Enhancing Light Outcoupling Efficiency via Anisotropic Low Refractive Index Electron Transporting Materials for Efficient Perovskite Light-Emitting Diodes.

Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (ne) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low ne of 1.59 along the z-axis direction. Optical simulations show that the low ne of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A-1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs.

Ce Site in Amorphous Iron Oxyhydroxide Nanosheet toward Enhanced Electrochemical Water Oxidation.

Iron oxyhydroxide has been considered an auspicious electrocatalyst for the oxygen evolution reaction (OER) in alkaline water electrolysis due to its suitable electronic structure and abundant reserves. However, Fe-based materials seriously suffer from the tradeoff between activity and stability at a high current density above 100 mA cm-2 . In this work, the Ce atom is introduced into the amorphous iron oxyhydroxide (i.e., CeFeOx Hy ) nanosheet to simultaneously improve the intrinsic electrocatalytic activity and stability for OER through regulating the redox property of iron oxyhydroxide. In particular, the Ce substitution leads to the distorted octahedral crystal structure of CeFeOx Hy , along with a regulated coordination site. The CeFeOx Hy electrode exhibits a low overpotential of 250 mV at 100 mA cm-2 with a small Tafel slope of 35.1 mVdec-1 . Moreover, the CeFeOx Hy electrode can continuously work for 300 h at 100 mA cm-2 . When applying the CeFeOx Hy nanosheet electrode as the anode and coupling it with the platinum mesh cathode, the cell voltage for overall water splitting can be lowered to 1.47 V at 10 mA cm-2 . This work offers a design strategy for highly active, low-cost, and durable material through interfacing high valent metals with earth-abundant oxides/hydroxides.

Cu/Cu2O nanocrystals for electrocatalytic carbon dioxide reduction to multi-carbon products.

We demonstrate the electrochemical conversion of carbon dioxide into multi-carbon products catalyzed by Cu/Cu2O nanocrystals, with a maximum C2+ faradaic efficiency of 75% in 0.10 M K2SO4 aqueous solution at -2.0 V versus Ag/AgCl and a partial current density of 34 mA cm-2.

Intramolecular charge transfer effect for highly efficient deep red and near infrared thermally activated delayed fluorescence.

Thermally activated delayed fluorescence (TADF) materials with emission in the deep red and near infrared (DR/NIR) region are underresearched due to the limited choice of strong donor/acceptor units. The current mainstream strategy for the design of DR/NIR TADFs is to increase the acceptor strength via the introduction of multiple sub-acceptor units, thereby narrowing the bandgap. In this work, the intramolecular charge transfer (ICT) effect was applied for the development of acceptor units to achieve efficient DR/NIR TADFs. The ICT effect within the acceptor unit enhanced the π-electron delocalization, lowered the LUMO and redshifted the emission wavelength. In addition, the fusion of the donor unit into the planar acceptor skeleton rigidified the molecular structure and reduced the non-radiative decay. This proof-of-concept study demonstrated that ICT is an undoubtedly effective strategy for the rational design of efficient DR/NIR TADFs.

Efficient Electrocatalytic Reduction of CO2 to Ethane over Nitrogen-Doped Fe2O3.

Non-copper electrocatalysts are seldom reported to generate C2+ products, and the efficiency over these catalysts is low. In this work, we report a nitrogen-doped γ-Fe2O3 (xFe2O3-N@CN) electrocatalyst, which yield C2H6 as the major product in an H-cell. At -2.0 V vs Ag/Ag+, the Faradaic efficiency (FE) for ethane reaches 42% with a current density of 32 mA cm-2. This is the first report about selective CO2 reduction to ethane (C2H6) over an iron-based catalyst. The results showed that the catalyst possessing FeO1.5-nNn sites enriched with oxygen vacancies was beneficial for the stabilization of *COOH intermediates. The exposure of two adjacent surfaces of Fe atoms was conducive to lowering the energy barrier for C-C coupling over FeO1.5-nNn sites, facilitating the generation of C2H6. This work provides a strategy for the design of a novel iron-based catalyst with tunable local coordination and electronic structures for converting CO2 into C2 products in the CO2RR.

[Enhancing Maternal-Infant Attachment in a Neonatal Intensive Care Unit During the Pandemic Prevention Period].

BACKGROUND & PROBLEMS: Parent-infant attachment is affected by parent-infant interaction. The limitations on related visitations during the COVID-19 pandemic suspended the opportunity to engage in kangaroo care (skin-to-skin contact) activities. These changes impacted parent-infant attachment in the neonatal intensive care unit. After investigation, the score of premature infant-parent attachment was found to be only 64.6 points during the period in which visitation limitations were in effect. PURPOSE: To enhance maternal-premature infant attachment during the pandemic period by 10% (from an average score of 64.6 to 71.1). RESOLUTION: This project involved nurses playing audio files provided by mothers to their premature infants, and recording a video and taking pictures of the infants during this process. This project used a cloud platform as bidirectional pipelines. Furthermore, emotional support and caring information were provided to the mothers via expressive arts therapy and phone interviews. RESULTS: After the intervention, the premature infant-parent attachment score rose to 74.4 from the pre-intervention score of 64.6. CONCLUSIONS: During pandemic control periods, traditional modes of care aimed at building infant-parent attachment are not applicable. The intervention project used was found to be an effective alternative approach to increasing maternal-premature infant attachment. Breaking the restrictions of time and place, this project applies family-centered care, and may provide a reference for developing software, hardware, and communication equipment for other care units related to newborns.

Three-dimensional inlay-guided endodontics applied in variant root canals: A case report and review of literature.

BACKGROUND: Root canal retreatment is common after root canal therapy in clinical situations. Especially, completing the retreatment of variant root canals can be challenging. This is particularly true for the molars located at the end of the dental arch. However, advancements in digital dental diagnosis and treatment techniques can solve these problems. Here, we describe a case of a maxillary second molar with a variant distobuccal root canal treated via a novel "inlay-guided endodontics" technique based on improved computer-generated programs. CASE SUMMARY: A 63-year-old man complained of a defect in the maxillary left second molar. The tooth, diagnosed with post-treatment endodontic disease, was initially treated by conventional methods, which were ineffective. Our "inlay-guided endodontics" technique was subsequently adopted, with the establishment of a precise integrated three-dimensional (3D) plate model of cone-beam computed tomography data and a digital impression of the dentition. An optimal root canal approach was generated for the "virtual file" in the 3D model. The plate data were imported into a 3D printer and printed. With the help of the guide plate, the file was accurately placed into the cervical third of the distal root canal. The root canal and prosthodontic treatments successfully proceeded subsequently. CONCLUSION: Our newly developed inlay guide plates may facilitate individualized and minimally invasive root canal treatment.

Efficacy and Safety of Ginkgo biloba in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Ginkgo biloba and its extract have been suggested to have a neuroprotective role in patients with acute ischemic stroke. We aimed to examine the efficacy and safety of Ginkgo biloba use in patients with acute ischemic stroke. We searched seven databases for randomized controlled studies examining the use of Ginkgo biloba in patients with acute ischemic stroke. Relevant studies were retrieved, screened, and data were extracted independently by two reviewers. Random effects meta-analyses were performed to evaluate the efficacy and safety outcomes of Ginkgo biloba. We subsequently assessed the certainty of evidence using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. We found 12 randomized controlled studies enrolling 1466 patients. Pooled results suggest that Ginkgo biloba use was associated with an improvement in neurological function among individuals with AIS with a reduction of 2.87 points on the National Institute of Health Stroke Scale score (95% CI: -4.01--1.74, p<0.001). Ginkgo biloba use was also associated with an improvement in activities of daily living and functional outcome (Mean Difference: 9.52; 4.66-14.33, p<0.001). Subgroup analysis suggest that the impact was larger when using an injectable formulation of Ginkgo biloba compared to the oral formulation. There was no apparent impact of Ginkgo biloba use on all-cause mortality (Risk ratio (RR): 1.21; 0.29-5.09, p=0.80) or cerebrovascular bleeding (RR: 0.82; 0.43-1.57, p=0.55). There was limited evidence on to support the use of gingko biloba in terms of improving quality of life and other stroke events. As such, more studies are needed before it can be recommended for routine use in improving neurological and cognitive function in patients with acute ischemic stroke.

Hierarchically heterostructured metal hydr(oxy)oxides for efficient overall water splitting.

The design of highly efficient electrocatalysts containing non-precious metals is crucial for promoting overall water splitting in alkaline media. In particular, Janus catalysts simultaneously facilitating the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are desirable. Herein, we fabricated a unique hierarchical heterostructure via growing Ni4W6O21(OH)2·4H2O (denoted as Ni-W-O) nanosheets on NiMoO4 rods, which was indispensable for regulating the morphology of the Ni-W-O structure. This heterostructure of Ni-W-O/NiMoO4 could be utilized as an electrocatalyst to realize superior activity for overall water splitting in 1.0 M KOH. It substantially promoted overall water splitting with 1.6 V at 30 mA cm-2, outperforming numerous bifunctional electrocatalysts under the same conditions. Notably, the remarkable stability for continuously splitting water endowed this hierarchical heterostructure with potential applications on a large scale. This work emphasizes the effectively controlled growth of heterostructured non-noble-metal catalysts for energy-conversion reaction.

[Efficacy of minocycline hydrochloride combined with flap surgery for chronic periodontitis: a Meta-analysis].

OBJECTIVE: This study aimed to evaluate the efficacy of 2% minocycline hydrochloride combined with flap surgery in the treatment of chronic periodontitis. The superiority of this therapy to simple flap surgery was also explored. METHODS: We searched the databases of CNKI, VIP, Wanfang, Chinese Biomedical Literature, PubMed, ScienceDirect, and Embase from inception to July 2017. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Then, Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of seven randomized controlled trials involving 217 patients were included. Meta-analysis showed that, in two groups, the changes in probing depth (PD) [MD=-0.55, 95%CI (-0.84, -0.26), P=0.000 2] and plaque index [MD=-0.08, 95%CI (-0.15, -0.01), P=0.03] at 3 and 6 months of PD [MD=-0.62, 95%CI (-1.04, -0.21), P=0.003] had statistically significant difference (P<0.05). The clinical attachment loss (CAL) [MD=-0.21, 95%CI (-0.47, 0.04), P=0.10] had no statistically significant difference after 3 months (P>0.05), but the improvement in CAL was significantly improved by minocycline hydrochloride combined with flap therapy. CONCLUSIONS: Periodontal flap combined with minocycline adjuvant therapy for chronic periodontitis is effective in short-term observations.

Magnetic-responsive switchable emulsions based on Fe3O4@SiO2-NH2 nanoparticles.

Magnetic-responsive switchable emulsions, which are stabilized by 3-aminopropyltriethoxy silane coated nanoparticles, have been developed in this study. The emulsions show excellent stability for dozens of days and more importantly perform complete demulsification on demand in several minutes. This study provides a facile and possible manipulation strategy to re-disperse the components, re-produce the stable emulsions, and re-trigger the demulsification performance without long-lasting effects.

Efficacy of minocycline hydrochloride combined with flap surgery for chronic periodontitis: a Meta-analysis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to evaluate the efficacy of 2% minocycline hydrochloride combined with flap surgery in the treatment of chronic periodontitis. The superiority of this therapy to simple flap surgery was also explored.</p><p><b>METHODS</b>We searched the databases of CNKI, VIP, Wanfang, Chinese Biomedical Literature, PubMed, ScienceDirect, and Embase from inception to July 2017. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Then, Meta-analysis was performed using RevMan 5.3 software.</p><p><b>RESULTS</b>A total of seven randomized controlled trials involving 217 patients were included. Meta-analysis showed that, in two groups, the changes in probing depth (PD) [MD=-0.55, 95%CI (-0.84, -0.26), P=0.000 2] and plaque index [MD=-0.08, 95%CI (-0.15, -0.01), P=0.03] at 3 and 6 months of PD [MD=-0.62, 95%CI (-1.04, -0.21), P=0.003] had statistically significant difference (P<0.05). The clinical attachment loss (CAL) [MD=-0.21, 95%CI (-0.47, 0.04), P=0.10] had no statistically significant difference after 3 months (P>0.05), but the improvement in CAL was significantly improved by minocycline hydrochloride combined with flap therapy.</p><p><b>CONCLUSIONS</b>Periodontal flap combined with minocycline adjuvant therapy for chronic periodontitis is effective in short-term observations.</p>

Astaxanthin enhances pemetrexed-induced cytotoxicity by downregulation of thymidylate synthase expression in human lung cancer cells.

Pemetrexed, a multitargeted antifolate agent, has demonstrated clinical activity in non-small cell lung cancer (NSCLC) cells. Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to pemetrexed. Astaxanthin exhibits a wide range of beneficial effects including anti-cancer and anti-inflammatory properties. In this study, we showed that down-regulating of TS expression in two NSCLC cell lines, human lung adenocarcinoma H1650 and squamous cell carcinoma H1703 cells, with astaxanthin were associated with decreased MKK1/2-ERK1/2 activity. Enforced expression of constitutively active MKK1 (MKK1-CA) vector significantly rescued the decreased TS mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with a MKK1/2 inhibitor (U0126 or PD98059) further decreased the TS expression in astaxanthin-exposed NSCLC cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting ERK1/2 activity enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Combination of pemetrexed and astaxanthin resulted in synergistic enhancing cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-MKK1/2, phopho-ERK1/2, and TS expression. Overexpression of MKK1/2-CA reversed the astaxanthin and pemetrexed-induced synergistic cytotoxicity. Our findings suggested that the down-regulation of MKK1/2-ERK1/2-mediated TS expression by astaxanthin is an important regulator of enhancing the pemetrexed-induced cytotoxicity in NSCLC cells.

Curcumin downregulates p38 MAPK-dependent X-ray repair cross-complement group 1 (XRCC1) expression to enhance cisplatin-induced cytotoxicity in human lung cancer cells.

Cisplatin is a well-studied and widely used chemotherapeutic agent and is effective in the treatment of the advanced human non-small cell lung cancer (NSCLC). Curcumin is a yellow pigment derived from the rhizome of Curcuma longa and has been proved to have antioxidant and antitumor properties. XRCC1 is an important scaffold protein involved in base excision repair and plays an important role in the development of lung cancer. In this study, we characterize the role of curcumin in the cytotoxicity, p38 MAPK activation, and XRCC1 expression affected by cisplatin in NSCLC cells. We show that curcumin enhanced the cytotoxicity induced by cisplatin in two NSCLC cells, A549 and H1703. Treatment with cisplatin alone increased XRCC1 mRNA and protein expression through p38 MAPK activation. Moreover, SB2023580 (p38 inhibitor) decreased the XRCC1 mRNA and protein stability upon cisplatin treatment. Knockdown of XRCC1 in NSCLC cells by transfection of XRCC1 siRNA or inactivation of p38 MAPK resulted in enhancing the cytotoxicity and cell growth inhibition induced by cisplatin. Curcumin inhibited the expression of XRCC1 in cisplatin-exposed NSCLC cells. Furthermore, transfection with constitutive active MKK6 or HA-p38 MAPK vectors rescued the XRCC1 protein level and also the cell survival suppressed by cisplatin and curcumin combination in A549 and H1703 cells. These findings suggested that the downregulation of XRCC1 expression by curcumin can enhance the chemosensitivity of cisplatin in NSCLC cells.

Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 µM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC.

Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC.

Resveratrol Enhances Etoposide-Induced Cytotoxicity through Down-Regulating ERK1/2 and AKT-Mediated X-ray Repair Cross-Complement Group 1 (XRCC1) Protein Expression in Human Non-Small-Cell Lung Cancer Cells.

Etoposide (VP-16), a topoisomerase II inhibitor, is an effective anti-cancer drug used for the treatment of non-small-cell lung cancer (NSCLC). Resveratrol is a naturally occurring polyphenolic compound that has been proved to have anti-cancer activity. XRCC1 is an important scaffold protein involved in base excision repair that is regulated by ERK1/2 and AKT signals and plays an important role in the development of lung cancer. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in etoposide treatment alone or combined with resveratrol-induced cytotoxicity in NSCLC cells has not been identified. In this study, etoposide treatment increased XRCC1 mRNA and protein expression through AKT and ERK1/2 activation in two NSCLC cells, H1703 and H1975. Knockdown of XRCC1 in NSCLC cells by transfection of XRCC1 siRNA or inactivation of ERK1/2 and AKT resulted in enhancing cytotoxicity and cell growth inhibition induced by etoposide. Resveratrol inhibited the expression of XRCC1 and enhanced the etoposide-induced cell death and anti-proliferation effect in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors could rescue the XRCC1 protein level and also the cell survival suppressed by co-treatment with etoposide and resveratrol. These findings suggested that down-regulation of XRCC1 expression by resveratrol can enhance the chemosensitivity of etoposide in NSCLC cells.

Down-regulation of ERK1/2 and AKT-mediated X-ray repair cross-complement group 1 protein (XRCC1) expression by Hsp90 inhibition enhances the gefitinib-induced cytotoxicity in human lung cancer cells.

Gefitinib (Iressa(R), ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. It has been shown that inhibition of Hsp90 function can enhance antitumor activity of EGFR-TKI. XRCC1 is an important scaffold protein in base excision repair, which could be regulated by ERK1/2 and AKT pathways. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in gefitinib alone or combination with an Hsp90 inhibitor-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. In this study, gefitinib treatment decreased XRCC1 mRNA and protein expression through ERK1/2 and AKT inactivation in two NSCLC cells, A549 and H1975. Knocking down XRCC1 expression by transfection with small interfering RNA of XRCC1 enhanced the cytotoxicity and cell growth inhibition of gefitinib. Combining treatment of gefitinib with an Hsp90 inhibitor resulted in enhancing the reduction of XRCC1 protein and mRNA levels in gefitinib-exposed A549 and H1975 cells. Compared to a single agent alone, gefitinib combined with an Hsp90 inhibitor resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors rescued the XRCC1 protein level as well as the cell survival suppressed by an Hsp90 inhibitor and gefitinib. These findings suggested that down-regulation of XRCC1 can enhance the sensitivity of gefitinib for NSCLC cells.

Down-regulation of MSH2 expression by Hsp90 inhibition enhances cytotoxicity affected by tamoxifen in human lung cancer cells.

The anti-estrogen tamoxifen has been used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Human MutS homolog 2 (MSH2), a crucial element of the highly conserved DNA mismatch repair system, and expression of MSH2 have been down-regulated by Hsp90 function inhibition in human lung cancer. Therefore, in this study, we examined whether MSH2 plays a role in the tamoxifen and Hsp90 inhibitor-induced cytotoxic effect on NSCLC cells. The results showed that treatment with tamoxifen increased MSH2 mRNA and protein levels. The combination treatment with PI3K inhibitors (LY294002 or wortmannin) or knockdown AKT expression by specific small interfering RNA could decrease tamoxifen-induced MSH2 expression. Both knocking down MSH2 expression and co-treatment of PI3K inhibitors enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Compared to a single agent alone, tamoxifen combined with an Hsp90 inhibitor resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced MSH2 expression. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and Hsp90 inhibitors for the treatment of NSCLC.

Human regulatory B cells combine phenotypic and genetic hallmarks with a distinct differentiation fate.

Regulatory B cells (B-reg) produce IL-10 and suppress inflammation in both mice and humans, but limited data on the phenotype and function of these cells have precluded detailed assessment of their contribution to host immunity. In this article, we report that human B-reg cannot be defined based on a phenotype composed of conventional B cell markers, and that IL-10 production can be elicited in both the CD27(+) memory population and naive B cell subset after only a brief stimulation in vitro. We therefore sought to obtain a better definition of IL-10-producing human B-regs using a multiparameter analysis of B cell phenotype, function, and gene expression profile. Exposure to CpG and anti-Ig are the most potent stimuli for IL-10 secretion in human B cells, but microarray analysis revealed that human B cells cotreated with these reagents resulted in only ∼0.7% of genes being differentially expressed between IL-10(+) and IL-10(-) cells. Instead, connectivity map analysis revealed that IL-10-secreting B cells are those undergoing specific differentiation toward a germinal center fate, and we identified a CD11c(+) B cell subset that was not capable of producing IL-10 even under optimal conditions. Our findings will assist in the identification of a broader range of human pro-B-reg populations that may represent novel targets for immunotherapy.