Unexpected Reaction Research Articles

A Novel Prehydrated Porcine-Derived Acellular Dermal Matrix: A Histological and Clinical Evaluation.

It is well known that soft tissue quality and quantity around dental implants is of paramount importance for later peri-implant health. For this purpose, the clinical and histological outcomes of the peri-implant mucosa, following soft tissue augmentation for soft tissue improvement with a novel prehydrated porcine acellular dermal matrix graft (PPADMG) in conjunction with simultaneous implant placement, were evaluated in this case series. Twenty-two patients were included in the study. They underwent a late implant placement protocol combined with PPADMG for soft tissue augmentation. A punch biopsy was taken at the time of uncovery of the submerged healed implant after a mean of 157 days healing time. Supracrestal soft tissue height (STH) was measured at the time of implant placement and uncovery. All sites showed a clinical increase in STH. The histological structure of the biopsies resembled a similar structure as found in the healthy oral mucosa. No unexpected tissue reactions could be found. Within the limits of this clinical and histological study, it may be concluded that STH improvement with this novel porcine-derived acellular dermal matrix, in combination with simultaneous implant placement, is a viable option to create a peri-implant tissue thickness and stability.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database.

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Protein desulfurization and deselenization.

Methods enabling the dechalcogenation of thiols or selenols have been investigated and developed for a long time in fields of research as diverse as the study of prebiotic chemistry, the engineering of fuel processing techniques, the study of biomolecule structures and function or the chemical synthesis of biomolecules. The dechalcogenation of thiol or selenol amino acids is nowadays a particularly flourishing area of research for being a pillar of modern chemical protein synthesis, when used in combination with thiol or selenol-based chemoselective peptide ligation chemistries. This review offers a comprehensive and scholarly overview of the field, emphasizing emerging trends and providing a detailed and critical mechanistic discussion of the dechalcogenation methods developed so far. Taking advantage of recently published reports, it also clarifies some unexpected desulfurization reactions that were observed in the past and for which no explanation was provided at the time. Additionally, the review includes a discussion on principal desulfurization methods within the framework of newly introduced green chemistry metrics and toolkits, providing a well-rounded exploration of the subject.

Lysosome passivation triggered by silver nanoparticles enhances subcellular-targeted drug therapy.

Frequently, subcellular-targeted drugs tend to accumulate in lysosomes after cellular absorption, a process termed the lysosomal trap. This accumulation often interferes with the drug's ability to bind to its target, resulting in decreased efficiency. Existing methods for addressing lysosome-induced drug resistance mainly involve improving the structures of small molecules or enveloping drugs in nanomaterials. Nonetheless, these approaches can lead to changes in the drug structure or potentially trigger unexpected reactions within organisms. To address these issues, we introduced a strategy that involves inactivating the lysosome with the use of Ag nanoparticles (Cy3.5@Ag NPs). In this method, the Cy3.5@Ag NPs gradually accumulate inside lysosomes, leading to permeation of the lysosomal membrane and subsequent lysosomal inactivation. In addition, Cy3.5@Ag NPs also significantly affected the motility of lysosomes and induced the occurrence of lysosome passivation. Importantly, coincubating Cy3.5@Ag NPs with various subcellular-targeted drugs was found to significantly increase the efficiency of these treatments. Our strategy illustrates the potential of using lysosomal inactivation to enhance drug efficacy, providing a promising therapeutic strategy for cancer.

Concise Synthesis of Thiazolo[4,5‐b]indoles via Ring Switch/Cyclization Sequences

AbstractThe unexpected reactions of indoline hemiaminals affords 2,5‐diaryl‐4‐hydroxythiazolines through a thioamidation/ring switch sequence. The key to success of this transformation is to use a thioamide as a thiazoline precursor under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance (17 examples, up to 99 % yield). Further transformations of the thiazolines provide a direct entry to dihydrothiazolo[4,5‐b]indoles and thiazolo[4,5‐b]indoles.

ANAPHYLACTIC SHOCK DUE TO PROPHYLACTIC ANTIBIOTICS IN PLANNED SECTIO CESAREAN : A CASE REPORT

Introduction: Anaphylactic reactions during pregnancy are complex to diagnose and manage, potentially ranging from mild symptoms to life-threatening situations for both the mother and fetus. With an incidence varying from 1.44 to 2.7 cases per 100,000 births and subtle, overlapping symptoms with other obstetric emergencies, accurate identification remains a challenge. Despite being underdiagnosed, severe anaphylactic events during pregnancy share symptoms with other critical conditions, making differentiation intricate. Prior reviews and recent data underscore the necessity for guidelines and public health actions, emphasizing the importance of vigilance and specific management strategies in obstetrics. Case report: This case involves Ny. S, a 33-year-old pregnant woman undergoing an elective C-section, who developed an allergic reaction to Cefazolin, necessitating an emergency procedure and subsequent ICU admission due to anaphylactic complications. Patient at 38 weeks pregnant, encountered an unexpected allergic reaction during a planned C-section, necessitating an emergency procedure. Post-surgery, she experienced severe complications, including pulmonary and laryngeal edema, requiring intensive care. With prompt medical attention and a comprehensive treatment plan, including medications and careful monitoring, her condition stabilized over several days. By October 21, 2023, she showed significant improvement, allowing her discharge with scheduled follow-up care. Discussion: The discussion encompasses the complexity of diagnosing anaphylaxis during pregnancy, highlighting challenges in laboratory confirmation, management protocols mirroring non-pregnant guidelines, and the importance of coordinated medical care to avert adverse maternal and fetal outcomes. It emphasizes the need for standardized protocols and consensus among healthcare providers to effectively manage maternal anaphylaxis, reflecting on the rarity of this condition and the potential risks it poses to both the mother and fetus. Conclusion: Anaphylactic reaction during an elective C-section, prompting urgent medical intervention involving mechanical ventilator support and meticulous care. Patient’s subsequent recovery and discharge, along with fluctuating lab results indicating an acute immune response, underscore the complexity of diagnosing and managing maternal anaphylaxis, emphasizing the need for standardized protocols and coordinated healthcare approaches.

Faber Polynomial Coefficient Inequalities for a Subclass of Bi-Close-To-Convex Functions Associated with Fractional Differential Operator

In this study, we begin by examining the τ-fractional differintegral operator and proceed to establish a novel subclass in the open unit disk E. The determination of the nth coefficient bound for functions within this recently established class is accomplished by the use of the Faber polynomial expansion approach. Additionally, we examine the behavior of the initial coefficients of bi-close-to-convex functions defined by the τ-fractional differintegral operator, which may exhibit unexpected reactions. We established connections between our current research and prior studies in order to validate our significant findings.

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

An unexpected side reaction in the transformation of an alcohol to an amine facilitated by triflic anhydride-pyridine

Two N-triflyl-4-vinyl-1,4-dihydropyridines 3 and 4 were identified as isomeric impurities in the mother liquor of a 3-step “telescopic” transformation of a secondary alcohol 1 to an amine 2 facilitated by triflic anhydride-pyridine. The vinyl ether moiety of impurities 3 and 4 was readily hydrolyzed under acidic condition to form a keto-alcohol product 5 where four chiral centers were established on a cyclopentane ring. Another keto-alcohol impurity 6 was also isolated from the same mother liquor and identified as a hydrolysis product of the putative vinyl ether intermediate V in support of postulating a plausible mechanism for such an unexpected side reaction. The unexpected finding of the vinyl ether intermediate V could be derivatized with electrophiles besides N-triflylpyridinium to form a variety of compounds with four chiral centers established on a cyclopentane ring.

Synthesis of Polycyclic Arenes Composed of Four-, Five-, Six-, and Eight-Membered Rings via an Unexpected Four-Membered Ring Formation Reaction.

The synthesis of polycyclic arenes composed of four-, five-, six-, and eight-membered rings via an unexpected four-membered ring formation reaction is reported. The carbonylation of an octalithiated tetraphenylene yielded a tricarbonylated arene containing a four-membered ring or a tetracarbonylated one, depending on the carbonyl reagents. The structures were determined by X-ray crystallography, and their electronic properties were examined by using absorption spectroscopy and cyclic voltammetry. The antiaromaticity of the four-, five-, and eight-membered rings of these compounds was studied by theoretical calculations.

Efficacy and Safety of Pea Protein and Xyloglucan Versus Simethicone in Functional Abdominal Bloating and Distension

BackgroundFunctional Abdominal Bloating and Distension (FABD) is a multifaceted condition related in part to trapped gas, with changes in the intestinal barrier and small intestinal bacterial overgrowth (SIBO), which lead to gas production. Currently, there are no treatments targeting the etiology of FABD.MethodsThis double-blind, multicenter, randomized study evaluated the safety and efficacy of a product containing xyloglucan and pea proteins (XG + PP) compared with simethicone, both administered orally (three times daily) for 20 consecutive days. Eighty-eight patients with FABD were randomly assigned to the two groups in a 1:1 ratio. Primary outcome was safety; secondary outcomes were (i) efficacy in alleviating the symptoms of FABD and (ii) efficacy in reducing SIBO, as assessed by hydrogen breath test (HBT).ResultsNo Adverse Events or Serious Unexpected Adverse Reactions were reported during the study. XG + PP showed a faster onset of action and a significant reduction in bloating and abdominal pain compared with simethicone. At Day 20, XG + PP drastically reduced abdominal girth when compared with simethicone, with an average reduction of 4.7 cm versus 1.8 cm. At Day 20, the XG + PP arm showed a significant reduction in HBT compared to baseline.ConclusionsThis study supports the evidence that FABD patients may benefit from a XG + PP-based treatment that acts on etiology and not just the symptoms.

Enhancing catalytic ozonation activity of aluminum oxide via fluorine-doping engineering for water purification

Manipulating the electron density of active sties to develop highly efficient catalysts is expected to be one of the most ideal approaches to facilitate overall efficiency of the heterogenous catalytic ozonation (HCO) process. In this study, we demonstrate a fluorine-doping engineering to optimize the HCO activity of aluminum oxide through an improved sol–gel method using NH4F (NF-Al2O3) and HF (HF-Al2O3) as the fluorine source. We provide evidence that the fluorine atom is successfully incorporated into crystal structure of NF-Al2O3 via the formation of Al-F-Al bonds, accompany with the generation of oxygen vacancy defects, which allow for ozone molecule adsorption and activation. In contrast, the fabricated HF-Al2O3 only features the presence of AlxFy·nH2O instead of Al-F-Al structure probably due to the unexpected etching reaction. The introduction of fluorine atom largely decreases the local electron density of neighboring Al of NF-Al2O3 catalyst evidenced by the two-fold increment in the amount of strong Lewis acid sites. Consequently, the HCO activity of NF-Al2O3 catalyst is found promotion by 42.9% over pure Al2O3 in terms of the degradation kinetic rate constant (kobs). The NF-Al2O3 catalyst exhibits a powerful capacity to selectively catalyze ozone molecule into singlet oxygen (1O2), rendering the HCO system with high-tolerance to coexisting water matrixes (e.g., humic acid, chlorine ions, carbonate). Moreover, NF-Al2O3 initiated HCO system can effectively purify wastewaters from textile industry with high-quality enough to be reused for textile dyeing. Therefore, our study provides a novel strategy to develop effective HCO catalysts for promoting wastewater treatment and reuse.

Identification of novel glucocerebrosidase chaperones by unexpected skeletal rearrangement reaction

Compound 5 was identified from a high-throughput screening campaign as a small molecule pharmacological chaperone of glucocerebrocidase (GCase), a lysosomal hydrolase encoded by the GBA1 gene, variants of which are associated with Gaucher disease and Parkinson’s disease. Further investigations revealed that compound 5 was slowly transformed into a regio-isomeric compound (6) in PBS buffer, plausibly via a ring-opening at hemiaminal moiety accompanied by subsequent intramolecular CC bond formation. Utilising this unexpected skeletal rearrangement reaction, a series of compound 6 analogues was synthesized which yielded multiple potent GCase pharmacological chaperones with sub-micromolar EC50 values as exemplified by compound 38 (EC50 = 0.14 μM).

Dearomative Ring‐Fused Azafulleroids and Carbazole‐Derived Metallofullerenes: Reactivity Dictated by Encapsulation in a Fullerene Cage

AbstractHerein, we report divergent additions of 2,2′‐diazidobiphenyls to C60 and Sc3N@Ih‐C80. In stark contrast to that of the previously reported bis‐azide additions, the unexpected cascade reaction leads to the dearomative formation of azafulleroids 2 fused with a 7‐6‐5‐membered ring system in the case of C60. In contrast, the corresponding reaction with Sc3N@Ih‐C80 switches to the C−H insertion pathway, thereby resulting in multiple isomers, including a carbazole‐derived [6,6]‐azametallofulleroid 3 and a [5,6]‐azametallofulleroid 4 and an unusual 1,2,3,6‐tetrahydropyrrolo[3,2‐c]carbazole‐derived metallofullerene 5, whose molecular structures have been unambiguously determined by single‐crystal X‐ray diffraction analyses. Among them, the addition type of 5 is observed for the first time in all reported additions of azides to fullerenes. Furthermore, unexpected isomerizations from 3 to 5 and from 4 to 5 have been discovered, providing the first examples of the isomerization of an azafulleroid to a carbazole‐derived fullerene rather than an aziridinofullerene. In particular, the isomerism of the [5,6]‐isomer 4 to the [5,6]‐isomer 5 is unprecedented in fullerene chemistry, contradicting the present understanding that isomerization generally occurs between [5,6]‐ and [6,6]‐isomers. Control experiments have been carried out to rationalize the reaction mechanism. Furthermore, representative azafulleroids have been applied in organic solar cells, thereby resulting in improved power conversion efficiencies.

Unusual reaction of (E)-2-[(benzo[d]thia-zol-2-yl-imino)-meth-yl]-5-(di-ethyl-amino)-phenol with tri-phenyl-borane: crystal structures and optical properties.

The mol-ecular and crystal structure of (E)-2-[(benzo[d]thia-zol-2-yl-imino)-meth-yl]-5-(di-ethyl-amino)-phenol (C18H19N3O2S, Et2N-Bz) and its unexpected reaction product with tri-phenyl-borane, 2,2-diphenyl-1,3-dioxa-2-borata-1,2-di-hydro-naphthalene [systematic name: N,N-diethyl-2,2-diphenyl-2H-1,3λ3,2λ4-ben-zodioxaborinin-7-amine, C23H24BNO2, (I)] are described. For Et2N-Bz, the hydroxyl group is involved in an intra-molecular hydrogen bond with the imino nitro-gen atom and the C=N bond displays an E configuration. The crystal packing is characterized by layers of inversion dimers parallel to the (10) plane and chains of mol-ecule in the a-axis direction formed through C-H⋯O inter-actions. Complex (I) crystallizes with two mol-ecules (A and B) in the asymmetric unit, which differ in the orientation of the ethyl groups. The 1,3-dioxa-2-borata-1,2,3,4-tetra-hydro-naphthalene ring displays a slight envelope conformation with the boron atom as the flap. In the crystal packing, chains of alternating A and B mol-ecules formed by C-H⋯O hydrogen bonds run in the b-axis direction. The UV-vis absorption and emission properties of the compounds are discussed and their aggregation-induced emission properties are further investigated.

Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms.

The liver has a central role in metabolism, therefore, it is susceptible to harmful effects of ingested medications (drugs, herbs, and nutritional supplements). Drug-induced liver injury (DILI) comprises a range of unexpected reactions that occur after exposure to various classes of medication. Even though most cases consist of mild, temporary elevations in liver enzyme markers, DILI can also manifest as acute liver failure in some patients and can be associated with mortality. Herein, we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms: Chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and myelofibrosis.

Facile access to C-N bonds via unexpected side reactions of Knoevenagel condensation and their application in high-efficiency organic solar cells

Facile access to C-N bonds via unexpected side reactions of Knoevenagel condensation and their application in high-efficiency organic solar cells

Modulating Anion Redox Reactions and Structural Evolution Through Fe‐Substitution in Li6CoO4 Hyper‐Lithiated Sacrificial Cathodes

AbstractUtilizing hyper‐lithiated materials can offer a variety of options for designing high‐energy lithium‐ion batteries. As sacrificial cathodes, they compensate for the initial loss of Li+ at the anode. During the first delithiation process, a Fe‐substituted Li6CoO4 (Li5.7Co0.7Fe0.3O4) supplies a large amount of Li+. Especially, the peroxide species formation and oxygen evolution are suppressed even though the charge compensation of oxygen is facilitated in Li5.7Co0.7Fe0.3O4. From a structural viewpoint, the anti‐fluorite structure changes to defective disordered phases during the Li+ extraction, and the proportion of the electrochemical‐inactive phase is more dominant in the case of Li5.7Co0.7Fe0.3O4 at the end of the charge. Consequently, the delithiated LixCo0.7Fe0.3O4 is deactivated in subsequent cycles, reducing unexpected electrochemical reactions after the Li+ provision as sacrificial cathodes. These findings provide a comprehensive understanding of the reaction mechanism of hyper‐lithiated materials and represent a significant step forward in developing high‐performance sacrificial cathodes.

DMFDDI: deep multimodal fusion for drug-drug interaction prediction.

Drug combination therapy has gradually become a promising treatment strategy for complex or co-existing diseases. As drug-drug interactions (DDIs) may cause unexpected adverse drug reactions, DDI prediction is an important task in pharmacology and clinical applications. Recently, researchers have proposed several deep learning methods to predict DDIs. However, these methods mainly exploit the chemical or biological features of drugs, which is insufficient and limits the performances of DDI prediction. Here, we propose a new deep multimodal feature fusion framework for DDI prediction, DMFDDI, which fuses drug molecular graph, DDI network and the biochemical similarity features of drugs to predict DDIs. To fully extract drug molecular structure, we introduce an attention-gated graph neural network for capturing the global features of the molecular graph and the local features of each atom. A sparse graph convolution network is introduced to learn the topological structure information of the DDI network. In the multimodal feature fusion module, an attention mechanism is used to efficiently fuse different features. To validate the performance of DMFDDI, we compare it with 10 state-of-the-art methods. The comparison results demonstrate that DMFDDI achieves better performance in DDI prediction. Our method DMFDDI is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/DHUDEBLab/DMFDDI.git.

Solvation structure reorganization and interface regulation of poly (glycidyl POSS)-based electrolyte for quasi-solid-state lithium-ion batteries

The interfacial stability and some unexpected side reactions in quasi-solid-state lithium-ion batteries (LIBs) impede the practical application of the in-situ crosslinked polymer electrolytes. Herein, a novel in-situ crosslinked polymer electrolyte with eight-armed crosslinked supramolecular structure is constructed via cationic ring-opening polymerization of glycidyl polyhedral oligomeric silsesquioxane (POSS). The strong electrostatic and hydrogen bonding interactions of the POSS blocks with anions reorganize the solvation structure, and the overall oxidation resistance of anions can be also effectively enhanced benefiting from the relatively electron-withdrawing effect of the POSS blocks. Simultaneously, a hierarchical cathode-electrolyte interphase with flexibility and oxidation resistance is constructed involving the boron difluoride radical-catalyzed cleavage of Si-O-Si linkages in POSS frameworks. The poly (glycidyl POSS)-based electrolyte enables the Li||NCM83 cell to possess a high capacity retention of 79.1 % after 500 cycles. Moreover, the SiOx||NCM83 battery shows a capacity retention of 87.6 % after 200 cycles. These insights gained form this work opens up an avenue for the development and practical application of quasi-solid-state LIBs.