Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates.

Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.

Chlorpyrifos-induced toxicity has no gender selectivity in the early fetal brain.

Organophosphorus pesticides induce gender-specific developmental neurotoxicity after birth, especially in adolescents and adults. However, whether and when the selectivity occurs in fetus remains unclear. In this study, we analyzed chlorpyrifos (CPF)-induced neurotoxicity in the early fetal brains of male and female mice. The gestational dams were administered 0, 1, 3, and 5 mg/(kg.d) CPF during gestational days (GD)7-11, and brains from the fetuses were isolated and analyzed on GD12. Fetal gender was identified by PCR technique based on male-specific Sry gene and Myog control gene. The body weight and head weight, the activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA), as well as the oxidative stress-related gene expression were examined. Our results showed that CPF pretreatment induced AChE inhibition in GD12 fetal brain. CPF treatment activated SOD and GPX but not CAT and MDA. For oxidative stress-related gene expression, CPF pretreatment increased mRNA expression of Sod1, Cat, Gpx1, and Gpx2 in the fetal brain on GD12. The statistical analysis did not show gender-selective CPF-induced toxicity. Moreover, our results showed that although the gestational exposure to CPF could elicit abnormalities in the early fetal brain, the toxicity observed was not gender-specific.

Diverse chiral assemblies of nanoparticles directed by achiral block copolymers via nanochannel confinement.

It is a challenging task to realize large-area manufacture of chiral geometries of nanoparticles in solid-state materials, which exhibit strongly chiroptical responses in the visible and near-infrared ranges. Herein, novel nanocomposites, made from mixtures of achiral block copolymers and nanoparticles in a geometrically confined environment, are conceptually proposed to construct the chiral assemblies of nanoparticles through a joint theoretical-calculation framework and experimental discussion. It is found that the nanochannel-confined block copolymers self-assemble into a family of intrinsically chiral architectures, which serve as structural scaffolds to direct the chiral arrangement of nanoparticles. Through calculations of chiral order parameters and simulations of discrete dipole approximation, it is further demonstrated that certain members of this family of nanoparticle assemblies exhibit intense chiroptical activity, which can be tailored by the nanochannel radius and the nanoparticle loading. These findings highlight the multiple levels of structural control over a class of chiral assemblies of nanoparticles and the functionalities of emerging materials via careful design and selection of nanocomposites.