溫馨一刻
留住孩子們成長的快樂時光。
窮在鄉下有遠親
聽說我家的桃子熟了，城裏的朋友周末抽空來品嚐采摘。怕我們破費，拉我們一家出門吃午飯。看著日日上升的疫情，不敢。朋友說他們會外賣帶過來。。。
給領導說，他們太客氣了。我們就按自己的方式待客吧：今天要去農貿市場買做酸豆角的原料，就給他們準備點帶回家的土特產。誰想小菜攤的綠色豇豆（試下來，綠色的豇豆比紫色的好）還不夠我上周預定的30斤呢。拿了十五斤，加兩把紫色的新鮮吃。
我自己做酸豆角用的：
讓朋友帶回家的：
自家的黃瓜不錯，一根藤上就有三條可摘，城裏人就喜歡新鮮的，留著他們自己摘：
新鮮玉米不錯，來一打：
來個walleye魚湯。頭尾釣回來的當天就被我和領導做了湯，剩下的就是肉了：
梯子準備好，桃子在樹上：
白桃（今年真不錯，摘了兩個禮拜了，還有這麽多。估計一顆樹今年不少於200斤的產量）：
蟠桃（還沒完全熟，可看到成群結隊的Japanese beetles，不敢等了）：
禮拜一給女兒寄點蟠桃過去。和她娘一樣的City girl，也喜歡農家新鮮蔬果。。。
（二0二一年七月十七日）
回答網友有關我家桃子的問題
我家桃樹種了三四年了。網上買來的。白桃不是一般店裏賣的4401的白桃。我家的小一些，酸一些。4401更象水蜜桃。蟠桃是一起買來的，也是白桃（有黃蟠桃的）。蟠桃熟了比較甜，沒有酸味，好吃一些。可惜蟲害太厲害，日本甲殼蟲等好幾種上來了，周末摘的時候還沒完全熟。家裏放幾天應該就好了。另外，我喜歡吃硬桃，領導喜歡軟的。
除了蟲害，就是黴菌。以往顆粒無收，就是黴菌，長著長著就蔫了，尤其蟠桃厲害。桃子開花後容易趕上冰凍和冰雹，所以，前幾年都是看花，沒吃到過。去年開始學習對付黴菌，用波爾多液，買來的，今年趕上好年成，加黴菌控製得不錯（沒有卷葉）。波爾多液一年處理兩次----葉長出來之前或葉落之後，噴樹幹樹枝。所以，樹不能長太高，我去年修理了一下，但往高處長的趨勢很難控製。。。這是我家領導買回來的波爾多液（fungicide）：
果樹是領導的功勞。我小時候水蜜桃吃得多，喜歡甜的桃子，這種酸甜的白桃一般，但有朋友喜歡。蟠桃正合我的胃口。
下一個目標是棗樹。據酒友說是棗七年。買回來兩顆，凍死了又發芽，去年開始離主樹一米遠，從根上發芽。我怕和去年一樣割草時把它們割了，就圍了兩顆。今天發現今年發出來的一顆居然小苗上開花結果了，才一尺高呢，主樹上有花，還沒見到果。但葉子也卷起來，我懷疑也有黴菌，需要處理。今秋明春和桃樹一起處理吧。
種果樹，最麻煩的事爛水果，引蒼蠅。需要勤快，經常埋。
（二0二一年七月十八日）
爹媽的愛哪能用錢來度量呢
周末邀請城裏的朋友來摘桃，來我家過一個農家樂周末。沒想到已經摘了兩個禮拜的白桃樹上還有那麽多；還沒完全熟的蟠桃樹大約是桃子比較甜，更吸引蟲害，每天五個十個地掉下來，剩下的不足早春的十分之一了。看著成群結隊的Japanese beetles於是也決定一起摘了。過磅一下，大約有60多斤白桃，30多斤蟠桃呢。
朋友帶走一些，分給城裏沒來的朋友，剩下幾十斤，左右鄰居同城的朋友分點, 辦公室的同事也分享一些。。當然，最重要的是遠在波士頓快兩年沒見麵的女兒了。老媽說第一次收這麽多，得給女兒寄點過去，不能隻給她看照片解饞。桃子容易爛，隻能走快遞服務，包裝好30個沒完全熟的蟠桃，加上六個差不多熟了的白桃。一個包裝6磅，今早就drop到郵局，70塊，比超市貴多了呢。連郵局工作人員都說priceless peaches！ I will do whatever I can to make sure it get there on time。。。
老媽感歎說：當年她們小的時候，吃頓麥當勞都得想想，五塊錢是我一個小時的工資啊。。。
後記
第二天下午三點女兒來短信說：好貴哦，不過蠻好吃的。。。
不錯不錯，今天大豐收，桃子到了芝加哥，DC，還有波士頓。。。等我退休了，多釣點魚，油炸好了就可以寄更多地方了。。。
（二0二一年七月十九日）
窮人家煮“豬食”
昨天酒友從DC回來了。樹上還有一些給他留著的桃子，就讓他全摘了，不然就讓日本甲殼蟲全報銷了。正好周末他要去看外地的兒女，就捎帶上鄰居叔叔阿姨的祝福。不想一摘又是30斤，還有十幾斤爛的。窮人家吃不完的桃子舍不得扔，和領導連夜猛削清理出一大鍋好的部分，然後就煮一鍋豬食。煮的時候加點糖，第二天早上涼了，再打成果醬。吃不完可以凍起來，4度冰箱放點隨時喝。估計夠兩老吃兩三個禮拜了。。。
（二0二一年七月二十一日）
再拿一個grant, 我又可以玩五年？
學校和Science Translational Medicine的news release昨天出來了，老板今天一進辦公室，就來找我說：電話裏一大堆病人留言呢。。。
這是昨天的News Release中一個：
Bayer's drug that turns a cancer-protective pathway toxic eradicates breast tumors in mice
Bayer's drug that turns a cancer-protective pathway toxic eradicates breast tumors in mice
by Angus Liu | Jul 21, 2021 2:00pm
Bayer's ErSO, recently licensed from Systems Oncology, eradicated tumors in mouse models of ER-positive breast cancers and reduced metastasis. (Bayer)
An investigational breast cancer drug Bayer recently licensed from Systems Oncology has shown strong antitumor responses in mice, offering early clues as to why the German pharma shelled out $25 million for the preclinical asset last September.
The drug, dubbed ErSO, works by over-activating a normally tumor-protective pathway to make it toxic for cancer cells. It eradicated both primary and metastatic tumors in mouse models of estrogen receptor-positive breast cancers, according to results published in Science Translational Medicine.
The pathway ErSO targets is called the anticipatory Unfolded Protein Response (aUPR). Through mild and transient activation, aUPR prepares ER-positive cancer cells for growth and protects them from stress such as anticancer treatment.
But in a PNAS study in 2015, a research team from the University of Illinois at Urbana-Champaign led by biochemistry professor David Shapiro, Ph.D., showed that massive and sustained activation of aUPR with a drug could instead inhibit protein synthesis, depriving ER-positive breast cancer cells key building blocks necessary for survival.
For the new research, Shapiro and colleagues identified ErSO as a more potent aUPR hyper-activator that could selectively kill ER-positive breast cancer cells.
In multiple mouse models of ER-positive breast cancer, ErSO quickly killed off tumor cells in high numbers just days after treatment. Combined data from four mouse models showed that 38 of 39 tumors regressed by over 95%, with about half of cases reduced to undetectable levels, the team reported. Even tumors that didn’t completely disappear and regrew after stopping treatment still remained fully sensitive to another cycle of ErSO, the team found.
In another mouse model bearing mutant, patient-derived breast tumors with low expression of ER, oral ErSO treatment outperformed standard-of-care therapies tamoxifen and AstraZeneca’s Faslodex (fulvestrant) at blocking tumor growth, the team found.
“Many of these breast cancers shrink by more than 99% in just three days,” Shapiro said in a statement. “ErSO is fast-acting and its effects on breast cancers in mice are large and dramatic.”
What’s more, the Bayer drug also significantly reduced cancer metastases at multiple locations, including the lung, bone and brain, the researchers showed.
The success of Faslodex has prompted several biopharma companies to develop next-generation selective ER downregulators (SERDs). They include Sanofi, which is moving its drug, amcenestrant, into a phase 3 trial against tamoxifen after showing promising early results in combination with Pfizer’s CDK4/6 inhibitor Ibrance.
Roche is pairing its SERD drug, giredestrant, with Ibrance in the phase 3 persevERA trial. And Radius Health is working with Menarini on an oral SERD dubbed elacestrant. It expects phase 3 data from the EMERALD trial later this year.
The UIUC team noted that in mouse models, second-generation SERDs typically induced moderate regression of primary tumors. Those that were tested against metastases showed limited efficacy. And resistance is still a risk with CDK4/6 inhibitors.
Compared with the common inhibitory modes of action against ER, ErSO could offer “a turn-on approach to convert a tumor-selective protective pathway into a lethal, targeted anticancer response,” the researchers wrote in the study. The drug’s ability to target metastatic tumors and its activity in ER-low tumors that are traditionally considered ER-negative could broaden its potential therapeutic range, the researchers said.
Bayer picked up global rights to ErSO in September for $25 million upfront, and Systems Oncology is eligible to receive milestone payments of up to $345 million.
While the current study found the drug was well tolerated in mice and dogs, further safety analyses are needed before it can be tested in humans, the UIUC team said. The researchers also plan to explore ErSO’s use against other types of ER-positive cancers.
至今還沒拿到過Bayer對我們研究的資助。這些合同的錢沒我的份。。。據說學校已經把patent賣了。以後我們就成了啦啦隊，希望自己的研究結果能造福百姓。。。
Pfizer也試著重複過我們的結果。關鍵在ER-negative乳腺癌細胞這個定義上，也是領域裏專家們讓我們為STM文章做很多revision的原因。我們的compound是一個和Tamoxifen作用原理完全不一樣的思路，我2008年的文章就開始了這個序幕--找一個estrogen binding pocket之外的compound來達到抑製estrogen receptor的功能。但當時的那個compound和drug要求的potency差太遠，一直到2015年才有了突破。目前這個是2015年找到的那個compound的第二代。。。但ER- negative是按Tamoxifen的作用原理來定義的，我們的作用原理是不是還能沿用那個定義，就成了爭論的焦點。。。最後Pfizer放棄，認為我們的compound可能不僅僅target estrogen receptor。。。
Bayer據說重複了我們的大多數試驗，但STM的文章是我們的，和Bayer沒有關係。PDX是小公司做的，他們有自己的一套體係，有contract實驗室，也知道如何推銷。Bayer不會發文章的，他們隻會往臨床方向推進。我們現在的研究方向還是走理論，臨床我們插不上手，包括病人分型，哪些基因表達是這個藥物殺死癌細胞必須的（文章接近完成），方便臨床挑選病人，當然還有別含estrogen receptor的癌症。。。小公司還是給我們的研究一些資助，不知道會維持多久，所以一個政府部門的grant還是很有必要的。
我隨時可以退休。領導知道我能幹到60歲，也不催我找工作了。我現在就掙點旅遊的錢，帶領導到處跑跑。。。
（二0二一年七月二十二日）
很歡喜地看你的Blog，忽然想到“真正讓人輕鬆的是心態，而不是狀態”。