Efficient derivation of dopaminergic neurons from SOX1(-) floor plate cells under defined culture conditions.

BACKGROUND: Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. METHODS: In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-β signaling pathways (SB431542) for 24 h under defined culture conditions. RESULTS: Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. CONCLUSIONS: Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.published_or_final_versio

Unsupervised 3D Learning for Shape Analysis via Multiresolution Instance Discrimination

Although unsupervised feature learning has demonstrated its advantages to reducing the workload of data labeling and network design in many fields, existing unsupervised 3D learning methods still cannot offer a generic network for various shape analysis tasks with competitive performance to supervised methods. In this paper, we propose an unsupervised method for learning a generic and efficient shape encoding network for different shape analysis tasks. The key idea of our method is to jointly encode and learn shape and point features from unlabeled 3D point clouds. For this purpose, we adapt HR-Net to octree-based convolutional neural networks for jointly encoding shape and point features with fused multiresolution subnetworks and design a simple-yet-efficient Multiresolution Instance Discrimination (MID) loss for jointly learning the shape and point features. Our network takes a 3D point cloud as input and output both shape and point features. After training, the network is concatenated with simple task-specific back-end layers and fine-tuned for different shape analysis tasks. We evaluate the efficacy and generality of our method and validate our network and loss design with a set of shape analysis tasks, including shape classification, semantic shape segmentation, as well as shape registration tasks. With simple back-ends, our network demonstrates the best performance among all unsupervised methods and achieves competitive performance to supervised methods, especially in tasks with a small labeled dataset. For fine-grained shape segmentation, our method even surpasses existing supervised methods by a large margin.Comment: Accepted by AAAI 2021. Code: https://github.com/microsoft/O-CNN/blob/master/docs/unsupervised.m

HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting different susceptibility to HIV fusion inhibitors with pocket- or membrane-binding domain

AbstractEnfuvirtide (T20), the first FDA-approved peptide HIV fusion/entry inhibitor derived from the HIV-1 gp41 C-terminal heptad-repeat (CHR) domain, is believed to share a target with C34, another well-characterized CHR-peptide, by interacting with the gp41 N-terminal heptad-repeat (NHR) to form six-helix bundle core. However, our previous studies showed that T20 mainly interacts with the N-terminal region of the NHR (N-NHR) and lipid membranes, while C34 mainly binds to the NHR C-terminal pocket region. But so far, no one has shown that C34 can induce drug-resistance mutation in the gp41 pocket region. In this study, we constructed pseudoviruses in which the Ala at the position of 67 in the gp41 pocket region was substituted with Asp, Gly or Ser, respectively, and found that these mutations rendered the viruses highly resistant to C34, but sensitive to T20. The NHR-peptide N36 with mutations of A67 exhibited reduced anti-HIV-1 activity and decreased α-helicity. The stability of six-helix bundle formed by C34 and N36 with A67 mutations was significantly lower than that formed by C34 and N36 with wild-type sequence. The combination of C34 and T20 resulted in potent synergistic anti-HIV-1 effect against the viruses with mutations in either N- or C-terminal region in NHR. These results suggest that C34 with a pocket-binding domain and T20 containing the N-NHR- and membrane-binding domains inhibit HIV-1 fusion by interacting with different target sites and the combinatorial use of C34 and T20 is expected to be effective against HIV-1 variants resistant to HIV fusion inhibitors

1st Place Solution of Egocentric 3D Hand Pose Estimation Challenge 2023 Technical Report:A Concise Pipeline for Egocentric Hand Pose Reconstruction

This report introduce our work on Egocentric 3D Hand Pose Estimation workshop. Using AssemblyHands, this challenge focuses on egocentric 3D hand pose estimation from a single-view image. In the competition, we adopt ViT based backbones and a simple regressor for 3D keypoints prediction, which provides strong model baselines. We noticed that Hand-objects occlusions and self-occlusions lead to performance degradation, thus proposed a non-model method to merge multi-view results in the post-process stage. Moreover, We utilized test time augmentation and model ensemble to make further improvement. We also found that public dataset and rational preprocess are beneficial. Our method achieved 12.21mm MPJPE on test dataset, achieve the first place in Egocentric 3D Hand Pose Estimation challenge

N-Cyclo­hexyl-4-[(2-nitro­anilino)­meth­yl]thio­phene-2-sulfonamide

In the title compound, C17H21N3O4S2, an intra­molecular N—H⋯O hydrogen bond involving the proximate amine and nitro groups is observed. In the crystal, inter­molecular N—H⋯O hydrogen bonds involving the amine and SO2 groups occur. One of the notro O atoms is disordered over two conformations with occupancies of 0.578 (12) and 0.422 (12)

An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10 CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes

Perioperative Outcomes of Using Different Temperature Management Strategies on Pediatric Patients Undergoing Aortic Arch Surgery: A Single-Center, 8-Year Study

Background: With the widespread application of regional low-flow perfusion (RLFP), development of surgical techniques, and shortened circulatory arrest time, deep hypothermia is indispensable for organ protection. Clinicians have begun to increase the temperature to reduce hypothermia-related adverse outcomes. The aim of this study was to evaluate the safety and efficacy of elevated temperatures during aortic arch surgery with lower body circulatory arrest (LBCA) combined with RLFP.Methods: We retrospectively analyzed data from 207 consecutive pediatric patients who underwent aortic arch repair with LBCA & RLFP between January 2010 and July 2017 and evaluated different hypothermia management strategies. The overall cohort was divided into three groups: deep hypothermia (DH, 20.0–25.0°C), moderate hypothermia (MoH, 25.1–30.0°C) and mild hypothermia (MH, 30.1–34.0°C).Results: The percentage of AKI-1 occurrences was significantly increased in the MH group (51.52%) compared to those in the DH (25.40%) and MoH (37.84%) groups (P = 0.036); prolonged hospital stay occurrences were decreased with elevated temperature (DH 47.62%, MoH 28.83%, MH 18.18%, P = 0.006). Neurological complications, peritoneal dialysis, hepatic dysfunction, 30-day hospital mortality, delay extubation occurrences were no significant among the groups. Logistic analysis showed that the MH group was negatively associated with post-op AKI-1 compared with the DH group [OR = 0.329 (0.137–0.788), P = 0.013], no differences were found between the MoH and the MH group. Compared to other groups, the intubation time (P = 0.006) and postoperative hospital stay (P = 0.009) were significantly decreased in the MH group. Multivariate logistic analysis showed hypothermia levels were not significant with prolonged hospital stay.Conclusions: This retrospective analysis demonstrated that for pediatric patients undergoing surgeries with RLFP & LBCA, three different gradient temperature management strategies are available: deep, moderate, and mild hypothermia. Utilizing mild or moderate hypothermia is safe and feasible. Although the number of AKI-1 occurrences in the MH group was significantly increased compared to those in the other groups, further analysis showed no significance in the MoH and MH group, mild hypothermia management is as safe as others when used appropriately