Two-Photon-Responsive "TICT + AIE" Active Naphthyridine-BF2 Photoremovable Protecting Group: Application for Specific Staining and Killing of Cancer Cells.

The combined effects of twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) phenomena have demonstrated a significant influence on excited-state chemistry. These combined TICT and AIE features have been extensively utilized to enhance photodynamic and photothermal therapy. Herein, we demonstrated the synergistic capabilities of TICT and AIE phenomena in the design of the photoremovable protecting group (PRPG), namely, NMe2-Napy-BF2. This innovative PRPG incorporates TICT and AIE characteristics, resulting in four remarkable properties: (i) red-shifted absorption wavelength, (ii) strong near-infrared (NIR) emission, (iii) viscosity-sensitive emission property, and (iv) accelerated photorelease rate. Inspired by these intriguing attributes, we developed a nanodrug delivery system (nano-DDS) using our PRPG for cancer treatment. In vitro studies showed that our nano-DDS manifested effective cellular internalization, specific staining of cancer cells, high-resolution confocal imaging of cancerous cells in the NIR region, and controlled release of the anticancer drug chlorambucil upon exposure to light, leading to cancer cell eradication. Most notably, our nano-DDS exhibited a substantially increased two-photon (TP) absorption cross section (435 GM), exhibiting its potential for in vivo applications. This development holds promise for significant advancements in cancer treatment strategies.

ESIPT-, AIE-, and AIE + ESIPT-Based Light-Activated Drug Delivery Systems and Bioactive Donors for Targeted Disease Treatment.

Targeted release of bioactive molecules for therapeutic purposes is a key area in the biomedical field that is growing quickly, where bioactive molecules are released passively or actively from drug delivery systems (DDSs) or bioactive donors. In the past decade, researchers have identified light as one of the prime stimuli that can implement the efficient spatiotemporally targeted delivery of drugs or gaseous molecules with minimal cytotoxicity and a real-time monitoring ability. This perspective emphasizes recent advances in the photophysical properties of ESIPT- (excited-state intramolecular proton transfer), AIE- (aggregation-induced emission), and AIE + ESIPT-attributed light-activated delivery systems or donors. The three major sections of this perspective describe the distinctive features of DDSs and donors concerning their design, synthesis, photophysical and photochemical properties, and in vitro and in vivo studies demonstrating their relevance as carrier molecules for releasing cancer drugs and gaseous molecules in the biological system.

Switching photorelease to singlet oxygen generation by oxygen functionalization of phenothiazine photocages.

A phenothiazine-based photoremovable protecting group (PRPG) for single and dual release of carboxylic acids was developed. The change in the oxidation state of the sulfur atom of the phenothiazine PRPG resulted in singlet oxygen generation, rather than photorelease. The difference in the photochemistry between oxygen-free and oxygen-functionalized phenothiazine was investigated and supported by DFT calculations.

Green Light-Activated Single-Component Organic Fluorescence-Based Nano-Drug Delivery System for Dual Uncaging of Anticancer Drugs.

Developing green or red light-activated drug delivery systems (DDSs) for cancer treatment is highly desirable. Herein, we have reported a green light-responsive single component-based organic fluorescence nano-DDS by simply anchoring 2-hydroxy-6-naphthacyl (phototrigger) on both sides of the 1,5-diaminonaphthalene (DAN) chromophore. This green light (λ ≥ 500 nm)-activated DDS released two equivalents of the anticancer drug (valproic acid) in a spatio-temporally controlled manner. Our photoresponsive DDS [DAN-bis(HO-Naph-VPA)] exhibited interesting properties such as excited-state intramolecular proton transfer (ESIPT) accompanied with aggregation-induced emission (AIE) phenomena. AIE initiated the photorelease, and ESIPT enhanced the rate of the photorelease. Further, in vitro studies revealed that our green light-activated nano-DDS exhibited good cytocompatibility, excellent cellular internalization, and effective cancer cell killing ability.

Global sensitivity analysis of randomized trials with nonmonotone missing binary outcomes: Application to studies of substance use disorders.

In this paper, we present a method for conducting global sensitivity analysis of randomized trials in which binary outcomes are scheduled to be collected on participants at prespecified points in time after randomization and these outcomes may be missing in a nonmonotone fashion. We introduce a class of missing data assumptions, indexed by sensitivity parameters, which are anchored around the missing not at random assumption introduced by Robins (Statistics in Medicine, 1997). For each assumption in the class, we establish that the joint distribution of the outcomes is identifiable from the distribution of the observed data. Our estimation procedure uses the plug-in principle, where the distribution of the observed data is estimated using random forests. We establish n$\sqrt {n}$ asymptotic properties for our estimation procedure. We illustrate our methodology in the context of a randomized trial designed to evaluate a new approach to reducing substance use, assessed by testing urine samples twice weekly, among patients entering outpatient addiction treatment. We evaluate the finite sample properties of our method in a realistic simulation study. Our methods have been implemented in an R package entitled slabm.

A water soluble light activated hydrogen sulfide donor induced by an excited state meta effect.

We have utilized an m-amino benzyl based photoremovable protecting group (PRPG) to develop a new water soluble H2S donor. It efficiently releases H2S on demand in a spatio-temporally controlled fashion by an excited state "meta effect" with good chemical and photochemical quantum yield in an aqueous environment. The efficient photorelease of H2S under physiological conditions was also demonstrated by in vitro studies.

Spectrum of diffuse parenchymal lung diseases with special reference to idiopathic pulmonary fibrosis and connective tissue disease: An eastern India experience.

OBJECTIVE: To evaluate the clinical spectrum of diffuse parenchymal lung diseases (DPLD) encountered in the Indian setting and to compare idiopathic pulmonary fibrosis (IPF) and connective tissue disease associated DPLD (CTD-DPLD), the two commonest aetiologies. MATERIALS AND METHODS: A prospective study of clinical, imaging and laboratory parameters of patients diagnosed as DPLD and followed up in the Pulmonary Medicine Department of a tertiary-care teaching institution in eastern India was conducted over a period of one year. RESULTS: 92 patients of DPLD were diagnosed in the study period with IPF (n = 35, 38.04%), CTD-DPLD (n = 29, 31.5%), hypersensitivity pneumonitis (n = 10, 10.9%), sarcoidosis (n = 5, 5.4%) and silicosis (n = 5, 5.4%) being the common causes. The CTD-DPLD group had a lower mean age (39.5 ± 1.86 vs 56.9 ± 1.12 years), a longer duration of symptoms (3.5 ± 0.27 vs 2.5 ± 0.26 years), more extra pulmonary manifestations, significantly more base line FVC and 6-minute-walk-distance than the IPF patients. 19 patients of IPF (54%) opted for treatment. All the IPF patients had a significant fall in FVC after six months (mean change -0.203 ± 0.01 litres) compared to the CTD-DPLD group (mean change - 0.05 ± 0.04 litres.). CONCLUSION: CTD-DPLD patients belong to a younger age group, with longer duration of symptoms, more extrapulmonary features, better physiological parameters and better response to therapy than IPF patients. Larger prospective epidemiological studies and enrolment in clinical trials are necessary for better understanding of the spectrum of diffuse parenchymal lung disorders and their therapeutic options.

A cross-sectional prospective study of pleural effusion among cases of chronic kidney disease.

BACKGROUND: Pleural effusions of diverse aetiologies are encountered in patients with chronic kidney disease (CKD). The objectives of the present study were to examine the frequency of occurrence, causes, clinical features and management strategies of pleural effusion in patients with CKD including renal transplant recipients. METHODS: A prospective cross-sectional observational analysis of pleural effusion in adult patients with CKD (stages 3 to 5) attending the Departments of Nephrology and Respiratory Medicine of a tertiary care institution in Eastern India was performed over a period of one year (February 2010 to January 2011). RESULTS: Pleural effusion was found in 29 out of 430 patients with CKD (6.7%) and in two out of 34 post-renal transplant recipients (5.9%) evaluated during the study period. The mean age was 37.35 +/- 1.8 (mean +/- SEM [standard error of mean]) with a male to female ratio of 2:1. Exudates and transudates were found in equal frequencies. Heart failure was the single most common cause (41.9%, 13 of 31). Tuberculosis (TB) (n = 8, 25.8%) and uraemic effusions (n = 6, 19.4%) were responsible for the majority of exudates. Unilateral effusion with a normal heart size had a positive predictive value of 83.3% for non-heart failure aetiology. CONCLUSIONS: Symptomatic pleural effusion was present in a small proportion of 6.7%; (n = 29) patients with CKD including post-renal transplant recipients. Heart failure, TB and uraemic effusions accounted for most of the cases. Differentiating TB from uraemic effusion requires a combined clinico-pathological approach and this differentiation is absolutely necessary for proper management.