Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Objective This study aims to achieve high-yield functional expression of the human voltage-gated potassium channel K_V3.1 using an Escherichia coli cell-free protein synthesis system, thereby providing a novel synthetic approach for drug screening, structural analysis and functional characterization of K_V3.1. Methods K_V3.1 was expressed in an Escherichia coli cell-free protein synthesis system for 10 hours in the presence of peptide surfactant A₆K. The secondary structure of K_V3.1 was analyzed by circular dichroism spectroscopy. The potassium channel activity of the recombinant protein liposome K_V3.1-A₆K was investigated using fluorescent dyes Oxonol VI as indicators, which are capable of reflecting alterations in membrane potential. Results Soluble K_V3.1 protein was successfully synthesized, achieving a purified yield of up to 1.2 mg/mL via an Escherichia coli cell-free protein synthesis system. Circular dichroism spectroscopy revealed that K_V3.1 exhibited characteristic α-helical secondary structures. Membrane potential fluorescence assays demonstrated that the K_V3.1-A₆K proteoliposomes, which were reconstructed with surfactant peptide A₆K, exhibited remarkable potassium ion permeability. Conclusion This study successfully achieved high-yield expression of human K_V3.1 with activity using an Escherichia coli-based cell-free protein synthesis system. This innovative method not only significantly enhances the expression yield of K_V3.1, but also maintains its functional activity, thereby establishing a novel and efficient synthetic platform for drug screening and advancing our understanding of structure-function relationships in K_V3.1 research.
Humans ; Escherichia coli/metabolism* ; Shaw Potassium Channels/biosynthesis* ; Cell-Free System ; Circular Dichroism ; Protein Biosynthesis ; Recombinant Proteins/metabolism* ; Membrane Potentials ; Shab Potassium Channels

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

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Lung cancer is the malignant tumor with the highest incidence and mortality among the Chinese.Tumor node metastasis(TNM)staging established by the American Joint Committee on Cancer(AJCC)and International Union Against Cancer(UICC)is a commonly used criterion,but it still has limitations in judging the prognosis of non-small cell lung cancer(NSCLC)patients.With the advantages of real-time and convenient sampling,the immune score based on peripheral blood biomarkers have the ability to predict prognosis and efficacy of NSCLC patients,which have been developed and validated in clinical studies.However,clinical impleruentation of peripheral immune scores is still not widely in NSCLC patients.Therefore,this study introduces and evaluates the 6 peripheral immune scores and reviews the reseach progress of them in the treatment of NSCLC.

Objective:To describe disability rates of dementia in community residents aged 65 years and over in China,and explore related risk factors of disability.Methods:This study conducted an in-depth data analysis of the China Mental Health Survey.World Health Organization Disability Assessment Schedule 2.0(WHODAS 2.0)was used to assess dementia disability,Community Screening Interview for Dementia(CSID)and Geriatric Mental Status Examination(GMS)were used for dementia screening and diagnosing.Univariate analysis was used to calcu-late the weighted disability rates of dementia in population and in patients,and their population distribution.Multiple linear regression and logistic regression were used to analyze the risk factors of the occurrence of dementia disability and its severity.Results:The weighted disability rate of dementia was 2.1％in population,and 38.6％in pa-tients.The disability rates of comorbid dementia in population and in patients were higher than those of patients with only dementia.Female,older age,lower education level,lower economic status,and lower cognitive test scores in CSID had higher disability rates of dementia in population.Female and urban resident had higher disability rates of dementia in patients.Multiple linear regression showed economic status(β=0.11),gender(β=0.11),age(β=0.10),and treatment in the last 12 months(β=-0.20)were statistically associated with WHODAS 2.0 scores.Multiple logistic regression showed female(OR=2.81)and treatment in the last 12 months(OR=2.38)were statistically associated with disability.Conclusions:Persons with low economic status,female and elderly peo-ple are the high-risk groups for dementia disability.It should be paid attention to prevent dementia and its conse-quential disabilities.

Objective To explore the effect and mechanism of bone marrow-derived mesenchymal stem cell-conditioned medium(MSC-CM)on diabetic foot ulcer(DFU)in rats.Methods The model of diabetes mellitus type 2(T2DM)were induced by high fat diet and intraperitoneal injection of STZ in SD rats.DFU models were made by operation on hind limbs in diabetic rats.The rats were di-vided into four groups:normal control(NC)group,diabetes mellitus control(DM-C)group,MSC-CM group and mesenchymal stem cell(MSC)group,6 rats in each gruop.The MSC-CM group was injected with bone marrow-derived MSC-CM around ulcers.MSC group was injected with bone marrow-derived MSC.The other two groups were treated with injection of PBS.After the treatment,wound clousure,re-epithelialization(thickness of the stratum granulosums of the skin was detected by HE staining),cell proliferation(ki-67 was detected by immunohistochemistry),angiogenesis(CD31 was detected by immunofluorescence),autophagy(LC3B was detected by immunofluorescence and Western blot,autolysosome was observed by electron microscopy)and pyroptosis(IL-1 β,NLRP3,caspase-1,GSDMD and GSDMD-N were detected by Western blot)in ulers were evaluated.Results After the treatment,the wound area,IL-1β,caspase-1,GSDMD and GSDMD-N in MSC-CM group were lower than those in DM-C group.Thickness of the stratum gran-ulosums of the skin,ki-67,CD31 and LC3B in MSC-CM group were higher than those in DM-C group.The injection of MSC-CM to rats with DFU enhanced the wound healing process by accelerating wound closure,promoting cell proliferation and angiogenesis,enhan-cing cell autophagy and reducing cell pyroptosis in ulcers.Conclusion MSC-CM could be a novel cell-free therapeutic approach to treat rats with DFU accelerating the wound healing process.

Objective: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. Methods: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Results: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Conclusion Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.