The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.

Pelagic gillnet (driftnet) fisheries account for some 34% of Indian Ocean tuna catches. We combined published results from 10 bycatch sampling programmes (1981−2016) in Australia, Sri Lanka, India and Pakistan to estimate bycatch rates for cetaceans across all Indian Ocean tuna gillnet fisheries. Estimated cetacean bycatch peaked at almost 100 000 ind. yr −1 during 2004−2006, but has declined by over 15% since then, despite an increase in tuna gillnet fishing effort. These fisheries caught an estimated cumulative total of 4.1 million small cetaceans between 1950 and 2018. These bycatch estimates take little or no account of cetaceans caught by gillnet but not landed, of delayed mortality or sub-lethal impacts on cetaceans (especially whales) that escape from gillnets, of mortality associated with ghost nets, of harpoon catches made from gillnetters, or of mortality from other tuna fisheries. Total cetacean mortality from Indian Ocean tuna fisheries may therefore be substantially higher than estimated here. Declining cetacean bycatch rates suggest that such levels of mortality are not sustainable. Indeed, mean small cetacean abundance may currently be 13% of pre-fishery levels. None of these estimates are precise, but they do demonstrate the likely order of magnitude of the issue. Countries with the largest current gillnet catches of tuna, and thus the ones likely to have the largest cetacean bycatch are (in order):

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The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently approved vaccines for COVID-19 are engendering hope, finding new ways to cure the viral pandemic is still a quest for researchers worldwide. Major pandemics in history have been of viral origin, such as SARS, MERS, H1NI, Spanish flu, and so on. A larger emphasis has been on discovering potential vaccines, novel antiviral drugs, and agents that can mitigate the viral infection symptoms; however, a relatively new area, RNA interference (RNAi), has proven effective as an antiviral agent. The RNAi phenomenon has been largely exploited to cure cancer, neurodegenerative diseases, and some rare diseases. The U.S. Food and Drug Administration has recently approved three siRNA products for human use that garner significant hope in siRNA therapeutics for coronaviruses. There have been some commentaries and communications addressing this area. We have summarized and illustrated the significance and the potential of the siRNA therapeutics available as of April 30, 2021 to combat the ongoing viral pandemic and the emerging new variants such as B.1.1.7 and B.1.351. Numerous successful in vitro studies and several investigations to address the clinical application of siRNA therapeutics provide great hope in this field. This seminal Review describes the significance of siRNA-based therapy to treat diverse viral infections in addition to the current coronavirus challenge. In addition, we have thoroughly reviewed the patents approved for coronaviruses, the major challenges in siRNA therapy, and the potential approaches to address them, followed by innovation and prospects.

Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0-143.5) months, significantly longer compared to 93.7 (95% CI, 60.3-127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer. (Cancer Sci 2010; 101: 2137-2144 B reast cancer is the most common cancer in women in the UK and USA.(1,2) The life-threatening complications in breast cancer patients are metastases. The leading metastatic site of this disease is bone, dominantly osteolytic lesions, which result in severe bone pain, fracture, spinal cord compression, and hypercalcemia. It is critical to understand the reason for the predisposition of breast cancer to metastasize to bone, which may provide novel approaches to prevent and treat the diseasespecific bone lesions. In the past decade, a group of proteins which play pivotal roles in regulating formation of bone and cartilage, namely bone morphogenetic proteins (BMPs), have been investigated intensively in cancer due to their potential link to malignant bone lesions.BMPs are members of the transforming growth factor-b (TGF-b) superfamily. To date, more than 20 BMPs have been identified in humans. BMPs play critical roles in fetal and postnatal development, and also the homeostasis of various tissues and organs. BMPs have been indicated in development and progression of several malignancies, including breast cancer, prostate cancer, lung cancer, colorectal cancer, melanoma, osteosarcoma, etc. Aberrations in BMPs expression have been indicated in breast cancer. Decreased expression of...

1. Bycatch is the most significant threat to marine megafauna (sea turtles, marine mammals, elasmobranchs, seabirds) worldwide, and the leading cause of the decline of several cetacean species. The bycatch issue in the Indian Ocean is poorly understood, but high bycatch levels in gillnet fisheries have been documented for the past two decades, in both small-scale and semi-industrial fisheries. Unfortunately, methods to reduce bycatch are often unavailable, financially non-viable or socially unacceptable to fishermen. Using a network of trained boat captains in the tuna drift gillnet fishery in theArabian Sea, targeted catch and bycatch data were collected from 2013 to 2017 off the coast of Pakistan (northern Indian Ocean). Two fishing methods using multifilament gillnets were used: surface deployment and subsurface deployment (i.e. headline of net set below 2 m depth).3. Predicted catch rates for targeted species did not differ significantly between the two fishing practices, although a drop in tuna (6.2%) and tuna-like (10.9%) species captures was recorded in subsurface sets. The probability of cetacean bycatch, however, was 78.5% lower in subsurface than in surface sets. 4. Cetacean bycatch in tuna drift gillnet fisheries has the potential to be significantly reduced at a relatively low cost for fishers. However, further research with an appropriate sampling design and a large sample size is required to confirm the efficacy of the proposed mitigation method. The acceptability and adoption of subsurface setting by fishers also needs to be further investigated. Despite some limitations, this preliminary study also highlights the importance of crew-based observer data as an alternative source of data when observers cannot be deployed on fishing vessels.