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Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration of metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated the multiomics data of our large TNBC cohort (n=465) to develop the ferroptosis atlas. We discovered that TNBCs had heterogeneous phenotypes in ferroptosis-related metabolites and metabolic pathways. The luminal androgen receptor (LAR) subtype of TNBC was characterized by the upregulation of oxidized phosphatidylethanolamines and glutathione metabolism (especially GPX4), which allowed the utilization of GPX4 inhibitors to induce ferroptosis. Furthermore, we verified that GPX4 inhibition not only induced tumor ferroptosis but also enhanced antitumor immunity. The combination of GPX4 inhibitors and anti-PD1 possessed greater therapeutic efficacy than monotherapy. Clinically, higher GPX4 expression correlated with lower cytolytic scores and worse prognosis in immunotherapy cohorts. Collectively, this study demonstrated the ferroptosis landscape of TNBC and revealed an innovative immunotherapy combination strategy for refractory LAR tumors. Citation Format: Fan Yang, Yi Xiao, Jia-Han Ding, Yi-Zhou Jiang, Zhi-Ming Shao. Ferroptosis Heterogeneity in Triple-Negative Breast Cancer Reveals an Innovative Immunotherapy Combination Strategy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-13.

Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells, binds to nucleic acids in mRNA processing, stabilization, translation and transcription. However, little is known about the influence of PCBP1 on macrophages and its specific mechanism in inflamed intestines. In this study, conditional depletion of Pcbp1 in macrophages protected mice from progression of dextran sulfate sodium induced colitis and resulted in significant alleviation of colitis. Pcbp1 deficiency markedly decreased C-C motif chemokine ligand 2 (CCL2) production by colonic CX3C motif chemokine receptor 1+ (CX3CR1+) macrophages and reduced accumulation of pro-inflammatory macrophages and production of pro-inflammatory cytokines, such as IL-6 and TNF-α, in the inflamed colon. RNA-immunoprecipitation analysis indicated that PCBP1 might interact with Ccl2 mRNA and regulate its expression in macrophages. PCBP1 expression in inflamed intestines also correlated significantly with IBD severity in patients, suggesting a critical involvement of PCBP1 in intestinal inflammation. We anticipate that our findings will facilitate the development of novel therapeutic approaches for IBD by targeting the specific function of immune cells in the local microenvironment, thereby helping to reduce adverse effects.

Fish possess a powerful IFN system to defend against aquatic virus infections. Nevertheless, spring viremia of carp virus (SVCV) causes large-scale mortality in common carp and significant economic losses to aquaculture. Therefore, it is necessary to investigate the strategies used by SVCV to escape the IFN response. In this study, we show that the SVCV nucleoprotein (N protein) negatively regulates cellular IFN production by degrading stimulator of IFN genes (STING) via the autophagy-lysosome–dependent pathway. First, overexpression of N protein inhibited the IFN promoter activation induced by polyinosinic-polycytidylic acid and STING. Second, the N protein associated with STING and experiments using a dominant-negative STING mutant demonstrated that the N-terminal transmembrane domains of STING were indispensable for this interaction. Then, the N protein degraded STING in a dose-dependent and autophagy-lysosome–dependent manner. Intriguingly, in the absence of STING, individual N proteins could not elicit host autophagic flow. Furthermore, the autophagy factor Beclin1 was found to interact with the N protein to attenuate N protein–mediated STING degradation after beclin1 knockdown. Finally, the N protein remarkably weakened STING-enhanced cellular antiviral responses. These findings reveal that SVCV uses the host autophagic process to achieve immune escape, thus broadening our understanding of aquatic virus pathogenesis.

A two-state reactivity scenario is revealed for an energetically high-lying complex growth pathway based on a structural investigation on [TaO3(CO2)n]+ (n = 2–5) complexes.

To assess exercise therapies that aim to enhance proprioception in individuals with chronic ankle instability (CAI).Five databases (PubMed, Embase, Cochrane Library, Web of Science, and EBSCO) were searched in October 2021.Randomized controlled trials involving exercise therapy conducted on individuals with CAI were included.Data were extracted by 2 independent reviewers using a standardized form. Methodological quality and risk of bias were assessed with the Physiotherapy Evidence Database scale.The end trial weighted mean difference and standard deviations were analyzed, and the synthetic value for the improvement in error scores of ankle joint position sense in multiple directions was evaluated.Eleven trials with 333 participants were eligible for inclusion in this systematic review and were included in the network meta-analysis. Foot and ankle muscle strengthening exercise showed the highest probability of being among the best treatments (surface under the cumulative ranking [SUCRA]=74.6%). The next 2 were static balance exercise only (SUCRA=67.9%) and corrective exercise (SUCRA=56.1%). The SUCRA values of proprioceptive exercise, dynamic balance exercise only, aquatic exercise, rehabilitation exercise with brace, mixed static/dynamic balance exercise, and control were at relatively low levels and scored at 49.6%, 48.8%, 47.8%, 47.7%, 44.0%, and 13.5%, respectively.Foot and ankle muscle strengthening exercise may have a good effect when used to improve joint position sense in individuals with CAI. The more complex balance exercise intervention becomes, the less effective the proprioceptive outcome.

To determine whether individuals with and without Chronic Ankle Instability (CAI) can improve their ankle movement discrimination sensitivity by repeated exposure to an ankle proprioceptive task requiring landing.A repeated-measures study.University laboratory.24 university students, 11 with CAI and 13 without CAI.Ankle proprioception was measured using the Ankle Inversion Discrimination Apparatus for Landing (AIDAL) over 3 occasions: AIDAL-1 and AIDAL-2 separated with a 10-min interval, and AIDAL-3 at 24 h post AIDAL-2.Better Cumberland Ankle Instability Tool (CAIT) questionnaire scores were correlated with higher AIDAL scores (rho = 0.465, p = 0.022). Two-way ANOVA showed a significant CAI main effect for step landing ankle inversion proprioception, with CAI worse (F = 8.410, p = 0.008), but the Time main effect across the 3 AIDAL tests was not significant (F = 1.552, p = 0.223).The AIDAL assessment was sensitive in terms of discriminating between individuals with or without CAI. However, the step-down component of the AIDAL proprioceptive task was possibly too challenging. For CAI, physical therapy exercises should take into account the difficulty of the training task, so that a demonstrable learning effect can be achieved.

While investigators have often compared ankle proprioception between groups with and without chronic ankle instability (CAI), findings have been inconsistent. Possibly this is because ankle proprioceptive impairment in this population is task-specific. Thus, we aimed to compare ankle inversion proprioception in individuals with and without CAI in two task conditions: (i) when standing (not challenging) and (ii) when on a step-down landing (minimally-challenging). Ankle inversion proprioception was measured in both conditions for 38 recreational sport player volunteers with CAI ( n = 19) and without CAI ( n = 19). We used the Active Movement Extent Discrimination Apparatus (AMEDA) for the standing condition and the Ankle Inversion Discrimination Apparatus-Landing (AIDAL) for step-down landing. From analysis of variance (ANOVA) tests, CAI and non-CAI participants performed equally well on the AMEDA when standing; but the CAI group performed significantly worse than the non-CAI group on the AIDAL step-down landing task ( p = 0.03). Within the non-CAI group, the AIDAL proprioceptive scores, as area under the receiver operating characteristics curve (AUC), were significantly higher than their AMEDA AUC scores ( p = 0.03), while there was no significant difference between AIDAL and AMEDA AUC scores in the CAI group. Cumberland Ankle Instability Tool CAIT scores were significantly correlated with AIDAL scores (Spearman’s rho = 0.391, p = 0.015), but not with the AMEDA scores; and there was no significant correlation between the AIDAL and AMEDA scores. Thus, an ankle inversion proprioceptive deficit was evident for persons with CAI on the step-down AIDAL, and in a dose-response way, but not evident on the standing AMEDA, suggesting that ankle proprioceptive impairment is task-specific. Selected proprioceptive tests must present some minimal degree of challenge to the ankle joint in a functional task in order to differentiate CAI from non-CAI participants.

Multiparous women are at a higher risk of gestational diabetes mellitus (GDM) than primiparas. Physical activity during pregnancy has been shown to be beneficial for GDM, but there is little evidence on the association between physical activity and glycemic control among women with GDM, whether primiparas or multiparas. Thus, the objective of the present study was to examine the association between physical activity and glycemic control in women with GDM and to determine what, if any, effects result from number of parous events.A prospective cohort of 1162 women with GDM was recruited, with 604 multiparas (51.98%). The general linear model was used to calculate the risk difference and its 95% confidence interval (95%CI) to quantify the impact of parous events on glycemic control in pregnancy as well as the association between physical activity time and glycemic control.Among 1162 women with GDM, the median daily activity time was 65 min (interquartile range (IQR): 45-90 min), and the abnormal plasma glucose (PG) percentage, calculated as number of abnormal PG tests divided by the total number of PG tests, was 40.00% (IQR: 22.22%-66.67%). The percentage of abnormal PG was stabilized and statistically lower with daily physical activity time exceeding 60 min among primiparas (IQR: 30.89%-44.43%) and exceeding 90 min among multiparas (ranged from 27.76% to 38.82%). After adjusting for potential confounders, primiparas tended to have a lower percentage of abnormal PG than do multiparas (rate difference = -0.39, 95%CI: -3.61 to 2.84). The same amount of physical activity time was significantly less effective for multiparas than for primiparas (trend p-value0.01).In women with GDM, being multiparous is associated with less effective glycemic control through physical activity, such that multiparas need more physical activity to achieve glycemic control at a similar level to primiparas.

Introduction: Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs. Aim: This study aims to explores the bioactivity and the anti-cancer mechanism of XSH. Methods: In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti-cancer mechanism of XSH. Results: Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were β-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted. Discussion: Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with β-sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells. Conclusion: This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis.

During recovery from heat stress, plants clear away the heat-stress-induced misfolded proteins through the ubiquitin-proteasome system (UPS). In the UPS, the recognition of substrate proteins by E3 ligase can be regulated by the N-terminal acetyltransferase A (NatA) complex. Here, we determined that Arabidopsis STRESS-RELATED UBIQUITIN-ASSOCIATED-DOMAIN PROTEIN FACTOR 1 (SUF1) interacts with the NatA complex core subunit NAA15 and positively regulates NAA15. The suf1 and naa15 mutants are sensitive to heat stress; the NatA substrate

Objective To investigate the effects of whole body vibration on chronic ankle instability-associated sensorimotor deficits in balance, strength, joint position sense and muscle activity. Data sources Electronic databases including Cochrane Library, PubMed, Embase, Web of Science, EBSCO, China National Knowledge Infrastructure and WanFang were searched from database inception up to 31 March 2022. Methods The risk of bias and methodological quality of included studies were assessed using the Cochrane tool and Physiotherapy Evidence Database (PEDro) scale respectively. Standardized mean difference (SMD) and mean differences (MD) with 95% confidence interval (CI) were calculated using the RevMan 5.3 software. Meta-regression was conducted with Stata 16. Results Eight studies, with 315 subjects were eventually included in this review with an average PEDro score of 6.1/10. Significant effects of whole body vibration on balance (SMD = 0.61, 95% CI: 0.12 to 1.09, P = 0.01), and on the posterolateral direction (MD = 5.52, 95% CI: 1.02 to 10.01, P = 0.02) and medial direction (MD = 3.90, 95% CI: 0.87 to 6.94, P = 0.01) of the star excursion balance test were found. Whole body vibration significantly improved the peak torque (SMD = 0.36, 95% CI: 0.04 to 0.69, P = 0.03), joint position sense (SMD = 0.60, 95% CI: 0.10 to 1.11, P = 0.02), and muscle activity in tibialis anterior (SMD = 0.46, 95% CI: 0.04 to 0.88, P = 0.03) and gastrocnemius (SMD = 0.68, 95% CI: 0.14 to 1.23, P = 0.01). Conclusions The current evidence supports the use of whole body vibration to improve sensorimotor deficits involving balance, strength, joint position sense, and muscle activity in people with chronic ankle instability.

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant–pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

The mechanism(s) of how bacteria acquire tolerance and then resistance to antibiotics remains poorly understood. Here, we show that glucose abundance decreases progressively as ampicillin-sensitive strains acquire resistance to ampicillin. The mechanism involves that ampicillin initiates this event via targeting pts promoter and pyruvate dehydrogenase (PDH) to promote glucose transport and inhibit glycolysis, respectively. Thus, glucose fluxes into pentose phosphate pathway to generate reactive oxygen species (ROS) causing genetic mutations. Meanwhile, PDH activity is gradually restored due to the competitive binding of accumulated pyruvate and ampicillin, which lowers glucose level, and activates cyclic adenosine monophosphate (cAMP)/cAMP receptor protein (CRP) complex. cAMP/CRP negatively regulates glucose transport and ROS but enhances DNA repair, leading to ampicillin resistance. Glucose and Mn 2+ delay the acquisition, providing an effective approach to control the resistance. The same effect is also determined in the intracellular pathogen Edwardsiella tarda. Thus, glucose metabolism represents a promising target to stop/delay the transition of tolerance to resistance.

Purpose: 1) to explore the test-retest reliability of a new device for measuring ankle inversion proprioception during walking, i.e., the Ankle Inversion Discrimination Apparatus—Walking (AIDAW) in individuals with or without Chronic Ankle instability (CAI); 2) to assess its discriminant validity in differentiating individuals with or without CAI; 3) to investigate its convergent validity by examining its association with Cumberland Ankle Instability Tool (CAIT) and the Y Balance Test (YBT).Methods: For test-retest reliability, 15 participants with CAI and 15 non-CAI healthy controls were recruited. Participants completed the AIDAW test twice with a 7-day interval. The area under the receiver operating curve (AUC) was obtained as the AIDAW score. The intraclass correlation coefficient (ICC) and MDC90 were calculated. For the validity study, another 20 individuals with CAI and 20 non-CAI healthy controls were involved. The AIDAW scores were analyzed by an independent samples t-test, and the optimal cutoff value of AIDAW scores to best distinguish individuals with CAI was calculated by Youden’s index. Spearman or Pearson correlation analysis was used to analyze the correlation between AIDAW proprioceptive scores and the CAIT and final YBT scores.Results: For test-retest reliability, the ICC values for the CAI, non-CAI, and the whole group were 0.755, 0.757, and 0.761 respectively. The MDC90 of the CAI and non-CAI group was 0.04 and 0.05. Regarding discriminant validity, the AIDAW proprioceptive discrimination scores in the CAI group were significantly lower than those in the non-CAI group (p = 0.003); and the cutoff score for distinguishing CAI from the non-CAI participants was 0.759. For convergent validity, the AIDAW scores were significantly correlated with the functional balance YBT final scores (p = 0.001) and the CAIT scores (p = 0.009).Conclusion: The AIDAW is a reliable and valid device for evaluating ankle inversion proprioception during walking in individuals with and without CAI. AIDAW can be used as a clinical assessment tool to discriminate CAI from non-CAI individuals and to monitor effects of rehabilitation. The AIDAW proprioceptive discrimination scores were significantly and positively correlated with YBT and CAIT scores.

Efficient sound transmission across the water-air interface has always been expected in the field of ocean exploration. However, the existing researches are mainly concentrated on the narrow-band transmission based on resonance, which greatly limits the transmission capacity and efficiency. Here, we combined the air-based and water-based metafluids to realize an exponential gradient impedance matching layer for broadband water-air sound transmission. By cooperatively adjusting the sound velocity and thickness in the matching layers, we modulated the required acoustic parameters of each layer into a reasonable range, which can be conveniently achieved by the proposed metafluids. A matching layer sample was constructed and validated in a water tank. Experimental results show that the proposed matching layer can achieve an average sound energy transmission enhancement above 16.7dB from 880Hz to 1760Hz across the water-air interface. Moreover, we use the proposed matching layer to demonstrate a multicolor picture transmission from air to water, which shows extremely high communication capacity and accuracy. Our work is promising for more applications based on water-air transmission and opens a new avenue to the design and implementation of the extreme impedance matching case.

Tuning the mass density and bulk modulus independently is the key to manipulate the propagation of sound wave. Acoustic metamaterials provide a feasible method to realize various acoustic parameters. However, the relevant studies are mainly concentrated in air, and the huge impedance difference makes it difficult to directly extend these airborne structures to underwater application. Here, we propose a metafluid to realize independent manipulation of the mass density and bulk modulus underwater. The metafluid is composed of hollow regular polygons immersed in the water. By adjusting the side number of the hollow regular polygons and choosing proper materials, the effective mass density and bulk modulus of the metafluid could be modulated independently. Based on the flexible adjustment method, metafluids with same impedance but different sound velocities are designed and used to realize an underwater impedance-matched gradient index lens. In addition, by combining the proposed metafluid with other artificial structures, acoustic parameters with great anisotropy can be achieved, which is exemplified by the design and demonstration of an impedance-matched underwater acoustic carpet cloak. This work can expand the practicability of underwater metamaterials and pave the way for future potential engineering applications in the practical underwater devices.

Streptococcus agalactiae (GBS) is an important pathogenic bacteria that infected both aquatic animals and human beings, causing huge economic loss. The increasing cases of antibiotic-resistant GBS impose challenges to treat such infection by antibiotics. Thus, it is highly demanded for the approach to tackle antibiotic resistance in GBS. In this study, we adopt a metabolomic approach to identify the metabolic signature of ampicillin-resistant GBS (AR-GBS) that ampicillin is the routine choice to treat infection by GBS. We find glycolysis is significantly repressed in AR-GBS, and fructose is the crucial biomarker. Exogenous fructose not only reverses ampicillin resistance in AR-GBS but also in clinic isolates including methicillin-resistant Staphylococcus aureus (MRSA) and NDM-1 expressing Escherichia coli. The synergistic effect is confirmed in a zebrafish infection model. Furthermore, we demonstrate that the potentiation by fructose is dependent on glycolysis that enhances ampicillin uptake and the expression of penicillin-binding proteins, the ampicillin target. Our study demonstrates a novel approach to combat antibiotic resistance in GBS.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer. High fibrosis, marked by increased collagen fibers, is widespread in TNBC and correlated with tumor progression. However, the molecular features of fibrosis and why it results in a poor prognosis remain poorly understood. Based on multiomics datasets of TNBC, we evaluated the pathological fibrosis grade of 344 samples for further analysis. Genomic, transcriptomic, and immune changes were analyzed among different subgroups of fibrosis. High fibrosis was an independent adverse prognosis predictor and had interactions with low stromal tumor-infiltrating lymphocytes. Genomic analysis identified copy number gains of 6p22.2-6p22.1 (

We report a novel elastomer possessing high stretchability, elasticity and self-healing ability, achieved by thio-β-diketone-Cu(ii) coordination and H-bonding dual crosslinking. Flexible sensors are fabricated based on the elastomer.

In today’s education and teaching reform, the traditional teaching method in the teaching of polymer materials has been gradually replaced with various new teaching methods. Among them, the case analysis method is a very effective teaching method, which has been applied to the teaching of polymer materials. Through example-based teaching, students’ participation can be effectively improved, and their theoretical knowledge can be fully utilized. This would have a positive role in promoting the improvement of students’ knowledge system and their learning ability. In regard to this, this article analyzes the application of case analysis in the teaching of polymer materials so as to improve its efficiency and quality.

The knockout (KO) of the cystine transporter xCT causes ferroptosis, a type of iron-dependent necrotic cell death, in mouse embryonic fibroblasts, but this does not occur in macrophages. In this study, we explored the gene that supports cell survival under a xCT deficiency using a proteomics approach. Analysis of macrophage-derived peptides that were tagged with iTRAQ by liquid chromatography-mass spectrometry revealed a robust elevation in the levels of carnosine dipeptidase II (CNDP2) in xCT KO macrophages. The elevation in the CNDP2 protein levels was confirmed by immunoblot analyses and this elevation was accompanied by an increase in hydrolytic activity towards cysteinylglycine, the intermediate degradation product of glutathione after the removal of the γ-glutamyl group, in xCT KO macrophages. Supplementation of the cystine-free media of Hepa1-6 cells with glutathione or cysteinylglycine extended their survival, whereas the inclusion of bestatin, an inhibitor of CNDP2, counteracted the effects of these compounds. We established CNDP2 KO mice by means of the CRISPR/Cas9 system and found a decrease in dipeptidase activity in the liver, kidney, and brain. An acetaminophen overdose (350 mg/kg) showed not only aggravated hepatic damage but also renal injury in the CNDP2 KO mice, which was not evident in the wild-type mice that were receiving the same dose. The aggravated renal damage in the CNDP2 KO mice was consistent with the presence of abundant levels of CNDP2 in the kidney, the organ prone to developing ferroptosis. These collective data imply that cytosolic CNDP2, in conjugation with the removal of the γ-glutamyl group, recruits Cys from extracellular GSH and supports redox homeostasis of cells, particularly in epithelial cells of proximal tubules that are continuously exposed to oxidative insult from metabolic wastes that are produced in the body.

Purpose : To investigate the clinical effects and complications that may arise as a result of ipsilateral clavicle turnover during tumorous bone defect repair of the proximal humerus, and to explore the feasibility of performing combined free fibula transplantation and internal fixation in reducing complications Methods: We treated 13 patients with clavicle turnover or free fibular transplantation from September 1998 to February 2020. There were 7 males and 6 females with the average age of 26.2 years (7–50 years). The histological diagnoses were osteosarcoma in 6 patients (Enneking IIB), giant cell tumors in 3 patients (Campanacci III) and one patient each with Ewing’s sarcoma (Enneking IIB), chondrosarcoma (Canceration of multiple osteochondromatosis), fibrosarcoma and metastatic cancer of bone (Bone metastasis of lung cancer). Pathological fractures were found in 7 of the 13 patients. Results : The operation was successfully performed for all 13 patients. We followed 12 patients for 18 to 274 months (average 92.7 months). For 6 patients treated with simple clavicle turnover using a short plate, the average healing time was 7 months (4–12 months). Among them, there were 3 cases of clavicle fracture and 3 cases of overturned bone healed well. For the 7 patients treated with clavicle turnover and free fibula using a long plate, the healing time was 6.7 months. However, one patient died of tumor metastasis 19 months after operation, without reversal of clavicle fracture and other complications. Conclusion : Clavicle turnover is a feasible method for the treatment of tumorous bone defect of the proximal humerus. Flipping clavicle fracture is the most common complication. The application of total clavicle fixation and free fibular transplantation strengthens the flipping clavicle and reduces the risk of clavicle fracture.

Proteasome is a large proteolytic complex that consists of a 20S core particle (20SP) and 19S regulatory particle (19SP) in eukaryotes. The proteasome degrades most cellular proteins, thereby controlling many key processes, including gene expression and protein quality control. Proteasome dysfunction in plants leads to abnormal development and reduced adaptability to environmental stresses. Previous studies have shown that proteasome dysfunction upregulates the gene expression of proteasome subunits, which is known as the proteasome bounce-back response. However, the proteasome bounce-back response cannot explain the damaging effect of proteasome dysfunction on plant growth and stress adaptation. To address this question, we focused on downregulated genes caused by proteasome dysfunction. We first confirmed that the 20SP subunit PBE is an essential proteasome subunit in Arabidopsis and that PBE1 mutation impaired the function of the proteasome. Transcriptome analyses showed that hypoxia-responsive genes were greatly enriched in the downregulated genes in pbe1 mutants. Furthermore, we found that the pbe1 mutant is hypersensitive to waterlogging stress, a typical hypoxic condition, and hypoxia-related developments are impaired in the pbe1 mutant. Meanwhile, the 19SP subunit rpn1a mutant seedlings are also hypersensitive to waterlogging stress. In summary, our results suggested that proteasome dysfunction downregulated the hypoxia-responsive pathway and impaired plant growth and adaptability to hypoxia stress.

Proprioception is essential for neuromuscular control in relation to sport injury and performance. The effect of landing heights and loads on ankle inversion proprioceptive performance in individuals with or without chronic ankle instability (CAI) may be important but are still unclear. Forty-three participants (21 CAI and 22 non-CAI) volunteered for this study. The Ankle Inversion Discrimination Apparatus for Landing (AIDAL), with one foot landing on a horizontal surface and the test foot landing on an angled surface (10°, 12°, 14°, 16°), was utilized to assess ankle proprioception during landing. All participants performed the task from a landing height of 10 cm and 20 cm with 100% and 110% body weight loading. The four testing conditions were randomized. A repeated measures ANOVA was used for data analysis. The result showed that individuals with CAI performed significantly worse across the four testing conditions (p = 0.018). In addition, an increased landing height (p = 0.010), not loading (p > 0.05), significantly impaired ankle inversion discrimination sensitivity. In conclusion, compared to non-CAI, individuals with CAI showed significantly worse ankle inversion proprioceptive performance during landing. An increased landing height, not loading, resulted in decreased ankle proprioceptive sensitivity. These findings suggest that landing from a higher platform may increase the uncertainty of judging ankle positions in space, which may increase the risk of ankle injury.