Emerging Role of Sorting Nexin 17 in Human Health and Disease.

The distortion of the cellular membrane transport pathway has a profound impact on cell dynamics and can drive serious physiological consequences during the process of cell sorting. SNX17 is a member of the Sorting Nexin (SNX) family and plays a crucial role in protein sorting and transport in the endocytic pathway. SNX17, SNX27, and SNX31 belong to the SNX-FERM subfamily and possess the FERM domain, which can assist in endocytic transport and lysosomal degradation. The binding partners of SNX27 have been discovered to number over 100, and SNX27 has been linked to the development of Alzheimer's disease progression, tumorigenesis, cancer progression, and metastasis. However, the role and potential mechanisms of SNX17 in human health and disease remain poorly understood, and the function of SNX17 has not been fully elucidated. In this review, we summarize the structure and basic functions of SNX protein, focusing on providing current evidence of the role and possible mechanism of SNX17 in human neurodegenerative diseases and cardiovascular diseases.

Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study.

BACKGROUND: Emergency agitation is a common postoperative complication in patients under general anesthesia, which can lead to unpredictable damages such as shedding of drainage tube and bleeding from the wound. The purpose of the study is to investigate whether intraoperative infusion of Magnesium Sulfate reduces the incidence of emergency agitation (EA) in patients undergoing radical mastectomy, and to evaluate its safety and efficacy. METHODS: A total of 70 patients were randomly assigned to two groups: the Magnesium group (M group) and the control group (C group). After a routine intravenous anesthetic induction, patients in the M group received a 30 mg/kg bolus of intravenous magnesium during the first hour and then a continuous infusion of 10 mg/kg ×h until the end of the surgery, patients in the C group received 0.9% saline at the same volume and rate. The sedation-agitation scale (SAS) and the visual analogue scale were used to assess agitation and pain, respectively. RESULTS: Compared to the C group, the M group reduced the incidence of EA significantly (odds ratio 0.26, 95% confidence interval 0.09-0.71, P = 0.009). The postoperative pain score of the magnesium sulfate group(0(0,1)) was lower than that of the control group(2(0,3)) at T0 (P = 0.011). Additionally, the M group required a lower dosage of remifentanil during surgery compared to the C group(300.4 ± 84 versus 559.3 ± 184 µg, respectively, P<0.001). CONCLUSIONS: the intraoperative infusion of magnesium sulfate is a safe and effective method for reducing the incidence of emergency agitation in patients undergoing radical mastectomy. TRAIL REGISTRATION: The study was registered in Chictr.org with the identifier: ChiCTR2300070595 on 18/04/2023.

Evolutionary overview of sarcopenia - bibliometric study on the Web of science: A review.

Sarcopenia is an age-related degenerative disease associated with adverse outcomes such as falls, functional decline, weakness, and mortality. Exploring the dynamic evolutionary path and patterns of sarcopenia research topics within a temporal framework from the perspective of strategic coordinate maps and data flow can help identify the development rules of sarcopenia themes. After searching, a total of 16,326 articles were obtained. There are few early research topics, but the development maturity of the topics is high; the number of late research topics continues to increase, showing a trend of diversified development. The differentiation and fusion of the theme evolution path are obvious, and the theme inheritance index is high. The development trend of this research field is promising. The mature and stable professional topics such as "RESISTANCE EXERCISE" and "SURVIVAL" that appeared in the late stage belong to the core topics, while newly emerging topics like "FRACTURES" and "PROTEIN" belong to the marginal topics, indicating that the research on muscle and bone metabolism in the field of sarcopenia has yet to be further in-depth, and the "CANCER" topic is a highly promising research topic with strong development potential.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

[Effects of resistance training on mitochondrial function in skeletal muscle of aging rats].

Objective: To investigate the effects of resistance exercise on mitochondrial function in skeletal muscle of aging rats. Methods: Forty male Sprague-Dawley rats were randomly assigned to 4 groups, 2-month sedentary control group (C1; n=10), 2-month with resistance training group (R1; n=10), 6-month sedentary control group (C2; n=10), 6-month with resistance training group (R2; n =10 ). Rats in R1 and R2 groups were arranged for resistance training for 8 weeks. This program consisted of interval running on a treadmill, speed 15 m·min-1, 35° incline, duration 15 s, interval 30 s, 4 times/group, 3 groups/cycle, 2 cycles per day, 6 days per week, a total of 8 weeks. The expressions of mitochondrial fusion protein 2(Mfn2) and dynamin-related protein 1(DRP1) in rat quadriceps were detected by Western blot, and the changes of mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and Ca2+ concentration were measured by flow cytometry. Results: ①Compared with C1 group, the expression of DRP1 protein in R1 group was increased (P＜0. 01), and the Mfn2 protein in R1 group had no significant difference, both DRP1 and Mfn2 protein in C2 group were decreased (P＜0. 01);compared with C2 group, the DRP1 and Mfn2 protein in R2 group were similarly increased (P＜0. 01, P＜0. 05);compared with R1 group, the DRP1 and Mfn2 protein in R2 group were both decreased (P＜0. 01). ② Compared with C1 group, the Ca2+ content of R1 group was decreased (P＜0. 01) and the Ca2+ content of C2 group was increased (P＜0. 01);Compared with C2 group, the content of Ca2+ in R2 group was decreased (P＜0. 01);compared with R1 group, the Ca2+ content in R2 group was increased (P＜0. 01). ③ Compared with C1 group, the ROS content in R1 group was increased, but there was no significant difference, while the ROS content in C2 group was increased (P＜0. 01);compared with C2 group, ROS content in R2 group was decreased (P＜0. 01); compared with R1 group, the ROS content in R2 group was increased (P＜0. 01). ④ Compared with group C1, the levels of ΔΨm in C2 group was decreased (P＜0. 01);Compared with C2 group, The ΔΨm of R2 group was increased(P＜0. 01); Compared with group R1, the ΔΨm of R2 group was decreased, but there was no statistical difference. Conclusion: During the aging process of rats, mitochondria of quadriceps femoral muscle showed Ca2+ accumulation, increased reactive oxygen species, decreased mitochondrial membrane potential, decreased fusion protein and other phenomena, and resistance training could effectively improve these changes.

Four linear Cu(II)3 subunit-based coordination polymers with various inter-subunit connections, spin ground-states and intra-/inter-subunit magnetic couplings.

Four new 4-amino-1,2,4-triazole (atr)-based coordination polymers, {[Cu2(atr)(H2O)(µ-OH)2(pa)]·H2O}n (), {[Cu3(atr)2(H2O)2(µ-OH)2(npa)2]·2H2O}n (), {[Cu3(atr)5(dca)(µ-OH)(ClO4)2](ClO4)2}n () and {[Cu3(atr)2(H2O)(µ3-OH)(µ-OH)2(spa)]·1.5H2O}n () (pa(2-) = phthalate, npa(2-) = 3-nitrophthalate, dca(-) = dicyanamide and spa(3-) = 4-sulfophthalate), were successfully obtained by varying the carboxylate- and cyanide-modified magnetic bridges. Structural determinations reveal that the former three samples are bent one-dimensional chains constructed from linear Cu(II)3 subunits and different inter-subunit connections. In , linear {Cu3(µ-N1,N2-atr)2(µ-OH)2}(4+) and {Cu3(µ-COO)2(µ-OH)2}(4+) subunits are alternately connected in a sharing-vertex manner to give a ferrimagnetic S = 1/2 spin ground-state. The linear {Cu3(µ-N1,N2-atr)2(µ-OH)2}(4+) building block of is repeatedly bridged by pairs of single-atom bridging carboxylate groups of the npa(2-) ligand leading to a paramagnetic S = 1/2 spin ground-state. By contrast, each linear {Cu3(µ-N1,N2-atr)4}(6+) core in is periodically propagated by four-fold heterobridges (µ-OH(-), µ-ClO4(-), µ-N1,N2-atr and µ-dca(-)) to generate an overall diamagnetic S = 0 spin ground-state. Complex is a three-dimensional pillared-layer framework composed of linear {Cu3(µ-N1,N2-atr)2(µ-OH)2}(4+)-based layers and ditopic spa(3-) connectors, which exhibits a ferrimagnetic S = 1/2 spin ground-state and a metamagnetic transition resulting from the competition between the weak interchain/interlayer antiferromagnetic interaction and the enhanced external magnetic field. In addition, different intra- and inter-subunit magnetic strengths are observed in with the coupling constants 182 < -Jintra < 43 and -127 < Jinter < 51.2 cm(-1). These interesting magnetostructural results are significant and helpful for the cyclic polyazolate-based magnetic materials.

[The changes of p-Akt/MuRF1/FoxO1 proteins expressions in the conditions of training and immobilization in rats' gastrocnemius muscle].

This study was aimed to investigate the changes of muscle protein synthesis and degradation under different movement conditions, so as to provide theoretical basis for muscle atrophy mechanism. Sprague Dawley (SD) rats were randomly divided into control, endurance training (treadmill training), hind limb overhanging and eccentric training (treadmill training, angle -16º) groups. The gastrocnemius muscles of rats were taken and weighed. The muscle was sectioned, and HE staining was employed to determine the cell's cross-sectional area. Protein expression of p-Akt was measured by immunohistochemistry; and the expressions of MuRF1 and FoxO1 were determined by Western blot. The results showed that, compared with control group, hind limb overhanging and eccentric training groups exhibited decreased muscle weight and cross-sectional area, but endurance training group did not show any changes. The expressions of p-Akt in endurance and eccentric training groups, not in hind limb overhanging group, were significantly higher than that in control group. Compared with that of control, MuRF1 protein remained unchanged in endurance training groups, but was increased in eccentric training and hind limb overhanging groups; FoxO1 protein was decreased in endurance training group, but was increased in eccentric training and hind limb overhanging groups. These results indicate that movement (endurance and eccentric training) can activate Akt expression, but does not increase muscle weight, whereas eccentric training and hind limb overhanging can increase the expressions of MuRF1 and FoxO1, and induce amyotrophy, suggesting MuRF1 and FoxO1 are major determinant factors in muscle atrophy.