Transition metal-free [3 + 3] annulation of cyclopropanols with ß-enamine esters to assemble nicotinate derivatives.

A metal-free and efficient approach for the synthesis of structurally important nicotinates through 4-HO-TEMPO-mediated [3 + 3] annulation of cyclopropanols with ß-enamine esters is presented. This protocol features high atom efficiency, green waste, simple operation and broad substrate scope. Moreover, the experiments of gram-scale synthesis and recovery of oxidants make this strategy more sustainable and practical.

Visual analysis of global air pollution impact research: a bibliometric review (1996-2022).

The impact of air pollution is one of the hotspots attracting continuous scholarly attention, but the comprehensive statistical and visual analysis reviews are few. Employing the method of bibliometric analysis, this paper took the relevant literature from 1996 to April 2022 on the Web of Science as the research object. Through the methods of keyword co-occurrence analysis and burst analysis, the spatiotemporal evolution trend, cooperation network, outstanding scholars, knowledge base, and research focus of air pollution impact research are visually presented. Via constructing a common word matrix of high-frequency words, clustering analysis is used to aggregate high-frequency keywords into 24 clusters. By the strategic coordinate analysis method, the relationships within and between clusters were revealed. The main findings include (1) research on the impact of air pollution mainly focusing on human health; (2) the six keywords with the highest centrality are California, hydrocarbons, dioxide, generation, Asia, and diesel; (3) these 11 clusters may be developed into future research hotspots: particulate matter, nitrogen oxides, mortality, ozone, pollution, air quality, asthma, children, epidemiology, aerosols, and polycyclic aromatic hydrocarbons; and (4) seven topics are research hot: daily mortality, long-term exposure, coronary heart disease, concentration, North China plain, traffic-related air pollution, and air pollution.

Efficacy and safety of early anticoagulation after endovascular treatment in patients with atrial fibrillation.

BACKGROUND: The timing for initiating anticoagulant therapy in acute ischaemic stroke (AIS) patients with atrial fibrillation who recanalised after endovascular treatment (EVT) is unclear. The objective of this study was to evaluate the effect of early anticoagulation after successful recanalisation in AIS patients with atrial fibrillation. METHODS: Patients with anterior circulation large vessel occlusion and atrial fibrillation who were successfully recanalised by EVT within 24 hours after stroke in the Registration Study for Critical Care of Acute Ischemic Stroke after Recanalization registry were analysed. Early anticoagulation was defined as the initiation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) within 72 hours after EVT. Ultra-early anticoagulation was defined if it was initiated within 24 hours. The primary efficacy outcome was the score on the modified Rankin Scale (mRS) at day 90, and the primary safety outcome was symptomatic intracranial haemorrhage within 90 days. RESULTS: Overall, 257 patients were enrolled, of whom 141 (54.9%) initiated anticoagulation within 72 hours after EVT, including 111 within 24 hours. A significant shift towards better mRS scores at day 90 was associated with early anticoagulation (adjusted common OR 2.08 (95% CI 1.27 to 3.41)). Symptomatic intracranial haemorrhage was comparable between patients treated with early and routine anticoagulation (adjusted OR 0.20 (95% CI 0.02 to 2.18)). Comparison of different early anticoagulation regimens showed that ultra-early anticoagulation was more significantly associated with favourable functional outcomes (adjusted common OR 2.03 (95% CI 1.20 to 3.44)) and reduced the incidence of asymptomatic intracranial haemorrhage (OR 0.37 (95% CI 0.14 to 0.94)). CONCLUSIONS: In AIS patients with atrial fibrillation, early anticoagulation with UFH or LMWH after successful recanalisation is associated with favourable functional outcomes without increasing the risk of symptomatic intracranial haemorrhages. TRIAL REGISTRATION NUMBER: ChiCTR1900022154.

[Effect of electroacupuncture on the expressions of TRPV1, P2X3 receptors in bladder of rats with interstitial cystitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL 32) and "Huiyang" (BL 35) on the pain, urodynamic and the expressions of transient receptor poteintial vanilloid 1 (TRPV1) and P2X3 receptors in bladder of rats with interstitial bladder (IC), and to explore the possible mechanism on EA for IC. METHODS: A total of 24 Wistar female rats were randomly divided into a blank group, a model group and an EA group, 8 rats in each group. In the model group and the EA group, IC model was established by intraperitoneal injection of cyclophosphamide by 150 mg/kg at once. EA was applied at "Ciliao" (BL 32) and "Huiyang" (BL 35) in the EA group for 20 min, with continuous wave, 30 Hz in frequency, once a day for 3 consecutive days. Mechanical pain threshold of bladder and urodynamic indexes (first urination time, bladder effective volume and urination pressure) were observed after model establishment and after intervention, the expressions of TRPV1 and P2X3 receptors in the bladder were detected by Western blot. RESULTS: After model establishment, the mechanical pain threshold of bladder was decreased in the model group and the EA group compared with that in the blank group (P<0.01). After intervention, the mechanical pain threshold of bladder in the model group was lower than the blank group (P<0.01), and that in the EA group was higher than the model group (P<0.01). The urodynamic of the rats in the blank group was normal, obvious abnormal contraction during the filling period of bladder was found in the rats of the model group, while no abnormal contraction during the filling period was found in the rats of the EA group. After model establishment, in the model group and the EA group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.01). After intervention, in the model group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.05); in the EA group, the first urination time was later than the model group (P<0.05), while bladder effective volume and urination pressure were higher than the model group (P<0.05). Compared with the blank group, the protein expressions of TRPV1 and P2X3 receptors in bladder were up-regulated in the model group (P<0.01); compared with the model group, the protein expressions of TRPV1 and P2X3 receptors in bladder were down-regulated in the EA group (P<0.05). CONCLUSION: EA can relieve bladder pain and improve urodynamic in IC rats. The mechanism may be related to the down-regulation on the expressions of TRPV1 and P2X3 receptors and the further inhibition on the abnormal input of bladder signal.

Effects of Electroacupuncture with Different Waveforms on Chronic Prostatitis/Chronic Pelvic Pain Syndromes: A Randomized Controlled Trial.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in adult men. Evidence has demonstrated that acupuncture is effective for treating CP/CPPS. Electroacupuncture (EA) is a combination of traditional acupuncture and electrical stimulation, and the waveform is one of the key factors influencing EA effects. Different waveforms contain different stimulating parameters, thus generating different effects. However, the effects of different waveforms of EA on CP/CPPS remain unclear and there is no recommended standard for the application of EA waveforms. At the same time, the waveform prescription of CP/CPPS is also different, so exploring the influence of different waveforms on CP/CPPS patients will also provide a certain treatment basis for clinical treatment. A total of 108 eligible patients were recruited from the Seventh People's Hospital affiliated to the Shanghai University of Traditional Chinese Medicine from March 18, 2021, to January 31, 2022, according to inclusion and exclusion criteria. All subjects were randomly divided into three groups (continuous wave 4 Hz, continuous wave 20 Hz, and extended wave 4/20 Hz) in a ratio of 1 : 1 : 1. Patients in all three groups were treated for the same duration of 20 minutes, with intervention twice a week for 4 weeks. The changes in chronic prostatitis index (NIH-CPSI), erectile function index 5 (IIEF-5), Hospital Anxiety and Depression Scale (HADS), and NIH-CPSI response rate in three groups were compared after the intervention, and the occurrence of adverse events in patients during treatment was observed. After 4 weeks of treatment, the CP/CPPS response rates were 66.7%, 62.5%, and 88.2% in the 4 Hz, 20 Hz, and 4/20 Hz groups, respectively. The reaction rate of CP / CPPS in 4 / 20 Hz group was higher than that in 4 Hz group and 20 Hz group. (P < 0.05). During treatment, the difference between NIH-CPSI scores between 4 Hz and 4/20 Hz was insignificant (P > 0.05). NIH-CPSI scores were lower in the 4/20 Hz group than in the 4 Hz and 20 Hz groups (P < 0.05). After treatment, there was no significant difference in the pain and discomfort subscales (P > 0.05) between the 4 Hz and 20 Hz groups and there were significantly lower pain and discomfort scores in the 4/20 Hz group (P < 0.05) compared to the 4 Hz and 20 Hz groups. There was no significant difference in the reduction of urination symptoms and quality of life among the three groups (P > 0.05). Compared with before treatment, IIEF-5 scores of the three groups were improved (P < 0.05). After treatment, there was no significant difference between the IIEF-5 scores in 4 Hz and 20 Hz (P > 0.05), while the IIEF-5 score in 4/20 Hz was significantly higher than that in 4 Hz and 20 Hz, and the change was significant (P < 0.05). The HADS scores decreased in all the three groups (P < 0.05), but there was no significant difference in HADS scores between the three groups (P > 0.05). Adverse events were mild and transient, and no serious adverse events occurred in each group. Both the expansive and continuous waveforms of EA can effectively alleviate symptoms such as prostatitis, erectile dysfunction, anxiety, and depression in patients with CP/CPPS. Expansion waves are superior to continuous waves in improving erectile function and pain symptoms in chronic prostatitis and can be used as a preferred waveform for the treatment of CP/CPPS. Trial Registration. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2100044418.

Synergistic surface oxygen defect and bulk Ti3+ defect engineering on SrTiO3 for enhancing photocatalytic overall water splitting.

SrTiO3 as a photocatalytic overall water splitting material has received extensive attention in recent years, while effectively suppressing Ti3+ is the key to enhancing the photocatalytic performance. Herein, a polymerizable complexation method is employed to enable Al3+ uniformly enter into SrTiO3 lattice for reducing Ti3+, and substituting Ti4+ with the formation of oxygen vacancy. Thus, the photogenerated carrier transport is promoted, and the resulting appropriate surface oxygen vacancy is also conducive to the adsorption of water molecules and OH*. The optimized 2% Al3+-doped SrTiO3 possesses a lower Ti3+ concentration, compared with the same sample prepared by the solid-phase griding method. Consequently, 2% Al-STO sample deposited co-catalysts achieves the highest activity and durability with the H2 and O2 evolution rates of 1.256 mmol·h-1 and 0.692 mmol·h-1 (0.04 g catalyst), respectively, corresponding to the AQE value of 55.46% at 365 nm. The characterizations and DFT calculation results reveal that the uniform Al3+ doping promotes the increase in the surface oxygen vacancy, which is beneficial for accelerating the reduction reaction and facilitating carrier separation and migration, therefore enhancing the overall water splitting reaction.

Enhancement of metal ion-induced hole transfer on the water oxidation performance of a BiVO4 photoanode.

Appropriate metal ions can act as transport media for enhancing the water oxidation of a BiVO4 photoanode by balancing the hole transfer and consumption in a reaction.

The Importance of Tumor Necrosis Factor-α-Induced Protein-8 Like-2 in the Pathogenesis of Cervical Cancer and Preeclampsia via Regulation of Cell Invasion.

Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) as a novel negative immune regulator plays an important role in several human diseases. However, its influences in cervical cancer and preeclampsia (PE) remain unclear. This study aims to explore the important role of TIPE2 in cervical cancer and PE via regulating cell invasion. TIPE2 expression in the cervical cancer tissues or the placenta of PE patients was detected. Human cervical cancer cell lines and trophoblasts were transfected with adenovirus expressing human TIPE2 and green fluorescent protein (GFP) (Ad-TIPE2), or the control adenovirus expressing GFP (Ad-GFP). Xenograft models were also constructed on nude mice, aiming to clarify how TIPE2 affects in vivo growth of cervical cancer cells. TIPE2 was down-regulated in the tumor tissues or placenta of patients with cervical cancer or PE. As a result, CaSKi and Hela cells in the Ad-TIPE2 group had decreased migration and invasion, with significant up-regulations of TIPE2 and E-cadherin, but down-regulations of ß-catenin and N-cadherin. Ad-TIPE2 decreased the volume and weight of xenograft tumors in the nude mice, with the down-regulation of Ki67. The quantity of cells (HTR8/SVneo and JEG3 cells) transfected with Ad-TIPE2 had increased, with up-regulations of TIPE2, matrix metalloproteinase (MMP)-2 and MMP-9. TIPE2 overexpression could reduce the invasion and migration of cervical cancer cells via inhibiting the epithelial-mesenchymal transition (EMT) process, and promote trophocyte invasion via upregulating the expression of MMPs, and it may be used as a potential therapeutic target for cervical cancer and PE.

Sequential Catalytic Annulations: Divergent Synthesis of Heterocycles through a Radical [1,4]-Oxygen Shift.

A radical [1,4]-oxygen-atom transfer has been realized by the reaction of linear alkyne-tethered ketoximes and ethynylbenziodoxolones (EBX) under sequential catalytic conditions. Mechanism studies indicate that the O atom transfer experiences a cascade O atom radical cyclization/alkynylation/N-O bond photocleavage and subsequent N,O-diradical rearrangement. By the diversification of catalytic sequences, a series of structurally important 3H-pyrrol-3-ones and chlorinated furo[3,2-b]pyrroles are divergently synthesized along with an O atom shift under the catalysis of Cu/Ir photosensitization and Cu/Ir photosensitization/AlCl3, respectively.

[Role of innate immunity in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome: Advances in studies].

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in men, which has a high incidence and seriously affects the quality of life of the patients. The possible pathogenic factors of the disease include urine reflux, hidden infection, central sensitization, oxidative stress, and abnormal immune response, among which abnormal immune response plays a significant role in its development and progression. Immune response involves innate immunity and adaptive immunity, and most previous studies focused on adaptive immunity. In recent years, more and more attention has been paid to the role of the innate immune system in the pathogenesis of CP/CPPS. Studies show that mast cells, macrophages, Toll-like receptors and related cytokines in the innate immune system are all involved in the development and progression of CP/CPPS. As the innate immune system is the first barrier of the immune response of the body, studies on innate immunity will provide some new ideas for the diagnosis and treatment of CP/CPPS.

The Second Chromosome Promotes the Adaptation of the Genus Flammeovirga to Complex Environments.

Approximately 10% of bacterial strains contain more than one chromosome; however, in contrast to the primary chromosomes, the mechanisms underlying the formation of the second chromosomes and the significance of their existence remain unclear. Species of the genus Flammeovirga are typical polysaccharide-degrading bacteria, and herein, we report complete genome maps of this genus. These genomes all had multireplicons and second chromosomes. The second chromosome, much larger than plasmids and even megaplasmids, had rRNA and a disparity of 1% relative to the main chromosome in guanine-cytosine (GC) content. The largest chromosomes carried core genes for cellular processes, while the second chromosomes were enriched with genes involved in the transport and metabolism of inorganic ions and carbohydrates, particularly genes encoding glycoside hydrolases and polysaccharide lyases, which constituted the genetic basis for the strains' excellent capabilities to utilize polysaccharides. The second chromosomal evolution had a higher mutation rate than the primary chromosomes. Furthermore, the second chromosomes were also enriched in horizontal transfer genes and duplicated genes. The primary chromosomes were more evolutionarily conserved, while the second chromosomes were more plastic, which might be related to their different roles in the bacterial survival process. This study can be used as an example to explain possible formation mechanisms and functions of the second chromosomes, providing a reference for peer research on the second chromosomes. In particular, the second chromosomes were enriched in polysaccharide-degrading enzymes, which will provide theoretical support for using genomic data to mine tool-type carbohydrase resources. IMPORTANCE For decades, the typical bacterial genome has been thought to contain a single chromosome and a few small plasmids carrying nonessential genes. However, an increasing number of secondary chromosomes have been identified in various bacteria (e.g., plant symbiotic bacteria and human pathogens). This study reported three complete genomes of the polysaccharide-degrading marine bacterial genus Flammeovirga, revealed that they harbor two chromosomes, and further identified that the presence of a multireplicon system is a characteristic of complete Flammeovirga genomes. These sequences will add to our knowledge on secondary chromosomes, especially within Bacteroidetes. This study indicated that the second chromosomes of the genus Flammeovirga initially originated from an ancestral plasmid and subsequently expanded by gene duplication or by obtaining heterologous genes with functions, thus promoting host strains to adapt to complex living environments (e.g., to degrade more diverse polysaccharides from marine environments). These findings will promote the understanding of the evolution and function of bacteria with multireplicon systems.

Comparison of Biochemical Characteristics, Action Models, and Enzymatic Mechanisms of a Novel Exolytic and Two Endolytic Lyases with Mannuronate Preference.

Recent explorations of tool-like alginate lyases have been focused on their oligosaccharide-yielding properties and corresponding mechanisms, whereas most were reported as endo-type with α-L-guluronate (G) preference. Less is known about the ß-D-mannuronate (M) preference, whose commercial production and enzyme application is limited. In this study, we elucidated Aly6 of Flammeovirga sp. strain MY04 as a novel M-preferred exolytic bifunctional lyase and compared it with AlgLs of Pseudomonas aeruginosa (Pae-AlgL) and Azotobacter vinelandii (Avi-AlgL), two typical M-specific endolytic lyases. This study demonstrated that the AlgL and heparinase_II_III modules play indispensable roles in determining the characteristics of the recombinant exo-type enzyme rAly6, which is preferred to degrade M-enriched substrates by continuously cleaving various monosaccharide units from the nonreducing end, thus yielding various size-defined ΔG-terminated oligosaccharides as intermediate products. By contrast, the endolytic enzymes Pae-rAlgL and Avi-rAlgL varied their action modes specifically against M-enriched substrates and finally degraded associated substrate chains into various size-defined oligosaccharides with a succession rule, changing from ΔM to ΔG-terminus when the product size increased. Furthermore, site-directed mutations and further protein structure tests indicated that H195NHSTW is an active, half-conserved, and essential enzyme motif. This study provided new insights into M-preferring lyases for novel resource discoveries, oligosaccharide preparations, and sequence determinations.

Sheng Jing Decoction Can Promote Spermatogenesis and Increase Sperm Motility of the Oligozoospermia Mouse Model.

Sheng Jing Decoction (SJD), as a traditional Chinese medicine prescription, is mainly be used to treat male infertility. However, the pharmacological functions and molecular mechanisms of SJD are poorly understood. In this study, we investigated the functions of SJD on spermatogenesis and sperm motility and explored the potential mechanisms involved. Here, we demonstrated that high, medium, and low doses of SJD are effective in restoring the impairments of the whole body and testicular tissue by cyclophosphamide inducing and to rescue the damage of testicular tissue cells including Sertoli cells and germ cells. SJD can partly restore the decrease in sperm concentration, sperm vitality, sperm motility, and normal sperm morphology rate in oligozoospermic mouse models. Ki67 staining analyses confirm SJD can promote testicular tissue cell proliferation. Real-time RT-PCR analyses also reveal that SJD can upregulate the expression of proliferation-associated gene Lin28a and differentiation-associated genes Kit, Sohlh2, and Stra8. SJD can also reduce the impairment of mitochondrial membrane potential (MMP) and sperm plasma membrane integrity by cyclophosphamide inducing. Our results reveal that SJD is effective in improving both sperm quantity and quality by increasing the sperm concentration, sperm vitality, sperm motility, and normal sperm morphology rate. SJD can promote spermatogenesis by upregulating the expression of the proliferation-associated gene Lin28a and the differentiation-associated genes (Kit, Sohlh2, and Stra8). SJD can sustain MMP and sperm plasma membrane integrity to increase sperm motility.

Opposing and Operated Side Electroacupuncture Generates Similar Analgesic Effects on Pain after Knee Surgery.

The purpose of this study was to investigate whether opposing electroacupuncture (EA) could produce similar analgesic effects as operated side EA after knee surgery in rats. Sprague Dawley rats were randomly divided into the sham surgery group, and three surgery groups: opposing EA, operated side EA, and model. After surgery, compared with the sham surgery group, three kinds of pain behavior test methods (mechanical withdrawal threshold (MWT), cumulative pain score [CPS], and mechanical hypersensitivity of knee) were used to assess the pain behavior of the rats in the surgery groups. After knee surgery, the three surgery groups were intervened for three consecutive days: EA on the nonoperated side in the opposing EA group, EA on the operated side in the operated side EA group, and no intervention in the model group. It was shown that MWT was higher and CPS was lower in the two EA groups than in the model group on the first and second days after surgery. On the third day after surgery, MWT in the two EA groups was the highest among the 3 days, CPS was the lowest among the 3 days, and the number of nonvocalizations in rats also increased compared with the model group. Moreover, the MWT of the nonoperated side increased more in the opposing EA group than in the model and operated side EA groups. This indicated that both opposing EA and operated side EA methods can be used to relieve pain after knee joint surgery.

CircLRRK1 targets miR-223-3p to inhibit the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway.

INTRODUCTION: Many studies have shown that circular RNAs (circRNAs) are related to the occurrence of preeclampsia (PE). However, the role of circLRRK1 in the progression of PE is unclear. METHODS: The identification and localization of circLRRK1 were verified by Actinomycin D (ActD) assay, Ribonuclease R (RNase R) digestion assay and subcellular localization assay. Moreover, the proliferation of trophoblast cells was detected by 3-(45)-dimethylthiahiazo (-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and colony formation assay. Furthermore, the migration and invasion of trophoblast cells were determined by wound healing assay and transwell assay. Meanwhile, Western blot (WB) analysis was used to examine the protein levels of migration markers and PI3K/AKT signaling pathway markers. In addition, the interaction between circLRRK1 and miR-223-3p was confirmed by dual-luciferase reporter assay and biotin-labeled RNA pull-down assay. RESULTS: Our results showed that circLRRK1 was significantly highly expressed in PE patients. Silenced circLRRK1 could markedly enhance the proliferation, migration and invasion of trophoblast cells. Additionally, we found that circLRRK1 could target miR-223-3p. MiR-223-3p overexpression also promoted the proliferation, migration and invasion of trophoblast cells. The rescue experiments revealed that miR-223-3p inhibitor could reverse the promoting effect of circLRRK1 silencing on the proliferation, migration and invasion of trophoblast cells. Furthermore, circLRRK1 silencing could activate the PI3K/AKT signaling pathway by targeting miR-223-3p. DISCUSSION: CircLRRK1 could suppress the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway via targeting miR-223-3p, suggesting that circLRRK1 might be a potential biomarker for the treatment of PE.

TRIM52 positively mediates NF-κB to promote the growth of human benign prostatic hyperplasia cells through affecting TRAF2 ubiquitination.

AIMS: Benign prostatic hyperplasia (BPH) is a progressive disease, which severely affects men's health. Here, we sought to analyze the functions and mechanism of action of the tripartite motif protein 52 (TRIM52), a novel prostate basal cell biomarker in BPH. MATERIALS AND METHODS: Immunohistochemistry assay was performed in sectioned human BPH tissues, BPH-1 cells, and prostate RWPE-1 cells, to detect the expressions of TRIM52 and NF-κB. Western blotting and qRT-PCR analyses were conducted to measure the relative protein and mRNA expression levels, respectively. Further, lentiviral transfection was performed in BPH-1 and RWPE-1 cells to study the overexpression and siRNA knockdown of TRIM52. Dual-luciferase reporter assay was applied to evaluate the relationship between NF-κB and TRIM52. Furthermore, CCK-8 assay and flow cytometry were employed to analyze cell proliferation and apoptosis. KEY FINDINGS: TRIM52 and NF-κB levels were elevated in BPH tissues, and TRIM52 expression positively correlated with NF-κB expression. TRIM52 silencing suppressed the growth of BPH-1 cells and decreased the promoter activity of NF-κB. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), suppressed TRIM52-induced proliferation of RWPE-1 cells and inhibited NF-κB promoter activity in oeTRIM52 transfected RWPE-1 cells. Silencing TRIM52 also inhibited TRAF2 ubiquitination in BPH-1 cells. Further, NF-κB promoter activity in siNC transfected cells was enhanced by the recombinant protein TNF-α and inhibited by siTRIM52. SIGNIFICANCE: TRIM52 accelerated the growth of BPH-1 cells by upregulating NF-κB, and TRIM52 could promote TRAF2 ubiquitination. These findings might contribute to the understanding of the biological functions and action mechanisms of TRIM52 in BPH.

Predictive value of the surgical pleth index for the hemodynamic responses to trachea intubation and skin incision.

Surgical pleth index (SPI) has been widely investigated in assessing the nociceptive level. The aim of this study was to investigate the relationship between SPI level and patient responses to trachea intubation and skin incision. A total of 40 patients undergoing open abdominal general surgery were recruited for analyses. The patients were monitored with electrocardiogram, non-invasive blood pressure, SpO2, invasive blood pressure and SPI before anesthesia induction. Anesthesia was induced with midazolam, propofol, sufentanil and rocuronium and maintained with sufentanil and sevoflurane. Blood pressure, heart rate and SPI were recorded for analyses during the peri-intubation and peri-incision periods. A receiver operating characteristic (ROC) curve analysis was performed to analyze the predictive value of blood pressure, heart rate (HR) and SPI for hemodynamic responses for trachea intubation and skin incision. SPI had a similar changing trend to systolic blood pressure (SBP) and diastolic blood pressure (DBP). The SPI level was linearly correlated with SBP, DBP and HR. SPI increased significantly after intubation and incision in patients with positive but not negative responses to intubation and incision. The ROC analysis showed that only SBP level is predictive of intubation responses. These data suggested that SPI elevated under the noxious stimulation by intubation and incision, but it was not predictive of the hemodynamic responses to intubation and incision.

Biochemical characteristics and synergistic effect of two novel alginate lyases from Photobacterium sp. FC615.

BACKGROUND: Macroalgae and microalgae, as feedstocks for third-generation biofuel, possess competitive strengths in terms of cost, technology and economics. The most important compound in brown macroalgae is alginate, and the synergistic effect of endolytic and exolytic alginate lyases plays a crucial role in the saccharification process of transforming alginate into biofuel. However, there are few studies on the synergistic effect of endolytic and exolytic alginate lyases, especially those from the same bacterial strain. RESULTS: In this study, the endolytic alginate lyase AlyPB1 and exolytic alginate lyase AlyPB2 were identified from the marine bacterium Photobacterium sp. FC615. These two enzymes showed quite different and novel enzymatic properties whereas behaved a strong synergistic effect on the saccharification of alginate. Compared to that when AlyPB2 was used alone, the conversion rate of alginate polysaccharides to unsaturated monosaccharides when AlyPB1 and AlyPB2 acted on alginate together was dramatically increased approximately sevenfold. Furthermore, we found that AlyPB1 and AlyPB2 acted the synergistic effect basing on the complementarity of their substrate degradation patterns, particularly due to their M-/G-preference and substrate-size dependence. In addition, a novel method for sequencing alginate oligosaccharides was developed for the first time by combining the 1H NMR spectroscopy and the enzymatic digestion with the exo-lyase AlyPB2, and this method is much simpler than traditional methods based on one- and two-dimensional NMR spectroscopy. Using this strategy, the sequences of the final tetrasaccharide and pentasaccharide product fractions produced by AlyPB1 were easily determined: the tetrasaccharide fractions contained two structures, ΔGMM and ΔMMM, at a molar ratio of 1:3.2, and the pentasaccharide fractions contained four structures, ΔMMMM, ΔMGMM, ΔGMMM, and ΔGGMM, at a molar ratio of ~ 1:1.5:3.5:5.25. CONCLUSIONS: The identification of these two novel alginate lyases provides not only excellent candidate tool-type enzymes for oligosaccharide preparation but also a good model for studying the synergistic digestion and saccharification of alginate in biofuel production. The novel method for oligosaccharide sequencing described in this study will offer a very useful approach for structural and functional studies on alginate.

Upregulation of Heme Oxygenase-1 by Hemin Alleviates Sepsis-Induced Muscle Wasting in Mice.

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.