Risk of Gallstone Disease in Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

OBJECTIVE: Apart from renal stones, primary hyperparathyroidism (PHPT) has been linked to the occurrence of gallstone disease (GSD). Nevertheless, the association is not consistent across all studies. The present systematic review and meta-analysis aims to collate the hitherto available evidence and provide a pooled estimate of the association between GSD and PHPT. METHODS: PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched from inception till May 10, 2023 for observational studies reporting the prevalence of GSD (in terms of absolute numbers) in patients with PHPT. The pooled prevalence of GSD and odds ratio with 95% CI of the occurrence of GSD in patients with PHPT as compared to age- and sex-matched controls were calculated. Subgroup analysis was performed based on patient ethnicity (Indian/Caucasian). Statistical analysis was carried out using R version 4.2.2. Random-effects model with Hartung-Knapp adjustment was used for analyses. RESULTS: A total of 7 observational studies were included, pooling data from 15 949 patients with PHPT. The pooled prevalence of GSD in patients with PHPT was 16% (95% CI: 7%, 25%, I2 = 99%), being 13% (95% CI: 0%, 66%, I2 = 76%) in Indians, and 17% (95% CI: 4%, 31%, I2 = 99%) in Caucasians. Data consolidated from 3 studies showed that the pooled odds ratio of occurrence of GSD in patients with PHPT compared to controls was 1.77 (95% CI: 1.60, 1.97, P < .001, I2 = 0%). CONCLUSIONS: GSD is more prevalent in patients with PHPT than in the general population. Thus, PHPT may be considered an additional risk factor for GSD.

Mineralocorticoid receptor antagonists with sodium-glucose co-transporter-2 inhibitors in heart failure: a meta-analysis.

BACKGROUND AND AIMS: To investigate the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) with concomitant mineralocorticoid receptor antagonist (MRA) use in heart failure (HF) regardless of ejection fraction (EF) and explore the risk of MRA-associated adverse events in individuals randomized to SGLT2i vs. placebo. METHODS: PubMed/MEDLINE, Web of Science, Embase, and clinical trial registries were searched for randomized controlled trials/post-hoc analyses evaluating SGLT2i in HF with or without MRA use (PROSPERO: CRD42023397129). The main outcomes were composite of first hospitalization or urgent visit for HF/cardiovascular death (HHF/CVD), HHF, and CVD. Others were all-cause mortality, composite renal and safety outcomes. Hazard ratios (HR)/risk ratios were extracted. Fixed-effects meta-analyses and subgroup analyses were performed. RESULTS: Five eligible studies were included, pooling data from 21 947 people with HF (type 2 diabetes mellitus, n = 10 805). Compared to placebo, randomization to SGLT2i showed a similar reduction in HHF/CVD and HHF in people who were or were not using MRAs [HHF/CVD: hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.68-0.81 vs. HR 0.79; 95% CI 0.72-0.86; P-interaction = .43; HHF: HR 0.74; 95% CI 0.67-0.83 vs. HR 0.71; 95% CI 0.63-0.80; P-interaction = .53], with a suggestion of greater relative reduction in CVD in chronic HF people randomized to SGLT2i and using MRAs irrespective of EF (HR 0.81; 95% CI 0.72-0.91 vs. HR 0.98; 95% CI 0.86-1.13; P-interaction = .034). SGLT2i reduced all-cause mortality (P-interaction = .27) and adverse renal endpoints regardless of MRA use (P-interaction = .73) despite a higher risk of volume depletion with concomitant MRAs (P-interaction = .082). SGLT2i attenuated the risk of mild hyperkalaemia (P-interaction < .001) and severe hyperkalaemia (P-interaction = .051) associated with MRA use. CONCLUSIONS: MRAs did not influence SGLT2i effects on the composite of HHF/CVD, HHF or all-cause mortality; however, findings hinted at a more pronounced relative reduction in CVD in chronic HF patients regardless of EF who were randomized to SGLT2i and receiving an MRA compared to those randomized to SGLT2i and not receiving MRAs. SGLT2i attenuated the risk of MRA-associated treatment-emergent hyperkalaemia. These findings warrant further validation in well-designed randomized controlled trials.

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects.

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities.

Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: A meta-analysis and meta-regression of randomized controlled trials.

AIMS: To pool the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF). METHODS: PubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1-year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti-gout drugs (SUA-lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse-variance method with a random-effects model. Mixed-effects model univariate meta-regression analysis was performed. RESULTS: Five RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout-related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45-0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P-interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57-0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between-trial heterogeneity (HR 0.46, 95% CI 0.39-0.55; I2 = 0%). Univariate meta-regression found no impact of baseline SUA, SUA lowering on follow-up, diuretic use, or other variables on their anti-gout effects. CONCLUSION: We found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA-lowering effects suggests that metabolic and anti-inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti-gout benefits.

Reagentless Chemistry "On-Water": An Atom-Efficient and "Green" Route to Cyclic and Acyclic ß-Amino Sulfones via aza-Michael Addition Using Microwave Irradiation.

A reagentless, catalyst-free, and sustainable methodology was developed for facile access to cyclic and acyclic ß-amino sulfones "on-water" using a microwave. A variety of aromatic and aliphatic amines undergo double aza-Michael addition on the surface of the water with water-insoluble divinyl sulfones upon microwave irradiation at 150 °C for 10 min to mostly afford solid cyclic ß-amino sulfones as easily separable products in excellent yields by simple filtration avoiding any workup steps. Thus, all atoms of the substrates are reflected in the product making it a 100% atom-efficient method. Both electron-rich and electron-deficient amines participated well in the reaction as well as good functional group tolerance was observed. The competitive experiments expectedly revealed faster reaction kinetics for electron-rich amines. The methodology was extended to acyclic ß-amino sulfones by interacting phenyl/ethyl vinyl sulfones with various amines in a similar manner. Expectedly, the method afforded very low environmental factors (in a range of 0.05-0.5) and a high Ecoscale score (up to 94). In an attempt toward sustainable development, this reagent-free, metal-free, organic solvent-free, cost-effective protocol is certainly a viable alternative to the available methods for ß-amino sulfones.

Mechanochemical Duff Reaction in Solid Phase for Easy Access to Mono- and Di-formyl Electron-Rich Arenes.

A sustainable alternative to the century-old Duff reaction was developed by adopting a solid-phase mechanochemical route. A series of mono-formyl electron-rich arenes were prepared in high yields in silica as the solid reaction media using a combination of hexamethylenetetramine (HMTA) as the formyl source and a small amount of H2SO4 in a mixer mill. The use of toxic, costly, and low-boiling trifluoroacetic acid was avoided in the new mold of the mechanochemical Duff reaction. The mono-formyl phenols were obtained with exclusive ortho-selectivity, whereas unprecedented para-formylation was observed for other electron-rich aromatics. By controlling the stoichiometry of HMTA, the method offers easy access to di-formylated phenols as well. The scalability of the reaction was validated with selected substrates at the gram-scale level. In a case study, a mechanochemical tandem reaction was explored in the synthesis of a rhodol derivative. The solvent-free, metal-free mild method of formylation, with the absence of tedious work-up steps and shorter reaction times using an inexpensive mineral acid, is a sustainable alternative to the available methods for aromatic formylation.

Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis.

PURPOSE: Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM. METHODS: PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations and/or cardiovascular death (HHF/CVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPERO:CRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed. RESULTS: We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHF/CVD in only T2DM without HF history (HR = 0.84; 95%CI, 0.77-0.91; I2 = 14%; p < 0.001), but not in those with HF history (HR = 0.96; 95%CI, 0.85-1.08; I2 = 14%; p = 0.4) (p-interaction < 0.1). GLP-1RAs reduced incident HHF in T2DM with or without HF history (HR = 0.89; 95%CI, 0.80-0.98; I2 = 41%; p < 0.05) (p-interaction = 0.28). Sensitivity analysis excluding REWIND trial accentuated the impact of baseline HF history on both HHF/CVD and HHF (p-interaction < 0.05). Benefits on MACE with GLP-1RAs were consistently seen in T2DM regardless of HF history (p-interaction = 0.8). CONCLUSION: GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHF/CV death were observed in those with HF history.

Corneal Confocal Microscopy Abnormalities in Children and Adolescents With Type 1 Diabetes.

OBJECTIVE: Utility of corneal confocal microscopy (CCM) in children and adolescents with type 1 diabetes mellitus (T1DM) without neuropathic symptoms or signs and minimal abnormality in large and small nerve fiber function tests remains largely undetermined. This study aimed to evaluate the performance of CCM in comparison to thermal detection thresholds (TDT) testing and nerve conduction studies (NCS) for detecting neuropathy in children with T1DM. METHODS: A cohort of children and adolescents with T1DM (n = 51) and healthy controls (n = 50) underwent evaluation for symptoms and signs of neurological deficits, including warm detection threshold, cold detection threshold, vibration perception threshold, NCS, and CCM. RESULTS: Children with T1DM had no or very minimal neuropathic symptoms and deficits based on the Toronto Clinical Neuropathy Score, yet NCS abnormalities were present in 18 (35%), small fiber dysfunction defined by an abnormal TDT was found in 13 (25.5%) and CCM abnormalities were present in 25 (49%). CCM was abnormal in a majority of T1DM children with abnormal TDT (12/13, 92%) and abnormal NCS (16/18, 88%). CCM additionally was able to detect small fiber abnormalities in 13/38 (34%) in T1DM with a normal TDT and in 9/33 (27%) with normal NCS. CONCLUSION: CCM was able to detect corneal nerve loss in children with and without abnormalities in TDT and NCS.

A polydiacetylene (PDA) impregnated poly(vinylidene fluoride) (PVDF) membrane for sensitive detection of fluoride ions.

Fluoride is present in groundwater and drinking water across the world and plays crucial roles in regulating oral health. Although a 0.7-1.2 ppm concentration of fluoride in water supplies is deemed optimal for enamel development and dental health, its higher concentration causes endemic fluorosis, acute gastric, urolithiasis, and kidney infection, making the detection of fluoride highly important. However, the standard methods of fluoride detection, such as potentiometric or ion-selective detection, require specific instruments and often pre-treatment before analysis and do not offer the scope for on-site detection. Herein, we report the development of a polydiacetylene (PDA) grafted poly(vinylidene fluoride) (PVDF) membrane for sensitive solid-phase detection of fluoride. The sensors were prepared by functionalizing PDA with the boronic acid functionality as the F- recognition unit and impregnating it on PVDF strips. Upon exposure to fluoride, the strips displayed a visible color change from blue to red. The solid-phase sensor showed selectivity against common anions and can detect F- ions as low as 0.11 ppm. The real sample analysis in water and toothpaste and validation by ion chromatography demonstrate its potential application as an efficient lab-on-membrane for fluoride ions.

A coumarin coupled tetraphenylethylene based multi-targeted AIEgen for cyanide ion and nitro explosive detection, and cellular imaging.

A coumarin coupled tetraphenylethylene based AIEgen (TPE-Lac) with an intense greenish-yellow emission has been synthesized and utilized for multipurpose sensing and imaging applications. TPE-Lac acts as a sensitive sensor for the detection of cyanide ions (CN-) with an immediate turn-off response in the presence of many other interfering cations and anions. The limit of detection (LOD) was as low as 33 nM, which is well below the permissible limit set by the World Health Organization (WHO). Cyanide detection in the solid phase was successfully demonstrated by drop-casting the solution of the TPE-Lac probe on TLC plates and measuring and analysing the fluorescence response by ImageJ analysis. TPE-Lac was further employed in the detection of explosive nitroaromatics in solution and solid phases. Also, TPE-Lac was found suitable as an imaging agent and could easily percolate into live H520 cells giving bright fluorescence from the intra-cellular region. Easy and cost-effective synthesis, fast response and low LODs are some of the advantages of this AIEgen over available molecular probes for the same purpose.

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence.

OBJECTIVE: COVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19. METHODS: We performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19. RESULTS: COVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted. CONCLUSION: The recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.

Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis.

PURPOSE: Observations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates. METHODS: PubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated. RESULTS: We included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model). CONCLUSIONS: Statin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides.

A simple electrical mortar-pestle was used for the development of a green and facile mechanochemical route for the catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10-15 min in a chemoselective manner by controlling the stoichiometry of N-halosuccinimides (NXS, X = Br, I, and Cl). It was observed that PEG-400 plays a key role in controlling the reactivity of the substrates and to afford better regioselectivity. Almost exclusive para-selectivity was observed for the aromatic substrates with free o- and p-positions for mono- and dihalogenations. As known, the decarboxylation (or desulfonation) was observed in the case of salicylic acids and anthranilic acids (or sulfanilic acids) leading to 2,4,6-trihalogenated products when 3 equiv of NXS was used. Simple instrumentation, metal-free approach, cost-effectiveness, atom economy, short reaction time, and mild reaction conditions are a few noticeable merits of this environmentally sustainable mechanochemical protocol.

Glycaemic efficacy and safety of mealtime faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: To summarize all relevant randomized controlled trials (RCTs) and provide precise effect estimates of glycaemic efficacy/safety of faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus. METHODS: PubMed/Cochrane Library were systematically searched till October 10, 2020, to identify RCTs with duration ≥16 weeks, evaluating efficacy/safety of mealtime injections of faster aspart compared to insulin aspart in people with type 1 diabetes mellitus and type 2 diabetes mellitus. Studies using faster aspart as continuous subcutaneous insulin infusion were excluded. Continuous and dichotomous outcome variables (expressed as estimated treatment difference and rate ratio in RCTs, respectively) were pooled using generic inverse variance method with fixed/random-effects model. For each outcome variable, subgroup analysis between type 1 diabetes mellitus and type 2 diabetes mellitus was performed. RESULTS: We included five RCTs; three of type 1 diabetes mellitus (n = 1963) and two of type 2 diabetes mellitus (n = 1780). All had low risk of bias. Faster aspart was associated with small but significant improvement in HbA1c than insulin aspart (MD: -0.06%, 95% CI: -0.10, -0.02, p = 0.005, I2  = 19%). HbA1c reduction was statistically significant only in type 1 diabetes mellitus on subgroup analysis (MD: -0.08%, 95% CI: -0.14, -0.02, p = 0.005, I2  = 47%). Besides, faster aspart was associated with reduced postprandial plasma glucose (PPG) increment at 1 h/2 h after meal test and increased 1,5-anhydroglucitol compared to insulin aspart. Early postprandial hypoglycaemic episodes were higher with faster aspart; however, overall and nocturnal hypoglycaemic episodes were not different from insulin aspart. CONCLUSIONS: Faster aspart is associated with reduced HbA1c , PPG increment and comparable overall hypoglycaemic episodes with regard to insulin aspart.

Mechanochemical Synthesis of Organic Dyes and Fluorophores.

The syntheses of dyes and fluorophores have significant commercial importance. In recent years, mechanochemistry has emerged as a green and sustainable alternative for the synthesis of conventional dyes, new fluorophores, and also synthetic modification of known dyes for their use as chemosensors. The dyestuffs based on BODIPYs, rhodamine, fluorescein, perylenedimides, coumarins, benzothiazoles, etc. were synthesized or derivatized by grinding or milling. The synopsis aims to pay key attention to their synthesis and the applications as chemosensors will be briefly covered.

COVID-19-associated mucormycosis: An updated systematic review of literature.

In its wake, the COVID-19 pandemic has ushered in a surge in the number of cases of mucormycosis. Most cases are temporally linked to COVID-19; hence, the entity is described as COVID-19-associated mucormycosis (CAM). The present systematic review was undertaken to provide an up-to-date summary of the hitherto available literature on CAM. PubMed, Scopus and Google Scholar databases were systematically searched using appropriate keywords till 14 May 2021, to identify case reports/case series pertaining to mucormycosis in patients with COVID-19. Relevant data extracted included demographic characteristics, comorbidity profile, clinical category of mucormycosis, glucocorticoid use, treatment offered and patient outcome. We identified 30 case reports/case series, pooling data retrieved from 99 patients with CAM. Most cases were reported from India (72%). The majority of the patients was male (78%) and had diabetes mellitus (85%). A prior history of COVID-19 was present in 37% patients with mucormycosis developing after an initial recovery. The median time interval between COVID-19 diagnosis and the first evidence of mucormycosis infection or CAM diagnosis was 15 days. Glucocorticoid use was reported in 85% of cases. Rhino-orbital mucormycosis was most common (42%), followed by rhino-orbito-cerebral mucormycosis (24%). Pulmonary mucormycosis was observed in 10 patients (10%). The mortality rate was 34%; the use of adjunct surgery, which was undertaken in 81% of patients, was associated with better clinical outcomes (p < .001). In conclusion, CAM is an emerging problem necessitating increased vigilance in COVID-19 patients, even those who have recovered. CAM portends a poor prognosis and warrants early diagnosis and treatment.

Mechanochemical Pd(II)-Catalyzed Direct and C-2-Selective Arylation of Indoles.

A mechanochemical method for the preparation of synthetically useful 2-arylindoles is developed using Pd(II) as the catalyst in the absence of phosphine ligands in a ball-mill. The developed protocol is highly C-2 selective and tolerant of structural variations with electron-rich and electron-deficient substituents both in indoles and iodoarenes. Arylation is possible in both unprotected indoles and N-protected indoles with the electron-donating group with the former substrate being relatively slower to react and little less yielding. Indoles with a deactivated five-membered ring could also take part in the reaction with ease. The scalability of the reaction was demonstrated by conducting the reaction in the gram scale. In general, the reactions were achieved in a shorter time than the conventional methods.

Metal-free C(sp2)-H functionalization of azoles: K2CO3/I2-mediated oxidation, imination, and amination.

The direct C2-H oxidation and imination of a wide variety of azoles was achieved by using a commercially available simple K2CO3/I2 reagent combination. The iodinated azole adduct, produced via the in situ generation of N-heterocyclic carbene, is the key intermediate for C2-H oxidation, imination, and amination of azoles. Significantly, these reactions proceed under mild conditions with high to excellent yields, are scalable to large quantity and exhibit a broad substrate scope. Interestingly, this direct C2-H imination method allowed us to access various pharmacologically active N6-alkyl or N6-aryl substituted benzimidazoquinazolinone scaffolds through intramolecular C-H imination in a sequential one-pot reaction.

Water-Dispersible Rhodamine B Hydrazide Loaded TiO2 Nanoparticles for "Turn On" Fluorimetric Detection and Imaging of Orthosilicic Acid Accumulation In-Vitro in Nephrotoxic Kidney Cells.

Silica (SiO2) is the inevitable form of silicon owing to its high affinity for oxygen, existing as a geogenic element perpetrating multifarious health problems when bioavailable via anthropogenic activities. The hydrated form of silica viz. orthosilicic acid (H4SiO4) excessively displays grave toxicity, attributed to prolonged exposure and incessant H+ ions generating capacity inflicting pulmonary toxicity and renal toxicity silica. The diverse deleterious potency of silica highlights the desirability of selective and sensitive detection of toxic species (mainly orthosilicic acid) bioaccumulation in affected living human cells. In this paper we have reported, the design of water-dispersible turn-on fluorimetric sensing material for the detection of orthosilicic acid in the aqueous phase and in live cells. The sensing material was prepared by adsorbing a suitable rhodamine derivative (i.e., Rhodamine B hydrazide (Rh1)) on water dispersible TiO2 nanoparticles. The function of the sensing system, which is composed of Rh1 and TiO2 (Rh1@TiO2), is accredited to H+ ion (from orthosilicic acid) induced spirolactam ring-opening of the rhodamine derivative generating orange fluorescence and bright pink colouration. The sensing system was efficiently utilized for fluorimetric detection and imaging of orthosilicic acid accumulation in-vitro in human kidney cells (HK cells). To the best of our knowledge, this is the first time this sensing system (Rh1@TiO2) is reported for detection of toxic silica species accumulation in-vitro in human kidney cells. The advantages, such as good water dispersibility, the absence of organic solvents during fluorimetric studies, quick turn-on type signal transduction, low-level imaging, which are offered by the synthesized sensing material (Rh1@TiO2), make it a potential candidate to fabricate medical tool for early identification of silicainduced nephrotoxicity, which can help to reduce the burden and risk of chronic kidney disease development.