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The physicochemical properties of the polysaccharides in Polygonatum kingianum, a Chinese medicinal herb used for both medicine and food, have not been fully studied. This study isolated three polysaccharides (PKP-1, PKP-2, and PKP-3) from the dry rhizomes of P. kingianum, with an average molecular weight of approximately 3137 Da, 5341 Da and 3755 Da, respectively. Structural analysis showed that all the three polysaccharides are fructans with ß-D-Fruf-(2→, →6)-ß-D-Fruf-(2→, →1)-ß-D-Fruf-(2→, →1,6)-ß-D-Fruf-(2→ and →6)-α-D-Glcp-(1→ glycosidic bond type. Notably, PKP-2 contains both acetyl groups and trace amounts of mannose residues. Scanning electron microscopy indicated that each polysaccharide possesses unique surface morphology. Thermal analysis showed that the three polysaccharides have good thermal stability. Rheological studies further revealed that all the three polysaccharides are typical shear thinning fluids. In vitro experiments showed that PKP-1 and PKP-2 significantly promote the secretion of NO and cytokines (TNF-α, IL-6) in macrophages by activating the NF-κB signaling pathway, thereby demonstrating potential immunomodulatory activity. These findings lay a theoretical foundation for the potential application of Polygonatum polysaccharides in the food industry.

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BACKGROUND: Metabolic acidosis plays a key role in transient global cerebral ischemiareperfusion (I/R) induced delayed neuronal death (DND) of the hippocampal CA1 region of gerbils. Na+ coupled HCO3 - transporters (NBCs) mediated Na+/HCO3- - co-transportation can be activated by the pH gradient of intracellular and extracellular environments induced by acidosis. However, whether NBCs are activated and involved in I/R-induced neuronal injury is unknown. OBJECTIVE: In this work, we studied neuronal apoptosis, astrocyte activation, and hippocampusdependent memory task using a well-established transient global cerebral I/R model of gerbils and investigated whether the specific NBCs inhibitor S0859 could reverse this injury. METHODS: To explore the role of S0859 in I/R-induced DND, we established a transient global cerebral I/R model of Mongolian gerbils and studied neuronal apoptosis by using Nissl stain and TUNEL assay. The excitability and NBCs current were analyzed by whole-cell patch-clamp, while the cognitive function was evaluated by Barnes maze. RESULTS: We found that I/R increased the NBCs current, inhibited the excitability of CA1 neurons, and led to apoptosis in CA1 neurons. Selective NBCs inhibitor S0859 protected CA1 neurons from I/R induced neuronal cell death, astrocyte accumulation, and spatial memory impairment. CONCLUSION: These findings indicate that NBCs mediate transient global cerebral I/R induced DND of CA1 neurons, and NBCs inhibitors could be a promising target to protect neuronal functions after I/R.

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AIM: To identify the effect of patients with diabetes mellitus (DM) with traumatic brain injury (TBI) in Taiwan. MATERIAL AND METHODS: Data from the trauma registry in Chang Gung Memorial Hospital, Linkou, Taiwan were collected and reviewed. Several clinical characteristics and outcomes were extracted and analyzed. The trauma databank includes 3090 patient medical records, of which 475 patients were identified as having DM. Because several baseline characteristics of patients with TBI in the DM group differed from those in the non-DM group, we performed propensity score matching to eliminate confounding factors. RESULTS: After propensity score matching, 895 patients with TBI comprised the non-DM group, and no significant differences were noted in the baseline characteristics between groups. Patients in the DM group had more craniotomies, longer hospital stays, and longer ICU stays. We also segmented the DM group into two subgroups based on survival status. Compared with the survivor group, the nonsurvivor group had a significantly higher serum glucose level. Furthermore, patients with DM were divided into four subgroups according to their serum glucose level. The in-hospital mortality rate was higher in the subgroup with glucose levels greater than 200mg/dL than in the other subgroups. A receiver-operating-characteristic analysis revealed that the ability of serum glucose level to predict in-hospital mortality was modest, with an area under the curve of 0.641 and an associated optimal cutoff of 206 mg/dl. CONCLUSION: DM should be considered a risk factor for patients with TBI receiving neurosurgical intervention and a predictor of longer hospitalization and stay in an intensive care unit. Moreover, in patients with TBI with DM, higher admission serum glucose levels are associated with a higher in-hospital mortality rate.

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Our previous study identified that the Mycobacterium abscessus subsp. abscessus T28 sequevar does not fully represent inducible macrolide resistance. Thus, we initiated a correlation study between genotypes and phenotypes. In total, 75 isolates from patients with skin and soft tissue infections were enrolled in the study. These strains were tested against 11 antimycobacterial agents using Sensitire RAPMYCO plates and the CLSI-recommended broth microdilution method. In order to analyze erm(41) and partial hsp65, rpoB, secA1, and rrl genes, bacterial genomic DNA was extracted from bacteria. The MEGA X software was used for phylogenetic analyses. The most active agents against most M. abscessus species were amikacin and tigecycline. Clarithromycin was effective toward M. abscessus subsp. massiliense and nearly all M. abscessus subsp. abscessus C28 sequevars. Two varieties of M. abscessus subsp. abscessus T28 sequevars did not represent inducible macrolide resistance. Most M. abscessus species showed intermediate susceptibility to cefoxitin and imipenem. Six additional agents were less effective against M. abscessus species. Following phylogenetic analyses, two outliers of M. abscessus subsp. abscessus T28 sequevars seem to represent no inducible macrolide resistance. In addition, we discovered genetic mosaicism of hsp65, rpoB, and secA1 in M. abscessus species was common. T28 sequevars of M. abscessus subsp. abscessus do not fully represent inducible macrolide resistance. The outlier of erm(41) phylogeny of the M. abscessus subsp. abscessus T28 sequevar is possibly due to macrolide susceptibility. Evaluation of the antimicrobial susceptibility of M. abscessus species is a reliable tool for assisting physicians in selecting the most effective antimycobacterial agent(s). IMPORTANCE Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm(41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl. However, not all M. abscessus subsp. abscessus T28 sequevars have inducible macrolide resistance. Exploration of the mechanism of macrolide resistance requires an understanding of genetic diversity. The genetic mosaicism of the erm(41), rpoB, hsp65, and secA1 genes within three subspecies of M. abscessus species is not uncommon. The T28 sequevar of erm(41) confers inducible macrolide resistance to the genetic mosaic strain. The development of new anti-M. abscessus species infection overcoming inducible macrolide resistance and/or acquired macrolide resistance is a crucial issue.

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BACKGROUND: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance. METHODS: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method. RESULTS: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time. CONCLUSION: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.

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OBJECTIVES: Interferon-γ release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. METHODS: We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. RESULTS: A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (P = 0.005) and increased Mitogen-Nil (P < 0.001) values after vaccination. For TB2-Nil value, a similar trend (P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than |± 0.10| IU/ml over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. CONCLUSION: COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration.

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To restore lost functions while repairing the neuronal structure after spinal cord injury (SCI), pharmacological interventions with multiple therapeutic agents will be a more effective modality given the complex pathophysiology of acute SCI. Toward this end, we prepared electrospun membranes containing aligned core-shell fibers with a polylactic acid (PLA) shell, and docosahexaenoic acid (DHA) or a brain-derived neurotropic factor (BDNF) in the core. The controlled release of both pro-regenerative agents is expected to provide combinatory treatment efficacy for effective neurogenesis, while aligned fiber topography is expected to guide directional neurite extension. The in vitro release study indicates that both DHA and BDNF could be released continuously from the electrospun membrane for up to 50 days, while aligned microfibers guide the neurite extension of primary cortical neurons along the fiber axis. Furthermore, the PLA/DHA/BDNF core-shell fibrous membrane (CSFM) provides a significantly higher neurite outgrowth length from the neuron cells than the PLA/DHA CSFM. This is supported by the upregulation of genes associated with neuroprotection and neuroplasticity from RT-PCR analysis. From an in vivo study by implanting a drug-loaded CSFM into the injury site of a rat suffering from SCI with a cervical hemisection, the co-delivery of DHA and BDNF from a PLA/DHA/BDNF CSFM could significantly improve neurological function recovery from behavioral assessment, as well as provide neuroprotection and promote neuroplasticity changes in recovered neuronal tissue from histological analysis.

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We study the instantaneous response of stimulated Brillouin scattering (SBS) in a fiber system phase modulated by a binary sequence waveform. The buildup time constant of SBS kinetics is investigated analytically and experimentally. A series of binary sequences with adjustable dwell time and sequence period is constructed in order to examine both buildup and suppressing processes for SBS in 15 m short fiber. For a fiber system with SBS buildup time constant within several nanoseconds, the Stokes intensity can be effectively suppressed by implementing a binary sequence phase modulation with a dwell time close to or even less than the buildup time constant. Stokes intensity can be suppressed in several sequence periods, which exhibit a damped-oscillation-like trend.

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BACKGROUND: Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics. OBJECTIVES: To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV. METHODS: A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV. RESULTS: Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV. CONCLUSIONS: HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.

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Traumatic brain injury (TBI) could result in edema and cause an increase in intracranial pressure of the brain resulting in mortality and morbidity. Although there is hyperosmolarity therapy available for this pathophysiological event, it remains controversial. Recently, several groups have shown docosahexaenoic acid (DHA) to improve functional and histological outcomes following brain injury based on reduction of neuroinflammation and apoptosis. However, the effect of DHA on blood-brain barrier (BBB) dysfunction after brain injury has not been fully studied. Here, a controlled cortical impact rat model was used to test the effect of a single dose of DHA administered 30 min post injury. Modified neurological severity score (mNSS) and forelimb asymmetry were used to determine the functional outcomes. Neuroimaging and histology were used to characterize the edema and BBB dysfunction. The study showed that DHA-treated TBI rats had better mNSS and forelimb asymmetry score than vehicle-treated TBI rats. Temporal analysis of edema using MRI revealed a significant reduction in edema level with DHA treatment compared to vehicle in TBI rats. Histological analysis using immunoglobulin G (IgG) extravasation showed that there was less extravasation, which corresponded with a reduction in aquaporin 4 and astrocytic metalloprotease 9 expression, and greater endothelial occludin expression in the peri-contusional site of the TBI rat brain treated with DHA in comparison to vehicle treatment. In conclusion, the study shows that DHA can exert its functional improvement by prevention of the edema formation via prevention of BBB dysfunction after TBI.

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BACKGROUND: The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. OBJECTIVES: To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. METHODS: We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. RESULTS: At 15-25% minority detection thresholds, 9-15% cases had underestimated DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68-82% in protease-reverse transcriptase region and 88-97% in integrase region at 5-25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. CONCLUSIONS: Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10-15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection.

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With the improvement of internet technology in health applications, the utilization of internet and social media as new survey methodologies and recruitment source for research participants have been encouraged, yet evidence of the feasibility in people living with HIV (PLHIV) study is still lacking. We conducted a cross-sectional survey to determine whether there are differences among PLHIV recruited from social media networks and health-care systems using an HIV stigma and discrimination questionnaire. The result revealed that PLHIV recruited from social media networks were younger, more sexually active, and had higher educational status and awareness of the country's HIV rights protection laws than those recruited from hospitals. By contrast, participants recruited from hospitals were more diverse regarding key population compositions, had lived with HIV for a longer duration, had a higher prevalence of concomitant physical disabilities than those recruited from social media networks, and fit Taiwan PLHIV characteristics described by 2016 census from Taiwan Centres for Disease Control. We conclude that sampling bias exists when utilizing social media networks for PLHIV studies.

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There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.

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OBJECTIVE: The impact of antithrombotic agents on patients with primary intracerebral hemorrhage (ICH) remains controversial, especially patients who require emergent craniotomy. This study was undertaken to evaluate clinical outcomes in operated patients with ICH with and without previous antithrombotic agents. METHODS: This is a retrospective cohort study. Between January 2001 and December 2013, all patients with ICH who received emergent craniotomy and who were present in Taiwan's National Health Insurance Research Database were screened and divided into those with previous antiplatelet therapy, anticoagulant therapy, and nonantithrombotic therapy according to their health care claims data within 3 months of index admission. The primary end points included in-hospital mortality and complications and short-term outcome. RESULTS: Of 18,872 eligible patients, 16,251 (87.1%) did not receive any antithrombotic therapy, 2267 patients had antiplatelet therapy, and 354 patients had anticoagulation therapy. After propensity score matching, significantly more blood transfusions and craniectomies were identified in the patients with previous antithrombotic treatment compared with those undergoing nonantithrombotic therapy. Compared with the nonantithrombotic treatment cohort, patients under previous anticoagulant treatment had significantly higher in-hospital mortality (odds ratio, 2.12; 95% confidence interval, 1.45-3.10). Furthermore, during the 6-month follow-up period, previous anticoagulant therapy was independently associated with a greater risk of all-cause mortality (P = 0.001). The in-hospital and 6-month all-cause mortality of patients with previous antiplatelet treatment was not significantly different from patients with nonantithrombotic treatment. CONCLUSIONS: These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated patients with ICH with previous antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy.

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Background: This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak. Methods: Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017. Results: A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL. Conclusions: During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.

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Background: Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (cSSTIs). The selection of antimycobacterial agents for successful treatment of such infections is a critical issue. Objectives: To investigate the antimicrobial susceptibility patterns of MABC isolates from skin and soft tissue to a variety of antimycobacterial agents. Methods: Sixty-seven MABC isolates were collected and partial gene sequencing of secA1, rpoB and hsp65 was used to classify them into three subspecies: M. abscessus subsp. abscessus (MAB), M. abscessus subsp. massiliense (MMA) and M. abscessus subsp. bolletii (MBO). The MICs of 11 antimycobacterial agents for these 67 isolates were determined using a broth microdilution method and commercial Sensititre RAPMYCOI MIC plates, as recommended by CLSI. Results: In total, 28 MAB, 38 MMA and 1 MBO were isolated from patients with cSSTIs at our hospital. Most MABC strains were resistant to ciprofloxacin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin and trimethoprim/sulfamethoxazole. In addition, most MABC strains were intermediately susceptible or resistant to cefoxitin. Eighteen of the 28 MABs and 1 MBO isolate harboured the T28 polymorphism in the erm(41) gene. Two of the 38 MMA isolates had an rrl A2059G point mutation. Most of the MABC strains were susceptible to amikacin and tigecycline. Conclusions: In Taiwan, amikacin, clarithromycin and tigecycline have good activity against MMA and MAB erm(41) C28 sequevar isolates, whereas amikacin and tigecycline, rather than clarithromycin, have good activity against both MBO and MAB erm(41) T28 sequevar isolates. Clinical trials are warranted to correlate these data with clinical outcomes.

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BACKGROUND: Acute hepatitis A is a fecal-oral transmitted disease related to inadequate sanitary conditions. In addition to its traditional classification, several outbreaks in the men who have sex with men (MSM) population have resulted in acute hepatitis A being recognized as a sexually transmitted disease. However, few studies have clarified the clinical manifestations in these outbreaks involving the MSM population. METHODS: Beginning in June 2015, there was an outbreak of acute hepatitis A involving the MSM population in Northern Taiwan. We conducted a 15-year retrospective study by recruiting 207 patients with the diagnosis of acute hepatitis A that included the pre-outbreak (January 2001 to May 2015) and outbreak (June 2015 to August 2016) periods in a tertiary medical center in Northern Taiwan. Using risk factors, comorbidities, presenting symptoms, laboratory test results and imaging data, we aimed to evaluate the clinical significance of acute hepatitis A in the MSM population, where human immunodeficiency virus (HIV) coinfection is common. RESULTS: There was a higher prevalence of reported MSM (p < 0.001), HIV (p < 0.001) and recent syphilis (p < 0.05) coinfection with acute hepatitis A during the outbreak period. The outbreak population had more prominent systemic symptoms, was more icteric with a higher total bilirubin level (p < 0.05) and had a 7-times higher tendency (p < 0.05) to have a hepatitis A relapse. CONCLUSIONS: The clinical course of acute hepatitis A during an outbreak involving the MSM and HIV-positive population is more symptomatic and protracted than in the general population.

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A series of phenanthroline-based ligands have been synthesised and their influence as bidentate nitrogen ligands in heteroleptic [Cu(P^P)(N^N)]+ photosensitisers in light-driven water reduction has been studied. In this noble-metal-free Cu-Fe-based photocatalytic water reduction system, the structural effects of the nitrogen ligands have been explored, including the steric and electronic effects of substituents at the 2,9- and 4,7-positions of phenanthroline. Ligands were prepared that led to increased hydrogen generation, with turnover numbers (TONCu ) of up to 1388 being observed. All the new complexes were electrochemically and photophysically characterised. We demonstrate for the first time that the presence of fluorine in nitrogen ligands increases the efficacy of copper complexes in photocatalytic hydrogen production.

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Herein, we report a novel cobalt-catalyzed stereodivergent transfer hydrogenation of alkynes to Z- and E-alkenes. Effective selectivity control is achieved based on a rational catalyst design. Moreover, this mild system allows for the transfer hydrogenation of alkynes bearing a wide range of functional groups in good yields using catalyst loadings as low as 0.2 mol %. The general applicability of this procedure is highlighted by the synthesis of more than 50 alkenes with good chemo- and stereoselectivity. A preliminary mechanistic study revealed that E-alkene product was generated via sequential alkyne hydrogenation to give Z-alkene intermediate, followed by a Z to E alkene isomerization process.

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BACKGROUND: HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps. RESULTS: Here we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket delimited by two adjacent capsid monomers where C-A1 is predicted to bind. Isothermal titration calorimetry confirmed that C-A1 binds to hexameric capsid. Cyclosporine washout assays in Jurkat CD4+ T cells expressing engineered human TRIMCyp showed that C-A1 causes faster and greater escape from TRIMCyp restriction. Sub-cellular fractionation showed that small amounts of capsid accumulated in the nuclei of infected cells and C-A1 reduced the nuclear capsid. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. Depletion of Nup153, a nucleoporin located at the nuclear side of the nuclear pore that binds to HIV-1 capsid, made the virus less susceptible to TRIMCyp restriction, suggesting that Nup153 may help maintain some integrity of the viral core in the nucleus. Furthermore C-A1 increased binding of CPSF6, a nuclear protein, to capsid. CONCLUSIONS: Our results indicate that capsid is involved in post-nuclear entry steps preceding integration.

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