Thiocarbonyl-Based Hole Transport Materials with Enhanced Defect Passivation Ability for Efficient and Stable Perovskite Solar Cells.

Organic hole transporting materials (HTMs) are extensively studied in perovskite solar cells (PSCs). The HTMs directly contact the underlying perovskite material, and they play additional roles apart from hole transporting. Developing organic HTMs with defect passivation function has been proved to be an efficient strategy to construct efficient and stable PSCs. In this work, new organic molecules with thiocarbonyl (C═S) and carbonyl (C═O) functional groups are synthesized and applied as HTMs (named FN-S and FN-O). FN-S with C═S can be facilely obtained from FN-O containing C═O. Notably, the C═S in FN-S results in superior defect passivation ability compared to FN-O. Moreover, FN-S exhibits excellent hole extraction/transport capability. Conventional PSCs using FN-S as HTM show an impressive power conversion efficiency (PCE) of 23.25%, with excellent long-term stability and operational stability. This work indicates that simply converting C═O to C═S is an efficient way to improve the device performance by strengthening the defect passivation functionality.

Improvement of Perovskite Solar Cells Efficiency by Management of the Electron Withdrawing Groups in Hole Transport Materials: Theoretical Calculation and Experimental Verification.

Management of functional groups in hole transporting materials (HTMs) is a feasible strategy to improve perovskite solar cells (PSCs) efficiency. Therefore, starting from the carbazole-diphenylamine-based JY7 molecule, JY8 and JY9 molecules are incorporated into the different electron-withdrawing groups of fluorine and cyano groups on the side chains. The theoretical results reveal that the introduction of electron-withdrawing groups of JY8 and JY9 can improve these highest occupied molecular orbital (HOMO) energy levels, intermolecular stacking arrangements, and stronger interface adsorption on the perovskite. Especially, the results of molecular dynamics (MD) indicate that the fluorinated JY8 molecule can yield a preferred surface orientation, which exhibits stronger interface adsorption on the perovskite. To validate the computational model, the JY7-JY9 are synthesized and assembled into PSC devices. Experimental results confirm that the HTMs of JY8 exhibit outstanding performance, such as high hole mobility, low defect density, and efficient hole extraction. Consequently, the PSC devices based on JY8 achieve a higher PCE than those of JY7 and JY9. This work highlights the management of the electron-withdrawing groups in HTMs to realize the goal of designing HTMs for the improvement of PSC efficiency.

Theoretical calculations and experimental investigation toward the π-conjugated modulation in arylamine derivative-based hole transporting materials for perovskite solar cells.

Excellent hole transporting materials (HTMs) are beneficial to promote the performance of perovskite solar cells (PSCs). Herein, starting from the modulation of the π-conjugated groups of carbazole-diphenylamine derivatives, HTMs CY1 and CY2 were designed and investigated using density functional theory and Marcus theory. Theoretical simulations show that CY1 and CY2 exhibit appropriate HOMO/LUMO energy levels, small recombination energy, good optical properties and molecular stability. Compared with CY1, CY2 with a larger π-conjugated group on its side chain can yield a higher hole mobility and better charge separation. The experimental results confirm that CY2 in PSCs exhibits superior properties such as good hole transporting ability, good film morphology, and efficient charge extraction and dissociation at perovskite/HTM inerfaces. Therefore, a PSC device with CY2 yields a higher efficiency than those of CY1- and Spiro-OMeTAD-based devices. Hence, the results demonstrate that the strategy of the extended π-π conjugation on a side chain is a practicable approach to design potential HTMs for application in PSCs.

A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation.

PURPOSE: Disitamab vedotin (RC48) is an HER2-directed antibody-drug conjugate, emerging as an effective strategy for cancer therapy, which not only enhances antitumor immunity in previous animal models but also improves clinical outcomes for patients such as with gastric cancer, urothelium carcinoma, and HER2 low-expressing breast cancer. Here, we explore the combination therapeutic efficacy of this novel HER2-targeting ADC with immune checkpoint inhibitors in a human HER2-expressing syngeneic breast cancer model. METHODS: The human HER2+ cancer cell line is constructed by stable transfection and individual clones were isolated by single-cell sorting. Flow cytometry was performed to determine its binding activity. Cytotoxic effect was determined using an MTT assay with the supplement of RC48. Human PD-1 transgenic mice were used to analyze the in vivo antitumor effects of the ADC and its combination therapy with PD-1/PD-L1 antibody. RESULTS: The combination of RC48 and PD-1/PD-L1 immune checkpoint inhibition significantly enhanced tumor suppression and antitumor immunity. Tumor rejection in the synergistic groups was accompanied by massive T cell infiltration and immune marker activation. Furthermore, the combination therapy promoted immunological memory formation in the tumor eradication animals, protecting them from tumor rechallenge. CONCLUSION: A novel HER2-targeting ADC combined with immune checkpoint inhibitors can achieve remarkable effects in mice and elicit long-lasting immune protection in a hHER2+ murine breast cancer model. This study provides insights into the efficacy of RC48 therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.

A CO2-responsive hydrogel film for optical sensing of dissolved CO2.

CO2-monitoring plays an important role in medicine, environmental sciences, and food industries. Here, a new CO2-responsive hydrogel film was fabricated from branched polyethyleneimine (BPEI) and partially oxidized dextran (PO-Dex) via layer-by-layer (LBL) assembly, based on the in situ Schiff base reaction between the two polymers. The swelling behaviours of the films were studied using Fabry-Perot fringes on their reflection spectra. Like ordinary hydrogels, the BPEI/PO-Dex films swell in water. In addition, they swell to a larger degree when CO2 is introduced, due to the reaction between CO2 and the amino groups in BPEI. The CO2-induced swelling can be reported by the shift of the Fabry-Perot fringes on their reflection spectra; therefore, the BPEI/PO-Dex film can be used as an optical sensor for dissolved CO2. In the new sensor, the BPEI/PO-Dex film acts as a CO2-sensing material and Fabry-Perot cavity simultaneously. The introduction of ordered structure is no longer required. The response of the sensor to CO2 is linear and reversible. Unlike other hydrogel-based sensors that suffer from a slow response, the new sensor can respond to CO2 quickly, making it applicable for real-time, continuous monitoring of CO2 levels in solution.

Improved recombinant protein production by regulation of transcription and protein transport in Chinese hamster ovary cells.

OBJECTIVES: To identify genes that affected protein expression in Chinese hamster ovary (CHO) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein. RESULTS: Here two sub-clones from a methotrexate-treated parental recombinant CHO cell line were selected. The two sub-clones, with different expression levels (qp were 42.8 pg/cell/day and 14.0 pg/cell/day), were analyzed through RNA-seq. More than 600 genes were identified as differently expressed, and we found that the differentially expressed genes were involved in processes such as RNA processing, transcription, protein catabolism, and protein transport. Among these, we cloned genes encoding proteins that were involved in transcription and protein transport to investigate their effect on protein production. CONCLUSIONS: We found that some genes involved in transcription and protein transport would improve recombinant protein production in CHO cells.

A preliminary study on the potential of Mycoplasma pneumoniae to induce dyskaryotic change in respiratory epithelium in adult community-acquired pneumonia.

BACKGROUND: This study aimed to explore the cellular morphology of respiratory epithelium in Mycoplasma pneumonia (MpP) patients. MATERIALS AND METHODS: The cast-off cell morphological findings from bronchoscopic brushings in MpP and community-acquired pneumonia (CAP) caused by typical pathogens were reviewed. RESULTS: Compared with the CAP group, cellular dysplasia in respiratory tract epithelial brushings was significantly greater in MpP patients (P = 0.033). CONCLUSION: Unique biological characteristics and mechanisms of pathogenesis of Mycoplasma pneumoniae (Mp) may result in dyskaryotic changes in respiratory epithelium in adult MpP.

Cu-N dopants boost electron transfer and photooxidation reactions of carbon dots.

The broadband light-absorption ability of carbon dots (CDs) has inspired their application in photocatalysis, however this has been impeded by poor electron transfer inside the CDs. Herein, we report the preparation of Cu-N-doped CDs (Cu-CDs) and investigate both the doping-promoted electron transfer and the performance of the CDs in photooxidation reactions. The Cu-N doping was achieved through a one-step pyrolytic synthesis of CDs with Na2 [Cu(EDTA)] as precursor. As confirmed by ESR, FTIR, and X-ray photoelectron spectroscopies, the Cu species chelates with the carbon matrix through Cu-N complexes. As a result of the Cu-N doping, the electron-accepting and -donating abilities were enhanced 2.5 and 1.5 times, and the electric conductivity was also increased to 171.8 µs cm(-1) . As a result of these enhanced properties, the photocatalytic efficiency of CDs in the photooxidation reaction of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate is improved 3.5-fold after CD doping.

Rapid production of HIV-1 neutralizing antibodies in baculovirus infected insect cells.

Broadly neutralizing antibodies have been shown promise as prophylactic and therapeutic agents to provide passive protection against human immunodeficiency virus type 1 (HIV-1) infection. Such protein based microbicides are traditionally produced using mammalian cell expression system, which is not able to satisfy the increasing demand of these proteins in large scale. In this report, two of HIV-1 broadly neutralizing antibodies, b12 and VRC01, were successfully expressed in Sf9 insect cells by co-infection with baculoviruses respectively expressing the light and heavy chain of the antibodies. The purified antibodies are fully assembled as H2L2 (two heavy chains plus two light chains) heterodimer linked by covalent bonds. The b12 and VRC01 generated from insect cells reacted well to HIV-1 gp120, and their antigen binding ability is comparable to the mammalian cell-derived b12 as determined by ELISA and flow cytometry. Our data suggest that baculovirus/insect cell expression system can be utilized as an alternative to the mammalian expression system for the rapid production of HIV-1 broadly neutralizing antibodies.

Novel Conversions of a Multifunctional, Bio-sourced Lactone Carboxylic Acid.

The plant-derived compounds furfuryl alcohol and itaconic anhydride are known to undergo a Diels-Alder reaction at room temperature and in bulk to efficiently give an alkene-containing lactone carboxylic acid. Reported here is the conversion of this substance to a variety of derivatives via hydrogenation, epoxidation, or halolactonization reactions. Most notable is the formation of a set of three related acrylate or methacrylate esters (see graphical abstract) produced by direct acylative ring opening of ether bonds using Sc(OTf)3 and (meth)acrylic anhydride. These esters are viewed as promising candidates for use as biorenewable monomers in reversible addition-fragmentation chain transfer (RAFT) polymerization reactions.

Probabilistic Regularized Extreme Learning for Robust Modeling of Traffic Flow Forecasting.

The adaptive neurofuzzy inference system (ANFIS) is a structured multioutput learning machine that has been successfully adopted in learning problems without noise or outliers. However, it does not work well for learning problems with noise or outliers. High-accuracy real-time forecasting of traffic flow is extremely difficult due to the effect of noise or outliers from complex traffic conditions. In this study, a novel probabilistic learning system, probabilistic regularized extreme learning machine combined with ANFIS (probabilistic R-ELANFIS), is proposed to capture the correlations among traffic flow data and, thereby, improve the accuracy of traffic flow forecasting. The new learning system adopts a fantastic objective function that minimizes both the mean and the variance of the model bias. The results from an experiment based on real-world traffic flow data showed that, compared with some kernel-based approaches, neural network approaches, and conventional ANFIS learning systems, the proposed probabilistic R-ELANFIS achieves competitive performance in terms of forecasting ability and generalizability.

Do visual and step height factors cause imbalance during bipedal and unipedal stances? A plantar pressure perspective.

Objective: The plantar pressure analysis technique was used to explore the static balance ability and stability of healthy adult males under the influence of visual and step height factors during bipedal and unipedal stances. Methods: Thirty healthy adult males volunteered for the study. Experiments used the F-scan plantar pressure analysis insoles to carry out with eyes open (EO) and eyes closed (EC) at four different step heights. The plantar pressure data were recorded for 10 s and pre-processed to derive kinematic and dynamic parameters. Results: For unipedal stance, most of kinematic parameters of the subjects' right and left feet were significantly greater when the eyes were closed compared to the EO condition and increased with step height. The differences in toe load between right and left feet, open and closed eyes were extremely statistically significant (p < 0.001). The differences in midfoot load between the EO and EC conditions were statistically significant (p = 0.024) and extremely statistically significant between the right and left feet (p < 0.001). The difference in rearfoot load between EO and EC conditions was extremely statistically significant (p < 0.001) and statistically significant (p = 0.002) between the right and left feet. For bipedal stance, most of kinematic parameters of the subjects' EO and EC conditions were statistically significant between the right and left feet and increased with step height. The overall load's difference between EO and EC states was statistically significant (p = 0.003) for both feet. The overall load's difference between the right and left feet was extremely statistically significant (p < 0.001) in the EC state. The differences between the right and left feet of the forefoot and rearfoot load with EO and EC suggested that the right foot had a smaller forefoot load, but a larger rearfoot load than the left foot (p < 0.001). The differences between the forefoot and rearfoot load of the subjects' both feet with EO and EC were extremely statistically significant (p < 0.001). Conclusion: Both visual input and step height factors, even the dominant foot, act on kinematic and dynamic parameters that affect the maintenance of static balance ability.

Discovery and characterization of Coturnix chinensis avian ß-defensin 10, with broad antibacterial activity.

A novel avian ß-defensin (AvBD), AvBD10, was discovered in the liver and bone marrow tissues from Chinese painted quail (Coturnix chinensis) in the present study. The complete nucleotide sequence of quail AvBD10 contains a 207-bp open reading frame that encodes 68 amino acids. The quail AvBD10 was expressed widely in all the tissues from quails except the tongue, crop, breast muscle, and thymus and was highly expressed in the bone marrow. In contrast to the expression pattern of AvBD10 in tissues from quail, the chicken AvBD10 was expressed in all 21 tissues from the layer hens investigated, with a high level of expression in the kidney, lung, liver, bone marrow, and Harderian glands. Recombinant glutathione S-transferase (GST)-tagged AvBD10s of both quail and chicken were produced and purified by expression of the two cDNAs in Escherichia coli, respectively. In addition, peptide according to the respective AvBD10s sequence was synthesized, named synthetic AvBD10s. As expected, both recombinant GST-tagged AvBD10s and synthetic AvBD10s of quail and chicken exhibited similar bactericidal properties against most bacteria, including Gram-positive and Gram-negative forms. However, no significant bactericidal activity was found for quail recombinant GST-tagged AvBD10 against Salmonella choleraesuis or for chicken recombinant GST-tagged AvBD10 against Proteus mirabilis.

SARS-CoV-2 infection of intestinal epithelia cells sensed by RIG-I and DHX-15 evokes innate immune response and immune cross-talk.

SARS-CoV-2 causes a spectrum of clinical symptoms from respiratory damage to gastrointestinal disorders. Intestinal infection of SARS-CoV-2 triggers immune response. However, the cellular mechanism that how SARS-CoV-2 initiates and induces intestinal immunity is not understood. Here, we exploited SARS-CoV-2-GFP/ΔN trVLP pseudo-virus system and demonstrated that RIG-I and DHX15 are required for sensing SARS-CoV-2 and inducing cellular immune response through MAVS signaling in intestinal epithelial cells (IECs) upon SARS-CoV-2 infection. NLRP6 also engages in the regulation of SARS-CoV-2 immunity by producing IL-18. Furthermore, primary cellular immune response provoked by SARS-CoV-2 in IECs further cascades activation of MAIT cells and produces cytotoxic cytokines including IFN-γ, granzyme B via an IL-18 dependent mechanism. These findings taken together unveil molecular basis of immune recognition in IECs in response to SARS-CoV-2, and provide insights that intestinal immune cross-talk with other immune cells triggers amplified immunity and probably contributes to immunopathogenesis of COVID-19.

Enantioselective phytotoxicity of the herbicide imazethapyr and its effect on rice physiology and gene transcription.

Imazethapyr (IM) is a chiral herbicide and a widely used racemic mixture. This report investigated the enantioselectivity between R- and S-IM in rice and explored its causative mechanism at the physiological and molecular levels. The results suggested that R-IM inhibited acetolactate synthase (ALS) activity to a greater extent than S-IM, which reduced the synthesis of branched-chain amino acids (BCAAs). Additionally, most other amino acids showed enantioselectivity. On the cellular level, R-IM showed stronger toxicity against protoplasts than S-IM. A gene transcription profile analysis showed that gene transcripts in many metabolic pathways, including amino acid metabolism, photosynthesis, starch and sugar metabolism, and the tricarboxylic acid cycle displayed enantioselectivity between the IM enantiomers. R-IM regulated more genes more strongly than S-IM. This study suggested that R-IM has stronger toxicity against plants than S-IM; this toxicity is caused not only by changing targeted enzyme activity and amino acid synthesis, but also by affecting gene transcription in other metabolic pathways directly or indirectly in an enantioselective manner.

Identification and characterization of an avian beta-defensin orthologue, avian beta-defensin 9, from quails.

In this study, a newly identified avian beta-defensin (AvBD) orthologue was isolated from Chinese painted quail (Coturnix chinensis) lung and bone marrow tissues. The complete nucleotide sequence of the gene contained a 204-bp open-reading frame encoding 67 amino acids. Homology, characterization, and comparison of the gene with AvBD from other avian species confirmed that it was quail AvBD9. To analyze and compare the expression pattern of AvBD9 in tissues from young and adult quails, layer hens, and broilers, reverse transcription polymerase chain reaction was performed using mRNA isolated from 21 different tissues. The AvBD9 expression pattern distribution was differed among quails of different ages, layer hens, and broilers. It was widely expressed in all the tissues except the trachea, liver, and kidney and was highly expressed in the lung and heart of young quails. Similarly, it was widely expressed in all the tissues of adult quails except for the liver, kidney, spleen, thymus, and Harderian gland. In layer hens, AvBD9 was widely expressed in all the tissues except the trachea, glandular stomach, and cecum. Similarly, it was widely expressed in all the tissues of broilers except for the trachea, glandular stomach, rectum, cecum, bone marrow, and cecal tonsil. Recombinant AvBD9 (rAvBD9) was produced and purified by expressing the gene in Escherichia coli. Additionally, peptide according to quail AvBD9 sequence was synthesized, named sAvBD9. As expected, both rAvBD9 and sAvBD9 exhibited strong bactericidal properties against 11 strains of bacteria, including Gram-positive and Gram-negative forms.

[Atypical pathogens in adult patients admitted with community-acquired pneumonia].

OBJECTIVE: To investigate the current status of atypical pathogen associated infections in community-acquired pneumonia (CAP) in adults, and their clinical attributes. METHODS: Clinical data, sputum specimens from acute phase, and paired sera from acute- and convalescent-phases of CAP in 153 adult patients were collected from May 2005 to May 2008 in multiple medical centers. Chlamydia pneumoniae (Cpn) IgG antibody, and Legionella pneumophila (LP) mixed IgG, IgA and IgM antibodies were determined by indirect immuno-fluorescent assay. Mycoplasma pneumoniae (Mpn) mixed IgG, IgA and IgM antibodies were determined by passive agglutination assay. All the sputum specimens were routinely cultured for bacterial isolation. RESULTS: Fifty-two (34%) out of the 153 cases were diagnosed as atypical CAP per the paired serum-antibody assay. Forty-seven of the 52 atypical CAP cases were infected by one atypical pathogen, 38 with Cpn, 4 with Mpn, and 5 with LP, while 5 out of the 52 atypical CAP cases were infected by 2 pathogens, Cpn and Mpnin 2, Cpn and LP in 3 cases. Eleven cases (21.2%) out of the 52 patients with atypical pneumonia were complicated with bacterial infection. Except peripheral white blood count was significant increased in the group of typical (bacterial only) pneumonia (WBC > 10 × 109)/L, P = 0.03), all the other clinical parameters did not show statistically significant difference between the typical and the atypical pneumonia groups. CONCLUSIONS: Our data suggest that Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are common pathogens of adult CAP. Chlamydia pneumoniae might be the most frequent atypical pathogen associated with atypical CAP.

Morphology Design of Co-electrospinning MnO-VN/C Nanofibers for Enhancing the Microwave Absorption Performances.

To enhance microwave loss abilities, constructing composites with one-dimensional (1D) structure is an excellent scheme. In this work, a high-efficiency microwave absorber of MnO nanograins decorated vanadium nitride/carbon nanofibers (MnO-VN/C NFs) was successfully prepared for the first time via co-electrospinning technology and subsequent nitriding treatment. Studying in detail the specific relationship between nitriding time and the morphology of the as-prepared NFs, the precipitations of MnO nanoparticles with tailored structures were attached on the surface of VN/C NFs to optimize their electromagnetic parameters. When the nitriding time was 2.0 h at 600 °C, the MnO-VN/C NFs displayed good microwave absorption performances: the minimum reflection loss (RL) value was -63.2 dB at 8.8 GHz, and the bandwidth of RL < -10 dB was up to 6.4 GHz from 11.6 to 18 GHz at the thickness of 2.8 mm. Meanwhile, the absorption bandwidth (RL< -10 dB) could cover the whole X and Ku band by adjusting the thickness, respectively. The outstanding performances could be attributed to the good impedance matching and various loss pathways including conductive loss and interfacial and dipole polarizations. In these regards, MnO-VN/C NFs are likely to be utilized as a high-efficiency microwave absorber. And the strategy in this work can provide great help to design other 1D structural microwave absorbers with a broader absorbing band.

Suppression of c-Met-Overexpressing Tumors by a Novel c-Met/CD3 Bispecific Antibody.

INTRODUCTION: Overexpression of c-Met, or hepatocyte growth factor (HGF) receptor, is commonly observed in tumor biopsies and often associated with poor patient survival, which makes HGF/c-Met pathway an attractive molecular target for cancer therapy. A number of antibody-based therapeutic strategies have been explored to block c-Met or HGF in cancers; however, clinical efficacy has been very limited, indicating that blockade of c-Met signal alone is not sufficient. Thus, an alternative approach is to develop an immunotherapy strategy for c-Met-overexpressing cancers. c-Met/CD3 bispecific antibody (BsAb) could bridge CD3-positive T lymphocytes and tumor cells to result in potent tumor cell killing. MATERIALS AND METHODS: A bispecific antibody, BS001, which binds both c-Met and CD3, was generated using a novel BsAb platform. Western blotting and T cells-mediated killing assays were utilized to evaluate the BsAb's effects on cell proliferation, survival and signal transduction in tumor cells. Subcutaneous tumor mouse models were used to analyze the in vivo anti-tumor effects of the bispecific antibody and its combination therapy with PD-L1 antibody. RESULTS: BS001 showed potent T-cell mediated tumor cells killing in vitro. Furthermore, BS001 inhibited phosphorylation of c-Met and downstream signal transduction in tumor cells. In A549 lung cancer xenograft model, BS001 inhibited tumor growth and increased the proportion of activated CD56+ tumor infiltrating lymphocytes. In vivo combination therapy of BS001 with Atezolizumab (an anti-programmed cell death protein1-ligand (PD-L1) antibody) showed more potent tumor inhibition than monotherapies. Similarly, in SKOV3 xenograft model, BS001 showed a significant efficacy in tumor growth inhibition and tumor recurrence was not observed in more than half of mice treated with a combination of BS001 and Pembrolizumab. CONCLUSION: c-Met/CD3 bispecific antibody BS001 exhibited potent anti-tumor activities in vitro and in vivo, which was achieved through two distinguished mechanisms: through antibody-mediated tumor cell killing by T cells and through inhibition of c-Met signal transduction.

Two novel duck antibacterial peptides, avian beta-defensins 9 and 10, with antimicrobial activity.

Two novel avian beta-defensins (AvBDs) isolated from duck liver were characterized and their homologies with other AvBDs were analyzed. They were shown to be duck AvBD9 and AvBD10. The mRNA expression of the two genes was analyzed in 17 different tissues from 1-28-dayold ducks. AvBD9 was differentially expressed in the tissues, with especially high levels of expression in liver, kidney, crop, and trachea, whereas AvBD10 was only expressed in the liver and kidney of ducks at all the ages investigated. We produced and purified GST-tagged recombinant AvBD9 and AvBD10 by expressing the two genes in Escherichia coli. Both recombinant proteins exhibited antimicrobial activity against several bacterial strains. The results revealed that both recombinant proteins retained their antimicrobial activities against Staphylococcus aureus under a range of different temperatures (-70 degrees C -100 degrees C) and pH values (pH 3-12).