A radical approach for the selective C-H borylation of azines.

Boron functional groups are often introduced in place of aromatic carbon-hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1-3. Current approaches based on transition-metal-catalysed activation of carbon-hydrogen bonds are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines (nitrogen-containing aromatic heterocycles), which are key components of many pharmaceutical and agrochemical products6. Here we report an azine borylation strategy using stable and inexpensive amine-borane7 reagents. Photocatalysis converts these low-molecular-weight materials into highly reactive boryl radicals8 that undergo efficient addition to azine building blocks. This reactivity provides a mechanistically alternative tactic for sp2 carbon-boron bond assembly, where the elementary steps of transition-metal-mediated carbon-hydrogen bond activation and reductive elimination from azine-organometallic intermediates are replaced by a direct, Minisci9-style, radical addition. The strongly nucleophilic character of the amine-boryl radicals enables predictable and site-selective carbon-boron bond formation by targeting the azine's most activated position, including the challenging sites adjacent to the basic nitrogen atom. This approach enables access to aromatic sites that elude current strategies based on carbon-hydrogen bond activation, and has led to borylated materials that would otherwise be difficult to prepare. We have applied this process to the introduction of amine-borane functionalities to complex and industrially relevant products. The diversification of the borylated azine products by mainstream cross-coupling technologies establishes aromatic amino-boranes as a powerful class of building blocks for chemical synthesis.

Emerging role of lipophagy in liver disorders.

Lipophagy is a selective degradation of lipids by a lysosomal-mediated pathway, and dysregulation of lipophagy is linked with the pathological hallmark of many liver diseases. Downregulation of lipophagy in liver cells results in abnormal accumulation of LDs (Lipid droplets) in hepatocytes which is a characteristic feature of several liver pathologies such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Contrarily, upregulation of lipophagy in activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and cirrhosis. Lipid metabolism reprogramming in violent cancer cells contributes to the progression of liver cancer. In this review, we have summarized the recent studies focusing on various components of the lipophagic machinery that can be modulated for their potential role as therapeutic agents against a wide range of liver diseases.

Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors.

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.

Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice.

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.

Diagnostic and therapeutic value of EVs in lungs diseases and inflammation.

Extracellular vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarize the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease, asthma, and sarcoidosis.

Chiral Recognition of Amino Acids Using CC2 Porous Organic Cages.

Enantiomers have the same physical properties but different chemical properties due to the difference in the orientation of groups in space and thus Chiral discrimination is quite necessary, as an enantiomer of drug can have lethal effects. In this study, we used the CC2 cage for chiral discrimination of amino acids using density functional theory. The results indicated the physisorption of amino acids in the central cavity of the cage. Among the four selected amino acids, proline showed maximum interactions with the cage and maximum chiral discrimination energy is also observed in the case of proline that is 2.78 kcal/mol. Quantum theory of atoms in molecules and noncovalent interaction index analyses showed that the S enantiomer in each case has maximum interactions. The charge transfer between the analyte and surface is further studied through natural bond orbital analysis. It showed sensitivity of cage for both enantiomers, but a more pronounced effect is seen for S enantiomers. In frontier molecular orbital analysis, the least EH-L gap is observed in the case of R proline with a maximum charge transfer of -0.24 e-. Electron density difference analysis is carried out to analyze the pattern of the charge distribution. The partial density of state analysis is computed to understand the contribution of each enantiomer in overall density of the complexes. Our results show that S-CC2 porous organic cages have a good ability to differentiate between two enantiomers. S-CC2 porous organic cages efficiently differentiated the S enantiomer from the R enantiomers of selected amino acids.

Geometric, Electronic, and Optoelectronic Properties of Carbon-Based Polynuclear C3O[C(CN)2]2M3 (where M = Li, Na, and K) Clusters: A DFT Study.

Carbon-based polynuclear clusters are designed and investigated for geometric, electronic, and nonlinear optical (NLO) properties at the CAM-B3LYP/6-311++G(d,p) level of theory. Significant binding energies per atom (ranging from -162.4 to -160.0 kcal mol-1) indicate excellent thermodynamic stabilities of these polynuclear clusters. The frontier molecular orbital (FMOs) analysis indicates excess electron nature of the clusters with low ionization potential, suggesting that they are alkali-like. The decreased energy gaps (EH-L) with increased alkali metals size revael the improved electrical conductivity (σ). The total density of state (TDOS) study reveals the alkali metals' size-dependent electronic and conductive properties. The significant first and second hyperpolarizabilities are observed up to 5.78 × 103 and 5.55 × 106 au, respectively. The ßo response shows dependence on the size of alkali metals. Furthermore, the absorption study shows transparency of these clusters in the deep-UV, and absorptions are observed at longer wavelengths (redshifted). The optical gaps from TD-DFT are considerably smaller than those of HOMO-LUMO gaps. The significant scattering hyperpolarizability (ßHRS) value (1.62 × 104) is calculated for the C3 cluster, where octupolar contribution to ßHRS is 92%. The dynamic first hyperpolarizability ß(ω) is more pronounced for the EOPE effect at 532 nm, whereas SHG has notable values for second hyperpolarizability γ(ω).

Transition Metal Sensing with Nitrogenated Holey Graphene: A First-Principles Investigation.

The toxicity of transition metals, including copper(II), manganese(II), iron(II), zinc(II), hexavalent chromium, and cobalt(II), at elevated concentrations presents a significant threat to living organisms. Thus, the development of efficient sensors capable of detecting these metals is of utmost importance. This study explores the utilization of two-dimensional nitrogenated holey graphene (C2N) nanosheet as a sensor for toxic transition metals. The C2N nanosheet's periodic shape and standard pore size render it well suited for adsorbing transition metals. The interaction energies between transition metals and C2N nanosheets were calculated in both gas and solvent phases and were found to primarily result from physisorption, except for manganese and iron which exhibited chemisorption. To assess the interactions, we employed NCI, SAPT0, and QTAIM analyses, as well as FMO and NBO analysis, to examine the electronic properties of the TM@C2N system. Our results indicated that the adsorption of copper and chromium significantly reduced the HOMO-LUMO energy gap of C2N and significantly increased its electrical conductivity, confirming the high sensitivity of C2N towards copper and chromium. The sensitivity test further confirmed the superior sensitivity and selectivity of C2N towards copper. These findings offer valuable insight into the design and development of sensors for the detection of toxic transition metals.

Role of Delocalization, Asymmetric Distribution of π-Electrons and Elongated Conjugation System for Enhancement of NLO Response of Open Form of Spiropyran-Based Thermochromes.

Switchable nonlinear optical (NLO) materials have widespread applications in electronics and optoelectronics. Thermo-switches generate many times higher NLO responses as compared to photo-switches. Herein, we have investigated the geometric, electronic, and nonlinear optical properties of spiropyranes thermochromes via DFT methods. The stabilities of close and open isomers of selected spiropyranes are investigated through relative energies. Electronic properties are studied through frontier molecular orbitals (FMOs) analysis. The lower HOMO-LUMO energy gap and lower excitation energy are observed for open isomers of spiropyranes, which imparts the large first hyperpolarizability value. The delocalization of π-electrons, asymmetric distribution and elongated conjugation system are dominant factors for high hyperpolarizability values of open isomers. For deep understanding, we also analyzed the frequency-dependent hyperpolarizability and refractive index of considered thermochromes. The NLO response increased significantly with increasing frequency. Among all those compounds, the highest refractive index value is observed for the open isomer of the spiropyran 1 (1.99 × 10-17 cm2/W). Molecular absorption analysis confirmed the electronic excitation in the open isomers compared to closed isomers. The results show that reversible thermochromic compounds act as excellent NLO molecular switches and can be used to design advanced electronics.

Mitigating Drug Stability Challenges Through Cocrystallization.

Drug stability plays a significant role in the pharmaceutical industry from early-phase drug discovery to product registration as well as the entire life cycle of a product. Various formulation approaches have been employed to overcome drug stability issues. These approaches are sometimes time-consuming which ultimately affect the timeline of the product launch and may further require formulation optimization steps, affecting the overall cost. Pharmaceutical cocrystal is a well-established route to fine tune the biopharmaceutical properties of drugs without covalent modification. This article highlights the role of cocrystallization in mitigating the stability issues of challenging drug molecules. Representative case studies wherein the drug stability issue is addressed through pharmaceutical cocrystals have been discussed briefly and are summarized in tabular form. The emphasis has been made on the structural information of cocrystals and understanding the mechanism that improves the stability of the parent drug through cocrystallization. Besides, a guided strategy has been proposed to modulate the stability of drug molecules through cocrystallization approach. Finally, the stability concern of fixed-dose or drug combinations and the challenges associated with cocrystals are also touched.

Quercetin ameliorates thioacetamide-induced hepatic fibrosis and oxidative stress by antagonizing the Hedgehog signaling pathway.

The Hedgehog (Hh) pathway has emerged as a potential target for effectual hepatic repair based on convincing clinical and preclinical evidence that proves its significance in regulating hepatic damage. The purpose of this study is to probe the effect of quercetin on liver fibrosis through the modulation of the Hh pathway. Healthy male Wistar rats were divided into four groups (n = 10). The control group was treated with saline, rats in the remaining three groups received twice a week intoxication with intraperitoneal injections of thioacetamide (200 mg/kg) for the induction of hepatic fibrosis for 6 weeks. After 28 days of quercetin and silymarin treatment, histological changes, serum biochemical index, antioxidant enzyme activity, key mediators of Hh pathway and inflammation were analyzed. Serological analysis showed statistically improved cholesterol, H.D.L-Cholesterol, and L.D.L-Cholesterol in the treatment groups. Superoxide dismutase and glutathione levels were found to be increased after the treatment with quercetin and silymarin. mRNA expression of important mediators of the Hh signaling, and inflammation including Shh, Ihh, Ptch-1, Smo, Hhip, Gli-3, TNF-α, NFκ-ß, and Socs-3 were significantly downregulated after the use of quercetin and silymarin. Quercetin also minimized the thioacetamide-induced histopathological changes, as confirmed by a lower degree of hepatic lobule degeneration, the intralobular occurrence of inflammatory cells, and a lower degree of hepatocytic necrosis. Sudan Black B staining showed remarked lipids improvements in the treatment groups. Taken together, these findings demonstrate that quercetin could ameliorate hepatic fibrosis by antagonizing the hedgehog pathway and also suggest the hedgehog pathway as a potential therapeutic target for the treatment of liver fibrosis.

Genetic Analysis of Sodium Channel Genes in Pediatric Epilepsy Patients of Pakistan.

Epilepsy affects millions of people worldwide. Although antiepileptic drugs work for the majority of epileptic patients, these drugs do not work for some of the patients, subjecting them to drug-resistant epilepsy (DRE). Voltage-gated sodium channels act as targets for a number of antiepileptic drugs, and the genes encoding these channels can play a crucial role in developing drug-resistant epilepsy. This case-control (100 control: 101patients) study evaluated the association of sodium channel genes SCN1A and SCN2A with drug-resistant epilepsy. The cases were further accounted in two categories, drug-resistant and drug-responsive epileptic patients. The polymorphic sites rs794726754, rs1057518252, rs121918809, rs12191792, rs121917932, c.730 G > T, c.735 G > T, c.736 A > T, rs10167228, and rs2298771 of the SCN1A gene and rs17183814 of SCN2A gene were selected for mutational analysis. The DNA was isolated, amplified by PCR, and then, was run through 1% agarose gel. The sequencing was performed, and the sequences were observed through BioEdit software for any change in DNA sequence. In our study, no polymorphism was observed in the studied SNPs except for rs2298771. For rs2298771, a significant difference existed in the distribution of genotypic and allelic frequencies (p < 0.01) among the case and control group. Furthermore, the genotypic and allelic frequencies of the two categories of cases (drug responder drug resistant) were calculated. The genotypic and allelic frequencies of drug-responsive and drug-resistant epileptic patients did not differ significantly (p > 0.01). Our study indicated that the rs2298771 polymorphism of SCN1A may not be associated with chance of developing DRE in the Pakistani population.

Genetic Analysis of CYP2C9 with Reference to Drug Response in Epilepsy Patients of Pakistan.

Epilepsy is a major global issue. Epilepsy patients are treated with AED (antiepileptic drugs). Interindividual variability in drug response has been documented in several studies. The resistance to drug response may be attributed to genetic polymorphism. The current study was undertaken to investigate the CYP2C9 gene polymorphism associated with antiepileptic drug (AED) resistance in the Pakistani population. The current study included 337 individuals including 100 control subjects, 110 drug-resistant subjects, and 127 drug responders. Genomic DNA was isolated from blood, and amplification of rs1799853 (430C > T) and rs1057910 was carried out by polymerase chain reaction. Genotypes of CYP2C9 SNPs were determined by Sanger's sequencing. Astounding results were observed in the current study that none of the well-known reported SNPs of CYP2C9 was found in our Pakistani cohorts. However, a novel missense variant (c.374G > A) was found only in drug-resistant patients of the current study. According to the in silico analysis performed by PolyPhen-2, it was observed that this nonsynonymous substitution is likely to be pathogenic. The results of our study demonstrated that rs1799853 and rs1057910 may be involved in drug resistance in the Pakistani population. However, some other variants on CYP2C9 may play a critical role in AED resistance that needs to be explored.

TLR-8, TNF-α, and ESR-1α Gene Polymorphism Susceptibility in Onset of Arthritis.

Arthritis is a genetic disorder characterized by bones and joint degradation assisted by severe pain and inflammation. It is evident by the studies that 0 candidate genes variations play vital role in its development and progression. Therefore, we investigated the genetic variation of TLR-8, TNF, and ESR-1α genes in the Pakistani population. A case-control study comprising 300 RA, 316 OA, and 412 control subjects was conducted. PCR-RFLP and direct sequencing methods were used for determining genetic variations. Analysis was performed by using PLINK and MEGA 6.0 software. Allelic and genetic frequencies of polymorphisms identified on rs3764879 (TLR-8), rs3764880 (TLR-8), rs5744080 (TLR-8), rs1800629 (TNF), rs2228480 (ESR-1α), and rs1451501590 (ESR-1α) were significantly varied among RA, OA, and controls. Novel functional mutations SCV000844945 and SCV000844946 on TLR-8 as well as a non-functional SCV000804801 and functional variation SCV000804802 on ESR-1α were also identified and reported for the first time in the studied population. Multiple site analyses indicated that polymorphisms on TLR-8 and ESR-1α genes were significant risk factors in disease onset to the next generation. In conclusion, TLR-08 and ESR-1α were significant in the onset of arthritis whereas the TNF was not found as a significant risk factor in the onset of RA and OA.

Mechanistic study of regulation of iron homeostasis by N. sativa seeds and P. ovata husks on high fat/high sucrose diet induced non-alcoholic fatty liver disease.

BACKGROUND: In recent years, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions. Characteristic findings in NAFLD patients are elevated iron stores, as iron plays an important role in the pathophysiology of chronic liver disease. The current study was aimed at investigating the possible protective effects of N. sativa seeds and P. ovata husks on the regulation of iron homeostasis in NAFLD. METHODS: Two age groups of Wistar rats (four weeks and twelve weeks old), further subdivided into four groups were fed on high fat/high sucrose (HF/SF) diet for sixteen weeks to induce NAFLD and randomized into three groups (HF/SF diet control (Group I), HF/SF diet with N. sativa seeds (Group II) and HF/SF diet with P. ovata husks (Group III) and normal diet, serving as negative control (Group 0). At the end of the experiment, histochemical analysis of hepatic sections, biochemical evaluates of the blood, and gene expression analysis were conducted. RESULTS: The results revealed that both N. sativa seeds and P. ovata husks possess the capacity to maintain iron homeostasis by regulating the level of blood hemoglobin, serum iron contents, expression of key genes involved in iron metabolism, and iron deposition in hepatic sections. While N. sativa seeds proved more effective. CONCLUSIONS: N. sativa seeds are a more potent iron regulator compared to P. ovata husks at reducing the iron overburden associated with NAFLD.

High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver.

BACKGROUND: Disproportionate fatty diet intake provokes hepatic lipid accumulation that causes non-alcoholic fatty liver disease, triggering the embryonically conserved Hedgehog (Hh) pathway in the adult liver. The present study incorporates exploring the impact of chronically administered unsaturated (D-1) and saturated (D-2) fat-enriched diets on hematological parameters, liver functioning, and lipid profile in the rat model. Besides, hepatohistology and real time gene expression analysis of Hh signaling pathway genes i.e., Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were carried out. METHODS AND RESULTS: Fifteen Rattus norvegicus (♂) of 200 ± 25 g weight were grouped into control, D-1, and D-2. Animals were fed on their respective diets for 16 weeks. Fatty diet intake resulted in neutropenia, lymphocytosis, monocytosis, polycythemia, and macrocytosis in both experimental groups. Altered liver injury biomarkers, hypertriglyceridemia, and significantly increased very-low-density lipoprotein VLDL were also noted in both high-fat diet (HFD) groups as compared to control. Hepatohistological examination showed disrupted microarchitecture, infiltration of inflammatory cells, cellular necrosis, widened sinusoidal spaces, and microvesicular steatotic hepatocytes in D-1 and D-2. Collagen deposition in both HFD groups marks the extent of fibrosis. Significant upregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated in D-1. In D-2 Shh, Hhip, and Smo expressions were upregulated, Ihh exhibited downregulation as compared to control. CONCLUSION: Excess fat deposits in liver due to chronic consumption of high-fat diet results in anomalous architecture and functioning. High-fat diet induced significant variations in Hh pathway genes expression; especially Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated. Infiltration of inflammatory cells ( ), widened sinusoidal spaces (▲), cellular necrosis, and micro vesicular steatotic hepatocytes (*) were shown in the liver. Significant collagen deposition in both HFD groups i.e. D-1 and D-2 confirmed liver fibrosis. Excessive intake of dietary fats impaired normal liver functioning and liver inflammation triggered Hh signaling in adult rats.

Diagnostic, prognostic and therapeutic potential of long noncoding RNAs in cancer.

Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in length and undergo splicing, capping, polyadenylation, and editing just like mRNA. Evidence is growing that they regulate transcription, splicing, RNA degradation, and translation of genes and that their expression has been linked to a variety of illnesses, including cancer. The advancement of next-generation and high-throughput sequencing has changed the way lncRNAs are identified and characterized, revealing a relationship between lncRNAs and several tumor types. Since then, they have gained a significant attraction as a promising candidate in cancer diagnosis, prognosis, and therapy. Furthermore, they are a good candidate for consideration as tumor biomarkers due to their high stability, better tissue/cell selectivity, aberrant expression in certain malignancies, and easy and noninvasive detection. In addition, lncRNAs are being examined as therapeutic targets in clinical trials for a variety of malignancies. This review highlights the potential of lncRNAs as biomarkers or therapeutic targets in light of the current progress, clinical investigations, and patents filed so far.

An Integrated Experimental and Theoretical Studies on the Corrosion Inhibition of Carbon Steel by Harmal Extracts.

The corrosion inhibition effect of the three extracts from Harmal roots (HRE), leaves (HLE), and flowers (HFE) were studied for carbon steel corrosion inhibition in 0.25 M H2SO4 solution. The electrochemical impedance study indicated that the three types of extracts decreased corrosion effectively through a charge transfer mechanism. Harmal roots and leaf extracts showed inhibition values of 94.1% and 94.2%, while it was 88.7% for Harmal flower extract at the inhibitor concentration of 82.6 ppm. Potentiodynamic polarization data revealed that Harmal extracts acted through predominant cathodic type inhibition. Both the corrosion current density and corrosion rate decreased significantly in the presence of Harmal extracts compared to blank solution. The corrosion rate (mpy) value was 63.3, 86.1, and 180.7 for HRE, HLE, and HFE, respectively. The adsorption-free energy change ΔGads (kJ·mol-1) values calculated from the Langmuir adsorption isotherm plots were for HRE (-35.08), HLE (-33.17), and HFE (-33.12). Thus, corrosion inhibition occurred due to the adsorption of Harmal extract on the carbon steel surface via the chemisorption mechanism. Moreover, a computational investigation using B3LYP/6-311G++(d,p) basis set in both gaseous and aqueous phases was performed for the major alkaloids (1-8) present in the Harmal extract.

Dynamic Phenomena and Complexation Effects in the α-Lithiation and Asymmetric Functionalization of Azetidines.

In this work it is demonstrated that enantiomerically enriched N-alkyl 2-oxazolinylazetidines undergo exclusive α-lithiation, and that the resulting lithiated intermediate is chemically stable but configurationally labile under the given experimental conditions that afford enantioenriched N-alkyl-2,2-disubstituted azetidines. Although this study reveals the configurational instability of the diastereomeric lithiated azetidines, it points out an interesting stereoconvergence of such lithiated intermediates towards the thermodynamically stable species, making the overall process highly stereoselective (er > 95:5, dr > 85:15) after trapping with electrophiles. This peculiar behavior has been rationalized by considering the dynamics at the azetidine nitrogen atom, the inversion at the C-Li center supported by in situ FT-IR experiments, and DFT calculations that suggested the presence of η3-coordinated species for diastereomeric lithiated azetidines. The described situation contrasted with the demonstrated stability of the smaller lithiated aziridine analogue. The capability of oxazolinylazetidines to undergo different reaction patterns with organolithium bases supports the model termed "dynamic control of reactivity" of relevance in organolithium chemistry. It has been demonstrated that only 2,2-substituted oxazolinylazetidines with suitable stereochemical requirements could undergo C=N addition of organolithiums in non-coordinating solvents, leading to useful precursors of chiral (er > 95:5) ketoazetidines.

High-fat diet-induced splenic, hepatic, and skeletal muscle architecture damage: cellular and molecular players.

The trend of consuming food high in calories, fat, and sugar with little nutritional value and reduced physical exercise has resulted in an alarming ratio of overweight and obese subjects worldwide. Low-grade chronic inflammation is the key feature of obesity that causes an increase in pro-inflammatory cytokines and decrease in anti-inflammatory cytokines in circulation. The current study was aimed to investigate the effect of high-fat diet on the architecture of spleen, liver, and skeletal muscle and changes in the expression of hepatic cytokines. Two groups of experimental rats were established, against control that were given different percentage of fats in their diet. After a period of sixteen weeks, rats were dissected and their organs were excised out and processed accordingly. Spleen sections of experimental groups, revealed increased recruitment of lymphocytes, sinusoidal dilatations, necrotic lymphocytes, increased ratio of white-to-red pulp, and hemosiderin and iron deposits in red pulp indicating immune system activation. Hepatic sections showed enlarged sinusoidal spaces, disruptive hepatocytes, necrosis and dilation of portal veins. Sections of skeletal muscle showed degenerating fibers, increased fat accumulation, and recruitment of macrophages. Elevated expression of IFN-γ and decreased expression of IFN-α and IFN-ß cytokines verified the adverse effect of high-fat diet on immune system as well. Fats tend to accumulate in organs due to increased intake of fat-rich diet disturbing their normal function and histology. In addition, gene expression analysis of cytokines confirmed the effect of high-fat diet as an inflammatory agent.