Integrated Microfluidic-Transistor Sensing System for Multiplexed Detection of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.

Early juvenile cataract in newly diagnosed type 1 diabetic patients: a description of two cases.

OBJECTIVES: To analyze and summarize the clinical characteristics and treatment of juvenile patients with type 1 diabetes mellitus (T1DM) complicated by early cataract. CASE PRESENTATION: This retrospective study collected clinical data from 210 children and adolescents newly diagnosed with T1DM who were admitted to the Department of Pediatrics, Tongji Hospital (Wuhan) between 2015 and 2022. Among 210 patients with T1DM, early cataract developed within 3 months before diabetes onset and 12 months thereafter in 2 (0.95 %) patients. The two patients were both females, aged 13 and 9 years, respectively. In both cases, cataracts in both eyes appeared in the early stages of T1DM, showing a short course and rapid development. After intensive insulin treatment for stringent and stable blood glucose control, one patient underwent cataract extraction with significant improvement, and her visual acuity returned to normal. The other patient received intensive insulin therapy and insulin pump therapy for 8 years. Subsequently, she underwent cataract surgery after achieving stable blood glucose levels, without complete recovery of vision. CONCLUSIONS: Cataract is a rare complication in the early stages of T1DM in children and adolescents. Ophthalmic surgery is the preferred treatment for patients with diabetic cataract after achieving stable glycemic control, which may help prevent visual impairment.

High-altitude hypoxia promotes BRD4-mediated activation of the Wnt/ß-catenin pathway and disruption of intestinal barrier.

Hypobaric hypoxia, commonly experienced at elevated altitudes, presents significant physiological challenges. Our investigation is centered on the impact of the bromodomain protein 4 (BRD4) under these conditions, especially its interaction with the Wnt/ß-Catenin pathway and resultant effects on glycolytic inflammation and intestinal barrier stability. By combining transcriptome sequencing with bioinformatics, we identified BRD4's key role in hypoxia-related intestinal anomalies. Clinical parameters of altitude sickness patients, including serum BRD4 levels, inflammatory markers, and barrier integrity metrics, were scrutinized. In vitro studies using CCD 841 CoN cells depicted expression changes in BRD4, Interleukin (IL)-1ß, IL-6, and ß-Catenin. Transepithelial electrical resistance (TEER) and FD4 analyses assessed barrier resilience. Hypoxia-induced mouse models, analyzed via H&E staining and Western blot, provided insights into barrier and protein alterations. Under hypoxic conditions, marked BRD4 expression variations emerged. Elevated serum BRD4 in patients coincided with intensified Wnt signaling, inflammation, and barrier deterioration. In vitro, findings showed hypoxia-induced upregulation of BRD4 and inflammatory markers but a decline in Occludin and ZO1, affecting barrier strength-effects mitigated by BRD4 inhibition. Mouse models echoed these patterns, linking BRD4 upregulation in hypoxia to barrier perturbations. Hypobaric hypoxia-induced BRD4 upregulation disrupts the Wnt/ß-Catenin signaling, sparking glycolysis-fueled inflammation and weakening intestinal tight junctions and barrier degradation.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

The influence of rolling pressure on the changes in non-volatile compounds and sensory quality of congou black tea: The combination of metabolomics, E-tongue, and chromatic differences analyses.

Rolling represents an essential stage in congou black tea processing. However, the influence of rolling pressure on tea flavor and non-volatile compounds remains unclear. Herein, a combination of untargeted metabolomics, tea pigments quantification, E-tongue, colorimeter and sensory evaluation was used to evaluate the effect of rolling pressure on black tea quality. As the rolling pressure increased, theaflavins (TFs), thearubigins (TRs), and theabrownins (TBs) significantly elevated. The tea metabolic profiles fluctuated and 47 metabolites were identified as key differential metabolites including flavan-3-ols, flavonol/flavone glycosides, phenolic acids, amino acids. These substances altered possibly due to the variations in enzymatic oxidation of tea phenolics and amino acids. Overall, black tea with moderate rolling pressure presented higher sweetness, lower bitterness, and higher quality index (10 TFs + TRs)/TBs. The results were verified by a validation batch. This study provided new insights into the regulation of rolling pressure and a guidance for black tea processing.

Occurrence, Concentration and Toxicity of 54 Polycyclic Aromatic Hydrocarbons in Butter during Storage.

Polycyclic aromatic hydrocarbons (PAHs) are a class of highly carcinogenic compounds with a lipophilic nature. This study investigated the characterization of PAH24 contamination in twenty-one types of butter and five types of margarines using the QuEChERS pretreatment coupled with GC-QqQ-MS. Additionally, low-temperature storage experiments were conducted to explore the variations in oxidation index as well as the PAH levels. The results revealed that PAH24 concentrations in butter and margarine were 50.75-310.64 µg/kg and 47.66-118.62 µg/kg, respectively. The PAH4 level in one type of butter reached 11.24 µg/kg beyond the EU standards. Over 160 days of storage at 4 °C, acid value (AV), peroxide value (POV), and acidity significantly increased, while malondialdehyde (MDA) content and carbonyl value (CGV) fluctuated. Concentrations of PAH24 and oxidized PAHs (OPAHs) experienced a notable reduction of 29.09% and 63.85%, respectively. The slow reduction in naphthalene (NaP) indicated the dynamic nature of PAHs during storage. However, the toxic equivalency quotients (TEQs) decreased slightly from a range of 0.65-1.90 to 0.39-1.77, with no significant difference. This study contributes to the understanding of variations in PAHs during storage, which is of great significance for food safety.

Biodegradation mechanisms of polycyclic aromatic hydrocarbons: Combination of instrumental analysis and theoretical calculation.

Polycyclic aromatic hydrocarbons (PAHs) are a common class of petroleum hydrocarbons, widely encountered in both environment and industrial pollution sources. Owing to their toxicity, environmental persistence, and potential bioaccumulation properties, a mounting interest has been kindled in addressing the remediation of PAHs. Biodegradation is widely employed for the removal and remediation of PAHs due to its low cost, lack of second-contamination and ease of operation. This paper reviews the degradation efficiency of degradation and the underlying mechanisms exhibited by algae, bacteria, and fungi in remediation. Additionally, it delved into the application of modern instrumental analysis techniques and theoretical investigations in the realm of PAH degradation. Advanced instrumental analysis methods such as mass spectrometry provide a powerful tool for identifying intermediates and metabolites throughout the degradation process. Meanwhile, theoretical calculations could guide the optimization of degradation processes by revealing the reaction mechanisms and energy changes in PAH degradation. The combined use of instrumental analysis and theoretical calculations allows for a comprehensive understanding of the degradation mechanisms of PAHs and provides new insights and approaches for the development of environmental remediation technologies.

Difficult Blood Typing Caused by Rouleaux Agglutination in Patient with Acute Brain Trauma: a Case Report.

BACKGROUND: Rouleaux agglutination is a common cause of difficult blood typing, but it is rarely reported in patients with acute brain trauma. METHODS: This article describes a 69-year-old male with head injury who was admitted to the hospital. Blood typing showed type O, Rh(D) positive, but the Rh(D) control was also positive. After ruling out the possibility of the patient having abnormal autoantibodies, it was suspected that rouleaux agglutination might be the cause. Microscopic examination of the specimen revealed rouleaux agglutination, which was believed to be the cause of the false-positive Rh(D) control result. The patient's red blood cells were treated with physiological saline and retested by microcolumn gel card testing. RESULTS: The retest showed negative Rh(D) control results, indicating normal results. The patient subsequently received normal blood transfusion. CONCLUSIONS: Laboratory personnel should be aware of the possibility of difficult blood typing caused by rouleaux agglutination in various diseases, especially in relatively rare traumatic diseases.

In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

Pneumonia During the COVID-19 Pandemic in Hubei Province, China: a Case Report of Mucormycosis.

BACKGROUND: Mucor infection cannot be ignored in patients with pulmonary shadowing with cavitation. This paper reports a case of mucormycosis during the COVID-19 pandemic in Hubei Province, China. METHODS: An anesthesiology doctor was initially diagnosed as COVID-19 due to changes in lung imaging. After anti-infective, anti-viral, and symptomatic supportive treatment, some of symptoms were relieved. But some symptoms -'chest pain and discomfort', accompanied by chest sulking and short breath after activities, did not ease. At last, Lichtheimia ramose was detected later by metagenomic next generation sequencing (mNGS) in the bronchoalveolar lavage fluid (BALF). RESULTS: After adjusting amphotericin B for anti-infective treatment, the patient's infection lesions were shrunk and the symptoms were significantly relieved. CONCLUSIONS: The diagnosis of invasive fungal infections is very difficult, and mNGS can make an accurate pathogenic diagnosis of invasive fungal diseases for the clinic and provide a basis for clinical treatment.

Development of a new cellular immunological detection method for tuberculosis based on HupB protein induced IL-6 release test.

Objective: As a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein. Methods: HupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings. Results: Cytokine's screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis. Conclusion: This study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.

Determination, exposure and risk assessment of PAHs in natural vitamin E isolated from vegetable oil industry.

Natural vitamin E, which is mainly extracted from vegetable oil deodoriser distillate (VODD), is likely contaminated by carcinogenic polycyclic aromatic hydrocarbons (PAHs). A total of 26 commercial vitamin E products from six countries were investigated for 16 EPA PAHs using QuEChERS combined with gas chromatography triple quadrupole mass spectrometry (GC-QQQ-MS). The concentrations of total PAHs in the samples ranged from 46.5 µg kg-1 to 215 µg kg-1, while the concentrations of PAH4 (BaA, Chr, BbF and BaP) ranged from 4.43 µg kg-1 to 20.1 µg kg-1. Risk assessment indicates that maximum intake of PAHs is 0.2 mg day-1, which is less than the LD50 and no observed adverse effect levels (NOAEL) of PAHs. However, chronic carcinogenicity of PAHs needs to be considered. The results suggested that PAH concentrations as well as toxicity equivalent should be considered as important indicator of risk of vitamin E products.

Concentrations, influencing factors, risk assessment methods, health hazards and analyses of polycyclic aromatic hydrocarbons in dairies: a review.

The occurrence of polycyclic aromatic hydrocarbons (PAHs) in dairies has been widely reported. Consumers may be overly exposed to PAHs through dairies causing health risks. Hazards can be reduced by controlling influencing factors in the full-chain of dairy production. This review briefly introduces research trends and analytical methods concerning PAHs in dairies. Additionally, this review discusses influencing factors of PAH concentrations in various dairies to avoid PAHs' formation and accumulation during manufacture. Relevant regulations are referred to and the reported risk assessment methods are summarized. Furthermore, indicators of health risks including TEQBaP, the number and the rate of over-standard are calculated based on PAH concentrations. Through analyses, we find PAH and BaP contamination in dairies are complex problems depending on environment, processing and storage. There was a significant correlation between fat contents and PAH concentrations. Results of infant formula in certain research were worrying and those of smoked cheeses are remarkably high indicating the dangerous smoking process. It is significant to monitor PAHs and calculate TEQBaP from meadows to feeders. Moreover, the existing regulations are insufficient and need strengthening. The data and discussions in this review contribute to worldwide Big Data, further scientific investigation and regulations for PAHs in dairies.

Rapid Determination of Oxygenated and Parent Polycyclic Aromatic Hydrocarbons in Milk Using Supercritical Fluid Chromatography-Mass Spectrometry.

Liquid milks are consumed worldwide in large amounts, especially by adolescents and infants. Thus, their health quality linked with polycyclic aromatic hydrocarbon (PAH) contamination has attracted great concern. This study developed a rapid and sensitive supercritical fluid chromatography (SFC)-MS method to determine two typical oxygenated PAHs (OPAHs) and EU 15+1PAHs except for benzo[k]fluoranthene (BkF) in three types of liquid milks: 10 ultra heat treated (UHT) milks, 8 pasteurized milks, and 4 extended-shelf-life pasteurized milks. The instrumental analysis was 15 min with a recovery of 67.66-118.46%, a precision of 1.45-14.68%, detection limits of 0.04-0.24 µg/kg, and quantification limits of 0.13-0.78 µg/kg. We found 9-fluorenone, anthraquinone, 15 EU priority PAHs, and benzo[a]pyrene toxic equivalent quantity (BaPeq) in the 22 milk samples, which were 0.32-1.56 µg/kg, 0.40-1.74 µg/kg, 0.57-8.48 µg/kg, and 0.01-17.42 µg/kg, respectively. The UHT milks and whole fat milks showed higher PAH concentrations than other investigated samples, where the maximum levels of BaP and PAH4 were 0.77 and 3.61 µg/kg, respectively. PAH4 dominantly contributed to the PAH8 concentration and was detected in 73% and 32% of samples at more than 1.0 and 2.0 µg/kg, respectively. The results suggest that raw milks should be strictly monitored and extensively investigated for PAH4 and BaP concentrations for future risk assessment, limitations, and dietary guidance.

Adsorption kinetics of 20 glucocorticoids at environmentally relevant concentrations in wastewater by powdered activated carbons and development of surrogate models.

Glucocorticoids (GCs) are widely used in the treatment of the coronavirus disease of 2019 (COVID-19), and the toxicity of GCs to aquatic organisms has aroused widespread concern. Powdered activated carbon (PAC) has proven effective in removing various trace organic pollutants. In this study, the adsorption behaviors of 20 typical GCs onto PACs were investigated at environmentally relevant concentrations (ng/L) in real wastewater, using four commercially available PACs (HDB, WPH, 20BF, PWA). The results showed that PAC adsorption was feasible for GC removal at ng/L concentrations. After adsorption for 60 min, the GC removal efficiencies obtained by HDB, WPH, 20BF, and PWA were 90-98 %, 89-97 %, 84-96 %, and 71-90 %, respectively. The adsorption processes of 20 GCs on PACs were well fitted by the pseudo-second-order kinetics model (with R 2 >0.98). Among the four PACs, HDB achieved the highest rates because of the electrostatic attraction between HDB (positively charged) and the complex of GCs and natural organic matter (GC-NOM, negatively charged). Among the 20 GCs, compounds with substitutions of halogen atoms or five-membered rings at C-17 achieved higher adsorption rates because of the enhanced formation of hydrogen bonds and a resulting increase in electron density. In addition, surrogate models with total fluorescence (TF) and ultraviolet absorbance at 254 nm (UV254) were developed to monitor the attenuation trend of GCs during adsorption processes. Compared with the UV254 model, the TF model showed better sensitivity to GC monitoring, which could greatly simplify the water quality monitoring process and facilitate online monitoring of GCs in water.

Oxygenated polycyclic aromatic hydrocarbons in food: toxicity, occurrence and potential sources.

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are polycyclic aromatic hydrocarbons (PAHs) functionalized with at least one carbonyl group and are generally thought to be more toxic than PAHs. In this review, the physical-chemical properties, toxicity, occurrence, and potential sources of OPAHs in food were comprehensively discussed. The toxicities of 1,2-naphthoquinone, 1,4-naphthoquinone, 6H-benzo[cd]pyren-6-one, benzo[a]anthracene-7,12-quinone and 9,10-phenanthrenequinone were prominent among the OPAHs. Both 1,4-naphthoquinone and 1,2-naphthoquinone exhibited strong genotoxicity, cytotoxicity, and developmental toxicity. 6H-benzo[cd]pyren-6-one and benzo[a]anthracene-7,12-quinone showed high genotoxicity and cardiovascular toxicity. Although 9,10-phenanthrenequinone showed no genotoxicity, it exhibited almost the strongest cytotoxicity. For the majority of foods, the concentrations of OPAHs and PAHs were on the same order of magnitude. OPAHs tend to be positively correlated with the corresponding PAH concentrations in oil and fried food, while for barbequed food and seafood, no obvious correlation was found. In addition, 9-fluorenone, 9,10-anthraquinone, benzanthrone and 1,2-acenaphthenequinone had high abundance in food. Environmental pollution, food composition, storage conditions, heating methods, and other treatments influence the accumulation of OPAHs in food. Furthermore, oxygen and water played an important role in the transformation from PAHs to OPAHs. In short, this review guides the evaluation and further reduction of OPAH-related health risks in food.

Decreased circulating levels of free triiodothyronine in Sepsis children and correlation analysis.

BACKGROUND: Intensive physical stress in sepsis can induce the disorder of endocrine function and impact the clinical course and prognosis. Low T3 syndrome has been verified to be the predictive indicator of poor prognosis in several researches. Reports on the influence factors of thyroid hormonal levels in children with severe sepsis are rare. We aim to investigate the thyroid hormonal variations in the course of sepsis and analyze that how to be affected by clinical data and inflammatory biomarkers. METHODS: In the case-control study, 184 children with sepsis and 323 controls were included in Tongji Hospital, Wuhan, China, in 2019. Data on clinical and inflammatory parameters were collected from all participants. Circulating FT3(Free Triiodothyronine) levels were measured by Electrochemiluminescence immunoassay. Finally, we investigated the correlation between FT3 and related variables with linear regression analysis. RESULTS: Serum FT3 was lower in the sepsis group than in control group(2.59 + 1.17 vs 2.83 + 1.01 pg/mL, p < 0.05). Significant moderately negative correlations(|r| > 0.3) of FT3 levels with ferritin, PCT, duration of symptoms, SOFA score, and mortality were revealed. Moreover, we observed that FT3 had the positive correlation with albumin, as well as white blood cell count. CONCLUSIONS: Concentrations of serum FT3 are dramatically declined in sepsis children than in control children. Our results demonstrate that recognizing the potential abnormality of thyroid hormones in sepsis patients and examine timely through abnormal common clinical data and inflammatory biomarkers is a fine option.

CRISPR-Cas13 technology portfolio and alliance with other genetic tools.

The exploitation of CRISPR-Cas systems especially CRISPR-Cas9 has led to radical advances in genome editing, gene activation, gene repression, protein imaging, and beyond. However, these applications are limited to targeting of DNA rather than RNA. CRISPR-Cas13 is the first reported CRISPR system targeting RNA and thus opens a new avenue for transcription regulation. While a plethora of reviews have systematically documented CRISPR-Cas9 toolbox, this review focuses on CRISPR-Cas13 family, covering aspects of classification, structures, response to foreign invaders, and genetic toolbox. In particular, we compare CRISPR-Cas13 with other RNA regulation tools such as RNA interference and antisense RNA technology to ponder the possibility of combining them to engineer hierarchical regulatory networks fulfilling novel functions. Lastly, we summarize the wide applications of CRISPR-Cas13 toolbox and the status quo that requires amelioration. Overall, this review charts a landscape of CRISPR-Cas13 technology portfolio to provide insights for gene regulation, metabolic engineering and synthetic biology.

Case Report: Glycogen Storage Disease Type Ia in a Chinese Child Treated With Growth Hormone.

Background: Glycogen storage disease type Ia is a rare metabolic disorder that leads to excessive glycogen and fat accumulation in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay, and growth retardation. Here, we report on a patient with glycogen storage disease type Ia treated with growth hormone. Case Presentation: A 10-year-old boy had growth retardation for 6 years, and was admitted to clarify the cause of his short stature. We found that his bone age was 5.5 years, significantly lower than his physical age, while his serum IGF-1 and IGFBP-3 were 23.30 and 1620.0 ng/mL, respectively, both lower than normal. His medical history revealed that he had suffered from steatohepatitis, hyperlipidemia, and hypoglycemia since he was 11 months of age. Whole exome sequencing (WES) showed compound heterozygous mutations in exons 2 and 5 of the glucose-6-phosphatase (G6PC) gene on chromosome 17: c.G248A (p.R83H) and c.G648T (p.L216L). The patient was finally diagnosed with GSD Ia. After growth hormone (GH) treatment and corn starch therapy for 14 months, his height significantly increased (by 13 cm). The serum IGF-1 level increased to the normal range but his lipid levels and liver function did not significantly increase. Conclusion: We describe a young patient with a compound heterozygous G6PC variant in a Chinese family; his height increased significantly after growth hormone and corn starch interventions. This case emphasizes that WES is essential for early diagnosis, and that growth hormone treatment may increase the height of patients with GSD Ia safely.