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Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for chronic coronary syndromes (CCS) improves outcomes compared with angiography-guided PCI, however cardiac events still occur during long-term follow-up of FFR-negative patients. In the PREVENT study preventive PCI reduced cardiac-events in lesions which were FFR-negative (FFR > 0.80) and had intracoronary imaging defined vulnerable plaque. Coronary computed tomography angiography (CTA)-defined high risk plaque (HRP) is known to predict future cardiac events. We hypothesized that CTA defined HRP would identify which FFR-negative patients were at greatest risk of future cardiac events., Methods and Results: We examined 373 consecutive CCS patients undergoing CTA followed not more than 90 days later by invasive FFR. Cardiac events were defined as cardiac death, non-fatal acute coronary syndromes, and ischemia-driven revascularization. Clinical follow-up was performed in all patients at a median of 32 months. Revascularization was performed in 131 of the 373 patients due to an FFR ≤ 0.80 (Treat group), with the remaining 242 having revascularization deferred (Defer group) due to an FFR > 0.80. In the Treat group the cardiac event rates between patients with and without HRP on CTA were similar (9.4 % versus 10.1 %, p = 0.90), whilst in the Defer group they were higher in patients with HRP (21.1 % versus 4.7 %, Log-rank-p < 0.0001). In multivariate Cox hazard analysis the presence of HRP (Hazard-ratio 12.79, 95 %confidence-intervals: 3.57-45.83, p < 0.0001) was an independent predictor for cardiac events in the Defer group., Conclusions: HRP on CTA was associated with future cardiac events in patients in whom revascularization was deferred due to a negative invasive-FFR (UMIN000054067; CAPTURE)., Competing Interests: Declaration of competing interest All authors did not have any conflict of interest (COI) for this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The aims of this study were to investigate the electrophysiological features of hemifacial spasm (HFS) and post-facial paralysis synkinesis (PFPS) that contribute to differential diagnosis., Methods: This study was designed as a retrospective analysis, focusing on 132 patients diagnosed with HFS and 78 patients with PFPS between May and October 2023. Patient data were collected from existing medical records. The study aimed to analyze pre-existing electrophysiological data, including abnormal muscle response (AMR) and facial synkinesis, focusing on parameters such as AMR latency, amplitude, and duration., Results: In the HFS group, AMR could be induced in all patients, with synkinesis present in 31.8 %. In the PFPS group, AMR and synkinesis were induced in 79.5 % and 100 % of patients, respectively. Compared with the PFPS group, the HFS group had a shorter AMR latency and higher amplitude (P < 0.05). The duration of the AMR did not significantly differ between the two groups (P > 0.05). Synkinesis in the HFS group was typically accompanied or followed by an involuntary spasm episode, but not every eye closure or pouting led to synkinesis. In contrast, synkinesis in the PFPS group occurred with every voluntary movement and was synchronized with these movements., Conclusions: Patients with HFS and PFPS may exhibit similar clinical symptoms. Neurophysiological tests, particularly electromyography, provide valuable information for the differential diagnosis of HFS and PFPS., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; memberships, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Masson SAS.)

Phthalate esters (PAEs) are widely used as plasticizers and cause serious complex pollution problem in environment. Thus, strains with efficient ability to simultaneously degrade various PAEs are required. In this study, a newly isolated strain Rhodococcus sp. AH-ZY2 can degrade 500 mg/L Di-n-octyl phthalate completely within 16 h and other 500 mg/L PAEs almost completely within 48 h at 37 °C, 180 rpm, and 2 % (v/v) inoculum size of cultures with a OD 600 of 0.8. OD 600 = 0.8, 2 % (v/v). Twenty genes in its genome were annotated as potential esterase and four of them (3963, 4547, 5294 and 5359) were heterogeneously expressed and characterized. Esterase 3963 and 4547 is a type I PAEs esterase that hydrolyzes PAEs to phthalate monoesters. Esterase 5294 is a type II PAEs esterase that hydrolyzes phthalate monoesters to phthalate acid (PA). Esterase 5359 is a type III PAEs esterase that simultaneously degrades various PAEs to PA. Molecular docking results of 5359 suggested that the size and indiscriminate binding feature of spacious substrate binding pocket may contribute to its substrate versatility. AH-ZY2 is a potential strain for efficient remediation of PAEs complex pollution in environment. It is first to report an esterase that can efficiently degrade mixed various PAEs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb-drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Monoclonal antibody-based therapeutics have achieved remarkable success in treating a wide range of human diseases. However, conventional systemic delivery methods have limitations in insufficient target tissue permeability, high costs, repeated administrations, etc. Novel technologies have been developed to address these limitations and further enhance antibody therapy. Local antibody delivery via respiratory tract, gastrointestinal tract, eye and blood-brain barrier have shown promising results in increasing local concentrations and overcoming barriers. Nucleic acid-encoded antibodies expressed from plasmid DNA, viral vectors or mRNA delivery platforms also offer advantages over recombinant proteins such as sustained expression, rapid onset, and lower costs. This review summarizes recent advances in antibody delivery methods and highlights innovative technologies that have potential to expand therapeutic applications of antibodies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Kidney transplantation offers improved survival and quality of life compared to dialysis for most recipients; however, benefits for elderly patients (>70 years) remain uncertain. Using the Australia and New Zealand Dialysis and Transplant Registry (2009-2019), elderly transplant recipients were matched to a waitlisted dialysis patient by age, cause of end-stage kidney disease, and dialysis duration (paired controls). We censored dialysis patients at the time of transplant. Survival was compared using stratified Cox regression. Elderly transplant recipients (KTRs) (n = 465) were matched to waitlisted pairs. Transplant group mortality initially exceeded dialysis due to excess infection-related deaths (1.9 transplant versus 0.3 dialysis/100 patient-years, P = .03). Beyond month 9, a progressive survival benefit in favor of transplantation was apparent. Over a median follow-up of 1.7 years, mortality was 38% lower for KTRs (95% confidence interval 0.41-0.94, P = .02), and 5-year survival was 80% KTRs vs 53% dialysis (P < .001). Recipients of living and standard criteria donor kidneys acquired immediate survival advantage compared with dialysis, while recipients of expanded criteria donor's kidneys experienced elevated risk of death for the first 17 months. Compared with remaining on dialysis, elderly KTRs incur an increased risk of early posttransplant mortality but thereafter may anticipate progressively superior survival rates., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Sepsis, a clinical syndrome causing multi-organ failure, is one of the leading causes of morbidity and mortality. The effective treatment strategies for sepsis are limited. Some studies have demonstrated the benefits of kaempferol in countering sepsis, but its specific mechanism of action is unclear. The study aimed to investigate the anti-sepsis effects and mechanisms of kaempferol via sphingosine kinase 1/sphingosine-1-phosphate (SphK1/S1P) signaling pathway in a lipopolysaccharide (LPS)-induced sepsis model. We elucidated the effect of kaempferol on sepsis in LPS-induced RAW264.7 cells, HUVECs and septic mice. In RAW264.7 cells. We found that kaempferol decreased the levels of inflammatory mediators NO and PGE2. Western blot showed that kaempferol inhibited the expression of SphK1, p-p65 and p-IκB-α. LC-MS/MS analyze showed that kaempferol decreased S1P content in RAW264.7 cells. In HUVECs, we found that kaempferol promoted the expression of SphK1 and S1P, while kaempferol increased the expression levels of VE-Cadherin and β-catenin. In vivo, consistent with the in vitro results, kaempferol alleviated LPS-induced inflammatory responses and endothelial barrier damage. In addition, by immunofluorescence localization of F4/80, CD31 and SphK1, we found that kaempferol inhibited the expression of SphK1 in macrophages and increased the expression of SphK1 in endothelial cells. In summary, our present results not only suggested that kaempferol alleviated the inflammatory response and stabilizes the endothelial barrier in LPS-induced sepsis by regulating the SphK1/S1P signaling pathway, but also showed that kaempferol exhibited cell-specific effects on the regulation of SphK1 expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Hantavirus (HV), a pathogen of animal infectious diseases that poses a threat to humans, has attracted extensive attention. Clinically, HV can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), between which HFRS is mostly in Eurasia, and HPS is mostly in the Americas. This paper reviews the research progress of small-molecule inhibitors of HV., (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

In this work, a pre-wetting induced superhydrophilic/superlipophilic micro-patterned membrane with surface-loaded BiVO 4 nanoparticles (Bi/PDA@PT) was successfully prepared by electrospinning and polydopamine (PDA) surface modification technology for highly efficient emulsified oily wastewater separation. The results showed that the as-prepared membranes exhibited micro hole-patterned structures and the BiVO 4 nanoparticles were uniformly deposited on the surfaces of fibers to construct hierarchical porous structures by using PDA as an adhesive polymeric bridge. During the separation process of emulsified oily wastewater, the hierarchical porous structures in membranes significantly improved the separation flux, which was nearly 2-3 times than that of the non-patterned membranes. Based on the existence of PDA, the membranes exhibited prewetting-induced superoleophobicity under water and superhydrophobicity under oil, which made it possible for them to separate both water-in-oil and oil-in-water emulsified oily wastewater selectively and efficiently. Moreover, the BiVO 4 nanoparticles loaded on the membranes could degrade the oily contaminants adsorbed on the membranes (nearly 100%) under visible light. All these attractive features demonstrate that the Bi/PDA@PT membranes show a great potential for sustainable and efficient emulsified oily wastewater separation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Dexmedetomidine (Dex) has been noted to have neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the effect of Dex in diabetic hyperglycemia-exacerbated cerebral I/R injury and its underlying mechanism remain unclear., Main Methods: The infarct volume and brain edema were evaluated by 2,3,5-triphenyltetrazolium chloride staining and standard wet-dry method. Modified neurological severity score was utilized to assess the neurological deficits. The oxidative stress and inflammation were evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cell count kit-8 were applied to measure cell apoptosis and viability., Key Findings: Dex treatment reduced infarct volume, decreased brain water content and improved neurological deficit in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Dex treatment reduced the levels of ROS, MDA, TNF-α and IL-1β in the entire middle cerebral artery territory of diabetic mice subjected to MCAO/R, as well as in primary culture of mouse hippocampal neurons stimulated with 50 mM glucose and oxygen glucose deprivation/reperfusion. Dex treatment inhibited neuronal apoptosis induced by diabetic hyperglycemia-exacerbated cerebral I/R injury. Dex upregulated nuclear factor of activated T-cells 5 (NFAT5) and Sirtuin 1 (SIRT1) expression, induced NF-E2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and inhibited the acetylation of Nrf2. However, these changes triggered by Dex treatment were abrogated by NFAT5 knockdown., Significance: Dex protects against diabetic hyperglycemia-exacerbated cerebral I/R injury through attenuation of oxidative stress, inflammation and apoptosis. The underlying mechanism is at least the NFAT5/SIRT1/Nrf2 signaling pathway dependent., (Copyright © 2019. Published by Elsevier Inc.)

Chitin-glucan complex (CGC), the main component of fungal cell wall, is reported to have wide applications in the food and pharmaceutical industries because of its physical and physiological activities. In this study, CGC was extracted from the fruiting body of Termitomyces albuminosus (Berk.) Heim with the treatments of deproteination, demineralization and depigmentation to obtain a yield of 13.46%, and its properties were investigated. The results indicated that CGC from T. albuminosus contained glucan and chitin in a molar ratio of 46:54, with very low contents of proteins and inorganic salts. The chitin in CGC was in the α-form, with crystallinity index of 64.81% and degree of acetylation of 65.40%. The surface morphology of CGC was dense and firm with no nanofibers and nanopores as observed by scanning electron microscopy, and the peak degradation temperature was determined to be 314.88 °C. This study suggested that CGC from T. albuminosus was promising to be an alternative source of crustacean chitinous products in the industry of food, medicine, waste water treatment and so on in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Although not life threatening, spasmodic torticollis (ST) impairs patients' daily activity, socialization and work. The aim of this study was to evaluate the quality of life (QOL) and mental health in patients with ST after microvascular decompression (MVD)., Patients and Methods: From June 2014 to June 2017, patients with ST who underwent MVD in our department were included in this study. Toronto Western Sparse Torticollis Rating Scale (TWSTRS) were used to evaluate the ST symptoms. Quality of life was assessed by the craniocervical dystonia questionnaire (CDQ-24). Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI) were used to evaluate the mental health. Intraoperative findings and follow-up results were analyzed., Results: A total of 104 consecutive patients were enrolled in this study. At the 12 months follow-up, the total effective rate was 81.73%. After MVD surgery, 88(84.62%) ST patients experienced QOL improvement. The severity of ST symptoms was positively correlated with the CDQ-24 score(r = 0.31, P = 0.02). Forty-eight patients (46.16%) with ST have moderate to severe depression and nine (8.65%) have depression preoperatively. Pain and disability domains of TWSTRS were found have high relation with BDI-II score(r = 0.27, P = 0.02; r = 0.33, P = 0.03). There was a positive correlation of educational levels with the BDI-II scores(r = 0.45, P = 0.02)., Conclusion: ST affects patients' QOL both physically and mentally. MVD for ST not only provides high spasm-relief rate but also leads to significantly higher QOL after surgery. Not only ST symptoms, but also psychiatric status of patients should be routinely followed. Psychological care and psychopharmaceuticals should also be considered for these patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A water-soluble polysaccharide WSP1 was extracted from the fruiting body of Termitornyces albuminosus. Its molecular weight, monosaccharide composition and molecular structure were determined by GPC, GC-MS, UV spectroscopy, FT-IR spectroscopy, methylation analysis, NMR (1D and 2D) and AFM. Moreover, the antioxidant activity of WSP1 was evaluated in vitro by the tests of reducing power, scavenging ability on DPPH radical and hydroxyl radical, and chelating ability on ferrous ion. The results indicated that the molecular weight of WSP1 was 9 kDa, and it was mainly composed of fucose and galactose in a molar ratio of 1:3.09. Based on monosaccharide composition, methylation analysis and NMR, the possible repeating unit of WSP1 was presented as follows: →2-α-l-Fucp-1→ (6-α-d-Galp-1) 3 →. The antioxidant assay revealed that, in the concentration range tested in this experiment, WSP1 had strong scavenging ability on DPPH radical, suggesting that WSP1 could be potentially used as a powerful radical scavenger., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks. Two hundred seventy-nine patients (192 everolimus, 87 control) were followed for a median of 9 years (IQR 6.7, 11.2). Compared with control, everolimus use was not associated with a reduction in the risk of incident cancer, NMSC, or cancer-related death (unadjusted HR [95% CI] 0.86 [0.49-1.48], 0.58 [0.30-1.12], and 1.18 [0.32-4.38], respectively). Subgroup analyses showed a 56% reduction for NMSC in patients randomized to everolimus + reduced-dose calcineurin-inhibitor versus control (unadjusted HR 0.44 [0.21-0.92]), which remained significant after adjusting for age, gender and smoking (adjusted HR 0.45 [0.21-0.96]). Although de novo or early switch to everolimus did not alter the 9-year risk of incident cancer or cancer-related death, everolimus with reduced-dose calcineurin-inhibitor strategy may reduce the long-term risk of NMSC., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The investigations on their variation and distribution of 13 called waste-water marking pharmaceuticals (WWMPs) were conducted under 4 hydrophyte conditions (without plants, with submerged aquatic plant (Myriophyllum verticillatum L.), emergent aquatic plant cattail (Typha orientalis Presl) and floating aquatic plant (Lemna minor L.)) in a simulated urban river system. By the calculation of mass balance, the quantitative distribution of WWMPs in water phase, sediment and plant tissues was identified, and the overall removal efficiencies of target pharmaceuticals in the whole system could be determined. Without plants, high persistence of atenolol (ATL) (97.7%), carbamazepine (CBM) (102.8%), clofibric acid (CLF) (101.8%) and ibuprofen (IBU) (80.9%) was detected in water phase, while triclosan (TCS) (53.5%) displayed strong adsorption affinity in sediment. The removal under the planted conditions was considerably raised, compared with no plant condition for most WWMPs. However, TCS did not show obvious differences among the hydrophyte conditions due to its strong adsorption affinity and high hydrophobicity. The relatively higher removal was found for the hydrophilic (logK ow <1) or moderately hydrophobic (1ow <3) pharmaceuticals with submerged and emergent aquatic plants. The highly hydrophobic pharmaceuticals (logK ow >4.0) did not show significant differences among the whole tests in sediment. Mass balance calculation displayed the removal of CBM (5.6%-13.6%), CLF (4.0%-17.8%) and caffeine (8.4%-17.2%) through the plant uptake was relatively higher. For the rest WWMPs, only small parts (<6.0%) of the initial concentrations were found in plant tissues. The higher removal efficiencies of most WWMPs under the planted conditions indicated that aquatic plants indeed played an important role in the removal of WWMPs although the direct uptakes might not be a dominant pathway to the overall removal of WWMPs. Besides, the floating aquatic plant removed most WWMPs from the water phase efficiently. In contrast, submerged and emergent aquatic plants could effectively remove them in sediment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Intensive animal husbandry had aroused great environmental concerns in many developed countries. However, some developing countries are still undergoing the environmental pollution from livestock and poultry sectors. Driven by the large demand, China has experienced a remarkable increase in dairy and meat production, especially in the transformation stage from conventional household breeding to large-scale industrial breeding. At the same time, a large amount of manure from the livestock and poultry sector is released into waterbodies and soil, causing eutrophication and soil degradation. This condition will be reinforced in the large-scale cultivation where the amount of manure exceeds the soil nutrient capacity, if not treated or utilized properly. Our research aims to analyze whether the transformation of raising scale would be beneficial to the environment as well as present the latest status of livestock and poultry sectors in China. The estimation of the pollutants generated and discharged from livestock and poultry sector in China will facilitate the legislation of manure management. This paper analyzes the pollutants generated from the manure of the five principal commercial animals in different farming practices. The results show that the fattening pigs contribute almost half of the pollutants released from manure. Moreover, the beef cattle exert the largest environmental impact for unitary production, about 2-3 times of pork and 5-20 times of chicken. The animals raised with large-scale feedlots practice generate fewer pollutants than those raised in households. The shift towards industrial production of livestock and poultry is easier to manage from the environmental perspective, but adequate large-scale cultivation is encouraged. Regulation control, manure treatment and financial subsidies for the manure treatment and utilization are recommended to achieve the ecological agriculture in China., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Microvascular decompression (MVD) is the most useful treatment for hemifacial spasm (HFS). In cases of vertebral artery (VA) compression of the facial nerve, MVD is often difficult. In this study, we compared the outcome of the biomedical glue sling technique with the traditional technique in MVD for HFS involving the VA., Methods: A retrospective study of patients with HFS treated by MVD was conducted between January 2013 and December 2015. A total of 327 patients with VA-associated HFS underwent their first MVD at our institution. Among them, the traditional technique was performed in 153 patients and the biomedical glue sling technique was performed in 174 patients. We measured effectiveness at 1 day, 7 days, 1 month, 3 months, and 1 year after MVD surgery., Results: In the traditional technique group, the effective rates of MVD were 89.54%, 88.89%, 89.40%, 88.44%, and 86.71%, and the incidence rates of complication were 5.23%, 4.58%, 3.97%, 2.72%, and 0.70%. In the biomedical glue sling technique group, the effective rates of operation were 96.55%, 96.55%, 97.66%, 95.86%, and 95.76% (P < 0.05), and the incidence rates of complication were 8.62%, 8.62%, 7.60%, 4.73%, and 2.42% (P > 0.05)., Conclusion: When the HFS were associated with the VA, the effective rate of biomedical glue sling technique of MVD was higher than the traditional technique, and there was no statistical difference between the 2 groups about the incidence of complication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease., (Copyright © 2017. Published by Elsevier B.V.)

Engineered antibody domains (eAds) have emerged as a novel class of HIV-1 inhibitors and are currently under preclinical testing as promising drug candidates for prevention and therapy of HIV-1 infection. Reverse mutation of antibodies to germline sequences (germlining) could not only identify less mutated variants with lower probability of immunogenicity and other improved properties but also help elucidate their mechanisms of action. In this study, we sequentially reverted the framework (FRs) and complementary determining regions (CDRs) of m36, a human antibody heavy chain variable domain-based eAd targeting the coreceptor binding site of the viral envelope glycoprotein gp120, back to germline sequences. Two types of amino acid mutations and one region in the antibody V segment were identified that are critical for HIV-1 neutralization. These include four mutations to acidic acid residues distributed in the CDR1 and CDR2, two mutations to hydrophobic residues in the FR3 and CDR3, and partial FR2 and FR3 sequences flanking the CDR2 that are derived from a different gene family. An m36 variant with all five mutations in the FRs reverted back to germline showed slightly increased neutralizing activity against two HIV-1 isolates tested. Another variant with seven of twelve mutations in the V segment reverted retained potency within threefold of that of the mature antibody. These results, together with an analysis of m36-gp120-CD4 docking structures, could have implications for the further development of m36 and elucidation of its mechanism of potent and broad HIV-1 neutralization., (Published by Elsevier B.V.)

The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections., (Copyright © 2014 Institut Pasteur. All rights reserved.)

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The tetra-peptide FMRF-NH(2) is a cardioexcitatory peptide in the clam. Using the antibody against this peptide, FMRF-NH(2)-like immunoreactive material was detected in mammalian CNS. Subsequently, mammalian FMRF-NH(2) immunoreactive peptides were isolated from bovine brain and characterized to be FLFQPQRF-NH(2) (NPFF) and AGEGLSSPFWSLAAPQRF-NH(2) (NPAF). The genes encoding NPFF precursor proteins and NPFF receptors 1 and 2 are expressed in all vertebrate species examined to date and are highly conserved. Among many biological roles suggested for the NPFF system, the possible modulatory role of NPFF in nocicetion and opiate analgesia has been most widely investigated. Pharmacologically, NPFF-related peptides were found to exhibit analgesia and also potentiate the analgesic activity of opiates when administered intrathecally but attenuate the opiate induced analgesia when administered intracerebroventricularly. RF-NH(2) peptides including NPFF-related peptides were found to delay the rate of acid sensing ion channels (ASIC) desensitization resulting in enhancing acid gated currents, raising the possibility that NPFF also may have a pain modulatory role through ASIC. The genes for NPFF as well as NPFF-R2, preferred receptor for NPFF, are highly unevenly expressed in the rat CNS with the highest levels localized to the superficial layers of the dorsal spinal cord. These two genes are also present in the dorsal root ganglia (DRG), though at low levels in normal rats. NPFF and NPFF-R2 mRNAs were found to be coordinately up-regulated in spinal cord and DRG of rats with peripheral inflammation. In addition, NPFF-R2 immunoreactivity in the primary afferents was increased by peripheral inflammation. The findings from the early studies on the analgesic and morphine modulating activities suggested a role for NPFF in pain modulation and this possibility is further supported by the distribution of NPFF and its receptor and the regulation of the NPFF system in vivo.

VIS-NIR spectroscopy combined with multivariate analysis after the appropriate spectral data pre-treatment has been proved to be a very powerful tool for judgment of the relative pattern of the objects that have very similar properties. In this study, seventy transgenic tomatoes with antisense LeETR2 and 94 of their parents, non-transgenic ones were measured in VIS-NIR diffuse reflectance mode. Principal component analysis (PCA), discriminant analysis (DA) and partial least-squares discriminant analysis (PLSDA) were applied to classify tomatoes with different genes into two groups. Calibrations were developed using PLS regression with the leave-one-out cross-validation technique. The results show that differences between transgenic and non-transgenic tomatoes do exist and excellent classification can be obtained after optimizing spectral pre-treatment. The correct classifications for transgenic and non-transgenic tomatoes were both 100% using PLSDA after derivative spectral pre-treatment. The raw spectra with PLSDA model after the second derivative pre-treatment had the best satisfactory calibration and prediction abilities, with r(c)=0.97964, root mean square error of calibration (RMSEC)=0.099, r(cv)=0.97963, root mean square error of cross-validation (RMSECV)=0.0993 and a factor. The results in the present study show VIS-NIR spectroscopy together with chemometrics techniques could be used to differentiate transgenic tomato, which offers the benefit of avoiding time-consuming, costly and laborious chemical and sensory analysis.

In this paper, separations of organic compounds, such as, n-alkanes, alcohols, ethyl asters of C(1)-C(8) carboxylic acid, halogen derivatives, position-isomers of the replacement aromatic hydrocarbon, optical isomers of ethyl lactate and isoamyl alcohol, etc. were studied using 4'-cholestenoxycarbonyl-benzo-15-crown-5 liquid crystal crown ether (CH-B-15-C-5) as stationary phase in gas-solid chromatography (GSC), general gas-liquid chromatography (GLC) and crown ether liquid crystal gas-liquid chromatography (CL-GLC). Also, the chromatographic characteristics, such as the chemical stability, thermal stability, selectivity, polarity and operating temperature range, of the CH-B-15-C-5 as stationary phase for GSC, GLC and CL-GLC systems were studied. The results showed that the polarity of this chromatographic column is mean-weak; the chemical and thermal stabilities and the selectivity are good and the operating temperature range is wide. The results of separations of organic compounds are satisfactory.

Posttreatment with diethyldithiocarbamate (DEDTC) largely prevented the development of acute hepatocellular necrosis induced by diethylnitrosamine (DEN) and dimethylnitrosamine (DMN) in male Fischer rats as monitored by the release of glutamate-pyruvate transaminase and sorbitol dehydrogenase into the serum and by histologic examination. Liver cell necrosis was evident with a dose of 25 mg of DEN/kg and was progressive with increasing doses of DEN. DEDTC (50 mg/kg; three times at 4-hour intervals) was given at 4 or 8 hours after the administration of DEN (100 mg/kg), time points at which at least 50% and 75%, respectively, of the administered DEN had disappeared from both the serum and liver. Under these conditions, DEDTC prevented liver cell necrosis, except for a few isolated cells. Similar inhibition was also observed when DEDTC was given 4 hours after the administration of a necrogenic dose of DMN (20 mg/kg). DEDTC, when administered 4 hours after DEN, delayed the rate of clearance of DEN and of ethylation of DNA and RNA but did not significantly affect the total extent of ethylation of rat liver nucleic acids. These results offer further support for the multistep hypothesis for the development of liver cell necrosis.