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Biomedical subjects

Hao Shi

Publications and source records attributed to Hao Shi.

13 recordsLinked to original sources

Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article↗

Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.

The microenvironment in solid tumors represents an immunosuppressive therapeutic barrier to CAR T cell therapy, and it is currently unknown whether it can be reshaped by the deletion of negative regulators in CAR T cells. To address this knowledge gap, we evaluated the intrinsic and extrinsic effects of deleting the negative regulator Regnase-1 (Reg-1) in B7-H3-CAR T cells for the immunotherapy of osteosarcoma. Reg-1 knockout (KO) improved the antitumor activity of human and murine B7-H3-CAR T cells in vivo. In immune-competent models, Reg-1 KO also endowed murine B7-H3-CAR T cells with the ability to create a proinflammatory landscape characterized by an influx of interferon gamma (IFN-γ)-producing endogenous T cells and natural killer (NK) cells and a reduction of inhibitory myeloid cells, including M2-like macrophages. Thus, deleting Reg-1 has cell- and non-cell-autonomous benefits, nominating Reg-1 KO B7-H3-CAR T cells as a promising cell product for early-phase clinical testing in patients with solid tumors.

Animals↗

Spatially resolved multi-omics analysis of indigenous Bacillus-fortified high-temperature Daqu.

Layer-dependent patterns associated with indigenous Bacillus fortification on high-temperature Daqu remain unclear. Here, six indigenous functional Bacillus strains were combined to fortify Daqu at three inoculation levels (QH4, QH5, QH6), with non-fortified as the control (CK). Upper, middle, and lower shelf-layer samples were profiled by physicochemical measurements, volatilomics, organic acid analysis, untargeted metabolomics, 16S/ITS amplicon sequencing, and metagenomics. PERMANOVA showed significant effects of treatment, spatial layer, and their interaction on physicochemical, volatile, bacterial, and fungal profiles (P = 0.001). Among the three inoculation levels, QH5 showed the most balanced performance: QH5_M exhibited the highest observed mean peak temperature (63.3 °C; +4.5 °C relative to CK_M), and its group-mean temperature remained ≥ 60 °C for seven consecutive days. Multi-omics analyses indicated coordinated, non-linear, and layer-dependent differences associated with indigenous Bacillus fortification, with QH5_M showing the most pronounced combined thermal, pyrazine, substrate, microbial, and predicted functional profile. These findings indicate that moderate indigenous Bacillus fortification was associated with distinct layer-dependent thermal and flavor profiles and coordinated microbial, metabolic, and predicted functional differences.

Bacillus↗

KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.

UNLABELLED: NUP98 fusion oncoproteins (FO) are a hallmark of childhood acute myeloid leukemia. NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. In this study, we show that MYST family histone acetyltransferase (HAT) complex proteins, including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1, associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of KAT6A and KAT7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with menin inhibitor treatment, and was efficacious in menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r acute myeloid leukemia. SIGNIFICANCE: KAT6A and KAT7 associate with NUP98 FOs to drive leukemogenesis. Inhibition of their HAT activity is an effective therapeutic strategy in NUP98-r leukemias, including those resistant to menin inhibition. Moreover, combined KAT6A/7 and menin inhibition is synergistic, supporting clinical translation to improve outcomes for NUP98 FO-driven leukemias.

Humans↗

Development and validation of a deep learning model based on cascade mask regional convolutional neural network to noninvasively and accurately identify human round spermatids.

INTRODUCTION: The difficulty of identifying human round spermatids (hRSs) has impeded applications of the human round spermatid injection (ROSI) technique. RSs can be accurately screened through flow cytometric analysis utilizing the Hoechst fluorescence profile reflecting DNA, but this method is not suitable for isolating hRSs due to the toxicity associated with Hoechst staining. OBJECTIVE: To evaluate the capacity of a deep learning model grounded in a cascade mask region-based convolutional neural network (R-CNN) for the noninvasive and accurate identification of hRSs. METHODS: In this study, we presented the development and validation of a deep learning model for identifying hRSs through the analysis of 3457 optical light microscope images of sorted hRSs obtained via flow cytometric analysis. The model's accuracy and specificity were evaluated by calculating the mean average precision (mAP). Furthermore, a double-blind experiment was conducted to access the reliability of the proposed model in accurately identifying hRSs. It detected the expression of protamine (PRM1) and/or peanut lectin (PNA), which are established markers for RSs. RESULTS: Our deep learning-based model demonstrated a high precision, achieving a mAP of over 0.80 for isolating hRSs in test datasets. The expression of PRM1 and/or PNA was observed in all cells noninvasively selected by our AI model during an independent double-blind test. This phenomenon confirmed the accuracy and effectiveness of the proposed model. The model's capability for noninvasive and accurate isolation of hRSs among spermatogenic cells highlighted its robustness and generalizability for clinical applications. CONCLUSION: The deep learning AI model based on a cascade R-CNN has the ability to accurately identify hRSs among spermatogenic cells. The application of this noninvasive method, which requires no additional procedures in clinical practice, is able to facilitate the widespread implementation of ROSI technique. Therefore, it can provide patients with spermatogenic arrest the opportunity to become biological fathers.

Humans↗

Fetal central nervous system anomalies: comparison of magnetic resonance imaging and ultrasonography for diagnosis.

BACKGROUND: Evaluation of fetal central nervous system (CNS) agenesis by ultrasonography (US) is frequently limited, but magnetic resonance imaging (MRI) has its own advantages and is gaining popularity in displaying suspected fetal anomalies. The purpose of this study was to explore the value of MRI in detecting fetal CNS agenesis. METHODS: Thirty-four women (aged from 22 to 35 years, average 27 years) with complicated pregnancies (16 - 39 weeks of gestation, average 30 weeks) were examined with a 1.5 T superconductive MR unit within 24 hours after ultrasonography. Half-Fourier acquisition single-shot turbo spin-echo (HASTE) T(2)-weighted imaging (T(2)WI) sequence were performed in all patients, and fast low angle shot (FLASH) T(1)-weighted imaging (T(1)WI) sequence were applied sequentially in seven of them. Comparison of the results was made between the MRI and US findings as well as autopsy or postnatal follow-up MRI findings. RESULTS: The gyrus, sulcus, corpus callosum, thalamus, cerebellum, brainstem, and spinal cord of fetus were shown more clearly on T(2)-weighted MR images than on T(1)-weighted MR images. MRI corrected the diagnosis of US in 10 cases (10/34, 29.41%) and the diagnosis was missed only in 1 case (1/34, 2.94%). CONCLUSION: MRI has advantages to US in detecting fetal CNS anomalies and is a supplement to US in complicated pregnancies.

Adult↗

[Clinical significance of CD117/CD34 co-expression in adult patients with acute leukemia].

BACKGROUND & OBJECTIVE: CD117 is highly expressed in acute non-lymphoblastic leukemia (ANLL), and may be used as an immunologic marker of myeloid leukemia. However CD117 is also expressed in some acute lymphoblastic leukemia (ALL) cases. CD34 is highly expressed in both ALL and ANLL. This study was to explore the clinical significance of the co-expression of CD117/CD34 in adult patients with acute leukemia. METHODS: Flow cytometry (FCM) was used to detect the positive rate and expression level of CD117 in bone marrow mononuclear cells (BMMNCs) of 92 patients with ALL and 81 patients with ANLL. The difference between the rates of CD117 expression and CD117/CD34 co-expression in ALL patients and the difference of CD117/CD34 co-expression between ALL and ANLL patients were compared. Twenty healthy individuals were set as controls. RESULTS: The positive rate of CD117 was significantly lower in ALL than in ANLL (15.2% vs. 71.6%, P<0.001). The co-expression rate of CD117/CD34 was significantly lower in ALL than in ANLL (5.4% vs. 55.5%, P<0.001). The positive rate of CD117 was significantly higher than co-expression rate of CD117/CD34 in ALL (15.2% vs. 5.4%, P=0.029). CONCLUSIONS: CD117 may be used as an immunologic marker for acute myeloid leukemia. The co-expression rate of CD117/CD34 is lower than that of CD117 alone in ALL, and therefore, this may be used in the exclusive diagnosis of ALL.

Adolescent↗

A new serratane-type triterpene from Lycopodium phlegmaria.

A new serratane-type triterpene, lycophlegmarin (1), has been isolated from Lycopodium phlegmaria L. Four known related triterpenoids were also found from the title plant. The structure of the new compound was elucidated on the basis of detailed spectroscopic analysis and chemical method. Lycophlegmarin exhibited modest growth-inhibitory activity in vitro against human hepatoma cells BEL 7402.

Antineoplastic Agents, Phytogenic↗

Detection of COL4A5 gene mutations in Chinese patients with Alport's syndrome.

BACKGROUND: Mutations in the COL4A5 gene, encoding the alpha 5 chain of type IV collagen, are responsible for X-linked Alport's syndrome (XLAS), a progressive nephropathy characterized by glomerular basement membrane abnormalities and usually associated with progressive hearing loss and ocular lesions. METHODS: In this study, we analysed all 51 exons of the COL4A5 gene in 20 Chinese patients with XLAS or suspected XLAS from 16 families by using polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) DNA sequencing. RESULTS: Five gene mutations identified in five families were considered to be pathogenic, including one nonsense mutation in exon 1 (266C-->T, Gln22Term), two missense mutations in exons 31 (2757G-->T, Gly852Val) and 43 (4142C-->T, Pro1314Ser), and two splice site mutations in introns 1 and 25 just next to the 3' end of their respective exons (283+1G-->T, 2150+1G-->T). According to GenBank, these five mutations have not been reported previously. All male patients have typical clinical manifestations and pathological findings that closely correspond to the effects of the mutations. Furthermore, seven gene polymorphisms were detected in introns 18 and 10 and exons 20, 27, 29, 39 and 46. Only the substitution in intron 18 (1234+25G-->A) had a gene frequency significantly higher in patients than in normal individuals. CONCLUSION: Our study demonstrated the critical role of COL4A5 gene mutations in the pathogenesis of XLAS. The linkage of the polymorphism to AS is still unknown.

China↗

Isomeric eremophilane lactones from Senecio tsoongianus.

From the whole plant of Senecio tsoongianus, two pairs of epimers, tsoongianolides A (1) and B (2), and tsoongianolides C (3) and D (4), and two new sesquiterpene lactones, tsoongianolides E (5) and F (6), all of which possess the eremophilane skeleton, were isolated. Two known eremophilane dimers (7) and (8) were also obtained from this species. Their absolute structures were elucidated by 1D- and 2D-NMR techniques and by X-ray diffraction studies, along with chemical evidence.

Isomerism↗

The natural diterpenoid kamebanin.

Kamebanin, alternatively called rel-(-)-(1R,4R,8S,9R,10S,13S,16R)-2,8,16-trihydroxy-5,5,9-trimethyl-14-methylenetetracyclo[11.2.1.0(1,10).0(4,9)]hexadecan-15-one, C(20)H(30)O(4), is a natural diterpenoid which has cytotoxic and antibacterial activity. The molecule is composed of three six-membered rings, which all adopt chair conformations, and one five-membered ring, which adopts an envelope conformation. The conjugated alpha-methylenecyclopentanone ring is the active part in the molecule due to the ring strain. All three hydroxy groups serve as hydrogen-bond donors and acceptors, forming a continuous two-dimensional network.

Journal Article↗

Macrocalyxin I.

The title compound, 2-[1,2,3,4,4a,4b,5,6,7,8,8a,9-dodecahydro-7-hydroxy-4b,8,8-trimethylphenanthren-2-yl]propenoic acid, C20H30O3, is a naturally occurring diterpenoid which was isolated from Rabdosia macrocalyx. The hydroxy and carboxy groups, which are located at the two ends of the molecule, both serve as simultaneous hydrogen-bond donors and acceptors. Two intermolecular O-H...O hydrogen bonds are present and link each molecule to four neighbours, thus forming an extensive hydrogen-bond network within the crystal.

Crystallography, X-Ray↗