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There is growing consensus among the social scientist that for the development of rural economy, rural non-farm sector should be thriving. The present study is an attempt to study the factors enabling the rural households of Punjab to participate in the rural non-farm activities. In the present study, the household level data of National Sample Survey Organization’s employment-unemployment 50th round and 68th round is utilized. The rural households of Punjab are categorized into; self-employed, casual labourer, regular or salary earners and others in farm as well as non-farm sector. The logit regression model for both the rounds are utilised to study the factors impacting the participation as self-employed, casual labourers, and regular wage earners in rural non-farm sector. As compared to the year 1993-94, in the year 2011-12, the proportion of households earning their livelihood in rural non-farm sector has increased. Moreover, the proportion of casual labourer in rural non-farm sector has also increased. The choice of occupations among the self-employed, regular salary earners and causal labourer in the rural non-farm sector is also changing in Punjab. The factors like education, number of skilled members in the households, head’s education, household belonging to developed districts significantly impacted the choice of working in rural non-farm sector of Punjab. The study recommends that with increase in investment in education and developing the infrastructure in rural areas can develop the rural non-farm sector.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in food, cosmetics, and biomedical research. However, human safety following exposure to TiO2 NPs remains to be fully understood. The aim of this study was to evaluate the in vitro safety and toxicity of TiO2 NPs synthesized via the Stöber method under different washing and temperature conditions. TiO2 NPs were characterized by their size, shape, surface charge, surface area, crystalline pattern, and band gap. Biological studies were conducted on phagocytic (RAW 264.7) and non-phagocytic (HEK-239) cells. Results showed that washing amorphous as-prepared TiO2 NPs (T1) with ethanol while applying heat at 550 °C (T2) resulted in a reduction in the surface area and charge compared to washing with water (T3) or a higher temperature (800 °C) (T4) and influenced the formation of crystalline structures with the anatase phase in T2 and T3 and rutile/anatase mixture in T4. Biological and toxicological responses varied among TiO2 NPs. T1 was associated with significant cellular internalization and toxicity in both cell types compared to other TiO2 NPs. Furthermore, the formation of the crystalline structure induced toxicity independent of other physicochemical properties. Compared with anatase, the rutile phase (T4) reduced cellular internalization and toxicity. However, comparable levels of reactive oxygen species were generated following exposure to the different types of TiO2, indicating that toxicity is partially driven via non-oxidative pathways. TiO2 NPs were able to trigger an inflammatory response, with varying trends among the two tested cell types. Together, the findings emphasize the importance of standardizing engineered nanomaterial synthesis conditions and evaluating the associated biological and toxicological consequences arising from changes in synthesis conditions.

Although silica nanoparticles (SNPs) are generally thought to be biocompatible and safe, the adverse effects of SNPs were also reported in previous studies. SNPs cause follicular atresia via the induction of ovarian granulosa cell apoptosis. However, the mechanisms for this phenomenon are not well understood. This study focuses on exploring the relationship between autophagy and apoptosis induced by SNPs in ovarian granulosa cells. Our results showed that 25.0 mg/kg body weight (b.w.)/intratracheal instillation of 110 nm in diameter spherical Stöber SNPs caused ovarian granulosa cell apoptosis in follicles in vivo. We also found that SNPs mainly internalized into the lumens of the lysosomes in primary cultured ovarian granulosa cells in vitro. SNPs induced cytotoxicity via a decrease in viability and an increase in apoptosis in a dose-dependent manner. SNPs increased BECLIN-1 and LC3-II levels, leading to the activation of autophagy and increased P62 level, resulting in the blockage of autophagic flux. SNPs increased the BAX/BCL-2 ratio and cleaved the caspase-3 level, resulting in the activation of the mitochondrial-mediated caspase-dependent apoptotic signaling pathway. SNPs enlarged the LysoTracker Red-positive compartments, decreased the CTSD level, and increased the acidity of lysosomes, leading to lysosomal impairment. Our results reveal that SNPs cause autophagy dysfunction via lysosomal impairment, resulting in follicular atresia via the enhancement of apoptosis in ovarian granulosa cells.

Ambient particulate matters (PMs) have adverse effects in human and animal female reproductive health. Silica nanoparticles (SNPs), as a major component of PMs, can induce follicular atresia via the promotion of ovarian granulosa cell apoptosis. However, the molecular mechanisms of apoptosis induced by SNPs are not very clear. This work focuses on revealing the mechanisms of ER stress on SNP-induced apoptosis. Our results showed that spherical Stöber SNPs (110 nm, 25.0 mg/kg b.w.) induced follicular atresia via the promotion of granulosa cell apoptosis by intratracheal instillation in vivo; meanwhile, SNPs decreased the viability and increase apoptosis in granulosa cells in vitro. SNPs were taken up and accumulated in the vesicles of granulosa cells. Additionally, our results found that SNPs increased calcium ion (Ca

BACKGROUND Altered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory-induced vascular-mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug-delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues. METHODS Patients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non-CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy. RESULTS Sinonasal vascularity was increased significantly in CRSsNP and CRSwNP (p < 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM-1)-positive blood vessels. Pro-angiogenic gene expression, including PECAM1 and platelet-activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (p < 0.05). The fenestration sizes between endothelial cells (17-280 nm) were larger in CRSwNP compared with CRSsNP (10-33 nm) patients and controls (4-12 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls. CONCLUSION Significant increases in vascularity, the pro-angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation-driven vascular dysregulation in CRS pathology.

Background Chronic inflammation is known to cause alterations in vascular homeostasis that directly affects blood vessel morphogenesis, angiogenesis, and tissue permeability. These phenomena have been investigated and exploited for targeted drug delivery applications in the context of cancers and other disease processes. Vascular pathophysiology and its associated genes and signaling pathways, however, have not been systematically investigated in patients with chronic rhinosinusitis (CRS). Understanding the interplay between key vascular signaling pathways and top biomarkers associated with CRS may facilitate the development of new targeted delivery strategies and treatment paradigms. Herein, we report findings from a gene meta-analysis to identify key vascular pathways and top genes involved in CRS. Methods Proprietary software (Illumina BaseSpace Correlation Engine) and open-access data sets were used to perform a gene meta-analysis to systematically determine significant differences between key vascular biomarkers and vascular signaling pathways expressed in sinonasal tissue biopsies of controls and patients with CRS. Results Thirteen studies were initially identified, and then reduced to five after applying exclusion principle algorithms. Genes associated with vasculature development and blood vessel morphogenesis signaling pathways were identified to be overexpressed among the top 15 signaling pathways. Out of many significantly upregulated genes, the levels of pro angiogenic genes such as early growth response (EGR3), platelet endothelial cell adhesion molecule (PECAM1) and L-selectin (SELL) were particularly significant in patients with CRS compared to controls. Discussion Key vascular biomarkers and signaling pathways were significantly overexpressed in patients with CRS compared to controls, suggesting a contribution of vascular dysfunction in CRS pathophysiology. Vascular dysregulation and permeability may afford opportunities to develop drug delivery systems to improve efficacy and reduce toxicity of CRS treatment.

Silica nanoparticles (SNPs) can cause abnormal spermatogenesis in male reproductive toxicity. However, the toxicity and toxicological mechanisms of SNPs in testosterone synthesis and secretion in Leydig cells are not well known. Therefore, this study aimed to determine the effect and molecular mechanism of low doses of SNPs in testosterone production in Leydig cells. For this, mouse primary Leydig cells (PLCs) were exposed to 100 nm Stöber nonporous spherical SNPs. We observed significant accumulation of SNPs in the cytoplasm of PLCs via transmission electron microscopy (TEM). CCK-8 and flow cytometry assays confirmed that low doses (50 and 100 μg/mL) of SNPs had no significant effect on cell viability and apoptosis, whereas high doses (more than 200 μg/mL) decreased cell viability and increased cell apoptosis in PLCs. Monodansylcadaverine (MDC) staining showed that SNPs caused the significant accumulation of autophagosomes in the cytoplasm of PLCs. SNPs activated autophagy by upregulating microtubule-associated protein light chain 3 (LC3-II) and BCL-2-interacting protein (BECLIN-1) levels, in addition to downregulating sequestosome 1 (SQSTM1/P62) level at low doses. In addition, low doses of SNPs enhanced testosterone secretion and increased steroidogenic acute regulatory protein (StAR) expression. SNPs combined with rapamycin (RAP), an autophagy activator, enhanced testosterone production and increased StAR expression, whereas SNPs combined with 3-methyladenine (3-MA) and chloroquine (CQ), autophagy inhibitors, had an opposite effect. Furthermore, BECLIN-1 depletion inhibited testosterone production and StAR expression. Altogether, our results demonstrate that low doses of SNPs enhanced testosterone secretion via the activation of autophagy in PLCs.

Chronic rhinosinusitis (CRS) is a debilitating inflammatory disorder of the sinonasal mucosa that substantially diminishes patient quality of life. Progress surrounding management of this disease has been crippled by a lack of therapeutic innovation. It has been posited that increased vascularity within the diseased sinuses of patients with CRS may allow for improved systemic drug delivery via nanoscale liposomal carriers. Such a system could enhance drug distribution, accumulation, and retention within the sinuses, ultimately leading to improved patient outcomes. PEGylated liposomes loaded with indocyanine green (ICG) were synthesized, characterized and systemically administered in a mouse model of CRS. Accumulation and retention of ICG in sinonasal tissue were evaluated. Compared to healthy controls, CRS mice showed significant sinonasal tissue accumulation and retention of PEGylated liposomal ICG for up to 21 days (P 0.001). Conversely, free ICG was eliminated from the body after 24 h in both groups.

Rationale: Intraoperative bleeding impairs physicians' ability to visualize the surgical field, leading to increased risk of surgical complications and reduced outcomes. Bleeding is particularly challenging during endoscopic-assisted surgical resection of hypervascular tumors in the head and neck. A tool that controls bleeding while marking tumor margins has the potential to improve gross tumor resection, reduce surgical morbidity, decrease blood loss, shorten procedure time, prevent damage to surrounding tissues, and limit postoperative pain. Herein, we develop and characterize a new system that combines pre-surgical embolization with improved visualization for endoscopic fluorescence image-guided tumor resection. Methods: Silk-elastinlike protein (SELP) polymers were employed as liquid embolic vehicles for delivery of a clinically used near-infrared dye, indocyanine green (ICG). The biophysical properties of SELP, including gelation kinetics, modulus of elasticity, and viscosity, in response to ICG incorporation using rheology, were characterized. ICG release from embolic SELP was modeled in tissue phantoms and via fluorescence imaging. The embolic capability of the SELP-ICG system was then tested in a microfluidic model of tumor vasculature. Lastly, the cytotoxicity of the SELP-ICG system in L-929 fibroblasts and human umbilical vein endothelial cells (HUVEC) was assessed. Results: ICG incorporation into SELP accelerated gelation and increased its modulus of elasticity. The SELP embolic system released 83 ± 8% of the total ICG within 24 hours, matching clinical practice for pre-surgical embolization procedures. Adding ICG to SELP did not reduce injectability, but did improve the gelation kinetics. After simulated embolization, ICG released from SELP in tissue phantoms diffused a sufficient distance to deliver dye throughout a tumor. ICG-loaded SELP was injectable through a clinical 2.3 Fr microcatheter and demonstrated deep penetration into 50-µm microfluidic-simulated blood vessels with durable occlusion. Incorporation of ICG into SELP improved biocompatibility with HUVECs, but had no effect on L-929 cell viability. Principle Conclusions: We report the development and characterization of a new, dual-functional embolization-visualization system for improving fluorescence-imaged endoscopic surgical resection of hypervascular tumors.