iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain1. Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues2-6. The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development7-10. However, current approaches do not incorporate microglia or address their role in organoid maturation11-21. Here we generated microglia-sufficient brain organoids by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac)22. In organoid cocultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro) and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2+ lipid droplets that exported cholesterol and its esters, which were taken up by NPCs in the organoids. We also detected PLIN2+ lipid droplet-loaded microglia in mouse and human embryonic brains. Overall, our approach substantially advances current human brain organoid approaches by incorporating microglial cells, as illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPCs that leads to improved neurogenesis.

Biomimetic Synchronization in Biciliated Robots.

Direct mechanical coupling is known to be critical for establishing synchronization among cilia. However, the actual role of the connections is still elusive-partly because controlled experiments in living samples are challenging. Here, we employ an artificial ciliary system to address this issue. Two cilia are formed by chains of self-propelling robots and anchored to a shared base so that they are purely mechanically coupled. The system mimics biological ciliary beating but allows fine control over the beating dynamics. With different schemes of mechanical coupling, artificial cilia exhibit rich motility patterns. Particularly, their synchronous beating display two distinct modes-analogous to those observed in C. reinhardtii, the biciliated model organism for studying synchronization. Close examination suggests that the system evolves towards the most dissipative mode. Using this guideline in both simulations and experiments, we are able to direct the system into a desired state by altering the modes' respective dissipation. Our results have significant implications in understanding the synchronization of cilia.

Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE: To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE: 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT: By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS: Frequency. RESULTS: The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION: The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

Distinct epigenetic modulation of differentially expressed genes in the adult mouse brain following prenatal exposure to low-dose bisphenol A.

Bisphenol A (BPA) is a common component in the manufacture of daily plastic consumer goods. Recent studies have suggested that prenatal exposure to BPA can increase the susceptibility of offspring to mental illness, although the underlying mechanisms remain unclear. In this study, we performed transcriptomic and epigenomic profiling in the adult mouse brain following prenatal exposure to low-dose BPA. We observed a sex-specific transcriptional dysregulation in the cortex, with more significant differentially expressed genes was observed in adult cortex from male offspring. Moreover, the upregulated genes primarily influenced neuronal functions, while the downregulated genes were significantly associated with energy metabolism pathways. More evidence supporting impaired mitochondrial function included a decreased ATP level and a reduced number of mitochondria in the cortical neuron of the BPA group. We further investigated the higher-order chromatin regulatory patterns of DEGs by incorporating published Hi-C data. Interestingly, we found that upregulated genes exhibited more distal interactions with multiple enhancers, while downregulated genes displayed relatively short-range interactions among adjacent genes. Our data further revealed decreased H3K9me3 signal on the distal enhancers of upregulated genes, whereas increased DNA methylation and H3K27me3 signals on the promoters of downregulated genes. In summary, our study provides compelling evidence for the potential health risks associated with prenatal exposure to BPA, and uncovers sex-specific transcriptional changes with a complex interplay of multiple epigenetic mechanisms.

Clinical characteristics and detection of MYB-QKI fusions in patients with angiocentric glioma.

PURPOSE: Angiocentric glioma (AG), a benign tumor identified within the last two decades, was officially included in the 2007 WHO Classification of Tumors of the Central Nervous System, WHO grade I. The tumor is relatively rare, with only approximately 100 cases reported. We aim to complement the characteristics and long-term prognosis of AG, as well as to detect MYB-QKI fusions. METHODS: The characteristics of all cases collected between 1 March 2009 and 1 March 2023 at the Beijing Sanbo Brain Hospital, Capital Medical University, were summarized and analyzed. Additionally, all fourteen patients were tested for MYB-QKI fusions. RESULTS: AG more predominantly occurs in adolescents (median age 16.5-year-old), and commonly presents with drug-resistant epilepsy. AG is frequently localized in the supratentorial regions and only one patient is in the brainstem. Brain parenchyma atrophy, and stalk-like signs can observe in imaging. Pathologically, tumor cells are perivascular pseudorosettes, presenting immunoreactivity for GFAP, S-100, Vimentin, "dot-like" staining for EMA, and low proliferative activity. Focal cortex dysplasia was observed in four patients. Twelve of fourteen (85.7%) patients were found with MYB-QKI fusions. Completely surgical resection typically has a satisfactory prognosis with long-term follow-up. CONCLUSION: AG is a rare benign tumor with a favorable prognosis after complete resection, characterized by refractory epilepsy, frequently occurring in adolescents. MYB-QKI fusions were detected in most AG patients, as a good defining genetic alteration pathologically. The potential presence of focal cortical dysplasia (FCD) may affect the prognosis of epilepsy.

The correlation between lung ultrasound scores and outcomes of high-flow nasal cannula therapy in infants with severe pneumonia.

OBJECTIVE: The study aimed to explore the effectiveness of bedside lung ultrasound (LUS) combined with the PaO2/FiO2 (P/F) ratio in evaluating the outcomes of high-flow nasal cannula (HFNC) therapy in infants with severe pneumonia. METHODS: This retrospective study analyzed the clinical data of 150 infants diagnosed with severe pneumonia and treated with HFNC therapy at our hospital from January 2021 to December 2021. These patients were divided into two groups based on their treatment outcomes: the HFNC success group (n = 112) and the HFNC failure group (n = 38). LUS was utilized to evaluate the patients' lung conditions, and blood gas results were recorded for both groups upon admission and after 12 h of HFNC therapy. RESULTS: At admission, no significant differences were observed between the two groups in terms of age, gender, respiratory rate, partial pressure of oxygen, and partial pressure of carbon dioxide. However, the P/F ratios at admission and after 12 h of HFNC therapy were significantly lower in the HFNC failure group (193.08 ± 49.14, 228.63 ± 80.17, respectively) compared to the HFNC success group (248.51 ± 64.44, 288.93 ± 57.17, respectively) (p < 0.05). Likewise, LUS scores at admission and after 12 h were significantly higher in the failure group (18.42 ± 5.3, 18.03 ± 5.36, respectively) than in the success group (15.09 ± 4.66, 10.71 ± 3.78, respectively) (p < 0.05). Notably, in the success group, both P/F ratios and LUS scores showed significant improvement after 12 h of HFNC therapy, a trend not observed in the failure group. Multivariate regression analysis indicated that lower P/F ratios and higher LUS scores at admission and after 12 h were predictive of a greater risk of HFNC failure. ROC analysis demonstrated that an LUS score > 20.5 at admission predicted HFNC therapy failure with an AUC of 0.695, a sensitivity of 44.7%, and a specificity of 91.1%. A LUS score > 15.5 after 12 h of HFNC therapy had an AUC of 0.874, with 65.8% sensitivity and 89.3% specificity. An admission P/F ratio < 225.5 predicted HFNC therapy failure with an AUC of 0.739, 60.7% sensitivity, and 71.1% specificity, while a P/F ratio < 256.5 after 12 h of HFNC therapy had an AUC of 0.811, 74.1% sensitivity, and 73.7% specificity. CONCLUSION: Decreased LUS scores and increased P/F ratio demonstrate a strong correlation with successful HFNC treatment outcomes in infants with severe pneumonia. These findings may provide valuable support for clinicians in managing such cases.

Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?

BACKGROUND: Surveillance of pancreatic cysts are necessary due to risk of malignant transformation. However, reported progression rates to advanced neoplasia are variable and the high frequency of surveillance scans may pose a considerable burden on healthcare resources. PURPOSE: To validate the effectiveness of the Fukuoka Guidelines surveillance regime and determine if a longer surveillance interval can be established. MATERIAL AND METHODS: All magnetic resonance imaging (MRI) studies of the pancreas performed at our institution between January 2014 and December 2016 with at least one pancreatic cystic lesion and follow-up MRI or computed tomography (CT) over at least two years were reviewed for size, worrisome feature (WF), and high-risk stigmata (HRS) at diagnosis and follow-up imaging (up to year 6). Reference standards for advanced neoplasia were based on endoscopic ultrasound, fine needle aspiration cytology, or the presence of ≥2 WF or ≥1 HRS on imaging. Comparison of MRI features of progression and outcomes of diagnostic endpoints between lesions <20 mm and ≥20 mm was performed. RESULTS: A total of 270 patients were included (201 cysts <20 mm, 69 cysts ≥20 mm). Compared with cysts <20 mm, cysts ≥20 mm were more likely to be associated with WF or HRS (40.6% vs. 12.4%; P ≤0.00001), demonstrate increase in size of ≥5 mm in two years (20.3% vs. 10.9%; P = 0.049), and develop advanced neoplasia (24.6% vs. 0.5%; P <0.00001). CONCLUSION: Pancreatic cysts <20 mm have a low risk of developing WF and HRS and surveillance interval may be lengthened.

Plant uptake of CO2 outpaces losses from permafrost and plant respiration on the Tibetan Plateau.

High-latitude and high-altitude regions contain vast stores of permafrost carbon. Climate warming may result in the release of CO2 from both the thawing of permafrost and accelerated autotrophic respiration, but it may also increase the fixation of CO2 by plants, which could relieve or even offset the CO2 losses. The Tibetan Plateau contains the largest area of alpine permafrost on Earth. However, the current status of the net CO2 balance and feedbacks to warming remain unclear, given that the region has recently experienced an atmospheric warming rate of over 0.3 °C decade-1 We examined 32 eddy covariance sites and found an unexpected net CO2 sink during 2002 to 2020 (26 of the sites yielded a net CO2 sink) that was four times the amount previously estimated. The CO2 sink peaked at an altitude of roughly 4,000 m, with the sink at lower and higher altitudes limited by a low carbon use efficiency and a cold, dry climate, respectively. The fixation of CO2 in summer is more dependent on temperature than the loss of CO2 than it is in the winter months, especially at higher altitudes. Consistently, 16 manipulative experiments and 18 model simulations showed that the fixation of CO2 by plants will outpace the loss of CO2 under a wetting-warming climate until the 2090s (178 to 318 Tg C y-1). We therefore suggest that there is a plant-dominated negative feedback to climate warming on the Tibetan Plateau.

The effect of extracellular polymeric substances on MICP solidifying rare earth slags and stabilizing Th and U.

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.

Real-World Validation of a Computer-Aided Diagnosis System for Prediction of Polyp Histology in Colonoscopy: A Prospective Multicenter Study.

INTRODUCTION: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. METHODS: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. RESULTS: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. DISCUSSION: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.

FOXO1-regulated lncRNA CYP1B1-AS1 suppresses breast cancer cell proliferation by inhibiting neddylation.

PURPOSE: Overactivated neddylation is considered to be a common event in cancer. Long non-coding RNAs (lncRNAs) can regulate cancer development by mediating post-translational modifications. However, the role of lncRNA in neddylation modification remains unclear. METHODS: LncRNA cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in breast cancer tissues was evaluated by RT-PCR and TCGA BRCA data. Gain and loss of function experiments were performed to explore the role of CYP1B1-AS1 in breast cancer cell proliferation and apoptosis in vitro and in vivo. Luciferase assay, CHIP-qPCR assay, transcriptome sequencing, RNA-pulldown assay, mass spectrometry, RIP-PCR and Western blot were used to investigate the regulatory factors of CYP1B1-AS1 expression and the molecular mechanism of CYP1B1-AS1 involved in neddylation modification. RESULTS: We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with prognosis. In vivo and in vitro functional experiments confirmed that CYP1B1-AS1 inhibited cell proliferation and induced apoptosis. Mechanistically, CYP1B1-AS1 was regulated by the transcription factor, forkhead box O1 (FOXO1), and could be upregulated by inhibiting the PI3K/FOXO1 pathway. Moreover, CYP1B1-AS1 bound directly to NEDD8 activating enzyme E1 subunit 1 (NAE1) to regulate protein neddylation. CONCLUSION: This study reports for the first time that CYP1B1-AS1 inhibits protein neddylation to affect breast cancer cell proliferation, which provides a new strategy for the treatment of breast cancer by lncRNA targeting neddylation modification.

Enlargement of opisthenar microcirculatory area predicts impaired heart function in severe acute coronary syndrome patients.

BACKGROUND: Impaired microcirculation in acute coronary syndrome (ACS) patients manifests inadequate recovery and adverse clinical outcome. Here, we analyzed correlations between peripheral microcirculation and heart function in ACS patients. METHODS: Opisthenar microvessel area (OMA) were measured with optical coherence tomography angiography (OCTA), cardiac functional indexes (echocardiograph) were assessed 48-72 h after therapeutic interventions. RESULTS: Results showed that OMA normalized with heart rate (OMA-HR) were significantly greater in ACS patients with percutaneous intervention (ACS-PCI, n = 25, stenosis >80%) compared to those with pharmacological intervention (ACS-PI, n = 23, stenosis <50%, p = .02). Ejection fraction (EF) and fractional shortening (FS), which were not different between two groups, showed negative correlations with OMA-HR in ACS-PCI (EF: r = -0.512, p = .009; FS: r = -0.594, p = .002). Cardiac output (CO) inversely correlated with OMA-HR in both groups (r = -0.697, p < .0001; r = -0.527, p = .01). Neutrophil to lymphocyte ratio (NLR) on admission was greater in ACS-PCI group. NLR, which was negatively associated with EF or FS, was positively associated with OMA-HR in all patients. The area under the curve (AUC) for OMA-HR was 0.683 (specificity 0.696 and sensitivity 0.72, p = .02). OMA-HR at >376.5 µm2 predicts reduced FS and CO (p = .002, p = .005, respectively). Summary OMA-HR predicts inadequate recovery of the heart in severe ACS patients post-PCI.

Distinguishing glutamate and glutamine in in vivo 1 H MRS based on nuclear spin singlet order filtering.

PURPOSE: The signals of glutamate (Glu) and glutamine (Gln) are often significantly overlapped in routine 1 H-MR spectra of human brain in vivo. Selectively probing the signals of Glu and Gln in vivo is very important for the study of the metabolisms in which Glu and Gln are involved. METHODS: The Glu-/Gln- targeted pulse sequences are developed to selectively probe the signals of Glu and Gln. The core part of the Glu-/Gln- targeted pulse sequences lies on the preparation of the nuclear spin singlet orders (SSOs) of the five-spin systems of Glu and Gln. The optimal control method is used to prepare the SSOs of Glu and Gln with high efficiency. RESULTS: The Glu-/Gln- targeted pulse sequences have been applied on phantoms to selectively probe the signals of Glu and Gln. Moreover, in the in vivo experiments, the signals of Glu and Gln in human brains of healthy subjects have been successfully probed separately. CONCLUSION: The developed Glu-/Gln- targeted pulse sequences can be used to distinguish the 1 H-MR signals of Glu and Gln in human brains in vivo. The optimal control method provides an effective way to prepare the SSO of a specific spin system with high efficiency and in turn selectively probe the signals of a targeted molecule.

Effective linewidth compression of a single-longitudinal-mode fiber laser with randomly distributed high scattering centers in the fiber induced by femtosecond laser pulses.

Femtosecond lasers can be used to create many functional devices in silica optical fibers with high designability. In this work, a femtosecond laser-induced high scattering fiber (HSF) with randomly distributed high scattering centers is used to effectively compress the linewidth of a fiber laser for the first time. A dual-wavelength, single-longitudinal-mode (SLM) erbium-doped fiber laser (EDFL) is constructed for the demonstration, which is capable of switching among two single-wavelength operations and one dual-wavelength operation. We find that the delayed self-heterodyne beating linewidth of the laser can be reduced from >1 kHz to <150 Hz when the length of the HSF in the laser cavity increases from 0 m to 20 m. We also find that the intrinsic Lorentzian linewidth of the laser can be compressed to several Hz using the HSF. The efficiency and effectiveness of linewidth reduction are also validated for the case that the laser operates in simultaneous dual-wavelength lasing mode. In addition to the linewidth compression, the EDFL shows outstanding overall performance after the HSF is incorporated. In particular, the optical spectrum and SLM lasing state are stable over long periods of time. The relative intensity noise is as low as <-150 dB/Hz@>3 MHz, which is very close to the shot noise limit. The optical signal-to-noise ratios of >85 dB for single-wavelength operation and >83 dB for dual-wavelength operation are unprecedented over numerous SLM fiber lasers reported previously. This novel method for laser linewidth reduction is applicable across gain-medium-type fiber lasers, which enables low-cost, high-performance, ultra-narrow linewidth fiber laser sources for many applications.

Long-period D-fiber grating based robust and efficient bidirectional coupler for whispering gallery mode excitation.

A robust and efficient bidirectional coupler for whispering gallery mode (WGM) excitation based on a long-period grating (LPG) inscribed in D-fiber is theoretically and experimentally demonstrated. The LPG coupling the fundamental core mode to the forward propagating cladding modes according to the phase-matching condition not only enhances the evanescent field of the fiber but also selectively excites the WGM in a wavelength band of interest. Experimental results show that a maximum resonance contrast as high as 10.5 dB and a quality factor (Q-factor) on the order of 104 can be achieved in an LPG coupled spherical silica WGM resonator with a diameter of 242 µm, where the LPG with a pitch of 680 µm is fabricated by arc-discharging in a side-polished D-fiber with a maximum polishing depth of 56 µm. In addition to high robustness and efficiency, such an LPG-based WGM coupler also demonstrates bidirectionality, i.e., it is independent of the injection direction of the input light, which provides a reliable and flexible fiber coupler for the WGM resonator based practical applications.

Rayleigh backscattering-based simultaneous linewidth narrowing of a multi-wavelength DFB laser array with an arbitrary wavelength spacing.

Simultaneous linewidth narrowing of a multi-wavelength laser array with an arbitrary wavelength spacing based on Rayleigh backscattering is experimentally demonstrated. Rayleigh backscattering from a single 30 m high numerical aperture fiber (HNAF) is employed to simultaneously narrow the linewidths of a DFB laser array consisting of four distributed feedback (DFB) semiconductor lasers with different wavelengths. Experimental results show that the instantaneous linewidths of the four DFB lasers can be simultaneously narrowed from megahertz to kilohertz no matter whether the wavelength spacing between the lasers is equally spaced or not, verifying the self-adaptivity of Rayleigh backscattering on laser linewidth narrowing. The method demonstrated here is also applicable for on-chip waveguides without wavelength dependence, providing a more compact narrow linewidth laser array for the wavelength-multiplexing division system and other promising applications.

Protecting human amnion and chorion matrices during processing: Performance enhancement in a diabetic mouse model and human co-culture system.

Recent evidence suggests that protecting human amnion and chorion matrices (HACM) during processing enhances the performance of HACM for wound repair and tissue regeneration. We utilised a diabetic (db/db) delayed wound healing mouse model. Treatment of db/db full-thickness excisional wounds with HACM, processed with a polyampholyte preservative accentuated the proliferative phase of wound healing that decreased the time necessary to heal wounds. Polyampholyte protection improved the preservation of growth factors and cytokines during room temperature storage following E-beam sterilisation and improved its function in wound healing applications. Our findings indicate protected HACM tissue up-regulated MIP2, NF-kB, TNF-α, KI-67, and Arg1 (0.6-fold to 1.5-fold) but those changes were not statistically significant. Immunofluorescent assessment identifying cell activity illustrated an induction of the proliferative phase of wound healing and a switch from an inflammatory macrophage phenotype (M1) to a pro-regenerative macrophage phenotype (M2a). Genomic profiling of 282 genes was performed using Nanostring from co-cultures of human macrophages and fibroblasts. The polyampholyte + HACM-treated group, compared with the HACM or polyampholyte alone groups, had a statistically significant up-regulation (32-368 fold) of 12 genes primarily involved in macrophage plasticity including CLC7, CD209, CD36, HSD11B1, ICAM1, IL1RN, IL3RA, ITGAX, LSP1, and PLXDC2 (adj. p-value < 0.05). The polyampholyte alone group demonstrated statistically significant down-regulation of four genes ADRA2, COL7A1, CSF3, and PTGS2 (adj. p < 0.05). The HACM alone group up-regulated four genes ATG14, CXCL11, DNMT3A, and THBD, but the results were not statistically significant. Biomechanical measurements indicated that wounds treated with polyampholyte-protected HACM had more tensile integrity compared with wounds treated with HACM alone. These findings indicate that better protection of HACM during processing stabilises the HACM matrix, which may lead to improved wound healing outcomes.

Application of problem-based self-designed experiments in physiology laboratory teaching.

A physiology laboratory course plays an important role in improving the scientific abilities of medical students. This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. The study subjects were divided into two groups, i.e., students enrolled in 2019 were assigned to the traditional course control group (n = 146) and students enrolled in 2021 were assigned to the improved course test group (n = 128). Students in the test group were required to conduct self-designed experiments based on the questions for each experimental theme, in addition to completing the specified experimental items. At the end of the course, the differences in academic achievements between the two groups were compared. The results showed that compared to the control group, the students in the test group spent less time finishing the specified experimental items (P < 0.05). More students in the test group obtained good results in the operation assessment for the specified experiments (P < 0.05), and a significant increase in the number of winners in discipline-wise competitions, participants in scientific research projects, and academic publications was observed in the test group. Most of the students in the test group agreed that the self-designed experiment promoted their scientific thinking, helped them better understand theoretical knowledge, and improved their hands-on operation and team cooperation abilities. Our research showed that our teaching reform promoted students' self-directed learning and problem-solving abilities, stimulated their enthusiasm for scientific research, and was conducive to the cultivation of innovative medical talents.NEW & NOTEWORTHY This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. Students in the test group were required to conduct self-designed experiments based on questions for each experimental theme, in addition to completing the specified experimental items. The results showed that the teaching reform promoted the students' self-directed learning and problem-solving ability, stimulated their enthusiasm for scientific research, and was conducive to cultivating innovative medical talents.

Conductive Polymer-Based Interactive Shelving System for Real-Time Inventory Management.

Stockouts constitute a major challenge in the retail industry. Stockouts are caused by errors related to manual stockkeeping and by the misplacement of items on shelves. Such errors account for up to 4% of lost sales. Real-time inventory management systems for misplaced items or missing stock detection in retail stores are limited. Accordingly, a conductive polymer-based interactive shelving system for real-time inventory management is developed. The system comprises an 80 × 48 sensor array fabricated by screen-printing a piezoresistive carbon-based conductive polymer layer onto gold interdigitated electrodes deposited on a flexible substrate. Each sensing pixel has dimensions of 5 mm × 5 mm and a sensing area of 4 mm × 4 mm. The sensor mat can detect the shape and weight features of stockkeeping units (SKUs), which can then be analyzed by a TensorFlow model for SKU identification. The developed system is characterized for functional resistance range, uniformity, repeatability, and durability. The accuracy of SKU identification achieved using shape features only and the accuracy of SKU identification achieved using both shape and weight features is 95% and 99.2%, respectively. The key novelty of the work is the development of a deep learning-embedded interactive smart shelving system for retail inventory management by using the shape and weight features of SKU. Also, the developed system helps to detect the SKU if they are stacked one over the other. Furthermore, multiple sensor mats implemented on various shelves in a retail store can be modularized and integrated for monitoring under the control of a single PC. Accordingly, the proposed retail inventory tracking system can facilitate the development of automated "humanless" shops.

Diagnosis, treatment and genetic analysis of a child with infantile neuroaxonal dystrophy.

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disease characterized by early hypotonia, and rapid progression to psychomotor development regression, pyramidal tract positivity, and spastic quadriplegia. In this report, we describe a Chinese patient with INAD who presented with hypotonia, delayed motor and language development, and subsequently improved with rehabilitation training. Genetic testing revealed that the patient had compound heterozygous PLA2G6 gene variants, with the heterozygous c.496dupG (p.Glu166fsTer32) variant inherited from her father and the heterozygous c.2189T>G (p.Met730Arg) variant inherited from her mother. The p.Met730Arg was a novel variant. The protein structure predicts that the structural stability of the mutant protein may change, and the in vivo experimental results show that the expression of the mutant protein decrease. This study enriches the PLA2G6 gene mutation spectrum, and improves the clinicians' diagnostic awareness of INAD.