Genetic polymorphisms of BACH2, a key gene regulating Th2 immune response, increasing risk of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR. METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between 'SNP-SNP' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy. RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele 'A' of rs905670 (OR = 1.36, p = 0.018) and mutant allele 'G' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05). CONCLUSION: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.

First report of Stagonosporopsis pogostemonis causing root rot on Strawberry in China.

In Henan, strawberry cultivation occurs on approximately 10,000 hectares, with annual production approaching 230,000 tons. In April 2022, a root rot disease with a 10% incidence rate was observed on the strawberry cultivars 'Ningyu' and 'Sweet Charlie' grown in plastic greenhouses (0.7 ha) located in Xingyang (113.39°E, 34.79°N), Henan, China. Disease symptoms included yellowing of the outer mature leaves, stunted growth, and subsequent wilting of the entire plant. The roots developed dark brown spots, which gradually turned necrotic (Figures 1a, 1b). To determine the causal agent, four symptomatic plants (two plants per cultivar) were collected. Twelve symptomatic root tissues (three root tissue samples per plant) were surface sterilized with 75% ethanol and 0.1% mercuric chloride, washed thrice in sterile water, air dried, and then placed on PDA at 25°C for 3 days. Eight pure isolates were obtained by hyphal-tip isolation (Fang 2007). Each colony had a dark olivaceous green to brown, cottony appearance with a round margin, and the reverse side was grey-black near the center (Figure 1c). Conidia were ellipsoidal, aseptate, with rounded ends, and 3.1 to 4.8 µm × 1.0 to 2.5 µm in size (Figure 1d). Chlamydospores were ellipsoidal, pale brown, and 7.9 to 11.9 µm × 7.6 to 10.7 µm in size (Figure 1e). A representative fungus isolate, designated as Z5, was selected for further molecular identification. Genomic DNA was extracted from the mycelia of isolate Z5, and four gene partial regions (ITS, TUB2, RPB2, and LSU) were amplified using the primer pairs ITS1/ITS4, Bt-2a/Bt-2b, RPB2-5F/RPB2-7CR and LROR/LR5, respectively (White et al.1990, O'Donnell et al.1997, Reeb et al. 2004, Rehner and Samuels 1994). PCR products were sequenced and submitted to GenBank with the following accession numbers OQ130480 (ITS), OQ190093 (TUB2), OQ190092 (RPB2), and OQ255570 (LSU). BLASTn search revealed that the ITS, TUB2, RPB2, and LSU gene sequences of isolate Z5 showed 99.42% (513/516 bp), 99.69% (320/321 bp), 100% (1071/1071 bp), and 100% (857/857 bp) identity with those of ex-type S. pogostemonis stain ZHKUCC 21-0001 (Dong et al. 2021), respectively. A phylogenetic tree was constructed showing that Z5 clustered with S. pogostemonis (Figure 2). The isolates in this study were identified as S. pogostemonis based on morphological and molecular evidence. To confirm pathogenicity, five one-month-old 'Ningyu' cultivar strawberry seedlings were planted in sterilized nursery soil mixed with wheat grains (0.5% w/w) coated with Z5 mycelia (Fang 2007). An equal number of strawberry seedlings were placed in pots filled with non-infected potting mix to serve as controls. The seedlings were kept in a greenhouse under a 12 h light/dark photoperiod at 25°C. After two weeks, the inoculated seedlings displayed symptoms such as leaf wilting and root necrosis, similar to those observed in the greenhouses, while the control seedlings showed no symptoms (Figures 1f, 1g). The experiment was performed thrice. The identical fungus was re-isolated from the symptomatic roots and identified as S. pogostemonis based on morphological characteristics and molecular analysis, thus fulfilling Koch's postulates. This is the first report of S. pogostemonis causing root rot on strawberries worldwide. Our findings will contribute to a more comprehensive study on investigating and managing this disease.

Biocompatible formulation of a hydrophobic antimicrobial peptide L30 through nanotechnology principles and its potential role in mouse pneumonia model infected with Staphylococcus aureus.

Hydrophobic antimicrobial peptide L30, a potential antibiotic candidate, has poor water solubility and hemolytic activity. Herein, a biocompatible nano-formulation composed of liposomes and dendritic mesoporous silica encapsulation (LDMSNs@L30) was constructed for L30 to solve the limits for its clinical development. The characterization, antimicrobial activity and therapeutic effect of LDMSNs@L30 on Staphylococcus aureus 9 (cfr+) infected mice models were investigated. LDMSNs@L30 displayed a smooth, spherical, and monodisperse nanoparticle with a hydrodynamic diameter of 177.40 nm, an encapsulation rate of 56.13%, a loading efficiency of 32.26%, a release rate of 66.5%, and effective slow-release of L30. Compared with free L30, the formulation could significantly increase the solubility of L30 in PBS with the maximum concentration from 8 µg/mL to 2.25 mg/mL and decrease the hemolytic activity of hydrophobic peptide L30 with the HC5 from 65.36 µg/mL to more than 500 µg/mL. The nano delivery system LDMSNs@L30 also exhibited higher therapeutic effects on mice models infected with S. aureus 9 (cfr+) than those of free L30 after 7 days of treatment by reducing the lung inflammation and the inflammatory cytokines levels in plasma, showing better health score and pulmonary pathological improvement. Our research suggests that nano-formulation can be expected to be a promising strategy for peptide drugs in therapeutic applications.

A Novel Calibration Method of Line Structured Light Plane Using Spatial Geometry.

The line structured light plane calibration method using a plane target cannot produce satisfactory calibration results due to inaccurate positioning of the calibrated points. Field of view noise and sensor noise affect the target light stripe extraction and camera parameter calculation during the calibration process. These factors will cause the calculation of the coordinates of the calibrated point to deviate, and thus affect the light plane calibration. To solve this problem, we propose a new method to calculate the calibrated point based on spatial geometry. Firstly, for the projection line corresponding to the feature point on the light stripe and the corresponding line on the target, a common perpendicular of these two lines above is established, and since the sum of the squares of the distances from the midpoint to the two straight lines is the smallest, the midpoint of the common perpendicular is taken as the calibrated point. Secondly, the target is moved to different positions, and the non-collinear calibrated points are calculated. Finally, the parameters of the light plane are obtained by fitting these calibrated points. This method requires only a checkerboard target, and has a simple calibration process. The experimental results show that the average error of the calibration method proposed in this paper is 0.011 mm, which is less than the 0.031 mm of the calibration method based on the plane target with cross-ratio invariant.

Surface Modification with CuFeS2 Nanocrystals to Improve the Efficiency and Stability of Perovskite Solar Cells.

Poor stability retards the industrialization of perovskite solar cells (PSCs). One of the effective ways to solve this issue is to modify the perovskite surface to improve the efficiency and stability of the PSCs. Herein, we synthesized CuFeS2 nanocrystals and applied them to modify the perovskite surface. The efficiency of the PSCs with CuFeS2 modification is improved to 20.17% from 18.64% for the control devices. Some investigations demonstrate that the CuFeS2 modification passivates the perovskite surface defects and induces better energy band arrangement. Furthermore, the stability of the PSCs with CuFeS2 modification is improved compared with the devices without CuFeS2 modification. The efficiency of the PSCs with CuFeS2 modification maintains 93% of its initial value, whereas that of the devices without CuFeS2 modification decreases to 61% of the initial value. This work demonstrates that CuFeS2 is a novel material used as a modification layer to enhance the efficiency and stability of the PSCs.

Highly efficient and stable quasi two-dimensional perovskite solar cells via synergistic effect of dual additives.

Recently, quasi two-dimensional (Q-2D) perovskites with alternating cations in the interlayer space (ACI) have attracted more attentions owing to their elevated stability compared with three-dimensional (3D) analogs. While the efficiency of the devices derived from Q-2D perovskites is much smaller than that based on 3D perovskites. Here, we utilized urea and methoxyamine hydrochloride (MOAH) dual additives to acquire high quality Q-2D ACI perovskite GA(MA)5Pb5I16 (GA = guanidinium, MA = methylammonium) films. The efficiency of the perovskite solar cells (PSCs) derived from the Q-2D perovskite films induced by the synergistic effect of urea and MOAH dual additives increases to 20.32% from 17.21% for the devices without additive. This efficiency enhancement could be attributed to the enlarged grain size, improved crystallinity, optimized quantum well thickness distribution, and reduced trap states of the perovskite films. Moreover, the solar cells with dual additives present improved stability. The efficiency of devices with dual additives holds 95% of the original value after storage for 1600 h in ambient air. These results prove that the synergistic effect of urea and MOAH is an effective method to achieve highly efficient and stable Q-2D PSCs.

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results.

Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 108, 3.75 × 108 or 5.0 × 108 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.

Highly efficient and stable red perovskite quantum dots through encapsulation and sensitization of porous CaF2:Ce,Tb nanoarchitectures.

Lead halide perovskite quantum dots (PQDs) are extremely unstable when exposed to oxygen, water and heat, especially red CsPbBrxI3-x (x = 0, 0.5, 1.2) PQDs. This seriously hinders their practical application. Here, red CsPbBrxI3-x (x = 0, 0.5, 1.2) PQDs have been successfully encapsulated in porous CaF2:Ce,Tb hierarchical nanospheres (HNSs), which not only greatly improved the stability of PQDs, benefitting from the protection of the CaF2 shell, but also maintained the high photoluminescence quantum yield (PLQY) of PQDs, benefitting from the sensitization of Tb3+ ions. More importantly, porous CaF2:Ce,Tb nanoarchitectures can prevent aggregation quenching and anion exchange of PQDs. Therefore, the CaF2:Ce,Tb&CsPbBrxI3-x (x = 0, 0.5, 1.2) composite powder can have high PLQY comparable to that of the PQD powder. In view of this, CaF2:Ce,Tb&CsPbBr1.2I1.8 composite based red light-emitting diodes (LEDs) are prepared, and they are very suitable as a supplementary light source for plant lighting. Furthermore, white LEDs are also prepared by coating the CaF2:Ce,Tb&CsPbBr3 and CaF2:Ce,Tb&CsPbBr1.2I1.8 composite on a 450 nm chip. The optimum luminous efficiency is 61.2 lm W-1, and the color rendering index is 91, which are comparable to the current highest values. This shows that the composite composed of PQDs has great potential in LED lighting.

Prevalence of dyslipidemia and associated risk factors among adult residents of Shenmu City, China.

OBJECTIVE: Dyslipidemia is a leading risk factor for cardiovascular and cerebrovascular diseases. By collecting the blood lipid profiles among adult residents of Shenmu City in Shaanxi Province, China, we aim to assess and elucidate the prevalence and risk factors of dyslipidemia in this city. METHOD: Stratified multistage sampling was used to survey 4,598 permanent adult residents in five areas of Shenmu (2 communities in the county seat, 2 in the southern area and 2 in the northern area) from September 2019 to December 2019. Questionnaire surveys and physical examinations were conducted. Data were analyzed using SPSS software version 26.0. RESULTS: The average level of total cholesterol (TC) is 4.47mmol/L, that of triglyceride (TG) 1.32mmol/L, high-density lipoprotein cholesterol (HDL-C) 1.27mmol/L, apolipoprotein A1 (ApoA1) 1.44g/L, low-density lipoprotein cholesterol (LDL-C) 2.7mmol/L and apolipoprotein B (ApoB) 0.97g/L. The prevalence of hypercholesterolemia (HTC), hypertriglyceridemia (HTG), low high-density lipoprotein (HDL-C) and high low-density lipoprotein (LDL-C) is 22.4%, 33.3%, 14.5%, and 5.81%, respectively, and the overall prevalence of dyslipidemia is 48.27%. Furthermore, blood lipid levels and prevalence of dyslipidemia vary by region, age, gender, occupation and educational level. Nine risk factors of dyslipidemia were identified, which are living in county seat or northern industrial area, increasing age, male, overweight or obesity, abdominal obesity, smoking, hypertension, abnormal glucose metabolism (pre-diabetes or diabetes) and hyperuricemia. CONCLUSION: The blood lipid levels and dyslipidemia prevalence of adults in Shenmu City are higher comparing to national averages of China. Combining risk factors of dyslipidemia, early detection and public health interventions are necessary in high-risk population for associated cardiovascular and cerebrovascular diseases prevention.

High-Performance Perovskite Solar Cells Based on NaCsWO3@ NaYF4@NaYF4:Yb,Er Upconversion Nanoparticles.

Extending photoelectric response to the near-infrared (NIR) region using upconversion luminescent (UCL) materials is one promising approach to obtain high-efficiency perovskite solar cells (PSCs). However, challenges remain due to the shortage of highly efficient UCL materials and device structure. NaCsWO3 nanocrystals exhibit near-infrared absorption arising from the local surface plasmon resonance (LSPR) effect, which can be used to boost the UCL of rare-earth-doped upconversion nanoparticles (UCNPs). In this study, using NaCsWO3 as the LSPR center, NaCsWO3@NaYF4@NaYF4:Yb,Er nanoparticles were synthesized and the UCL intensity could be enhanced by more than 124 times when the amount of NaCsWO3 was 2.8 mmol %. Then, such efficient UCNPs were not only doped into the hole transport layer but also used to modify the perovskite film in PSCs, resulting in the highest power conversion efficiency (PCE) reaching 18.89% (that of the control device was 16.01% and the PCE improvement was 17.99%). Possible factors for the improvement of PSCs were studied and analyzed. It is found that UCNPs can broaden the response range of PSCs to the NIR region due to the LSPR-enhanced UCL and increase the visible light reabsorption of PSCs due to the scattering and reflection effect, which generate more photocurrent in PSCs. In addition, UCNPs modify the perovskite film by effectively filling the holes and gaps at the grain boundary and eliminating the perovskite surface defects, which lead to less carrier recombination and then effectively improve the performance of PSC devices.

Analysis of Prevalence and Risk Factors of Adult Self-Reported Allergic Rhinitis and Asthma in Plain Lands and Hilly Areas of Shenmu City, China.

Objective: The main aim of this study was to investigate the prevalence and risk factors of adult self-reported allergic rhinitis and asthma in plain lands and hilly areas of Shenmu City in China, and analyze the differences between regions. Methods: The multi-stage stratified random sampling was applied in a cross-sectional survey of adult residents in Shenmu City, from September to December 2019. The unconditional logistic regression analysis was used to screen the influence factors of allergic rhinitis and asthma. Results: 4,706 adults participated in the survey, and 99% (4,655 in 4,706) completed the questionnaires. The prevalence of allergic rhinitis was 25.4%, and the prevalence of asthma was 9.4%. The prevalence of the allergic rhinitis without asthma, asthma without allergic rhinitis, and the combined allergic rhinitis with asthma were 18.9, 2.9, and 6.5%, respectively. The prevalence of allergic rhinitis and asthma existed regional differences. The prevalence of adult self-reported allergic rhinitis was 41.5% in plain lands areas and 22.1% in hilly areas. The prevalence of adult self-reported asthma was 12.8% in plain lands and 8.8% in hilly areas. The prevalence of allergic rhinitis and asthma existed seasonal differences, with the highest prevalence from July to September. The analysis of risk factors showed that higher education [middle and high school (OR 1.72, 95%CI 1.42-2.07); college and above (OR 2.67, 95%CI 1.99-3.59)], comorbidities of other allergic diseases (OR 3.90, 95%CI 3.23-4.70), family history of allergies (OR 2.89, 95%CI 2.36-3.53), and plain lands areas (OR 2.51, 95%CI 2.06-3.05) were the risk factors for the allergic rhinitis without asthma. Aging [40-49 years old (OR 4.29, 95%CI 1.02-18.13); 50-59 years old (OR 5.89, 95%CI 1.40-24.76); ≥60 years old: (OR 6.14, 95%CI 1.41-26.71)], never-smokers (OR 1.66, 95%CI 0.99-2.80), comorbidities of other allergic disorders (OR 2.17, 95%CI 1.42-3.32), and family history of allergies (OR 2.20, 95%CI 1.40-3.47) were the risk factors for the asthma without allergic rhinitis. Advanced age [30-39 years (OR 2.16, 95%CI 1.23-3.82); 40-49 years (OR 2.86, 95%CI 1.56 to 5.25); 50-59 years (OR 2.95, 95%CI 1.58-5.51); ≥60 years old (OR 2.27, 95%CI 1.09-4.72)], higher education [middle and high school (OR 2.23, 95%CI 1.62-3.07); college and above (OR 4.28, 95%CI 2.72-6.74)], non-agricultural workers (OR 1.70, 95%CI 1.18-2.43),never-smokers (OR 2.26, 95%CI 1.51-3.39), comorbidities of other allergic diseases (OR 4.45, 95%CI 3.37-5.88), family history of allergies (OR 5.27, 95%CI 3.98-6.97), and plain lands areas (OR 2.07, 95%CI 1.51-2.86) were the risk factors for the combined allergic rhinitis with asthma. Conclusions: The prevalence of allergic rhinitis and asthma in Shenmu City was relatively high, with regional differences. Genetic and environmental factors were the important risk factors associated with allergic rhinitis and asthma. Our research would provide data support for preventing and controlling allergic rhinitis and asthma in this region in the future, and appropriate prevention and control programs should be formulated according to the characteristics of different regions.

Strong upconverting and downshifting emission of Mn2+ ions in a Yb,Tm:NaYF4@NaLuF4/Mn:CsPbCl3 core/shell heterostructure towards dual-model anti-counterfeiting.

Herein, a Yb,Tm:NaYF4@NaLuF4/Mn:CsPbCl3 quasi-core/shell heterostructure is synthesized with the assistance of silica. The strong upconverting and downshifting emission of Mn2+ ions was observed in the nanocomposite with a quasi-core/shell structure. The FRET process further improves the energy utilization efficiency of PQDs for UCNPs, which depends on the quasi-core/shell heterostructure. Considering the dual-model fluorescence emission behavior of Mn2+ ions, the stable Yb,Tm:NaYF4@NaLuF4/Mn:CsPbCl3 nanocomposite is used in anti-counterfeiting applications.

Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials.

PURPOSE: Our preclinical studies demonstrated the potential of chimeric antigen receptor (CAR)-glypican-3 (GPC3) T-cell therapy for hepatocellular carcinoma (HCC). We report herein the first published results of CAR-GPC3 T-cell therapy for HCC. PATIENTS AND METHODS: In two prospective phase I studies, adult patients with advanced GPC3+ HCC (Child-Pugh A) received autologous CAR-GPC3 T-cell therapy following cyclophosphamide- and fludarabine-induced lymphodepletion. The primary objective was to assess the treatment's safety. Adverse events were graded using the Common Terminology Criteria for Adverse Events (version 4.03). Tumor responses were evaluated using the RECIST (version 1.1). RESULTS: A total of 13 patients received a median of 19.9 × 108 CAR-GPC3 T cells by a data cutoff date of July 24, 2019. We observed pyrexia, decreased lymphocyte count, and cytokine release syndrome (CRS) in 13, 12, and nine patients, respectively. CRS (grade 1/2) was reversible in eight patients. One patient experienced grade 5 CRS. No patients had grade 3/4 neurotoxicity. The overall survival rates at 3 years, 1 year, and 6 months were 10.5%, 42.0%, and 50.3%, respectively, according to the Kaplan-Meier method. We confirmed two partial responses. One patient with sustained stable disease was alive after 44.2 months. CAR T-cell expansion tended to be positively associated with tumor response. CONCLUSIONS: This report demonstrated the initial safety profile of CAR-GPC3 T-cell therapy. We observed early signs of antitumor activity of CAR-GPC3 T cells in patients with advanced HCC.

Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation.

Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IR injury-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.

Ursodeoxycholic acid protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction through acting on ALDH1L2.

Mitochondrial dysfunction plays an important role in acute kidney injury (AKI). Thus, the agents improving the mitochondrial function could be beneficial for treating AKI. Ursodeoxycholic acid (UDCA) has been demonstrated to prevent mitochondrial dysfunction under pathology, however, its role in AKI and the underlying mechanism remain unknown. This study aimed to evaluate the effect of UDCA on cisplatin-induced AKI. In vivo, C57BL/6 J mice were treated with cisplatin (25 mg/kg) for 72 h to induce AKI through a single intraperitoneal (i.p.) injection with or without UDCA (60 mg/kg/day) administration by gavage. Renal function, mitochondrial function and oxidative stress were analyzed to evaluate kidney injury. In vitro, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cells (HK2) were treated with cisplatin with or without UDCA treatment for 24 h. Transcriptomic RNA-seq was preformed to analyze possible targets of UDCA. Our results showed that cisplatin-induced increments of serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C were significantly reduced by UDCA along with ameliorated renal tubular injury evidenced by improved renal histology and blocked upregulation of neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). Meanwhile, the apoptosis induced by cisplatin was also markedly attenuated by UDCA administration. In vitro, UDCA treatment protected against tubular cell apoptosis possibly through antagonizing mitochondrial dysfunction and oxidative stress by targeting ALDH1L2 which was screened out by an RNA-seq analysis. Knockout of ALDH1L2 by CRISPR/Cas9 greatly blunted the protective effects of UDCA in renal tubular cells. Moreover, UDCA did not diminish cisplatin's antineoplastic effect in human cancer cells. In all, our results demonstrated that UDCA protects against cisplatin-induced AKI through improving mitochondrial function through acting on the expression of ALDH1L2, suggesting a clinical potential of UDCA for the treatment of AKI.

Facile Synthesis of Methylammonium Lead Iodide Perovskite with Controllable Morphologies with Enhanced Luminescence Performance.

Organic-inorganic hybrid perovskites with well-defined morphology have attracted much attention due to their unique photophysical properties. However, controlling the morphology of nanocrystalline perovskite to improve its photoelectric application remains a challenge. In this article, using a modified solution deposition method, we successfully synthesized uniform methylammonium lead iodide (MAPbI3) nanoplates, nanocubes, and nanorods and investigated the effect of morphology on the photoelectric properties of these materials. We found that the morphology can be controlled by regulating the amounts of reactant methylammonium iodide (MAI) and the rate at which MAPbI3 precursor is added into toluene solution, and that the corresponding size distributions can be optimized by tuning the final vacuum-drying temperature. The morphology has an obvious effect on the bandgap optimization and fluorescence enhancement of MAPbI3, and the nanoplates exhibit stronger photoluminescence intensity and have a longer carrier lifetime than nanocubes and nanorods. The results show that the morphologies of MAPbI3 perovskite nanocrystals can be controlled by tuning the synthesizing conditions, and the MAPbI3 perovskite nanocrystals with special morphology can be used in special nanosize optoelectronic devices.

Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury.

BACKGROUND: Some researches revealed that mitochondrial dysfunction is associated with various kidney injury. However, the role of mitochondrial dysfunction in the pathogenesis of acute kidney injury (AKI) still needs evidence. METHODS: We evaluated the effect of mitochondrial complex I inhibitor rotenone on folic acid (FA)-induced AKI in mice. RESULTS: Strikingly, the mice pretreated with rotenone at a dose of 200 ppm in food showed exacerbated kidney injury as shown by higher levels of blood urea nitrogen and creatinine compared with FA alone group. Meanwhile, both renal tubular injury score and the expression of renal tubular injury marker neutrophil gelatinase-associated lipocalin were further elevated in rotenone-pretreated mice, suggesting the deteriorated renal tubular injury. Moreover, the decrements of mitochondrial DNA copy number and the expressions of mitochondrial Cytochrome c oxidase subunit 1, mitochondrial NADH dehydrogenase subunit 1, and mitochondria-specific superoxide dismutase (SOD2) in the kidneys of FA-treated mice were further reduced in rotenone-pretreated mice, indicating the aggravated mitochondrial damage. In parallel with the SOD2 reduction, the oxidative stress markers of malondialdehyde and HO-1 displayed greater increment in AKI mice with rotenone pretreatment in line with the deteriorated apoptotic response and inflammation. CONCLUSION: Our results suggested that the inhibition of mitochondrial complex I activity aggravated renal tubular injury, mitochondrial damage, oxidative stress, cell apoptosis, and inflammation in FA-induced AKI.

Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12.

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

Enhanced Performance of Perovskite Solar Cells by Using Ultrathin BaTiO3 Interface Modification.

Efficiency promotion has been severely constrained by charge recombination in perovskite solar cells (PSCs). Interface modification has been proved to be an effective way to reduce the interfacial charge recombination. In this work, a mesoporous TiO2 (mp-TiO2) layer was modified by an ultrathin BaTiO3 layer to suppress charge recombination in PSCs. The ultrathin BaTiO3 modification layer was prepared by the spin coating method using a barium salt solution. The concentration of the barium salt solution was optimized, and the effect of the BaTiO3 modification layer on the performance of the cells was also investigated. The modification layer can not only successfully retard charge recombination but also effectively boost the rate of electron extraction at the interface, resulting in enhanced open-circuit voltage ( Voc), short circuit current density ( Jsc), and fill factor. Furthermore, the hysteresis of the PSCs was also significantly reduced after the modification. By optimizing and employing the BaTiO3 modification layer, the power conversion efficiency of the cells was increased from 16.13 to 17.87%.

Selective Targeting of Glioblastoma with EGFRvIII/EGFR Bitargeted Chimeric Antigen Receptor T Cell.

The heterogeneous expression of EGFRvIII [variant III mutant of epidermal growth factor receptor (EGFR)] in glioblastoma has significant impact on the clinical response to the treatment of EGFRvIII-specific chimeric antigen receptor-engineered T (CAR T) cells. We hypothesized that CAR T cells that could target both EGFRvIII and the form of EGFR expressed on tumor cells, but not EGFR on normal cells, would greatly improve efficacy without inducing on-target, off-tumor toxicity. Therefore, we developed a humanized single-chain antibody, M27, with a single specificity that binds to an epitope found both on wild-type EGFR- and EGFRvIII-overexpressing tumor cells, but not EGFR-expressing normal cells, including primary keratinocytes, on which wild-type EGFR is highly expressed. M27-derived CAR T cells effectively lysed EGFRvIII- or EGFR-overexpressing tumor cells, but showed no observable toxicity on normal cells. Inclusion of the CD137 (4-1BB) costimulatory intracellular domain in the M27-28BBZ CAR provided CAR T cells with higher tumor lysis activity than when not included (as in the M27-28Z CAR). The growth of established EGFR- or EGFRvIII-overexpressing glioma xenografts was suppressed by M27-28BBZ CAR T cells as well. The growth of heterogeneic xenograft tumors, created by mixing EGFR- and EGFR-overexpressing glioblastoma cells, was also effectively inhibited by M27-28BBZ CAR T cells. The survival of mice in the orthotopic models was significantly prolonged after M27-28BBZ CAR T-cell infusion. These results suggested that tumor-selective, bitargeted anti-EGFR/EGFRvIII CAR T cells may be a promising modality for the treatment of patients with EGFR/EGFRvIII-overexpressing glioblastoma. Cancer Immunol Res; 6(11); 1314-26. ©2018 AACR.