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Gong HY, Wang KQ, Tang SG. Hunan Yi Ke Da Xue Xue Bao 2000;25:248-250. [Article in Chinese] In order to find an effective drug to cure patients with chronic hepatitis [...]

Severe acute pancreatitis (SAP) is an acute inflammatory injury disease with significant mortality rate and currently without effective strategy being available. Inflammation and oxidative stress play central roles in the etiology of SAP. Micheliolide (MCL), an active monomeric component isolated from Michelia champaca, has been proved its multiple therapeutic properties including anti-inflammatory, antioxidant and anti-cancer. Nevertheless, the therapeutic effect and underlying mechanism of MCL in SAP still remain unclear. Here, we found that caerulein with lipopolysaccharide (LPS)-induced SAP murine models exhibited severe pancreatic injury, including necrosis, edema, and vacuolation of acinar cells in the pancreas, elevated serum levels of amylase and lipase, and reduced number of the exocrine cells. As expected, MCL treatment alleviated these side effects. Mechanistically, MCL triggered nuclear factor erythroid 2-related factor 2 (Nrf2) activation, thereby activating Nrf2-regulated antioxidative pathways and inhibiting nuclear factor kappa B p65 (NF-κB p65)-mediated inflammatory response, resulting in protection against pancreatic injury in SAP mice. In addition, Nrf2 gene deficiency abolished the beneficial effects of MCL on SAP-induced pancreatic inflammation and oxidative stress and blocked the ability of MCL to alleviate the pancreatic injury in SAP mice. Collectively, these findings indicated that the suppression of SAP-induced pancreatic injury by MCL was at least in part due to Nrf2-mediated anti-oxidation effect and inhibition of inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aims: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH., Methods: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a -/- ) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1a ΔVSMC ) mice were used to confirm the regulatory role of HTR1A on PP., Results: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH., Conclusions: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Immune checkpoint blockade, such as monoclonal antibodies targeting programmed cell death protein 1 (PD-1), has been a major breakthrough in the treatment of several cancers, but has limited effect in colorectal cancer (CRC), which is a highly prevalent cancer worldwide. Current chemotherapy-based strategies to boost PD-1 response have many limitations. And the role of peripheral immunity in boosting PD-1 response continues to attract attention. Therefore, candidate combinations of PD-1 blockade need to be drugs with multi-targets and multi-modulatory functions. However, it is still unknown whether traditional Chinese medicines with such property can enhance the applicability and efficacy of PD-1 blockade in colorectal cancer., Methods: Euphorbia Pekinensis extract (EP) was prepared and the constituents were analyzed by HPLC. CRC cells were used for in vitro experiments, including cell viability assay, colony formation assay, flow cytometry for 7-AAD staining, western blotting for caspase 3 and caspase 7, HMGB1 and ATP detection. An orthotopic CT26 mouse model was subsequently used to investigate the combination of EP and PD-1 blockade therapy. Tumor volume and tumor weight were assessed, tumor tissues were subjected to histopathological HE staining and TUNEL staining, and tumor-infiltrating immune cells were evaluated by immunofluorescence staining. RNA-sequencing, target prediction and pathway analysis were further employed to explore the mechanism. Molecular docking and cellular thermal shift assay (CETSA) were utilized to verify the direct target of the core component of EP. And, loss-of-function analysis was carried to confirm the upstream-downstream relationship. Flow cytometry was employed to analyze CD8 + T cells in the peripheral blood and spleen., Results: The main constituents of EP are diterpenoids and flavonoids. EP dramatically suppresses CRC cell growth and exerts its cytotoxic effect by triggering immunogenic cell death in vitro. Moreover, EP synergizes with PD-1 blockade to inhibit tumorigenesis in tumor-bearing mice. Disruption of ISX nuclear localization by helioscopinolide E is a central mechanism of EP-induced apoptosis in CRC cell. Meanwhile, EP activates immune response by upregulating Phox2b to reshape the immune microenvironment. In addition, EP regulates peripheral immunity by regulating the T cell activation and proliferation, and the ratio of CD8 + T cells in peripheral blood is drastically increased, thereby enhancing the therapeutic efficacy of anti-PD1 immunotherapy., Conclusion: EP triggers intra-tumor immunogenic cell death and modulates the immunoregulatory signaling to elicit the tumor immunogenicity. Moreover, EP participates in transcriptional activation of immune response-related pathways. Consequently, multiple stimulating functions of EP on macro- and micro-immune potentiates the anti-tumor effect of PD-1 blockade in CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

To understand the effects of nitrogen deposition on element cycling and nutrient limitation status in forest ecosystems, we examined the effects of nitrogen deposition on the stoichiometric characteristics of forest soil-microbial-extracellular enzymes in Pinus yunnanensis forest. We conducted a field experiment with control (CK, 0 g N·m -2 ·a -1 ), low nitrogen (LN, 10 g N·m -2 ·a -1 ), medium nitrogen (MN, 20 g N·m -2 ·a -1 ) and high nitrogen (HN, 25 g N·m -2 ·a -1 ) since 2019. We collected soil samples (0-5 cm, 5-10 cm and 10-20 cm) at September 2022, and measured the contents of soil organic, total nitrogen, total phosphorus, microbial biomass carbon, nitrogen and phosphorus (MBC, MBN, MBP) and the activities of C, N, and P acquisition enzymes. The results showed that nitrogen deposition significantly reduced soil organic content, C:N and C:P by 6.9%-29.8%, 7.6%-45.2% and 6.5%-28.6%, and increased soil total N content and N:P by 10.0%-45.0% and 19.0%-46.0%, respectively. Nitrogen addition did not affect soil total P content. Except for soil C:N and C:P, soil nutrient content and stoichiometric ratio were highest in 0-5 cm soil layer. MN and HN treatments significantly decreased MBN by 11.0%-12.7%. MBC, MBP, and their stoichiometry did not change significantly under nitrogen deposition. Soil microbial nutrient content in 0-5 cm soil layer was significantly higher than that in other soil layers. Nitrogen deposition significantly decreased the activities of cellobiose hydrolase and leucine aminopeptidase (decreased by 14.5%-16.2% and 48.7%-66.3%). HN treatment promoted β-1,4-glucosidase activity (increased by 68.0%), but inhibited soil enzyme stoichiometric carbon to nitrogen ratio and nitrogen to phosphorus ratio (decreased by 95.4% and 88.4%). LN and MN treatment promoted β-1,4-N-acetylglucosaminidase activity (increased by 68.3%-116.6%), but inhibited enzyme stoichiometric carbon to phosphorus ratio (decreased by 14.9%-29.4%). Alkaline phosphatase activity had no significant change. Soil enzyme activities were significantly decreased with increasing soil depth. Soil total N and total P and microbial nutrients were negatively correlated with vector angle (representing microbial nitrogen or phosphorus limitation), while vector length (representing microbial carbon limitation) was consistently significantly positively correlated with vector angle, suggesting the synergistic promotion between microbial carbon limitation and phosphorus limitation. Nitrogen deposition gradually shifted to phosphorus limitation while alleviating microbial nitrogen limitation in P. yunnanensis forest. In addition, microbial activities in this region was limited by C availability, and the relationship between microbial C and P limitation was proportional.

Background & Aims: Endoplasmic reticulum (ER) stress of hepatocytes plays a causative role in non-alcoholic fatty liver disease (NAFLD). Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. Whether ER stress regulates HNF4α expression remains unknown. The aim of this study was to delineate the machinery of HNF4α protein degradation and explore a therapeutic strategy based on protecting HNF4α stability during NAFLD progression., Methods: Correlation of HNF4α and tribbles homologue 3 (TRIB3), an ER stress sensor, was evaluated in human and mouse NAFLD tissues. RNA-sequencing, mass spectrometry analysis, co-immunoprecipitation, in vivo and in vitro ubiquitination assays were used to elucidate the mechanisms of TRIB3-mediated HNF4α degradation. Molecular docking and co-immunoprecipitation analyses were performed to identify a cell-penetrating peptide that ablates the TRIB3-HNF4α interaction., Results: TRIB3 directly interacts with HNF4α and mediates ER stress-induced HNF4α degradation. TRIB3 recruits tripartite motif containing 8 (TRIM8) to form an E3 ligase complex that catalyzes K48-linked polyubiquitination of HNF4α on lysine 470. Abrogating the degradation of HNF4α attenuated the effect of TRIB3 on a diet-induced NAFLD model. Moreover, the TRIB3 gain-of-function variant p.Q84R is associated with NAFLD progression in patients, and induces lower HNF4α levels and more severe hepatic steatosis in mice. Importantly, disrupting the TRIB3-HNF4α interaction using a cell-penetrating peptide restores HNF4α levels and ameliorates NAFLD progression in mice., Conclusions: Our findings unravel the machinery of HNF4α protein degradation and indicate that targeting TRIB3-TRIM8 E3 complex-mediated HNF4α polyubiquitination may be an ideal strategy for NAFLD therapy., Impact and Implications: Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. However, the mechanism of HNF4α protein degradation remains unknown. Herein, we reveal that TRIB3-TRIM8 E3 ligase complex is responsible for HNF4α degradation during NAFLD. Inhibiting the TRIB3-HNF4α interaction effectively stabilized HNF4α protein levels and transcription factor activity in the liver and ameliorated TRIB3-mediated NAFLD progression. Our findings demonstrate that disturbing the TRIM8-TRIB3-HNF4α interaction may provide a novel approach to treat NAFLD and even other liver diseases by stabilizing the HNF4α protein., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted 'reduction, replacement and refinement' principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection., (© 2024. The Author(s).)

Study Design: Randomized controlled trial., Objectives: To compare the effect and safety of 2 anesthetic methods using in the operation of Transforaminal Endoscopic Lumbar Discectomy., Methods: From the January of 2020 to the December of 2021, 230 consecutive patients that underwent TELD were applied with two methods of anesthesia. All the patients were divided into two groups. The Monitored Anesthesia Care (MAC) group used the local anesthesia (LA) with MAC that based on the combination of dexmedetomidine and butorphanol tartrate. The LA group used the local anesthesia only. Then the Visual Analogic Scale (VAS) through the operating period was compared between the two groups at the time points of before operation (T0), inserting of the puncture needle (T1), establishing of the working cannula (T2), excision of the fibrous rings (T3) and immediately postoperatively (T4). Also, the satisfaction degree of the patients for the course of the operations and the occurrence of the complications were compared between the two groups., Results: There were no differences of the VAS around the operating area at the time point of T0. Then the MAC group expressed lower scores at all other points of T1, T2, T3 and T4. Then the satisfaction degree of the MAC group was superior than the LA group. No difference was observed for the occurrence of the complications., Conclusions: MAC based on the combination of dexmedetomidine and butorphanol tartrate is an ideal method of anesthesia for TELD with enough effect and safety., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Helicobacter pylori (Hp) infection is highly prevalent globally and is predominantly managed by antibiotics. Recently, the anti-adhesive, antioxidant, antitoxin, immunomodulatory, anti-coagulant, and anti-infective activities of fucoidan, a polysaccharide extracted from brown seaweeds, have been widely studied, and the results showed promise. Fucoidan has the potential to be utilized in Hp eradication therapy. Our present clinical study was designed to evaluate the efficiency of Lewuyou ® , a fucoidan plant drink (FPD) in eradicating Hp in humans., Methods: This multi-center, clinical study was conducted between October 2020 and July 2021. Hp infection was confirmed by urea breath test (UBT). A total of 122 patients with confirmed Hp infection were enrolled; after exclusion of incomplete data, 85 eligible patients (37 males and 48 females aged 20-81 years) were included in the final analysis. FPD (50 mL per vial) was orally administered twice daily for a 4-week cycle, and 41 patients completed an 8-week cycle., Results: No adverse event (AE) was reported in all 122 participants who had consumed FPD. The Hp eradication rate and clearance rate were 77.6% (66/85) and 20.0% (17/85), respectively, after 4 weeks of FPD consumption and 80.5% (33/41) and 26.8 (11/41) , respectively, after 8 weeks of consumption., Conclusions: The 4- and 8-week protocols of FPD consumption were safe and effective at reducing Hp load on the gastric mucosa, with Hp eradicated in the majority of participants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-63/coif). All authors report that Blue Regale Clinical Nutrition Technology Co., Ltd. provides product support for this study. QHP is from Blue Regale Clinical Nutrition Technology Co., Ltd., Kunshan, China. The authors have no other conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD., (© 2023. The Author(s).)

Objective: To understand the facial emotion recognition of male veterans with chronic schizophrenia and the relationship between facial emotion recognition and interpersonal communication to provide a reference for designing social skills training programmes., Method: Fifty-six eligible male patients with chronic schizophrenia who were admitted to our hospital from October 2020 to April 2021 were selected, and 24 healthy people were selected as controls. Facial emotion recognition, social communication skills and self-perceived interpersonal disturbance were assessed using a facial emotion recognition stimulus manual, the Social Skills Checklist (SSC) and the Interpersonal Relationship Integrative Diagnostic Scale (IRIDS). Disease status was assessed using the Positive and Negative Syndrome Scale., Results: Both the control group and the patient group had the highest recognition accuracy for neutral faces. The recognition rate for neutral expression was higher in the control group than in the patient group (p = 0.008). The rate of neutral expressions identified as happiness was higher in the patient group than in the control group (p = 0.001). The identification of anger as happiness was higher in the control group than in the patient group (p = 0.026), and the pattern of misidentification was similar between the control group and the patient group. The accuracy of facial emotion recognition was negatively associated with the age of onset (p < 0.05). The recognition accuracy for happiness was negatively associated with negative symptoms, general pathological symptoms and total scale scores (p < 0.05). The total score for expression recognition was negatively associated with the negative symptom subscale scores (p < 0.05), and there was no correlation between expression recognition and positive symptoms (p > 0.05). The recognition accuracy for happiness was negatively correlated with the IRIDS conversation factor (p < 0.05). The recognition accuracy for happiness and anger and the total scores for facial emotion recognition were negatively correlated with the SSC subscale score and the total score (p < 0.05 and p < 0.01, respectively). The main influencing factors on facial emotion recognition were the SSC total score (p < 0.001) and the positive factor score (p = 0.039)., Conclusion: Veterans with chronic schizophrenia have facial emotion recognition impairments affected by negative symptoms. There is a correlation between facial emotion recognition and interpersonal communication., Highlights: 1. There are extensive facial expression recognition disorders in schizophrenia. 2. The pattern of misidentification was similar in both the control group and the patient group, with the tendency for happiness to be identified as a neutral emotion, anger as happiness, and fear as neutral emotion and anger. 3. Based on the comprehensive assessment of social cognitive impairment in patients with schizophrenia, prospective studies of standardised interventions are designed to provide support for clinical practice., (© 2023. The Author(s).)

The development of sorbents for flue gas desulfurization in a dry mode is essential to control emission of sulfur dioxide. Based on the novel concept of "treating waste with waste", a low-cost and highly activated calcium-based sorbent (ACS) was prepared using coal fly ash, CaO and waste gypsum as the raw materials via the one-step incipient wetness impregnation method. Based on characterization using scanning electron microscopy and nitrogen adsorption-desorption, the ACS possessed a fibrous and netted structure with high porosity, which improved SO 2 adsorption greatly. The SO 2 adsorption capacity of ACS with coal fly ash/CaO/CaSO 4 = 1/2/1 was high, up to 44.26 mg g -1 , with 100% removal efficiency at 150 °C. In the absence of O 2 , SO 2 was rapidly adsorbed on the sorbent to form CaSO 3 according to in situ DRIFTS analysis, while when O 2 was present in the flue gas, SO 2 /SO 3 2- tended to be oxidized into SO 4 2- species. Moreover, the presence of NO can further enhance the SO 2 adsorption capacity of the ACS due to the formation of adsorbed NO 2 or nitrate species with strong oxidizing properties. Therefore, the ACS can be considered as a sustainable sorbent with the advantage of employing fly ash for the removal of sulfur dioxide., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene that alters cellular homeostasis, particularly in the striatum and cortex. Astrocyte signaling that establishes and maintains neuronal functions are often altered under pathological conditions. We performed single-nuclei RNA-sequencing on human HD patient-induced pluripotent stem cell (iPSC)-derived astrocytes and on striatal and cortical tissue from R6/2 HD mice to investigate high-resolution HD astrocyte cell state transitions. We observed altered maturation and glutamate signaling in HD human and mouse astrocytes. Human HD astrocytes also showed upregulated actin-mediated signaling, suggesting that some states may be cell-autonomous and human specific. In both species, astrogliogenesis transcription factors may drive HD astrocyte maturation deficits, which are supported by rescued climbing deficits in HD drosophila with NFIA knockdown. Thus, dysregulated HD astrocyte states may induce dysfunctional astrocytic properties, in part due to maturation deficits influenced by astrogliogenesis transcription factor dysregulation., Competing Interests: The authors declare no competing interests. Some authors have additional affiliations as noted below: Andrea M. Reyes-Ortiz: Genentech, Inc., South San Francisco, California. Edsel M. Abud: Scripps Research Translational Institute, La Jolla, California and Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, California. Ryan G. Lim: Modulo Bio, Inc., San Diego, California. Wayne W. Poon: NeuCyte, Inc., Mountain View, California. Patent Pending: GENERATION AND APPLICATION OF FUNCTIONAL HUMAN ASTROCYTES FROM PLURIPOTENT STEM CELLS. Inventors: Edsel Abud, Wayne Poon., (© 2022 The Authors.)

As protection for nuclear power plants is quite necessary, the nuclear fuel is sealed in zirconium alloy thin wall cladding. During service, fuel rods might be damaged caused by wall-thickness thinning, cladding corrosion and cracking, etc. This will cause the coolant to enter into the fuel rod, which may lead to the failure of the fuel assembly. However, current diagnostic methods have limitations due to the special structure of the fuel assembly and the underwater and radioactive environment. In this paper, a novel inspection method is proposed to recognize the failure of a fuel rod. The fuel rod failure can be detected based on the presence or absence of coolant inside the fuel rod by using an ultrasonic plate wave. The inspection model and process algorithm are proposed for in-service inspection. The relationship between signal and scanning position is established and analyzed. Both ultrasound field simulation and experiment have been carried out for validation. The corresponding results illustrate that the failed nuclear fuel rod of the whole fuel assembly (including the internal rods) can be effectively detected without the influence of the near-field region by using the proposed method.

In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Objective: The aim of the study is to explore the contribution and mechanism of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in pancreatic ductal adenocarcinoma (PDAC) progression., Methods: Expressions of circFGFR1, microRNA (miR)-532-3p, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were assessed by quantitative real-time polymerase chain reaction or in situ hybridization. Fluorescence in situ hybridization determined the subcellular localization of circFGFR1. Immunohistochemistry was used to detect PIK3CB expression in PDAC tissues. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Wound healing, transwell, and flow cytometry assays examined the migration, invasion, and apoptosis. Dual-luciferase and RNA pull-down assay verified the interactions between circFGFR1/PIK3CB and miR-532-3p. In vivo xenograft tumor growth and lung metastasis were assessed in nude mice., Results: Functionally, knockdown of circFGFR1 restrained in vitro PDAC cell growth, migration, invasion, and in vivo xenograft tumor growth and lung metastasis. In addition, circFGFR1 could sponge miR-532-3p to upregulate PIK3CB level. Rescue experiments revealed that the tumor-suppressive effects caused by miR-532-3p mimics could be reversed by circFGFR1 or PIK3CB overexpression., Conclusions: Our data revealed that circFGFR1 driven the malignant progression of PDAC by targeting miR-532-3p/PIK3CB axis, suggesting that inhibition of circFGFR1 might be considered as a therapeutic target for PDAC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To explore the efficacy of microwave ablation (MWA) in the treatment of hepatic alveolar echinococcosis (HAE) with a diameter of ≤5 cm., Method: From June 2014 to January 2020, patients diagnosed with HAE were retrospectively analyzed. After balancing the confounding factors by propensity score matching (PSM) , the patients were divided into MWA group (n = 20) and radical operation group (n = 20) by 1:1 matching. The safety and effectiveness of MWA were assessed by comparing the differences between the two groups in terms of postoperative general laboratory indices, grading of postoperative complications, length of postoperative hospitalization, the outcome of treatment, and disease recurrence., Result: After PSM, all confounders were not statistically different (P>0.05) . Compared with the radical surgery group, patients in the MWA group had lower postoperative ALT and WBC elevations (P<0.001) , shorter postoperative hospital stay (P<0.001) ) , lower hospital costs (P<0.001) . The effective rate of the two groups was 100%. There was no statistical difference in the incidence of postoperative complications and recurrence rate (P>0.05)., Conclusion: MWA is a safe and effective means of treating HAE ≤ 5 cm in diameter., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis., (© 2021 Institute of Botany, Chinese Academy of Sciences.)

Background: Microwave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE., Methods: This study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23-48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA., Results: MWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85-4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23-48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05)., Conclusions: MWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE., (© 2022. The Author(s).)

Background: Major depressive disorder (MDD) is the most common mental disorder associated with suicide attempts. When a patient first visits the clinic, clinicians are often expected to make concrete diagnose about acute suicidal risk. However, the timeliness of suicide attempts correlates with patients with MDD has not been tested., Methods: We divided 1718 first-episode and untreated MDD outpatients into those who did not have suicide attempts (non-attempts), recent suicide attempters (≤14 days before assessment) and long - dated suicide attempters (> 30 days before assessment). Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, 14 - item Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S) was assessed. Body mass index, some glycolipid metabolism and thyroid hormone parameters were measured. A gradient-boosted decision trees statistical model was used to generate equally weighted classification for distinguishing recent and long - dated suicide attempters from non-attempts., Results: The classifier identified higher excitement, hostility, anxiety, depression symptoms and higher free thyroxine (FT4) as risk factors for recent suicide attempters with an estimated accuracy of 87% (sensitivity, 59.1%; specificity, 61.2 %). For long - dated suicide attempters' risk factors, single status, higher anxiety and hostility symptoms, higher LDLC and lower BMI, the estimated accuracy was 88% (sensitivity, 52.8%; specificity, 49.6%)., Conclusions: Risk factors for suicide attempt among patients with MDD can be identified by integrating demographic, clinical, and biological variables as early as possible during the first time see a doctor., (Copyright © 2021. Published by Elsevier B.V.)

Imaging and serological approaches play an important role in the diagnosis and treatment of alveolar echinococcosis; however, they also suffer from some problems during their applications in clinical practices, which urges the identification of potential diagnostic markers. Novel serological, genomics and proteomics diagnostic markers alone or in combination may increase the sensitivity and specificity in early diagnosis of alveolar echinococcosis, which play vital roles in monitoring of disease courses and prognostic evaluation. This review mainly presents the advances in the studies on novel diagnostic markers for alveolar echinococcosis.

To clarify the effects of alternation of drying and wetting on the formation of soil preferential flow in arid valley, taking the wasteland in the arid valley of Honghe River as the research object, we analyzed the soil preferential flow characteristics before and after the simulation of drying and wetting alternation based on dyeing tracer method, water breakthrough curve, and image processing technology. The results showed that, under the simulated alternation of drying and wetting, the matrix flow occurred in the 0-10 cm soil layer, the dyeing depth reached 35 cm, the horizontal width of the preferred path was only 3-10 cm, and the dyeing area curve fluctuated little. Simulated alternation of drying and wetting led to significant increases in the steady effluent, macropores number, and macroporosity. In the 0-20 cm soil layer, the steady effluent after alternation of drying and wetting was about 0.27 cm 3 ·s -1 higher than that non-alternation of drying and wetting, macropores number in dyeing area was about 1.4 times higher, and the macroporosity was 13.4% higher. The macropores number was positively correlated with stable flow rate. After simulated alternation of drying and wetting, the number of macropores from large to small was 0.6-0.8 mm＞0.8-1.0 mm＞1.0-1.5 mm＞1.5-2.0 mm＞2.0-3.7 mm, while under non-alternation of drying and wetting, it was 0.8-1.0 mm＞0.6-0.8 mm＞1.0-1.5 mm＞2.0-3.7 mm＞1.5-2.0 mm. The macropores number in each pore size range was significantly correlated with the dyeing area ratio. After simulated alternation of drying and wetting, the correlation increased, and the dominant factor affecting the occurrence of preferential flow changed from the macropores number in the pore size range of 1.5-2.0 mm to that of 0.8-1.0 mm. Therefore, the alternation of drying and wetting would affect the characteristics of macropores, which caused the soil to be more prone to preferential flow and with higher magnitude.

In the Asian corn borer (ACB), Ostrinia furnacalis (Guenée), diapause is governed by a multigenetic constitution that responds to daylength and temperature with seasonality. The ACB displays uni- or multivoltinism, depending on its geographic specificity. Hence, warmer temperatures may result in alternation of voltinism in the ACB, which will help in understanding the ecological consequences of climate warming on insects. In the present study, we investigated the voltinism in two natural populations from Harbin (H) and Gongzhuling (G) as well as a laboratory (L) population (established from the H population in 2017) of the ACB, at ambient and elevated atmospheric CO 2 ( a CO 2 390 μL/L and e CO 2 750 μL/L) and temperature ( a T and E t = A t + 2 °C). From the diapause response, both the uni- and multivoltine ecotypes were coexisting in the H population. The neonate occurrence date of 50% individuals that induced diapause was ca. 10 days later in the G population than in the H population, but it was about 10 days earlier than in the L population. Comparing to the dates of onset and the peak of diapause induction, the G and L populations were less variable than the H population in response to a short and/or shortening daylength in the field. The univoltine individuals could not be eliminated completely after 19 generations of selection. Diapause incidence decreased with a climate-warming scenario, which was temporally specific and could be overridden by significantly low daily average temperatures. The e CO 2 did not directly impact the voltinism. On the basis of voltinism, the H population was sympatric for uni- and multivoltine ecotypes, with multivoltinism being dominant. The univoltinism trait was recessive. Climate warming could significantly override the effect of photoperiod, which was yearly dependent. Warmer temperatures and a decreased latitude (shortened daylength), and their interaction, would drive ACB evolution toward diapause homogeneity for multivoltinism.

DNA damage repair genes are modifiers of disease onset in Huntington's disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We show that PIAS1 is a component of the transcription-coupled repair complex, that includes the DNA damage end processing enzyme polynucleotide kinase-phosphatase (PNKP), and that PIAS1 is a SUMO E3 ligase for PNKP. Pias1 knockdown (KD) in HD mice had a normalizing effect on HD transcriptional dysregulation associated with synaptic function and disease-associated transcriptional coexpression modules enriched for DNA damage repair mechanisms as did reduction of PIAS1 in HD iPSC-derived neurons. KD also restored mutant HTT-perturbed enzymatic activity of PNKP and modulated genomic integrity of several transcriptionally normalized genes. The findings here now link SUMO modifying machinery to DNA damage repair responses and transcriptional modulation in neurodegenerative disease., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Magnesium (Mg) is an abundant and important cation in cells. Plants rely on Mg transporters to take up Mg from the soil, and then Mg is transported to anthers and other organs. Here, we showed that MGT6+/- plants display reduced fertility, while mgt6 plants are fertile. MGT6 is expressed in the anther at the early stages. Pollen mitosis and intine formation are impaired in aborted pollen grains (PGs) of MGT6+/- plants, which is similar to the defective pollen observed in mgt5 and mgt9 mutants. These results suggest that Mg deficiency leads to pollen abortion in MGT6+/- plants. Our data showed that mgt6 organs including buds develop significantly slower and mgt6 stamens accumulate a higher level of Mg, compared with wild-type (WT) and MGT6+/- plants. These results indicate that slower bud development allows mgt6 to accumulate sufficient amounts of Mg in the pollen, explaining why mgt6 is fertile. Furthermore, we found that mgt6 can restore fertility of mgt5 , which has been reported to be male sterile due to defects in Mg transport from the tapetum to microspores and that an additional Mg supply can restore its fertility. Interestingly, mgt5 fertility is recovered when grown under short photoperiod conditions, which is a well-known factor regulating plant fertility. Taken together, these results demonstrate that slow development is a general mechanism to restore mgt s fertility, which allows other redundant magnesium transporter (MGT) members to transport sufficient Mg for pollen formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Qian, Wang, Yu, Guo, Zhao, Wang, Yang, Huang and Yang.)

We examined nutrient release and ecological stoichiometric characteristics of litters under N deposition in an evergreen broadleaved forest in Mopan Mountain in central Yunnan. Nylon net bag method was used for in situ decomposition of leaf litter and twig litter. There were four treatments, including control (CK, 0 g N·m -2 ·a -1 ), low nitrogen (LN, 5 g N·m -2 ·a -1 ), medium nitrogen (MN, 15 g N·m -2 ·a -1 ), and high nitrogen (HN, 30 g N·m -2 ·a -1 ). The results showed that after one year of N addition, the contents of C and N in leaf litter, twig litter and soil increased gradually with the increases of N addition rates, with increases of 0.3%-8.2% and 4.9%-69.0%, respectively. C/N gradually decreased with increasing N addition rates, with a decrease of 0.8%-37.8%. There was no significant difference in P content, C/P and N/P of twig litter under different treatments. Treatment duration and N application rate significantly affected the N and P contents and stoichiometric ratios of leaf litter, twig litter and soil. During the 1-year decomposition process, the residual rates of C, N and P in litters were successively in the modes of release, leaching-enriched-released and leaching-enriched. Exogenous N addition significantly inhibited the release process of C, N and P in litter. The contents of C and P in soil were significantly positively correlated with the contents of N and P in litter, while the contents of N in soil were significantly positively correlated with the contents of C and N in litter. There was a significant correlation of stoichiometric characteristics between litter and soils of evergreen broadleaved forest under N deposition. Our results were helpful to understand the response mechanism of litter decomposition process of forest ecosystem to N deposition.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Several missense mutations in the orphan transporter FLVCR2 have been reported in Fowler syndrome. Affected subjects exhibit signs of severe neurological defects. We identified the mouse ortholog Mfsd7c as a gene expressed in the blood-brain barrier. Here, we report the characterizations of Mfsd7c-KO mice and compare these characterizations to phenotypic findings in humans with biallelic FLVCR2 mutations. Global KO of Mfsd7c in mice resulted in late-gestation lethality, likely due to CNS phenotypes. We found that the angiogenic growth of CNS blood vessels in the brain of Mfsd7c-KO embryos was inhibited in cortical ventricular zones and ganglionic eminences. Vascular tips were dilated and fused, resulting in glomeruloid vessels. Nonetheless, CNS blood vessels were intact, without hemorrhage. Both embryos and humans with biallelic FLVCR2 mutations exhibited reduced cerebral cortical layers, enlargement of the cerebral ventricles, and microcephaly. Transcriptomic analysis of Mfsd7cK-KO embryonic brains revealed upregulation of genes involved in glycolysis and angiogenesis. The Mfsd7c-KO brain exhibited hypoxia and neuronal cell death. Our results indicate that MFSD7c is required for the normal growth of CNS blood vessels and that ablation of this gene results in microcephaly-associated vasculopathy in mice and humans.

The article "LncRNA FEZF1-AS1 promoted chemoresistance, autophagy and epithelial-mesenchymal transition (EMT) through regulation of miR-25-3p/ITGB8 axis in prostate cancer, by Z.-H. Wang, J.-H. Wang, K.-Q. Wang, Y. Zhou, J. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24(5): 2281-2293-DOI: 10.26355/eurrev&#95;202003&#95;20494-PMID: 32196579" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20494.

From February 2018 to January 2019, a field experiment of simulated nitrogen (N) depo-sition was conducted in Pinus armandii and Pinus yunnanensis plantations in the subalpine region of central Yunnan, China. The litterbag method was used for in situ litter (leaf and twig) decomposition experiment in both plantations. Four levels of N addition were applied, i.e ., control (CK, 0 g N·m -2 ·a -1 ), low nitrogen (LN, 5 g N·m -2 ·a -1 ), medium nitrogen (MN, 15 g N·m -2 ·a -1 ), and high nitrogen (HN, 30 g N·m -2 ·a -1 ). The results showed that the annual decomposition rates of leaf and twig in P. armandii were 34.8% and 18.0%, which were higher than the 32.2% (leaf) and 16.1% (twig) in P. yunnanensis. Under N deposition, the LN treatment reduced the time of 95% mass loss of leaf and twig litter in P. armandii by 0.202 and 1.624 years, the MN treatment reduced by 0.045 and 1.437 years, and the HN treatment increased by 0.840 and 2.112 years, respectively. In the P. yunnanensis plantation, the LN treatment reduced the time of 95% mass loss of leaf and twig litter by 0.766 and 4.053 years, while the MN treatment increased by 0.366 and 0.455 years, and the HN treatment increased by 0.826 and 0.906 years, respectively. Litter (leaf and twig) decomposition of both P. armandii and P. yunnanensis were promoted by low N treatment and inhibited by high N treatment. The effects of N deposition on litter decomposition of two plantations were significantly correlated with the contents of cellulose and lignin in litter. In conclusion, the responses of litter decomposition to N deposition mainly depended on the litter substrate, especially cellulose and lignin contents.

Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae), often called the Asian corn borer, is a complicated pest because of its complex biological features, such as its adult dynamics, host choice, and life span. This complexity has been causing difficulties in both pest forecasting and control for more than 60 years. One likely explanation for this complexity is that O. furnacalis has several varieties that vary based on some specific features. During 2015-2017, postmedial line-based varieties of male O. furnacalis were identified as distinct clades (I, II, and III), which were then compared based on COI gene sequences, male sacculus construction, life span, male dynamics, and host preference. The results showed that: (1) clades II and III were more closely related to each other than Clade I, because they both completed two generations per year, more were captured in 2016 or fewer were captured in 2015, and they were more closely related according to phylogenetic inference; (2) all three clades shared some features, such as life spans under various rearing conditions, similar dynamic trends, and three teeth on the male sacculus; and (3) all three clades were significantly different from O. nubilalis based on genetic sequences, postmedial line pattern of the forewing, and sacculus construction. Overall, if O. furnacalis is categorized into clades, the species' features are likely to be a combination or mixture of the features of each individual clade. Our findings help explain the biological complexity of O. furnacalis. Future investigations on each individual clade are essential for improving forecasting and control of this pest.

Magnetically recyclable Fe 3 O 4 -CuO was synthesized by a one-step hydrothermal method and characterized by scanning electron microscopy coupled with energy dispersive spectrometer (SEM-EDS) and X-ray diffraction (XRD). The degradation of azo dye acid orange 7 (AO7) by percarbonate (SPC) activated with Fe 3 O 4 -CuO was studied. The effects of Fe 3 O 4 -CuO catalyst loading, SPC concentration, pH value, and common chloride ions on AO7 degradation in the Fe 3 O 4 -CuO/SPC system were evaluated. The main reaction mechanism of AO7 degradation was analyzed. The results show that Fe 3 O 4 -CuO could effectively activate SPC to degrade AO7 and the reaction was accelerated with the increase of Fe 3 O 4 -CuO dosage. The increase of SPC dosage was favorable for the degradation of AO7, but excessive SPC dosage inhibited the degradation of AO7. Common ions (e.g., Cl - ) in dye wastewater could promote the degradation of AO7, and the degradation rate increased with increasing concentration of Cl - . The reaction mainly occurred on the surface of the catalyst, and·OH was identified as the main active species for the degradation of AO7. The catalyst Fe 3 O 4 -CuO showed excellent stability owing to the high catalytic activity remaining after 4 cycles of repeated use. The Fe 3 O 4 -CuO/SPC system achieved a high mineralization rate in the process of decolorization of AO7.

Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury-preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury-preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up-regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury-preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair. Cover Image for this issue: doi: 10.1111/jnc.14741., (© 2019 International Society for Neurochemistry.)

Aberrant neuronal development and the persistence of mitotic cellular populations have been implicated in a multitude of neurological disorders, including Huntington's disease (HD). However, the mechanism underlying this potential pathology remains unclear. We used a modified protocol to differentiate induced pluripotent stem cells (iPSCs) from HD patients and unaffected controls into neuronal cultures enriched for medium spiny neurons, the cell type most affected in HD. We performed single-cell and bulk transcriptomic and epigenomic analyses and demonstrated that a persistent cyclin D1 + neural stem cell (NSC) population is observed selectively in adult-onset HD iPSCs during differentiation. Treatment with a WNT inhibitor abrogates this NSC population while preserving neurons. Taken together, our findings identify a mechanism that may promote aberrant neurodevelopment and adult neurogenesis in adult-onset HD striatal neurons with the potential for therapeutic compensation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

To clarify the morphological characteristics of soil preferential flow and the effect of plant roots on its formation, plants from the typical vegetation types of an artificial woodland (Leucaena acacia) and a dry watershed grassland (Heteropogon contortus) of Yuanmou County, Jinsha River were selected as the experimental objects. Based on the staining and tracing method combined with Photoshop CS5 and the Image-Pro Plus 6.0 image processing technology, we analyzed the morphological and distribution characteristics of soil preferential flow under the two planting types and examined the effects of plant roots. We found significant difference in soil preferential flow dyeing area between the woodland and grassland species, and the overall variation trend of the forestland dyeing area ratio decreased with increasing soil depth. The dyeing area of the grassland decreased monotonously with the increases of soil depth. The occurrence degree of soil preferential flow in forest was higher than that of grassland. Root systemaffected the formation of soil preferential flow. At the root diameter ranges of 0≤d≤5 mm and d>10 mm, root length density of the woodland showed a monotonous decreasing trend with increasing soil depth, while in the root diameter range of 5 mm5 mm. The overall change trend of soil preferential flow dyeing area of two vegetation types in the study area decreased with increasing soil depth. Plant root system was closely related to the formation of soil preferential flow. Fine roots could promote while coarse roots may retard the formation of preferential flows.

Objective: To compare the therapeutic effect of electroacupuncture (EA) of single-acupoint Zusanli (ST36) and multi-acupoints Zusanli (ST36), Shangjuxu (ST37) and Neiguan (PC6) in promoting the recovery of gastrointestinal movement in laparoscopic cholecystectomy (LC) patients undergoing general anesthesia., Methods: A total of 70 LC patients (American Society of Anesthesiologists [ASA] grade I and II) were recruited and randomly divided into control ( n ＝23), single ST36 ( n ＝23) and ST36＋ST37＋PC6 ( n ＝24) groups. The patients in the control group only received routine basic treatments (postoperative fasting and water deprivation, intravenous drip of biotics, water-electrolyte and acid-base balancing, oxygen uptake, etc). EA (10 Hz, 5 mA, 30 min every time) was applied to the abovementioned single-acupoint or multi-acupoints groups before, and 4, 22, 34 and 46 h after the operation. The time-points of postoperative borborygmus recovery, first anal exhaust and defecation, post-operative abdominal distension (mild, moderate and severe), nausea and vomiting (grade Ⅰ， Ⅱ， Ⅲ and Ⅳ) at 6, 24 and 48 h after surgery were recorded and analyzed., Results: Compared to the control group, the time of borborygmus recovery, first anal exhaust and defecation were markedly earlier in both single ST36 and ST36＋ST37＋PC6 groups ( P <0.01, P <0.05, P <0.001). The number of patients who had mild plus moderate abdominal distention, and nausea (grade Ⅱ＋Ⅲ) at 24 h after ope-ration was significantly lower in both single ST36 and ST36＋ST37＋PC6 groups than in the control group ( P <0.05). No significant differences were found between the two EA groups in the time of borborygmus recovery, first anal exhaust and defecation, and in the number of patients with mild plus moderate abdominal distention and those with nausea ( P >0.05)., Conclusion: EA of both single ST36 and ST36＋ST37＋PC6 can promote gastrointestinal function recovery in LC patients, without remarkable difference between them.

Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

The secretome of mesenchymal stem cell (MSC) offers a series of immunoregulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. After the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST through caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were reduced, whereas transforming growth factor-beta (TGF-β) and tumor necrosis factor-stimulated gene 6 protein (TSG-6) levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.

Using a cell-based cytotoxicity assay, two new polyhydroxylated sterols, 16(S),22(S)-epoxy-3β,5α,6β,20(R),23(R),25-hexahydroxy-7-ergostene and 3β,7β,8α,25-tetrahydroxy-5,22E-ergostadiene were isolated from the ethyl acetate portion of the ethanolic extract of Monascus purpureus. Their structures were elucidated by spectroscopic analysis and in comparison with those reported in the literature. Both compounds showed cytotoxic activity against the lung adenocarcinoma (A549) with IC 50 values of 12.6 and 18.5 μM, exhibited moderate activities against human ovarian cancer (A2780), with IC 50 values of 8.8 and 9.4 μM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Gaseous elemental mercury (GEM) is commonly known as a hazardous heavy metal in the atmosphere and is harmful to living organisms. GEM is chemically stable and has a long residence time in the atmosphere; hence, it can be transported over long distances with air masses and is regarded as a global pollutant. We study the transportation and transformation mechanisms of GEM and its potential anthropogenic and natural contribution sources. GEM, conventional atmospheric pollutants, and meteorological parameters were monitored at a coastal site in Ningbo during the summer and autumn of 2017. The results were as follows. ① The concentrations of GEM ranged from 0.97-10.95 ng·m -3 and the mean and standard deviation (SD) were (2.32±0.90) ng·m -3 , whereby the mean summer concentration was lower than the mean autumn concentration. ② The diurnal variations of GEM, ozone (O 3 ), and gaseous oxidized mercury (GOM) during summer/autumn and sunny/rainy days suggest that higher levels of O 3 and that strong solar radiation accounted for the rapid photochemical oxidation of GEM. The intensity of oxidation on sunny days was higher than that on rainy days. ③ Correlation analysis showed that GEM was significantly positively correlated with PM 2.5 ( R =0.65, P <0.01), PM 10 ( R =0.47, P <0.01), NO 2 ( R =0.46, P <0.01), and CO ( R =0.57, P <0.01). Local and regional sources of GEM were mainly related to fossil fuel combustion. ④ The photochemical oxidation rate of GEM was influenced by the concentrations of oxidants (e.g., O 3 ), gas-particle partitioning between GEM and particles, and light extinction effects of PM 2.5 , water vapor, and NO 2 . ⑤ Potential source contribution analysis (PSCF) indicated that the northwestern Zhejiang Province (including Ningbo City), the southern Anhui Province, and most of Jiangxi Province constitute a triangular area that is a potential source contribution to NBUEORS atmospheric GEM pollution during the summer. Local, regional, and long-range sources all had strong impacts on GEM pollution. During the autumn, the potential sources were mainly in the northern Zhejiang Province, and the source was smaller than that during the summer. GEM pollution during the autumn was mainly influenced by local and regional sources. Therefore, the control of atmospheric GEM pollution in the Yangtze River delta should apply inter-regional prevention and comprehensive control strategies in order to reduce atmospheric mercury pollution.

Prognosis and treatment evaluation of spinal cord injury (SCI) are still in the long-term research stage. Prognostic factors for SCI treatment need effective biomarker to assess therapeutic effect. Quantitative diffusion tensor imaging (DTI) may become a potential indicators for assessing SCI repair. However, its correlation with the results of locomotor function recovery and tissue repair has not been carefully studied. The aim of this study was to use quantitative DTI to predict neurological repair of SCI with transplanting collagen/chitosan scaffold binding basic fibroblast growth factor (bFGF). To achieve our research goals, T10 complete transection SCI model was established. Then collagen/chitosan mixture adsorbed with bFGF (CCS/bFGF) were implanted into rats with SCI. At 8 weeks after modeling, implanting CCS/bFGF demonstrated more significant improvements in locomotor function according to Basso-Beattie-Bresnahan (BBB) score, inclined-grid climbing test, and electrophysiological examinations. DTI was carried out to evaluate the repair of axons by diffusion tensor tractgraphy (DTT), fractional anisotropy (FA) and apparent diffusion coefficient (ADC), a numerical measure of relative white matter from the rostral to the caudal. Parallel to locomotor function recovery, the CCS/bFGF group could significantly promote the regeneration of nerve fibers tracts according to DTT, magnetic resonance imaging (MRI), Bielschowsky's silver staining and immunofluorescence staining. Positive correlations between imaging and locomotor function or histology were found at all locations from the rostral to the caudal (P < 0.0001). These results demonstrated that DTI might be used as an effective predictor for evaluating neurological repair after SCI in experimental trails and clinical cases.

We explored the effects of microtopography changes from artificial intervention of soil and water conservation (contour reverse-slope terrace, CRT) on tree growth in a degraded woodland on hillslope in water resource area of Songhua dam in Kunming City. The differences of the diameter at breast height (DBH), tree height, new branch increment, and leaf area index (LAI) of dominant tree species in different plots were compared through dynamic monitoring. Then, the causes of differences were analyzed by combining the soil water availability. The results showed that the maximum and mean values of DBH and height of Pinus yunnanensis (dominant species) in contour reverse-slope terrace plot were larger than those in control plot (CK), and the proportion of small-sized and low-dwarf trees in degraded forest community was higher, which indicated that the growth potential of new and seriously degraded forest was stimulated. The annual variation rate of the ave-rage new branch length and diameter of P. yunnanensis in different plots reached 72.4% and 39.1%, respectively. The changes of new branch growth of P. yunnanensis, LAI of plots, and the new branch growth rate were greater in CRT than those in CK. Soil water content was significantly correlated with both the new branch growth and LAI. The ratio of available water in plot (64.2%) was higher than that in CK (54.7%). During the rainy season (from May to September), the available water in CRT existed longer, which was conducive to tree growth and the improvement of plant community structure in degraded woodland.

The sporopollenin precursors, as a general constituent of sexine, are synthesized in the tapetum and deposited on the pollen surface after transportation and processing. The polyketide synthase condenses the acyl-CoA into a hydroxyalkyl α-pyrone, which is predicted to be a component of the sporopollenin precursors. In this study, we found that the rice POLYKETIDE SYNTHASE 1 (OsPKS1) was the orthologue of Arabidopsis POLYKETIDE SYNTHASE A/LESS ADHESIVE POLLEN 6 (PKSA/LAP6) through sequence alignment. The OsPKS1 knockout mutants obtained by Crispr-Cas9-mediated editing exhibited a complete male sterile phenotype. Cytological observations revealed that abnormal bacula deposition and ubisch body structures for sexine formation led to pollen rupture in ospks1. The expression analysis showed that the OsPKS1 was highly expressed in tapetal cells and anther locules from stage 9 to stage 11 during anther development in rice. Subcellular localization demonstrated that the OsPKS1 protein was preferentially localized to the ER. The genomic sequence of OsPKS1 driven by the PKSA/LAP6 promoter restored the sexine pattern of Arabidopsis pksa/lap6. These results indicated that OsPKS1 is required for sexine layer formation in rice and functionally conserved in the sporopollenin synthesis pathway., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bacterial laccases are potential enzymes for biotechnological applications, such as detoxification of industrial effluents, decolorization of textile, and dimerization of phenolic acids, due to their remarkable advantages, including broad substrate spectrum, high thermostability, wide pH scope, and tolerance to alkaline environments. L386W/G417L/G57F (abbreviated as WLF), a good mutant of CotA-laccase from Bacillus pumilus W3, has been constructed and reported by our laboratory with highly improved catalytic efficiency. However, the low-functional expression level of mutant WLF in Escherichia coli was a shortcoming. Three mutants, namely, K317N/WLF, D501G/WLF, and K317N/D501G/WLF, were constructed through site-directed mutagenesis to improve the functional expression of WLF in this study. The soluble and active expression of D501G/WLF and K317N/D501G/WLF in E. coli enhanced 4.48-fold and 3.63-fold level, respectively. The K317N/WLF failed to increase the soluble expression level, but slightly improved the stability of CotA-laccase. Results showed that not only the position 501 is significant for functional expression of B. pumilus W3 CotA, but also these mutants still remained its high thermostability, resistance of alkaline with salt, and conspicuous decolorizing efficiency. This work is the first to improve the soluble expression of B. pumilus CotA-laccase in E. coli by site-directed mutagenesis. The D501G/WLF and K317N/D501G/WLF will be suitable candidates for biotechnological applications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this study, we established a Cre/loxP mutant recombination system (Cre/lox71-66 system) for markerless gene deletion to facilitate our follow-up rational genetic engineering to the strain Bacillus pumilus W3. This modified method uses two mutant loxP sites, which after recombination creates a double-mutant loxP site that is poorly recognized by Cre recombinase, facilitating multiple gene deletions in a single genetic background. Two selected genes, cotA and sigF, were continuously knocked out and verified at different levels using this method. This method is simple and efficient and can be easily implemented for multiple gene deletions in B. pumilus., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the correlations of MC4R and MSH2 with adult obesity, a total of 46 patients with early-stage colon cancer were treated in our hospital between February 2008 and February 2009 and were enrolled., Patients and Methods: Venous blood was regularly drawn from subjects of the observation group and 48 healthy subjects for 6 years. Expression levels of MC4R and MSH2 genes were tested using quantitative polymerase chain reaction analyses, and the ensuing proteins were determined using enzyme-linked immunosorbent assays and Western blotting and immunohistochemical analyses. Finally, correlations with body mass index (BMI) and the presence of colon cancer were identified using multivariate analyses., Results: Compared with the control group, MSH2 mRNA and protein expression increased significantly over time (p < 0.05) in patients with colon cancer. Moreover, MSH2 expression was correlated with colon cancer progression, and MC4R mRNA and protein expression increase concurrently in comparison with the control group (p < 0.05). Also, the mean BMI among patients with colon cancer was 30.8, whereas that among control subjects was only 21.4. These data indicate a relationship between BMI and colon cancer., Conclusions: Expression of MSH2 in patients with colon cancer may promote the expression of the obesity gene MC4R, potentially contributing to body weight gains.

In order to elucidate the heat-induced wheat gluten gel formation mechanism, changes in chemical interactions and protein conformation were investigated during gelation. The contribution of ionic and hydrogen bonds were found to decrease from 0.746 and 4.133g/L to 0.397 and 2.733g/L, respectively, as the temperature increased from 25 to 90°C. Moreover, the free SH content remarkably decreased from 37.91 to 19.79μmol/g during gelation. Ultraviolet absorption spectra and intrinsic fluorescence spectra suggested that wheat gluten unfolded during the heating process. In addition, wheat gluten gels treated at 80 and 90°C exhibited a "steric hindrance" effect, which can be attributed to the formation of aggregates. Fourier transform infrared spectra suggested that the random coil content increased at low temperatures (40 and 50°C), whereas the content of intermolecular β-sheets due to protein aggregation increased from 38.10% to 44.28% when the gelation temperature was 90°C., (Copyright © 2016 Elsevier Ltd. All rights reserved.)