1 Croatian Kuna = 23.009 Pakistani Rupee

1 Peruvian Nuevo Sol = 46.9691 Pakistani Rupee

1 Dominican Peso = 2.9006 Pakistani Rupee

1 Papua New Guinean Kina = 46.54 Pakistani Rupee

1 Brunei Dollar = 112.9658 Pakistani Rupee

Flipkartએ લખ્યું કે, અમે ટૂંક સમયમાં પરત આવીશું, અને આપણે સાથે મળીને આ મુશ્કેલીથી બહાર આવીશું

PHPKB Multi-Language 9 suffers from an authenticated directory traversal vulnerability.

PHPKB Multi-Language 9 suffers from an image-upload.php remote authenticated code execution vulnerability.

Simple patch for OpenSSL 0.9.7c that adds a PKCS#12 brute-forcing option which takes in a wordlist.

Microsoft Windows Vista/7 suffers from a DLL hijacking vulnerability in lpksetup.exe.

PEBBLE BEACH: Gary Woodland took a two-shot lead over two-time defending champion Brooks Koepka and Justin Rose into the back nine at Pebble Beach on Sunday in the final round of the US Open Golf Championship.

U.S. President Donald Trump is reportedly demanding US$1.3 billion a year to maintain American troops in Korea. That is a whopping 53.3 percent higher than the W1.4 trillion Korea had to pay last year. A senior U.S. official told the Chosun Ilbo on Thursday, "The U.S. faces many difficulties, includ...

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.

Calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK)-mediated calcium signaling has been widely reported to function in plant development and various stress responses, particularly in ion homeostasis. Sugars are the most important primary metabolites, and thus sugar homeostasis requires precise regulation. Here, we describe a CBL2-CIPK6-Tonoplast-Localized Sugar Transporter2 (TST2) molecular module in cotton (Gossypium hirsutum) that regulates plant sugar homeostasis, in particular Glc homeostasis. GhCIPK6 is recruited to the tonoplast by GhCBL2 and interacts with the tonoplast-localized sugar transporter GhTST2. Overexpression of either GhCBL2, GhCIPK6, or GhTST2 was sufficient to promote sugar accumulation in transgenic cotton, whereas RNAi-mediated knockdown of GhCIPK6 expression or CRISPR-Cas9-mediated knockout of GhTST2 resulted in significantly decreased Glc content. Moreover, mutation of GhCBL2 or GhTST2 in GhCIPK6-overexpressing cotton reinstated sugar contents comparable to wild-type plants. Heterologous expression of GhCIPK6 in Arabidopsis (Arabidopsis thaliana) also promoted Glc accumulation, whereas mutation of AtTST1/2 in GhCIPK6-overexpressing Arabidopsis similarly reinstated wild-type sugar contents, thus indicating conservation of CBL2-CIPK6-TST2-mediated sugar homeostasis among different plant species. Our characterization of the molecular players behind plant sugar homeostasis may be exploited to improve sugar contents and abiotic stress resistance in plants.

In vitro approaches for predicting drug-drug interactions (DDIs) caused by alterations in transporter protein regulation are not well established. However, reports of transporter regulation via nuclear receptor (NR) modulation by drugs are increasing. This study examined alterations in transporter protein levels in sandwich-cultured human hepatocytes (SCHH; n = 3 donors) measured by liquid chromatography–tandem mass spectrometry–based proteomic analysis after treatment with N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide (T0901317), the first described synthetic liver X receptor agonist. T0901317 treatment (10 μM, 48 hours) decreased the levels of organic cation transporter (OCT) 1 (0.22-, 0.43-, and 0.71-fold of control) and organic anion transporter (OAT) 2 (0.38-, 0.38-, and 0.53-fold of control) and increased multidrug resistance protein (MDR) 1 (1.37-, 1.48-, and 1.59-fold of control). The induction of NR downstream gene expression supports the hypothesis that T0901317 off-target effects on farnesoid X receptor and pregnane X receptor activation are responsible for the unexpected changes in OCT1, OAT2, and MDR1. Uptake of the OCT1 substrate metformin in SCHH was decreased by T0901317 treatment. Effects of decreased OCT1 levels on metformin were simulated using a physiologically-based pharmacokinetic (PBPK) model. Simulations showed a clear decrease in metformin hepatic exposure resulting in a decreased pharmacodynamic effect. This DDI would not be predicted by the modest changes in simulated metformin plasma concentrations. Altogether, the current study demonstrated that an approach combining SCHH, proteomic analysis, and PBPK modeling is useful for revealing tissue concentration–based DDIs caused by unexpected regulation of hepatic transporters by NR modulators.

Metabolic reprogramming is critical for the polarization and function of tumor-associated macrophages (TAM) and hepatocarcinogenesis, but how this reprogramming occurs is unknown. Here, we showed that receptor-interacting protein kinase 3 (RIPK3), a central factor in necroptosis, is downregulated in hepatocellular carcinoma (HCC)–associated macrophages, which correlated with tumorigenesis and enhanced the accumulation and polarization of M2 TAMs. Mechanistically, RIPK3 deficiency in TAMs reduced reactive oxygen species and significantly inhibited caspase1-mediated cleavage of PPAR. These effects enabled PPAR activation and facilitated fatty acid metabolism, including fatty acid oxidation (FAO), and induced M2 polarization in the tumor microenvironment. RIPK3 upregulation or FAO blockade reversed the immunosuppressive activity of TAMs and dampened HCC tumorigenesis. Our findings provide molecular basis for the regulation of RIPK3-mediated, lipid metabolic reprogramming of TAMs, thus highlighting a potential strategy for targeting the immunometabolism of HCC.

Yeah, I’ll have a venti double dirty chai pumpkin spice latte to go, no foam. What do you mean you don’t have an espresso machine?...

Read our live coronavirus updates HERE Coronavirus: The symptoms

More than one million people have recovered from coronavirus worldwide, according to the latest figures from the John Hopkins University.

He invited Sylvester Stallone and Arnold Schwarzenegger to also take part.

What does our crystal ball say the new year will bring for celebs? Sex tapes, terrible singing and off-the-cuff sofa jokes that ignite the far right. Sounds great!

There are two ways to spend New Year’s Eve, as best as I can tell: you either dirty the floor of a house party and spend the smallest of the small hours running desperately out of drinkable alcohol until you realise it’s 7am and the sun is up and you just watched yourself pour Pepsi Max into half a cup of Bailey’s until they both curdled into a sort of vomitty pâté; or you watched Jools at home with a blanket over your legs, in bed with your teeth brushed by 10 past 12. You get absolutely zero points for guessing which one of the two I saw the new year in with. My body is still shaking.

Fair to say, too, that celebrities have yet to emerge blinkingly into the new decade. In the Christmas lull, the famous go into one of two modes of hibernation: either posting a succession of matching-pyjama family selfies in million-pound mansions that are identically decorated with plush beige carpets and tasteful but anonymous tonal greys; or going on holiday somewhere unthinkably lush and posting: “How’s the weather back home!” while sizzling in a hammock over aquamarine Maldivian waters. What I am saying is that there is no news, all right, and we can’t spend 1,200 words having a go at Cats again, so we simply have to preview the year 2020 and have a stab at guessing what the world of fame has for us. Is it a cop-out? Or is it actually quite a decent effort for someone who still has “brandy” in his system and who many doctors would advise shouldn’t be sitting upright at this still-early stage in his hangover? Well exactly. Let’s get on with it.

A solicitor who offered pro-bono legal advice at the Splendour in the Grass festival in 2018 tells a public hearing of a "military-style" operation, which saw shopkeepers and bar staff among those strip-searched by police.

"As members of the Hopkins community, you are heirs to an extraordinary tradition & of excellence, action, and service & that stretches back more than a hundred years before the birth of this nation," said Attorney General Holder.

Flipkart Group CFO Emily McNeal has quit to pursue a career opportunity outside the Walmart Group.

The post India: Flipkart names Sriram Venkataraman as CFO of its commerce biz appeared first on DealStreetAsia.

About Peking University International Cancer Institute (PKUICI)
Peking University International Cancer Institute(PKUICI) was formally established in 2019. With the support of School of Basic Medical Sciences, Cancer Hospital, People's Hospital, Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, School of Pharmaceutical Sciences, School of Public Health, College of Engineering and other affiliated hospitals of Peking University, PKUICI is aimed to attract and create wor…

In vitro and rodent studies suggest ophiopogonin D could help prevent doxorubicin-induced cardiotoxicity.

These delicious dessert squares skip the crust and the refined sugar. They're quick and easy to make for lightly sweet snacks during fall and winter.

Since pumpkins generally require around 75 to 100 frost-free days, it's a good idea to get a jumpstart on planting them.

There's no 'turning into a pumpkin at midnight' because the pumpkin is where it's at!

What’s the best pumpkin for pumpkin pie? Maybe not a pumpkin at all.

How would you like to carve a Jack-o-lantern from one of these three record-breaking pumpkins from this weekend?

The Transition Movement - a community-centered response to peak oil and climate change - has been described as "the biggest urban brainwave of the century." Join us to chat with its founder.

The founder of the Transition Movment is out with another book. This time, he takes a global look at how grassroots community efforts may provide a blueprint for systemic, cultural change.

The new study shows that drones can handle longer aid delivery trips than previously thought.

When rob Hopkins watched "An Inconvenient Truth", he vowed never to fly again. When he watched "Chasing Ice", he decided to get back on a plane. Here's why.

Learn how to elevate a basic DIY pumpkin pie spice blend with these simple tweaks.

This super easy recipe makes a plant-based pumpkin pudding that is rich, creamy, healthy, and delicious.

This recipe's secret ingredient leads to a rich and creamy plant-based pumpkin pie that also happens to be healthy and easy to make.

Especially when civility is in tatters, why do we feel the need to judge little things that bring others joy?

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