Compound Z526 alleviates chemotherapy-induced cachectic muscle loss by ameliorating oxidative stress-driven protein metabolic imbalance and apoptosis.

Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.

Anti-diabetic effect of Ornithogalum caudatum Jacq. polysaccharides via the PI3K/Akt/GSK-3ß signaling pathway and regulation of gut microbiota.

This study evaluated the anti-diabetic effect of polysaccharides isolated from Ornithogalum caudatum and their underlying mechanisms. To achieve this, a type 2 diabetes mellitus mouse model was established using a combination of a high-fat diet and low-dose streptozotocin injection. The mice were treated with Ornithogalumcaudatum polysaccharides (OCPs) for 4 weeks. OCPs treatment significantly decreased body weight loss, fasting blood glucose levels, and plasma insulin levels in diabetic mice. Additionally, compared with the untreated group, OCPs treatment significantly decreased total cholesterol, triacylglycerol, and low-density lipoprotein-cholesterol levels, but increased those of high-density lipoprotein-cholesterol in diabetic mice. Moreover, antioxidant enzyme activity and histopathology results revealed that OCPs effectively alleviated oxidative stress and streptozotocin-induced lesions by increasing antioxidant enzyme activity. Results from mechanistic studies showed that OCPs treatment significantly increased the expression of p-PI3K, p-Akt, and p-GSK-3ß in the liver. Moreover, OCPs optimized the gut microbiota composition of diabetic mice by significantly decreasing the Firmicutes/Bacteroidetes ratio and increasing the levels of beneficial bacteria (Muribaculaceae_norank, Prevotellaceae_UCG-001 and Alloprevotella). Overall, these findings suggest that OCPs exert anti-diabetic effects by triggering the PI3K/Akt/GSK-3ß signaling pathway and regulating the gut microbiota.

Comparative Analysis of Metabolic Compositions and Trace Elements of Ornithogalum caudatum with Different Growth Years.

As a traditional medicine with extensive history, Ornithogalum caudatum has high nutritional and medicinal value. However, its quality evaluation criteria are insufficient because it is not included in the pharmacopeia. Simultaneously, it is a perennial plant, and the medicinal ingredients change with the growth years. Currently, studies on the synthesis and accumulation of metabolites and elements in O. caudatum during different growth years are unavailable. To address this issue, in this study, the 8 main active substances, metabolism profiles, and 12 trace elements of O. caudatum from different growth years (1, 3, and 5 years old) were analyzed. The main substances of O. caudatum changed significantly in different years of growth. Saponin and sterol contents increased with age; however, the polysaccharide content decreased. For metabolism profiling, ultrahigh-performance liquid chromatography tandem mass spectrometry was performed. Among the three groups, 156 differential metabolites with variable importance in projection values >1.0 and p < 0.05 were identified. Among the differential metabolites, 16 increased with increasing years of growth and have the potential to become age-identified markers. A trace element study showed that the contents of K, Ca, and Mg were higher, and the ratio of Zn/Cu was less than 0.1%. Heavy metal ions in O. caudatum did not increase with age. The results of this study provide a basis to evaluate the edible values of O. caudatum and facilitate further exploitation.

Association analysis for SNPs of LIPE and ITGB4 genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.

Comparison of 14 respiratory pathogens among hospitalized children during and after the COVID-19 outbreak in Chaoshan area.

BACKGROUND: Since January 2020, measures has been adopted in the Chaoshan area to limit the spread of COVID-19. Restrictions were removed after August 2020. At the same time, children returned to school. We previously reported the changes of 14 main respiratory pathogens in hospitalized children before and during the COVID-19 outbreak in Chaoshan area. However, the changes of respiratory pathogen spectrum in hospitalized children after the epidemic are still unknown, which will be elucidated in this study. METHODS: There are 6201 children hospitalized with respiratory tract infection were enrolled in the study, which were divided into two groups: 2533 from outbreak group (1 January 2020-31 December 2020), and 3668 from post-outbreak group (1 January 2021-31 December 2021). Pharyngeal swab samples were collected. 14 respiratory tract pathogens were detected by liquid chip technology. RESULTS: The positive rate of pathogen detection is significantly lower in the outbreak group (65.42%, 1657/2533) than that in the post-outbreak group (70.39%, 2582/3668; χ2 = 17.15, P < 0.05). The Influenza A virus (FluA) detection rate was 1.9% (49) in 2020, but 0% (0) in 2021. The detection rates of Bordetella pertussis (BP) decreased from 1.4% (35) in 2020 to 0.5% (17) in 2021. In contrast, the detection rates of  Influenza B virus (FluB), Cytomegalovirus (CMV), Haemophilus influenzae (HI), Streptococcus pneumoniae (SP) increased from 0.3% (8), 24.7% (626), 2.0% (50) and 19.4% (491) in 2020 to 3.3% (121), 27.9% (1025), 4.6% (169), 22.8% (836) in 2021, respectively (P < 0.01). CONCLUSIONS: The detection rates of pathogens such as FluA, FluB, CMV, HI, SP, BP were statistically different between 2020 and 2021. From 2020 to 2021, the positive rates of Flu, CMV, HI and SP increased, while the positive rates of FluA and BP decreased. After the COVID-19 prevention and control measures are gradually relaxed, the positive rate of respiratory pathogens in children aged from 6 months to 6 years will increase.

A Rapid Antimicrobial Resistance Diagnostic Platform for Staphylococcus aureus Using Recombinase Polymerase Amplification.

Antimicrobial resistance (AMR) has posed a global threat to public health. The Staphylococcus aureus strains have especially developed AMR to practically all antimicrobial medications. There is an unmet need for rapid and accurate detection of the S. aureus AMR. In this study, we developed two versions of recombinase polymerase amplification (RPA), the fluorescent signal monitoring and lateral flow dipstick, for detecting the clinically relevant AMR genes retained by S. aureus isolates and simultaneously identifying such isolates at the species level. The sensitivity and specificity were validated with clinical samples. Our results showed that this RPA tool was able to detect antibiotic resistance for all the 54 collected S. aureus isolates with high sensitivity, specificity, and accuracy (all higher than 92%). Moreover, results of the RPA tool are 100% consistent with that of PCR. In sum, we successfully developed a rapid and accurate AMR diagnostic platform for S. aureus. The RPA might be used as an effective diagnostic test in clinical microbiology laboratories to improve the design and application of antibiotic therapy. IMPORTANCE Staphylococcus aureus is a species of Staphylococcus and belongs to Gram-positive. Meanwhile, S. aureus remains one of the most common nosocomial and community-acquired infections, causing blood flow, skin, soft tissue, and lower respiratory tract infections. The identification of the particular nuc gene and the other eight genes of drug-resistant S. aureus can reliably and quickly diagnose the illness, allowing doctors to prescribe treatment regimens sooner. The detection target in this work is a particular gene of S. aureus, and a POCT is built to simultaneously recognize S. aureus and analyze genes representing four common antibiotic families. We developed and assessed a rapid and on-site diagnostic platform for the specific and sensitive detection of S. aureus. This method allows the determination of S. aureus infection and 10 different AMR genes representing four different families of antibiotics within 40 min. It was easily adaptable in low-resource circumstances and professional-lacking circumstances. It should be supported in overcoming the continuous difficulty of drug-resistant S. aureus infections, which is a shortage of diagnostic tools that can swiftly detect infectious bacteria and numerous antibiotic resistance indicators.

Association analysis for SNPs of KRT26 and TCHH genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Cashmere fineness is getting thicker, which is one of the key problems in cashmere breeding, however, there have been no systematic studies on the molecular regulation of cashmere fineness. The aim of this study was to investigate the relationship between KRT26 and TCHH gene polymorphism and production performance in Liaoning cashmere goats (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence alignment and PCR-Seq polymorphism of KRT26 and TCHH genes and analyzed the effect of SNPs on production performance by SPSS software. Two SNPs sites (A559T and A6839G) of two genes were detected. The AA genotype of KRT26 A559T locus was the dominant genotype. AG and GG at TCHH A6839G locus were the dominant genotypes. AAAA was the dominant haplotype combination. The results showed that KRT26 and TCHH genes were associated with cashmere fineness of LCG, and A559T (AA) and A6839G (GG) genotypes were the preferred marker genotypes for cashmere fineness, which provided more theoretical basis for further research on cashmere fineness.

Association analysis for SNPs of MSTN and IGFBP-3 genes with body size and other production traits in Liaoning Cashmere Goats.

Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.

Association analysis between reproduction genes INHA, PGR, RARG with lamb and other traits of Liaoning cashmere goats.

Reproductive traits have a high economic value in goat breeding, and increasing the number of lambs produced by ewes is of great importance to improve the production efficiency of goat farming. Lambing traits in goats are low heritability traits, but their genetic basis is ultimately determined by genes. This study aimed to investigate the relationship between INHA, RARG, and PGR gene polymorphisms and production performance, such as lambing, cashmere production, milk production, and body size in Liaoning cashmere goats. A total of six single nucleotide polymorphisms (SNPs) loci were identified in these three genes, G144A and T504C on the INHA gene, A56G, G144A, G490C on the RARG gene, and G109519T on the PGR gene. For lambing and cashmere production traits, the AA genotype of G144A on the INHA gene, TT on the T504C genotype, GG genotype of G144A on the INHA gene, A56G, G144A, and T504C on RARG and G109519T on PGR gene are dominant genotypes. AATT is a dominant haplotype combination. Allele G can be used as a molecular marker for lambing, cashmere, and milk production traits in Liaoning cashmere goats. Marker-assisted selection can be used for early selection to achieve improvement of genetic traits in Liaoning cashmere goats.

Association analysis for SNPs of BAAT and COL1A1 genes with cashmere production performance and other production traits in Liaoning cashmere goats.

This study aimed to investigate the relationship between the polymorphism of bile acid-CoA: amino acid N-acyltransferase (BAAT) and collagen type I alpha 1 chain (COL1A1) genes and the production performance of Liaoning Cashmere goat (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence comparison of BAAT and COL1A1 genes and PCR-Seq polymorphism, and the effect of SNPs on production performance was analyzed by SPSS software. The results showed that three SNPs loci were detected in BAAT gene: G7900A, T7967C, C7998T, and one SNP locus T6716C was detected in COL1AL gene. At G7900A locus, the dominant genotype for cashmere performance was GG, and the dominant genotype for body measurement traits and milk production traits was AG. At T7967C locus, the dominant genotype for cashmere performance was TT, and the dominant genotype for body measurement traits and milk production traits was CC. At C7998T locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. At the T6716C locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. H1H1: AACC is the dominant haplotype combination. Therefore, this study will provide a reliable reference for future research on cashmere production performance, body measurement traits, and milk production traits of LCG.

Long non­coding RNA NEAT1 promotes mouse granulosa cell proliferation and estradiol synthesis by sponging miR­874­3p.

It has been reported that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in follicular growth and multiple ovarian diseases, but not the physiological function of NEAT1 in mouse granulosa cells (mGCs). Therefore, the aim of the present study was to investigate the biological roles and regulatory mechanisms of NEAT1 in mGCs. The biological effects of NEAT1 on mGCs proliferation, apoptosis, production of 17ß-Estradiol (E2) and progesterone (P4) were investigated using MTS, flow cytometry and enzyme-linked immunosorbent assays, respectively. The association between NEAT1 and microRNA (miR)-874-3p was verified using luciferase reporter assay and RNA immunoprecipitation analysis. The results demonstrated that the knockdown of NEAT1 in mGC cells significantly promoted mGCs cell proliferation, inhibited apoptosis and increased the production of E2 and P4 in mGCs. The interference-mediated effect of NEAT1 on mGCs could be partially reversed by the downregulation of miR-874-3p. Overall, these results indicated that NEAT1 served as a competing endogenous RNA by competitively binding with miR-874-3p, thereby modulating mGCs proliferation and the production of E2 and P4 in mGCs.

Association between the cashmere production performance, milk production performance, and body size traits and polymorphism of COL6A5 and LOC102181374 genes in Liaoning cashmere goats.

The purpose of this study was to analyze the relationship between COL6A5 (collagen type VI alpha 5 chain) and LOC102181374 (alcohol dehydrogenase 1) genes and the production performance of Liaoning cashmere goats by single nucleotide polymorphism (SNP). We have searched for SNP loci of COL6A5 and LOC102181374 genes through sequence alignment and PCR experiments, and have used SPSS and SHEsis software to analyze production data. We obtained five SNP loci in total, including three SNP loci (G50985A, G51140T, G51175A) in COL6A5 gene and two SNP loci (A10067G, T10108C) in LOC102181374 gene. The genotypes G50985A (AG), G51140T (GT), G51175A (AA), A10067G (AA), and T10108C (CC) of these loci have certain advantages in improving the production performance of Liaoning cashmere goats. The haplotype combinations that can improve production performance in COL6A5 gene were H1H5:AGGGAG, H4H4:GGGGAA, and H4H4:GGGGAA. H3H3:GGCC and H2H4:AGTT were the dominant combinations in LOC102181374 gene. At G51175A and A10067G loci, we found that H1H2:AAAG and H1H3:AGAA have dominant effects. These results may provide some support for the molecular breeding of production traits in Liaoning cashmere goats.

Regulation of feather follicle development and Msx2 gene SNP degradation in Hungarian white goose.

BACKGROUND: Hungarian white goose has excellent down production performance and was introduced to China in 2010. The growth and development of feather follicles has an important impact on down production. Goose feather follicles can be divided into primary and secondary feather follicles, both of which originate in the embryonic stage. Msx2 (Msh Homeobox 2) plays a regulatory role in tissues and organs such as eyes, teeth, bones and skin. However, its regulatory mechanism on goose feather follicles development remains unclear. RESULTS: Msx2 gene first increased, then decreased and increased at the end (E13, E18, E23, E28) during embryonic feather follicle development, and the expression level was the highest at E18. The pEGFP-N1-Msx2 overexpression vector and si-Msx2 siRNA vector were constructed to transfect goose embryo dermal fibroblasts. The results showed that the cell viability of ov-Msx2 group was significantly increased, and the gene expression levels of FGF5 and TGF-ß1 genes were significantly down-regulated (P < 0.05), the expressions of PCNA, Bcl2, CDK1, FOXN1 and KGF genes were significantly up-regulated (P < 0.05). After transfection of siRNA vector, the cell viability of the si-Msx2 group was significantly decreased (P < 0.01) compared with the si-NC group. TGF-ß1 expression was significantly up-regulated (P < 0.05), FGF5 expression was extremely significantly up-regulated (P < 0.01), while PCNA, Bcl2, CDK1, FOXN1 and KGF gene expression was significantly down-regulated (P < 0.05). High-throughput sequencing technology was used to mine the exon SNPs of Msx2. A total of 11 SNP loci were screened, four of the SNPs located in exon 1 were missense mutations. The feather follicle diameter of the GC genotype at the G78C site is significantly larger than that of the other two genotypes. CONCLUSIONS: Msx2 maybe inhibit the apoptosis of goose dermal fibroblasts and promotes their proliferation. G78C can be used as a potential molecular marker for downy Variety.

Association analysis of single-nucleotide polymorphism in prolactin and its receptor with productive and body conformation traits in Liaoning cashmere goats.

The results of this study showed that the single-nucleotide polymorphism (SNP) sites of the PRL and PRLR genes have a certain association with the milk production performance, body size and cashmere performance of Liaoning cashmere goats (LCGs). Through our designed experiment, the potential SNPs of LCG were detected by sequence alignment, and two SNPs were found on two genes. The CC genotype of the PRL gene is the dominant genotype among the three genotypes. The GG genotype of the PRLR gene is the dominant genotype among the two genotypes. At the same time, the two genotypes also have good performance in cashmere production and body size. Through the screening of haplotype combination, the milk fat rate >  7.6 %, the milk protein rate >  5.6 %, the milk somatic cell number <  1500  × â€¯10 3  mL - 1 , the cashmere fineness <  15.75  µ m, the chest girth >  105 cm, the chest depth >  33 cm, and the waist height >  67.5 cm are considered as screening indexes for comprehensive production performance of Liaoning cashmere goats. It is concluded that the GCGC type is the dominant haplotype combination. According to our research data, we found that the biological indicators of Liaoning cashmere goat milk are higher than the national standards, so we think it is very significant to study the milk production performance of our experiment. Further research can be done on goat milk production and body conformation traits around PRL gene and PRLR gene.

Discovery of Meso-(meta-Pyridinium) BODIPY Photosensitizers: In Vitro and In Vivo Evaluations for Antimicrobial Photodynamic Therapy.

Antimicrobial photodynamic therapy (aPDT) has emerged as a novel and promising approach for the treatment of pathogenic microorganism infections. The efficacy of aPDT depends greatly on the behavior of the photosensitizer. Herein, we report the design, preparation, antimicrobial photodynamic activities, as well as structure-activity relationships of a series of photosensitizers modified at the meso position of a 1,3,5,7-tetramethyl BODIPY scaffold with various pyridinyl and pyridinium moieties. The photodynamic antimicrobial activities of all photosensitizers have been tested against Staphylococcus aureus, Escherichia coli, Candida albicans, and Methicillin-resistant S. aureus (MRSA). The methyl meso-(meta-pyridinium) BODIPY photosensitizer (3c) possessed the highest phototoxicity against these pathogens at minimal inhibitory concentrations (MIC) ranging from 0.63 to 1.25 µM with a light dose of 81 J/cm2. Furthermore, 3c exhibited an impressive antimicrobial efficacy in S. aureus-infected mice wounds. Taken together, these findings suggest that 3c is a promising candidate as the antimicrobial photosensitizer for combating pathogenic microorganism infections.

Discovery of a Monoiodo Aza-BODIPY Near-Infrared Photosensitizer: in vitro and in vivo Evaluation for Photodynamic Therapy.

Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other halogenated aza-BODIPY PSs. 4 and 15 as monoiodinated aza-BODIPY dyes containing p-methoxyphenyl moiety were identified to be potent NIR aza-BODIPY-type PSs with IC50 values against HeLa cells at a light dose of 54 J/cm2 as low as 76 and 81 nM, respectively. 4 possessed superior phototoxicity, low dark toxicity, and good thermal/photostability and distributed majorly in mitochondria in cells. Apoptosis was verified to be the main cell death pathway, and in vitro reactive oxygen species generation was demonstrated. In vivo whole-body fluorescence imaging and ex vivo organ distribution studies suggested that 4 afforded an excellent PDT effect with a low drug dose under single-time light irradiation and revealed advantages over known PSs of ADPM06 and Ce6.

Design, Synthesis and Biological Evaluation of Novel 1,2,5-Oxadiazol-3- Carboximidamide Derivatives as Indoleamine 2, 3-Dioxygenase 1 (IDO1) Inhibitors.

BACKGROUND AND OBJECTIVE: Indoleamine-2,3-dioxygenase 1 (IDO1), which catalyzes the degradation of L-tryptophan (L-Trp) to N-formyl kynurenine (NFK) in the first and rate-limiting step of Kynurenine (KYN) pathway has been identified as a promising therapeutic target for cancer immunotherapy. The small molecule Epacadostat developed by Incyte Corp is the most advanced IDO1 inhibitor in clinical trials. METHODS: In this study, various amidine derivatives were individually installed as the polar capping group onto the amino ethylene side chain to replace the sulfamoylamino moiety of Epacadostat to develop novel IDO1 inhibitors. A series of novel 1,2,5-oxadiazol-3-carboximidamide derivatives were designed, prepared, and evaluated for their inhibitory activities against human IDO1 enzyme and cellular IDO1. RESULTS: In vitro human IDO1 enzyme and cellular IDO1 assay results demonstrate that the inhibitory activities of compound 13a and 13b were comparable to Epacadostat, with the enzymatic IC50 values of 49.37nM and 52.12nM and cellular IC50 values of 12.34nM and 14.34nM, respectively. The anti-tumor efficacy of 13b is slightly better than Epacadosta in Lewis Lung Cancer (LLC) tumor-bearing mice model. CONCLUSION: 13b is a potent IDO1 inhibitor with therapeutic potential in tumor immunotherapy.

Anchoring BODIPY photosensitizers enable pan-microbial photoinactivation.

Photodynamic antimicrobial chemotherapy (PACT) is an effective strategy to inactivate pathogenic and resistant microbes. However, pan-microbial photoinactivation has hardly achieved. In this manuscript, we built anti-microbial PSs based on 2,6-diiodo-1,3,5,7-tetramethyl BODIPY (2I-BDP) using anchoring strategy through modifications on boron atom with bis-cationic moieties. With appropriate bis-cationic anchoring, we could achieve effective PACT for pan-microbial photoinactivation via straight forward modifications. Our studies suggested that integration of an efficient photosensitizer, good amphiphilicity, as well as tight interaction with microbial membrane could be essential for effective PACT.

Reply to Comment on "Water-Soluble Fluorescent Probe with Dual Mitochondria/Lysosome Targetability Superoxide Detection in Live Cells and in Zebrafish Embryos".

Recently, we published a paper on the detection of superoxide (O2•-) with a water-soluble fluorescent probe (ACS Sens. 2018, 3, 59-64), and Francesco Tampieri et al. provided comments on our publication, mostly on the detection medium (deionized water) we used. Herein we present our responses to the addressed questions to explain that although KO2 decomposes in aqueous environment, the results we obtained did not affect the general trend, since evidence from the literature afforded the correlation between KO2 in aqueous media as a surrogate of superoxide and enzymatically produced O2•- for the probes wherein the deprotection pathway operated. Moreover, fluorescence imaging on cells and zebrafish embryos under PMA stimulation confirmed the effectiveness of our probe to detect superoxide using KO2 as a convenient source. The detailed studies from Francesco Tampieri and coauthors are scientifically meaningful for the reliable evaluation of fluorescent probes using KO2 as a surrogate of superoxide.

Optical design of double-grating and double wave band spectrometers using a common CCD.

A new type of optical system comprising double-grating and double wave band spectrometers is designed for atmospheric detection. The optical system can bring oxygen A band (758-778 nm) and water vapor absorption band (758-880 nm) on a charge-coupled device (CCD) at the same time for ultrahigh resolution spectrum measurement. Each absorbed band with three observation directions of atmospheric radiation is imaged in different positions of a common CCD. The spectral resolution is less than 0.07 nm in oxygen A band (758-778 nm), and the spectral resolution is less than 0.28 nm in water vapor absorption band (758-880 nm). Three end faces of the optical fiber are on the slit plane for each wave band, and each end face corresponds to an observation angle. The optical fiber core diameter is 600 µm, the slit width is 25 µm, and the slit length is 18.4 mm. The principle of smile correction is analyzed. The smile of the Czerny-Turner double-grating spectrometer can be compensated by using the tilt field lens in front of the focal plane. The design results corroborate that the maximum smile of the double-grating spectrometer is 5 µm and that the approach of correcting smile is effective. The stray light is analyzed, and the approaches of suppressing the stray light are proposed.