Functional Neural Networks in Human Brain Organoids.

Human brain organoids are 3-dimensional brain-like tissues derived from human pluripotent stem cells and hold promising potential for modeling neurological, psychiatric, and developmental disorders. While the molecular and cellular aspects of human brain organoids have been intensively studied, their functional properties such as organoid neural networks (ONNs) are largely understudied. Here, we summarize recent research advances in understanding, characterization, and application of functional ONNs in human brain organoids.

Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions.

Bioengineering of a human physiologically relevant microfluidic blood-cerebrospinal fluid barrier model.

The human blood-cerebrospinal fluid barrier (hBCSFB) plays a crucial role in regulating brain interstitial fluid homeostasis, and disruption of the hBCSFB is associated with various neurological diseases. Generation of a BCSFB model with human physiologically relevant structural and functional features is crucial to reveal the cellular and molecular basis of these diseases and discover novel neurologic therapeutic agents. Unfortunately, thus far, few humanized BCSFB models are available for basic and preclinical research.

Rational Design and Acoustic Assembly of Human Cerebral Cortex-Like Microtissues from hiPSC-Derived Neural Progenitors and Neurons.

Development of biologically relevant and clinically relevant human cerebral cortex models is demanded by mechanistic studies of human cerebral cortex-associated neurological diseases and discovery of preclinical neurological drug candidates. Here, rational design of human-sourced brain-like cortical tissue models is demonstrated by reverse engineering and bionic design. To implement this design, the acoustic assembly technique is employed to assemble hiPSC-derived neural progenitors and neurons separately in a label-free and contact-free manner followed by subsequent neural differentiation and culture.

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

Background: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1).

Size- and density-dependent acoustic differential bioassembly of spatially-defined heterocellular architecture.

Emerging acoustic bioassembly represents an attractive strategy to build cellular closely-packed organotypic constructs in a tunable manner for biofabrication. However, simultaneously assemble heterogeneous cell types into heterocellular functional units with spatially-defined cell arrangements, such as complementary and sandwich cytoarchitectures, remains a long-lasting challenge. To overcome this challenge, herein we present an acoustic differential bioassembly technique to assemble different cell types at the distinct positions of the acoustic field based on their inherent physical characteristics including cellular size and buoyant density.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

Purpose: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia.

Patients And Methods: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose.

Association between body mass index at diagnosis and outcomes in Chinese children with newly diagnosed acute lymphoblastic leukemia.

Purpose: Studies of the association between body mass index (BMI) at diagnosis and treatment outcome in children with acute lymphoblastic leukemia (ALL) have yielded inconsistent results. Hence, we conducted a retrospective study in a large cohort of Chinese children with ALL treated with contemporary protocols.

Patients And Methods: A total of 1437 children (62.

Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse.

Purpose: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.

Soft Ring-Shaped Cellu-Robots with Simultaneous Locomotion in Batches.

Untethered mini-robots can move single cells or aggregates to build complex constructs in confined spaces and may enable various biomedical applications such as regenerative repair in medicine and biosensing in bioengineering. However, a significant challenge is the ability to control multiple microrobots simultaneously in the same space to operate toward a common goal in a distributed operation. A locomotion strategy that can simultaneously guide the formation and operation of multiple robots in response to a common acoustic stimulus is developed.

[Clinical effect of the SCMC APL-2010 regimen in treatment of acute promyelocytic leukemia in children: an analysis of 44 cases].

Objective: To study the clinical effect of the SCMC APL-2010 regimen in the treatment of acute promyelocytic leukemia (APL) in children.

Methods: A retrospective analysis was performed for the clinical data of 44 children with APL who received treatment with the SCMC APL-2010 regimen between April 2010 and July 2016. The Kaplan-Meier survival analysis was used to evaluate event-free survival (EFS) rate and overall survival (OS) rate.

Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia.

Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT.

Long-term results of the risk-stratified treatment of childhood acute lymphoblastic leukemia in China.

Long-term follow-up data for childhood acute lymphoblastic leukemia (ALL) are scarce in China because of lacking population-based and hospitalized registry system. This retrospective study, conducted at Shanghai's Children's Medical Center in China (SCMC), aimed to investigate the long-term results of childhood ALL and to identify prognostic factors. The Pediatric Oncology Network Database, designed by St.

[Analysis of clinical manifestation and genetic mutation in a child with X-linked chondrodysplasia punctata 2].

Objective: To analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.

Methods: The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members.

Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with reciprocal translocations.

Background: Mixed-lineage leukemia (MLL) with multifarious partner genes leads to aggressive leukemia with dismal outcomes.

Methods: Using panel-based targeted sequencing, we examined 90 cases with MLL-rearranged (MLL-r) childhood acute leukemia, including 55 with acute lymphoblastic leukemia (ALL) and 35 with acute myeloid leukemia (AML).

Results: MLL breakpoints and complete rearrangements were identified.

A fast and low-cost microfabrication approach for six types of thermoplastic substrates with reduced feature size and minimized bulges using sacrificial layer assisted laser engraving.

Since polydimethylsiloxane (PDMS) is notorious for its severe sorption to biological compounds and even nanoparticles, thermoplastics become a promising substrate for microdevices. Although CO laser engraving is an efficient method for thermoplastic device fabrication, it accompanies with poor bonding issues due to severe bulging and large feature size determined by the diameter of laser beam. In this study, a low-cost microfabrication method is proposed by reversibly sealing a 1 mm thick polymethylmethacrylate (PMMA) over an engraving substrate to reduce channel feature size and minimize bulges of laser engraved channels.

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice.

Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL.

Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes a rate-limiting purine biosynthesis enzyme, in 24/358 (6.

Effect of immunization against GnRH on hypothalamic and testicular function in rams.

The objective was to determine effects of active immunization against GnRH on reproductive function in Tibetan rams. Peripubertal Tibetan rams (n = 30) were randomly and equally allocated into three groups: control (no treatment); surgically castrated; or immunized against 100-μg d-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin in Specol adjuvant at 24 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 4-week intervals until rams were killed (40 weeks).

L-asparaginase induces in AML U937 cells apoptosis via an AIF-mediated mechanism.

Acute Myeloid Leukemia (AML), a cancer of the myeloid line of blood cells, progresses rapidly and is typically fatal within weeks or months if left untreated. Asparaginases are a class of enzymatic anti-leukemia agents that induce apoptosis in leukemia cell lines; however, the role of L-asparaginase in the induction of apoptosis in AML cells has not been investigated. In this study, we investigated the apoptosis-inducing effect of L-asparaginase and its underlying mechanism in AML U937 cells.