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 evaluate trauma repair and reconstruction surgery mediated by near-infrared-Ⅱ (NIR-Ⅱ) imaging in practice of enhanced recovery after surgery (ERAS) principles.Methods:A retrospective study was conducted to analyze the data of 38 patients who had undergone trauma repair and reconstruction surgery mediated by near-infrared-Ⅱ (NIR-Ⅱ) imaging in practice of ERAS principles at Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital from May 2021 to December 2021. There were 22 males and 16 females with an age of (50.3±2.7) years. To implement ERAS, NIR-Ⅱ imaging was used for patency evaluation after vascular anastomosis in 14 cases, for skin flap harvesting and perfusion monitoring in 13 cases, and for evaluation of arterial/venous blood supply after finger replantation in 11 cases. Visual analogue scale (VAS) pain scores at 2, 7 and 14 days after surgery, length of hospital stay, patient satisfaction [by Chinese Hospital Patient Experience and Satisfaction Monitor (CHPESM)], limb function recovery (by Likert scale) and postoperative complications were recorded.Results:All patients were followed up for more than 14 days. All surgeries succeeded. The reconstructed limbs or flaps survived to recover basically normal shape and function. The VAS scores for all patients were (2.1±0.6) points, (1.6±0.6) points and (0.8±0.4) points on postoperative 2, 7 and 14 days, respectively. The length of hospital stay was (9.8±3.4) days, and the patient satisfaction was >95% at discharge. As for the recovery of limb function at the last follow-up evaluated by the Likert 5-point scale, 12 cases experienced no stiffness, 8 ones mild stiffness, 11 ones slightly severe stiffness, 3 ones moderate to severe stiffness, 2 ones severe stiffness, and 2 ones complete stiffness. Complications related to the surgery occurred in none of the patients.Conclusion:In practice of ERAS principles, application of NIR-Ⅱ imaging in trauma repair and reconstruction surgery can effectively alleviate pain, improve satisfaction, reduce hospital stay, and accelerate functional recovery for the patients.

Objective:To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization.Methods:The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed.Results:(1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm 3 and cone size <2 cm 3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference ( P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm ( RR=3.084, 95% CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm 3 and those with cone size ≥2 cm 3 ( RR=1.700, 95% CI: 0.935-3.092; P=0.077). Conclusion:The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.