Rapid Electrochemical Detection of Bacterial Sepsis in Cirrhotic Patients: A Microscaffold-Based Approach for Early Intervention.

Sepsis is a dysregulated inflammatory response leading to multiple organ failure. Current methods of sepsis detection are time-consuming, involving nonspecific clinical signs, biomarkers, and blood cultures. Hence, efficient and rapid sepsis detection platforms are of utmost need for immediate antibiotic treatment. In the current study, a noninvasive rapid monitoring electrochemical sensing (ECS) platform was developed for the detection and classification of plasma samples of patients with liver cirrhosis by measuring the current peak shifts using the cyclic voltammetry (CV) technique. A total of 61 hospitalized cirrhotic patients with confirmed (culture-positive) or suspected (culture-negative) sepsis were enrolled. The presence of bacteria in the plasma was observed by growth kinetics, and for rapidness, the samples were co-encapsulated in microscaffolds with carbon nanodots that were sensitive enough to detect redox changes occurring due to the change in the pH of the surrounding medium, causing shifts in current peaks in the voltammograms within 2 h. The percentage area under the curve for confirmed infections was 94 and that with suspected cases was 87 in comparison to 69 and 71 with PCT, respectively. Furthermore, the charge was measured for class identification. The charge for LPS-absent bacteria ranged from -400 to -600 µC, whereas the charge for LPS-containing bacteria class ranged from -290 to -300 µC. Thus, the developed cost-effective system was sensitive enough to detect and identify bacterial sepsis.

Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis.

PURPOSE: Surgical excision of metastases is the only curative treatment strategy in peritoneal carcinomatosis management, and the completeness of tumor resection determines the success of the surgery. Tumor-specific fluorescence-guided probes can improve the outcomes of cytoreductive surgery and thereby prognosis. This study aimed to develop and evaluate the feasibility of fluorescently labeled ultrasmall porous silica nanoparticles (UPSN) for image-guided resection of peritoneally disseminated tumors of different origins. METHODS: Ultrasmall fluorescent nanoprobes were synthesized and characterized for their physicochemical properties and stability. Tumor-specific uptake and biodistribution profiles were evaluated in syngeneic CT26 colorectal and KPC-689 pancreatic cancer murine models. The practicability of real-time optical UPSN-guided resection was examined in the CT26 colorectal cancer model using a surgical stereomicroscope. Quantitative measurements of tumor sensitivity and specificity were performed. Histopathological examination validated in vivo findings about tumor-specific accumulation and safety of ultrasmall fluorescent probes. RESULTS: As-synthesized UPSNs were successfully surface modified with Cy5 or Cy3 dyes maintaining sub-15 nm size and near neutral charge which is beneficial for optimized in vivo pharmacokinetics. UPSN-Cy5 demonstrated high tumor-specific uptake and favorable biodistribution profiles in peritoneal metastasis models of CT26 and KPC tumors. Dye-conjugated UPSN enabled resection of microscopic lesions and achieved a higher tumor-to-background ratios in comparison to FDA-approved indocyanine green (ICG) dye in both models. Microscopic evaluation showed tumor localization and off-target safety profile of the UPSN-Cy5. CONCLUSION: Ultrasmall fluorescent probes were effective in surgical resection of peritoneal metastases with high sensitivity and specificity, thus emerging as promising tumor agnostic agents for image-guided cancer surgery.

Vitamin D intervention as a curative measure for glucose intolerance in obese children and adolescents: a systematic review on randomized control trials.

Vitamin D deficiency is associated with obesity and its associated metabolic disorders, as specified in many epidemiological studies. The assertion that vitamin D can mitigate insulin insensitivity in obese children and adolescents lacks adequate empirical substantiation. Thus, the study utilized some clinical trials on vitamin D interventions to examine the impact of vitamin D supplementation on insulin resistance in obese children and adolescents. The literature was extracted by applying the PRISMA method through electronic databases such as Scopus, Science Direct, Medline, the Cochrane Library, and PubMed from 2012 to 2022. All the articles were in English, and the inclusion criteria for each article were based on the study design and the anthropometric and biochemical parameters of the subjects. A total of 572 research articles were acquired, out of which only seven closely adhered to the inclusion criteria of the study. The studies in this systematic review are based on randomized control trials. The age range of the children in this study spans from 2 to 19 years, and the follow-up period ranges from 3 to 12 months. The range of daily vitamin D doses provided varied from 2000 to 10,000 IU. The results indicate that four randomized controlled trials have demonstrated a positive impact on glycemic parameters, such as insulin levels, fasting blood sugar, and insulin resistance, in the subjects following vitamin D treatment. However, the three trials did not provide sufficient evidence to support a statistically significant effect. CONCLUSION: The present review highlights that a significant proportion of the studies incorporated in the analysis demonstrate that the administration of vitamin D may be a preventive measure in ameliorating insulin resistance among pediatric patients with obesity, but it is advisable to implement a prolonged intervention with a substantial sample size and perform micro-level analysis at the gene level to evaluate the impact of vitamin D treatment. WHAT IS KNOWN: • Childhood obesity and its associated metabolic disorder is a concerned global problem. • Several studies showed an association of vitamin D deficiency with adiposity- induced metabolicdisorders which are still controversial. This study focused on finding interlink between vitamin Dsupplementation with obesity induced insulin resistance in children and adolescents. WHAT IS NEW: • This study supports that high dosage of Vitamin D in long term may be protective against insulinresistance in obese paediatric individuals. • A new factor is also reported in the study that vitamin D may alter the composition of gut microbiotawhich represents a compelling approach to the therapeutic management of obesity and diabetes.

A patient with anti-f in India identified by extensive immunohematologic workup.

Anti-f is produced by exposure to the compound antigen ce (f) on red blood cells (RBCs), expressed when both c and e are present on the same protein (cis position). Although anti-f was discovered in 1953, there are few cases reported worldwide because the presence of anti-f is often masked by anti-c or anti-e and is not generally found as a single antibody. In the present case, anti-f was identified by using three-cell screening and 11-cell identification panels. The identification of anti-f was further supported by additional testing, including (1) Rh antigen typing; (2) antibody identification panels (enzyme-treated panel [ficin] and an in-house-constructed Rh panel); (3) look-back and phenotyping of donor RBC units, which were responsible for alloimmunization; and (4) molecular testing of the patient's RBCs.

Mathematical modeling and kinetics of batch and continuous electro-catalytic oxidation of pharmaceutical-contaminated wastewater.

An accurate yet simple model is the key to the design and control of intricate electro-catalytic oxidation of pharmaceutical contaminated wastewater. For both batch and unsteady-state continuous flow stirred tank reactors (CSTR), batch reactor models have been used earlier. Further, these models do not correlate rate to the operating conditions, and consider pseudo-first/second-order kinetics. Here, first-principles models are proposed by formulating unsteady-state mass balances, modifying them to attain realistic final conditions, and incorporating fractional variable-order kinetics. Following integral analysis, analytical solutions are obtained. These are independently applicable to design, unlike a numerical solution. Nonlinear regression is performed to estimate the model parameters from the transient experimental data. The simulations yield markedly accurate model parameters together with a better fit to the experimental data of Ti/RuO2-mediated amoxicillin-trihydrate electro-oxidation, for CSTR and batch reactors. For the batch reactor, the operating conditions are varied one at a time. Their effects on the model parameters are elucidated based on the oxidant and transformation species formed. The computed optimum model parameters are: rate constant 3.318 × 10-3 mg-0.092 m1.276 min-1, order 1.092, initial rate 4.032 × 102 mg m-2 min-1, and final conversion 90.6% in 180 min. The corresponding operating conditions are: pH 2.0, feed 50 mg L-1, electrolyte 2 g L-1, and current 1 A. A simple generalized power-law correlation, associating rate to the operating conditions, is then estimated. Statistical analysis of these models using central composite design delivers R2 0.99, predicted R2 0.96, and optimum set close to the above. The corresponding sensitivity analysis and generalized correlation, both show applied current to be the most significant operating condition. The dynamic modeling approaches proposed here can be extended to model, control, and scale-up complex reaction systems.

Factors associated with health-related quality of life in a cohort of cancer survivors in New Jersey.

BACKGROUND: Although there is extensive literature on correlates of health-related quality of life (HRQoL) among cancer survivors, there has been less attention paid to the role of socioeconomic disadvantage and survivorship care transition experiences in HRQoL. There are few large cohort studies that include a comprehensive set of correlates to obtain a full picture of what is associated with survivors' HRQ0L. This cohort study of recent cancer survivors in New Jersey aimed to explore the association between social determinants of health, health history, health behaviors, survivorship care experiences, and psychosocial factors in HRQoL. METHODS: Eligible survivors were residents of New Jersey diagnosed with genitourinary, female breast, gynecologic, colorectal, lung, melanoma, or thyroid cancers. Participants completed measures of social determinants, health behaviors, survivorship care experiences, psychosocial factors, and HRQoL. Separate multiple regression models predicting HRQoL were conducted for each of the five domains (social determinants, health history, health behaviors, survivorship care experiences, psychosocial factors). Variables attaining statistical significance were included in a hierarchical multiple regression arranged by the five domains. RESULTS: 864 cancer survivors completed the survey. Lower global HRQoL was associated with being unemployed, more comorbidities, a less healthy diet, lower preparedness for survivorship, more unmet support needs, and higher fear about cancer recurrence. Two psychosocial factors, unmet support needs and fear of recurrence, played the most important role in HRQoL, accounting for more than 20% of the variance. Both unmet support needs and fear of recurrence were significant correlates of physical, functional, and emotional HRQoL domains. CONCLUSIONS: Interventions seeking to improve cancer survivors' HRQoL may benefit from improving coordinated management of comorbid medical problems, fostering a healthier diet, addressing unmet support needs, and reducing survivors' fears about cancer recurrence.

Exploiting the Biophysical Cues toward Dual Differentiation of hMSC's within Geometrical Patterns.

A wide variety of cues from the extracellular matrix (ECM) have been known to affect the differentiation of stem cells in vivo. In particular, the biophysical cues and cell shape have been known to affect the stem cell function, yet very little is known about the interplay between how these cues control differentiation. For the first time, by using photolithography to pattern poly(ethylene glycol) (PEG), patterns of square and triangular geometries were created, and the effect of these structures and the biophysical cues arising were utilized to differentiate cells into multiple lineages inside a same pattern without the use of any adhered protein or growth factors. The data from these studies showed that the cells present at the edges were well elongated, exhibit high aspect ratios, and differentiated into osteogenic lineage, whereas the cells present at the center exhibit lower aspect ratio and were primarily adipogenic lineage regardless of the geometry. This was correlated to the higher expression of focal adhesion proteins at the edges, the expression of which have been known to affect the osteogenic differentiation. By showing MSC lineage commitment relationships due to physical signals, this study highlights the importance of these cues and cell shape in further understanding stem cell behavior for tissue engineering applications.

Size variations of mesoporous silica nanoparticle control uptake efficiency and delivery of AC2-derived dsRNA for protection against tomato leaf curl New Delhi virus.

KEY MESSAGE: We report the size dependent uptake of dsRNA loaded MSNPs into the leaves and roots of Nicotiana benthamiana plants and accessed for their relative reduction in Tomato leaf curl New Delhi viral load. A non-GMO method of RNA interference (RNAi) has been recently in practice through direct delivery of double stranded RNA into the plant cells. Tomato leaf curl New Delhi virus (ToLCNDV), a bipartitie begomovirus, is a significant viral pathogen of many crops in the Indian subcontinent. Conventional RNAi cargo delivery strategies for instance uses viral vectors and Agrobacterium-facilitated delivery, exhibiting specific host responses from the plant system. In the present study, we synthesized three different sizes of amine-functionalized mesoporous silica nanoparticles (amino-MSNPs) to mediate the delivery of dsRNA derived from the AC2 (dsAC2) gene of ToLCNDV and showed that these dsRNA loaded nanoparticles enabled effective reduction in viral load. Furthermore, we demonstrate that amino-MSNPs protected the dsRNA molecules from nuclease degradation, while the complex was efficiently taken up by the leaves and roots of Nicotiana benthamiana. The real time gene expression evaluation showed that plants treated with nanoparticles of different sizes ~ 10 nm (MSNPDEA), ~ 32 nm (MSNPTEA) and ~ 66 nm (MSNPNH3) showed five-, eleven- and threefold reduction of ToLCNDV in N. benthamiana, respectively compared to the plants treated with naked dsRNA. This work clearly demonstrates the size dependent internalization of amino-MSNPs and relative efficacy in transporting dsRNA into the plant system, which will be useful in convenient topical treatment to protect plants against their pathogens including viruses. Mesoporous silica nanoparticles loaded with FITC, checked for its uptake into Nicotiana benthamiana.

Single-shot multispectral quantitative phase imaging of biological samples using deep learning.

Multispectral quantitative phase imaging (MS-QPI) is a high-contrast label-free technique for morphological imaging of the specimens. The aim of the present study is to extract spectral dependent quantitative information in single-shot using a highly spatially sensitive digital holographic microscope assisted by a deep neural network. There are three different wavelengths used in our method: λ=532, 633, and 808 nm. The first step is to get the interferometric data for each wavelength. The acquired datasets are used to train a generative adversarial network to generate multispectral (MS) quantitative phase maps from a single input interferogram. The network was trained and validated on two different samples: the optical waveguide and MG63 osteosarcoma cells. Validation of the present approach is performed by comparing the predicted MS phase maps with numerically reconstructed (F T+T I E) phase maps and quantifying with different image quality assessment metrices.

Association of interleukin-1, interleukin-6, collagen type I alpha 1, and osteocalcin gene polymorphisms with early crestal bone loss around submerged dental implants: A nested case control study.

STATEMENT OF PROBLEM: The reason for variations in peri-implant early crestal bone loss is unclear but may be due to genetic differences among individuals. PURPOSE: The purpose of this nested case control study was to investigate the association of single-nucleotide polymorphisms of interleukin-1, interleukin-6, collagen type I alpha1, and osteocalcin genes to early crestal bone loss around submerged dental implants. MATERIAL AND METHODS: Dental implants were placed in the mandibular posterior region (single edentulous space) of 135 participants selected according to predetermined selection criteria. Bone mineral density measurement by using dual energy X-ray absorptiometry, cone beam computed tomography scans at the baseline and after 6 months, and interleukin-1A-889 A/G (rs1800587), interleukin-1B-511 G/A (rs16944), interleukin-1B+3954 (rs1143634), interleukin-6-572 C/G (rs1800796), collagen type I alpha1 A/C (rs1800012), and osteocalcin C/T (rs1800247) genotyping were performed in all participants. Early crestal bone loss measured around dental implants was used to group participants into clinically significant bone loss (BL)>0.5 mm and clinically nonsignificant bone loss (NBL)≤0.5 mm. Early crestal bone loss was calculated as the mean of the difference of bone levels at the baseline and bone levels after 6 months as measured with cone beam computed tomography scans. The obtained data for basic characteristics, early crestal bone loss, and genotyping were tabulated and compared by using a statistical software program (α=.05). RESULTS: AA genotype and the A allele frequency of interleukin-1B-511 and GG genotype and the G allele frequency of interleukin-6-572 were significantly higher in BL than in NBL (P<.05). Multiple logistic analysis suggested that interleukin-1B-511 AA/GG+AG and interleukin-6-572 GG/CC+CG genotype expression were significantly associated with early crestal bone loss (AA/GG+AG; P=.014, GG/CC+CG; P=.047) around dental implants. Other risk factors were not significantly different (P>.05). CONCLUSIONS: Of the genes studied, individuals with interleukin-1B-511 AA (rs16944) or interleukin-6-572 GG (rs1800796) genotype had higher susceptibility to early crestal bone loss around dental implants.

Advancements in Three Dimensional In-Vitro Cell Culture Models.

The scientific field is observing a gradual shift from monolayer cultures to three-dimensional (3D) models, as they give a more relevant data in pre-clinical stages. This review summarizes the major techniques and materials used to develop 3D platforms, especially for cancer. It also discusses the challenges and some unresolved issues of the field and highlights some techniques that have made it to the market.

Role of mammalian long non-coding RNAs in normal and neuro oncological disorders.

Long non-coding RNAs (lncRNAs) are expressed at lower levels than protein-coding genes but have a crucial role in gene regulation. LncRNA is distinct, they are being transcribed using RNA polymerase II, and their functionality depends on subcellular localization. Depending on their niche, they specifically interact with DNA, RNA, and proteins and modify chromatin function, regulate transcription at various stages, forms nuclear condensation bodies and nucleolar organization. lncRNAs may also change the stability and translation of cytoplasmic mRNAs and hamper signaling pathways. Thus, lncRNAs affect the physio-pathological states and lead to the development of various disorders, immune responses, and cancer. To date, ~40% of lncRNAs have been reported in the nervous system (NS) and are involved in the early development/differentiation of the NS to synaptogenesis. LncRNA expression patterns in the most common adult and pediatric tumor suggest them as potential biomarkers and provide a rationale for targeting them pharmaceutically. Here, we discuss the mechanisms of lncRNA synthesis, localization, and functions in transcriptional, post-transcriptional, and other forms of gene regulation, methods of lncRNA identification, and their potential therapeutic applications in neuro oncological disorders as explained by molecular mechanisms in other malignant disorders.

Differential expression profiling of onco and tumor-suppressor genes from major-signaling pathways in Wilms' tumor.

PURPOSE: Wilms' tumor is the most-frequent malignant-kidney tumor in children under 3-4 years of age and is caused by genetic alterations of oncogenes (OG) and tumor-suppressor genes (TG). Wilms' tumor has been linked to many OG-&-TG. However, only WT1 has a proven role in the development of this embryonic-tumor. METHODS: The study investigates the level of mRNA expression of 16 OGs and 20 TGs involved in key-signaling pathways, including chromatin modification; RAS; APC; Cell Cycle/Apoptosis; Transcriptional Regulation; PI3K; NOTCH-&-HH; PI3K & RAS of 24-fresh Wilms'-tumor cases by capture-and-reporter probe Code-Sets chemistry, as CNVs in these pathway genes have been reported. RESULTS: Upon extensively investigating, MEN1, MLL2, MLL3, PBRM1, PRDM1, SMARCB1, SETD2, WT1, PTPN11, KRAS, HRAS, NF1, APC, RB1, FUBP1, BCOR, U2AF1, PIK3CA, PTEN, EBXW7, SMO, ALK, CBL, EP300-and-GATA1 were found to be significantly up-regulated in 58.34, 62.5, 79.17, 91.67, 58, 66.66,54, 58.34, 66.67, 75, 62.5, 62.5, 58, 79.17, 79.17, 75, 70.84, 50, 50, 75, 66.66, 62.50, 61.66, 58.34-and-62.50% of cases respectively, whereas BRAF, NF2, CDH1, BCL2, FGFR3, ERBB2, MET, RET, EGFR-and-GATA2 were significantly down regulated in 58, 87.50, 79.16, 54.16, 79.17, 91.66, 66.66, 58.33, 91.66-and-62.50% of cases, respectively. Interestingly, the WT1 gene was five-fold down regulated in 41.66% of cases only. CONCLUSION: Hence, extensive profiling of OGs and TGs association of major-signaling pathways in Wilms' tumor cases may aid in disease diagnosis. PBRM1 (up-regulated in 91.67% of cases), ERBB2 and EGFR (down-regulated in 91.66 and 91.66% of cases, respectively) could be marker genes. However, validation of all relevant results in a larger number of samples is required.

Clinical outcomes of flap versus flapless immediately loaded single dental implants in the mandibular posterior region: One-year follow-up results from a randomized controlled trial.

STATEMENT OF PROBLEM: Flapless implant placement with immediate functional loading has been reported in anterior locations. However, data on posterior locations are lacking. PURPOSE: The purpose of this randomized controlled trial was to determine and compare clinical outcomes of flap versus flapless surgically placed single posterior mandibular dental implants subjected to immediate functional loading. MATERIAL AND METHODS: Participants with missing mandibular first molar teeth were recruited and randomized into 2 groups (n=51): flapped and flapless. Dental implants were surgically placed and loaded immediately with interim restorations following implant protective occlusion. Outcome measures were implant failure, crestal bone loss, and periodontal parameters: modified plaque index, modified sulcus bleeding index, and pocket depths. Outcome data were recorded at baseline, 6-month, and 12-month follow-up visits. Cone beam computed tomography scans were used to calculate crestal bone loss, and periodontal outcomes were recorded by using a resin covered periodontal probe (α=.05). RESULTS: After 12 months, similar implant failure rates (P>.05) were found between the groups. Crestal bone loss in the flapped group was statistically higher than in the flapless group at 6 months (0.83 ±0.21 mm versus 0.75 ±0.23 mm) and at 12 months (1.04 ±0.27 mm versus 0.90 ±0.24 mm) from the baseline. The modified plaque index, modified sulcus bleeding index, and peri-implant probing depths (PDs) in both groups increased from the baseline to 6-month follow-ups (Baseline modified plaque index: 0.82 ±0.54 versus 0.79 ±0.21; Baseline modified sulcus bleeding index: 0.74 ±0.21 versus 0.70 ±0.43; Baseline PD: 1.25 ±0.37 mm versus 1.20 ±0.22 mm; 6 months modified plaque index: 1.54 ±0.70 versus 1.21 ±0.45; 6 months modified sulcus bleeding index: 1.93 ±0.54 versus 1.51 ±0.61; 6 months PD: 3.20 ±0.73 mm versus 2.80 ±0.43 mm). At 12-month follow-ups after repeated oral hygiene reinforcements, periodontal parameters had improved (decreased) significantly. CONCLUSIONS: Flapless implant insertion with immediate functional loading could be considered as an appropriate treatment option for providing functional restorations on the day of implant placement with minimal surgical intervention, reducing crestal bone loss, and periodontal complications.

Mobile Health Interventions and RCTs: Structured Taxonomy and Research Framework.

Mobile Health Interventions (MHIs) have addressed a range of healthcare challenges and have been evaluated using Randomized Controlled Trials (RCTs) to establish clinical effectiveness. Using PRISMA we conducted a systematic literature review of RCTs for MHIs and identified 70 studies which were analyzed and classified using Nickerson-Varshney-Muntermann (NVM) taxonomy. From the resultant iterations of the taxonomy, we extracted insights from the categorized studies. RCTs cover a wide range of health conditions including chronic diseases, general wellness, unhealthy practices, family planning, end-of-life, and post-transplant care. The MHIs that were utilized by the RCTs were varied as well, although most studies did not find significant differences between MHIs and usual care. The challenges for MHI-based RCTs include the use of technologies, delayed outcomes, patient recruitment, patient retention, and complex regulatory requirements. These variances can lead to a higher rate of Type I/Type II errors. Further considerations are the impact of infrastructure, contextual and cultural factors, and reductions in the technological relevancy of the intervention itself. Finally, due to the delayed effect of most outcomes, RCTs of insufficient duration are unable to measure significant, lasting improvements. Using the insights from seventy identified studies, we developed a classification of existing RCTs along with guidelines for MHI-based RCTs and a research framework for future RCTs. The framework offers opportunities for (a) personalization of MHIs, (b) use of richer technologies, and (c) emerging areas for RCTs.

Exploiting Substrate Cues for Co-Culturing Cells in a Micropattern.

Spatial distribution of cells and their interactions between neighboring cells in native microenvironments are of fundamental importance in determining cell fate decisions such as migration, growth, and differentiation. Controlling the spatial distribution of different cell types in defined geometries can replicate these native environments, which can be a useful model for several studies. While spatiotemporal control over multiple cell arrangements is required to achieve the complex tissue architecture, unfortunately, conventional cell patterning techniques usually allow only single patterning with a single cell type. In the present study, we introduce a simple lithographic method to pattern multiple cell types in a spatially controlled manner by utilizing the biophysical cues present at the corners of the patterned geometry. By fabricating micropatterns of different shapes, we demonstrate how the cell can be constrained to pattern along the corners of patterned geometries owing to the presence of topographical cues, leaving empty voids in the center that can be further utilized for patterning a second cell type. We also demonstrate that the cell alignment along the pattern is a dynamic process and the cells migrate from a more uniform cell-adhesive region toward the topographical cues. The cytoskeleton arrangement was geometry-dependent, which was confirmed through a series of in vitro evaluations, such as scanning electron microscopy and fluorescence microscopy. These findings have not only helped us in exploring the importance of these cues in guiding the cell fate but have also allowed us to develop a technique, which self-patterns the cells without any expensive exogenous cues and can be used as a model protocol to eventually organize cells into a specific pattern with micron-scale precision in vitro.

16S rRNA gene profiling of rhizospheric microbial community of Eichhornia crassipes.

The rhizosphere of a plant is an important interface for the plant-microbe interaction that plays a significant role in the uptake and removal of heavy metal from contaminated sites. Eichhornia crassipes is a free-floating macrophyte and a well-known metal hyperaccumulator. It is a promising plant, which harbors a diverse microbial community in its rhizosphere. Therefore it is hypothesized that it can be a good habitat for microorganisms that supports plant growth and increases its phytoremediation potential. The rhizospheric DNA was extracted from the procured plant samples. The library was prepared and sequenced using the Illumina platform. 16S rRNA data from the Next Generation Sequencing (NGS) platform was analyzed using the QIIME software package. Alpha diversity was estimated from statistical indices i.e. Shannon index, Chao1 index, and observed species. The rarefaction plots, rank abundance curve, krona graph, and heat map were generated to study the rhizospheric community in detail. Metagenome consisted of 225,408 flash reads, 185,008 non-chimeric sequences with 17,578 Operational Taxonomic Units (OTU's), and 4622 OTU's without singletons. The data of present study are available at NCBI Bioproject (PRJNA631882). The taxonomic analysis of OTU's showed that the sequences belonged to major Phyla revealing the dominance of Proteobacteria, Bacteroidetes, Cyanobacteria, and Verrucomicrobia. The most abundant Genera in the sampled rhizosphere recorded were Thiothrix and Flavobacterium.

A review on traditional uses, phytochemistry, pharmacology, and clinical research of dietary spice Cuminum cyminum L.

Cuminum cyminum L. is a versatile spice belonging to family Apiaceae. Though the plant has pan-tropical distribution but it is indigenous to Egypt, the Mediterranean, and South Asian countries. It exhibits numerous culinary, traditional, and pharmacological attributes. Its traditional uses also validate its immense pharmacological potential. Cuminum cyminum is the hub of numerous bioactives such as alkaloids, flavonoids, terpenoids, and so forth. Cuminaldehyde is the major bioactive, rendered to most of its pharmacological as well as clinical significance. The present study comprised of current knowledge on its taxonomy, nutritional, traditional, phytochemistry, pharmacology (antimicrobial, antioxidant, anti-inflammation, antidiabetic, wound healing, anticancer, etc.), toxicology, and clinical attributes. Besides, the mechanism of action is also well explained. The present study provides a rationale for further bioprospection of this wonder plant. Future studies are needed to fill the research gaps, particularly on relevant phytocompound isolation, their pre-clinical and clinical characterization, evaluation, and structure-activity relationship. Moreover, well-designed and highly appropriate clinical and placebo trials are still needed to demonstrate the trustworthy role of cumin on human health.

Stereoselective formal [3 + 3] annulation of 3-alkylidene-2-oxindoles with ß,γ-unsaturated α-keto esters.

1,4-Diazabicyclo[2.2.2]octane (DABCO)-catalyzed [3 + 3] cycloaddition reaction of 3-alkylidene-2-oxindole and ß,γ-unsaturated α-keto esters under mild reaction conditions afforded the spirocyclohexene-oxindole with excellent diastereoselectivity. The [3 + 3] annulation is found to proceed through a vinylogous Michael-aldol cascade reaction and it allows rapid access to a diverse set of highly functionalized spirocyclohexene-oxindoles. Also, a bioactivity study of the compounds on mammalian sarcoma cells has reflected cell growth inhibitory/anti-cancer properties.

Involvement of fatty acid synthase in right ventricle dysfunction in pulmonary hypertension.

Apart from pulmonary vascular resistance and right ventricle (RV) hypertrophy, metabolic dysfunction also plays a major role in pathophysiology of pulmonary hypertension (PH). Recently, we have shown that fatty acid synthase (FAS), an enzyme involved in de novo fatty acid synthesis, plays a pivotal role in PH as its inhibition was protective and decreased pulmonary vascular remodelling, RV pressure and hypertrophy and improved endothelial functions. However, the precise mechanism behind protective effect of FAS inhibition on right ventricle dysfunction associated with PH is not completely understood. Therefore, the present study delineated the mechanism of protective effect of FAS inhibition on RV dysfunction associated with PH. siRNA mediated inhibition of FAS reduced FAS expression, hypertrophy, inflammation, apoptosis, autophagy and improved the glucose oxidation, mitochondrial membrane potential and ATP level in hypoxic cardiomyocytes. In monocrotaline (MCT) treated rats, FAS inhibition by C75 (2 mg/kg, i.p., once a week from 21 to 35 days) decreased the expression and activity of FAS and palmitate level. C75 also improved cardiac functions and mitochondrial membrane potential leading to decreased apoptosis in RV of MCT treated rats. In conclusion, our study reveals that inhibition of FAS decreases RV hypertrophy and improves cardiac function associated with PH by perking up metabolic functions.