predictions are simple and accurate. We examined the predictive performance of the albumin-to-glutamyl transpeptidase ratio (AGTR), plasma atherogenicity index (AIP), and serum uric acid to high-density lipoprotein cholesterol ratio (UHR) for MAFLD to design practical, inexpensive, and reliable models., Methods: The National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle dataset, which contained 12,654 participants, was filtered and randomly separated into internal validation and training sets. This study examined the relationships of the AGTR and AIP with MAFLD using binary multifactor logistic regression. We then created a MAFLD predictive model using the training dataset and validated the predictive model performance with the 2017-2018 NHANES and internal datasets., Results: In the total population, the predictive ability (AUC) of the AIP, AGTR, UHR, and the combination of all three for MAFLD showed in the following order: 0.749, 0.773, 0.728 and 0.824. Further subgroup analysis showed that the AGTR (AUC1 = 0.796; AUC2 = 0.690) and the combination of the three measures (AUC1 = 0.863; AUC2 = 0.766) better predicted MAFLD in nondiabetic patients. Joint prediction outperformed the individual measures in predicting MAFLD in the subgroups. Additionally, the model better predicted female MAFLD. Adding waist circumference and or BMI to this model improves predictive performance., Conclusion: Our study showed that the AGTR, AIP, and UHR had strong MAFLD predictive value, and their combination can increase MAFLD predictive performance. They also performed better in females., (© 2024. The Author(s).)

Objectives: To explore the rules of acupoint selection in the treatment of neurogenic bladder (NB) with acupuncture and moxibustion by using data mining., Methods: The clinical research literatures on acupuncture treatment of NB were collected from PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP Database and China Biology Medicine from retrieved to January 1, 2023. The acupoint prescription database was established using Excel 2019. SPSS Modeler 18.0 and SPSS Statistics 26.0 softwares were used to conduct the frequency, meri-dians, locations, specific acupoints analysis and association rules analysis, factor analysis, cluster analysis, etc., to explore the characteristics and rules of acupoint selection in acupuncture and moxibustion treatment of NB., Results: Totally 313 papers were included, including 110 acupoints with a total frequency of 1 995. The high-frequency acupoints are Zhongji (CV3), Guanyuan (CV4), Sanyinjiao (SP6), etc. The commonly used meridians are the Bladder Meridian of Foot Taiyang and Conception Vessel. The involved acupoints are mostly located in the lumbosacral region and abdomen, and intersection acupoints, mu -front acupoints and back- shu acupoints are the majority in the specific acupoints. The core acupoints group was analyzed, and 17 groups of association rules, 7 factors and 6 effective cluster groups were obtained., Conclusions: Acupuncture and moxibustion treatment of NB follows the therapeutic principles of toni-fying the kidney, invigorating the spleen, and soothing the liver. The core acupoints group is CV3-CV4-SP6.

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitochondria are the most important energy supply centers in the cell, the changes in function and structure are implicated in many diseases. Among them, Aβ peptide, one of the targets of Alzheimer's disease, is closely related to mitochondrial autophagy, during the process of mitochondrial autophagy, the mitochondrial matrix will undergo acidification and the pH will be obviously reduced. Herein, a quinolinium-based NIR fluorescent probe QM12 was rationally designed and synthesized for the simultaneous imaging of Aβ aggregates and mitochondrial pH with different emission readout. The probe QM12 exhibited excellent selective toward Aβ aggregates, and can also trace the real-time changes of mitochondrial pH, which could serve as a promising tool for the pathological study of Alzheimer's disease, especially the cross talk between different biomarkers of Alzheimer's disease., 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.)

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C 5 →C 20 -olide, while compound 3 possesses unique degraded C 18 and C 19 . The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity., 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 Ltd. All rights reserved.)

Abstract: Aldehyde dehydrogenase 2 (ALDH2) protects the ischemic heart by activating adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling. However, the molecular mechanisms linking ALDH2 and AMPK signaling are not fully understood. This study aimed to explore the potential mechanisms linking ALDH2 and AMPK in myocardial ischemic injury. An ischemic model was established by ligating the left anterior descending coronary artery in rats. The overexpression or knockdown of ALDH2 in H9c2 cells treated with oxygen-glucose deprivation was obtained through lentivirus infection. Transferase-mediated dUTP nick-end labeling was used to evaluate apoptosis in an ischemic rat model and oxygen-glucose deprivation cells. ALDH2 activity, mitochondrial oxidative stress markers, adenosine triphosphate, respiratory control ratio, and cell viability in H9c2 cells were evaluated using a biological kit and 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide. Protein expression of ALDH2 , 4-hydroxynonenal, thioredoxin-1 (Trx-1), and AMPK-proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway was detected through Western blotting. ALDH2 activation reduced ischemic-induced myocardial infarct size and apoptosis. ALDH2 protected mitochondrial function by enhancing mitochondrial respiratory control ratio and adenosine triphosphate production, alleviated mitochondrial oxidative stress, and suppressed myocardial apoptosis. Moreover, ALDH2 attenuated ischemia-induced oxidative stress and maintained Trx-1 levels by reducing 4-hydroxynonenal, thereby promoting AMPK-PGC-1α signaling activation. Inhibiting Trx-1 or AMPK abolished the cardioprotective effect of ALDH2 on ischemia. ALDH2 alleviates myocardial injury through increased mitochondrial biogenesis and reduced oxidative stress, and these effects were achieved through Trx1-mediating AMPK-PGC1-α signaling activation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique., Methods: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected., Results: After modeling, compared with the blank group, the body mass and CTT were reduced ( P <0.01); fecal trait scores, fecal water contents and diarrhea index increased ( P <0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased ( P <0.01), and fecal trait score, fecal water content and diarrhea index increased ( P <0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated ( P< 0.01), while fecal trait scores, fecal water contents and diarrhea index declined ( P <0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group ( P< 0.05), while CTT increased in the acupuncture group ( P <0.01), the body mass increased and fecal trait score was dropped in the moxibustion group ( P <0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group ( P <0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group ( P <0.05), and the Richness index in the western medication group increased ( P< 0.05) when compared with those in the model group. The relative abundance of Bacteroidetes , Proteobacteria and Prevotella increased ( P <0.05), and that of Firmicutes and Muribaculaceae decreased ( P <0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes , Proteobacteria and Prevotella was reduced ( P <0.05), while that of Firmicutes and Muribaculaceae increased ( P <0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group ( P <0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated ( P <0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased ( P <0.05) in the model group. The relative abundance of LPS biosynthesis was dropped ( P <0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased ( P <0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group., Conclusions: Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.

Meteorological conditions play a key role in the occurrence and evolution of atmospheric complex pollution. Considering the different pollution formation mechanisms of PM 2.5 and O 3 , statistical calculation and in-depth learning methods were used to construct the PM 2.5 and O 3 meteorological condition indexes based on long-term pollution meteorological observation data. A research method was developed to study the meteorological characteristics and impact contribution of atmospheric complex pollution by using the meteorological condition index, and quantitative analysis of the distribution and variation of pollution excluding the influence of regional meteorological differences was also conducted. The results showed that in the summer of 2021, the pollution meteorological conditions in the key regions in central and eastern China were generally worse in the north and better in the south(index:"2+26" cities>the border area of Jiangsu, Anhui, Shandong, and Henan>the Yangtze River Delta) and the worst in June and the best in July. The "double high" pollution began to appear when the PM 2.5 meteorological condition index>30 and O 3 meteorological condition index>100; meanwhile, the unfavorable meteorological conditions for O 3 also promoted the increase in PM 2.5 concentration, resulting in the frequency of "double high" increases with the increase in O 3 meteorological condition index. Compared with that during the same period last year, ρ (PM 2.5 ) of each region decreased by 3.9 μg·m -3 , 3.3 μg·m -3 , and 1.4 μg·m -3 due to the contribution of the improvement in the pollution meteorological conditions, which is nearly 58.5% on average of the total decrease in PM 2.5 concentration. However, the change in O 3 pollution meteorological conditions was better in the north and worse in the south, and the overall deterioration in the Yangtze River Delta Region led to approximately 2.8 μg·m -3 growth for the O 3 concentration. The PM 2.5 and O 3 concentrations after excluding the impact of meteorological differences showed different distribution characteristics from the air quality monitoring, in which the high concentrations of PM 2.5 were distributed along the Bohai Sea, the inter-provincial border, and the south of the region, whereas the high concentrations of O 3 were concentrated along the Taihang Mountains, around Mount Tai, and in parts of the Yangtze River Delta. The daily concentration variations in a single city during a specific pollution control period could be used as a basis for evaluating the effectiveness of local supervision and control, which will provide a reference for the dynamic supervision and daily scheduling of local control management.

Nonlinear waves were found in various types of physical, chemical, and biological excitable media, e.g., in heart muscle. They can form three-dimensional (3D) vortices, called scroll waves, that are of particular significance in the heart, as they underlie lethal cardiac arrhythmias. Thus controlling the behavior of scroll waves is interesting and important. Recently, the optical feedback control procedure for two-dimensional vortices, called spiral waves, was developed. It can induce directed linear drift of spiral waves in optogenetically modified cardiac tissue. However, the extension of this methodology to 3D scroll waves is nontrivial, as optogenetic signals only penetrate close to the surface of cardiac tissue. Here we present a study of this extension in a two-variable reaction-diffusion model and in a detailed model of cardiac tissue. We show that the success of the control procedure is determined by the tension of the scroll wave filament. In tissue with positive filament tension the control procedure works in all cases. However, in the case of negative filament tension for a sufficiently large medium, instabilities occur and make drift and control of scroll waves impossible. Because in normal cardiac tissue the filament tension is assumed to be positive, we conclude that the proposed optical feedback scheme can be a robust method in inducing the linear drift of scroll waves that can control their positions in cardiac tissue.

Objective: The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation. Autophagy is a catabolic process responsible for maintaining cellular homeostasis. In recent years, autophagy has been demonstrated to play an important role in neuroinflammation. Resolvin D1 (RvD1) is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities. However, whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation. The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways., Methods: Mouse microglial cells (BV-2) were cultured, treated with RvD1, and examined by Western blotting, confocal immunofluorescence microscopy, transmission electron microscopy, and flow cytometry., Results: RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes. Importantly, RvD1 had no significant effect on the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II (CaMK II) activation. Moreover, by downregulating ATG5, the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy., Conclusion: The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy, highlighting its therapeutic potential against neuroinflammation., (© 2023. Huazhong University of Science and Technology.)

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes., (© 2023. The Author(s).)

Introduction: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown., Objectives: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis., Methods: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered., Results: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca 2+ influx and ATP release in lung epithelial cells., Conclusions: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis., 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. Production and hosting by Elsevier B.V.)

The efficient total synthesis of anti-tumor natural product pongaflavone ( 1 ) was described starting from commercially available 2,4-dihydroxyacetophenone ( 9 ) via seven steps and in 16% overall yield. Its two natural analogues pongachromene ( 2 ) and 7,8-(2",2"-dimethylpyrano)-5,3',4'-trihydroxy-3-methoxyflavone ( 3 ) were also synthesized following the similar procedure with the yields of 11% and 18%, respectively. Their preliminary anti-tumor activities were evaluated by the inhibition effect on A549 cells. The result showed that this kind of natural products exhibited different levels of anti-tumor activity. Among them, pongachromene ( 2 ) displayed the best anti-tumor activity.

Background and Objective: Nuclear segmentation in cervical cell images is a crucial technique for automatic cytopathology diagnosis. Experimental evaluation of nuclear segmentation methods with datasets is helpful in promoting the advancement of nuclear segmentation techniques. However, public datasets are not enough for a reasonable and comprehensive evaluation because of insufficient quantity, single data source, and low segmentation difficulty., Methods: Therefore, we provide the largest dataset for cervical nuclear segmentation (CNSeg). It contains 124,000 annotated nuclei collected from 1,530 patients under different conditions. The image styles in this dataset cover most practical application scenarios, including microbial infection, cytopathic heterogeneity, overlapping nuclei, etc. To evaluate the performance of segmentation methods from different aspects, we divided the CNSeg dataset into three subsets, namely the patch segmentation dataset (PatchSeg) with nuclei images collected under complex conditions, the cluster segmentation dataset (ClusterSeg) with cluster nuclei, and the domain segmentation dataset (DomainSeg) with data from different domains. Furthermore, we propose a post-processing method that processes overlapping nuclei single ones., Results and Conclusion: Experiments show that our dataset can comprehensively evaluate cervical nuclear segmentation methods from different aspects. We provide guidelines for other researchers to use the dataset. https://github.com/jingzhaohlj/AL-Net., 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. Published by Elsevier B.V.)

Triacylglycerols (TAG) from microalgae can be used as feedstocks for biofuel production to address fuel shortages. Most of the current research has focused on the enzymes involved in TAG biosynthesis. In this study, the effects of malic enzyme (ME), which provides precursor and reducing power for TAG biosynthesis, on biomass and lipid accumulation and its response to salt stress in Dunaliella salina were investigated. The overexpression of DsME1 and DsME2 improved the lipid production, which reached 0.243 and 0.253 g/L and were 30.5 and 36.3% higher than wild type, respectively. The transcript levels of DsME1 and DsME2 increased with increasing salt concentration (0, 1, 2, 3, and 4.5 mol/L NaCl), indicating that DsME s participated in the salt stress response in D. salina . It was found that cis-acting elements associated with the salt stress response were present on the promoters of two DsME s. The deletion of the MYB binding site (MBS) on the DsME2 promoter confirmed that MBS drives the expression of DsME2 to participate in osmotic regulation in D. salina . In conclusion, ME s are the critical enzymes that play pivotal roles in lipid accumulation and osmotic regulation.

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P <0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Background: The pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available., Methods: Here, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.g., western blotting, immunofluorescence and immunohistochemistry staining)., Results: We assessed the levels of DA neuron injury and oxidative stress in MPTP-induced PD mice and MPP + -induced MN9D cells after treating them with T-MSCs or T-MSCs-Exo. Furthermore, T-MSCs-Exo miRNA sequencing analysis revealed that miR-100-5p-enriched T-MSCs-Exo directly targeted the 3' UTR of NOX4, which could protect against the loss of DA neurons, maintain nigro-striatal system function, ameliorate motor deficits, and reduce oxidative stress via the Nox4-ROS-Nrf2 axis in PD models., Conclusions: The study suggests that miR-100-5p-enriched T-MSCs-Exo may be a promising biological agent for the treatment of PD. Schematic summary of the mechanism underlying the neuroprotective actions of T-MSCs-Exo in PD. T-MSCs Exo may inhibit the expression level of the target gene NOX4 by delivering miR-100-5p, thereby reducing ROS production and alleviating oxidative stress via the Nox4-ROS-Nrf2 axis, thus improving DA neuron damage in PD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Oxidation and removal of highly toxic sulfides and amines are particularly important for environmental and human security but remain challenging. Here, incorporating an excellent photosensitizer, donor-acceptor-donor (D-A-D)-type 4,4'-(benzo[ c ][1,2,5]thiadiazole-4,7-diyl)dibenzoic (H 2 L), into metal-organic frameworks (MOFs) has been manifested to promote the charge separation, affording four three-dimensional (3D) MOFs (isostructural 1-Co / 1-Zn with Co 2 /Zn 2 units, and 2-Gd / 2-Tb with Gd/Tb-cluster chains) as photocatalysts in the visible light-driven air-O 2 -mediated catalytic oxidation and removal of hazardous phenylsulfides and benzylamines. Impressively, structure-property correlation illustrated that the transition metal centers assembled in MOFs play an important role in the photocatalytic activity, and we can conclude that 1-Zn can be a robust heterogeneous catalyst possessing good light adsorption and fast charge separation in oxidation removal reactions of both benzylamines and phenylsulfides under visible light irradiation and room temperature with excellent activity/selectivity, stability, and reusability.

CF 3 -substituted imidoyl sulfoxonium ylides (TFISYs) are extraordinarily versatile and powerful synthons for use in cyclization chemistry that affords diverse CF 3 -substituted N-heterocycles. We first reacted TFISYs as a two-atom synthon with readily available azoalkenes and then subjected the products to metal-free formal (4+2) cycloaddition chemistry. This protocol features mild conditions and broad substrate scope, is simple to operate, and provides highly functionalized trifluoromethylpyridazines that are widely found in bioactive molecules.

Objective: To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells., Methods: Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay., Results: Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase ( P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 ( P < 0.05), CDC2 ( P < 0.01) and Bcl-2 ( P < 0.001) in HL-60 and Jurkat cells., Conclusion: Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by the loss of Shieldin proteins can be resensitized by the constitutive association of DYNLL1 with MRE11. These results define the temporal and functional dynamics of the 53BP1-centric DNA end resection factors in cells., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)