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The introduction of a trifluoromethyl (CF3) group can dramatically improve a compound’s biological properties. Despite the well-established importance of trifluoromethylated compounds, general methods for the trifluoromethylation of alkyl C–H bonds remain elusive. Here we report the development of a dual-catalytic C(sp3)–H trifluoromethylation through the merger of light-driven, decatungstate-catalysed hydrogen atom transfer and copper catalysis. This metallaphotoredox methodology enables the direct conversion of both strong aliphatic and benzylic C–H bonds into the corresponding C(sp3)–CF3 products in a single step using a bench-stable, commercially available trifluoromethylation reagent. The reaction requires only a single equivalent of substrate and proceeds with excellent selectivity for positions distal to unprotected amines. To demonstrate the utility of this new methodology for late-stage functionalization, we have directly derivatized a broad range of approved drugs and natural products to generate valuable trifluoromethylated analogues. Preliminary mechanistic experiments reveal that a ‘Cu–CF3’ species is formed during this process and the critical C(sp3)–CF3 bond-forming step involves the copper catalyst.Despite the importance of trifluoromethylated compounds, direct catalytic methods for the conversion of C(sp3)–H bonds into the corresponding C(sp3)–CF3 analogues have remained elusive. This transformation has now been achieved by the merger of copper catalysis with decatungstate photocatalysis, enabling the C(sp3)–H trifluoromethylation of abundant feedstocks, natural products and pharmaceuticals.

PurposeThe purpose of this paper is to identify opportunities and challenges for small- to medium-sized pre-owned fashion enterprises (SMEs) in Vietnam. While recent studies have identified the growth of pre-owned fashion in developed economies, pre-owned clothing remains negatively associated by some consumers with overseas charity donations of second-hand clothes to Vietnam, following the economic upheaval of the 1980s.Design/methodology/approachQualitative data were collected via semi-structured in-depth interviews with founders and/or owners of pre-owned fashion SMEs (n = 5, aged 25–40 years) with physical stores located in Ho Chi Minh City alongside online retail platforms. All interviewees are significant industry and consumer influencers.FindingsYounger Vietnamese consumers are motivated by (1) pre-owned fashion's value for money compared to buying new western branded luxury items and (2) the ability of pre-owned and vintage fashion to allow the wearer to create a unique personal style. While Vietnamese consumers and retailers associate “sustainable fashion” with various, often unrelated concepts, the impact of global and local discourse around sustainable fashion in the last five years has generally supported wider interest in pre-owned fashion.Originality/valueThis study contributes to the relatively modest pool of English-language research on the fashion and textiles industry in Vietnam, a global fast-fashion manufacturing hub. The findings advance understanding of how pre-owned fashion is growing as a high-end niche market despite significant supply chain restrictions as well as a lingering perception of pre-owned fashion as charitable donations.

Parvovirus B19 is a non-enveloped DNA virus of the Parvoviridae family, which usually causes erythema infectiosum in children. Although rare in adults, this virus can cause severe complications, including encephalitis. We report a case of a 50-year-old male patient, previously healthy, who was admitted to the hospital with high fever, headache, nausea, vomiting, and rapidly progressing to impaired consciousness. The patient was intubated and placed on mechanical ventilation. A lumbar puncture was performed, which showed mild leukocytosis with normal protein and glucose levels, and negative cultures. Tests to exclude common causes of encephalitis such as HSV, Influenza, Dengue, and HIV were all negative. Brain magnetic resonance imaging revealed corpus callosum lesions, while electroencephalography showed diffuse theta slow waves. Multiplex Polymerase chain reaction (PCR) of the cerebrospinal fluid confirmed the diagnosis of Parvovirus B19 infection. The patient was treated empirically with empirical broad-spectrum antibiotics (meropenem and vancomycin) and supportive intensive care. After seven days, the patient made a complete recovery without neurological sequelae and was discharged in a stable condition. This report emphasizes that Parvovirus B19, although generally considered a benign agent in children, can cause encephalitis in healthy adults and should be considered in the differential diagnosis of encephalitis of unknown etiology.

Lam and Abramovich offer five things to know about transgender-inclusive care. These include, population studies estimate that 0.5% of adults (about 25 million people worldwide) identify as transgender, medical guidelines on providing care for transgender individuals have been published and transgender men with a cervix are less likely than cisgender women to have up-to-date Papanicolaou screening.

This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH. A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the Cmax and AUC estimates for all INH dosages. Ninety studies were included in this systematic review. TB status significantly affected the INH Cmax and AUC estimates. In healthy volunteers, the dose-normalized INH Cmax and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized Cmax and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized Cmax and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH Cmax and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2. The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity. •TB status significantly affects INH Cmax and AUC leading to lower drug exposure•Current INH dosing regimen for TB adult and pediatric patients may be inadequate•INH Cmax and AUC increases as dose increases•NAT2 polymorphism impact INH concentration and may require individualized dosing

The use of the character wang 忘 (forgetting) in the Zhuangzi 莊子 has been widely recognized in traditional and contemporary Chinese scholarship, but its meaning remains unclear. This article reviews some notable studies in Sinophone academia concerning the notion of wang in the Zhuangzi . The studies, though not necessarily focused on wang , shed light on different aspects of the concept, including its relation to self-cultivation, aesthetics, ethics, and ontology. While some scholars see wang as a form of elimination, others stress its relation to other concepts such as shi 適 (fitting). The relation of these two concepts, however, is not yet clear. There are also debates over what makes wang possible, with some linking it to dao 道 and some directing our attention to our daily experience. Despite the limited attention paid to wang to date, the studies reviewed show that it is a crucial aspect of Zhuangzian philosophy and deserves further study.

An effective strategy has been developed for the photoredox-catalyzed decarboxylative addition of cyclic amino acids to both vinylogous amides and esters leading to uniquely substituted heterocycles. The additions take place exclusively trans to the substituent present on the dihydropyridone ring affording stereochemical control about the new carbon-carbon bond. These reactions are operationally simplistic and afford the desired products in good to excellent isolated yields.

Background Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models. Clarifying the underlying mechanism by which OGA inhibition leads to the reduction of pathological tau and identifying translatable measures to guide human dosing and efficacy determination would significantly facilitate the clinical development of OGA inhibitors for the treatment of tauopathies. Methods Genetic and pharmacological approaches are used to evaluate the pharmacodynamic response of OGA inhibition. A panel of quantitative biochemical assays is established to assess the effect of OGA inhibition on pathological tau reduction. A “click” chemistry labeling method is developed for the detection of O-GlcNAcylated tau. Results Substantial (>80%) OGA inhibition is required to observe a measurable increase in O-GlcNAcylated proteins in the brain. Sustained and substantial OGA inhibition via chronic treatment with Thiamet G leads to a significant reduction of aggregated tau and several phosphorylated tau species in the insoluble fraction of rTg4510 mouse brain and total tau in cerebrospinal fluid (CSF). O-GlcNAcylated tau is elevated by Thiamet G treatment and is found primarily in the soluble 55 kD tau species, but not in the insoluble 64 kD tau species thought as the pathological entity. Conclusion The present study demonstrates that chronic inhibition of OGA reduces pathological tau in the brain and total tau in the CSF of rTg4510 mice, most likely by directly increasing O-GlcNAcylation of tau and thereby maintaining tau in the soluble, non-toxic form by reducing tau aggregation and the accompanying panoply of deleterious post-translational modifications. These results clarify some conflicting observations regarding the effects and mechanism of OGA inhibition on tau pathology, provide pharmacodynamic tools to guide human dosing and identify CSF total tau as a potential translational biomarker. Therefore, this study provides additional support to develop OGA inhibitors as a treatment for Alzheimer’s disease and other neurodegenerative tauopathies.

Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively.

This paper highlights the transformation of pre-owned fashion into sustainable consumption in Vietnam. It contrasts generational perceptions: older consumers often view pre-owned fashion negatively as reminiscent of overseas charity donations, while younger consumers value these items for their uniqueness, affordability, and as symbols of ‘eco-awareness’, based on observations of local media, two prominent pre-owned fashion platforms, and an online survey of young Vietnamese consumers. The study reveals that online media endorsements by celebrities and the role of social commerce, serving both as a selling platform and e-community, are key factors in transforming pre-owned fashion into sustainable consumption among young Vietnamese consumers. This research enhances the limited English-language literature on Vietnam’s pre-owned fashion industry, illustrating how e-communities can transform responsible consumption among young Vietnamese consumers.