Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity.

Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.

Electrostatically Self-Assembled Magnetic Nanoparticles for High-Temperature Resistant and Friction-Controlled Lubrication System.

Magnetic-responsive surfactants are considered promising smart lubricating materials due to their significant stimulation response to applied magnetic fields. In this study, four magneto-responsive surfactants are successfully fabricated and encapsulated on the surface of molybdenum disulfide nanosheets (MoS2@C18H37N+(CH3)3[XCl3Br]-, X = Fe, Ce, Gd, and Ho) as base-oil components using electrostatic self-assembly, thereby constructing a multi-functional magnetic lubrication system (MoS2@STAX). Magnetorheological measurements confirm the remarkable responsiveness of MoS2@STACe lubricants at high shear rates and applied magnetic fields, which is further corroborated by the constant proximity of the magnet. The formation of dense carbon and tribo-chemical films between the friction interfaces at elevated temperatures is the primary factor contributing to the significant reduction in frictional wear. Notably, the magnetic lubricant demonstrates a pronounced response behavior when subjected to an applied magnetic field in the ceramic tribopair, even at lower magnetic fields. This work presents concepts for the development of high-temperature resistant and tunable lubrication additives by designing the material structure and controlling the magnetic stimulation.

Photoredox/Copper-Cocatalyzed Domino Annulation of Oxime Esters and NH4SCN: Access to Fully Substituted 2-Aminothiazoles.

Domino cyclization of oxime esters and NH4SCN facilitated by photoredox and copper cocatalysis has been established. Various structurally diverse fully substituted 2-aminothiazoles have been obtained in good yields at room temperature. It is featured by mild conditions, favorable functional group tolerance, and wide substrate scope. The present reaction is amenable to gram-scale synthesis, which is expected to find potential applications in organic synthesis and drug discovery. A plausible reaction mechanism is proposed.

Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies.

PURPOSE: This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). RESULTS: The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). CONCLUSIONS: CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.

Analysis of the clinical efficacy of visualization of percutaneous endoscopic lumbar discectomy combined with annulus fibrosus suture in lumbar disc herniation.

The objective of this study is to compare the clinical effectiveness of visualization of percutaneous endoscopic lumbar discectomy (VPELD) combined with annulus fibrosus suture technique and simple percutaneous endoscopic lumbar discectomy (PELD) technique in the treatment of lumbar disc herniation. A retrospective analysis was conducted on 106 cases of lumbar disc herniation treated with foraminoscopic technique at our hospital from January 2020 to February 2022. Among them, 33 cases were treated with VPELD combined with annulus fibrosus suture in group A, and 73 cases were treated with PELD in group B. The preoperative and postoperative visual analogue scale (VAS), functional index (Oswestry Disability Index, ODI), healing of the annulus fibrosus, intervertebral space height, and postoperative recurrence were recorded and compared between the two groups. All patients underwent preoperative and postoperative MRI examinations, and the average follow-up period was 12 ± 2 months. Both groups showed significant improvements in postoperative VAS and ODI scores compared to the preoperative scores (P < 0.05), with no statistically significant difference between the groups during the same period (P > 0.05). There was no significant decrease in intervertebral space between the two groups after surgery (P > 0.05). Group A showed significantly lower postoperative recurrence rate and better annulus fibrosus healing compared to group B (P < 0.05). The VPELD combined with annulus fibrosus suture technique is a safe, feasible, and effective procedure for the treatment of lumbar disc herniation. When the indications are strictly adhered to, this technique can effectively reduce the postoperative recurrence rate and reoperation rate. It offers satisfactory clinical efficacy and can be considered as an alternative treatment option for eligible patients.

CircHSPB6 Promotes Tumor-Associated Macrophages M2 Polarization and Infiltration to Accelerate Cell Malignant Properties in Lung Adenocarcinoma by CCL2.

Circular RNAs (circRNAs) are reported to be involved in the tumorigenesis of lung adenocarcinoma (LUAD). Here, this study focused on studying the function and mechanism of circHSPB6 in LUAD progression. Levels of genes and proteins were tested using qRT-PCR and western blotting analyses. The 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and transwell assays were adopted for in vitro assays. In vivo assay was conducted using mouse xenograft models. The binding between let-7a-2-3p and circHSPB6 or CCL2 was validated using RIP and dual-luciferase reporter assays. The M2 polarization of tumor-associated macrophages (TAMs) was analyzed by flow cytometry. LUAD tissues and cells showed high circHSPB6 expression, knockdown of circHSPB6-suppressed LUAD cell proliferation, migration, invasion, and induced cell apoptosis in vitro, as well as hindered tumor growth in vivo. Mechanistically, circHSPB6/let-7a-2-3p/CCL2 forms a feedback loop. CircHSPB6 could regulate CCL2 expression via sponging let-7a-2-3p. Further rescue assays showed that the effects of circHSPB6 silencing on LUAD cells were reversed by let-7a-2-3p inhibition or CCL2 overexpression. Moreover, circHSPB6 promoted the M2 polarization and infiltration of TAMs by CCL2. Functionally, circHSPB6 knockdown in A549 and H1299 cells inhibited TAM M2 polarization and then suppressed cell proliferation, migration, invasion, and emergency medical technicians (EMT) progression, while these effects were reversed by CCL2 up-regulation CircHSPB6 induced TAM M2 polarization to promote LUAD cell proliferation, migration, invasion, and EMT progression through let-7a-2-3p/CCL2 axis.

The impact of vegetation reconstruction on soil erosion in the Loess plateau.

Vegetation restoration not only extensively reshapes spatial land use patterns but also profoundly affects the dynamics of runoff and sediment loss. However, the influence of vegetation restoration on runoff and sediment yield from a regional perspective are scarce. This study therefore focused on 85 sites within the "Grain for Green" Project (GGP) region on the Loess Plateau, to investigate the impacts of the GGP on soil erosion. The results revealed a notable reduction in sediment loss and runoff due to vegetation restoration. Since the inception of the GGP in 1999, approximately 4.1 × 106 ha of degraded lands have been converted into forestlands, shrublands, and grasslands, resulting in an average annual reduction of 1.4 × 109 m3 in runoff and a decrease of 3.6 × 108 t in annual sediment loss on the whole Loess Plateau, with the GGP contributing approximately 26.7% of the sediment reduction in the Yellow River basin. The reduced soil erosion has mainly been regulated by vegetation cover, soil properties (clay, silt, and sand), slope, and precipitation on the Loess Plateau. The insights gained offer valuable contributions to large-scale assessments of changes in soil erosion in response to vegetation reconstruction and enhance our understanding of the spatial configurations associated with soil erosion control measures.

Recent progress in plant-derived polysaccharides with prebiotic potential for intestinal health by targeting gut microbiota: a review.

Natural products of plant origin are of high interest and widely used, especially in the food industry, due to their low toxicity and wide range of bioactive properties. Compared to other plant components, the safety of polysaccharides has been generally recognized. As dietary fibers, plant-derived polysaccharides are mostly degraded in the intestine by polysaccharide-degrading enzymes secreted by gut microbiota, and have potential prebiotic activity in both non-disease and disease states, which should not be overlooked, especially in terms of their involvement in the treatment of intestinal diseases and the promotion of intestinal health. This review elucidates the regulatory effects of plant-derived polysaccharides on gut microbiota and summarizes the mechanisms involved in targeting gut microbiota for the treatment of intestinal diseases. Further, the structure-activity relationships between different structural types of plant-derived polysaccharides and the occurrence of their prebiotic activity are further explored. Finally, the practical applications of plant-derived polysaccharides in food production and food packaging are summarized and discussed, providing important references for expanding the application of plant-derived polysaccharides in the food industry or developing functional dietary supplements.

Antioxidant Effects of Rhodoxanthin from Potamogeton crispus L. on H2 O2 -Induced RAW264.7 Macrophages Cells.

Potamogeton crispus L. (P. crispus) is the type of a widely distributed perennial herbs, which is rich in rhodoxanthin. In this research work, five antioxidant indexes in vitro were selected to study the antioxidant activity of rhodoxanthin from P. crispus (RPC). A model of hydrogen peroxide (H2 O2 ) -induced oxidative damage in RAW264.7 cells was established to analyze the antioxidant effect and potential mechanism of RPC. The levels of ROS, MDA and the activities of oxidation related enzymes by H2 O2 were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression of Nrf-2, HO-1, SOD1 and SOD2 was measured by qRT-PCR assay. According to the results, RPC had free radical scavenging ability for 2, 2-diphenyl-1-trinitrohydrazine (DPPH), 2,2'-azinobis(3-ethylbenzo-thiazoline-6-sulfonic acid radical ion) (ABTS), hydroxyl radical and superoxide anion. RPC significantly decreased the level of MDA and ROS and LDH activity, while increased GSH level and activities of SOD, GSH-Px and CAT. It was showed that RPC could increase the mRNA expression of Nrf-2, HO-1, SOD1 and SOD2 in RAW264.7 cells in a dose-dependently manner. In summary, RPC treatment could effectively attenuate the H2 O2 -induced cell damage rate, and the mechanism is related to the reduction of H2 O2 induced oxidative stress and the activation of Nrf-2 pathway.

Digital versus slit-beam marking for toric intraocular lenses in cataract surgery.

PURPOSE: To compare the visual outcomes of digital and slit-beam manual marking for toric intraocular lenses (IOL) in cataract surgery. SETTING: Single-center, Beijing Tongren Hospital, China. DESIGN: Retrospective study. METHODS: All patients with cataracts and regular corneal astigmatism greater than 0.75 diopters (D) underwent cataract surgery and astigmatism correction between June 2019 and June 2020. To mark the target axis of the toric IOL and the location of the incision, intraoperative digital marking was used by Callisto eye image-guided system in one group, while preoperative manual slit-beam marking was used in the other group. Uncorrected and best-corrected spectacle visual acuity, refraction, toric IOL axis, total higher order aberrations, coma, spherical aberration, and trefoil were evaluated at 1, 4, and 12 weeks postoperatively. RESULTS: Seventy-two eyes of 58 patients were included. At 3 months after surgery, the mean residual refractive cylinder was 0.42 ± 0.45D in the digital group and 0.39 ± 0.40D in the manual group (P = 0.844). There were no significant differences between groups in spherical equivalent refraction, uncorrected and best-corrected spectacle visual acuity, or the parameters of vector analysis. All toric IOL alignment errors were within 10° of the intended axis, and among them, about 42% of eyes in the digital group and 61% of eyes in the manual group had a rotation of 0-2° (P = 0.038). Trefoil in the manual group decreased postoperatively compared with the digital group (P = 0.012). Other aberration analyses did not reveal any statistical differences between groups. CONCLUSIONS: Accurate slit-beam manual marking and digital image-guided marking are equally effective for toric IOL alignment.

Natural oscillation frequencies of a Rayleigh sphere levitated in standing acoustic waves.

Acoustic levitation is an important method of container-free processing, which counteracts gravity through exerting the acoustic radiation force on levitated objects. The Gorkov potential function is used to simplify the calculation of the acoustic radiation force acting on a Rayleigh sphere whose radius is much smaller than the wave length. For the case of a plane standing wave levitation system, a systematic analysis of the sphere dynamics is provided in the axial direction, assuming a small perturbation around the stable equilibrium locations. A generalized extension to an arbitrary standing wave field is provided, which gives formal expressions of the axial and transverse natural oscillation frequencies for the sphere. Particular emphasis is put on the natural oscillation frequencies with and without taking gravity into consideration. The computational results for Gauss and Bessel standing waves are provided as two special cases, which show that the transverse natural oscillation frequency will be overestimated when neglecting gravity, especially for a sphere with a relatively large density. Corresponding experiments are conducted to verify the dependence of the transverse natural oscillation frequency on the sphere density. The results obtained in this work are expected to provide a theoretical guide for enhancing the levitation stability and inversing the physical parameters from the sphere dynamics.

Driving factors of ecosystem services and their spatiotemporal change assessment based on land use types in the Loess Plateau.

A clear understanding of the driving factors for different ecosystem services (ESs) is quite essential for sustainable ecosystem management. It is important to strengthen research in ESs and social sustainable development to identify the main driving factors of different ESs. This study assessed carbon sequestration (CS), water yield (WY) and soil conservation (SC) from 2000 to 2018 in the Loess Plateau using CASA (The Carnegie-AmesStanford Approach), InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) and RUSLE (Revised Universal Soil Loss Equation) models. The spatial heterogeneity, trade-offs and synergies and driving factors were explored in the whole Loess Plateau. The results showed that the WY, CS and SC had increased from 2000 to 2018. The spatial relationships between WY and SC, SC and CS, and WY and CS were mainly synergistic. Annual mean precipitation (MAP) was the dominant driving factor of WY, while normalized difference vegetation index (NDVI) and slope (SL) had the strongest explanatory power for CS and SC. The LU was the most critical factor affecting the ESs in the different climatic zones. These results could act as a reference for decision-makers on how to control various influencing factors of ESs to improve the local ecology under local conditions.

Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies.

BACKGROUND: Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride-glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis. METHODS: Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results. RESULTS: Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29-2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18-1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47-2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23-1.29, I2 = 0%, P < 0.001). CONCLUSIONS: A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline.

MiR-335-3p inhibits cell proliferation and induces cell cycle arrest and apoptosis in acute myeloid leukemia by targeting EIF3E.

Here, we aimed to investigate the biological roles and the regulatory mechanisms of miR-335-3p in acute myeloid leukemia (AML). We first found miR-335-3p was significantly downregulated in blood samples from leukemia patients and cell lines using reverse transcription quantitative polymerase chain reaction. Through CCK-8 assay and flow cytometry, we observed that miR-335-3p overexpression significantly inhibited cell proliferation and induced cell cycle G0/G1 arrest and apoptosis in AML cell lines (THP-1 and U937). Moreover, miR-335-3p directly targets EIF3E and negatively regulated its expression. More importantly, EIF3E overexpression reversed the effects of miR-335-3p on cell proliferation, G1/S transition, and apoptosis. Furthermore, miR-335-3p overexpression obviously downregulated the expression of CDK4, Cyclin D1, and Bcl-2, while upregulated the expression of p21 and Bad, which were significantly rescued by the cotransfection of pcDNA3.1-EIF3E. Collectively, our study proposes that miR-335-3p/EIF3E axis could be a promising therapeutic target to mitigate the progression of AML.

Postoperative Radiotherapy in Pathological T2-3N0M0 Thoracic Esophageal Squamous Cell Carcinoma: Interim Report of a Prospective, Phase III, Randomized Controlled Study.

BACKGROUND: The role of postoperative radiotherapy in pathological T2-3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma. MATERIALS AND METHODS: Patients aged 18-72 years with pathological stage T2-3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease-free survival. The secondary endpoints were local-regional recurrence rate, overall survival, and radiation-related toxicities. RESULTS: From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow-up time was more than 1 year or who had died. The median follow-up time was 45.6 months. The 3-year disease-free survival rates were 75.1% (95% confidence interval [CI] 65.9-85.5) in the postoperative radiotherapy group and 58.7% (95% CI 48.2-71.5) in the surgery group (hazard ratio 0.53, 95% CI 0.30-0.94, p = .030). Local-regional recurrence rate decreased significantly in the radiotherapy group (10.0% vs. 32.5% in the surgery group, p = .001). The overall survival and distant metastasis rates were not significantly different between two groups. Grade 3 toxicity rate related to radiotherapy was 12.5%. CONCLUSION: Postoperative radiotherapy significantly increased disease-free survival and decreased local regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma with acceptable toxicities in this interim analysis. Further enrollment and follow-up are warranted to validate these findings in this ongoing trial. IMPLICATIONS FOR PRACTICE: The value of adjuvant radiotherapy for patients with node-negative esophageal cancer is not clear. The interim results of this phase III study indicated that postoperative radiotherapy significantly improved disease-free survival and decreased local-regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. The distant metastasis rates and overall survival rates were not different between the two groups. Adjuvant radiotherapy should be considered for pathologic T2-3N0M0 thoracic esophageal squamous cell carcinoma. Prospective trials to identify high-risk subgroups are needed.

Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: Information on the optimal salvage regimen for recurrent esophageal cancer is scarce. We aimed to assess the patterns of locoregional failure, and evaluate the therapeutic efficacy of salvage therapy along with the prognostic factors in recurrent thoracic esophageal squamous cell carcinoma (TESCC) after radical esophagectomy. METHODS: A total of 193 TESCC patients who were diagnosed with recurrence after radical surgery and received salvage treatment at our hospital were retrospectively reviewed from 2004 to 2014. The patterns of the first failure were assessed. The post-recurrence survival rate was determined using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. RESULTS: The median time of failure was 7.0 months. Among the 193 patients, 163 exhibited isolated locoregional lymph node (LN) recurrence and 30 experienced locoregional LN relapse with hematogenous metastasis. Among the 193 patients, LN recurrence was noted at 302 sites; the most common sites included the supraclavicular (25.8%; 78/302) and mediastinal LNs (44.4%; 134/302), particularly stations 1 to 6 for the mediastinal LNs (36.4%; 110/302). The median overall survival (OS) was 13.1 months after recurrence. In those treated with salvage chemoradiotherapy, with radiotherapy, and without radiotherapy, the 1-year OS rates were 68.5, 55.0, and 28.6%; the 3-year OS rates were 35.4, 23.8, and 2.9%; and the 5-year OS rates were 31.8, 17.2, 2.9%, respectively (P < 0.001). Furthermore, patient survival in those who received salvage chemoradiotherapy was significantly better than those treated with salvage radiotherapy alone (P = 0.044). Multivariate analysis showed that the pathological TNM stage and salvage treatment regimen were independent prognostic factors. CONCLUSIONS: Supraclavicular and mediastinal LN failure were the most common types of recurrence after R0 surgery in TESCC patients. Salvage chemoradiotherapy or radiotherapy could significantly improve survival in esophageal cancer with locoregional LN recurrence.

A non-aggregated silicon(IV) phthalocyanine-lactose conjugate for photodynamic therapy.

To develop a highly efficient photosensitizer for photodynamic therapy (PDT), we have designed and synthesized a phthalocyanine-lactose conjugate (Pc-Lac) through axial modification of silicon(IV) phthalocyanine with lactose moieties. With the lactose substituents, Pc-Lac is highly hydrophilic and non-aggregated with efficient reactive oxygen species (ROS) generation in aqueous media. With these desirable properties, Pc-Lac shows high photocytotoxicity and cellular uptake toward HepG2 cells. In addition, in vivo fluorescence imaging shows that Pc-Lac could selectively remain at tumor site, leading to its enhanced photodynamic efficacy against H22 tumor-bearing mice. Therefore, Pc-Lac shows a great potential as a highly efficient molecular photosensitizer for PDT.

Cationic liposome codelivering PI3K pathway regulator improves the response of BRCA1-deficient breast cancer cells to PARP1 inhibition.

Although some progresses have been made in breast cancer therapy, effective treatment for BRCA1-deficient breast cancer remains to be a great challenge. It has been demonstrated that the PI3K pathway is inappropriately activated in BRCA1-deficient breast cancers which can be downregulated by microRNA 451 (miR-451). In addition, although PARP1 inhibitors showed relatively positive results in both preclinical and clinical studies, additional efforts to decrease drug resistance as well as reduce systematic toxicity need to be addressed. To this end, by encapsulating the miR-451 mimic and PARP1 inhibitor in the same cationic liposome, we examined the potential of enhancing the response of PARP1 inhibition on BRCA1-deficient breast cancer by regulating the PI3K pathway. Our results revealed that in BRCA1-deficient human breast cancer cell line, PARP1 inhibition resulted in DNA damage with viability decrease, G2/M arrest as well as apoptosis. In contrast, single PI3K inhibition induced G1 arrest along with retarded cell proliferation. However, it was noted that combination of PARP inhibitor and PI3K regulator could exert synergetic function to evidently decrease cell proliferation compared with PARP inhibition alone, which was also confirmed by in vivo antitumor assay using xenograft tumor models. Collectively, our results offer an alternative but superior strategy for the therapy of BRCA1-deficient human breast cancers which may benefit the clinical applications.

Reactivation of resolved hepatitis B virus infection combined with nephrotic syndrome in a patient after allogeneic haematopoietic stem cell transplantation.

BACKGROUND: After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. CASE PRESENTATION: We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival. She had pretransplant serological markers of a resolved HBV infection (HBsAg-negative, anti-HBc and anti-HBs positive). However, she developed HBVr combined with nephrotic syndrome (NS) 16 months after HSCT. Her histological renal lesion was mesangial proliferative glomerulonephritis. IgA+, IgM+, and C1q deposits but not HBV antigens (HBsAg and HBcAg) were identified in her renal biopsy material. Long-term entecavir and immunosuppression resulted in decrease of HBV virus replication, amelioration of proteinuria and stabilisation of renal function. CONCLUSIONS: Entecavir combined with immunosuppression has efficacy in the treatment of HBVr combined with NS after allo-HSCT, but long course of treatment is needed. Closely monitoring and antiviral prophylaxis might be necessary for allo-HSCT recipients to prevent reactivation of resolved HBV infection and its related complications.

How will different types of industry policies and their mixes affect the innovation performance of wind power enterprises? Based on dual perspectives of regional innovation environment and enterprise ownership.

Evaluating the effectiveness and functional boundary of different types of industry policies and their mixes on the innovation performance of wind power enterprises (WPEs) is an important but unresolved key issue. This study, based on dual perspectives of regional innovation environment and enterprise ownership, empirically examines the impacts of different types of industry policies and their mixes on enterprise innovation. The results show that different types of policies have significantly different effects on innovation performance of WPEs; policy mixes have a significant synergy but may not be fully effective, and environmental-side policy and demand-side policy mixes still show significant inhibition. Taking into account boundary conditions, this study finds that policy mixes are implemented better in regions with weak innovation environments, especially in terms of the innovation performance of private-owned WPEs in the region. However, there is no significant impact for WPEs located in regions with strong innovation environments and state-owned enterprises in regions with weak innovation environments. This study expands an understanding of external boundaries for the effective implementation of different industry policies and their mixes, and has important implications for China in improving the applicability and matching ability of policies in the wind power industry.