Mitochondrial stress and aging: Lessons from C. elegans.

Aging is accompanied by a progressive decline in mitochondrial function, which in turn contributes to a variety of age-related diseases. Counterintuitively, a growing number of studies have found that disruption of mitochondrial function often leads to increased lifespan. This seemingly contradictory observation has inspired extensive research into genetic pathways underlying the mitochondrial basis of aging, particularly within the model organism Caenorhabditis elegans. The complex and antagonistic roles of mitochondria in the aging process have altered the view of mitochondria, which not only serve as simple bioenergetic factories but also as signaling platforms for the maintenance of cellular homeostasis and organismal health. Here, we review the contributions of C. elegans to our understanding of mitochondrial function in the aging process over the past decades. In addition, we explore how these insights may promote future research of mitochondrial-targeted strategies in higher organisms to potentially slow aging and delay age-related disease progression.

What are the pandemic's shocks on carbon emission trading? The different management applications.

Maintaining the stability of the carbon market is of great significance for China to meet its goal of "Double Carbon," but at the beginning of 2020 the COVID-19 pandemic emerged and the economy was greatly affected. A natural question is whether it impacted domestic carbon markets. This paper thus presents the event research method on eight carbon emission trading markets in China, because it can timely exhibit the benefits investors gained during the COVID-19 pandemic and also can overcome the difficulty of separating those benefits from the overall performance of the carbon market via high-frequency data. The results herein confirm that China's carbon market has reacted negatively to the COVID-19 pandemic, which mainly relates to the mandatory blockade and isolation policy adopted by the central government. The production and operation activities of enterprises decreased along with the demand for carbon quotas. Because of the panic, investors also had a negative attitude towards the carbon market, influencing the supply and demand curve of carbon quotas and causing a decline in carbon prices. Under the effectiveness of government epidemic prevention and control policies, we further find that the negative impact was gradually eliminated. Overall, our findings offer some important information for the decision-making of governments, carbon market investors, and policymakers.

miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction.

Osteoarthritis (OA) is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals. To improve the quality of life for patients with OA, the primary goal for OA treatment is to relieve the pain. During OA progression, nerve ingrowth was observed in synovial tissue and articular cartilage. These abnormal neonatal nerves act as nociceptors to detect OA pain signals. The molecular mechanisms for transmitting OA pain in the joint tissues to the central nerve system (CNS) is currently unknown. MicroRNA miR-204 has been demonstrated to maintain the homeostasis of joint tissues and have chondro-protective effect on OA pathogenesis. However, the role of miR-204 in OA pain has not been determined. In this study, we investigated interactions between chondrocytes and neural cells and evaluated the effect and mechanism of miR-204 delivered by exosome in the treatment of OA pain in an experimental OA mouse model. Our findings demonstrated that miR-204 could protect OA pain by inhibition of SP1- LDL Receptor Related Protein 1 (LRP1) signaling and blocking neuro-cartilage interaction in the joint. Our studies defined novel molecular targets for the treatment of OA pain.

Roles of focal adhesion proteins in skeleton and diseases.

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

The impact of maternal ABO blood type on obstetric and perinatal outcomes after frozen embryo transfer.

RESEARCH QUESTION: Does the maternal ABO blood type affect obstetric and perinatal outcomes following frozen embryo transfer (FET)? DESIGN: A retrospective study was performed at a university-affiliated fertility centre, involving women with singleton and twin deliveries conceived by FET. Subjects were divided into four groups based on ABO blood type. The primary end-points were obstetric and perinatal outcomes. RESULTS: A total of 20,981 women were involved, with 15,830 having singletons and 5151 delivering twins. In singleton pregnancies, women with blood group B had a slight but significantly increased risk of gestational diabetes mellitus compared to women with blood group O (adjusted odds ratio [aOR] 1.16; 95% confidence interval [CI] 1.01-1.34). Furthermore, singletons born to women with the B antigen (blood type B or AB) were more likely to be large for gestational age (LGA) and with macrosomia. In twin pregnancies, blood type AB was related to a decreased risk of hypertensive diseases of pregnancy (aOR 0.58; 95% CI 0.37-0.92), while blood type A was associated with a higher risk of placenta praevia (aOR 2.04; 95% CI 1.15-3.60). When compared with the O blood group, twins from the AB blood group had a lower risk of low birthweight (aOR 0.83; 95% CI 0.71-0.98) but a higher risk of LGA (aOR 1.26; 95% CI 1.05-1.52). CONCLUSIONS: This study demonstrates that the ABO blood group may influence the obstetric and perinatal outcomes for both singletons and twins. These findings emphasize that patient characteristics could be, at least partly, responsible for adverse maternal and birth outcomes following IVF.

Definition of a Novel Immunogenic Cell Death-Relevant Gene Signature Associated with Immune Landscape in Gastric Cancer.

Immunogenic cell death (ICD) induces anti-tumor immunity and aids in dismantling the immunosuppressive immune microenvironment (TME), which belongs to a type of regulated cell death. The differentiation of gastric cancer (GC) subtypes and the discovery of prognostic biomarkers are crucial for its treatment because GC is a disease that is both highly heterogeneous and aggressive. However, although the induction of ICD in tumor cells is associated with a favorable prognosis, the exact mechanism of its role in GC remains unclear. Transcriptome profiling data and clinical data of GC patients were retrieved from The Cancer Genome Atlas (TCGA) database. Herein, patients were classified with the consensus clustering algorithm, and the associated biological functions and immune microenvironment infiltration were explored based on the expression of ICD-associated genes. A risk score signature consisting of 11 ICD-related genes was established via the least absolute shrinkage and selection operator regression (LASSO) method. We have retrieved similar studies in recent years and compared them with our study using the time-dependent receiver operating characteristic (ROC) curves. Gene set variation analysis (GSVA) and single sample gene set enrichment analysis (ssGSEA) were performed to explore the association between the signature and tumor microenvironment (TME). Two distinct subtypes associated with ICD in GC were identified, each with a different prognosis. The ICD-high expression subtype was associated with higher immune cell infiltration and a better prognosis. The ICD-related gene signature containing 11 genes (CGB5, Z84468.1, APOA5, EPHA8, CLEC18C, TLR7, MUC7, MUC15, CTLA4, CALB2, and UGT2B28), could independently and accurately predict the prognosis of GC. In this study, an ICD-based classification was conducted to assist in the diagnosis and personalized therapy for GC. The ICD-related genes risk score model was established to predict prognosis.

[Changes in Land Use Carbon Emissions and Coordinated Zoning in China].

Carbon emissions from land use changes have become one of the main sources of regional carbon emissions. In order to explore its changes, based on the MCD12Q-LUCC data of MODIS from 2001 to 2019 using the carbon emission coefficient method, clustering, and outlier analysis method, the spatial characteristics of land use carbon emissions in various provinces in China in the past 19 years were discussed from the perspectives of carbon emission economy contributive coefficient, carbon ecological support coefficient, and their coupling and coordination relationship. The results showed that:① from 2000 to 2019, the national land use carbon emissions increased significantly; however, after 2011, the growth rate of carbon emissions became flat, whereas the growth of carbon sinks was relatively slow, and the gap between the two was still large. ② Clustering and outlier analysis showed that during the study period, the high-value agglomeration centers of land use carbon emissions in various provinces and cities across the country shifted from Guangdong, Jiangsu, and other provinces to Hebei, Shanxi, Inner Mongolia, and other provinces, and the agglomeration status became increasingly obvious. ③ The economy contributive coefficient of carbon emissions in all provinces and cities across the country had the spatial characteristics of being high in the south and low in the north, and the ecological support coefficient gradually developed from high in the west to low in the east, followed by that in the north, and the coupling coordination between the two showed a downward trend. ④ Based on the economy contributive of carbon emissions and carbon ecological support, this study divided the provinces into four categories:low-carbon maintenance area, economic development area, carbon sink development area, and comprehensive optimization area. We also put forward our own development suggestions, striving to achieve carbon neutrality and low-carbon sustainable development.

Optimizing Levilactobacillus brevis NPS-QW 145 Fermentation for Gamma-Aminobutyric Acid (GABA) Production in Soybean Sprout Yogurt-like Product.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid with various physiological functions. Levilactobacillus brevis NPS-QW 145 strains active in GABA catabolism and anabolism can be used as a microbial platform for GABA production. Soybean sprouts can be treated as a fermentation substrate for making functional products. This study demonstrated the benefits of using soybean sprouts as a medium to produce GABA by Levilactobacillus brevis NPS-QW 145 when monosodium glutamate (MSG) is the substrate. Based on this method, a GABA yield of up to 2.302 g L-1 was obtained with a soybean germination time of one day and fermentation of 48 h with bacteria using 10 g L-1 glucose according to the response surface methodology. Research revealed a powerful technique for producing GABA by fermentation with Levilactobacillus brevis NPS-QW 145 in foods and is expected to be widely used as a nutritional supplement for consumers.

Air-Stable Flexible Photodetector Based on MXene-Cs3Bi2I9 Microplate Schottky Junctions for Weak-Light Detection.

Weak-light detection technology is widely used in various fields, including industry, high-energy physics, precision analysis, and reflection imaging. Metal-semiconductor-metal (MSM) photodetectors demonstrate high detectivity and high response speed and are one of the suitable structures for the preparation of weak-light detectors. However, traditional MSM photodetectors tend to exhibit high dark currents, which are not conducive to performance improvement. Here, a MXene-Cs3Bi2I9-MXene weak-light detector is proposed. Based on the MXene-Cs3Bi2I9 Schottky junctions, the dark current is reduced by 2 orders of magnitude and the responsivity is significantly improved compared with the traditional Cr/Au-Cs3Bi2I9-Cr/Au MSM photodetector. The device demonstrates excellent photodetection capacity with a photoresponsivity of 6.45 A W-1, a specific detectivity of 9.45 × 1011 Jones, and a fast response speed of 0.27/2.32 ms. Especially, the device yielded a superior weak-light detectable limit of 10.66 nW cm-2 and demonstrated excellent optical communication capability. Moreover, such a flexible device shows little degradation in photodetection performance after extreme bending for 4500 cycles, proving remarkable bending endurance and flexibility. The obtained results highlight the great potential of such Cs3Bi2I9/MXene devices as a stable and environmentally friendly candidate for weak-light detection.

Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-synovitis in Knee Osteoarthritis.

OBJECTIVE: The objective of this study is to investigate whether quantitatively measured infrapatellar fat pad (IPFP) signal intensity alteration is associated with joint effusion-synovitis in people with knee osteoarthritis (OA) over two years. METHODS: Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed effects models assessed the associations between IPFP signal intensity alteration and effusion-synovitis over two years. RESULTS: In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. CONCLUSION: Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.

The anti-hepatocellular carcinoma effects of polysaccharides from Ganoderma lucidum by regulating macrophage polarization via the MAPK/NF-κB signaling pathway.

The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Ganoderma lucidum polysaccharide (GLPS) is a major bioactive component of Ganoderma lucidum, a well-known medicinal mushroom. Although the immunomodulatory and anti-tumor effects of GLPS have been proven, GLPS's effect on inhibiting hepatocellular carcinoma (HCC) by regulating macrophage polarization is little known. Our data showed that GLPS notably inhibited the growth of a Hepa1-6 allograft. The expression of M1 marker CD86 was higher in the tumor tissue of the GLPS treatment group than in the control group in vivo. In vitro, the phagocytic activity and NO production of macrophages were increased by GLPS treatment. Moreover, it was discovered that GLPS was able to increase the expression of the M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines comprising IL-12a, IL-23a, IL-27 and TNF-α, but inhibited macrophage polarization towards the M2 phenotype by decreasing the expression of CD206, Arg-1, and inflammation-related cytokines comprising IL-6 and IL-10. The data suggest that GLPS may regulate macrophage polarization. Mechanistically, GLPS increased the phosphorylation of MEK and ERK. In addition, the phosphorylation of IκBα and P65 was increased by GLPS treatment. These data showed that GLPS can regulate the MAPK/NF-κB signaling pathway responsible for M1 polarization. In a nutshell, our research puts forward a new application of GLPS in anti-HCC treatment by regulating macrophage polarization through activating MAPK/NF-κB signaling.

Effect of refined management on the recovery of patients undergoing sinusitis surgery via nasal endoscopy.

OBJECTIVE: To explore the effect of refined management in the operation room on promoting postoperative recovery in patients undergoing sinusitis surgery via nasal endoscopy. METHODS: In this retrospective study, the clinical data of 80 patients undergoing endoscopic sinus surgery were divided into study group (SG) and control group (CG) according to different nursing methods, with 40 cases in each group. The CG only received routine nursing, while the SG adopted refined management in addition to routine nursing. Postoperative pain, depression, anxiety, and nursing satisfaction were compared between the two groups. RESULTS: There was no significant difference in Visual Analogue Scale (VAS) score between the two groups before operation (P>0.05). After operation, VAS of the SG (1.05±0.24) was significantly better than that of the CG (2.39±0.45), the nursing satisfaction rate of the SG (92.5%) was higher than that of the CG (65.0%), and the overall effective rate of nursing in the SG (95.0%) was higher than that of the CG (77.5%) (all P<0.05). The patients of SG had a lower rate of postoperative complications than CG patients (P<0.05). The operation time and postoperative recovery time of the SG were shorter than those of the CG, and the intraoperative blood loss was less than that of the CG. Smoking history, family history, dust mite allergy, pollen allergy, pet keeping, opening air conditioner use, airing of bed linen, and window ventilation were the main prognostic factors of patients with sinusitis (P<0.05). Family history, duration of immunotherapy, gender and complications were the factors affecting the prognosis of patients with sinusitis (P<0.05). The incidence of depression and anxiety in the SG were lower than those in the CG (P<0.05). The postoperative quality of life in the SG was better than that in the CG (P<0.05). CONCLUSION: Refined nursing can effectively alleviate pain, improve patients' satisfaction of nursing, and also significantly improve patient's depression and anxiety in endoscopic sinus surgery.

Influence of calcium sulfate incorporated with gluconolactone coagulant on the quality of whole soybean flour tofu.

This work proposes a novel method for whole soybean flour tofu preparation by combining calcium sulfate (CS) and glucose-delta-lactone (GDL) coagulation. Importantly, the characteristics of the synthesized gel and the quality were studied. MRI and SEM results showed that the whole soybean flour tofu possessed satisfactory water holding capacity and water content at a CS to GDL ratio of 3:2, significantly improving the cross-linking network gel in tofu and accounting for its similar color to soybeans. Furthermore, GC-IMS analysis showed that the whole soybean flour tofu prepared at a 3:2 ratio had more flavor components (51 types) than commercially available ones (CS or GDL tofu) and exhibited satisfactory results during consumer sensory evaluation. Overall, this method is effective and applicable for the industrial preparation of whole soybean flour tofu.

A Zn(II)(2)Cys(6) transcription factor MPsGeI suppresses pigment biosynthesis in Monascus.

High-quality natural edible pigments known as monascus pigments (MPs) are widely used in food, medicine, and chemical industries as active functional ingredients. At the transcriptional level, the expression of MPs genes are tightly controlled, limiting their productivity and color value. Hitherto our understanding of the regulation of expression of MPs genes has been rather limited. Here, we describe a pathway-specific Zn(II)(2)Cys(6) transcription factor involved in the MPs biosynthetic cluster named MPsGeI, which encodes a 813-amino-acid protein with six introns. Expression of all MPs biosynthetic genes and accumulation of MPs were remarkably increased in ΔMPsGeI strain, and MPs production was significantly reduced in MPsGeI over-expressing strain. Results clearly demonstrated that MPsGeI negatively regulates MPs accumulation via transcriptional regulation of MPs biosynthetic genes, and plays a central repressive role in MPs' biosynthesis. Transcriptomic analyses revealed that MPsGeI disruptant regulated higher concentrations of precursors flowing to pigment and resulted in accumulation of a large amount of red MPs in hyphae. This work offers an efficient method for increasing MPs's productivity and color value and provides novel insights into the regulatory mechanisms of fungal cellular processes, which will assist to enhance MPs production and application.

In-pipette-tip kapok fiber-supported liquid extraction/in-situ derivatization coupled with high-performance liquid chromatography for conveniently determining three furfurals.

This study presents an in-pipette-tip kapok fiber-supported liquid extraction/in-situ derivatization (in-pipette-tip KF-SLE-ISD) method for simultaneous enrichment and derivatization of furfurals. Briefly, 3 mg of natural kapok fiber, which was loaded in an assembled pipette-tip, was used to support 12.5 µL of extractant (ethyl acetate/toluene, 75:25, v/v) containing 10 mM 2,4-dinitrophenylhydrazine. The in-pipette-tip KF-SLE-ISD procedure was conveniently conducted by aspirating/releasing 1 mL of sample solution 10 cycles, allowing simultaneous extraction and derivatization of furfurals. Then, 100 µL of acetonitrile was aspirated/released 5 cycles for elution, 10 µL of which was directly analyzed by high-performance liquid chromatography. The limits of quantitation were in ranges of 0.10-0.45 µg/mL. The method showed satisfied linearity (R2 > 0.99), precision (RSD < 8.53%) and relative recovery (90.34-114.71%), which was successfully applied to determine furfurals in various samples (e.g., honeys, juices and glucose injections). The proposed method has the merits of effectiveness, simplicity, low cost, wide availability and ease of automation.

"Two-in-one" dual-function luminescent MOF hydrogel for onsite ultra-sensitive detection and efficient enrichment of radioactive uranium in water.

In consideration of the severe hazards of radioactive uranium pollution and the growing demand of uranium resources, the novel sensor/adsorbent composite was creatively developed to integrate the dual functions for on-site detection of uranium contamination and efficient recovery of uranium resources. By hybridizing the luminescent 3D terbium (III) metal-organic framework (Tb-MOF) with sodium alginate (SA) gel using terbium (III) as cross-linker, the Tb-MOF/Tb-AG was fabricated with multi-luminescence centers and sufficient binding sites for uranium. Notably, the ultra-high sensitivity with detection limit as low as 1.2 ppt was achieved, which was 4 orders of magnitude lower than the uranium contamination standard in drinking water (USEPA) and even comparable to the sensitivity of the ICP-MS. Furthermore, the very wide quantification range (1.0 ×10-9-5.0 ×10-4 mol/L), remarkable adsorption capacity (549.0 mg/g) and outstanding anti-interference ability have been achieved without sophisticated sample preparation procedures. Applied in complex natural water samples from Uranium Tailings and the Pearl River, this method has shown good detection accuracy. The ultra high sensitivity and great adsorption capacity for uranium could be ascribed to the synergistic coordination, hydrogen bonding and ion exchange between uranium and Tb-MOF/Tb-AG. The mechanisms were explored by infrared spectroscopy, batch experiments, X-ray photoelectron studies and energy dispersive spectroscopic studies. In addition, the Tb-MOF/Tb-AG can be reused for uranium adsorption.

LncRNA WEE2-AS1 is a diagnostic biomarker that predicts poor prognoses in patients with glioma.

BACKGROUND: Glioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma. METHODS: Gene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal-Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan-Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels. RESULTS: We found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment. CONCLUSION: These findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma.

Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-ß/Smad2 signaling in chondrocytes.

TGF-ß signaling is crucial for modulating osteoarthritis (OA), and protein phosphatase magnesium-dependent 1A (PPM1A) has been reported as a phosphatase of SMAD2 and regulates TGF-ß signaling, while the role of PPM1A in cartilage homeostasis and OA development remains largely unexplored. In this study, we found increased PPM1A expression in OA chondrocytes and confirmed the interaction between PPM1A and phospho-SMAD2 (p-SMAD2). Importantly, our data show that PPM1A KO substantially protected mice treated with destabilization of medial meniscus (DMM) surgery against cartilage degeneration and subchondral sclerosis. Additionally, PPM1A ablation reduced the cartilage catabolism and cell apoptosis after the DMM operation. Moreover, p-SMAD2 expression in chondrocytes from KO mice was higher than that in WT controls with DMM induction. However, intraarticular injection with SD-208, repressing TGF-ß/SMAD2 signaling, dramatically abolished protective phenotypes in PPM1A-KO mice. Finally, a specific pharmacologic PPM1A inhibitor, Sanguinarine chloride (SC) or BC-21, was able to ameliorate OA severity in C57BL/6J mice. In summary, our study identified PPM1A as a pivotal regulator of cartilage homeostasis and demonstrated that PPM1A inhibition attenuates OA progression via regulating TGF-ß/SMAD2 signaling in chondrocytes and provided PPM1A as a potential target for OA treatment.

Quantifying the Leaping Motion Using a Self-Propelled Bionic Robotic Dolphin Platform.

Kinematic analysis of leaping motions can provide meaningful insights into unraveling the efficient and agile propulsive mechanisms in dolphin swimming. However, undisturbed kinematic examination of live dolphins has been very scarce due to the restriction of close-up biological observation with a motion capture system. The main objective of this study is to quantify the leaping motion of a self-propelled bionic robotic dolphin using a combined numerical and experimental method. More specifically, a dynamic model was established for the hydrodynamic analysis of a changeable submerged portion, and experimental data were then employed to identify hydrodynamic parameters and validate the effectiveness. The effects of wave-making resistance were explored, indicating that there is a varying nonlinear relationship between power and speed at different depths. In addition, the wave-making resistance can be reduced significantly when swimming at a certain depth, which leads to a higher speed and less consumed power. Quantitative estimation of leaping motion is carried out, and the results suggest that with increase of the exiting velocity and angle, the maximum height of the center of mass (CM) increases as well; furthermore, a small exiting angle usually requires a much larger exiting velocity to achieve a complete exiting motion. These findings provide implications for optimizing motion performance, which is an integral part of underwater operations in complex aquatic environments.

Two-institution results of Stereotactic Body Radiation Therapy (SBRT) for treating adrenal gland metastases from liver cancer.

OBJECTIVE: Stereotactic Body Radiation Therapy (SBRT) has been found beneficial for adrenal gland metastases (AGMs) with a high local control rate and low toxicity. The role of SBRT for AGMs in patients with liver cancer has not been well-discussed before. We, therefore, report our two-institution experience to further elaborate on the feasibility and effectiveness of SBRT in the treatment of AGMs from liver cancer. METHODS: A total of 23 liver cancer patients (19 males, 4 females) with 24 AGMs treated by SBRT from July 2006 to April 2021 were retrospectively included in this study. Toxicity was assessed based on clinical adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The effectiveness was assessed based on local control (LC), progression-free survival (PFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Univariate analyses were compared by log-rank test. The relevant covariates were evaluated using Cox proportional hazards models. RESULTS: The median dose was 40 Gy in 5 fractions, with the corresponding median biological effective dose (BED10, α/ß = 10 Gy) of 72 Gy. The median overall follow-up time was 15.4 months (range: 4.2-70.6 months). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 25.0%, 20.8%, 33.3%, and 20.8%, respectively. All 6 patients with AGMs accompanying symptoms had varying degrees of alleviation after SBRT. The 0.5-, 1-year and 2-year LC rates were 87.5%, 77.8%, and 77.8%, respectively. The 0.5-, 1-year and 2-year OS rates were 95.5%, 66.8%, and 41.1%, respectively. The treatments were all tolerated with only one patient reporting a grade-3 hepatic injury. The univariate analysis concluded that only gross tumor volume (GTV) < 34.5 ml (p = 0.039) was associated with a favorable LC rate. After multivariate analysis, favorable predictors correlated with OS were GTV < 34.5 ml (p = 0.043), systemic therapy (p = 0.017), and without additional organ metastasis after SBRT (p = 0.009). CONCLUSION: Our results suggest that SBRT is a safe and effective technique to treat AGM from liver cancer, especially for small GTV (< 34.5ml). Moreover, the small metastatic lesion volume, fewer metastatic lesions, and intervention of systemic therapy are more likely to improve OS.