Search

Xiao-Li Yang,1,&ast; Wen-Yao Xie,2,&ast; Yi-Min Cai,3 Hong-Ying Tang,1 Mei-Yi Tao,3 Zhou-Min Shen,3 Hong-Jiao Chen4 1Department of Liver Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 2Interventional Operating Room, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 3Department of Nursing, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 4Medical College of Hunan Normal University, Changsha, 410013, People’s Republic of China&ast;These authors contributed equally to this studyCorrespondence: Yi-Min Cai, Nursing department, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, Jiefang West Road, Changsha, 410005, People’s Republic of China, Tel +86 13787129085, Fax +0731-83928047, Email cyimin2022@163.comPurpose: To understand existing negative emotions in patients with coronary heart disease after percutaneous coronary stent implantation (PCI) and analyse its influencing factors.Methods: Patients with coronary heart disease after PCI in three tertiary hospitals in Changsha City from April to September 2018 were selected as the research subjects. The self-designed general information questionnaire assessed irritability, depression and anxiety (IDA) on a self-rating scale. It was used to examine patients’ existing negative emotions with coronary heart disease after PCI and analyse the influencing factors.Results: 203 questionnaires were distributed, and 202 valid questionnaires were recovered, with an effective recovery rate of 99.5%. The IDA score of patients with coronary heart disease after PCI was 17.01± 7.60 points, the incidence of negative emotions was 63.8%, and the incidences of depression, anxiety and irritability were 39.6%, 8.4% and 15.8%, respectively. Negative emotion was taken as the dependent variable and a patient’s general data, such as lifestyle and disease, as the independent variables. A univariate analysis was conducted to obtain gender, age, educational level, marital status, work status, per capita monthly household income, sleep status, etc. Seven factors were identified as the influencing factors of negative emotions in patients with coronary heart disease after PCI, and the difference was statistically significant (P< 0.05).Conclusion: Most patients with coronary heart disease after PCI tend to exhibit negative emotions such as anxiety and depression. Medical staff should attach great importance to evaluating any negative feelings in this group and take timely targeted intervention measures to prevent and mitigate the occurrence and development of these adverse emotions in patients with coronary heart disease after PCI.Keywords: coronary heart disease, postoperative PCI, negative emotions, influencing factors

Aim: The goal of this study was to analyze the expression of human kallikrein 11 (hK11) in low rectal carcinoma (LRC) tissues, as well as its association with the clinicopathologic features of LRC patients and its prognostic significance.Methods: Between January 1998 and January 2003, 126 patients with LRC were randomized to receive laparoscopic-assisted abdominoperineal resection (APR). Their hK11 expression levels were examined by immunostaining on paraffin-embedded tumor specimens. Then the association of hK11 expression with clinicopathologic characteristics and patients' prognosis was analyzed.Results: The positive degree of immunohistochemical staining in cancerous tissues (1.86 +/- 0.02) was higher than that in the control group (1.18 +/- 0.11, P = 0.008). Strong positive hK11 staining associated significantly with various clinicopathologic features, such as Dukes Staging (P < 0.001), histological differentiation grade (P = 0.003), CEA level (P = 0.01), lymph node metastasis (P < 0.001), and invasion depth (P = 0.002). Patients with weak hK11 positive expression showed better survival rates of 5-year follow-up than those with strong positive expression (80.85% for weak positive expression and 58.23% in strong positive expression, respectively; P < 0.01 for analyses). Using Cox regression analysis of the 126 patients, strong positive expression of hK11, Dukes Staging, lymph node metastasis, and invasion depth seemed to be independent prognostic indicators (P < 0.01, P = 0.02, P < 0.01 and P < 0.01, respectively).Conclusion: hK11 may be another prognostic biomarker of LRC. Knowledge of hK11 expression in LRC tissues could contribute to the prediction of prognosis of LRC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stress management is one element of the lifestyle modification that is recommended for blood pressure control. Reduction in sympathetic arousal may be achieved through a series of audio relaxation training. AIMS: The purpose of this study was to evaluate the short-term and long-term effects of two audio relaxation programs for blood pressure reduction in older adults. METHODS: This clinical randomized study consists of 12-sessions of intervention, with one-month and three-month follow up measures. 41 older adults were randomly assigned to either listening to a 12-minute audio relaxation program or a 12-minute Mozart andante. At each session, blood pressures were recorded. RESULTS: For both groups, the reduction in systolic and diastolic blood pressures after the 12-session intervention training was statistically and clinically significant. The reduction in systolic blood pressure was greater in the audio relaxation group than the Mozart group. The adherence to the program at one-month and three-month was 54% and 66% respectively. The blood pressure at one-month and three-month were not significantly different than the initial measurement. CONCLUSIONS: Significant blood pressure reduction can be achieved through a brief 12-minute audio relaxation program with older adults. Guided relaxation may be more effective in lowering blood pressure than plain music. [ABSTRACT FROM AUTHOR]

Background: CISD-1 is a mitochondrial iron-sulfate [2Fe-2S] protein known to be associated with various human diseases, including cancer and diabetes. Previously, we demonstrated that CISD-1 deficiency in worms lowers glucose and ATP levels. In this study, we further explored how worms compensate for lower ATP levels by analyzing changes in cytoplasmic and mitochondrial iron content, AMPK activities, and total lipid profiles., Materials and Methods: Expression levels of CISD-1 and CISD-1::GFP fusion proteins in wild-type worms (N2), cisd-1-deletion mutants (tm4993 and syb923) and GFP insertion transgenic worms (PHX953 and SJL40) were examined by western blot. Fluorescence microscopy analyzed CISD-1::GFP pattern in PHX953 embryos and adults, and lipid droplet sizes in N2, cisd-1, aak-2 and aak-2;cisd-1 worms. Total and mitochondrial iron content, electron transport complex profiles, and AMPK activity were investigated in tm4993 and syb923 mutants. mRNA levels of mitochondrial β-oxidation genes, acs-2, cpt-5, and ech-1, were quantified by RT-qPCR in various genetic worm strains. Lipidomic analyses were performed in N2 and cisd-1(tm4993) worms., Results: Defects in cisd-1 lead to an imbalance in iron transport and cause proton leak, resulting in lower ATP production by interrupting the mitochondrial electron transport chain. We identified a signaling pathway that links ATP deficiency-induced AMPK (AMP activated protein kinase) activation to the expression of genes that facilitate lipolysis via β-oxidation., Conclusion: Our data provide a functional coordination between CISD-1 and AMPK constitutes a mitochondrial bioenergetics quality control mechanism that provides compensatory energy resources., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In-stent restenosis is characterized by a significant reduction in lumen diameter within the stented segment, primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia. PFN1 (profilin-1), an actin-sequestering protein extensively studied in amyotrophic lateral sclerosis, remains less explored in neointimal hyperplasia., Methods: Utilizing single-cell RNA sequencing alongside data from in-stent restenosis patients and various experimental in-stent restenosis models (swine, rats, and mice), we investigated the role of PFN1 in promoting VSMC phenotype switching and neointimal hyperplasia., Results: Single-cell RNA sequencing of stenotic rat carotid arteries revealed a critical role for PFN1 in neointimal hyperplasia, a finding corroborated in stented swine coronary arteries, in-stent restenosis patients, PFN1 SMC-IKO (SMC-specific PFN1 knockout) mice, and PFN1 overexpressed mice. PFN1 deletion was shown to suppress VSMC phenotype switching and neointimal hyperplasia in PFN1 SMC-IKO mice subjected to a wire-injured model. To elucidate the observed discordance in PFN1 mRNA and protein levels, we identified that METTL3 (N 6 -methyladenosine methyltransferase) and YTHDF3 (N 6 -methyladenosine-specific reader) enhance PFN1 translation efficiency in an N 6 -methyladenosine-dependent manner, confirmed through experiments involving METTL3 knockout and YTHDF3 knockout mice. Furthermore, PFN1 was mechanistically found to interact with the phosphorylation of ANXA2 (annexin A2) by recruiting Src, promoting the phosphorylation of STAT3, a typical transcription factor known to induce VSMC phenotype switching., Conclusions: This study unveils the significance of PFN1 N 6 -methyladenosine modification in VSMCs, demonstrating its role in promoting phenotype switching and neointimal hyperplasia through the activation of the p-ANXA2 (phospho-ANXA2)/STAT3 pathway.

In the present study, we presented the detailed procedure and experience of endoscope-assisted transoral procedure of accessory parotid gland (APG) tumor resection. The surgical steps and tips were described and summarized clearly in our video. Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Mutations in the RNA helicase DDX3X, implicated in various cancers and neurodevelopmental disorders, often impair RNA unwinding and translation. However, the mechanisms underlying the impairment and the differential interactions of DDX3X mutants with wild-type (WT) X-linked DDX3X and Y-linked homolog DDX3Y remain elusive. This study reveals that specific DDX3X mutants more frequently found in disease form distinct hollow condensates in cells. Using a combined structural, biochemical, and single-molecule microscopy study, we show that reduced ATPase and RNA release activities contribute to condensate formation and these catalytic deficits result from inhibiting the catalytic cycle at multiple steps. Proteomic investigations further demonstrate that these hollow condensates sequester WT DDX3X/DDX3Y and other proteins crucial for diverse signaling pathways. WT DDX3X enhances the dynamics of heterogeneous mutant/WT hollow condensates more effectively than DDX3Y. These findings offer valuable insights into the catalytic defects of specific DDX3X mutants and their differential interactions with wild-type DDX3X and DDX3Y, potentially explaining sex biases in disease., (© 2024. The Author(s).)

Huntington's disease (HD) is associated with dysregulated choline metabolism, but the underlying mechanisms remain unclear. This study investigated the expression of key enzymes in this pathway in R6/2 HD mice and human HD postmortem brain tissues. We further explored the therapeutic potential of modulating choline metabolism for HD. Both R6/2 mice and HD patients exhibited reduced expression of glycerophosphocholine phosphodiesterase 1 (GPCPD1), a key enzyme in choline metabolism, in the striatum and cortex. The striatum of R6/2 mice also showed decreased choline and phosphorylcholine, and increased glycerophosphocholine, suggesting disruption in choline metabolism due to GPCPD1 deficiency. Treatment with citicoline significantly improved motor performance, upregulated anti-apoptotic Bcl2 expression, and reduced oxidative stress marker malondialdehyde in both brain regions. Metabolomic analysis revealed partial restoration of disrupted metabolic patterns in the striatum and cortex following citicoline treatment. These findings strongly suggest the role of GPCPD1 deficiency in choline metabolism dysregulation in HD. The therapeutic potential of citicoline in R6/2 mice highlights the choline metabolic pathway as a promising target for future HD therapies., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Postural instability and gait disorder and cognitive dysfunction are common symptoms of Parkinson's disease (PD). Scale assessment is frequently used in the clinic to evaluate PD, but this technique is limited by its lack of sensitivity to changes in disease progression and its difficulty in capturing subtle movements and changes in cognitive function. It is currently believed that high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve motor and cognitive dysfunction in patients with PD, though it remains controversial. Therefore, it is imperative to monitor and dynamically identify changes in postural instability and gait disorder, as well as those in cognitive dysfunction, in PD to develop targeted interventions. In this study, we observed the effect of high-frequency rTMS on gait disorders and cognitive functions in patients with PD by comparing data from wearable devices and eye-tracking devices before and after treatment., Methods: A total of 159 patients with PD were included in this study. A GYENNO MATRIX wearable gait analyzer was used to monitor the objective gait data (including the timed up-and-go, narrow-track, and turning tests), the Eyeknow eye-tracking evaluation system was used to monitor the patient's eye movement cognition data (including the smooth pursuit, pro-saccade, and anti-saccade tests), and gait and cognitive function-related scales, including the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment (MoCA), were evaluated at the same time before and after high-frequency rTMS treatment., Results: The mean step length, mean stride velocity, stride length, and mean step frequency of patients with PD in the timed up-and-go test all increased compared with those before rTMS treatment, whereas the mean stride time and double support decreased. In the narrow-track test, the mean stride velocity increased and the mean stride time decreased. In the turning test, the turning left duration, turning right duration, mean duration, mean number of steps, and average step duration decreased, while the mean angular velocity increased after rTMS treatment. Compared with those before rTMS treatment, the latency period of patients with PD in overlapping saccades decreased, the completion time of overlapping saccades decreased, and the average saccade speed increased. In the anti-saccade test, the completion time decreased and the average saccade speed increased after rTMS treatment. Compared with those before rTMS treatment, the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and MoCA scores increased, and the MoCA sub-items improved in terms of visual-spatial and executive function, language, abstraction, delayed recall, and orientation after rTMS treatment., Conclusion: High-frequency rTMS may be an effective therapy for improving gait disorders and cognitive functions in patients with PD., 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 Tang, Liao, Li, Zhang, Yao, Xing, Zhao, He, Zan and Li.)

Macroautophagy/autophagy-lysosome function promotes growth and survival of cancer cells, making them attractive targets for cancer therapy. One intriguing lysosomal target is PPT1 (palmitoyl-protein thioesterase 1). PPT1 inhibitors derived from chloroquine block autophagy, have significant antitumor activity in preclinical models and are being developed for clinical trials. However, the role of PPT1 in tumorigenesis remains poorly understood. Here we report that in melanoma cells, acute siRNA or pharmacological PPT1 inhibition led to increased ferroptosis sensitivity and significant loss of viability, whereas chronic PPT1 knockout using CRISPR-Cas9 produced blunted ferroptosis that led to sustained viability and growth. Each mode of PPT1 inhibition produced lysosome-autophagy inhibition but distinct proteomic changes, demonstrating the complexity of cellular adaptation mechanisms. To determine whether total genetic loss of Ppt1 would affect tumorigenesis in vivo, we developed a Ppt1 conditional knockout mouse model. We then crossed it into the BrafCA, PtenloxP, Tyr:CreERT2 melanoma mouse model to investigate the impact of Ppt1 loss on tumorigenesis. Loss of Ppt1 had no impact on melanoma histology, time to tumor initiation, or survival of tumor-bearing mice. These results suggest that chemical PPT1 inhibitors produce different adaptations than genetic PPT1 inhibition, and additional studies are warranted to fully understand the mechanism of chloroquine derivatives that target PPT1 in cancer. Abbreviations : 4-HT: 4-hydroxytamoxifen; BRAF: B-Raf proto-oncogene, serine/threonine kinase; cKO: conditional knockout; CRISPR-Cas9: clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9; DC661: A specific PPT1 inhibitor; DMSO: dimethyl sulfoxide; Dox; doxycycline hyclate; Easi-CRISPR: efficient additions with ssDNA inserts-CRISPR; GNS561/ezurpimtrostat: A PPT1 inhibitor; Hug: human guide; iCas: inducible CRISPR-Cas9; KO: knockout; LC-MS/MS: Liquid chromatography-tandem mass spectrometry; LDLR: low density lipoprotein receptor; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NT: non-target; PTEN: phosphatase and tensin homolog; PPT1: palmitoyl-protein thioesterase 1; RSL3: RAS-selective lethal small molecule 3; SCRIB/SCRB1: scribble planar cell polarity protein; Tyr:CreERT2 : tyrosinase-driven Cre recombinase fused with the tamoxifen-inducible mutant ligand binding domain of the human estrogen receptor; UGCG: UDP-glucose ceramide glucosyltransferase; WT: wild-type.

The activation of innate immunity and associated interferon (IFN) signaling have been implicated in cancer, but the regulators are elusive and links to tumor suppression remain undetermined. Here, we found that Parkin, an E3 ubiquitin ligase altered in Parkinson's Disease, was epigenetically silenced in cancer and its reexpression by clinically approved demethylating therapy stimulated transcription of a potent IFN response in tumor cells. This pathway required Parkin E3 ubiquitin ligase activity, involved the subcellular trafficking and release of the alarmin High Mobility Group Box 1 (HMGB1) and was associated with inhibition of NF-κB gene expression. In turn, Parkin-expressing cells released an IFN secretome that upregulated effector and cytotoxic CD8+ T cell markers, lowered the expression of immune inhibitory receptors TIM3 and LAG3, and stimulated high content of the self renewal/stem cell factor, TCF1. PRKN-induced CD8+ T cells selectively accumulated in the microenvironment and inhibited transgenic and syngeneic tumor growth in vivo. Therefore, Parkin is an epigenetically regulated activator of innate immunity and dual mode tumor suppressor, inhibiting intrinsic tumor traits of metabolism and cell invasion, while simultaneously reinvigorating CD8 T cell functions in the microenvironment.

Multiple reaction monitoring (MRM) is a powerful and popular technique used for metabolite quantification in targeted metabolomics. Accurate and consistent quantitation of metabolites from the MRM data is essential for subsequent analyses. Here, we developed an automated tool, MRMQuant, for targeted metabolomic quantitation using high-throughput liquid chromatography-tandem mass spectrometry MRM data to provide users with an easy-to-use tool for accurate MRM data quantitation with minimal human intervention. This tool has many user-friendly functions and features to inspect and correct the quantitation results as required. MRMQuant possesses the following features to ensure accurate quantitation: (1) dynamic signal smoothing, (2) automatic deconvolution of coeluted peaks, (3) absolute quantitation via standard curves and/or internal standards, (4) visualized inspection and correction, (5) corrections applicable to multiple samples, and (6) batch-effect correction.

It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low-density sEV subpopulation. This low-density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell-derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Aged patients with melanoma (>65 years old) have more aggressive disease relative to young patients (<55 years old) for reasons that are not completely understood. Analysis of the young and aged secretome from human dermal fibroblasts identified >5-fold levels of IGF-binding protein 2 (IGFBP2) in the aged fibroblast secretome. IGFBP2 functionally triggers upregulation of the PI3K-dependent fatty acid biosynthesis program in melanoma cells. Melanoma cells co-cultured with aged dermal fibroblasts have higher levels of lipids relative to those co-cultured with young dermal fibroblasts, which can be lowered by silencing IGFBP2 expression in fibroblasts prior to treating with conditioned media. Conversely, ectopically treating melanoma cells with recombinant IGFBP2 in the presence of conditioned media from young fibroblasts or overexpressing IGFBP2 in melanoma cells promoted lipid synthesis and accumulation in melanoma cells. Treatment of young mice with rIGFBP2 increases tumor growth. Neutralizing IGFBP2 in vitro reduces migration and invasion in melanoma cells, and in vivo studies demonstrate that neutralizing IGFBP2 in syngeneic aged mice reduces tumor growth and metastasis. Our results suggest that aged dermal fibroblasts increase melanoma cell aggressiveness through increased secretion of IGFBP2, stressing the importance of considering age when designing studies and treatment., Significance: The aged microenvironment drives metastasis in melanoma cells. This study reports that IGFBP2 secretion by aged fibroblasts induces lipid accumulation in melanoma cells, driving an increase in tumor invasiveness. Neutralizing IGFBP2 decreases melanoma tumor growth and metastasis., (©2024 The Authors; Published by the American Association for Cancer Research.)

Huntington's disease (HD) is characterized by progressive involuntary chorea movements and cognitive decline. Recent research indicates that metabolic disturbance may play a role in its pathogenesis. Bile acids, produced during cholesterol metabolism in the liver, have been linked to neurodegenerative conditions. This study investigated variations in plasma bile acid profiles among individuals with HD. Plasma levels of 16 primary and secondary bile acids and their conjugates were analyzed in 20 healthy controls and 33 HD patients, including 24 with symptoms (symHD) and 9 carriers in the presymptomatic stage (preHD). HD patients exhibited significantly higher levels of glycochenodeoxycholic acid (GCDCA) and glycoursodeoxycholic acid (GUDCA) compared to healthy controls. Conversely, isolithocholic acid levels were notably lower in the HD group. Neurotoxic bile acids (glycocholic acid (GCA) + glycodeoxycholic acid (GDCA) + GCDCA) were elevated in symHD patients, while levels of neuroprotective bile acids (ursodeoxycholic acid (UDCA) + GUDCA + tauroursodeoxycholic acid (TUDCA)) were higher in preHD carriers, indicating a compensatory response to early neuronal damage. These results underscore the importance of changes in plasma bile acid profiles in HD and their potential involvement in disease mechanisms. The identified bile acids (GCDCA, GUDCA, and isolithocholic acid) could potentially serve as markers to distinguish between HD stages and healthy individuals. Nonetheless, further research is warranted to fully understand the clinical implications of these findings and their potential as diagnostic or therapeutic tools for HD.

In this study, the mercury-tolerant strain LTC105 was isolated from a contaminated soil sample collected from a molybdenum-lead mine in Luanchuan County, Henan Province, China. The strain was shown to be highly resistant to mercury, with a minimum inhibitory concentration (MIC) of 32 mg·L -1 . After a 24-h incubation in LB medium with 10 mg·L -1 Hg 2+ , the removal, adsorption, and volatilization rates of Hg 2+ were 97.37%, 7.3%, and 90.07%, respectively, indicating that the strain had significant influence on mercury removal. Based on the results of Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), the investigation revealed that the primary function of LTC105 was to encourage the volatilization of mercury. The LTC105 strain also showed strong tolerance to heavy metals such as Mn 2+ , Zn 2+ , and Pb 2+ . According to the results of the soil incubation test, the total mercury removal rate of the LTC105 inoculation increased by 16.34% when the initial mercury concentration of the soil was 100 mg·L -1 and by 62.28% when the initial mercury concentration of the soil was 50 mg·kg -1 . These findings indicate that LTC105 has certain bioremediation ability for Hg-contaminated soil and is a suitable candidate strain for microbial remediation of heavy metal-contaminated soil in mining areas., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A novel methodology for the synthesis of nitrones via palladium-catalyzed redox cross-coupling of nitro compounds and alcohols is established. The protocol is a mild, convenient, ligand-free, and scalable synthesis method that can be compatible with various nitro compounds and alcohols. Nitrone is a significant multifunctional platform synthon which can be synthesized directly and efficiently via this tactic from commercially available and cheap raw materials.

DNA polymerase theta (Polθ)-mediated end-joining (TMEJ) repairs DNA double-strand breaks and confers resistance to genotoxic agents. How Polθ is regulated at the molecular level to exert TMEJ remains poorly characterized. We find that Polθ interacts with and is PARylated by PARP1 in a HPF1-independent manner. PARP1 recruits Polθ to the vicinity of DNA damage via PARylation dependent liquid demixing, however, PARylated Polθ cannot perform TMEJ due to its inability to bind DNA. PARG-mediated de-PARylation of Polθ reactivates its DNA binding and end-joining activities. Consistent with this, PARG is essential for TMEJ and the temporal recruitment of PARG to DNA damage corresponds with TMEJ activation and dissipation of PARP1 and PAR. In conclusion, we show a two-step spatiotemporal mechanism of TMEJ regulation. First, PARP1 PARylates Polθ and facilitates its recruitment to DNA damage sites in an inactivated state. PARG subsequently activates TMEJ by removing repressive PAR marks on Polθ., (© 2024. The Author(s).)

The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency. Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes cohesin acetylation on chromatin, resulting in uncontrolled chromatin loop extrusion, defective DNA replication, and apoptosis. Collectively, our findings uncover an endogenous, cell autonomous function of DCAF15 in sustaining AML proliferation through post-translational control of cohesin dynamics., (© 2024. The Author(s).)

Milk fat content is a critical indicator of milk quality. Exploring the key regulatory genes involved in milk fat synthesis is essential for enhancing milk fat content. STF-62247 (STF), a thiazolamide compound, has the potential to bind with ALG5 and upregulate lipid droplets in fat synthesis. However, the effect of STF on the process of milk fat synthesis and whether it acts through ALG5 remains unknown. In this study, the impact of ALG5 on milk fat synthesis and its underlying mechanism were investigated using bovine mammary epithelial cells (BMECs) and mouse models through real-time PCR, western blotting, Oil Red O staining, and triglyceride analysis. Experimental findings revealed a positive correlation between STF and ALG5 with the ability to synthesize milk fat. Silencing ALG5 led to decreased expression of FASN, SREBP1, and PPARγ in BMECs, as well as reduced phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. Moreover, the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway were restored when ALG5 silencing was followed by the addition of STF. These results suggest that STF regulates fatty acid synthesis in BMECs by affecting the PI3K/AKT/mTOR signaling pathway through ALG5. ALG5 is possibly a new factor in milk fat synthesis.

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle., Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis., Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups ( P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR., Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Antibiotic residue stands as a significant ongoing environmental issue, with aquaculture being a major source of annual antibiotic discharge into the ocean. Nevertheless, there is still an incomplete evaluation of antibiotic residues in the Beibu Gulf, an area encompassed by two prominent aquaculture nations, China and Vietnam. The present systematic review and meta-analysis was conducted to examine the presence antibiotic residues in the Beibu Gulf based on published studies. Data were obtained through eight databases up to December 19th, 2023, and were updated on April 15th, 2024. The pooled concentration of antibiotic residues in seawater was 5.90 (ng/L), ranging from 5.73 to 6.06 (ng/L), and was 8.03 (ng/g), ranging from 7.77 to 8.28 (ng/g) in sediments. Fluoroquinolones, tetracyclines, and macrolides were identified as the main antibiotics found in both seawater and sediment samples. The Beibu Gulf showed higher antibiotic levels in its western and northeastern areas. Additionally, the nearshore mangrove areas displayed the highest prevalence of antibiotic residues. It is strongly advised to conduct regular long-term monitoring of antibiotic residues in the Beibu Gulf. Collaborative surveys covering the entire Beibu Gulf involving China and Vietnam are recommended., 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.)

Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.

Background: Folic acid (FA) supplementation before and in early pregnancy is known to improve outcomes such as reducing neural tube defects; however, little is known about groups in Australia at risk of low FA use., Aim: To determine whether differences exist in FA supplementation rates between Australian-born women and migrant women, with a secondary aim of examining the sociodemographic characteristics of women who are not supplementing with FA in early pregnancy., Methods: A retrospective cohort study from January 2018-July 2022 in a high-migrant population in Western Sydney, Australia. Multivariate logistic regression analysis was conducted adjusting for confounders including place of birth, age, ethnicity, parity, history of diabetes, and type of conception., Findings: There were 48,045 women who met inclusion criteria; 65% of whom were migrants. We identified that 39.4% of the study population did not report FA supplementation by early pregnancy. Women who were migrants were more likely to report FA usage than those born in Australia (aOR 1.24; 95%CI 1.17-1.31). Women least likely to report use of FA were women < 20 years of age (aOR 0.54; 95%CI 0.44-0.67) and multiparous women (aOR 0.84; 95%CI 0.82-0.86). Women with type 1 or type 2 diabetes were more likely to report FA use (aOR 1.66; 95%CI 1.11-2.48, aOR 1.30; 95%CI 1.05-1.61)., Conclusion: A significant proportion of the population did not report FA supplementation before or during early pregnancy. To increase uptake of FA supplementation, clinicians and public health messaging should target at-risk groups., 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.)

The role of polyunsaturated fatty acid (PUFA) biosynthesis in acute myeloid leukemia (AML) remains largely undefined. A comparative expression analysis of 35 genes encoding fatty acid biosynthesis enzymes showed that fatty acid desaturase 1 (FADS1) was highly expressed across multiple AML subtypes relative to healthy controls and that elevated FADS1 expression correlates with worse overall AML patient survival. Functionally, shRNA-mediated inhibition of FADS1 reduced AML cell growth in vitro and significantly delayed leukemia onset in an AML mouse model. AML cell lines depleted of FADS1 arrested in the G1/S-phase of the cell cycle, acquired characteristics of myeloid maturation and subsequently died. To understand the molecular consequences of FADS1 inhibition, a combination of mass spectrometry-based analysis of complex lipids and gene expression analysis (RNA-seq) was performed. FADS1 inhibition caused AML cells to exhibit significant lipidomic remodeling, including depletion of PUFAs from the phospholipids, phosphatidylserine, and phosphatidylethanolamine. These lipidomic alterations were accompanied by an increase induction of inflammatory and stimulator of interferon genes (STING)-mediated type-1 interferon signaling. Remarkably, genetic deletion of STING largely prevented the AML cell maturation and death phenotypes mediated by FADS1 inhibition. Highlighting the therapeutic implications of these findings, pharmacological blockade of PUFA biosynthesis reduced patient-derived AML cell numbers ex vivo but not that of healthy donor cells. Similarly, STING agonism attenuated patient-derived-AML survival; however, STING activation also reduced healthy granulocyte numbers. Collectively, these data unveil a previously unrecognized importance of PUFA biosynthesis in leukemogenesis and that imbalances in PUFA metabolism can drive STING-mediated AML maturation and death., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear., Aim: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms., Methods: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro , human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence., Results: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS., Conclusion: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process., 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.)

Surface modification is a highly effective strategy for addressing issues in lithium-rich layered oxide (LLO) cathodes, including phase transformation, particle cracking, oxygen gas release, and transition-metal ion dissolution. Existing single-/double-layer coating strategies face drawbacks such as poor component contact and complexity. Herein, we present the results of a low-temperature atomic layer deposition (ALD) process for creating a TiO 2 /Al 2 O 3 bilayer on composite cathodes made of AS200 (Li 1.08 Ni 0.34 Co 0.08 Mn 0.5 O 2 ). Electrochemical analysis demonstrates that TiO 2 /Al 2 O 3 -coated LLO electrodes exhibit improved discharge capacities and enhanced capacity retention compared with uncoated samples. The TAA-5/AS200 bilayer-coated electrode, in particular, demonstrates exceptional capacity retention (∼90.4%) and a specific discharge capacity of 146 mAh g -1 after 100 cycles at 1C within the voltage range of 2.2 to 4.6 V. The coated electrodes also show reduced voltage decay, lower surface film resistance, and improved interfacial charge transfer resistances, contributing to enhanced stability. The ALD-deposited TiO 2 /Al 2 O 3 bilayer coatings exhibit promising potential for advancing the electrochemical performance of lithium-rich layered oxide cathodes in lithium-ion batteries.

Prior studies showed that polyglutamine-expanded androgen receptor (AR) is aberrantly acetylated and that deacetylation of the mutant AR by overexpression of nicotinamide adenine dinucleotide-dependent (NAD+-dependent) sirtuin 1 is protective in cell models of spinal and bulbar muscular atrophy (SBMA). Based on these observations and reduced NAD+ in muscles of SBMA mouse models, we tested the therapeutic potential of NAD+ restoration in vivo by treating postsymptomatic transgenic SBMA mice with the NAD+ precursor nicotinamide riboside (NR). NR supplementation failed to alter disease progression and had no effect on increasing NAD+ or ATP content in muscle, despite producing a modest increase of NAD+ in the spinal cords of SBMA mice. Metabolomic and proteomic profiles of SBMA quadriceps muscles indicated alterations in several important energy-related pathways that use NAD+, in addition to the NAD+ salvage pathway, which is critical for NAD+ regeneration for use in cellular energy production. We also observed decreased mRNA levels of nicotinamide riboside kinase 2 (Nmrk2), which encodes a key kinase responsible for NR phosphorylation, allowing its use by the NAD+ salvage pathway. Together, these data suggest a model in which NAD+ levels are significantly decreased in muscles of an SBMA mouse model and intransigent to NR supplementation because of decreased levels of Nmrk2.

Plasma lipid levels are commonly measured using traditional methods such as triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CH). However, the use of newer technologies, such as nuclear magnetic resonance (NMR) with post-analysis platforms, has made it easier to assess lipoprotein profiles in research. In this study involving ApoE-deficient mice that were fed high-fat diets, significant changes were observed in TG, CH, free cholesterol (FC), and phospholipid (PL) levels within the LDL fraction. The varied proportions of TG in wild-type mice and CH, FC, and PL in ApoE -/- mice were strikingly different in very low-density lipoproteins (VLDL), LDL, intermediate-density lipoprotein (IDL), and HDL. This comprehensive analysis expands our understanding of lipoprotein subfractions and the impacts of the APOE protein and high-fat diet in mouse models. The new testing method allows for a complete assessment of plasma lipids and their correlation with genetic background and diet in mice.

The coming of the hyper-aged society in Taiwan prompts us to investigate the relationship between the metabolic status of sarcopenic patients and their most adverse outcome-death. We studied the association between any plasma metabolites and the risk for mortality among older Taiwanese sarcopenic patients. We applied a targeted metabolomic approach to study the plasma metabolites of adults aged ≥65 years, and identified the metabolic signature predictive of the mortality of sarcopenic patients who died within a 5.5-year follow-up period. Thirty-five sarcopenic patients who died within the follow-up period ( Dead cohort) had shown a specific plasma metabolic signature, as compared with 54 patients who were alive ( Alive cohort). Only 10 of 116 non-sarcopenic individuals died during the same period. After multivariable adjustment, we found that sex, hypertension, tetradecanoyl-carnitine (C14-carnitine), and docosahexaenoic acid (DHA)-containing phosphatidylcholine diacyl (PCaa) C38:6 and C40:6 were important risk factors for the mortality of sarcopenic patients. Low PCaa C38:6 levels and high C14-carnitine levels correlated with an increased mortality risk; this was even the same for those patients with hypertension (HTN). Our findings suggest that plasma PCaa C38:6 and acylcarnitine C14-carnitine, when combined, can be a better early biomarker for evaluating the mortality risk of sarcopenia patients.

In the field of drug discovery, understanding how small molecule drugs interact with cellular components is crucial. Our study introduces a novel methodology to uncover primary drug targets using T andem A ffinity P urification for identification of D rug- B inding P roteins (TAP-DBP). Central to our approach is the generation of a FLAG-hemagglutinin (HA)-tagged chimeric protein featuring the FKBP12(F36V) adaptor protein and the TurboID enzyme. Conjugation of drug molecules with the FKBP12(F36V) ligand allows for the coordinated recruitment of drug-binding partners effectively enabling in-cell TurboID-mediated biotinylation. By employing a tandem affinity purification protocol based on FLAG-immunoprecipitation and streptavidin pulldown, alongside mass spectrometry analysis, TAP-DBP allows for the precise identification of drug-primary binding partners. Overall, this study introduces a systematic, unbiased method for identification of drug-protein interactions, contributing a clear understanding of target engagement and drug selectivity to advance the mode of action of a drug in cells.

Background: Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified., Aim: To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms., Methods: Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments., Results: A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc . FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression., Conclusion: The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9., Competing Interests: Conflict-of-interest statement: All other authors have nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune response pathway independently of its enzymatic activity. TXNRD1 localizes to cytoplasmic chromatin fragments and interacts with cGAS in a senescence-status-dependent manner, which is necessary for the SASP. TXNRD1 enhances the enzymatic activity of cGAS. TXNRD1 is required for both the tumor-promoting and immune surveillance functions of senescent cells, which are mediated by the SASP in vivo in mouse models. Treatment of aged mice with a TXNRD1 inhibitor that disrupts its interaction with cGAS, but not with an inhibitor of its enzymatic activity alone, downregulated markers of inflammaging in several tissues. In summary, our results show that TXNRD1 promotes the SASP through the innate immune response, with implications for inflammaging. This suggests that the TXNRD1-cGAS interaction is a relevant target for selectively suppressing inflammaging., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM2.1 or B16-F10 melanoma cells eliminates clock function and diminishes hypoxic gene expression and tumorigenesis, which could be rescued by ectopic expression of HIF1α in YUMM2.1 cells. By contrast, over-expressed wild-type or a transcriptionally inactive mutant Bmal1 non-canonically sequester myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM2.1 cells from a Sox10 high to a Sox9 high immune resistant, mesenchymal cell state that is found in human melanomas. Our work describes a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton., (© 2024. The Author(s).)

Background: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer., Present Situation: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy., Aim of Review: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer., 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.)

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o -bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.