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之前我发过颜宁赖以成名的葡萄糖转运蛋白论文被质疑抄袭的事，这是目前的最新情况。

转帖地址：https://yanruntao.org/nature/

给Nature杂志的信（英文版）

《自然》杂志资深编辑建议我把投诉给贵刊的质疑信贴在颜宁博士2014和2015年两篇葡萄糖转运蛋白论文下面的评论栏，以便读者可以看到我的质疑。

这是经过了一年多与贵刊打交道后到目前为止的最新进展。虽然杂志的《评论》是读者自己注册后便可贴上去的，但我的评论需要经过编辑审查。我只能投诉颜宁博士没引用我们的论文，因为负责此事的资深编辑认为我们的论文应该被引用。其它方面，由于颜宁的论文是受到了同行审查的，我可以贴哪些缺陷，但不能有misconduct/fool the readers/misleading the scientifc community 等字眼，否则当即被删除。事实上，有这类指控内容的，我都贴不上，因为给我设计了专门的只要我 log in 就消失了“发送”键的页面。

科学论文打假，在西方往往需要漫长的过程。然而，到了上周，我的质疑信就可以贴在《评论》栏了，还是资深编辑告诉我的。我经过了周末的思考后，本周一才贴上去的，而且有“发送键”。已经贴在那里2天了。《自然》杂志的《评论》栏是公开的网站，是希望更多读者看到。我保有资深编辑给我的信。

那么，我就可以把此信在网络上公开了。因为总有网友提议要把英文版贴出来，知道我质疑颜宁论文造假/欺骗的内容是什么。毕竟这一科学发现被列为“十大科学进展”，也令颜宁博士获得了贵校终身冠名讲席教授的职位、美国科学院院士称号，也获得了中华人民共和国百万元级别的科学荣誉奖“Seek Truth Award”（中文：求是奖）。

我把此信附在下面。《自然》杂志下面的评论栏里也有，只是在2014 和 2015 两篇论文的下面。我本来是贴在2014论文下面的，是资深编辑看了后建议质疑哪篇的就分开贴在哪篇的评论里。下面的版本是我的质疑信，分开贴在了《自然》杂志的两篇论文的评论栏目里。

这也是科普内容，科学家们读了我的质疑信后便会去读原论文，对比研究，验证我的质疑是否有理有据，有没有冤枉颜宁博士，同时对“十大科学进展”之一的科学知识有了掌握。也是直接科普世界科学界“十大科学进展”的内容。

然而，质疑是一方观点，应该有反方的答疑。一年多了，不论是在中文世界还是在英文世界，我都没收到颜宁博士对质疑的答疑（“碰瓷”不是科学用语）。估计是杂志社不让我看到。那就需要更多的科学家们进行探索真相。这就需要更多的科学家有知情权，了解我质疑的内容，并亲自看原文，以确定质疑是不是应该得到答疑、我的质疑是否有道理。

我不知道谁是颜宁论文的审稿人，但我知道中国国内媒体当年公开发表了三位美国著名科学家对颜宁论文的高度评价，都是美国科学院院士，有一位诺贝尔奖得主。显然，他们是看过颜宁2014年发表的葡萄糖载体（她称之为转运蛋白）论文的。载体和转运蛋白，也是从英文翻译过来的，一个是carrier, 一个是transporter，至今二者通用。科学真理都是在质疑中被矫正、鉴定出来的。真理是不怕质疑的。

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Dear Nature,

My name is Runtao Yan. I am writing you with a concern about Dr. Nieng Yan, a Member of the U.S. National Academy of Sciences (NAS). I believe she is guilty of scientific misconduct and I have evidence to prove it.

1.”latch gate” theory—misled the scientific community

In the paper published in 2014 (Nature, 510, 121-125), she identified a “latch” which was one of her two major findings (the other main finding was “the Glut1 working model”).

In Fig. 3 and Fig. 5, she named it an ICH domain and explained its function as such: “The ICH domain serves as a latch that tightens the intracellular gate.”(p.123) “Because of the extensive interactions between TMD and ICH, the ligand-free protein may prefer an outward-open conformation.” (p.124)

In fact, the XylE and Glut1 are transporters belonging to the Facilitated Diffusion Superfamily, whose function (direction and efficiency) solely depends on the substrate concentration gradient across the membrane, and functionally no sidedness. This means the glucose can be transported from one side of the membrane to the other and vice versa. It is impossible for a “facilitated diffusion transporter” to have a “LATCH GATE” to maintain the out-facing direction. If so, they are no longer “Diffusion Transporters”. Instead, they are “GATED CHANNELS.”

If Dr. Nieng Yan’s “outward-open latch” theory was true, then the glucose transporters CANNOT RELEASE accumulated glucose into the extracellular space adjacent to the blood capillary, because the “Latch Gate” causes the transporter to bear outward-open conformation with the inside closed by the latch, such that the glucose inside can’t get into the translocation pathway of the transporter.

In nature, glucose transporters DO release accumulated glucose into the extracellular space adjacent to the blood capillary by facilitated diffusion.

Apparently, Dr. Nieng Yan never carried out a biochemical assay for any Facilitated Diffusion Superfamily transporters and merely assumed that the glucose was transported only from outside to inside of the cells, and that the glucose concentration inside was always lower than the outside, thus making up an artificial “outward-open conformation latch gate” theory without any scientific data support. The reviewers should have caught that, because in the paper, she mentioned that the XylE and Glut1 are the members of facilitated diffusion superfamily.

She found the ICH latch domain from a crystallized symporter (XylE), and predicted that “substrate-free uniporters have a preferred open conformation”(P.124), that means that all of the uniporters should no longer be the “Facilitated Diffusion Superfamily” members.

In addition, if the latch gate has no function at all, then it should have been eliminated during the 3 billion years of transporter evolution.

How would such an illogical and unrealistic “theory”, without any biochemical analysis or any scientific data support, be accepted by Nature reviewers, and hence misleading the scientific community?

I don’t know the answer. However, if I were to guess, I believe there to be two possibilities (merely from my own imagination). (A) some reviewers may not be in the transporter field and have never done any biochemical assays to know that the facilitated diffusion transporters are functionally non-sided, and blindly trusted Dr Nieng Yan. (B) perhaps, the reviewer in the transporter field at that time may be reluctant to challenge Dr. Nieng Yan’s scientific work due to fear of losing funding from the Chinese government by collaboration. Of course, these are merely hypotheses, as there could be numerous answers.

2.Make a fool of the scientific community

The “four conformational structures” described in the paper to prove her major scientific contribution cannot prove the working model. When the transporter (also called carrier) was in occluded inward-facing conformation, which means a glucose molecule was inside the transporter, Dr. Nieng Yan stated that it is evidence that the glucose has entered the transporter from the inside of the cell (see Fig 5). However, the glucose could be transported from the outside of the cell during the crystallization. That is why we had to use radioactive labeled substrates in our experiments .

A simple example illustrates my point. If I show a picture to a child of a man on a boat on the north bank of a river and explain to him/her that this is evidence that the man just boarded the boat on the north bank, the child should reasonably question this evidence since the man could have remained on board after ferrying from the south bank to the north bank.

Is this truly her level of logical thinking, or is she deliberately deceiving? She should know that her “four conformational structures” cannot prove the working model of a transporter. How could she have known whether the glucose was from the inside of the cell, or transported from outside the cell to inside during crystallization? It is impossible for her to distinguish this without radioactively labeling the substrate.

3.Deception

Even if the “four-conformation structures” in the paper could prove that it is the working model of a transporter (in fact it could not), she did not find the four structures. In her paper, she said that the four structures are required for a complete transport cycle. However, there are only two crystal structures of E. coli xylose transporter (proton co-transporter, i.e. symporter), and one human glucose transporter Glut-1 (uniporter). Even after combining them (symporter and uniporter) together, she only obtained THREE structures. When she concluded “A working model of Glut1” (bold words) from Fig.5, her conclusion was based on “Predicted data” from Fig5’s detailed descriptions (small words) . In other words, the conclusion should be: “Predicted working model of Glut1” instead of an actual “working model of Glut1”. The essence of this play is deception.

In this case, it is impossible for her to propose a working model for Glut1 when lacking the basic experiments of “four conformation structure” cycle as she stated in her paper that (1) “the conformational switch from inward-facing to outward-facing of symporters remains to be elucidated”; and (2) The outward-open structure remains to be captured.

4.Dr. Nieng Yan did not disclose the source of the “published biochemical data”

Since she did not obtain four crystal structures and had no way to identify the working model based on only three structures, she attempted to fix it by providing more “evidence” in Discussion section, in which she said: “On the basis of our structural analysis and published biochemical data, we propose a working model for Glut1” (P124 ). If she thought she did not need to give reference because the biochemical experiments were done in her lab, she should not have said “Predicted” in Fig.5.

No matter who did it, the fact is that the cystine-scan method created by RT Yan & PC Maloney (1995 PNAS 92:5973-5976）was the only biochemical method to identify the membrane transport working model.

5.Make a fool of colleagues in 2015 Nature paper

Dr. Nieng Yan also lead astray her colleagues when she wrote in her 2015 Nature paper (Nature 526:391-396) that occluded inward-facing conformation was the evidence that a glucose molecule inside the carrier was entered from the inside of the cell, and occluded outward-facing conformation was the evidence that the glucose molecule must entered from outside of the cell. She should know better, having studied transporters. Thinking back to my earlier boating example, if there is no boat ticket to check, how do you know where the man boarded the boat (just like if you do not use radioactive labeling).