Systematic Photophysical Interaction Studies Between Newly Synthesised Oxazole Derivatives and Silver Nanoparticles: Experimental and DFT Approach.

In this study, the photophysical properties of oxazole derivatives such as 5-(furan-2-yl) -4-tosyloxazole (OX-1) and 5-(2-bromothiazol-4-yl)-4-tosyloxazoles (OX-2) were investigated using theoretical and experimental techniques. The ground and excited state dipole moments were empirically obtained utilising the solvatochromic shift technique and several solvatochromic correlations such as Lippert's, Bakhshiev's, KawskiChamma- Viallet's, and solvent polarity equations. The ground state dipole moments, HOMO-LUMO and molecule electrostatic potential map were also computed using ab initio calculations and evaluated using Gaussian 09 W software. Furthermore, spectroscopic interactions between newly synthesised dyes (OX-1 and OX-2) and freshly synthesised silver nanoparticles (size 40 nm) were studied. Increased absorbance and widening of absorption spectra for both dyes in the presence of varied quantities of silver nanoparticles show the potential of dye-nanoparticle interactions. Fluorescence quenching has been detected for both dyes in the presence of colloidal silver nanoparticles, indicating dynamic quenching, and a significant overlap between the absorption and emission spectra of the silver nanoparticle reveals that fluorescence quenching is also due to energy transfer.

Imaging of brain metastasis in non-small-cell lung cancer: indications, protocols, diagnosis, post-therapy imaging, and implications regarding management.

Increased survival (due to the use of targeted therapies based on genomic profiling) has resulted in the increased incidence of brain metastasis during the course of disease, and thus, made it essential to have proper imaging guidelines in place for brain metastasis from non-small-cell lung cancer (NSCLC). Brain parenchymal metastases can have varied imaging appearances, and it is pertinent to be aware of the various molecular risk factors for brain metastasis from NSCLC along with their suggestive imaging appearances, so as to identify them early. Leptomeningeal metastasis requires additional imaging of the spine and an early cerebrospinal fluid (CSF) analysis. Differentiation of post-therapy change from recurrence on imaging has a bearing on the management, hence the need for its awareness. This article will provide in-depth literature review of the epidemiology, aetiopathogenesis, screening, detection, diagnosis, post-therapy imaging, and implications regarding the management of brain metastasis from NSCLC. In addition, we will also briefly highlight the role of artificial intelligence (AI) in brain metastasis screening.

A split influenza vaccine formulated with a combination adjuvant composed of alpha-D-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs.

BACKGROUND: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. RESULTS: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ+ effector memory T-helper/memory cells, IL-17A+ total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A+ total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A+ T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ+ late effector CTLs and effector memory T-helper/memory cells, IL-17A+ total CTLs, late effector CTLs, and CXCL10+ myeloid cells in blood, as well as lung CXCL10+ plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs. CONCLUSIONS: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Estimation of height and width of bone in anterior hard palate as a donor site for autogenous bone graft using IOPA by long cone paralleling technique.

OBJECTIVE: The purpose of this study was to determine the amount of bone available for harvesting from the anterior palate region using IOPA (Intra Oral Peri Apical) radiographs. MATERIALS AND METHODS: A total of 80 patients visiting the outpatient Department of Periodontics were selected. Two groups of male and female consisting 40 patients each were made. They were further subdivided into two groups based on age, 18-30 and 31-60 years of age, each with twenty patients. The patients were subjected to radiographic examination consisting of IOPA radiographs. All IOPA radiographs were taken using long cone paralleling technique. Availability of bone for harvesting, above the apices of teeth was calculated. RESULTS: The bone available in the incisor region was approximately 6.5 to 6.9 mm in height and 7.4 to 8 mm in width, in canine region 6.35 to 6.65 mm in height and 7.6 to 8.1 mm width, and in the premolar region 3.65 to 3.75 mm in height and width. When the bone height and width were compared gender and age wise for CI (central incisors), LI (lateral incisors), canine and premolars, using Student's t- test the results were not statistically significant. CONCLUSION: For the purpose of harvesting autogenous bone, from the region of incisor and canine approximately 6.35 to 6.9 mm height and 7.4 to 8.1 mm width of bone may be harvested maintaining a safe distance from the apices of the teeth and the nasal floor. The premolar region does appear to yield sufficient bone at safe distances from the maxillary sinus and the apices of the premolars.

Mimicking the Synaptic Weights and Human Forgetting Curve Using Hydrothermally Grown Nanostructured CuO Memristor Device.

In the present investigation, we have fabricated copper oxide (CuO) thin film memristor by employing a hydrothermal method for neuromorphic application. The X-ray diffraction pattern confirms the films are polycrystalline in nature with the monoclinic crystal structure. The developed devices show analog memory and synaptic property similar to biological neuron. The size dependent synaptic behavior is investigated for as-prepared and annealed CuO memristor. The results suggested that the magnitude of synaptic weights and resistive switching voltages are dependent on the thickness of the active layer. Synaptic weights are improved in the case of the as-prepared device whereas they are inferior for annealed CuO memristor. The rectifying property similar to a biological neuron is observed only for the as-prepared device, which suggested that as-prepared devices have better computational and learning capabilities than annealed CuO memristor. Moreover, the retention loss of the CuO memristor is in good agreement with the forgetting curve of human memory. The results suggested that hydrothermally grown CuO thin film memristor is a potential candidate for the neuromorphic device development.

Drug-sensitive FGFR3 mutations in lung adenocarcinoma.

Background: Lung cancer is the leading cause of cancer-related deaths across the world. In this study, we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. Materials and methods: Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500 × (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing mutant and wild-type FGFR3 constructs were characterized for anchorage independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models. Results: We present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and shows that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend toward better overall survival, compared with patients lacking actionable alterations or those harboring KRAS mutations. Conclusion: We present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma.

Identification of motility-associated progesterone-responsive differentially phosphorylated proteins.

Progesterone is one of the regulators of sperm motility and hyperactivation. In human spermatozoa, the effects of progesterone are thought to be mediated by protein phosphorylation. In the present study, we identified 22 proteins that are differentially phosphorylated (12 phosphorylated and 10 dephosphorylated) by progesterone in human spermatozoa. Functionally, the differentially phosphorylated proteins are predicted to have cytoskeletal localisation and to be associated with sperm motility. 5µM of progesterone to capacitated increased the phosphorylation of tyrosine residues in the principal piece and protein tyrosine kinase activity increased by almost 3.5-fold. For the first time, we demonstrate that tyrosine phosphatases are also activated in response to progesterone and that inhibition of tyrosine phosphatases attenuates dephosphorylation of flagellar proteins. We propose that progesterone activates both kinase and phosphatase pathways, leading to changes in the phosphorylation of many proteins in sperm flagella to increase motility.

Association of season of birth with DNA methylation and allergic disease.

BACKGROUND: Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. METHODS: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns. RESULTS: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally. CONCLUSIONS: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.

Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood: findings from 2 Isle of Wight birth cohorts 12 years apart.

BACKGROUND: While the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence. OBJECTIVE: To assess time trends of wheeze, rhinitis and aero-allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort. METHODS: The IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age. RESULTS: Over the 12-year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated for asthma decreased by 15.9% (45.5 vs. 29.6, P < 0.001), 3.9% (18.9 vs. 15, P = 0.020) and 8.2% (31.7 vs. 23.5, P = 0.001), respectively. Conversely, current rhinitis and lifetime rhinitis prevalence increased by 5.5% (22.6 vs. 28.1, P = 0.004) and 13% (18.6 vs. 31.7, P < 0.001), respectively. Atopic status remained stable; however, house dust mite (HDM) sensitisation decreased by 5.6% (19.2 vs. 13.6, P = 0.004) and grass sensitisation increased by 3.5% (12.9 vs. 16.4, P = 0.054). Male sex, parental history of asthma and HDM sensitisation were significantly associated with lifetime wheeze in both cohorts, while maternal smoking during pregnancy was a significant risk factor only in the earlier IoW cohort. Parental history of rhinitis and grass sensitisation was significantly associated with lifetime rhinitis in both cohorts, while HDM sensitisation was significant only for the IoW cohort. CONCLUSION: Contrasting changes were noted with falling wheeze and HDM sensitisation but rising rhinitis and grass sensitisation prevalence. Changing prevalence of aero-allergen sensitisations may explain the different time trends observed in these cohorts.

The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort.

BACKGROUND: Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised. OBJECTIVES: To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort. METHODS: K-means cluster analysis was undertaken among 309 currently wheezing subjects at 18 years in the Isle of Wight birth cohort (N = 1456). Thirteen disease-characterising clustering variables at 18 years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18 years of life. RESULTS: Six wheeze clusters were identified. Cluster 1 (12.3%) male-early-childhood-onset-atopic-wheeze-with-normal-lung-function had male predominance, normal spirometry, low bronchodilator reversibility (BDR), intermediate bronchial hyper-responsiveness (BHR), high atopy prevalence and more admissions. Cluster 2 (24.2%) early-childhood-onset-wheeze-with-intermediate-lung-function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female-early-childhood-onset-atopic-wheeze-with-impaired-lung-function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent-onset non-atopic wheeze, low BDR and BHR, impaired but non-obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female-late-childhood-onset-wheeze-with-normal-lung-function showed no specific atopy association, normal spirometry, low BDR, BHR and symptom severity. Cluster 6 (9.7%) male-late-childhood-onset-atopic-wheeze-with-impaired-lung-function had high atopy and rhinitis prevalence, increased BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy. CONCLUSIONS AND CLINICAL RELEVANCE: Young adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking-associated undiagnosed wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health.

Characterization of a novel functional porcine CD3+CD4lowCD8α+CD8ß+ T-helper/memory lymphocyte subset in the respiratory tract lymphoid tissues of swine influenza A virus vaccinated pigs.

The pig is emerging as a physiologically relevant biomedical large animal model. Delineating the functional roles of porcine adaptive T-lymphocyte subsets in health and disease is of critical significance, which facilitates mechanistic understanding of antigen-specific immune memory responses. We identified a novel T-helper/memory lymphocyte subset in pigs and performed phenotypic and functional characterization of these cells under steady state and following vaccination and infection with swine influenza A virus (SwIAV). A novel subset of CD3+CD4lowCD8α+CD8ß+ memory T-helper cells was identified in the blood of healthy adult pigs under homeostatic conditions. To understand the possible functional role/s of these cells, we characterized the antigen-specific T cell memory responses by multi-color flow cytometry in pigs vaccinated with a whole inactivated SwIAV vaccine, formulated with a phytoglycogen nanoparticle/STING agonist (ADU-S100) adjuvant (NanoS100-SwIAV). As a control, a commercial SwIAV vaccine was included in a heterologous challenge infection trial. The frequencies of antigen-specific IL-17A and IFNγ secreting CD3+CD4lowCD8α+CD8ß+ memory T-helper cells were significantly increased in the lung draining tracheobronchial lymph nodes (TBLN) of intradermal, intramuscular and intranasal inoculated NanoS100-SwIAV vaccine and commercial vaccine administered animals. While the frequencies of antigen-specific, IFNγ secreting CD3+CD4lowCD8α+CD8ß+ memory T-helper cells were significantly enhanced in the blood of intranasal and intramuscular vaccinates. These observations suggest that the CD3+CD4lowCD8α+CD8ß+ T-helper/memory cells in pigs may have a protective and/or regulatory role/s in immune responses against SwIAV infection. These observations highlight the heterogeneity and plasticity of porcine CD4+ T-helper/memory cells in response to respiratory viral infection in pigs. Comprehensive systems immunology studies are needed to further decipher the cellular lineages and functional role/s of this porcine T helper/memory cell subset.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India.

AIMS: Sinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. METHODS: This was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. RESULTS: The data of 27 patients were evaluated from the year 2015-2022. The median age was 42 years (IQR:30-56) and 85.2% (n = 23) were males. The ECOG-PS was 0-1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2-3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0-25.6) and 23months (95%CI:5.94-40.06) respectively. CONCLUSION: NACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.

Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Field application of Ca-doped ZnO nanoparticles to maize and wheat plants.

Nanoparticles play a vital role in modern agriculture to provide the nutrients required by plants. Herein, we report the preparation of calcium-doped zinc oxide nanoparticles (CZO NPs) via a simple and cost-effective co-precipitation method, with the aim of realizing increased fertilizer response. The synthesized nanoparticles were analyzed to study their physicochemical properties using various characterization techniques. The X-ray diffraction pattern showed a small shift in peak position towards higher values of 2θ and reduced crystal size after the zinc oxide (ZnO) matrix had been doped with Ca. Field-emission scanning electron microscopy images clearly revealed a grain-like surface morphology. The X-ray photoelectron spectroscopy study produced evidence of Zn2+ substitution by Ca2+ and enhanced Zn-O bond strengths in the CZO samples. Two major crops, maize (Zea mays L.) and wheat (Triticum aestivum L.) were selected to study the impact of the CZO NP-based nanofertilizer on plant growth. During the study, the effect of the CZO-based fertilizer on growth parameters such as seed germination, root and shoot length, plant height, root and stem width, number of leaves, and leaf size was studied based on comparisons with control plants. We observed significantly increased plant growth parameters after the application of the CZO NP-based fertilizers.

Winter weather versus group thermoregulation: what determines survival in hibernating mammals?

For socially hibernating mammals, the effectiveness of huddling as a means of energy conservation should increase with group size. However, group size has only been linked to increased survival in a few hibernating species, and the relative importance of social structure versus winter conditions during hibernation remains uncertain. We studied the influence of winter weather conditions, social group composition, age-structure, and other environmental factors and individual attributes on the overwinter survival of hoary marmots (Marmota caligata) in the Yukon Territory, Canada. Juvenile hoary marmot survival was negatively correlated with the mean winter (November to May) Pacific Decadal Oscillation (PDO) index. Survival in older age-classes was negatively correlated with PDO lagged by 1 year. Social group size and structure were weakly correlated with survival in comparison to PDO. The relationship between winter PDO and survival was most likely due to the importance of snowpack as insulation during hibernation. The apparent response of hoary marmots to changing winter conditions contrasted sharply with those of other marmot species and other mammalian alpine herbivores. In conclusion, the severity of winter weather may constrain the effectiveness of group thermoregulation in socially hibernating mammals.

Progesterone activates Janus Kinase 1/2 and activators of transcription 1 (JAK1-2/STAT1) pathway in human spermatozoa.

Ejaculated spermatozoa undergo capacitation and acrosome reaction by responding to extrinsic clues and activate signalling cascades to induce protein tyrosine phosphorylation. In the present study, we investigated the existence, the Janus kinase (JAK) and activator of transcription (STAT) pathway and determined its physiological relevance. JAK1 and STAT1 are localised on the equatorial region and the midpiece of their human spermatozoa, JAK2 is detected on the sperm tail. Capacitation leads to phosphorylation of JAK2 but not JAK1 and STAT1. In the uncapacitated sperm, phosphorylated JAK2 (pJAK2) is localised mainly in the tail region; in response to capacitation, the JAK2 is phosphorylated in the midpiece and the head region along with the tail. Progesterone (5 µm) leads to phosphorylation of JAK1, JAK2 and STAT1 in a time-dependent manner. In progesterone-treated spermatozoa, the JAK2 in the tail is hyperphosphorylated, the JAK2 in the head and the midpiece is dephosphorylated. We conclude that in human spermatozoa, the JAK1/2 pathway is activated upon capacitation and is further modulated by progesterone; the biological processes controlled by this pathway in sperm need to be elucidated.