DollJournal 玩偶日志

Silicone & TPE Doll Enthusiast，Companion & emotional experience, styling & care sharing. 硅胶 / TPE人偶爱好者，分享多款玩偶带来的陪伴与情感体验、造型与保养等.

[DollJournal 玩偶日志 @DollJournalCN]

昨天重阳节敬老活动，见到李大爷，他轻声说：“你那娃娃真好用”，我帮他选了一个半身玩偶。李大爷是我们小镇的第一个大学生，八一年读地质部的一个重点本科大学。大爷现在无儿无女，没老婆，租房子住，前段时间办理低保，成为我们镇第一个领低保的本科生，几十年后也是第一.#Doll #lovedoll #Dolltale

[DollJournal 玩偶日志 @DollJournalCN]

她的呻吟声在寂静的房间里回荡，完全不像喇叭发出的声音。如此真实的体验，让我当她是人一样草。嘴巴吮吸她丰满的乳房，拍打她鼓圆的屁股，牛子撞击她的小穴，它受到刺激，收缩和转动的频率更大，淫水流出洞口，天啊，她比人还更棒。手机屏幕闪烁：“真实与虚幻的界限已经消失。#Doll #lovedoll

[DollJournal 玩偶日志 @DollJournalCN]

我扯下帐篷，提起鼓胀的牛子，快速捅进福地湿穴，紧致的包裹感，层层收紧的摩擦，润滑柔软的褶皱，节奏的吸允收缩，牛子欢快地冲刺，挺进。索菲亚的呼吸逐渐急促，我抬起头���凝视着她精致的的面容，“你感觉到了吗？”我轻声问，索菲亚低沉的叹息回应着，屁股微微扭动，似乎忘情地享���. #Doll

[DollJournal 玩偶日志 @DollJournalCN]

我手掌抓紧她丰满的乳房，指尖轻捻坚挺的乳头，感受到它们的微微颤动，屏幕再次亮起：“她的身体回应你的触摸。”我低头，大力吮吸那粉嫩的尖端，索菲亚的身体微微颤抖，低沉的叹息从她唇间溢出。天啊❗️她怎么比真人更完美？一股热浪从胯下涌起，把帐篷撑起直挺她的福地 #Doll #LoveDoll

[DollJournal 玩偶日志 @DollJournalCN]

我的唇触碰到索菲亚脸，扶住她的细腰。将礼服从她的肩头���下，红光映照在她的肩膀上，皮肤散发出温暖的琥珀色。我俯下身，咬她的锁骨。手机屏幕再次亮起：“你的嘴在她的皮肤上留下了印记。”我抬头，看到自己的唇印在索菲亚的锁骨上微微泛红，心跳加速, 解开剩下的纽扣，直到礼服滑落到地。#LoveDoll

[DollJournal 玩偶日志 @DollJournalCN]

我的手掌覆盖在索菲亚的后背，感受着如丝绸般的触感。拇指轻轻滑过她的脊柱，体温的微凉与她不可思议的柔软交织在一起。我俯下身，嘴唇靠近她的颈侧，吸入淡淡的薰衣草香气，那是贝拉最爱的香水。“贝拉，”我低声呼唤，声音沙哑而颤抖。屏幕上闪烁的信息似乎变得温暖：“她们是同一个人.#Doll #Dolltale

[DollJournal 玩偶日志 @DollJournalCN]

丹尼尔的指尖轻��地沿着索菲亚的脊骨滑动，停在最后几个纽扣处，心中涌动着无法抵挡的冲动。盐灯的红光在她裸露的肌肤上投下温暖的阴影，仿佛每一寸肌肤都在随他的触碰而轻微起伏。“她在呼吸，”他低声喃语，尽管理智告诉他这不可能。屏幕再次亮起：“是的，她在为你呼吸。”#Doll #DollTale

[DollJournal 玩偶日志 @DollJournalCN]

他的手指悬停在屏幕上，心脏在剧烈跳动,盐灯的光芒随着他的犹豫闪烁。“你是谁？”他键入后又删除，觉得太过直接，容易暴露不安。“你一直在看？”他最终发送，声音在空荡的空间中显得格外响亮。回复几乎立刻到来：“一直都在。你抚摸索菲亚的方式比贝拉更温柔，更慢，时间更长.#LoveDoll#Doll

[DollJournal 玩偶日志 @DollJournalCN]

午夜，丹尼尔锁上了门，调暗灯光，让音乐充满了整个房间。索非亚身披黑色缎子，站在红色华服的贝拉旁边。这两具精致的玩偶在他私密的庇护所中静候着他的到来。“今晚，”他嘴角勾起一抹狡黠的微笑，“我��来点新花样。”他为她们换上新衣，调整灯光，拍下了一张完美捕捉她们魅力的照片#Doll#Dolltale

[DollJournal 玩偶日志 @DollJournalCN]

He dressed them in fresh outfits, adjusted the lighting ,snapped perfect photo that showcased their allure. Suddenly, his phone vibrated with an anonymous message: “I see you’ve chosen your favorite. But when no one is watching, who will capture your attention?” Daniel froze#Doll

[DollJournal 玩偶日志 @DollJournalCN]

midnight, Daniel secured the door, dimmed the lights and let music fill the air. Sophia, draped in black satin, stood beside Bella, who wore a striking red gown. These exquisite love dolls awaited him in his intimate sanctuary. he said “I’m trying something new ”#Doll#DollTale

[DollJournal 玩偶日志 @DollJournalCN]

他为她们换上新衣，调整灯光，拍下了一张完美捕捉她们魅力的照片。就在这时，他的手机突然震动，收到了一条匿名信息：“我看到你选择了你最爱的。但在无人注视时，谁会吸引你的注意？”丹尼尔顿时僵住，脊背一阵寒意。谁知道他的秘密？而这似乎只是个开始。
#lovedoll

[DollJournal 玩偶日志 @DollJournalCN]

Exploring a beautiful doll store, appreciating the texture & charm of these art dolls.
探访人偶实体店，感受人偶独有的质感与陪伴魅力。
Filmed in the Greater Bay Area
#Doll #DollCollection #DollJournal

[David R. Liu @davidrliu]

Base editing and prime editing clinical trial landscape, including today’s GSD type I clinical readout from @BeamTx.

[DollJournal 玩偶日志 @DollJournalCN]

Exploring beautiful dolls , appreciating the texture & charm of these dolls.
体验人偶,感受人偶独有的质感与陪伴魅力。

#Doll #DollCollection#ArtDoll.

[DollJournal 玩偶日志 @DollJournalCN]

Exploring a beautiful doll store, appreciating the texture & charm of these art dolls，it should be huge demand for these robot dolls.
体验人偶实体店，感受人偶独有的质感与陪伴魅力,人偶机器人的市场广阔。
Filmed in the Greater Bay Area
#Doll #DollCollection #Robot

[DollJournal 玩偶日志 @DollJournalCN]

Exploring a beautiful doll store, appreciating the texture & charm of these art dolls.
探访人偶实体店，感受人偶独有的质感与陪伴魅力。
Filmed in the Greater Bay Area
#Doll #DollCollection #DollJournal

[DollJournal 玩偶日志 @DollJournalCN]

Exploring a beautiful doll store, appreciating the texture & charm of these art dolls.
探访人偶实体店，感受人偶独有的质感与陪伴魅力。
Filmed in the Greater Bay Area
#DollJournal #ArtDoll #DollCollection

[DollJournal 玩偶日志 @DollJournalCN]

Exploring a beautiful doll store, appreciating the texture & charm of these art dolls.

探访人偶实体店，感受人偶独有的质感与陪伴魅力。

#DollJournal #ArtDoll #DollCollection

[J Keynes @JKeynesAlpha]

$PRME 👀Potential $BMY Milestones Exceed 5x Market Cap for a Revolutionary Platform

This is a very long-duration investment for me. I entered around $1.50 and averaged up a bit around $3. I plan to DCA another significant block if and when management raises capital, depending on the terms and whether the clinical thesis continues to hold.

At roughly $570 million in market cap at the October 5 close, Prime Medicine strikes me as unusually inexpensive relative to its scientific platform and the magnitude of its opportunities. Bristol Myers Squibb’s agreement includes more than $3.5 billion in potential milestone payments, over six times that market cap, plus royalties. Their value depends on the probability of success, when payments arrive and the costs of execution. The scale still deserves attention.

BMS committed $55 million upfront and a $55 million equity investment. The potential milestones include up to $1.4 billion for development and more than $2.1 billion for commercialization. BMS brings the resources to develop, manufacture and commercialize the resulting T-cell therapies, which use engineered immune cells to treat disease. That relationship gives Prime a route into cancer and immunology alongside its internal genetic-disease programs.

What attracts me is prime editing’s breadth. It can make all 12 types of single-letter DNA substitutions, insert or delete DNA, and repair a wide range of disease-causing mutations. At Morgan Stanley, CEO Allan Reine described its capabilities with a memorable phrase: “we can put in whole new sentences.” The goal is precise repair of the genetic instructions underlying disease. Safety, effectiveness and durability must be established through clinical evidence.

PASSIGE extends that ambition to gene-sized DNA. Prime editing installs a landing site in the genome, and another enzyme inserts a larger DNA sequence at that chosen location. This could eventually allow one treatment to address many different mutations within a gene.

Discussing the improved research system eePASSIGE, David Liu said “many if not most loss-of-function genetic diseases could be ameliorated or rescued,” conditional on results in cultured human cells translating into clinical treatment. In plain English, a healthy gene could potentially restore a function that a damaged gene has lost. The reach of that possibility is enormous.

AI is helping improve the technology, too. Liu’s lab developed OptiPrime, which predicts how well editing guide RNAs will perform and helps researchers select promising designs. Liu described the goal as making prime editing “as easy to use as possible.” Separate 2026 research used AI to redesign part of the editing machinery, improving its stability and editing performance in preclinical experiments. These are tangible advances in the research tools underlying the field; their contribution to individual commercial products will need to be demonstrated.

Reine’s explanation of the platform economics is one of the most compelling parts of the thesis. At H.C. Wainwright, he said:

“Once we have true proof of concept in the clinic of our LNP, we think it could be very cost effective and very fast to go into additional indications.”

He then described “a flywheel that we think is going to create a tremendous amount of value.”

The LNP is a delivery system made from tiny fat-based particles that carry the editing machinery into liver cells. Prime expects to reuse that delivery system, manufacturing processes and substantial portions of the regulatory work across additional treatments. Changing the editing instructions could then expand the platform into more mutations and diseases. Successful human results are the essential foundation for those efficiencies.

The chronic granulomatous disease treatment, PM359, already provides an important human proof point. Chronic granulomatous disease, or CGD, is an inherited immune disorder that leaves certain white blood cells unable to fight infections effectively. Prime’s treatment targets a specific subtype by correcting a DNA deletion in a patient’s own blood-forming stem cells, aiming to restore the missing infection-fighting function.

Results from the first two patients were published in the New England Journal of Medicine. Functional neutrophils, a type of white blood cell, reached 69% and 83% by day 30, with restored enzyme activity and early clinical benefit. Longer follow-up remains important. The treatment also requires conditioning chemotherapy, which carries its own risks.

This explains Liu’s description of the first result as “the Alyssa Tapley moment for prime editing.”

Alyssa was a British teenager, aged 13 when she received base-edited donor immune cells in 2022 after conventional treatments failed to control her leukemia. The treatment produced remission and enabled a subsequent stem-cell transplant. Her case became a landmark demonstration of base editing’s ability to help save a patient’s life. Liu saw a corresponding breakthrough when Prime corrected a CGD patient’s own stem cells and restored the missing immune function.

The baby story is KJ, treated in Philadelphia for CPS1 deficiency, a genetic disorder that prevents the body from properly clearing toxic ammonia. His personalized base-editing treatment and initial recovery demonstrated how editing, liver delivery, manufacturing and regulatory coordination could come together rapidly for an individual patient. These patient stories make the scientific promise much more tangible.

The 2025 New York Times article about Prime’s CGD patients also highlighted the difficult economics. A transformative treatment can struggle to reach commercialization when its eligible population is tiny and development costs are high. Prime had discontinued the program. Reine subsequently explained that greater FDA flexibility around patient numbers and manufacturing requirements made pursuing approval more financially workable.

The planned filing for the CGD treatment is a Biologics License Application, the application seeking FDA permission to market the therapy. Prime targets the first half of 2027. Describing discussions about the patient evidence, Reine said at Goldman Sachs:

“The FDA was fully on board with that data package being sufficient from a patient standpoint to get to approval.”

He subsequently said Prime plans to treat another adolescent, with manufacturing work also influencing the filing timeline. That is management’s account of the potential pathway. Completing the application, satisfying manufacturing requirements and obtaining FDA approval remain necessary steps.

Reine expects a limited commercial opportunity for this particular CGD subtype and believes Prime can reach patients with relatively modest additional expense. I see value in helping those patients, demonstrating clinical execution and potentially establishing the first approved prime-editing medicine.

The Wilson disease treatment, PM577a, is a major reason I remain bullish. Wilson disease is an inherited disorder that prevents the body from handling copper properly. Copper accumulates and can damage the liver, brain and other organs. Prime’s treatment aims to repair a specific mutation in the ATP7B gene so liver cells can restore copper transport through a single infusion.

Prime announced the first patient dosed on October 5, with initial clinical data expected in 2027. A follow-on treatment targeting another common Wilson mutation could expand the patient population using the shared delivery system.

Reine’s most bullish description of the preclinical Wilson results was:

“If we can recapitulate that data in the clinic, we think we could at least genetically cure these patients.”

That statement retains the crucial condition: the animal results must translate into people. The trial will use several measurements, including copper PET scans before treatment and around six to eight weeks afterward, to assess whether copper moves through the liver and into bile more normally. The goal is evidence that repairing the gene restores its function and could allow patients to discontinue existing treatment safely.

The alpha-1 antitrypsin deficiency treatment, PM647, adds another substantial opportunity. This inherited disease involves a faulty protein that can accumulate in the liver, while too little functional protein reaches the lungs to protect them. Patients can develop progressive liver disease and lung damage.

Prime’s treatment aims to correct the underlying mutation so the liver produces normal, functional protein. It received FDA clearance to begin human testing on September 24, with initial clinical data expected in 2027. It uses the same liver delivery system as the Wilson disease treatment.

Reine explained why he believes this approach could stand out:

“Taking a patient back to wild-type protein under endogenous control with a permanent change has the potential to really be a best-in-class therapy.”

In plain English, the ambition is to restore the normal protein while preserving the body’s natural control over its production. Reine also said: “Obviously, it’s all data-dependent.” Competition is substantial, and Prime must demonstrate its efficacy, safety and durability in humans.

The positive, binding resolution of the Beam arbitration removed a material uncertainty around Prime’s alpha-1 treatment. The tribunal determined that it falls within Prime’s contractual field, that Prime had not breached the agreement, and that no monetary damages were owed. That supports Prime’s ability to develop and commercialize this program.

Cystic fibrosis is another potentially enormous application. It is an inherited disease involving a faulty CFTR protein, which helps control salt and water movement in cells. The resulting thick, sticky mucus can clog airways, trap bacteria and cause repeated infections and progressive lung damage. Prime is working on correcting the genetic defect in lung cells to restore CFTR function.

At Goldman Sachs, Reine said: “We really think this is the optimal therapy for CF.” His reasoning is that correcting the gene could restore normal protein production under the body’s natural controls. He also described potential benefit for patients whose mutations or intolerance leave them underserved by existing medicines. This is a preclinical program, and delivering sufficient editing machinery into the right lung cells remains a major challenge.

The CF Foundation committed up to an additional $24 million after an earlier commitment of up to $15 million. Current work includes a mutation called G542X, alongside broader approaches using hotspot editing and PASSIGE. I view that continuing support as meaningful evidence that this program deserves serious development.

Commercial gene editing already exists. Vertex reported $76.4 million in Q2 2026 revenue from Casgevy, an approved gene-editing treatment for sickle cell disease and transfusion-dependent beta thalassemia. These are inherited blood disorders affecting hemoglobin, the protein that carries oxygen. Casgevy uses a different editing technology, and its sales demonstrate that gene-editing medicines can obtain approval, reach patients and generate revenue.

In his September Harvard interview, Liu said these therapies “can be financially viable for diseases where there are at least thousands of patients whom you can treat.” Shared development work, larger addressable populations and therapies that cover multiple mutations could all help Prime’s eventual economics.

The financing risk needs to be confronted honestly. Prime’s August 6 Q2 release reported $108.8 million including restricted cash. Cash, cash equivalents and investments excluding restricted cash were $95.1 million. The quarterly net loss was $42.1 million, and management guided to cash runway into 2027. First-half operating cash usage was $83.8 million. Securing additional funding matters.

The 10-Q explicitly states that “substantial doubt exists about the Company’s ability to continue as a going concern” over the twelve months following issuance of the financial statements. Management’s financing plans were too uncertain to eliminate that doubt under the accounting standard. I take this seriously. Continued operations depend on obtaining additional capital, reducing expenditures and/or executing the business plan. Funding on acceptable terms is uncertain, and shareholders could face substantial dilution.

Reine has discussed potential funding through BMS milestones and additional partnerships. At Goldman Sachs, he identified $185 million in potential preclinical BMS milestones and expressed confidence that the first one or two could be achievable in the near to medium term, without committing to a date. These remain contingent sources of funding. My plan to add around a raise depends on the runway it secures and the dilution required.

Regulation matters, too. I want rigorous safety standards and workable pathways that recognize reusable platform evidence. Chinese developers are advancing competing approaches, including in alpha-1 antitrypsin deficiency. The U.S. needs a regulatory environment capable of supporting responsible commercialization of these technologies. Reine’s account of the CGD pathway gives me some encouragement.

I agree that biotech is risky. I see no scam here. I see serious science, published human results, clinical development and credible partners, alongside a company with a genuine funding challenge.

For someone willing to follow the evidence and management over the next five years, I can see a path to a 10-bagger. A 100-bagger over ten years is my exceptionally ambitious upside scenario if the platform produces multiple successful therapies and a scalable commercial business. Those outcomes require clinical success, approvals, reimbursement, commercial execution and enough value creation to overcome dilution. Failure could cause a substantial or total loss.

The opportunity cost deserves to be seen clearly. Capital committed here could spend years waiting for data, financing, approvals and commercial scale. Other investments could compound during that period. Patience includes following the evidence and reassessing the thesis.

I know very few, if any, small-cap companies with this combination of scientific depth, platform breadth and magnitude of potential. That is why I am willing to carry the opportunity cost.

This is a very long-duration stock for patient holders. It is not a get-rich-quick scheme.