The assumption that oxidative addition is the key step during the cross-coupling reaction of aryl halides has led to the development of a plethora of increasingly complex metal catalysts, thereby ...obviating in many cases the exact influence of the base, which is a simple, inexpensive, and necessary reagent for this paramount transformation. Here, a combined experimental and computational study shows that the oxidative addition is not the single kinetically relevant step in different cross-coupling reactions catalyzed by sub-nanometer Pt or Pd species, since the reactivity control is shifted toward subtle changes in the base. The exposed metal atoms in the cluster cooperate to enable an extremely easy oxidative addition of the aryl halide, even chlorides, and allow the base to bifurcate the coupling. With sub-nanometer Pd species, amines drive to the Heck reaction, carbonate drives to the Sonogahira reaction, and phosphate drives to the Suzuki reaction, while for Pt clusters and single atoms, good conversion is only achieved using acetate as a base. This base-controlled orthogonal reactivity with ligand-free catalysts opens new avenues in the design of cross-coupling reactions in organic synthesis.
Background and Aims
Sustained virologic response (SVR) to interferon (IFN)‐free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous ...pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN‐free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH.
Approach and Results
The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline BL) and after (follow‐up FU) IFN‐free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08‐1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve AUROC, < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86‐0.92) in most patients, especially if assessed in a sequential manner.
Conclusions
Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An “immediate” HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.
Larvae of some insect species (Coleoptera and Lepidoptera) can consume and biodegrade synthetic polymers, including polyethylene, polystyrene, polyvinyl chloride, and polypropylene. Multiple chemical ...(polymer mass loss and shift of the molecular weight, alterations in chemical functionality, formation of biodegraded intermediates, CO2 production), physical (surface hydrophobicity, thermal analysis), and biological approaches (antibiotic treatment, gut dysbiosis, isolation of plastic microbial degraders) have provided evidence for polymer biodegradation in the larva digestive tract. However, the extent and rate of biodegradation largely depend on the physicochemical structure of the polymer as well as the presence of additives. Additionally, toxicology associated with plastic biodegradation has not been investigated. This knowledge gap is critical to understand the gut symbiont-host interaction in the biodegradation process, its viability in the long term, the effects of plastic additives and their metabolites, and the phenotypic traits linked to a plastic-rich diet might be transferred in successive generations. Likewise, plastic-eating larvae represent a unique case study for elucidating the mechanisms of toxic action by micro- and nanoplastics because of the high concentration of plastics these organisms may be intentionally exposed to. This perspective review graphically summarizes the current knowledge on plastic biodegradation by insect larvae and describes the physiological processes (digestive and immune systems) that may be disrupted by micro- and nanoplastics. It also provides an outlook to advance current knowledge on the toxicity assessment of plastic-rich diets and the environmental risks of plastic-containing by-products (e.g., insect manure used as fertilizer).
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•Plastivores are emerging as a biotechnological system for managing plastic waste.•Microplastic- and nanoplastic-derived sublethal effects are unknown in plastivores.•Plastivores are a suitable model for exploring the mechanisms of toxic action of micro(nano)plastics.
•Staging and grading form cornerstone during cancer management.•Current TNM staging (2017) of oral cancer has included major modifications.•Recent research proposed new grading assessing ...differentiation and dissociation.
Oral squamous cell carcinoma (OSCC) is a common malignancy of the head and neck region. OSCC has a relatively low survival rate and the incidence of the disease is increasing in some geographic areas. Staging and grading of OSCC are established prerequisites for management, as they influence risk stratification and are the first step toward personalized treatment. The current AJCC/UICC TNM staging (8th edition, 2017) of OSCC has included significant modifications through the incorporation of depth of invasion in the T stage and extracapsular spread/extranodal extension in the N stage. Further modifications for AJCC 8 have been suggested. On the other hand, the World Health Organization (WHO) classification (4th edition, 2017) still endorses a simple, differentiation-based histopathologic grading system of OSCC (despite its low prognostic value) and ignores factors such as tumor growth pattern and dissociation, stromal reactions (desmoplasia, local immune response), and tumor-stroma ratio. The various controversies and possible developments of the current staging and grading criteria of OSCC are briefly discussed in this update together with possible applications of artificial intelligence in the context of screening and risk stratification.
•Removal of contaminants of emerging concern by MOF nanoadsorbents was comprehensively reviewed.•Comprehensively information was provided for applications of MOF nanoadsorbents in water ...industry.•Areas of future research for the removal of various contaminants in MOF nanoadsorbents were suggested.
Over the last two decades, various contaminants of emerging concern (CECs), such as endocrine disrupting compounds, along with pharmaceuticals and personal care products (PPCPs), have been of interest to the water industry because of their incomplete removal during the typical water and wastewater treatment processes. Recently, the potential environmental applications of metal-organic frameworks (MOFs) and MOF-based nanoadsorbents (MOF-NAs) have been widely studied. In particular, the use of these nanoadsorbents for CECs in water and wastewater treatment processes has been a rapidly growing area of interest in the recent literature due to their unique physicochemical properties. Therefore, it is necessary to understand the adsorption phenomena of various CECs by MOF-NAs, particularly because the physicochemical properties of various CECs create unique challenges for the removal of these compounds from water. In addition, the adsorption of CECs on MOF-NAs is significantly influenced by the physicochemical properties of the MOF-NAs and the water quality conditions. Therefore, this review provides a comprehensive assessment of recent studies on the removal of various CECs (e.g., analgesics, antibiotics, antiepileptics, antiseptics, and etc.) with different physicochemical properties by various MOF-NAs under various water quality conditions (e.g., pH, background ions/ionic strength, natural organic matter, and temperature). In addition, this review briefly discusses the recent literature on the synthesis of MOF-NAs, regeneration of MOF-NAs, and removal of CECs during water and wastewater treatment processes.
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This work shows an easy and eco-friendly methodology to obtain almost pristine anatase phase of TiO2 by using furfural, a biomass-derived molecule, as a bio-template. The ...photocatalytic activity was studied following the degradation of methylene blue and phenol under artificial solar irradiation. Results were compared against those obtained on a commercial pristine anatase TiO2. The pseudo first-order, the second-order and the intraparticle diffusion kinetic models were verified. The textural and surface chemistry properties of the materials were correlated with the surface density of molecules adsorbed in equilibrium. The reaction-rate showed an almost perfect quadratic regression as a function of the surface density. Theoretical estimations of the density of states by DFT + U were performed showing that the total electron charge in the oxygen bonded to anatase TiO2 increased due to carbon doping in agreement with the prediction of appearance of atomic orbitals 2p from carbon atom in the hybrid material. C-doping is responsible of the red-shift from 3.14 to 2.94 eV observed for a Ti15O32C super-cell than pristine anatase Ti16O32. The increase in the activity of the C-doped TiO2 photocatalyst was due to the decrease in the energy band-gap promoting a higher absorption of photons from the visible light.
Dengue, caused by dengue virus (DENV) infection, is a public health problem worldwide. Although DENV pathogenesis has not yet been fully elucidated, the inflammatory response is a hallmark feature in ...severe DENV infection. Although vitamin D (vitD) can promote the innate immune response against virus infection, no studies have evaluated the effects of vitD on DENV infection, dendritic cells (DCs), and inflammatory response regulation. This study aimed to assess the impact of oral vitD supplementation on DENV-2 infection, Toll-like receptor (TLR) expression, and both pro- and anti-inflammatory cytokine production in monocyte-derived DCs (MDDCs). To accomplish this, 20 healthy donors were randomly divided into two groups and received either 1000 or 4000 international units (IU)/day of vitD for 10 days. During pre- and post-vitD supplementation, peripheral blood samples were taken to obtain MDDCs, which were challenged with DENV-2. We found that MDDCs from donors who received 4000 IU/day of vitD were less susceptible to DENV-2 infection than MDDCs from donors who received 1000 IU/day of vitD. Moreover, these cells showed decreased mRNA expression of TLR3, 7, and 9; downregulation of IL-12/IL-8 production; and increased IL-10 secretion in response to DENV-2 infection. In conclusion, the administration of 4000 IU/day of vitD decreased DENV-2 infection. Our findings support a possible role of vitD in improving the innate immune response against DENV. However, further studies are necessary to determine the role of vitD on DENV replication and its innate immune response modulation in MDDCs.
Blastocystis sp. is among the most frequent intestinal protists identified in humans globally. However, characterization of Blastocystis subtype diversity in humans is ongoing. We report here the ...identification of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening involving colonoscopy and fecal testing (microscopy, culture, PCR). The full‐length ssu rRNA gene sequence of the protist was generated using MinION long‐read sequencing technology. The validity of the novel subtype was confirmed via phylogenetic and pairwise distance analyses of the full‐length ST41 sequence and all other valid subtypes. The study provides reference material essential for conducting subsequent experimental studies.
Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer‐related mortality worldwide. Although the utility of ...noninvasive biomarkers based on circulating cell‐free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre‐ and postsurgery plasma samples will reveal OCSCC‐specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor‐specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head‐neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma‐derived cfDNA was analyzed by cfMBD‐seq, which is a high‐sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC‐specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma‐based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome‐wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA‐based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon ...histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex‐pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.
Not infrequently pathologists encounter cases in which the diagnosis of pleomorphic adenoma may prove difficult. In such cases, the diagnostic dilemma can be solved by asking three practical questions. However, due to the morphological diversity of pleomorphic adenoma there are pitfalls that make it difficult to give clear answers to these questions.
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