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Raman spectroscopy has become a popular analytical tool because of its ability to probe nondestructively and provide fingerprint information about materials. The advancements in the field of Raman spectroscopy and the expanding scope of applications warrant the introduction of the topic in the formal education curriculum. The introduction of Raman spectroscopy analysis in the educational curriculum helps the students learn the spectroscopy basics. Furthermore, component-wise familiarization and fabrication training will help the students to evolve their own methodologies to fabricate and customize the instrument for specific applications. Though many Raman spectrometers are commercially available, the high cost makes it unaffordable for most academic institutions. Herein, we describe an easy and cost-effective method to make a fully integrated portable Raman spectrometer and explain a few simple experiments which can be conducted at the classroom level using the fabricated device.

Light intensity is a critical environmental factor influencing plant growth and development. To survive high light conditions, plants have evolved various protective mechanisms, including non-photochemical quenching (NPQ). However, NPQ can limit effective photosynthetic yield when transitioning to low light conditions. This phenomenon is underexplored in cassava (Manihot esculenta), a starchy storage root crop known for its high biological efficiency and climate resilience. To address this knowledge gap, we assessed the photoprotective abilities and growth responses of six cassava varieties under natural environmental light conditions (control) and intermittent high light (IHL) conditions by adding 900 μmol m−2 s−1 using full-spectrum LED lights, on top of the natural ambient daylight. Our results demonstrated a significant impact of light treatment on aboveground biomass, total crop biomass, chlorophyll a and b content, photosynthetic rate, and NPQ values during transitions from low to high light and vice versa. Notably, cassava variety 'Sree Suvarna' exhibited the highest yield under both control and IHL conditions. These findings suggest that screening cassava varieties for their ability to postpone photoinhibition and recover quickly from photoinhibition may enhance photosynthetic performance. Such strategies have important implications for improving the efficiency and resilience of cassava crops, ultimately contributing to sustainable agricultural productivity. Excessive light can be detrimental to plant growth. To overcome this, plants employ photoprotective non-photochemical quenching (NPQ) mechanisms. This study evaluated NPQ kinetics and growth of six cassava (Manihot esculenta) varieties under natural and intermittent high light conditions. Exposure to high light significantly affected biomass production, chlorophyll content, and photosynthesis, with the variety 'Sree Suvarna' demonstrating the highest yield across all conditions. Identifying cassava varieties with effective NPQ regulation could improve photosynthetic efficiency and enhance crop resilience, supporting sustainable agricultural productivity. [ABSTRACT FROM AUTHOR]

Background: This study characterized undernutrition among children (0–24 months) by age groups specified for Infant and Young Child-feeding (IYCF) and determined the association between child malnutrition and IYCF. Methods: This cross-sectional survey recruited mother-children dyads (N = 1443). WHO standards were used to assess nutritional status and IYCF indicators. Multivariate analyses were performed to assess the association between IYCF and nutritional indicators. Results: Stunting, underweight, wasting, overweight, and obesity were prevalent in 33.1%, 26%, 20.2%, 4.6%, and 2.9% of the children, respectively. Age-wise distribution of undernutrition identified severity of stunting and underweight at 10–24 months (median < -1.6 SD; < -1.2 SD; 25th percentile at -2.6 & -2.2 SD respectively) and wasting highest at 0–6 months (25th percentile close to -2SD). Boys manifested higher stunting (lower value -5.2 SD) and were more wasted (lower value -4.7 SD). IYCF prevalence recorded early initiation at 45.2%, exclusive breastfeeding at 23.1%, and prelacteal and bottle-feeding at 37.5 and 22.5% respectively. Child minimum diet diversity (MDD) ≥4 was not achieved by 84%. Minimum meal frequency and minimum acceptable diet were achieved by 75% and 14% respectively. Bottle-feeding increased the odds of wasting [AOR: 1.501 (95% CI: 1.062–2.121)], severe stunting [AOR: 1.595 (95% CI: 1.079–2.358)] and underweight [AOR: 1.519 (95% CI 1.102–2.094)]. Wasting according to BAZ scores was associated with delayed initiation of breastfeeding [AOR: 1.387 (95% CI: 1.018–1.889)] and bottle feeding [AOR: 1.538 (95% CI: 1.087–2.175)]. Delayed introduction of complementary feeding increased the odds of severe stunting [AOR: 2.189 (95% CI: 1.090–4.399)]. Formula feeding increased the odds of underweight [AOR: 1.738 (95% CI: 1.046–2.888)] and obesity [AOR: 4.664 (95% CI: 1.351–16.10)]. Prelacteal feeding increased the odds of severe forms of stunting and underweight by 56% and 79% respectively, and overweight by 96%. Conclusion: Setting and age-specific interventions to improve age-appropriate child-feeding practices are vital to address the double burden of malnutrition in the critical age group. [ABSTRACT FROM AUTHOR]

A large group of keratin genes (n=54 in the human genome) code for intermediate filament (IF)-forming proteins and show differential regulation in epithelial cells and tissues. Keratin expression can be highly informative about the type of epithelial tissue, differentiation status of constituent cells and biological context (e.g. normal versus diseased settings). The foundational principles underlying the use of keratin expression to gain insight about epithelial cells and tissues primarily originated in pioneering studies conducted in the 1980s. The recent emergence of single cell transcriptomics provides an opportunity to revisit these principles and gain new insight into epithelial biology. Re-analysis of single-cell RNAseq data collected from human and mouse skin has confirmed long-held views regarding the quantitative importance and pairwise regulation of specific keratin genes in keratinocytes of surface epithelia. Furthermore, such analyses confirm and extend the notion that changes in keratin gene expression occur gradually as progenitor keratinocytes commit to and undergo differentiation, and challenge the prevailing assumption that specific keratin combinations reflect a mitotic versus a post-mitotic differentiating state. Our findings provide a blueprint for similar analyses in other tissues, and warrant a more nuanced approach in the use of keratin genes as biomarkers in epithelia. [ABSTRACT FROM AUTHOR]

Infant and young child feeding practices remain a public health challenge in India. We determined the socio-demographic risk factors for early initiation, exclusive breastfeeding and prelacteal feeding in the urban slums of Pune city. A cross sectional survey of mother (N=1443) children (< 2 years) dyads was performed. Socio-demographic, maternal and child characteristics were recorded. Breastfeeding practices were assessed using WHO indicators. Multiple logistic regression was employed to model associations between socio-demographic factors and breastfeeding indicators. Early initiation was reported by 45.2%, prelacteal feeding by 37.5% and exclusive breastfeeding by 23.7%. Caesarean delivery decreased the odds of early initiation (AOR: 0.403; 95% CI; 0.303.-0.536) and exclusive breastfeeding (OR: 0.675; 95% CI: 0. 478-0.953), while it increased the odds of prelacteal feeding (AOR: 3.525; 95% CI: 2.653-4.683). Delivery in a public health care facility increased the odds of early initiation (AOR: 1.439; 95% CI: 1.095-1.891) and exclusive breastfeeding (OR: 0.514; 95% CI: 0.366-0.720), while it decreased the odds of prelacteal feeding (AOR: 0.421; 95% CI: 0.318-0.559). Odds of early initiation decreased significantly in very low-birth-weight (AOR: 0.209; CI: 0.76-0.567) whereas, it increased odds of prelacteal feeding (AOR: 1.389; 95% CI: 0.640-3.019), (AOR: 0.483; 95% CI: 0.262-0.889). Religion other than Hindu or Muslim, age of the mother between 26-30 years increased the odds of exclusive breastfeeding and parity <2 increased the odds of prelacteal feeding. Interventions that address setting specific determinants, focusing on local contexts are essential to improve child feeding practices in urban slums. [ABSTRACT FROM AUTHOR]

High levels of the intermediate filament protein keratin 17 (K17) are associated with poor prognoses for several human carcinomas. Studies in mouse models have shown that K17 expression is positively associated with growth, survival, and inflammation in skin and that lack of K17 delays onset of tumorigenesis. K17 occurs in the nucleus of human and mouse tumor keratinocytes where it impacts chromatin architecture, gene expression, and cell proliferation. We report here that K17 is induced following DNA damage and promotes keratinocyte survival. The presence of nuclear K17 is required at an early stage of the double-stranded break (DSB) arm of the DNA damage and repair (DDR) cascade, consistent with its ability to associate with key DDR effectors, including A-H2A.X, 53BP1, and DNA-PKcs. Mice lacking K17 or with attenuated K17 nuclear import showed curtailed initiation in a two-step skin carcinogenesis paradigm. The impact of nuclear-localized K17 on DDR and cell survival provides a basis for the link between K17 induction and poor clinical outcomes for several human carcinomas. [ABSTRACT FROM AUTHOR]

Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences in nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte cell lines lacking K17 exhibit flatter nuclei relative to normal. Re-expression of wild-type K17, but not a mutant form lacking an intact nuclear localization signal (NLS), rescues nuclear morphology in KRT17-null cells. Analyses of primary cultures of skin keratinocytes from a mouse strain expressing K17 with a mutated NLS corroborated these findings. Proteomics screens identified K17-interacting nuclear proteins with known roles in gene expression, chromatin organization and RNA processing. Key histone modifications and LAP2β (an isoform encoded by TMPO) localization within the nucleus are altered in the absence of K17, correlating with decreased cell proliferation and suppression of GLI1 target genes. Nuclear K17 thus impacts nuclear morphology with an associated impact on chromatin organization, gene expression, and proliferation in epithelial cells. [ABSTRACT FROM AUTHOR]

Pollution of aquatic bodies with Lead and Mercury is a serious environmental issue, and there exists an unmet need to develop easy and portable detection techniques. Herein, we report a silver nanoparticle (AgNP) based system exhibiting high selectivity and distinct spectrophotometric behaviour towards these metal ions in the aqueous medium. Though many of the metal ions did not influence the characteristic plasmon spectral profile of AgNPs, Mercury caused the disappearance of absorbance at ~400 nm. Consequently, the yellow solution became colourless at around 7.6 ppm of Hg2+ ions. While the presence of Pb2+ ions induced a decrease in the initial plasmon intensity with the concomitant emergence of a new red-shifted band above 500 nm. As a result, the colour of the solution turned from yellow to red. These colour changes are found to fall well within the spectral responses of R, G and B filters of the digital camera. By making use of this, an android mobile application was developed for digitizing the colour values and for doing further quantitative analysis. The estimated concentration value by this method was found to be in good match with those obtained from absorbance measurement. The achieved lower detection limits were ~ 0.8 ppm for Hg2+ and ~ 1.5 ppm for Pb2+ ions. This illustrates the potential of the proposed combination of smartphone enabled system with AgNPs for easy discrimination and quantification of these two metal ions from the aqueous medium. [ABSTRACT FROM AUTHOR]

Cellular senescence is an outcome of the accumulation of DNA damage which induces the growth arrest in cells. Physiologically, it is presumed to be mediated by accumulation of reactive oxygen species (ROS). Here, we show that another free radical, nitric oxide (NO) produced during inflammation or present as an environmental pollutant can also induce cellular senescence. In primary cells and various immortalized cell lines, exposure to chronic NO, through external addition or internally generated by iNOS expression, leads to the activation of DNA damage response and causes cellular senescence. The phenotype generated by NO includes robust growth arrest, increase in the levels of the DNA damage foci, ROS, SAβ-gal staining, and inflammatory cytokines like IL-6 and IL-8, all hallmarks of cellular senescence similar to replicative senescence. Mechanistically, inhibitor and knockdown analysis revealed that NO mediates senescence through ATM kinase activation and the viability of cells is dependent on both ROS and ATM kinase involving the ATM-ROS-iNOS axis. Overall, we demonstrate that nitric oxide mediates cellular senescence through a novel free radical dependent genotoxic stress pathway. [ABSTRACT FROM AUTHOR]

An origami-based multilayer structure suitable for passive chipless radio frequency identification applications is presented in this paper. Contrary to the existing multilayer designs where metallic via is used for the interconnections, the proposed technique uses the folding of the structure designed in a flexible substrate. Thus, the multilayer structure is obtained from a thin printed circuit board that is folded to give the desired 3-D structure. The proposed structure consists of cascaded commensurate transmission line sections (also known as C-sections) coupled at alternative ends. The group delay (GD) characteristic of the C-sections is utilized for encoding. Broad side coupling of the structure is exploited here, which enables large GD with higher frequency selectivity. It is proved that to produce the same amount of delay, linearly cascaded C-sections demands five times more number of C-sections than that of a multilayered structure, which also signifies the factor of miniaturization of the proposed design. A coding capacity of 6 and 12 b is estimated from the simulation, respectively, for single group and multigroup of multilayered C-sections in the allowed industrial, scientific, and medical (ISM) bands. This shows for the first time that frequency domain chipless technology can be compatible with the use of ISM bands. It also allows a coding capacity of 43 b in the ultra-wideband band which is comparable with the EAN 13 barcode. [ABSTRACT FROM PUBLISHER]

In this Communication, a molecular beacon-based DNA switch (LMB) is developed as an efficient and reversible pH sensing probe. Remarkably, LMB exhibited reversible structural transition between the closed (molecular beacon) and open (A-motif) states very efficiently in synthetic vesicles and live cells without the need for any transfection agents. [ABSTRACT FROM AUTHOR]

Cells exposed to genotoxic stress induce cellular senescence through a DNA damage response (DDR) pathway regulated by ATM kinase and reactive oxygen species (ROS). Here, we show that the regulatory roles for ATM kinase and ROS differ during induction and maintenance of cellular senescence. Cells treated with different genotoxic agents were analyzed using specific pathway markers and inhibitors to determine that ATM kinase activation is directly proportional to the dose of the genotoxic stress and that senescence initiation is not dependent on ROS or the p53 status of cells. Cells in which ROS was quenched still activated ATM and initiated the DDR when insulted, and progressed normally to senescence. By contrast, maintenance of a viable senescent state required the presence of ROS as well as activated ATM. Inhibition or removal of either of the components caused cell death in senescent cells, through a deregulated ATM-ROS axis. Overall, our work demonstrates existence of an intricate temporal hierarchy between genotoxic stress, DDR and ROS in cellular senescence. Our model reports the existence of different stages of cellular senescence with distinct regulatory networks. [ABSTRACT FROM AUTHOR]

A novel fully printed 28-bits capacity chipless RFID tag using conical resonators is proposed here. The angle of aperture of these resonators is adjusted to suppress high order modes allowing an efficient use of the UWB frequency bandwidth. By using 12 resonators within a reduced dimension of 4.2x3 cm², a coding capacity of 28 bits is achieved, which is the highest coding capacity reported for a fully printed chipless tag. Several chipless tags are printed on flexible substrate and validated experimentally. [ABSTRACT FROM AUTHOR]

A time domain chipless RFID tag based on cascaded microstrip coupled transmission line sections (C-sections), which can operate in multi-frequency bands is presented. The group delay characteristics of the C-sections are exploited to generate the tag Identification (ID). The tag comprises cascaded commensurate group of C-sections and two cross-polarized ultra wide-band (UWB) antennas. Since the proposed tag can operate in multi-frequency bands, this paper proves the possibility of increasing the coding capacity compared to the existing time domain designs. A tag operating at ISM(Industrial Scientific and Medical) bands at 2.45 GHz and 5.8 GHz together with conformance of frequency and power regulations is discussed elaborately. The prototype of the device is fabricated and validated experimentally. The time domain characteristic of the tag is also validated experimentally by interrogating a short pulse. Furthermore, measurement results using commercial Ultra Wide Band (UWB) radar which can be used as a chipless RFID reader is also incorporated. The obtained results confirm the concept and the possibility of using temporal multi-frequency in chipless RFID. [ABSTRACT FROM AUTHOR]

This paper is mainly dedicated to the design of radio-frequency identification (RFID) tags, particularly the antennas that allow the tag to be fed, communicate, and exchange data with the reader. Good performance tags require optimized antenna that take into account numerous constraints as well as the environment of the application under consideration. Both conventional tags and robust tags are discussed. This paper also discusses how to transform a tag into an RFID sensor. [ABSTRACT FROM PUBLISHER]

Antigens released in vivo are of considerable interest in the immunodiagnosis of infectious diseases. Circulating antigen was isolated from bacteriologically confirmed tuberculous sera by ammonium sulphate precipitation. The protein fraction between 36% and 75% ammonium sulphate was reactive with tuberculosis (TB) sera showing the presence of circulating tubercular antigen (CTA). Fractionation of CTA on ultrogel AcA 34 gel filtration column gave 3 protein fractions CTA1, CTA2 and CTA3. CTA2 showed maximum antigenic activity by sandwich enzyme-linked immunosorbent assay (ELISA). SDS-PAGE fractionation and seroreactivity studies showed the presence of highly reactive tubercular antigen in CTA2-7 protein fraction by sandwich ELISA. Further fractionation of CTA2-7 on cation exchange fast-protein liquid chromatography (FPLC) gave 4 antigenic fractions, of which CTA2-7D was seroreactive similar to 31 kDa antigen (ESAS-7F) isolated from in vitro culture medium. Furthermore, CTA2-7D could inhibit binding of in vitro released ESAS-7F to affinity purified antibodies in inhibition ELISA. CTA2-7D antigen may be used as a target antigen in confirming active tubercular infection. Biochemical characterization showed circulating antigen CTA2-7D to be a lipoglycoprotein is released in vivo. ESAS-7F as a glycoprotein is released in vitro culture. [ABSTRACT FROM AUTHOR]

Development of selective, ultra-sensitive, rapid and facile methods for the detection of chemical residues of toxic pesticides and hazardous chemicals are quite important in food safety, environmental monitoring and safeguarding public health. Herein, we presented a fluorescent turn-on aptasensor based on sulphur-doped graphene quantum dot (S-GQD) utilizing specific recognition and binding property of aptamer for the ultra-sensitive and selective detection of omethoate (OM) which is a systemic organophosphorus pesticide. The detection method is based on tuning aggregation-disaggregation mechanism of S-GQD by way of conformational alteration of the recognition probe. Fluorescence 'turn-on' process includes aggregation-induced quenching of S-GQD with aptamer via S-GQD-aptamer complex formation and its subsequent fluorescence recovery with the addition of OM by structural switching of S-GQD-aptamer complex to aptamer-omethoate complex. The reported 'switch-on' aptasensor has exhibited a low limit of detection of 0.001 ppm with high selectivity for OM over other pesticides. [Display omitted] • Sulphur-doped graphene quantum dot-based fluorescence turn-on aptasensor was demonstrated for the detection of omethoate. • Detection method was based on conformational alteration of aptamer that mediated aggregation and disaggregation of S-GQD. • Sensing strategy was not demanding the modification of either the signal transmitting nanoparticle or the reporter probe. • The sensor exhibited very low limit of detection (1 ppb) and high selectivity towards omethoate. [ABSTRACT FROM AUTHOR]

In the above article , the authors declare that the affiliation “Neethu Emmanuel, Reethu Haridas, Arun Gopi, Manikantan Sajitha, and Yoosaf Karuvath are with the Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India” is to be correctly read as “Neethu Emmanuel, Reethu Haridas, Arun Gopi, Manikantan Sajitha, and Yoosaf Karuvath are with the Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. [ABSTRACT FROM AUTHOR]

The article discusses a medical study which explores the cause of bilateral pleural effusion combined with ascites in a 77-year-old Asian man. The patient also was suffering from general weakness, dyspnea, tachycardia, and tachypnea. Following testing through multiple means including colonscopy, thoracentesis, and computed tomography, the researchers identified peritoneal tuberculosis as the cause.

An abstract of the article "Pre treatment Effect of Methanolic Extract of Leucasaspera on CCl4 Induced Liver Fibrosis In Rats," by B. Latha and colleagues is presented.

Intratumoral delivery of IL-12 and GM-CSF induces local and systemic antitumor CD8+ T cell activation and tumor kill. However, the effector response is transient and is rapidly countered by CD4+ Foxp3+ T suppressor cell expansion. To determine whether depletion of the pre-existing T suppressor cell pool prior to treatment could diminish posttherapy regulatory cell resurgence, FVBneuN mice bearing advanced spontaneous mammary tumors were treated with cyclophosphamide (CY) 1 d before IL-12/GM-CSF therapy. Administration of CY mediated a significant delay in the post-IL-12/GM-CSF T suppressor cell rebound, resulting in a 7-fold increase in the CD8+ CTL/T suppressor cell ratio, a 3-fold enhancement of CTL cytotoxicity, and an extension of the effector window from 3 to 7 d. In long-term therapy studies, chronic chemoimmunotherapy promoted a dramatic enhancement of tumor regression, resulting in complete cure in 44% of the mice receiving CY plus IL-12/GM-CSF. Tumor eradication in the chronic therapy setting was associated with the ability to repeatedly rescue and maintain cytotoxic CD8+ T cell activity. These findings demonstrated that chronic administration of CY in conjunction with immune therapy enhances the initial induction of antitumor T effector cells and, more importantly, sustains their cytotoxic activity over the long-term via persistent blockade of homeostatic counter-regulation. [ABSTRACT FROM AUTHOR]

Flavonoids are plant metabolites that are dietary antioxidants and exert significant anti-tumor, anti-allergic, anti-inflammatory and anti-viral effects. It is generally accepted that Th-1 derived cytokines such as IL-2, IFNγ and IL-12 promote cellular immunity while Th-2 derived cytokines such as IL-4, IL-5, IL-6 exert negative immunoregulatory effects on cellular immunity while upregulating humoral immunity. The molecular mechanisms underlying the biological activities of flavonoids have not been elucidated. We hypothesize that the flavonoid, quercetin, exert significant anti-viral and anti-tumor effects possibly by modulating the production of Th-1 and Th-2 derived cytokines. Peripheral blood mononuclear cells (PBMC, 1×106 cells/ml) from normal subjects were cultured with different concentrations of quercetin (0.5–50 μM) for 24–72 h and supernates were quantitated for IFN-γ and IL-4 by ELISA and antiviral activity of IFNγ by bioassay. FACS analysis was done to determine the number of IFN-γ and IL-4 positive cells and RT-PCR was done to quantitate gene expression. Quercetin significantly induces the gene expression as well as the production of Th-1 derived IFNγ and the downregulates Th-2 derived IL-4 by normal PBMC. Further, quercetin treatment increased the phenotypic expression of IFNγ cells and decreased IL-4 positive cells by FACS analysis, which corroborate with protein secretion and gene expression studies. These results suggest that the beneficial immuno-stimulatory effects of quercetin may be mediated through the induction of Th-1 derived cytokine, IFNγ, and inhibition of Th-2 derived cytokine, IL-4. [Copyright &y& Elsevier]

Oil-secreting sebaceous glands (SGs) are critical for proper skin function; however, it remains unclear how different factors act together to modulate SG stem cells. Here, we provide functional evidence that each SG lobe is serviced by its own dedicated stem cell population. Upon ablating Notch signaling in different skin subcompartments, we find that this pathway exerts dual counteracting effects on SGs. Suppressing Notch in SG progenitors traps them in a hybrid state where stem and differentiation features become intermingled. In contrast, ablating Notch outside of the SG stem cell compartment indirectly drives SG expansion. Finally, we report that a K14:K5→K14:K79 keratin shift occurs during SG differentiation. Deleting K79 destabilizes K14 in sebocytes, and attenuates SGs and eyelid meibomian glands, leading to corneal ulceration. Altogether, our findings demonstrate that SGs integrate diverse signals from different niches and suggest that mutations incurred within one stem cell compartment can indirectly influence another. • Each sebaceous gland lobe is independently maintained by a dedicated stem cell pool • Notch directly promotes sebaceous gland stem cell differentiation into sebocytes • Notch also indirectly suppresses sebaceous gland differentiation from a distance • Keratin 79 is crucial for maintaining sebaceous and meibomian gland structural integrity Sebaceous glands secrete oils that moisturize and protect the skin. Veniaminova et al. show that sebaceous gland stem cells are both directly and indirectly regulated by Notch signaling. Furthermore, they show that proper maintenance of these glands in the skin and eyelid depends upon Keratin 79. [ABSTRACT FROM AUTHOR]

Direct visualization of soft organic molecules like cellulose is extremely challenging under a high-energy electron beam. Herein, we adopt two ionization damage extenuation strategies to visualize the lattice arrangements of the β-(1→4)-d-glucan chains in carboxylated nanocellulose fibers (C-NCFs) having cellulose II crystalline phase using high-resolution transmission electron microscopy. Direct imaging of individual nanocellulose fibrils with high-resolution and least damage under high-energy electron beam is achieved by employing reduced graphene oxide, a conducting material with high electron transmittance and Ag + ions, with high electron density, eliminating the use of sample-specific, toxic staining agents, or other advanced add-on techniques. Furthermore, the imaging of cellulose lattices in a C-NCF/TiO 2 nanohybrid system is accomplished in the presence of Ag + ions in a medium revealing the mode of association of C-NCFs in the system, which validates the feasibility of the presented strategy. The methods adopted here can provide further understanding of the fine structures of carboxylated nanocellulose fibrils for studying their structure-property relationship for various applications., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Graphene quantum dots (GQDs) are zero-dimensional materials that exhibit characteristics of both graphene and quantum dots. Herein, we report a rapid, relatively green, one-pot synthesis of size-tunable GQDs from graphene oxide (GO) by a sonochemical method with intermittent microwave heating, keeping the reaction temperature constant at 90 °C. The GQDs were synthesized by oxidative cutting of GO using KMnO 4 as an oxidizing agent within a short span of time (30 min) in an acid-free condition. The synthesized GQDs were of high quality and exhibited good quantum yield (23.8%), high product yield (>75%), and lower cytotoxicity (tested up to 1000 μg/mL). Furthermore, the as-synthesized GQDs were demonstrated as excellent fluorescent probes for bioimaging and label-free sensing of Fe(III) ions, with a detection limit as low as 10 × 10 -6 M., Competing Interests: The authors declare no competing financial interest.

A 77-year-old Asian man presented to the emergency department with bilateral pleural effusion and ascites accompanied with generalized weakness, dyspnea, tachycardia, and tachypnea. After an extensive workup that ruled out heart failure, pulmonary embolism, pneumonia, and malignancy-including extensive laboratory tests, electrocardiograms, chest x-ray, computed tomographic angiogram, computed tomography scans of the abdomen and pelvis, colonoscopy, thoracentesis, paracentesis, and exploratory laparoscopy-an elusive peritoneal tuberculosis was successfully identified. This case suggests that clinicians should consider extrapulmonary tuberculosis in their practice, given increasing immigration and the variety of populations present in our society. When tuberculosis is suspected, a negative smear for acid-fast bacillus, a lack of granulomas on histopathology, and failure to culture Mycobacterium tuberculosis do not exclude the diagnosis. Exploratory laparoscopy or minilaparotomy has a high level of sensitivity and specificity so should be considered.

A single intratumoral injection of IL-12 and GM-CSF-loaded slow-release microspheres induces T cell-dependent eradication of established primary and metastatic tumors in a murine lung tumor model. To determine how the delivery of cytokines directly to the microenvironment of a tumor nodule induces local and systemic antitumor T cell activity, we characterized therapy-induced phenotypic and functional changes in tumor-infiltrating T cell populations. Analysis of pretherapy tumors demonstrated that advanced primary tumors were infiltrated by CD4+ and CD8+ T cells with an effector/memory phenotype and CD4+CD25+Foxp3+ T suppressor cells. Tumor-associated effector memory CD8+ T cells displayed impaired cytotoxic function, whereas CD4+CD25+Foxp3+ cells effectively inhibited T cell proliferation demonstrating functional integrity. IL-12/GM-CSF treatment promoted a rapid up-regulation of CD43 and CD69 on CD8+ effector/memory T cells, augmented their ability to produce IFN-gamma, and restored granzyme B expression. Importantly, treatment also induced a concomitant and progressive loss of T suppressors from the tumor. Further analysis established that activation of pre-existing effector memory T cells was short-lived and that both the effector/memory and the suppressor T cells became apoptotic within 4 days of treatment. Apoptotic death of pre-existing effector/memory and suppressor T cells was followed by infiltration of the tumor with activated, nonapoptotic CD8+ effector T lymphocytes on day 7 posttherapy. Both CD8+ T cell activation and T suppressor cell purge were mediated primarily by IL-12 and required IFN-gamma. This study provides important insight into how local IL-12 therapy alters the immunosuppressive tumor milieu to one that is immunologically active, ultimately resulting in tumor regression.

A single intratumoral injection of IL-12 and GM-CSF-encapsulated microspheres induces the complete regression of advanced spontaneous tumors in her-2/neu transgenic mice. However, tumor regression in this model is transient and long-term cure is not achieved due to recurrence. Posttherapy molecular analysis of immune activation/suppression markers within the tumor microenvironment demonstrated a dramatic up-regulation of IFN-gamma and a concomitant down-regulation of Forkhead/winged-helix protein 3 (Foxp3), TGFbeta, and IL-10 expression. Therapy-induced reversion of immune suppression was transient since all three markers of suppression recovered rapidly and surpassed pretherapy levels by day 7 after treatment, resulting in tumor resurgence. Repeated treatment enhanced short-term tumor regression, but did not augment long-term survival. Serial long-term analysis demonstrated that although chronic stimulation enhanced the IFN-gamma response, this was countered by a parallel increase in Foxp3, TGFbeta, and IL-10 expression. Analysis of tumor-infiltrating T lymphocyte populations showed that the expression of Foxp3 and IL-10 was associated with CD4(+)CD25(+) T cells. Repeated treatment resulted in a progressive increase in tumor-infiltrating CD4(+)CD25(+)Foxp3(+) T suppressor cells establishing their role in long-term neutralization of antitumor activity. Analysis of tumor-infiltrating CD8(+) T cells demonstrated that although treatment enhanced IFN-gamma production, antitumor cytotoxicity was diminished. Monitoring of CD8(+) T cells that specifically recognized a dominant MHC class I her-2/neu peptide showed a dramatic increase in tetramer-specific CD8(+) T cells after the first treatment; however, continuous therapy resulted in the loss of this population. These results demonstrate that both enhanced suppressor activity and deletion of tumor-specific T cells are responsible for the progressive loss of efficacy that is associated with chronic immune therapy.

A single intratumoral injection of interleukin-12 and granulocyte-macrophage colony-stimulating factor-encapsulated microspheres induced the regression of advanced spontaneous mammary tumors, suppressed additional tumor development, and enhanced survival in her-2/neu transgenic mice. Posttherapy tumor eradication was dependent on both CD4+ and CD8+ T cells and correlated with the tumor infiltration kinetics of a transient effector T-cell response. Upon long-term monitoring, tumor regression was found to be temporary, and disease-free survival was not achieved despite the development of systemic anti-tumor cytotoxic T-cell memory and antibody responses. Repeated immunization of mice enhanced short-term tumor suppression, resulting in the complete regression of primary tumors in up to 40% of the mice, but did not improve long-term survival owing to recurrence. The failure of chronic therapy to achieve complete cure was associated with an inability to maintain the intensity of the posttherapy effector T-cell response in this model.

Controlled-release, injectable polymer microspheres provide a clinically feasible alternative to gene-modification for the local, sustained delivery of cytokines to tumors for cancer immunotherapy. Long-term release kinetics, bioactivity profiles, and stability of interleukin-2 (IL-2), interleukin-12 (IL-12), and granulocyte- macrophage colony-stimulating factor (GM-CSF)-encapsulated microspheres prepared by phase inversion nanoencapsulation (PIN) were evaluated. While all formulations released physiologically relevant quantities of cytokine for up to 30 days, the individual release kinetics were different. Recovery of specific activity after encapsulation was 40%, 60%, and 90%-that of pre-encapsulation levels for IL-2, GM-CSF and IL-12, respectively. Upon storage, the IL-12 microspheres rapidly lost activity, whereas IL-2 and GM-CSF microspheres remained stable for at least 9 weeks. These studies demonstrate that biochemical properties of microsphere formulations vary depending on the cytokine, and rigorous characterization of formulations is a prerequisite to in vivo testing.