Mild Procedure Research Articles

Management of cerebrospinal fluid leak after a minimally invasive lumbar decompression procedure: illustrative case.

Neurogenic claudication caused by lumbar stenosis is a prevalent disorder of the spinal canal for which many treatment options exist. The mild (minimally invasive lumbar decompression) procedure has recently been introduced as a safe and effective alternative to medical management in the treatment of lumbar stenosis. However, data on complications are rarely reported, and the incidence of complications, when reported, is frequently assessed at 0% in the literature. The case of a patient with a cerebrospinal fluid leak following a mild procedure performed at an outpatient facility who presented to an inpatient emergency department is discussed. After lumbar drainage failed, the patient required 2 operative procedures to rectify the leak. A seemingly innocuous procedure may have highly morbid complications requiring a lengthy inpatient stay and return trips to the operating room. The physicians and surgeons who manage these complications are frequently not those who performed the index procedure; they should be educated on the risks of the procedure and best practices for definitive management. https://thejns.org/doi/10.3171/CASE24497.

Chemoselective Anaerobic Dehydrogenation of Alcohols By Using Visible Light and a Positively Charged Deazaflavin Catalyst Regenerated by Acetonitrile Solvent

Three series of novel deazaflavinum salts differing in their substitutions at positions 5 (R = H, phenyl or mesityl), 7 and 8 (R = OMe, Me, H or Cl) were synthesized as potential catalysts of a novel chemoselective visible light–mediated anaerobic oxidation of primary and secondary alcohols to carbonyl compounds. This mild procedure uses acetonitrile as a solvent, which acts simultaneously as a sacrificial electron acceptor (in place of the oxygen usually used in photooxidation reactions) and therefore the reaction does not need any additives. Structural and properties‐versus‐catalytic activity studies identified 5‐mesityl‐7,8‐dimethoxy‐3‐methyldeazaflavinium chloride (3a‐Cl) as the most potent catalyst. 3a‐Cl was effective in non‐deuterated acetonitrile (CH3CN), unlike its original 5‐phenyl analogue 2a‐Cl, which is efficient only in deuterated solvent (CD3CN). This difference arises because the regeneration of the 2a‐Cl catalyst is slower in CH3CN than in CD3CN. Our method using the optimized 3a‐Cl photocatalyst and CH3CN as a sacrificial oxidant and solvent in one is a useful addition to synthetic organic chemistry. Anaerobic conditions prevent side oxygenation reactions and overoxidations that usually occur in air or oxygen. This property makes this method suitable for dehydrogenations of alcohols that possess additional group(s) sensitive to oxygenation.

Mild Opening Procedure to Obtain Open-ended yet Long Single-Wall Carbon Nanotubes for Subsequent Filling

Mild Opening Procedure to Obtain Open-ended yet Long Single-Wall Carbon Nanotubes for Subsequent Filling

Grafting of nonpolar polyisoprene as midblock and polar polylactide as outer block onto cellulose to produce bio-based thermoplastic elastomers

Sustainable cellulose-graft-diblock copolymers (cellulose-graft-polyisoprene-block-polylactide, MCC-g-PI-b-PLLA, MCC was chemically-modified microcrystalline cellulose) were designed and delicately synthesized for the first time by a mild and facile procedure via combining ring-opening polymerization and reversible addition-fragmentation chain transfer polymerization techniques, which conquered the difficulties in synthesis due to the distinct chemical properties among the MCC backbone, PI and PLLA blocks. Two separate glass transition temperatures were detected for MCC-g-PI-b-PLLA copolymers by differential scanning calorimetry, indicative of microphase separation, consistent with small-angle X-ray scattering and atomic force microscopy measurements. The α-form crystals of PLLA outer blocks were revealed by wide-angle X-ray diffraction measurement. The monotonic and step-cyclic tensile tests revealed that the mechanical property could be tuned by changing the molecular mass of PI midblock. The two ends of the soft PI midblock were anchored by rigid cellulose backbone and hard PLLA outer block, respectively, which served as physical crosslinking points. The rigid cellulose backbones brought the PI rubbery domains and PLLA hard domains together to form a whole hierarchical microstructure, endowing the copolymers with distinguished mechanical property. This work provided a feasible approach to producing environmental-friendly cellulose-based copolymers with fully biomass-derived feedstocks, having a profound impact on the development of sustainable polymer-based materials.

Synthesis and Characterization of Novel 2-Alkyl-1,3,4-Oxadiazoles Containing a Phenylazo Group.

An efficient method for the synthesis of novel phenylazo-containing moieties is described. The derivatives of 5-(4-(phenyldiazenyl)phenyl)-1,3,4-oxadiazole, substituted at position 2 of the heterocyclic scaffold with alkyl groups of different chain lengths, were prepared. The titled compounds were obtained using the appropriate 4-(5-alkyl-1,3,4-oxadiazol-2-yl)anilines, which were directed to diazotization and subsequently coupled to phenol, resorcinol, and N,N-dimethylaniline. Additionally, we report a mild and effective procedure for the preparation of 4-(5-alkyl-1,3,4-oxadiazol-2-yl)anilines via the selective reduction of the corresponding 2-alkyl-5-(4-nitrophenyl)-1,3,4-oxadiazoles using sodium borohydride-tin(II) chloride dihydrate as the reducing system. The chemical structures of the prepared compounds were confirmed by 1H- and 13C-NMR, IR, and UV-Vis spectroscopy.

Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment

With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.

Photoredox/Copper Dual-Catalyzed Phosphorothiolation of Propargylic Derivatives for the Switchable Synthesis of S-Alkyl, S-Vinyl and S-Allenyl Phosphorothioates.

Herein, we report a photoredox/copper dual-catalyzed selective phosphorothiolation of propargylic derivatives from easily accessible [P(O)SH] compounds. This reaction provides a general, mild and versatile procedure to synthesize a variety of synthetically useful S-alkyl, S-vinyl and S-allenyl phosphorothioates selectively from the same set of simple starting materials.

Mild and Stereoselective Synthesis of (1E,3E)-Dienes through Silver(I)-Catalyzed β-Hydride Migration from Allylic α-Diazo Esters

AbstractA mild procedure for the diastereoselective preparation of functionalized 1,3-dienes and their synthetic versatility are described herein. The silver-catalyzed decomposition of α-diazo-γ,δ-unsaturated esters through β-hydride migration at room temperature resulted in the stereoselective formation of 12 conjugated (1E,3E)-dienes. Further synthetic post-modifications included intramolecular Heck reaction and hydrogenation, leading to a novel substituted indene and an aliphatic diester, respectively. To rationalize the observed reaction outcome, a computational investigation of the mechanisms was conducted, emphasizing the importance of factors such as metallocarbenoid stability, substituent effects, and microkinetics simulations to better understand the reaction intricacies.

Photocatalyst-Free Visible Light-Induced C(sp2)-H Arylation of Quinoxalin-2(1H)-ones and Coumarins.

Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.

Carbon-in-carbon: Hybrid carbonized nanomaterials with multifunctional activities for the treatment of endophthalmitis

Infectious endophthalmitis (EO) is a severe eye condition characterized by inflammation of the eye’s internal fluids and tissues, often resulting from infection by bacteria or fungi. Patients with EO typically experience reduced vision, pain, and conjunctival infection. Despite the use of antibiotics, challenges such as inflammation and drug resistance remain. In this work, we have developed dextran/aliphatic diamines carbonized nanogels (DEX/ADA-CNGs) as board-spectrum antimicrobial agents by a one-step mild carbonization procedure. The CNGs exhibit not only antimicrobial properties but also show good drug delivery potential. Curcumin-based carbon quantum dots (Cur-CQDs) as an anti-inflammatory agent are loaded into DEX/ADA-CNGs to form hybrid carbon-in-carbon nanocomposites (Cur-CQDs@DEX/ADA-CNGs), showing combined antimicrobial, antioxidative, and anti-inflammatory activities. Impressively, CQDs@DEX/ADA-CNGs maintain strong antibacterial effectiveness against drug-resistant strains, with minimum inhibitory concentrations below 110 µg mL−1. The Cur-CQDs@DEX/ADA-CNGs have demonstrated high biocompatibility both in vitro and in vivo. In a rat model of EO, they rapidly (less than 5 days) reduce microbial infection and inflammation in the eye. Given these promising results, Cur-CQDs@DEX/ADA-CNGs show great potential as an enduring intravitreal treatment option for infectious EO.

A four-component protocol for tandem C–S and C–C bond formation to access thienopyrrolediones under transition-metal free conditions

A mild and simple multicomponent procedure has been established for the preparation of substituted thienopyrrolediones. The advantages of this strategy include the use of a cheap, stable and smell-free in nature sulfur source, readily available raw materials, wide substrate scope, easily-handled protocol and a simple metal free procedure.

I2-Mediated Site-Selective C-H Functionalization: Access to p-Amino-Substituted Unsymmetrical Benzils and Quinoxalines from Sulfoxonium Ylides.

An I2-mediated approach for selective C-H functionalization of unprotected aniline derivatives for synthesizing benzils and quinoxaline derivatives from sulfoxonium ylides has been described. Aniline derivatives and sulfoxonium ylides ornamented with different functional groups showed good compatibility. They afforded the corresponding products with moderate to high yields via a mild and simple procedure. Finally, we validated the practicality of this method by scaling up the reaction and further conversion of the synthesized derivatives into other valuable molecules.

Cytotoxicity evaluation of sub-10-nm silver colloid prepared by electrolytic synthesis procedure

Silver nanoparticles with smaller scales tend to exhibit higher cytotoxicity. In the present work, a mild electrolytic synthesis procedure is proposed and implemented for the preparation of sub-10-nm silver colloids in polarity organic solvent media by using the nonionic polymer as a stabilizer. The synthesized silver nanoparticles can be stably dispersed in salt, acid, and alkali dispersion media. The cell viability and cytotoxicity are investigated by fluorescein diacetate/propidium iodide double staining and thiazolium blue colorimetry in vitro. Under concentration-gradient and time-gradient tests, the synthesized silver nanoparticles exhibit significant cytotoxicity against the human hepatocellular carcinoma cells of HepG2 and the human non-small cell lung cancer cells of A549 at the exposure dose of 1.6 and 2.0 ug mL−1, respectively.

Scalable Synthesis of Bilayer Graphene at Ambient Temperature.

In this work, we develop for the first time a facile chemical lithiation-assisted exfoliation approach to the controllable and scalable preparation of bilayer graphene. Biphenyl lithium (Bp-Li), a strong reducing reagent, is selected to realize the spontaneous Li-intercalation into graphite at ambient temperature, forming lithium graphite intercalation compounds (Li-GICs). The potential of Bp-Li (0.11 V vs Li/Li+), which is just lower than the potential of stage-2 lithium intercalation (0.125 V), enables the precise lithiation of graphite to stage-2 Li-GICs (LiC12). Intriguingly, the exfoliation of LiC12 leads to the bilayer-favored production of graphene, giving a high selectivity of 78%. Furthermore, the mild intercalation-exfoliation procedure yields high-quality graphene with negligible structural deterioration. The obtained graphene exhibits ultralow defect density (ID/IG ∼ 0.14) and a considerably high C/O ratio (∼29.7), superior to most current state-of-the-art techniques. This simple and scalable strategy promotes the understanding of chemical Li-intercalation methods for preparing high-quality graphene and shows great potential for layer-controlled engineering.

Selective Methylation of Nucleosides via an In Situ Generated Methyl Oxonium.

A very mild and efficient procedure has been developed for the preparation of N-methylated uridine, pseudouridine, guanosine and inosine derivatives. This process was compatible with free hydroxyls within the ribose and did not require precautions on the protection or deprotection of other functionalities. The key to this extremely mild methylation without protection relied on the in situ generated methyl oxonium from the Wittig reagent and methanol. A putative mechanism for the selective methylation was also proposed.

Sulfated phenolic polymers as non-toxic antifouling agents

Nature-inspired highly sulfated bioactive polyphenols are recently emerging as antifouling agents with low or non-toxic effects to the environment representing a valuable alternative to the most used harmful biocides. In this frame, we report herein the preparation of sulfated derivatives of two phenolic polymers of tyrosol and gallic acid previously obtained via a convenient horseradish peroxidase/H2O2-catalyzed oxidation process. A mild sulfation procedure based on the use of sulfur trioxide triethylamine complex under microwave irradiation afforded the corresponding sulfated polymers OligoTyrS and OligoGallS in good yields (90–95 % w/w). Elemental analysis, FT-IR and MALDI-MS investigation provided evidence for an almost complete sulfation of the –OH groups. In line with a high degree of sulfation, OligoTyrS and OligoGallS exhibited lower antioxidant properties compared to the non-sulfated polymers as evaluated by the 2,2-diphenyl-1-picrylhydrazyl and ferric reducing/antioxidant power assays. In contrast to the non-sulfated polymers, OligoTyrS and OligoGallS showed a significant inhibitory effect against the settlement of mussel (Mytilus galloprovincialis) plantigrade without lethality effects and without affecting the selected biofilm-forming organisms like five marine bacteria and a diatom. Both sulfated polymers were also found to be non-toxic to the non-target species Artemia salina. The overall results presented herein put forward the potential of non-natural sulfated phenolic polymers as new non-toxic antifouling agents.

Evaluation of the Expansion and Neuronal Differentiation Potency of Cultured Olfactory Epithelium Progenitor Cells from a Rat Model of Depression.

Olfactory impairment has been reported in patients with depression and in rodent models of depression. Olfactory epithelium (OE) is the only peripheral neural tissue connected to the brain that has the potential for self-renewal. We hypothesized the olfactory deficit during depression may be related to the dysfunction of OE progenitor cells. The aim of the present study was therefore to evaluate the expansion and neuronal differentiation potency of cultured OE progenitor cells obtained from a rat model of depression. Rats were exposed to chronic unpredictable mild stress procedures to establish a depressive-like state. Depressive-like behavior and olfactory sensing function were then evaluated and compared with control rats. Primary OE progenitor cells were cultured in vitro. The proliferation potency and survival of OE progenitor cells were assessed by 5-Ethynyl-2'-deoxyuridine staining and Cell Counting Kit-8 (CCK8), respectively, while cellular apoptosis was measured by flow cytometry. The neuronal differentiation potency of OE progenitor cells was evaluated by measurement of the protein and mRNA level of β-3 tubulin, a marker of neural cells. mRNA expression associated with neural stemness was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Depressive-like rats showed decreased olfactory function. OE progenitor cells from depressive-like rats showed reduced cell proliferation/survival and neuronal differentiation potency. Moreover, OE progenitor cells from depressive-like rats showed decreased expression of mRNA related to neural stemness. These results indicate the impaired function of OE progenitor cells may contribute to the olfactory deficit observed during depression. The OE may therefore provide a window for the study of depression.

Chemo‐Enzymatic Synthesis of Navarixin by Using Aqueous Micellar Media: A Greener Approach

AbstractA mild and scalable chemo‐enzymatic procedure for the synthesis of the anticancer drug navarixin was developed in aqueous micellar media. We herein, report a greener methodology for the synthesis of a key chiral amine intermediate in the synthesis of navarixin using transaminases. This was obtained in high yields with an enantiomeric excess of >99.9 %. The current synthetic method represents a mild and sustainable procedure to afford the chiral amine intermediate in a single step without the use of expensive chiral ligands and auxiliaries. Furthermore, the chiral amine was used in the synthesis of navarixin which was obtained in high yield and an enantiomeric excess of >97.7 %.

Nephroprotective properties of Achillea millefolium green-formulated Au NPs in streptozotocin-induced diabetic nephropathy in mice: Introducing a novel therapeutic drug for the treatment of nephropathy

We have reported biosynthesis of Au NPs by using Achillea millefolium aqueous extract under mild procedure. Various techniques like UV–Vis, TEM, FE-SEM, EDS-elemental mapping and ICP-OES were used to characterize present nanoparticles. In the in vivo condition, streptozotocin (STZ) with dose of 60 mg/kg was used intraperitoneally for inducing diabetes in 100 mature male mice. The negative control mice were treated with normal saline and other mice were treated with glibenclamide (0.5 mg/kg) and Au nanoparticles (10 and 40 μg/kg) by gavage for 20 days. Additionally, 20 diabetic mice were considered as positive control and received the normal saline. Gold nanoparticles reduced the raised concentrations of urea and blood glucose in biochemical assays and volumes and lengths of vessels, loop of Henle, collecting ducts, and distal and proximal tubules in stereological assays in comparison with the untreated group. According to the obtained findings, gold nanoparticles can ameliorate the raised levels of biochemical parameters and prevent kidney structure damage in STZ-induced diabetic mice.

Efficient construction of a β-naphthol library under continuous flow conditions.

A β-naphthol library has been efficiently constructed utilizing a mild continuous flow procedure, relying on a tandem Friedel-Crafts reaction and starting from readily available arylacetyl chloride and alkynes. Multiple functionalized β-naphthols can be acquired within 160 s in generally high yields (up to 83%). Using an electron-rich phenylacetyl chloride derivative (4-OH- or 4-MeO-) provides spirofused triene dione as the primary product. A scale-up preparation affords a throughput of 4.70 g h-1, indicating potential large-scale application. Herein, we present a rapid, reliable, and scalable method to obtain various β-naphthols in the compound library.