In vitro flowering in Bambusa bambos (L.) Voss, an anatomical perspective.

Bamboo [Bambusa bambos (L.) Voss (Syn. Bambusa arundinacea Retz.)] is an important arborescent grass with immense socio economic implications. The plant exhibits unique biological and growth characteristics including a distinct monocarpic gregarious flowering behavior. Studies on in vitro flowering in bamboo are not uncommon. The present study focuses on effect of different growth regulators on in vitro flowering in B. bambos and analyzes the morphological and developmental changes accompanying the process. Multiple shoots were raised from B. bambos seeds on MS medium supplemented with 10 µM BAP. Anatomical sections showed intense mitotic activity in the apical meristem of the main shoot and formation of additional shoot buds along the margins. For multiplication, propagules of 7-9 shoots were transferred to maintenance medium containing 5 µM BAP. Longitudinal sections of propagules showed prolific cell divisions and formation of meristemoids, which continuously gave rise to new shoots upon subculture. In vitro induction of flowering in cultures was observed in multiple shoots after 8 weeks. Transfer of multiple shoots to MS basal medium containing 10 µM NAA resulted in rooting and proliferation of inflorescences. On medium supplemented with 10 µM 2,4-D callusing and development of shoot buds and somatic embryos was followed by development of inflorescences. The report outlines a protocol that can be used to raise and proliferate flowering cultures in B. bambos.

Effect of the electric field during annealing of organic light emitting diodes for improving its on/off ratio.

If an organic light emitting diode is to be used as part of a matrix addressed array, it should exhibit low reverse leakage current. In this paper we present a method to improve the on/off ratio of such a diode by simultaneous application of heat and electric field post device fabrication. A green OLED with excellent current efficiency was seen to be suffering from a poor on/off ratio of 10(2). After examining several combinations of annealing along with the application of a reverse bias voltage, the on/off ratio of the same device could be increased by three orders of magnitude, specifically when the device was annealed at 80 °C under reverse bias (-15 V) followed by slow cooling also under the same bias. Simultaneously, the forward characteristics of the device were relatively unaffected. The reverse leakage in the OLED is mainly due to the injection of minority carriers in the hole transport layer (HTL) and the electron transport layer (ETL), in this case, of holes in tris-(8-hydroxyquinoline)aluminum(Alq3) and electrons in 4,4',4''-tris(N-3-methylphenyl-N-phenylamino)triphenylamine (m-MTDATA). Hence, to investigate these layers adjacent to the electrodes, we fabricated their single layer devices. The possibility of bulk traps present adjacent to electrodes providing states for injection was ruled out after estimating the trap density both before and after the reverse biased annealing. The temperature independent current in reverse bias ruled out the possibility of thermionic injection. The origin of the reverse bias current is attributed to the availability of interfacial hole levels in Alq3 at the cathode work function level in the as-fabricated device; the suppression of the same being attributed to the fact that these levels in Alq3 are partly removed after annealing under an electric field.

A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI).

BACKGROUND: Agriculture is the single largest geo-engineering initiative that humans have initiated on planet Earth, largely through the introduction of unprecedented amounts of reactive nitrogen (N) into ecosystems. A major portion of this reactive N applied as fertilizer leaks into the environment in massive amounts, with cascading negative effects on ecosystem health and function. Natural ecosystems utilize many of the multiple pathways in the N cycle to regulate N flow. In contrast, the massive amounts of N currently applied to agricultural systems cycle primarily through the nitrification pathway, a single inefficient route that channels much of this reactive N into the environment. This is largely due to the rapid nitrifying soil environment of present-day agricultural systems. SCOPE: In this Viewpoint paper, the importance of regulating nitrification as a strategy to minimize N leakage and to improve N-use efficiency (NUE) in agricultural systems is highlighted. The ability to suppress soil nitrification by the release of nitrification inhibitors from plant roots is termed 'biological nitrification inhibition' (BNI), an active plant-mediated natural function that can limit the amount of N cycling via the nitrification pathway. The development of a bioassay using luminescent Nitrosomonas to quantify nitrification inhibitory activity from roots has facilitated the characterization of BNI function. Release of BNIs from roots is a tightly regulated physiological process, with extensive genetic variability found in selected crops and pasture grasses. Here, the current status of understanding of the BNI function is reviewed using Brachiaria forage grasses, wheat and sorghum to illustrate how BNI function can be utilized for achieving low-nitrifying agricultural systems. A fundamental shift towards ammonium (NH4(+))-dominated agricultural systems could be achieved by using crops and pastures with high BNI capacities. When viewed from an agricultural and environmental perspective, the BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop-livestock systems.

Evidence for biological nitrification inhibition in Brachiaria pastures.

Nitrification, a key process in the global nitrogen cycle that generates nitrate through microbial activity, may enhance losses of fertilizer nitrogen by leaching and denitrification. Certain plants can suppress soil-nitrification by releasing inhibitors from roots, a phenomenon termed biological nitrification inhibition (BNI). Here, we report the discovery of an effective nitrification inhibitor in the root-exudates of the tropical forage grass Brachiaria humidicola (Rendle) Schweick. Named "brachialactone," this inhibitor is a recently discovered cyclic diterpene with a unique 5-8-5-membered ring system and a gamma-lactone ring. It contributed 60-90% of the inhibitory activity released from the roots of this tropical grass. Unlike nitrapyrin (a synthetic nitrification inhibitor), which affects only the ammonia monooxygenase (AMO) pathway, brachialactone appears to block both AMO and hydroxylamine oxidoreductase enzymatic pathways in Nitrosomonas. Release of this inhibitor is a regulated plant function, triggered and sustained by the availability of ammonium (NH(4)(+)) in the root environment. Brachialactone release is restricted to those roots that are directly exposed to NH(4)(+). Within 3 years of establishment, Brachiaria pastures have suppressed soil nitrifier populations (determined as amoA genes; ammonia-oxidizing bacteria and ammonia-oxidizing archaea), along with nitrification and nitrous oxide emissions. These findings provide direct evidence for the existence and active regulation of a nitrification inhibitor (or inhibitors) release from tropical pasture root systems. Exploiting the BNI function could become a powerful strategy toward the development of low-nitrifying agronomic systems, benefiting both agriculture and the environment.

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post-COVID-19 Phenotype: A Single Center Experience.

BACKGROUND: Lung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS. METHODS: This study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed. RESULTS: This study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies. CONCLUSIONS: LTx is the definitive option for survival in select patients with severe post-COVID-19-associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.

Down regulation of transcripts involved in selective metabolic pathways as an acclimation strategy in nitrogen use efficient genotypes of rice under low nitrogen.

To understand the molecular mechanism of nitrogen use efficiency (NUE) in rice, two nitrogen (N) use efficient genotypes and two non-efficient genotypes were characterized using transcriptome analyses. The four genotypes were evaluated for 3 years under low and recommended N field conditions for 12 traits/parameters of yield, straw, nitrogen content along with NUE indices and 2 promising donors for rice NUE were identified. Using the transcriptome data generated from GS FLX 454 Roche and Illumina HiSeq 2000 of two efficient and two non-efficient genotypes grown under field conditions of low N and recommended N and their de novo assembly, differentially expressed transcripts and pathways during the panicle development were identified. Down regulation was observed in 30% of metabolic pathways in efficient genotypes and is being proposed as an acclimation strategy to low N. Ten sub metabolic pathways significantly enriched with additional transcripts either in the direction of the common expression or contra-regulated to the common expression were found to be critical for NUE in rice. Among the up-regulated transcripts in efficient genotypes, a hypothetical protein OsI_17904 with 2 alternative forms suggested the role of alternative splicing in NUE of rice and a potassium channel SKOR transcript (LOC_Os06g14030) has shown a positive correlation (0.62) with single plant yield under low N in a set of 16 rice genotypes. From the present study, we propose that the efficient genotypes appear to down regulate several not so critical metabolic pathways and divert the thus conserved energy to produce seed/yield under long-term N starvation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02631-5.

Risk Stratification in Low Grade Glioma: A Single Institutional Experience.

BACKGROUND: Low grade gliomas (LGG) are most often noted with the unpredictable overall survival and progression to higher grades. Objective: In the present study, we analyze the clinicopathological features influencing the prognostic outcomes and compared the features with criteria developed by EORTC. MATERIALS AND METHODS: We observed the 130 LGG clinical cases in single institute and maintained the follow-up for more than 5 years. In addition, the molecular details were confirmed with markers as IDH, 1p/19q codeletion, p53 and ATRX mutations. RESULTS: The mean age of patients as 37.67 years and male population contributing to 70%. We observed biased incidence among the male population with dominating occurrence at frontal and parietal lobes in the brain. 40.8% patients had oligodendroglioma, 33.8% astrocytoma, 19.2% oligoastrocytoma and 2.3% gemistocytic astrocytoma pathology. Patients who were subjected to chemotherapy and radiotherapy were noted with average survival of 29 months. Oligodendroglial tumors were found with progression free survival (PFS) of 25 months, oligoastrocytoma cases with 32 months, diffuse astrocytoma cases with 23 months while the gemistocytic astrocytoma cases had 22 months. The PFS for LGG cases was 4.7 years while the overall survival was 4.9 years. Mean survival of patients with KPS score <70 and >70 was 1.5 & 4.9 years respectively. 64 patients were observed with the tumor size >5 cm. In total, 72.3% of the patients were underwent GTR, 23.3% STR and 3.8% underwent biopsy. CONCLUSION: Taken together, the clinical symptoms, expression of molecular markers and the prognosis details provided by our results can help for better management of LGG cases. We further propose to use following five factors to accurately describe the prognosis and tumor recurrence: 1) Age >50 years, 2) tumor size >5 cm, 3) MIB index >5%, 4) KPS score < 70 and 5) gemistocytic pathology.

Intraabdominal hydatid cyst: a case report.

BACKGROUND: Hydatid disease is caused by Echinococcus granulosus, endemic in cattle and sheep-raising regions of the world such as Central Europe, South America, Australia, New Zealand and South Africa. Although hydatid disease is more common in liver and lung, it also affects brain, kidney, spleen and muscle. We present a case of intraabdominal hydatid cyst, diagnosed by fine needle aspiration cytology, producing an indentation of the liver, which is uncommon. CASE: A male patient presented with right side abdominal pain. On ultrasonography an intraabdominal solid mass (right hypochondrial) was revealed, and subsequently FNA was done. Smears were diagnostic of hydatid cyst. CONCLUSION: FNAC is a sensitive and rapid technique in diagnosis of hydatid cysts. The present case is unusual, owing to its presentation as a solid abdominal mass seeding over the liver and mimicking malignancy radiologically.

Immunogenicity and safety of an indigenously developed DTPw hepatitis B combination vaccine in Indian infants.

OBJECTIVE: To evaluate the safety and immunogenicity of an indigenous hepatitis B, diphtheria, tetanus and B. pertussis tetravalent vaccine (Shantetra) in comparison with Tritanrix HBTM in healthy Indian infants. DESIGN: Multicentric, randomized, single blind intention-to-treat study with 12-18 weeks of follow up period. SETTING: 5 out patient departments at tertiary care referral centers across India. PARTICIPANTS: 151 infants were randomized in a 2:1 ratio to recruit 101 in the Shantetra and 50 in the Tritanrix HBTM groups respectively. A total of 136 subjects completed the study. No patients were withdrawn from the study due to any adverse effects. INTERVENTIONS: Recruited subjects were randomized to receive three doses of either of the two DTPw-Hepatitis B combination vaccines as per the EPI schedule. MAIN OUTCOME MEASURES: Monitoring the humoral immune response (seroconversion rates) induced by each antigenic component three to six weeks after the last dose of vaccine in both the groups. RESULTS: Seroprotective immune response was observed in 98.9% subjects for diphtheria, tetanus and hepatitis B components in the Shantetra group as compared to 95.5% subjects in the Tritanrix HB group. Anti pertussis antibody response was seen in 89% and 91.1% in the Shantetra and Tritanrix HB groups, respectively. The commonly observed adverse events in both the groups were, pain at injection site, mild fever and transient crying. CONCLUSION: The safety and immunogenicity of indigenously developed DTPwHepatitis B combination vaccine was demonstrated in the present study.

Identification of rice landraces with promising yield and the associated genomic regions under low nitrogen.

With the priority of the low input sustainable rice cultivation for environment friendly agriculture, NUE of rice becomes the need of the hour. A set of 472 rice genotypes comprising landraces and breeding lines were evaluated for two seasons under field conditions with low and recommended nitrogen and >100 landraces were identified with relative higher yield under low nitrogen. Donors were identified for higher N uptake, N translocation into grains and grain yield under low N. Grains on secondary branches, N content in grain and yield appears to be the selection criterion under low N. Through association mapping, using minimum marker set of 50 rice SSR markers, 12 genomic regions were identified for yield and yield associated traits under low nitrogen. Four associated genomic regions on chromosomes 5, 7 and 10 were fine mapped and QTL for yield under low N were identified from the marker delimited regions. Three candidate genes viz., 2-oxoglutarate /malate translocator (Os05g0208000), alanine aminotransferase (Os07g0617800) and pyridoxal phosphate-dependent transferase (Os10g0189600) from QTL regions showed enhanced expression in the genotypes with promising yield under low N. Marker assisted selection using SSR markers associated with three candidate genes identified two stable breeding lines confirmed through multi-location evaluation.

Lymph node metastasis of soft tissue tumors: a cytomorphologic study.

OBJECTIVE: To study the frequency of regional lymph node metastasis of soft tissue tumors (STT) and to evaluate the utility of fine needle aspiration cytology (FNAC) as an initial investigative modality. STUDY DESIGN: A prospective and retrospective study of over 6 years (1998-2004) was performed to look for frequency of STT metastasizing to lymph nodes. FNAC of enlarged nodes was performed as a routine outpatient procedure after obtaining complete clinical details. Histopathology and immunohistochemistry were correlated where available. RESULTS: Lymph node enlargement was seen in 23 of 241 patients with STTs, of which 19 cases showed involvement (7.88%), synchronous with primary in 12 cases and metachronous in 7 cases. The most common sites of primary tumor were the lower extremity and head and neck region with involved regional lymph nodes. STTs commonly involving lymph nodes were rhabdomyosarcoma and extraskeletal Ewing's/primitive neuroectodermal tumor (PNET); other rare tumors included malignant granular cell tumor, epithelioid hemangioendothelioma, mediastinal ganglioneuroblastoma, angiosarcoma and epithelioid sarcoma. CONCLUSION: Lymph node aspirates should be examined for alien cells, particularly smears that are paucicellular and demonstrate cystic change. Lymph node metastasis of STT is rare and influences staging, treatment and prognosis. Enlarged regional nodes should be examined with FNAC.

Tumor-induced Osteomalacia: A Sherlock Holmes Approach to Diagnosis and Management.

Tumor-induced osteomalacia (TIO) is a subtype of paraneoplastic syndrome associated with hypophosphatemia due to renal phosphate wasting in adults. The humoral factor responsible for clinical picture known as fibroblast growth factor 23 (FGF23) is most often secreted by benign yet elusive mesenchymal tumors, difficult to localize, access, and excise completely; rarely, they are multiple and malignant. Paradoxical inappropriately normal or low levels of 1,25-dihydroxyvitamin D in the setting of hypophosphatemia is due to suppressive effect of FGF23. The following case report describes a 31-year-old male with symptoms of multiple fractures and severe muscle weakness, hypophosphatemia with elevated tubular maximum reabsorption of phosphate/glomerular filtration rate with low active Vitamin D, prompted assay for C-terminal FGF23, which was elevated multifold. The tumor was localized with whole body 68-Gadolinium DOTANOC positron emission tomography-computed tomography fusion scan in the left nasal cavity with ipsilateral maxillary antrum. It was excised through transnasal approach and found to be mesenchymal tumor on histopathology. At 1 week of follow-up, serum phosphate became normalized without supplementation. The patient is in follow-up for further measurement of FGF23 level and signs of recurrence. Because the occurrence of such a condition is rare and most often misdiagnosed or mismanaged for years, it is important to recognize this condition in differential diagnosis as potential curative surgical option is a reality.

Genetic mitigation strategies to tackle agricultural GHG emissions: The case for biological nitrification inhibition technology.

Accelerated soil-nitrifier activity and rapid nitrification are the cause of declining nitrogen-use efficiency (NUE) and enhanced nitrous oxide (N2O) emissions from farming. Biological nitrification inhibition (BNI) is the ability of certain plant roots to suppress soil-nitrifier activity, through production and release of nitrification inhibitors. The power of phytochemicals with BNI-function needs to be harnessed to control soil-nitrifier activity and improve nitrogen-cycling in agricultural systems. Transformative biological technologies designed for genetic mitigation are needed, so that BNI-enabled crop-livestock and cropping systems can rein in soil-nitrifier activity, to help reduce greenhouse gas (GHG) emissions and globally make farming nitrogen efficient and less harmful to environment. This will reinforce the adaptation or mitigation impact of other climate-smart agriculture technologies.

Enhanced expression of OsSPL14 gene and its association with yield components in rice (Oryza sativa) under low nitrogen conditions.

Nitrogen use efficiency (NUE) in rice crop is the need of the hour for reduction of nitrous oxide emission resulting from excess nitrogen (N) fertilizer application and also in reduction of cost of cultivation. Ten rice genotypes were grown under low and recommended dose of N application and characterized in terms of parameters related to yield, yield related components and NUE indicators. Wide genetic variability under low N conditions was observed with significant variation for 15 yield related parameters in interactions of genotypes and treatment. Limitation of N has led to the decrease of all yield and yield related parameters, but for grain filling % and 1000 grain weight. Two genotypes, Rasi and Varadhan have shown minimum differences between low and recommended N conditions. Correlation analysis of various yield components showed the importance of the secondary branches for the total grains under low N. Expression analysis of OsSPL14 (LOC_Os08g39890) gene reported to be associated with increased panicle branching and higher grain yield through real time PCR in leaf and three stages of panicle has shown differential temporal expression and its association with yield and yield related components across the genotypes. The expression of OsSPL14 at panicle stage 3, has shown correlation (P<0.05) with N% in grain. Since OsSPL14 is a functional transcription activator, its association of expression in leaf and three panicle stages with yield components as observed in the present study suggests the role of nitrogen metabolism related genes in plant growth and development and its conversion into yield components in rice.

Novel, Precise, Accurate Ion-Pairing Method to Determine the Related Substances of the Fondaparinux Sodium Drug Substance: Low-Molecular-Weight Heparin.

Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and validated by a novel ion-pair HPLC method. The separation of the drug and its degradation products was achieved with the polymer-based PLRPs column (250 mm × 4.6 mm; 5 µm) in gradient elution mode. The mixture of 100 mM n-hexylamine and 100 mM acetic acid in water was used as buffer solution. Mobile phase A and mobile phase B were prepared by mixing the buffer and acetonitrile in the ratio of 90:10 (v/v) and 20:80 (v/v), respectively. Mobile phases were delivered in isocratic mode (2% B for 0-5 min) followed by gradient mode (2-85% B in 5-60 min). An Evaporative Light Scattering Detector (ELSD) was connected to the LC system to detect the responses of chromatographic separation. Further, the drug was subjected to stress studies for acidic, basic, oxidative, photolytic, and thermal degradations as per ICH guidelines and the drug was found to be labile in acid, base hydrolysis, and oxidation, while stable in neutral, thermal, and photolytic degradation conditions. The method provided linear responses over the concentration range of the LOQ to 0.30% for each impurity with respect to the analyte concentration of 12.5 mg/mL, and regression analysis showed a correlation coefficient value (r(2)) of more than 0.99 for all the impurities. The LOD and LOQ were found to be 1.4 µg/mL and 4.1 µg/mL, respectively, for fondaparinux. The developed ion-pair method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness.

Leaf Phosphate Status, Photosynthesis, and Carbon Partitioning in Sugar Beet (IV. Changes with Time Following Increased Supply of Phosphate to Low-Phosphate Plants).

Changes in photosynthesis, carbon partitioning, and growth following resupply of orthophosphate (Pi) to moderately P-deficient plants (low-P) were determined for sugar beets (Beta vulgaris L. cv F58-554H1) cultured hydroponically in growth chambers. One set of plants was supplied with 1.0 mM Pi in half-strength Hoagland solution (control plants), and a second set (low-P plants) was supplied with 0.05 mM Pi. At the end of 2 weeks, the low-P plants were resupplied with 1.0 mM Pi. Low-P plants rapidly accumulated large amounts of Pi, and the photosynthesis rate increased to control values within 4 to 6 h. The rate of photosynthesis appeared to be controlled by ribulose-1,5-bisphosphate (RuBP); low P reduced photosynthesis and RuBP levels, and P resupply increased photosynthesis and RuBP in a manner parallel with time. Low-P treatment reduced adenylate levels substantially but not nicotinamide nucleotides; adenylate levels recovered to control values over 3 to 6 h. With low P, more photosynthate is allocated to non-P carbon compounds (e.g. starch, sucrose) than to sugar phosphates. When P is resupplied, sugar phosphates increase as starch and sucrose pools decrease; this increase in leaf (chloroplast) sugar phosphates was most likely responsible for the increases in RuBP and photosynthesis and may have increased adenylate levels (through enhanced levels of ribose-5-phosphate).

Lymph node infarction--a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever.

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance.

LivestockPlus: Forages, sustainable intensification, and food security in the tropics.

The increased use of grain-based feed for livestock during the last two decades has contributed, along with other factors, to a rise in grain prices that has reduced human food security. This circumstance argues for feeding more forages to livestock, particularly in the tropics where many livestock are reared on small farms. Efforts to accomplish this end, referred to as the 'LivestockPlus' approach, intensify in sustainable ways the management of grasses, shrubs, trees, and animals. By decoupling the human food and livestock feed systems, these efforts would increase the resilience of the global food system. Effective LivestockPlus approaches take one of two forms: (1) simple improvements such as new forage varieties and animal management practices that spread from farmer to farmer by word of mouth, or (2) complex sets of new practices that integrate forage production more closely into farms' other agricultural activities and agro-ecologies.

Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones.

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.