Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

The application of function-preserving pancreatic surgery as a restrictive resection technique is primarily targeted towards benign or those with borderline or low-grade lesions. This approach has been shown to significantly improve both short-term and long-term quality of life outcomes for patients following surgical intervention. In comparison to conventional laparoscopic procedures, robotic surgical systems have demonstrated superior efficacy and precision when employed in pancreas surgeries, and the safety and reliability are widely recognized within the medical community. Nevertheless, there remains a dearth of research investigating the specific appli-cations of robotic-assisted function-preserving pancreatic surgery. Consequently, the authors compre-hensive review the latest progress on robot-assisted function-preserving pancreatic surgery, while highlighting of surgical scope, techniques utilized during these procedures as well as associated prognostic considerations.

Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Kirsten rat sarcoma viral oncogene homolog(KRAS)is a type of gene closely related to human tumors.And it's an important medical index to access the tumor development,prognosis and the efficacy of chemoradiotherapy.RAS mutations,in which KRAS mutations account for up to 85%,are the most common oncogenic driving mutations in human tumors.The most frequent KRAS mutation sites are codons 12,13,61 and 146.Codon G12,as the most frequently mutated one,can be divided into multiple subtypes,with G12D mutation being the most common,followed by G12V,G12C,etc.Colorectal cancer(CRC)is one of the tumors with the highest frequency of KRAS mutations.Both G12D and G12V are the most common mutation subtypes in CRC.In the field of treatments for CRC with KRAS mutations,targeted therapy had not been possible until the release of KRASG12C inhibitors in 2013,and new drugs have been developed one after another since then.This study summarized the mutations of KRAS and the advances in clinical research,including the latest advances in targeted drugs,chemotherapy drugs,immunotherapy drugs,ferroptosis,and other treatment methods.Among them,in terms of targeted drugs,this review explored KRASG12C inhibitors(sotorasib,adagrasib,D-1553,IBI351,etc.),anti-angiogenic drugs(monoclonal antibodies such as bevacizumab,remdesizumab,etc),small molecule multi-target tyrosine kinase inhibitors such as sunitinib,etc.In terms of immunotherapy drugs,there have also been many advances,such as the ARETHUSA clinical trial,which found that temozolomide reduced the tumor mutational burden(TMB)of O-6-methylguanine-DNA methyltransferase(MGMT)deficiency and RAS mutation in patients with advanced metastatic colorectal cancer(mCRC),providing innovative ideas for patient immunotherapy.For example,the combination of xindilimab with bevacizumab,oxaliplatin,and capecitabine can be used for first-line treatment of RAS mutations,microsatellite stability(MSS),and unresectable mCRC.Relevant studies have shown that the combination therapy has good therapeutic potential and controllable tolerability safety.This review explored the mechanisms of KRAS mutations and the latest advances in clinical research and treatment,in order to provide reference for the treatment of KRAS mutated colorectal cancer.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective:To explore the standardization of totally implantable venous power port of nursing process in CT enhancement and application effect of contrast medium injection, so as to provide a safer and more efficient way for contrast medium injection in CT enhanced examination for patients with malignant tumors.Methods:A non-randomized prospective study was conducted, 358 patients with malignant tumors were selected in Sun Yat-sen Memorial Hospital, Sun Yat-sen University who underwent CT enhanced examination from August 1, 2022 to July 31, 2023, 179 patients who had been implanted totally implantable venous power port were selected as the experimental group, and the standardized nursing procedure was given. The other 179 patients were the control group, using radiology routine high-pressure intravenous indwelling needle as the contrast medium access, with routine peripheral venous nursing process. The incidence of contrast medium extravasation during CT enhanced examination was observed and compared between the two groups.Results:All the patients were included. There were 85 males and 94 females, aged (55.50±11.72) years old in the control group. There were 83 males and 96 females, aged (54.50±12.24) years old in the experimental group. The incidence of contrast medium extravasation was 0 in the experimental group and 3.35%(6/179) in the control group. The difference between the two groups was statistically significant (Fisher exact probability, P<0.05). Conclusions:The application of standardized nursing procedure of totally implantable venous power port to the injection of contrast medium in CT enhanced examination of malignant tumor patients, can significantly reduce the incidence of contrast medium extravasation.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Health behavior decision-making often involves the balance of gains and losses at different time points,which affects the choice and maintenance of health behaviors.As a cognitive processing method of"pre-experiencing"future events,Episodic Future Thinking(EFT)can promote the formation of health intentions and health behavior change by increasing the value of future health outcomes.This paper reviews the concept,intervention model and action effect of EFT in health behaviors,in order to provide references for nurses to innovate health education and behavior management from the perspective of behavioral economics.

Objective:To examine the association between macrophage migration inhibitory factor(MIF), Interleukin 6(IL-6), periodontal disease, and atherosclerosis in middle-aged and elderly individuals.Methods:This cross-sectional study enrolled 700 diabetic patients who were attending the endocrinology department of Beijing Hospital from January 2020 to December 2022.Out of these patients, 491 underwent a full-mouth periodontal examination.Among them, 106 were middle-aged and elderly.The study included 83 patients with complete data, aged between 45 and 70 years(mean age: 58.2±8.7 years).Among the included patients, 48 were male(57.8%)and 35 were female(42.2%).A questionnaire was administered to gather information about the patients, and serum levels of MIF and IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).The relationship between serum MIF and IL-6 levels and periodontitis and atherosclerosis was evaluated through univariate and multifactorial analyses conducted on middle-aged and elderly individuals.Results:There were 66 cases(79.5%)in the periodontitis stage Ⅰ/Ⅱ group and 17 cases(20.5%)in the stage Ⅲ/Ⅳ group.The serum MIF levels in the two groups were(2, 312.5±795.0)ng/L and(2, 939.8±665.0)ng/L, respectively( P<0.01).Similarly, IL-6 levels were(3.5±3.0)ng/L and(6.7±6.1)ng/L in the two groups( P>0.05).The findings revealed that for each 1 ng/L increase in MIF serum levels, the risk of severe periodontitis and increased carotid intima-media thickness(cIMT)increased by 0.1%.Furthermore, for each 1 ng/L increase in serum MIF and IL-6 levels, the risk increased by 0.2% and 38.9% respectively.Serum MIF levels were found to be associated with atherosclerosis as well as with various factors related to periodontitis, including periodontal probing depth, bleeding index, clinical attachment level, periodontal probing depth≥4 mm sites, clinical attachment level≥5%, and bleeding index >2%(all P<0.05). Conclusions:This study investigates the correlation between MIF and IL-6 levels with Periodontal disease and Atherosclerosis in middle-aged and elderly individuals.