Identification of ARF genes in Juglans Sigillata Dode and analysis of their expression patterns under drought stress.

BACKGROUND: Auxin response factor (ARF), a transcription factors that controls the expression of genes responsive to auxin, plays a key role in the regulation of plant growth and development. Analyses aimed at identifying ARF family genes and characterizing their functions in Juglans sigillata Dode are lacking. METHODS AND RESULTS: We used bioinformatic approaches to identify members of the J. sigillata ARF gene family and analyze their evolutionary relationships, collinearity, cis-acting elements, and tissue-specific expression patterns. The expression patterns of ARF gene family members under natural drought conditions were also analyzed. The J. sigillata ARF gene family contained 31 members, which were unevenly distributed across 16 chromosomes. We constructed a phylogenetic tree of JsARF genes and other plant ARF genes. Cis-acting elements in the promoters of JsARF were predicted. JsARF28 showed higher expressions in both the roots and leaves. A heat map of the transcriptome data of the cluster analysis under drought stress indicated that JsARF3/9/11/17/20/26 are responsive to drought. The expression of the 11 ARF genes varied under PEG treatment and JsARF18 and JsARF20 were significantly up-regulated. CONCLUSIONS: The interactions between abiotic stresses and plant hormones are supported by our cumulative data, which also offers a theoretical groundwork for comprehending the ARF mechanism and drought resistance in J. sigillata.

GSH-responsive degradable nanodrug for glucose metabolism intervention and induction of ferroptosis to enhance magnetothermal anti-tumor therapy.

The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy.

The mitochondria-targeted Kaempferol nanoparticle ameliorates severe acute pancreatitis.

Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.

Establishment of Agrobacterium-mediated transformation system to Juglans sigillata Dode 'Qianhe-7'.

An efficient genetic transformation system is of great significance for verifying gene function and improving plant breeding efficiency by gene engineering. In this study, a stable Agrobacterium mediated genetic transformation system of Juglans sigillata Dode 'Qianhe-7' was investigated using callus and negative pressure-assisted and ultrasonic-assisted transformation selection. The results showed that the axillary shoot leaves were suitable to induce callus and the callus proliferation rate could reach 516.27% when induction calli were cultured on DKW medium containing 0.5 mg L-1 indole-3-butyric acid, 1.2 mg L-1 2,4-dichlorophenoxyacetic acid and 0.5 mg L-1 kinetin for 18 d. In addition, negative pressure infection was the optimal infection method with the lowest browning rate (0.00%), high GFP conversion rate (16.67%), and better growth status. To further prove the feasibility of this genetic transformation system, the flavonol synthetase (JsFLS5) gene was successfully transformed into the into leaf-derived callus of 'Qianhe-7'. JsFLS5 expression and the content of total flavonoids in transformed callus were improved significantly compared with the untransformed callus, which proved that we had an efficient and reliable genetic transformation system using leaf-derived callus of Juglans sigillata.

Overexpression of JsFLS5 in calli improves salinity tolerance by maintaining active oxygen balance and reducing Na+ toxicity in Juglans sigillata.

The escalating global climate change significantly threatens plant growth, development, and production through salinity stress. Flavonoids, a crucial category of secondary metabolites, have been extensively studied for their role in modulating plant growth and development mechanisms in the face of biological and abiotic stress. The flavonol synthetase (FLS) gene plays a key role in the biosynthesis and accumulation of flavonoids. To investigate the correlation between salt tolerance and flavonol synthesis, JsFLS5 was overexpressed in the callus of Juglans sigillata cv. "Qianhe-7." This study shows that the upregulation of JsFLS5 significantly elevates the overall flavonoid content by modulating the expression of genes associated with flavonoid synthesis under salinity stress conditions. Additionally, the overexpressing callus exhibited enhanced resistance to salt stress compared to the wild-type callus, as evidenced by reduced levels of reactive oxygen species accumulation, electrolyte leakage, and malondialdehyde content in the overexpressing callus relative to the wild type (WT). Moreover, the overexpressing callus showed higher antioxidant enzyme activity and a more efficient ascorbic acid-glutathione cycle. Furthermore, the concentration of Na+ in the overexpressing callus was lower than WT, resulting in a decreased Na+ /K+ ratio. These findings suggest that JsFLS5 overexpression in calli effectively mitigates the oxidative damage induced by osmotic stress and reduces Na+ toxicity by enhancing flavonoid synthesis under salt stress conditions. Consequently, this study offers a novel perspective for comprehending the role of JsFLS5 in the response to abiotic stress in J. sigillata.

Environmental factors associated with incidence of developmental dysplasia of the hip: a systematic review and meta-analysis.

BACKGROUND: Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent. METHODS: A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence. RESULTS: Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence. CONCLUSION: The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates.

Soft Tissue Releases With Simultaneous Guided Growth Decrease Risk of Spastic Hip Displacement Recurrence.

BACKGROUND: Soft tissue release (STR) is an established treatment for spastic hip displacement, but recurrence of hip displacement is not uncommon. This study aims to (1) evaluate the recurrence of hip displacement after STR, (2) define associated factors of recurrence, and (3) elucidate the effects of guided growth on hip displacement recurrence. METHODS: The study subjects included 66 individuals with spastic cerebral palsy treated by STR with or without guided growth for hip displacement. The treatment goal was the maintenance of migration percentage (MP) to <40%. Recurrence was defined by a rebound of the MP by 5% or more after the first postoperative year. Children with recurrence were compared with those without recurrence using the Mann-Whitney U test and the χ 2 test. The risk factors for recurrence were evaluated using multiple logistic regression analysis. RESULTS: Nineteen individuals (29%) had a recurrence of hip displacement after the first postoperative year. They sustained a 2-fold increase in the rate of treatment failure ( P < 0.001) and reoperation ( P = 0.04). Age, sex, motor function, and preoperative radiographic parameters were comparable between individuals with and without recurrence. The use of guided growth was associated with less risk of recurrence than without (5% and 39%, respectively, odds ratio = 0.01 to 0.45, respectively) despite the similar risk of failure (35% and 48%, respectively, odds ratio = 0.15 to 4.82). CONCLUSIONS: Recurrence of the MP >5% after the first postoperative year is an important early indicator for failure to control MP to <40% and reoperation. Guided growth not only decreases coxa valga but also reduces the risk of recurrent hip displacement after STR. LEVEL OF EVIDENCE: Level III; case-control study.

Prediction of Surgical Outcomes of Radial Polydactyly From the Wassel-Flatt Type and Symmetry of Duplication.

BACKGROUND: The Wassel classification is commonly used for cases of radial polydactyly but has not been used to predict surgical outcomes. This study aimed to investigate the predictive factors of surgical outcomes using the Wassel type and symmetry of duplication. METHODS: Forty-five patients with 47 radial polydactylies were reviewed using the Japanese Society for Surgery of the Hand (JSSH) scores 4.6 years after minor thumb excision and reconstructive surgery. The symmetry index was defined as the metaphyseal width ratio of the minor thumb to the dominant thumb. The relationships between the JSSH scores and operation age, sex, side, follow-up duration, Wassel type, symmetric index, divergent angle, and joint angulation were analyzed by linear regression. RESULTS: The mean JSSH score of the 47 thumbs was 18.3 points (range, 15-20). Five thumbs had fair or poor outcomes (scores <17), all of which were Wassel type IV. The hypoplastic type had a better JSSH score (19.4) than other Wassel types. The symmetric index had a negative relationship with JSSH scores, especially for Wassel type IV (r=-0.68, P =0.001). Linear regression revealed that the symmetric index was the only independent factor significantly associated with JSSH scores among Wassel type IV polydactylies ( P <0.05). The receiver operating characteristic curve suggested a symmetric index <0.74 could predict good or excellent outcomes. CONCLUSION: The symmetry of the 2 duplicated thumbs is an important factor for surgical outcomes. The Wassel type IV polydactylies with a symmetric index >0.74 are at greater risk of fair or poor outcomes after excision and reconstruction, and further studies are warranted to confirm whether the Bilhaut-Cloquet procedure is a good choice. LEVEL OF EVIDENCE: Level IV-Case-control study.

Complications and Failure to Rescue After Inpatient Pediatric Surgery.

OBJECTIVE: To describe the frequency and patterns of postoperative complications and FTR after inpatient pediatric surgical procedures and to evaluate the association between number of complications and FTR. SUMMARY AND BACKGROUND: FTR, or a postoperative death after a complication, is currently a nationally endorsed quality measure for adults. Although it is a contributing factor to variation in mortality, relatively little is known about FTR after pediatric surgery. METHODS: Cohort study of 200,554 patients within the National Surgical Quality Improvement Program-Pediatric database (2012-2016) who underwent a high (≥ 1%) or low (< 1%) mortality risk inpatient surgical procedures. Patients were stratified based on number of postoperative complications (0, 1, 2, or ≥3) and further categorized as having undergone either a low- or high-risk procedure. The association between the number of postoperative complications and FTR was evaluated with multivariable logistic regression. RESULTS: Among patients who underwent a low- (89.4%) or high-risk (10.6%) procedures, 14.0% and 12.5% had at least 1 postoperative complication, respectively. FTR rates after low- and high-risk procedures demonstrated step-wise increases as the number of complications accrued (eg, low-risk- 9.2% in patients with ≥3 complications; high-risk-36.9% in patients with ≥ 3 complications). Relative to patients who had no complications, there was a dose-response relationship between mortality and the number of complications after low-risk [1 complication - odds ratio (OR) 3.34 (95% CI 2.62-4.27); 2 - OR 10.15 (95% CI 7.40-13.92); ≥3-27.48 (95% CI 19.06-39.62)] and high-risk operations [1 - OR 3.29 (2.61-4.16); 2-7.24 (5.14-10.19); ≥3-20.73 (12.62-34.04)]. CONCLUSIONS: There is a dose-response relationship between the number of postoperative complications after inpatient surgery and FTR, ever after common, "minor" surgical procedures. These findings suggest FTR may be a potential quality measure for pediatric surgical care.

Iptakalim alleviates synaptic damages via targeting mitochondrial ATP-sensitive potassium channel in depression.

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive-like phenotype in vivo (chronic mild stress-induced mice model of depression) and in vitro (corticosterone-induced cellular model). Further study showed that Ipt could upregulate the synaptic-related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP-sensitive potassium (Mito-KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.

Genu Valgum After Distal Femur Extension Osteotomy in Children With Cerebral Palsy.

BACKGROUND: Distal femur extension osteotomy (DFEO) is a common treatment for knee flexion contracture and crouch gait in patients with cerebral palsy (CP), but skeletally immature patients tend to develop genu valgum deformities after DFEO. This study aimed to report the tendency of valgus changes after DFEO and determine the risk factors for subsequent surgery for excessive genu valgum. METHODS: This retrospective case-control study included 25 children with CP who underwent DFEO in 44 limbs for knee flexion contractures ≥15 degrees at a mean age of 11.0 years. Radiologic measurements included the anatomic lateral distal femoral angle (aLDFA), anatomic tibiofemoral angle (aTFA), medial proximal tibia angle, and plate-condyle angle, postoperatively and at the latest follow-up. Age, sex, preoperative knee flexion contracture angle, Gross Motor Function Classification System level, and radiographic measurements were compared between children with and without subsequent guided growth for genu valgum. RESULTS: A significant valgus change was observed at the distal femur in the first postoperative year (aLDFA from 83.6 to 80.1 degrees, P<0.001; aTFA from 176.1 to 172.5 degrees, P<0.01; plate-condylar angle from 5.3 to 9.5 degrees, P<0.001). Valgus changes occurred in 36 of the 44 limbs (82%) by an average of -4.6 degrees in the aLDFA, and subsequent guided growth was performed in 5 patients (20%). Guided growth for genu valgum was associated with a greater postoperative valgus angle (aLDFA: 78.0 vs. 84.9 degrees, P<0.01) but not with age, Gross Motor Function Classification System level, or preoperative flexion contracture. CONCLUSIONS: Distal metaphyseal osteotomies and distally placed angled plates near the physis are associated with valgus changes following growth. We recommend making a slight varus alignment during DFEO to compensate for subsequent valgus changes. LEVEL OF EVIDENCE: Level III-therapeutic, retrospective comparative study.

Distal Femur Growth Modification Surgery Is Associated With Higher Surgical Wound Complication Rate.

BACKGROUND: Orthopaedic wound complications are often associated with extensive surgeries and patient medical conditions. However, we noticed wound complications in minor growth modification surgeries in children, including guided growth and epiphysiodesis. Herein, we report the complication rate and risk factors associated with pediatric growth modification surgeries. METHODS: This retrospective study reviewed surgical wound complications in 622 pediatric orthopaedic patients who underwent growth modification surgeries (418 children) or osteotomies (204 children) in the lower extremities in a single center between 2007 and 2019. The grades II and III complications assessed using the modified Clavien-Dindo-Sink complication classification system were compared between growth modification and osteotomy. Risk factors for complications, including the type of surgery, age, body mass index, neuromuscular disease, operation time, surgical sites per patient, surgical location, and implant types, were analyzed using the logistic regression. RESULTS: The complication rate was 6.9% per patient and 3.6% per surgical site (29 sites in 29 patients comprising 21 grade II and 8 grade III) in the growth modification group, which was >1.0% per patient and 0.6% per site in the osteotomy group (2 sites in 2 patients comprising 2 grade III infections; P =0.001). Among 418 patients with 797 surgical sites in the growth modification group, wound complications were associated with surgical location (5.2% at distal femur vs. 1.0% at proximal tibia, P =0.002) and implant type (0.5% using transphyseal screw vs. 4.3-10.5% using plates or staples, P =0.011). CONCLUSION: Surgical wound complication was associated with growth modification surgeries using plates or staples at the distal femur. Our results alert orthopaedic surgeons to this minor but unneglectable problem. Transphyseal screws may be the implant of choice for guided growth and epiphysiodesis at the distal femur in older children, considering the lower risks of wound complication. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The effectiveness of adding guided growth to soft tissue release in treating spastic hip displacement.

BACKGROUND: Guided growth at the proximal femur using one transphyseal screw corrects coxa valga and improves hip displacement in cerebral palsy. This study aimed to validate the effects of adding guided growth (GG) to soft tissue release (STR), in terms of decreasing the migration percentage (MP), compared to those with soft tissue alone. METHODS: This retrospective study comprised patients with cerebral palsy who underwent soft tissue release alone (Group STR) or soft tissue release plus guided growth (Group GG) for hip displacement (mean age, 8.1 years; mean follow-up, 4.9 years). Difference in the MP and rate of controlling MP <40% at 2 years postoperatively and rate of revision surgeries at 5 years postoperatively were compared between the groups. RESULTS: The two groups were comparable in age, side, and gross motor function level, but Group GG (n = 24) had more severe hip displacement preoperatively than did Group STR (n = 64). Group GG had a significantly greater 2-year decrease in the MP (-14.8% vs. -11.8%, p < 0.05) than did Group STR. Among patients with a pre-operative MP >50%, the rate of MP <40% was greater in Group GG (73%) than in Group STR (41%). Revision surgeries, mainly repeated guided growth and soft tissue release, were comparable between the groups. CONCLUSIONS: This is the first comparative study to support adding guided growth to soft tissue release, as it results in greater improvements in hip displacement than that with soft tissue release alone. Non-ambulatory patients or severe hip displacement with MP 50%-70% could benefit from this less aggressive surgery by controlling the MP under 40% without femoral osteotomy.

Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice.

Acute biliary pancreatitis (ABP) with a high mortality rate is an incurable digestive system disease induced by abnormal bile acid regurgitation due to the biliary obstruction. Dehydrocholic acid (DA) alleviates the severity of cholestatic hepatitis related to biliary inflammation, suggesting DA is potential to develop for the incurable ABP management. Here we identified DA potency and explored the underlying mechanism in ABP. Our data showed that DA administration not only reduced typically clinicopathological parameters including serum levels of amylase and lipase but also suppressed pancreatic tissue edema, necrosis and trypsin activation in ABP mice. We also found that DA significantly reduced the necrosis of pancreatic acinar cells induced by sodium taurocholate (NaT). Further experimental data showed the significant inhibitions of DA on mitochondrial membrane potential depolarization, ATP exhaustion, calcium overload and reactive oxygen species (ROS) erupted in acinar cells induced by NaT, indicating DA could avert acinar cell death through protecting the mitochondrial function, scavenging excessive oxidative stress and balancing calcium. The comprehensive study found DA elevated the expression of transcription factor EB (TFEB) in vitro thus to increase the functional lysosome content. Indeed, DA decreased the Microtubule-associated protein light chain 3 (LC3) II/I ratio as well as ubiquitin-binding protein p62 and Parkin expressions in vivo and in vitro, revealing autophagy restoration maybe through the improvement of TFEB-mediated lysosome biogenesis. These data indicate that DA improves ABP through the mitochondrial protection, antioxidant ability enhancement and autophagy recovery. In conclusion, our study proposes a potential therapy strategy for the incurable ABP.

Enhanced His@AuNCs oxidase-like activity by reduced graphene oxide and its application for colorimetric and electrochemical detection of nitrite.

Enzyme-mimicking (nanozyme)-based biosensors are attractive owing to their unique catalytic efficiency, multifunctionality, and tunable activity, but examples of oxidase-like nanozymes are quite rare. Herein, we demonstrated that histidine-capped gold nanoclusters (His@AuNCs) possessed intrinsic oxidase-like activity, which could directly oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to blue colored ox-TMB without H2O2. The assembly of reduced graphene oxide (RGO) with His@AuNCs could further improve its oxidase-like activity and the His@AuNCs/RGO nanocomposites had a lower Michaelis constant (Km) and higher catalytic constant (Kcat) for TMB oxidation. Furthermore, compared to other nanomaterials, the as-prepared His@AuNCs/RGO also exhibited enhanced electrocatalytic activity toward TMB. Interestingly, nitrite inhibited the catalytic (chromogenic) and electrocatalytic processes of His@AuNCs/RGO in the oxidation of TMB. The oxidase-like and electrocatalytic activity of His@AuNCs/RGO was evaluated with nitrite and TMB as substrates, and the results indicated that TMB and nitrite might share the same catalytic active sites. On the basis of these findings, a colorimetric and electrochemical sensor was developed with the His@AuNCs/RGO composite as an oxidase mimic for determination of nitrite with linear ranges of 10-500 µM and 2.5-5700 µM, respectively. The developed method was successfully applied to the detection of nitrites in real samples. The present work suggests that the oxidase-like nanozyme is not only suitable for colorimetric assay but also for development of electrochemical sensors in bioanalysis. Graphical abstract The colorimetric and electrochemical detection of nitrite using His@AuNCs/RGO.

An ethnopharmacological study of aromatic Uyghur medicinal plants in Xinjiang, China.

CONTEXT: An ethnobotanical survey was completed in a remote village and surrounding country of Xinjiang, where most Uyghur medicinal plants could be collected. This work clarifies and increases ethnobotanical data. OBJECTIVES: We surveyed and organized aromatic medicinal plants that are commonly used in clinical settings to provide a significant reference for studying new medical activities. MATERIALS AND METHODS: In the survey, informants who have traditional knowledge on aromatic Uyghur medicinal plants were interviewed between March 2014 and September 2014. Aromatic medicinal plant species and pertinent information were collected. Some therapeutic methods and modes of preparation of traditional aromatic medicinal plants were found. RESULTS: A total of 86 aromatic medicinal plant species belonging to 36 families were included in our study. We identified 34 plant species introduced from different regions such as Europe, India and Mediterranean areas. Fruits and whole plants were the most commonly used parts of plant, and most aromatic medicinal plants could be applied as medicine and food. We assigned the medicinal plants a use value (UV). Knowing the UV of species is useful in determining the use reliability and pharmacological features of related plants. CONCLUSIONS: Xinjiang is an area in which indigenous aromatic medicinal plants are diversely used and has therefore established a sound dimensional medical healthcare treatment system. Some aromatic Uyghur medicinal plants are on the verge of extinction. Hence, further strategies for the conservation of these aromatic medicinal plants should be prioritized.

E2F-1 promotes DAPK2-induced anti-tumor immunity of gastric cancer cells by targeting miR-34a.

Activation of the transcription factor E2F-1 gene is a negative event in dendritic cell (DC) maturation process. Down-regulation of E2F1 causes immaturity of DC thereby stopping antigen production which in turn leads to inhibition of immune responses. E2F-1-free stimulates the NF-kB signaling pathway, leading to activation of monocytes and several other transcription factor genes. In the study, we report that down-regulation of E2F-1 in DCs promote anti-tumor immune response in gastric cancer (GC) cells through a novel mechanism. DCs were isolated from peripheral blood mononuclear cells. E2F-1 small interfering RNA (E2F-1-shRNA) induced down-regulation of E2F-1 mRNA and protein expression in DCs. Furthermore, we identified the E2F-1-shRNA targeted the CD80, CD83, CD86, and MHC II molecules, promoted their expression, and induced T lymphocytes proliferation activity and up-regulation of IFN-I³ production and GC cell killing effect, which significantly correlated with the cytotoxic T lymphocytes activated by E2F-1-shRNA DCs. The higher expression of miR-34a was found which was significantly correlated with the DC enhancing anti-tumor immunity against gastric cancer cell, and miR-34a potently targeted DAPK2 and Sp1, both of which were involved in the deactivation of E2F-1. Moreover, in E2F-1-DC-down-regulation in mice, GC transplantation tumors displayed down-regulation of Sp1, DAPK2, Caspase3, and Caspase7 and progressed to anti-tumor immunity. Collectively, our data uncover an E2F-1-mediated mechanism for the control of DC anti-tumor immunity via miR-34a-dependent down-regulation of E2F-1 expression and suggest its contribution to GC immunotherapy.

Guided Growth of the Proximal Femur for Hip Displacement in Children With Cerebral Palsy.

BACKGROUND: Guided growth by 1 eccentric transphyseal screw has been used to correct lower limb deformities. Pilot animal studies showed encouraging results in producing varus deformity in the proximal femur. The purpose of this study was to report the preliminary results of guided growth surgery to treat spastic hip displacement. METHODS: This case series study included consecutive patients who received soft-tissue release and guided growth at the proximal femur from January 2004 to May 2012 with minimal 2-year follow-up. Surgical indications were children with spastic cerebral palsy aged 4 to 10 years, a gross motor function classification system level IV or V, and hip displacement on 1 or both sides. Study outcomes were Reimer's migration percentage (MP) and the head-shaft angle (HSA). RESULTS: Nine children with 13 spastic displaced hips received surgery at the age of 6.2 years and were followed up for a mean of 45.6 months. The mean MP improved significantly from 52.2% preoperatively to 45.8% at 3 months, 40.3% at 1 year, and 37.1% at 2 years after operation. HSA was unchanged in the first 3 months, and deceased from 173.3 to 166.4 degrees at 1 year (P<0.01) and to 162.7 degrees at 2 years postoperatively. The screw was usually backed out from the femoral epiphysis in the second postoperative year, and no radiologic bony bar or other surgical complications occurred. CONCLUSIONS: The immediate postoperative improvement of MP was the result of soft-tissue release. From postoperative 3 months to 2 years, the HSA was reduced by 10.6 degrees and the MP further improved by 8.7%. Less surgical dissection, faster recovery of motion, and less comorbidity than varus osteotomy make guided growth surgery a treatment option for coxa valga in spastic hip displacement in nonambulant cerebral palsy children. LEVEL OF EVIDENCE: Level IV-therapeutic, case series.