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Degos disease also known as malignant atrophic papulosis (MAP), is an autoinflammatory disease that mainly affects small- to medium-sized arteries. Gastrointestinal and nervous system are most commonly affected systems. Herein, we reported a case of Degos disease with disease onset during infantile and had severe neurological involvement., 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., (© 2024 Shi, Deng and Li.)

The title compound, C 12 H 10 N 2 O 3 , was obtained by the de-acetyl-ation reaction of 1-(6-amino-5-nitro-naphthalen-2-yl)ethanone in a concentrated sulfuric acid methanol solution. The mol-ecule comprises a naphthalene ring system bearing an acetyl group (C-3), an amino group (C-7), and a nitro group (C-8). In the crystal, the mol-ecules are assembled into a two-dimensional network by N⋯H/H⋯N and O⋯H/H⋯O hydrogen-bonding inter-actions. n -π and π-π stacking inter-actions are the dominant inter-actions in the three-dimensional crystal packing. Hirshfeld surface analysis indicates that the most important contributions are from O⋯H/H⋯O (34.9%), H⋯H (33.7%), and C⋯H/H⋯C (11.0%) contacts. The energies of the frontier mol-ecular orbitals were computed using density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-TZVP level of theory and the LUMO-HOMO energy gap of the mol-ecule is 3.765 eV., (© Shi et al. 2024.)

Objective: To investigate the postoperative lymph node metastasis status and related factors of patients with early-stage low-risk endometrial cancer evaluated by the Mayo criteria in order to make the preoperative evaluation more accurate. Methods: A total of 172 patients with early-stage low-risk endometrial cancer who underwent surgery in Sichuan Provincial Cancer Hospital from 2009 to 2018 and were evaluated as early low-risk according to the "Mayo criteria" were retrospectively enrolled, and were divided into lymph node metastasis group (7 cases) and non-metastasis group (165 cases) according to the results of postoperative pathological examination. The postoperative pathological examination results and prognosis of all patients were collected. The lymph node metastasis of the two groups was analyzed. The multiple logistic regression model was used to analyze the related factors of lymph node metastasis, and the area under the curve (AUC) of the relevant factors was calculated by using the receiver operating characteristic curve to predict the postoperative lymph node metastasis of patients. Results: The age of 172 patients was (53.0±8.6) years, and the follow-up [ M ( Q 1 , Q 3 )] was 64.1 (46.2, 91.4) months, among whom 2 relapsed and 1 died. Among the 7 patients with lymph node metastasis, 5 cases had pelvic lymph node metastasis, 1 case had pelvic lymph union and abdominal para-aortic lymph node metastasis, 1 case had isolated abdominal para-aortic lymph node metastasis, 3 cases had two lymph node metastases, and 4 cases had intrailiac lymph nodes being the most common metastasis site. Multivariate analysis showed that preoperative serum cancer antigen (CA) 125 was the relevant factor for postoperative lymph node metastasis, with an OR value (95% CI ) of 1.022 (1.001-1.043) ( P =0.042), with AUC (95% CI ) of CA125 predicting lymph node metastasis of 0.850 (0.761-0.939) ( P =0.002), and the optimal cut-off value of CA125 was 29.305 U/ml with the sensitivity of 85.7% and the specificity of 80.6%. Conclusions: When CA125>29.305 U/ml, patients with early-stage low-risk endometrial cancer assessed by the Mayo criteria, had an increased risk of lymph node metastasis. Therefore, adding preoperative serum CA125 level as an evaluation index on the basis of the classic "Mayo criteria" may help conduct more accurate preoperative evaluation and better identify early-stage low-risk EC patients.

The title compound, C 14 H 12 N 2 O 4 , was obtained from 2-acetyl-6-amino-naphthalene through two-step reactions of acetyl-ation and nitration. The mol-ecule comprises the naphthalene ring system consisting of functional systems bearing a acetyl group (C-2), a nitro group (C-5), and an acetyl-amino group (C-6). In the crystal, the mol-ecules are assembled into two-dimensional sheet-like structures by inter-molecular N-H⋯O and C-H⋯O hydrogen-bonding inter-actions. Hirshfeld surface analysis illustrates that the most important contributions to the crystal packing are from O⋯H/H⋯O (43.7%), H⋯H (31.0%), and C⋯H/H⋯C (8.5%) contacts., (© Shi et al. 2024.)

Background: This study aimed to explore the effect and mechanism of SCN5A overcoming ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in acute myeloid leukemia (AML) through promoting apoptosis., Research Design and Methods: The tissues derived from AML patients were divided into Sensitive group and Resistance group according to the presence of drug-resistance. Human AML cell line HL-60 and drug-resistant strain HL-60/ADR were divided into HL-60/ADR-vector group, HL-60/ADR-SCN5A group, HL-60-vector group and HL-60-SCN5A group. RT-qPCR was used to detect the mRNA expression level of SCN5A; MTT assay to assess the survival rate and proliferation level of cells; flow cytometry to determine the apoptosis level; and western blot to check the levels of SCN5A, P-glycoprotein (P-gp), MDR protein 1 (MRP1), MDR gene 1 (MDR1), breast cancer resistance protein (BCRP), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) proteins in cells., Results: SCN5A expressed lowly in drug-resistant AML tissues and cells. Up-regulation of SCN5A inhibited MDR in HL-60 cells, enhanced the chemosensitivity of HL-60/ADR, and increased the apoptosis levels of HL-60 and HL-60/ADR cells. However, over-expression of SCN5A inhibited the expression of MDR-related proteins., Conclusions: SCN5A may overcome ABC transporter-mediated MDR in AML through enhancing the apoptosis and inhibiting the expression of MDR proteins.

Objective: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism., Methods: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×10 5 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice., Results: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice., Conclusion: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS)., Methods: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors., Results: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036)., Conclusions: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Mapping neural circuits is critical for understanding the structure and function of the nervous system. Engineered viruses are a valuable tool for tracing neural circuits. However, current tracers do not fully meet the needs for this approach because of various drawbacks, such as toxicity and characteristics that are difficult to modify. Therefore, there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies. In this study, we constructed an engineered Sindbis virus (SINV) expressing enhanced green fluorescent protein (EGFP) reporter gene (SINV-EGFP) and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro. We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits. Although the efficiency of transmission was limited, the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction. Further, use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers., Competing Interests: None

Sudan I dye-based smart low molecular weight gelators with/without a perfluoroalkyl group have been successfully synthesized and characterized by rheological measurements, scanning electron microscopy (SEM), IR, and NMR spectroscopies. The gelation behaviors in response to temperature, pH changes, metal cations, and UV-vis light irradiation are investigated. Compounds 1 and 2 could selectively sense the Cu 2+ cation in the presence of other metal cations. Moreover, compound 2 with a perfluoroalkyl group shows phase selective gelation ability. This work also provides a valuable reference for exploiting photosensitive materials as chemosensors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Necrotizing fasciitis (NF) is a rare, severe soft tissue infection, characterized by rapid and extensive necrosis of the skin, subcutaneous tissue, and superficial and deep fascia. It is frequently misdiagnosed as other infectious diseases, leading to inappropriate treatment and potentially serious consequences. It may be complicated by septic shock and multiple organ failure with a fatal outcome., Patient Concerns: A 73-year-old woman presented with continuous itching, skin lesions, pain, and swelling of the outer side of her left leg. The patient was diagnosed with septic shock and multiorgan failure caused by left leg NF., Diagnosis: Septic shock and multiorgan failure caused by left leg NF., Interventions: Two surgeries were performed on the patient's leg, which effectively treated her septic shock and multiple organ dysfunction., Outcomes: The patient was followed up three times after her discharge. She had a good recovery, was generally well with no significant sequelae, and returned to her regular life., Conclusion: NF is an acute severe illness with high mortality. It is easily misdiagnosed, leading to delayed or erroneous treatment and serious (or potentially fatal) outcomes. Rapid and accurate diagnosis of NF is essential for patient recovery. In difficult cases, multidisciplinary consultations may be helpful. The management of NF includes early and thorough surgical debridement, antibiotics, and symptomatic treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Heavy reliance on petrochemical-based plastic foams in both industry and society has led to severe plastic pollution (the so-called "white pollution"). In this work, we develop a biodegradable, recyclable, and sustainable cellulose/bentonite (Cel/BT) foam material directly from resource-abundant natural materials (i.e., lignocellulosic biomass and minerals) via ambient drying. The strong resistance to the capillary force-driven structural collapse of the preformed three-dimensional (3D) network during the ambient drying process can be ascribed to the purpose-designed cellulose-bentonite coordination interaction, which provides a practical way for the locally scalable production of foam materials with designed shapes without complex processing and intensive energy consumption. Benefiting from the strong cellulose-bentonite coordination interaction, the Cel/BT foam material demonstrates high mechanical strength and outstanding thermal stability, outperforming commercial plastic polystyrene foam. Furthermore, the Cel/BT foam presents environmental impacts much lower than those of petrochemical-based plastic foams as it can be 100% recycled in a closed-loop recycling process and easily biodegraded in the environment (natural cellulose goes back to the carbon cycle, and bentonite minerals return to the geological cycle). This study demonstrates an energy-efficient ambient drying approach for the local and scalable production of an all-natural cellulose/bentonite foam for sustainable packaging, buildings, and beyond, presenting great potential in response to "white pollution" and resource shortage.

Emerging evidence suggests the regulation of microglial phenotype balance between M1 and M2 will be a potential therapeutic strategy for microglia-mediated neuroinflammation in Alzheimer's disease (AD). Herein, we evaluated the anti-neuroinflammatory effects and the underlying mechanism of a natural cyathane diterpenoid sarcodonin A (1) derived from the mushroom Sarcodon scabrosus and its six new derivatives (2-7). Lipopolysaccharide (LPS)-activated primary microglia and microglia cell lines were used as models. The nitrite test and immunostaining showed that the derivative named 6 was more effective in inhibiting neuroinflammation. qRT-PCR, ELISA, and western blotting revealed that 6 showed more significant suppression on mRNA and protein expression of proinflammatory M1 markers of TNF-α, IL-6, IL-1β, iNOS, and COX-2, while more obvious potentiation on mRNA and protein levels of anti-inflammatory M2 markers of IL-10 and ARG-1. In mechanism, western blotting demonstrated that 6 inhibited LPS-induced activation of MAPK, and prevented LPS-stimulated nuclear translocation of NF-κB p65. Molecular docking revealed that 1 and 6 constructed interactions with iNOS. Collectively, the present study indicated that 1 and 6 might support neuroprotection by reversing LPS-induced microglia M1 polarization, implying that sarcodonin A can be a promising candidate for developing new therapeutics against AD by targeting microglia-mediated neuroinflammation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The structure of the title com-pound, C 17 H 20 O 4 [systematic name: (1a S ,3a R ,4a S ,5a R )-15-(acet-oxy)linden-7(11),8-trieno-12,8-lactone or (4a R ,5 S ,5a R ,6a S ,6b R )-5-(acet-oxy-meth-yl)-4a,5,5a,6,6a,6b-hexa-hydro-3,6b-di-methyl-cyclo-propa[2,3]indeno-[5,6- b ]furan-2(4 H )-one, ent -chloranthalactone C], a natural product iso-lated from the whole plant Chloranthus japonicus Sieb., is a typical lin-den-ane-type sesquiterpenoid. The mol-ecule com-prises a bi-cyclo-[3.1.0]hexane ring ( A / B system) bearing an acetoxymethyl (C-4) group, a bi-cyclo-[4.3.0]nonane ring ( B / C system) containing a double bond (C-8/9) and a chiral quaternary carbon (C-10), and a 7(11)-en-12,8-olide structural moiety on the cyclo-hexan-8-ene ( C ring). In the tetra-cyclic skeleton, the 1,3-cyclo-propane ring has a β-con-figuration, and atoms H-5 and H 3 -14 have α- and β-orientations, respectively. In the crystal, the mol-ecules are assembled into a two-dimensional network by weak O⋯H/H⋯O inter-actions. Hirshfeld surface analysis illustrates that the greatest contributions are from H⋯H (55.2%), O⋯H/H⋯O (34.6%) and C⋯H/H⋯C (8.9%) contacts., (© Lu et al. 2022.)

Phosphoglycerate dehydrogenase (PHGDH) is abnormally expressed in numerous malignant tumor cells and catalyzes the first step of serine biosynthesis, thus becoming a key drug target for antitumor treatment. In this study, compound B2 bearing a benzene-1,3-diamine scaffold was identified by structure-based virtual screening as a novel PHGDH inhibitor with moderate enzymatic activity. The structure-activity relationship study led to the discovery of compound C25 possessing improved enzymatic inhibitory activity and potent inhibitory activity on the proliferation of cells overexpressing PHGDH. The enzyme kinetic assay confirmed that C25 inhibited PHGDH in a nicotinamide adenine dinucleotide (NAD + ) competitive manner. Molecular docking and mutagenesis experiment on PHGDH collectively revealed the binding site and key interaction residues of C25 in the PHGDH catalytic site. Taken together, this study provides information on the structural diversity for a further development of potent PHGDH inhibitors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: This article analyzed the safety and efficacy of ultrasound-guided mini-percutaneous nephrolithotomy (MPCNL) with low-pressure perfusion for the treatment of upper urinary tract stones in children., Methods: The clinical data of 690 patients (805 renal units) aged 1-7 years were retrospectively analyzed in terms of postoperative outcome., Results: The mean patient age was 3.7 ± 1.6 years, and the stone burden was 2.8 ± 2.1 cm 2 . A middle posterior calyceal puncture was created in 719 (89%) renal units, and 16F puncture tracts were the most common method used in 557 (69%) renal units. The stone-free rate was 711 (88%) renal units, and the mean operation time was 35 ± 15.3 min (between 15 and 110 min). Among all cases, the transfusion rate was 4 (0.6%) patients, and the mean decrease in hemoglobin was 1.3 ± 0.9 g/L. In addition, the incidence rates of fever, sepsis, perirenal effusion, and intraperitoneal effusion were 40 (5.9%), 3 (0.4%), 28 (4.1%), and 8 (1.2%) patients, respectively. After the operation, 348 patients were followed-up for 32.8 ± 11.3 months, and stone recurrence occurred in 136 (39%) of 348 patients., Conclusions: This study suggests that ultrasound-guided MPCNL with low-pressure perfusion technology is a safe and feasible treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Silybin, a peculiar flavonoid compound derived from the fruit and seeds of Silybum marianum , exhibits strong anti-inflammatory activities. In the present study, we found that silybin effectively alleviated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), via inhibition of dendritic cell (DC) activation and Th17 cell differentiation. Silybin treatment greatly ameliorated the disease severity and significantly declined inflammation and demyelination of the central nervous system (CNS) of EAE mice. Consistent with the disease development, silybin-treated bone marrow-derived DCs (BM-DCs) exhibited reduced costimulatory molecules (e.g., CD80 and CD86) and MHC II expression. These results demonstrated the distinguished bioactivity of silybin for suppressing DC activation, inhibiting pathogenic Th17 inflammatory cell responses, and, eventually, alleviating EAE severity. Taken together, our results show that silybin has high potential for the development of a novel therapeutic agent for the treatment of autoimmune diseases such as MS., 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 Yang and Shi.)

During our continuous efforts to pursue antifungal agents, some calycanthaceous alkaloid analogs showed diverse and promising bioactivities. Therefore, 34 new calycanthaceous alkaloid derivatives were further prepared and screened for bioactivities. As a result of the evaluation against a great deal of plant pathogen fungi, bacteria and human pathogenic fungi, a majority of them displayed potent bioactivity. In particular, compound b6 displayed remarkably activity and might be novel potential leading compound for further development of antifungal agent. The relationship between structure and biological activity was also discussed.

Two halophilic archaeal strains, Gai3-2 T and NJ-3-1 T , were isolated from salt lake and saline soil samples, respectively, collected in PR China. The 16S rRNA gene sequences of the two strains were 97.5% similar to each other. Strains Gai3-2 T and NJ-3-1 T had the highest sequence similarities to ' Halobonum tyrrellense ' G22 (96.7 and 97.8%, respectively), and displayed similarities of 91.5-93.5% and 92.3-94.7%, respectively, to Halobaculum members. Phylogenetic analysis revealed that the two strains formed different branches and clustered tightly with ' H. tyrrellense ' G22 and Halobaculum members. The average nucleotide identity (ANI), in silico DNA-DNA hybridization ( is DDH) and amino acid identity (AAI) values between the two strains were 83.1, 26.9 and 77.9%, respectively, much lower than the threshold values proposed as a species boundary. These values between the two strains and ' H. tyrrellense ' G22 (ANI 77.9-78.2%, is DDH 22.5-22.6% and AAI 68.8-69.3%) and Halobaculum members (ANI 77.53-77.63%, is DDH 21.8-22.3% and AAI 68.4-69.4%) were almost identical, and much lower than the recommended threshold values for species delimitation. These results suggested that strains Gai3-2 T and NJ-3-1 T represent two novel species of Halobaculum . Based on phenotypic, chemotaxonomic and phylogenetic properties, strains Gai3-2 T (=CGMCC 1.16080 T =JCM 33550 T ) and NJ-3-1 T (=CGMCC 1.16040 T =JCM 33552 T ) represent two novel species of the genus Halobaculum , for which the name Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov. are proposed.

Objective: To explore the prognostic factors of patients with advanced epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Methods: The clinical and pathological data of patients with stage Ⅲc-Ⅳ EOC underwent surgical treatment in Sichuan Cancer Center from January 1st, 2014 to December 31th, 2018 were retrospectively analyzed, and the prognosis was followed up. Results: (1) A total of 216 EOC patients were included in the study, whose age was (52.1±8.7) years old, the median follow-up time was 44.6 months (17.2-80.1 months), the median progression free survival (PFS) was 11.1 months (8.5-13.8 months), and the median overall survival (OS) was 40.0 months (32.7-47.3 months). (2) Among 216 patients with advanced EOC, there were 75 cases in the primary debulking surgery (PDS) group and 141 cases in the NACT+IDS group. Compared with the PDS group, the serum CA 125 level before treatment (median: 859.4 vs 1 371.0 kU/L), proportion of stage Ⅳ patients [5.3% (4/75) vs 23.4% (33/144)] and no visible residual disease (R0) cytoreduction rate in the NACT+IDS group were significantly higher [(41.3% (31/75) vs 61.7% (87/144); all P <0.05]. The median PFS in the NACT+IDS group was significantly shorter than that of the PDS group (9.1 vs 15.2 months; χ 2 =7.014, P= 0.008), but there was no significant difference in the median OS between the two groups (42.6 vs 38.0 months; χ 2 =1.325, P= 0.250). (3) Univariate analysis showed that body mass index (BMI), preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, time to initiation of postoperative chemotherapy and chemotherapy regimen were significantly correlated with PFS in the NACT+IDS group (all P <0.05); preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, postoperative chemotherapy regimen were significantly related with OS in the NACT+IDS group (all P <0.05). Multivariate analysis showed that BMI, postoperative residual tumor size, time to initiation of postoperative chemotherapy were independent factors of PFS in the NACT+IDS group (all P <0.05); preoperative serum CA 125 level, surgical-pathological stage, postoperative residual tumor size were independent factors of OS in the NACT+IDS group (all P <0.05). The results showed that the PFS of patients with normal preoperative serum CA 125 level and (or) chemotherapy ≤7 days after IDS was longer, while no significant difference comparable with those in the PDS group ( P >0.05), and OS was also showing an prolonged trend, but the difference was also not statistically significant ( P >0.05). Conclusions: Normal CA 125 before IDS and time received chemotherapy no longer than 7 days after IDS are two related factors of prognosis benefit in advance EOC patients treated with NACT+IDS. Therefore, timely adjustment of the dose and regimen of NACT to reduce CA 125 level to normal range in about three cycles before IDS, and strengthen IDS perioperative management to promote postoperative recovery and perform chemotherapy as soon as possible might help to improve the prognosis of patients.

Background: As human placenta-derived mesenchymal stem cells (hP-MSCs) exist in a physiologically hypoxic microenvironment, various studies have focused on the influence of hypoxia. However, the underlying mechanisms remain to be further explored., Aim: The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of hP-MSCs., Methods: A hypoxic cell incubator (2.5% O 2 ) was used to mimic a hypoxic microenvironment. Cell counting kit-8 and 5-ethynyl-20-deoxyuridine incorporation assays were used to assay the proliferation of hP-MSCs. The cell cycle was profiled by flow cytometry. Transcriptome profiling of hP-MSCs under hypoxia was performed by RNA sequencing. CD99 mRNA expression was assayed by reverse transcription-polymerase chain reaction. Small interfering RNA-mediated hypoxia-inducible factor 1α (HIF-1α) or CD99 knockdown of hP-MSCs, luciferase reporter assays, and the ERK1/2 signaling inhibitor PD98059 were used in the mechanistic analysis. Protein expression was assayed by western blotting; immunofluorescence assays were conducted to evaluate changes in expression levels., Results: Hypoxia enhanced hP-MSC proliferation, increased the expression of cyclin E1, cyclin-dependent kinase 2, and cyclin A2, and decreased the expression of p21. Under hypoxia, CD99 expression was increased by HIF-1α. CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell proliferation., Conclusion: Hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro ., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF- κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Tong Wang et al.)

Signal transducer and activator of transcription 3 (STAT3) is identified as a promising target for multiple cancer therapy and attracts widespread concern. Herein, we reported the discovery of a series of 2-acetyl-7-phenylamino benzofuran derivatives as STAT3 inhibitors using scaffold fusion strategy. Further structure activity relationship study led to the discovery of compound C6, which displayed the most potent anti-proliferation activities against MDA-MB-468 cells (IC 50  = 0.16 μM). Western blot assay demonstrated that C6 inhibited the activation of STAT3 (Tyr705) without influencing the phosphorylation of STAT1 (Tyr701). Further mechanistic studies indicated that C6 caused a notable G2/M cycle-arresting and early apoptosis in a concentration-dependent manner in MDA-MB-468 cells. Finally, molecular modelling study elucidated the binding mode of C6 in STAT3 SH2 domain., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Persistently activated signal transducer and activator of transcription 3 (STAT3) plays an important role in the development of multiple cancers, and therefore is a potential therapeutic target for cancer prevention. Herein, we report the rational design, synthesis, and biological evaluation of novel potent STAT3 inhibitors based on BBI608. Among them, compound A11 exhibited the most potent in vitro tumor cell growth inhibitory activities toward MDA-MB-231, MDA-MB-468 and HepG2 cells with IC 50 values as low as 0.67 ± 0.02 μM, 0.77 ± 0.01 μM and 1.24 ± 0.16 μM, respectively. Fluorescence polarization (FP) assay validated the binding of compound A11 in STAT3 SH2 domain with the IC 50 value of 5.18 μM. Further mechanistic studies indicated that A11 inhibited the activation of STAT3 (Y705), and thus reduced the expression of STAT3 downstream genes CyclinD1 and C-Myc. Simultaneously, it induced cancer cell S phase arrest and apoptosis in a concentration-dependent manner. An additional in vivo study revealed that A11 suppressed the MDA-MB-231 xenograft tumor growth in mice at the dose of 10 mg/kg (i.p.) without obvious body-weight loss. Finally, molecular docking study further elucidated the binding mode of A11 in STAT3 SH2 domain., 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 © 2020 Elsevier Masson SAS. All rights reserved.)

1. Tile-grey plumage is a unique and rare feather type of local chicken breeds in China, but its genetic mechanism and corresponding genes remain unknown. 2. In order to identify the genetic basis and molecular characteristics of tile-grey plumage, this experiment investigated variations of melanocortin 1 receptor ( MC1R ) gene in Yunnan Piao chickens with typical tile-grey plumage characteristics in contrast with three Yunnan local breeds as well as two standard breeds with different plumage colour, and analysed the association between genic variation and tile-grey plumage. 3. Through sequencing and comparison of the entire coding region of the MC1R gene, a total of 10 SNP loci were detected, of which eight were non-synonymous mutations that cause amino acid changes. The gene frequency and genotype frequency of the MC1R mutation sites in different breeds and different plumage colour groups revealed that C69T, T212C and A274G were significantly associated with tile-grey plumage. Eighteen haplotypes of the MC1R gene were constructed based on 10 nucleotide variations and eight amino acid variations. Haplotype distribution and the median joining network in breeds and plumage colour groups revealed a main haplotype ( hap2 ) for tile-grey plumage. Hap2 is unique to the tile-grey feather of Piao chicken, and the individuals carrying this haplotype account for 62.96% of the whole tile-grey chicken. 4. The results of this study are of significance for further analysis of the molecular basis of tile-grey plumage and the selective breeding of tile-grey plumage.

Objective: To investigate the effect of puerarin (Pue) on the proliferation and differentiation of osteoblasts and the expression of type I collagen(Coll I) mRNA in a high-glucose (HG) environment, and to provide evidence for the clinical treatment of diabetic osteoporosis(DOP)., Subjects and Methods: The proliferation of osteoblasts from three groups - the control group, the HS group, and the HG+Pue (10 -8 -10 -6 M) group - was cultivated for 72 h and evaluated using the methyl thiazolyltetrazolium (MTT) assay., Results: The MTT values and the ALP activities in all experimental groups were significantly lower than those in the control group, and the MTT values and the ALP activities in the HG+Pue group were significantly higher than those in the HS group. Coll I mRNA expression in all experimental groups was significantly lower than that in the control group, while that in the HG+Pue group was significantly higher than that in the HG group., Conclusions: The proliferation and differentiation of osteoblasts and the expression of Coll I mRNA were inhibited by high glucose, but Pue can increase the proliferation and differentiation as well as the expression of Coll I mRNA in the osteoblasts, indicating that Pue could be therapeutically beneficial against DOP., Competing Interests: The authors declare that they have no conflict of interest., (©by Acta Endocrinologica Foundation.)

Objective: The hyperglycemic environment of diabetes promotes chondrocyte (CH) apoptosis and is closely related to the occurrence and development of osteoarthritis (OA). This present study aimed to elucidate the relation between the cytoskeleton and the caspase-3 expression of human CHs in high glucose in vitro., Patients and Methods: We used different concentrations of glucose medium to test the effect of glucose on the CHs viability. Cytochalasin D and colchicine were used to prevent the aggregation of F-actin and β-tubulin. Besides, Z-DEVD-FMK (ZDF) or Apoptosis Activator 2 was used to inhibit or activate the caspase-3 expression. The intensity of F-actin and β-tubulin, cell viability, apoptosis, and caspase-3 expression were analyzed., Results: Three days of treatment of 30 mM or 40 mM glucose significantly decreased the CHs viability compared to the 10 mM but increased the caspase-3, apoptosis, collagen, and the aggregation of the F-actin and β-tubulin. However, the cytochalasin D and colchicine partly rejected the high-glucose induced caspase-3 upregulation, apoptosis, and CHs disability. Besides, these two anti-aggregation drugs also suppressed the Apoptosis Activator 2 induced caspase-3 upregulation and apoptosis. Furthermore, the application of ZDF could only prevent the F-actin aggregation, but not the β-tubulin., Conclusions: Long-term high glucose triggers the caspase-3 expression and leads to the CH apoptosis involving cytoskeleton aggregation. Inhibition of cytoskeleton aggregation through the F-actin or β-tubulin could alleviate the high glucose-induced caspase-3 upregulation.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome., Case Presentation: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide., Conclusion: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

Objective: To study the heritability of obesity in children aged 30-36 months in Xi'an, China, as well as the role of four single nucleotide polymorphisms (SNPs) associated with body mass index in the susceptibility to obesity in children., Methods: Random sampling was performed to select 1 637 children, aged 30-36 months, from four communities of Xi'an from March 2017 to December 2018. Physical assessment was performed for these children, and a questionnaire survey was conducted for parents. Then the Falconer regression method was used to calculate the heritability of childhood obesity. Venous blood samples were collected from 297 children who underwent biochemical examinations, among whom there were 140 children with obesity/overweight (obesity/overweight group) and 157 with normal body weight (normal body weight group). The MassARRAY RS1000 typing technique was used to detect CDKAL1 gene rs2206734, KLF9 gene rs11142387, PCSK1 gene rs261967, and GP2 gene rs12597579. The distribution of alleles and genotypes was compared between the obesity/overweight and normal body weight groups. An unconditional logistic regression model was used to investigate the benefits of dominant and recessive genetic models., Results: For the 1 637 children, the heritability of obesity from the parents was 83%±8%, and the heritability from mother was slightly higher than that from father (86%±11% vs 78%±12%). There were significant differences in the distribution of rs2206734 alleles and genotypes and rs261967 genotypes between the obesity/overweight and normal body weight groups (P<0.0125). The children carrying T allele at rs2206734 had a significantly higher risk of obesity than those carrying CC (OR=0.24, P<0.0125), and the children carrying GG at rs261967 had a significantly higher risk of obesity than those carrying A allele (OR=4.11, P<0.0125)., Conclusions: Genetic factors play an important role in the pathogenesis of obesity in children, and the SNPs of CDKAL1 rs2206734 and PCSK1 rs261967 are associated with the susceptibility to obesity in children aged 30-36 months in Xi'an.

HONO measurement was conducted using a wet-chemistry-based method at the Changzhou Environmental Monitoring Center in April 2017. HONO ranged from 0.2-13.9 μg·m -3 with an average of (2.9±2.3) μg·m -3 . O 3 , HCHO, volatile organic compounds, photolysis frequency, and meteorological parameters were simultaneously monitored.·OH concentration was simulated by a Master Chemical Mechanism box model and the daytime maximum·OH concentration ranged from 1.0×10 6 to 14×10 6 molecules per cubic centimeter. The formation rates of·OH by photolysis of HONO, O 3 , HCHO, H 2 O 2 , and alkene ozonolysis were calculated as well. The effects of the five sources on atmospheric oxidation capacity were revealed:O 3 photolysis (46.4%) > HONO photolysis (41.1%) > alkene ozonolysis (10.9%) > HCHO photolysis (1.5%) > H 2 O 2 photolysis (0.1%). HONO photolysis for OH radical production played a major role in the early morning, before with an increase in O 3 concentration, O 3 photolysis began to account for most of the·OH production. After 17:00, due to a significant decrease in the intensity of solar radiation, the alkene ozonolysis started playing a major role in the formation of·OH. The photolysis of formaldehyde and hydrogen peroxide played a negligible role in·OH radical production in this study.

Understanding the relationships among different ecosystem services is the basis for optimizing ecological protection strategy and achieving sustainable ecological management. Based on the ecosystem services and their spatial patterns in Southwest China, we analyzed tradeoffs and synergies of five ecosystem regulation services (water retention, soil retention, carbon sequestration, biodiversity conservation, and water purification) and five provision services (rice production, wheat production, corn production, vegetable production, and fruit production) using statistical analysis, ArcGIS technology and GeoDa software. Further, we identified the win-win areas of ecosystem servi-ces through overlay analysis, and discussing the influence of ecosystem types on win-win pattern. There were synergistic relationships among different types of regulation or provision services in Southwest China, while there were both synergies and trade-offs between regulation and provision services. The high win-win areas of the total ecosystem services in Southwest China were mainly distributed in Qionglai Mountains, Ailao Mountains, Dayao Mountains, as well as Lujiang River and Lancang River basins. The proportion of forest and farmland areas significantly affected all kinds of win-win trend.

PM 2.5 samples were collected from December 2017 to November 2018 at a northern suburb site of Nanjing. The concentrations of five amines, major water-soluble ions, organic carbon, and elemental carbon were determined. The five amines measured were methylamine, ethylamine, dimethylamine, trimethylamine, and aniline. The annual average of the total amine concentration was (54.2±29.2) ng·m -3 . Among these, dimethylamine was the most abundant[annual average:(20.2±13.7) ng·m -3 ], followed by methylamine[annual average:(13.1±6.3) ng·m -3 ], trimethylamine[annual average:(8.6±4.1) ng·m -3 ], ethylamine[annual average:(6.3±4.1) ng·m -3 ], and aniline[annual average:(5.9±3.9) ng·m -3 ]. The total amine concentration showed explicit seasonal variations:summer > autumn > spring > winter. The amine concentration on polluted days was higher than that on clean days. This may be influenced by aerosol acidity, promoting the partitioning of gaseous amine into the particulate phase. Aerosol acidity was also the major reason for the higher concentration of amine observed in summer than in other seasons. During new particle formation events, the concentrations of amines increased substantially. Positive matrix factorization (PMF) was utilized to identify the potential sources of amines, identifying six sources:industrial emission, agriculture emission, biomass burning, automobile emission, secondary formation, and dust. Methylamine and ethylamine mainly originated from secondary formation and automobile emissions. Dimethylamine and trimethylamine mainly originated from biomass burning, secondary formation, and automobile emissions; Aniline mainly originated from industrial emissions and biomass burning. A significant seasonal difference is observed with respect to the sources of amines. In spring and autumn, road dust sources account for a relatively high proportion. In summer, secondary sources are the main sources of amines. However, the diurnal variations of amine are not evident, and the secondary source, motor vehicle emission, and biomass combustion are the three main influencing factors.

Background: Gefitinib and sorafenib have been proved effective for the treatment of cancers in clinical practice for years. Materials & methods: We intended to integrate the structural features of gefitinib and sorafenib and construct structurally unique 7-aromatic ureido-4-anilinoquinazolines. Results: Most of the targets exhibited promising antitumor activities. 8u showed excellent antitumor activities against the three tested cell lines (IC 50 , 0.81-2.49 μM). The enzymatic, apoptosis assay of 8u were also performed to study their preliminary action of mechanism. Conclusion: 8u deserve further research as antitumor agents.

A common bioelectronics goal is to enable communication between biology and electronics, and success is critically dependent on the communication modality. When a biorelevant modality aligns with instrumentation capabilities, remarkable successes have been observed (e.g., electrodes provide a powerful tool to observe and actuate biology through its ion-based electrical modality). Emerging biological research demonstrates that redox is another biologically relevant modality, and recent research has shown that advanced electrochemical methods enable biodevice communication through this redox modality. Here, we briefly summarize the biological relevance of this redox modality and the use of redox mediators to enable access to this modality through electrochemical measurements. Next, we describe the fabrication of a catechol-chitosan redox capacitor that is redox-active but nonconducting and thus offers a unique set of molecular electronic properties that enhance access to redox-based information. Finally, we cite several recent studies that demonstrate the broad potential for this capacitor to access redox-based biological information. In summary, we envision the redox capacitor will become a vital component in the integrated circuitry of redox-linked bioelectronics., Competing Interests: The authors declare no competing financial interest.

Objective: To investigate the influence of pre-pregnancy parental body mass index (BMI), maternal weight gain during pregnancy, and their interaction on neonatal birth weight., Methods: A total of 1 127 pregnant women who underwent regular prenatal examinations and full-term singleton delivery in the First Hospital of Xi'an Jiaotong University from January 2017 to October 2018 were enrolled. The data on their pre-pregnancy BMI, maternal weight gain during pregnancy, pre-pregnancy BMI of the husband, and neonatal birth weight were collected. The interaction between pre-pregnancy parental BMI and maternal weight gain during pregnancy was analyzed, and their correlation with neonatal birth weight was analyzed., Results: Among the 1 127 full-term neonates, the detection rates of low birth weight neonates and macrosomia were 2.22% (25/1 127) and 3.82% (43/1 127) respectively. There were significant differences in pre-pregnancy parental BMI and maternal weight gain during pregnancy among the low birth weight, normal birth weight, and macrosomia groups (P<0.05). Neonatal birth weight was positively correlated with pre-pregnancy parental BMI and maternal weight gain during pregnancy (r=0.097-0.322, P<0.05). Low maternal weight before pregnancy increased the risk of low birth weight (RR=4.17, 95%CI: 1.86-9.38), and maternal overweight/obesity before pregnancy (RR=3.59, 95%CI: 1.93-6.67) and excessive weight gain during pregnancy (RR=3.21, 95%CI: 1.39-7.37) increased the risk of macrosomia. No interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy was observed., Conclusions: Pre-pregnancy parental BMI and maternal weight gain during pregnancy are related to neonatal birth weight, and there is no interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy.

Objective: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA., Methods: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment., Results: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group( P <0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group( P >0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group( P <0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference( P >0.05); there was significant difference between needle knife group and model group( P <0.05); there was no significant difference between electro-acupuncture group and needle-knife group( P >0.05). In gait change, there was significant difference between model group and electro-acupuncture group( P <0.05); there was no significant difference between needle-knife group and model group( P >0.05). In joint activity, there was significant difference between electro-acupuncture group and model group( P <0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group( P <0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group( P >0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly( P <0.01), the ultimate load of the electro-acupuncture group decreased( P >0.05), and the ultimate load of the needle-knife group increased( P >0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly( P <0.05), and the ultimate load of the needle-knife group increased significantly ( P <0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased( P >0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly( P <0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased( P >0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased( P >0.05), and the maximum displacement of the needle-knife group increased significantly( P <0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased( P >0.05). There was no significant difference in stiffness among groups( P >0.05)., Conclusions: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Antibodies are common recognition elements for molecular detection but often the signals generated by their stoichiometric binding must be amplified to enhance sensitivity. Here, we report that an electrode coated with a catechol-chitosan redox capacitor can amplify the electrochemical signal generated from an alkaline phosphatase (AP) linked immunoassay. Specifically, the AP product p-aminophenol (PAP) undergoes redox-cycling in the redox capacitor to generate amplified oxidation currents. We estimate an 8-fold amplification associated with this redox-cycling in the capacitor (compared to detection by a bare electrode). Importantly, this capacitor-based amplification is generic and can be coupled to existing amplification approaches based on enzyme-linked catalysis or magnetic nanoparticle-based collection/concentration. Thus, the capacitor should enhance sensitivities in conventional immunoassays and also provide chemical to electrical signal transduction for emerging applications in molecular communication., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19- O-benzoyl derivatives by semisynthesis and their neuritogenic activities were evaluated. 6 and 15 (10 μM) were investigated with opposite effects in PC12 cells. 6 exhibited a superior activity to sarcodonin G by promoting NGF-induced neurite outgrowth, while 15 showed an inhibitory effect. Supportingly, 6 and 15 (20 μM) significantly induced and suppressed neurite extension in primary cultured rat cortical neurons, respectively. In mechanism, the two derivatives were revealed to influence NGF-induced neurite outgrowth in PC12 cells through the regulation of PKC-dependent and -independent ERK/CREB signaling as well as the upstream TrkA receptor phosphorylation. Furthermore, a possible pattern of interaction among NGF, 6/15 and TrkA was presented using molecular simulations. It revealed that 6/15 may contribute to the stabilization of the NGF-TrkAd5 complex by establishing several hydrophobic and hydrogen-bond interactions with NGF and TrkA, respectively. Taken together, 6 and 15 modulate PKC-dependent and -independent ERK/CREB signaling pathways possibly by influencing the binding affinity of NGF to the receptor TrkA, and finally regulate neurite outgrowth in PC12 cells.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The growing importance of hydrogels in translational medicine has stimulated the development of top-down fabrication methods, yet often these methods lack the capabilities to generate the complex matrix architectures observed in biology. Here we show that temporally varying electrical signals can cue a self-assembling polysaccharide to controllably form a hydrogel with complex internal patterns. Evidence from theory and experiment indicate that internal structure emerges through a subtle interplay between the electrical current that triggers self-assembly and the electrical potential (or electric field) that recruits and appears to orient the polysaccharide chains at the growing gel front. These studies demonstrate that short sequences (minutes) of low-power (∼1 V) electrical inputs can provide the program to guide self-assembly that yields hydrogels with stable, complex, and spatially varying structure and properties.