Self-Catalyzed Synthesis of Length-Controlled One-Dimensional Nickel Oxide@N-Doped Porous Carbon Nanostructures from Metal Ion Modified Nitrogen Heterocycles for Efficient Lithium Storage.

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

Utilization of deep neuromuscular blockade combined with reduced abdominal pressure in laparoscopic radical gastrectomy for gastric cancer: An academic perspective.

BACKGROUND: Few studies have examined the specific efficacy of deep neuromuscular blockade (NMB) combined with pneumoperitoneal pressure reduction in laparoscopic radical gastrectomy (LRG) in the elderly. AIM: To investigate the application effect of deep neuromuscular blockade (NMB) combined with reduced pneumoperitoneum pressure in LRG for gastric cancer (GC) in elderly patients and its influence on inflammation. METHODS: Totally 103 elderly patients with GC treated in our hospital between January 2020 and January 2022 were retrospectively analyzed. Among them, 45 patients treated with surgery based on deep NMB and conventional pneumoperitoneum pressure were assigned to the control group, while the rest of the 58 patients who underwent surgery based on deep NMB and reduced pneumoperitoneum pressure were assigned to the observation group. The two groups were compared in the changes of the Leiden-surgical rating scale score, serum tumor necrosis fact-α (TNF-α) and interleukin 6 (IL-6) before and after therapy. The visual analogue scale (VAS) was adopted for evaluating the shoulder pain of patients at 8 h, 24 h and 48 h after the operation. The driving pressure of the two groups at different time points was also compared. Additionally, the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room, TOF% = 90% time and post-anesthetic recovery room (PACU) stay time were all recorded, and adverse PACU-associated respiratory events were also recorded. The postoperative hospitalization time and postoperative expenses of the two groups were counted and compared. RESULTS: No significant difference was found between the two groups at the time of skin incision, 60 minutes since the operation and abdominal closure after surgery (P > 0.05). The observation group exhibited significantly lower VAS scores than the control group at 24 and 48h after surgery (P < 0.05). Additionally, the observation group had significantly lower driving pressure than the control group at 5 min and 60 min after the establishment of pneumoperitoneum (P < 0.05). Additionally, the two groups were similar in terms of the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room and TOF% = 90% time (P > 0.05), and the observation group showed significantly lower TNF-α and IL-6 Levels than the control group at 24 h after therapy (P < 0.05). Moreover, the incidence of adverse events was not significantly different between the two groups (P > 0.05), and the observation group experienced significantly less hospitalization time and postoperative expenses than the control group (P < 0.05). CONCLUSION: Deep NMB combined with reduced pneumoperitoneum pressure can decrease the VAS score of shoulder pain and inflammatory reaction, without hindering the surgical vision and increasing adverse PACU-associated respiratory events, and can thus shorten the hospitalization time and treatment cost for patient.

In situ encapsulation of iron oxide nanoparticles into nitrogen-doped carbon nanotubes as anodic electrode materials of lithium ion batteries.

Fe-based oxides are considered as promising anode materials for lithium-ion batteries (LIBs) due to their high theoretical capacities, low cost, natural abundance and environmental friendliness. However, their severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, a hybrid of Fe2O3 nanoparticles encapsulated at the endpoints of nitrogen-doped CNTs (Fe2O3@NCNTs) is designed and prepared using a metal-catalyzed graphitization-nitridization driven tip-growth process and subsequent oxidation in air. When evaluated as an anode material for LIBs, this Fe2O3@NCNT hybrid exhibits a high capacity of 1145 mA h g-1 at 100 mA g-1, excellent rate capability of 907 mA h g-1 at 5.0 A g-1 and remarkable cycling stability of 856 mA h g-1 after 800 cycles at 1 A g-1, which are much superior to those of the Fe2O3/carbon black (CB) control material. The outstanding electrochemical performance benefits from the unique nanoarchitecture of Fe2O3@NCNTs, which provides a porous conductive matrix for effective electron-ion transport, and provides space confining carbon nanocaps as well as stress buffer nanocavities for robust structural stability during the lithiation/delithiation process. The results may pave the way for the rational structural design of high-performance metal oxide-based anode materials for next-generation LIBs.

Prognostic biomarker IL17A correlated with immune infiltrates in head and neck cancer.

BACKGROUND: The underlying functions and mechanisms of the Th17 pathway in Head and neck squamous cell carcinoma (HNSCC) progression and tumor immunology are still unclear. We investigated the correlation between IL17A expression and certain clinical parameters, tumor-infiltrating immune cells (TIICs) in TCGA HNSCC samples. METHODS: HNSCC files from the TCGA database were analyzed to obtain data on immune system infiltrates, gene expression, and related clinical information. R (Version 3.6.3) software, GEPIA, and TIMER online analysis tools were used to profile the relationship between the expression of IL17A and the prognosis, clinical stages, survival status and immune cell tumor-infiltrating levels of HNSCC patients. GEPIA and TIMER online analysis tools were used to verify the data. RESULTS: The expression of IL17A was significantly decreased in tumor tissues from HNSCC. IL17A expression was associated with M, N stage, lymphovascular invasion, and patients OS event. GSEA revealed that IL17A was closely related to humoral immune response, T cells response, and cytokine signal. TCGA database and TIMER online analysis indicated that the B cells and T cells levels were correlated with IL17A. The correlation between IL17A expression and correlated genes was analyzed. CONCLUSIONS: IL-17A plays a key role in HNSCC. The levels of IL17A are important values for the determination of the occurrence and development of the HNSCC. The IL17A and correlated genes may be potential immunotherapeutic targets for HNSCC.

Research Progress on Dipeptidyl Peptidase Family: Structure, Function and Xenobiotic Metabolism.

Prolyl-specific peptidases or proteases, including Dipeptidyl Peptidase 2, 4, 6, 8, 9, 10, Fibroblast Activation Protein, prolyl endopeptidase, and prolyl carboxypeptidase, belong to the dipeptidyl peptidase family. In human physiology and anatomy, they have homology amino acid sequences and similarities in the structure; however, they have distinct functions and play different roles. Some of them also play important roles in the metabolism of drugs containing endogenous peptides, xenobiotics containing peptides, and exogenous peptides. The major functions of these peptidases in both the metabolism of human health and bioactive peptides are of significant importance in the development of effective inhibitors to control the metabolism of endogenous bioactive peptides. The structural characteristics, distribution of tissue, endogenous substrates, and biological functions were summarized in this review. Furthermore, the xenobiotics metabolism of the dipeptidyl peptidase family is illustrated. All the evidence and information summarized in this review would be very useful for researchers to extend the understanding of the proteins of these families and offer advice and assistance in physiology and pathology studies.

Polysaccharides from Tetrastigma hemsleyanum Diels et Gilg: optimum extraction, monosaccharide compositions, and antioxidant activity.

The optimization of extraction of Tetrastigma hemsleyanum Diels et Gilg polysaccharides (THP) using ultrasonic with enzyme method and its monosaccharide compositions and antioxidant activity were investigated in this work. Single-factor experiments and response surface methodology (RSM) were performed to optimize conditions for extraction, and the independent variables were (XA) dosage of cellulase, (XB) extraction time, (XC) ultrasonic power, and (XD) ratio of water to the material. The extraction rate of THP was increased effectively under the optimum conditions, and the maximum (4.692 ± 0.059%) was well-matched the predicted value from RSM. THP was consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, while glucose was the dominant (26.749 ± 0.634%). According to the total antioxidant capacity assay with the FRAP method, DPPH, and hydroxyl radical scavenging assay, THP showed strong antioxidant activity with a dose-dependent behavior. The results indicated that THP has the potential to be a novel antioxidant and could expand its application in food and medicine.

Sensing and imaging of exosomal CD26 secreted from cancer cells and 3D colorectal tumor model using a novel near-infrared fluorogenic probe.

Cancer-derived exosomes or their specific components hold great promise for early diagnosis and precise staging of cancers. This work aimed to construct a novel enzyme-activatable fluorescent substrate for real-time detection and in situ imaging of a key exosomal surface protein CD26 in various biological systems, as well as to reveal the relevance of exosomal CD26 to the tumorigenesis. For these purposes, a group of Gly-Pro amides deriving from several near-infrared fluorophores were designed on the basis of the unique prolyl-cleaving dipeptidease activity of CD26, while molecular docking simulations were applied to assess the possibility of the designed amides as CD26 specific substrates. Following virtual screening and experimental validation, it was observed that GP-ACM displayed the best combination of high sensitivity and excellent specificity to CD26. The sensing and imaging ability of GP-ACM towards CD26 were examined in a range of biological systems, such as living cells, in situ tissues, and the exosomes secreted from cancer cells. Under physiological conditions, GP-ACM can be readily hydrolyzed by CD26 to release the fluorescent product ACM. The fluorescent product emits strong near-infrared fluorescence signals around 660 nm, which can be easily captured by the devices equipped with a fluorescence detector. GP-ACM prolyl-cleaving reaction shows excellent specificity and rapid response towards CD26, while its fluorescent product ACM displays good chemical stability and outstanding photostability. With the help of GP-ACM, CD26 in living cells, tissues and the tumor-secreted exosomes can be real-time monitored and in-situ imaged, while further investigations reveal that the exosomal CD26 activities are abnormally elevated with the progression of colon tumor. Collectively, the present study offers a practical optical assay for real-time monitoring CD26 activities in multiple complex biological systems including the exosomes secreted by tumor cells. The simplicity and effectiveness of this assay hold great potential for facilitating fundamental researches and clinical diagnosis of exosomal CD26 associated diseases.

Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications.

Tyrosinase (TYR, E.C. 1.14.18.1), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the ortho-hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR activity and their biomedical applications. The design strategies of various TYR substrates, alongside with several lists of all reported biochemical assays for sensing TYR including analytical conditions and kinetic parameters, are presented for the first time. Additionally, the biomedical applications and future perspectives of these optical assays are also highlighted. The information and knowledge presented in this review offer a group of practical and reliable assays and imaging tools for sensing TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases.

Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells.

Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids. In this study, we synthesized a series of pyrazolones and assayed their inhibitory effects against CES2 in vitro. Structure-activity relationship analysis of these pyrazolones reveals that the introduction of 4-methylphenyl unit (R1), 4-methylbenzyl (R2) and cyclohexyl (R3) moieties are beneficial for CES2 inhibition. Guided by these SARs results, 1-cyclohexyl-4-(4-methylbenzyl)-3-p-tolyl-1H- pyrazol-5(4H)-one (27) was designed and synthesized. Further investigations demonstrated that the compound 27 exhibited stronger CES2 inhibition activity with a lower IC50 value (0.13 µM). The inhibition kinetic study demonstrated that compound 27 inhibited the hydrolysis of CES2-fluorescein diacetate (FD) through non-competitive inhibition. In addition, the molecular docking showed that the core of pyrazolone, the cyclohexane moiety, 4-methylbenzyl and 4-methylphenyl groups in compound 27 all played important roles with the amino acid residues of CSE2. Also, compound 27 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. In brief, we designed and synthesized a novel pyrazolone compound with a strong inhibitory ability on CES2 and could inhibit the adipogenesis induced by mouse preadipocytes, which can be served as a promising lead compound for the development of more potent pyrazolone-type CES2 inhibitors, and also used as a potential tool for exploring the biological functions of CES2 in human being.

Effectiveness and safety of furazolidone-containing quadruple regimens in patients with Helicobacter pylori infection in real-world practice.

BACKGROUND & AIMS: The eradication rate of Helicobacter pylori (H pylori) has decreased largely because of the antibiotic resistance. We aimed to evaluate the effectiveness and safety of furazolidone-containing quadruple regimens for H pylori eradication. METHODS: This was an observational study of furazolidone-containing quadruple regimens for H pylori infection in real-world settings. Data sets were collected from the medical records and telephone interviews of patients referred to a specialist clinic for suspected H pylori reinfection from January 1, 2015, to January 1, 2018, at the First Affiliated Hospital of Nanchang University. Main outcome measures were the eradication rate and adverse reactions during medication. RESULTS: Among 584 patients with H pylori infection that met the inclusion criteria, 561 (96.1%) were treated for the first time, 19 (3.3%) had one, and 4 (0.5%) had two or more prior to furazolidone-containing quadruple regimens. The eradication rates for 10-day and 14-day regimens were 93.7% (95% CI: 91.5%-95.9%) vs 98.2% (95% CI: 95.6%-99.3%), respectively (P = 0.098). Adverse drug reactions occurred in 8.2% (48/584) with abdominal discomfort being the most common symptom. Overall adverse events with 10-day regimens were lower than 14-day regimens (6.1% vs 17.4%, P < 0.001). Logistic regression analysis indicated that poor adherence (adjusted odds ratio [AOR] = 46.5, 95% CI: 9.7-222.4) was correlated with failed eradication. Adverse drug reactions during medication were related to smoking and tobacco status, alcohol intake history, regimens combined with tetracycline, and poor adherence (all P < 0.05). CONCLUSIONS: Furazolidone-containing quadruple regimens proved both safe and highly effective in a real-world setting.

Identification and molecular characterization of a novel anti-lipopolysaccharide factor (ALF) from red swamp crayfish, Procambarus clarkii.

Anti-lipopolysaccharide factors are a group of small proteins with broad spectrum antiviral property and antibacterial activity. Herein, we obtained the genomic sequence of the Procambarus clarkii anti-lipopolysaccharide factor (PcALF) gene by using polymerase chain reaction to investigate its expression pattern in various tissues and in the immune tissues (Hepatopancreas) following exposure to pathogens. The deduced protein of PcALF was conserved; it displayed the signal peptides and putative lipo-polysaccharide binding domain, particularly the two conserved cysteine amino acid residues at both ends of the domain. The recombinant protein of PcALF was successfully expressed in Escherichia coli and rabbit anti-PcALF polyclonal antibodies were prepared. The qRT-PCR analysis showed unequal distribution of PcALF transcript in the examined tissues, however the transcript level was greatest in hepatopancreas. The challenge with peptidoglycan (PGN), lipo-polysaccharide (LPS) and Poly I:C significantly enhanced expression level of PcALF in hepatopancreas when compared with the PBS control. RNA interference of PcALF affected the mRNA expression levels of immune-related genes. Taken together, our data suggested that PcALF is an inducible protein and could play a key biological role in the innate immune defense of P. clarkii.

A novel copy number variation in CATSPER2 causes idiopathic male infertility with normal semen parameters.

STUDY QUESTION: Are genetic abnormalities in CATSPER (cation channel of sperm) genes associated with idiopathic male infertility with normal semen parameters and, if so, how do they affect male fertility? SUMMARY ANSWER: A novel copy number variation (CNV) in CATSPER2 causes idiopathic male infertility with normal semen parameters by disrupting the ability of sperm to penetrate viscous media, undergo hyperactivation and respond to progesterone. WHAT IS KNOWN ALREADY: CATSPER is the principle Ca2+ channel mediating extracellular Ca2+ influx into spermatozoa. Although several case reports have suggested a causal relationship between CATSPER disruption and human male infertility, whether genetic abnormalities in CATSPER genes are associated with idiopathic male infertility with normal semen parameters remains unclear. STUDY DESIGN, SIZE, DURATION: Spermatozoa were obtained from men attending the reproductive medical center at Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China between January 2014 and June 2016. In total, 120 men from infertile couples and 20 healthy male donors were selected to take part in the study, based on their normal semen parameters. PARTICIPANTS/MATERIALS, SETTING, METHODS: CATSPER and KSPER currents were assessed using the whole-cell patch-clamp technique. Whole-genome sequencing and TaqMan® CNV assays were performed to identify genetic variations. The expression levels of genes encoding the CATSPER complex were measured by quantitative real-time PCR and Western blot. Sperm motion characteristics and hyperactivation were examined with a computer-aided sperm analysis (CASA) system. Sperm responses to progesterone, assessed as increases in CATSPER current and intercellular Ca2+ concentrations ([Ca2+]i), as well as inducement of penetration ability and acrosome reaction, were examined by means of whole-cell patch-clamp technique, single-sperm [Ca2+]i imaging, penetration into methylcellulose assay and chlortetracycline staining, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: An infertile man with complete disruption of CATSPER current was identified. This individual has a novel CNV which disrupts one gene copy in the region 43894500-43950000 in chromosome 15 (GRCh37.p13 Primary Assembly, nsv3067119), containing the whole DNA sequence of CATSPER2. This CNV affected the expression of CATSPER2, resulting in dramatically reduced levels of CATSPER2 proteins in the individual's spermatozoa. Although this individual exhibited normal semen parameters, his spermatozoa showed impaired penetration ability, deficient hyperactivation, and did not respond to progesterone, in terms of monovalent current potentiation, [Ca2+]i increase, penetration ability enhancement and acrosome reaction inducement, which may explain the individual's idiopathic infertility. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our novel findings require more cases to support the CATSPER2 CNV identified in this study as a common cause of idiopathic male infertility in patients with normal semen parameters. Therefore, caution must be taken when extrapolating the use of this CNV as a potential biomarker for idiopathic male infertility. WIDER IMPLICATIONS OF THE FINDINGS: The findings from the unique human CATSPER 'knockout' model in this study not only confirm the essential roles of CATSPER in mediating progesterone response and regulating hyperactivation in human spermatozoa but also reveal that disruption of CATSPER current is a significant factor causing idiopathic male infertility. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by National Natural Science Foundation of China (81771644 and 31400996 to T.L.; 31230034 to X.Z.); National Basic Research Program of China (973 Program, 2015CB943003 to X.Z.); National Key Research and Development Program of China (2016YFC1000905 to T.L.); Natural Science Foundation of Jiangxi, China (20121BBG70021 and GJJ12015 to X.Z.; 20161BAB204167 and 20171ACB21006 to T.L.) and the open project of National Population and Family Planning Key Laboratory of Contraceptives and Devices Research (No. 2016KF07 to T.L.). The authors have no conflicts of interest to declare.

Liuwei Dihuang, a traditional Chinese medicinal formula, inhibits proliferation and migration of vascular smooth muscle cells via modulation of estrogen receptors.

The phenotypic modulation of vascular smooth muscle cells (VSMCs) serves an important role in atherosclerosis­induced vascular alterations, including vascular remodeling. However, the precise mechanisms underlying VSMC phenotypic modulation remain to be elucidated. Our previous study demonstrated that Liuwei Dihuang formula (LWDHF) could improve menopausal atherosclerosis by upregulating the expression of estrogen receptors (ERs). The present study examined the role of ERs in the effects of LWDHF on VSMC phenotypic modulation. VSMC proliferation and cell cycle progression were examined by MTT assay and flow cytometry, respectively. The expression levels of α­smooth muscle actin, osteopontin and ERs were determined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis. Cell ultrastructure was observed under an electron microscope. F­actin polymerization was detected by fluorescein isothiocyanate­phalloidin staining using fluorescence microscopy. A modified Boyden chamber assay was employed to assess VSMCs migration. Small interfering (si)RNA technology was used to examine the role of ERα in the effects of LWDHF on phenotypic modulation. The results indicated that LWDHF (3­12 µg/ml) inhibited proliferation and induced a cell cycle arrest in VSMCs treated with angiotensin II (Ang II; 100 nM) in a concentration­dependent manner. In addition, Ang II­stimulated migration of VSMCs and reorganization of actin were markedly inhibited by treatment with 12 µg/ml LWDHF. Results of RT­qPCR and western blotting demonstrated that LWDHF markedly stimulated transcription and expression of ERα and ERß, and inhibited VSMC synthetic phenotype. Furthermore, LWDHF­induced inhibition of phenotypic switching was partially suppressed by tamoxifen, and transfection with ERα siRNA markedly abolished the effects of LWDHF on VSMC phenotypic switching. In conclusion, these results revealed that ERα served an important role in LWDHF­induced regulation of the VSMC phenotype, including proliferation and migration.

Nickel Cobalt Sulfide Double-Shelled Hollow Nanospheres as Superior Bifunctional Electrocatalysts for Photovoltaics and Alkaline Hydrogen Evolution.

Transition metal chalcogenides with hollow nanostructures have been considered as promising substitutes as precious metal electrocatalysts for energy conversion and storage. We synthesized NiCo2S4 double-shelled ball-in-ball hollow spheres (BHSs) via a simple solvothermal route and applied them in both dye-sensitized solar cells (DSSCs) and hydrogen evolution reactions (HERs) at the same time, which were clean and sustainable ways to convert energy. Benefiting from their remarkable structure features and advantageous chemical compositions, NiCo2S4 BHSs composed of tiny crystals possessed large surface area, well-defined interior voids, and high catalytic activity. The DSSC with NiCo2S4 BHSs under 100 mW cm-2 irradiation possessed a power conversion efficiency of 9.49% (Pt, 8.30%). Besides, NiCo2S4 BHSs as a HER catalyst also possessed a small onset overpotential (27.9 mV) and a low overpotential (89.7 mV at 10 mA cm-2) under alkaline conditions. Therefore, this work offers a sensible strategy to synthesize bifunctional electrocatalysts for DSSCs and HERs.

An Optimized Two-Photon Fluorescent Probe for Biological Sensing and Imaging of Catechol-O-Methyltransferase.

A practical two-photon fluorescent probe was developed for highly sensitive and selective sensing of the activities of catechol-O-methyltransferase (COMT) in complex biological samples. To this end, a series of 3-substituted 7,8-dihydroxycoumarins were designed and synthesized. Among them, 3-BTD displayed the best combination of selectivity, sensitivity, reactivity, and fluorescence response following COMT-catalyzed 8-O-methylation. The newly developed two-photon fluorescent probe 3-BTD can be used for determining the activities of COMT in complex biological samples and bio-imaging of endogenous COMT in living cells and tissue slices with good cell permeability, low cytotoxicity, and high imaging resolution. All these findings suggest that 3-BTD holds great promise for developing therapeutic molecules that target COMT, as well as for exploring COMT-associated biological processes and its biological functions in living systems. Furthermore, the strategy also sheds new light on the development of fluorescent probes for other conjugative enzymes.

Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa.

STUDY QUESTION: Is diethylstilbestrol (DES), a prototypical endocrine-disrupting chemical (EDC), able to induce physiological changes in human spermatozoa and affect progesterone actions? SUMMARY ANSWER: DES promoted Ca2+ flux into human spermatozoa by activating the cation channel of sperm (CatSper) and suppressed progesterone-induced Ca2+ signaling, tyrosine phosphorylation and sperm functions. WHAT IS KNOWN ALREADY: DES significantly impairs the male reproductive system both in fetal and postnatal exposure. Although various EDCs affect human spermatozoa in a non-genomic manner, the effect of DES on human spermatozoa remains unknown. STUDY DESIGN, SIZE, DURATION: Sperm samples from normozoospermic donors were exposed in vitro to a range of DES concentrations with or without progesterone at 37°C in a 5% CO2 incubator to mimic the putative exposure to this toxicant in seminal plasma and the female reproductive tract fluids. The incubation time varied according to the experimental protocols. All experiments were repeated at least five times using different individual sperm samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human sperm intracellular calcium concentrations ([Ca2+]i) were monitored with a multimode plate reader following sperm loading with Ca2+ indicator Fluo-4 AM, and the whole-cell patch-clamp technique was performed to record CatSper and alkalinization-activated sperm K+ channel (KSper) currents. Sperm viability and motility parameters were assessed by an eosin-nigrosin staining kit and a computer-assisted semen analysis system, respectively. The ability of sperm to penetrate into viscous media was examined by penetration into 1% methylcellulose. The sperm acrosome reaction was measured using chlortetracycline staining. The level of tyrosine phosphorylation was determined by western blot assay. MAIN RESULTS AND THE ROLE OF CHANCE: DES exposure rapidly increased human sperm [Ca2+]i dose dependently and even at an environmentally relevant concentration (100 pM). The elevation of [Ca2+]i was derived from extracellular Ca2+ influx and mainly mediated by CatSper. Although DES did not affect sperm viability, motility, penetration into viscous media, tyrosine phosphorylation or the acrosome reaction, it suppressed progesterone-stimulated Ca2+ signaling and tyrosine phosphorylation. Consequently, DES (1-100 µM) significantly inhibited progesterone-induced human sperm penetration into viscous media and acrosome reaction. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Although DES has been shown to disturb progesterone actions on human spermatozoa, this study was performed in vitro, and caution must be taken when extrapolating the results in practical applications. WIDER IMPLICATIONS OF THE FINDINGS: The present study revealed that DES interfered with progesterone-stimulated Ca2+ signaling and tyrosine phosphorylation, ultimately inhibited progesterone-induced human sperm functions and, thereby, might impair sperm fertility. The non-genomic manner in which DES disturbs progesterone actions may be a potential mechanism for some estrogenic endocrine disruptors to affect human sperm function. STUDY FUNDING/COMPETING INTERESTS: National Natural Science Foundation of China (No. 31400996); Natural Science Foundation of Jiangxi, China (No. 20161BAB204167 and No. 20142BAB215050); open project of National Population and Family Planning Key Laboratory of Contraceptives and Devices Research (No. 2016KF07) to T. Luo; National Natural Science Foundation of China (No. 81300539) to L.P. Zheng. The authors have no conflicts of interest to declare.

A highly specific ratiometric two-photon fluorescent probe to detect dipeptidyl peptidase IV in plasma and living systems.

In this study, a highly specific ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized to monitor dipeptidyl peptidase IV in plasma and living systems. GP-BAN was designed on the basis of the catalytic properties and substrate preference of DPP-IV, and it could be readily hydrolyzed upon addition of DPP-IV under physiological conditions. Both reaction phenotyping and inhibition assays demonstrated that GP-BAN displayed good reactivity and high selectivity towards DPP-IV over other human serine hydrolases including FAP, DPP-VIII, and DPP-IX. The probe was successfully used to monitor the real activities of DPP-IV in complex biological systems including diluted plasma, while it could be used for high throughput screening of DPP-IV inhibitors by using human plasma or tissue preparations as enzyme sources. As a two-photon fluorescent probe, GP-BAN was also successfully used for two-photon imaging of endogenous DPP-IV in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue penetration ability. Taken together, a ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized for highly selective and sensitive detection of DPP-IV in complex biological systems, which could serve as a promising imaging tool to explore the biological functions and physiological roles of this key enzyme in living systems.

Morphology-Tuned Synthesis of Nickel Cobalt Selenides as Highly Efficient Pt-Free Counter Electrode Catalysts for Dye-Sensitized Solar Cells.

In this work, morphology-tuned ternary nickel cobalt selenides based on different Ni/Co molar ratios have been synthesized via a simple precursor conversion method and used as counter electrode (CE) materials for dye-sensitized solar cells (DSSCs). The experimental facts and mechanism analysis clarified the possible growth process of product. It can be found that the electrochemical performance and structures of ternary nickel cobalt selenides can be optimized by tuning the Ni/Co molar ratio. Benefiting from the unique morphology and tunable composition, among the as-prepared metal selenides, the electrochemical measurements showed that the ternary nickel cobalt selenides exhibited a more superior electrocatalytic activity in comparison with binary Ni and Co selenides. In particular, the three-dimensional dandelion-like Ni0.33Co0.67Se microspheres delivered much higher power conversion efficiency (9.01%) than that of Pt catalyst (8.30%) under AM 1.5G irradiation.

Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation.

Prevalence of axial symptoms after posterior cervical decompression: a meta-analysis.

PURPOSE: To investigate the prevalence of axial symptoms (AS) in patients following posterior cervical decompression. METHODS: We searched the PubMed, Embase, and Cochrane databases for relevant studies that reported the incidence of AS after posterior cervical decompression, and manually screened reference lists for additional studies. Relevant prevalence estimates were calculated. Subgroup analysis, sensitivity analysis and publication bias assessment were also performed. RESULTS: Our meta-analysis included 44 studies, with 893 AS cases in 2984 patients. The pooled AS prevalence was 28 % (95 % CI 24-32). The prevalence of AS was higher after expansive open-door laminoplasty (39 %) than after modified open-door laminoplasty (MOLP, 23 %) and laminectomy instrumented fusion (29 %). AS prevalence was also higher in those that wore a neck collar for 2-3 months (34 %) compared with 2 weeks (21 %). The lowest AS prevalence (9 %) was found in patients who underwent MOLP with C3 laminectomy and C7 spinous processes conserved. There was an intermediate AS prevalence after MOLP with C7 spinous processes conserved (16 %), MOLP with preservation of the unilateral posterior muscular-ligament complex (19 %), MOLP with C3 laminectomy (22 %), and MOLP with plate fixation (23 %). Prevalence of AS might be higher in patients <60 years and increased in populations with a higher proportion of females. CONCLUSIONS: Posterior cervical surgery carries a high risk of postoperative AS. Postoperative AS may be reduced through preserving posterior muscles and structures, stabilizing cervical vertebrae, and reducing external cervical immobilization time.