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Biomedical subjects

Bin Fang

Publications and source records attributed to Bin Fang.

At least 19 recordsLinked to original sources
PubMed2026

Integrative proteomics reveals MSH6 to modulate PARP inhibitor sensitivity in BRCA1/2-proficient ovarian cancer.

Ovarian cancer remains a leading cause of gynecologic cancer-related deaths worldwide. Deficiencies in BRCA1/2 are well-established biomarkers that predict sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). However, emerging evidence indicates that a subset of BRCA-proficient tumors also responds to PARPi therapy, suggesting the presence of additional molecular mechanisms. We hypothesized that the composition of the PARP1 protein complex and PARylation-mediated signaling contribute to PARPi response in BRCA-proficient HGSOC. We assessed PARPi response across a panel of BRCA-proficient ovarian cancer cell lines and identified distinct sensitive and resistant groups. Chemical proteomics with rucaparib revealed different PARP1 complexes including higher enrichment of MSH6 in sensitive cells. Co-immunoprecipitation analyses further confirmed differential assembly of PARP1-MSH6-PARP2 complexes between sensitive and resistant models. To explore PARylation signaling, we performed ADP-ribosylation proteomics using clickable NAD⁺ analogs, revealing distinct PARylation profiles between sensitive and resistant cell lines. CHAF1A, a known MSH6 interactor and PARP1 substrate, showed more pronounced reduction in ADP-ribosylation in PARPi-sensitive cells. Targeting MSH6 using CRISPR or siRNA decreased PARPi sensitivity. In addition, mTOR signaling was reduced in sensitive, but increased in resistant cells, following rucaparib treatment. Notably, MSH6 knockdown led to increased CHAF1A expression regardless of rucaparib treatment. Importantly, knockdown of CHAF1A significantly impaired cell viability, especially in A2780 cells, and suppressed mTOR signaling, suggesting that CHAF1A acts downstream of MSH6 to regulate the mTOR axis. Furthermore, co-treatment with mTORC1 inhibitors enhanced the cellular effects of rucaparib in resistant cells, suggesting a therapeutic potential of targeting downstream mTOR effectors to overcome intrinsic resistance. In conclusion, this study identifies the PARP1-MSH6 interaction to modulate PARPi sensitivity via CHAF1A-mTOR signaling in BRCA-proficient ovarian cancer. By integrating chemical proteomics and ADP-ribosylation proteomics, we delineate the interplay between PARP1 complex composition and signaling dynamics, highlighting MSH6 as a critical modulator of PARPi response and potential biomarker to enhance therapeutic efficacy in BRCA-proficient HGSOC.

Humans↗
PubMed2026

RAS-GTP Inhibition Overcomes Acquired Resistance to KRASG12C Inhibitors Mediated by Oncogenic and Wild-Type RAS Activation in Non-Small Cell Lung Cancer.

UNLABELLED: Small-molecule KRASG12C(OFF) inhibitors that bind to the inactive GDP-bound state of KRAS have demonstrated efficacy in patients with KRASG12C-mutant tumors, yet responses tend to be transient because of emergence of on-treatment resistance. Recently, RAS(ON) G12C-selective inhibitors, which bind to the active GTP-bound state of RAS, were described, and elironrasib is undergoing evaluation in multiple clinical trials. In this study, we generated resistant cell lines and patient-derived xenograft models to KRASG12C(OFF) and RAS(ON) G12C-selective inhibitors and interrogated resistance mechanisms using a multiomics strategy consisting of phosphoproteomics, whole-exome sequencing, and RNA sequencing combined with functional testing using small-molecule and CRISPR screens and RAS(ON) inhibitors being evaluated in clinical trials. Two models reactivated RAS signaling, either via KRASG12C gene amplification or NRASG13R mutation, and were vulnerable to dual inhibition by RAS(ON) G12C-selective and RAS(ON) multiselective inhibitors, RMC-4998 and RMC-7977. Two models, which lacked any discernable genomic alteration, acquired resistance associated with increased receptor tyrosine kinase activity and downstream persistent RAS activity and were sensitive to RAS-GTP inhibition by RMC-7977. Finally, one model displayed epithelial-mesenchymal transition, loss of RAS dependence, and acquired reliance on cell-cycle kinases and proteins associated with DNA damage response. This work highlights KRASG12C-selective inhibitor resistant states that parallel and complement clinical findings and demonstrate that a large subset could be overcome with a RAS(ON) multi-selective inhibitor as a stand-alone agent or in combination with other therapies. SIGNIFICANCE: Multi-omic characterization of resistance mechanisms to KRASG12C-selective inhibitors in non-small cell lung cancer provides insights that could inform precision medicine-based therapeutic approaches for improving the treatment of KRASG12C mutant tumors. See related article by Stern et al., p. 485.

Humans↗
PubMed2006

Simultaneous determination of uric acid and ascorbic acid at a ferrocenium-thioglycollate modified electrode.

Self-assembled monolayers (SAMS) of chemisorbed thioglycollate on a gold electrode surface have been used as a base interface for the electrostatic adsorption of ferrocenium ion. Electrochemical impedance spectra (EIS) and cyclic voltammetry (CV) were used to evaluate the electrochemical properties of the supramolecular film. The bare gold electrode failed to distinguish the oxidation peaks of ascorbic acid (AA) and uric acid (UA) in phosphate buffer solution (PBS, pH 7.0), while the ferrocenium-thioglycollate modified electrode could separate them efficiently. In differential pulse voltammetric measurements, the prepared gold electrode could separate AA and UA signals, allowing the simultaneous determination of AA and UA. Under optimal conditions and within the linear range of 1.0 x 10(-6) to 5.0 x 10(-4) M, the detection limits of AA and UA achieved were 2.0 x 10(-7) and 1.0 x 10(-7) M, respectively. The applicability of the prepared electrode was demonstrated by measuring AA and UA in human urine without any pretreatment.

Journal Article↗
PubMed2006

Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers.

A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv1.5 blockers. In in vitro studies, several compounds exhibited very good potency for blockade of Kv1.5. Compound 8i showed good selectivity for blockade of Kv1.5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ventricular ERP.

Animals↗
PubMed2006

Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition.

The molecular basis for the substrate specificity of human caspase-3 has been investigated using peptide analog inhibitors and substrates that vary at the P2, P3, and P5 positions. Crystal structures were determined of caspase-3 complexes with the substrate analogs at resolutions of 1.7 A to 2.3 A. Differences in the interactions of caspase-3 with the analogs are consistent with the Ki values of 1.3 nM, 6.5 nM, and 12.4 nM for Ac-DEVD-Cho, Ac-VDVAD-Cho and Ac-DMQD-Cho, respectively, and relative kcat/Km values of 100%, 37% and 17% for the corresponding peptide substrates. The bound peptide analogs show very similar interactions for the main-chain atoms and the conserved P1 Asp and P4 Asp, while interactions vary for P2 and P3. P2 lies in a hydrophobic S2 groove, consistent with the weaker inhibition of Ac-DMQD-Cho with polar P2 Gln. S3 is a surface hydrophilic site with favorable polar interactions with P3 Glu in Ac-DEVD-Cho. Ac-DMQD-Cho and Ac-VDVAD-Cho have hydrophobic P3 residues that are not optimal in the polar S3 site, consistent with their weaker inhibition. A hydrophobic S5 site was identified for caspase-3, where the side-chains of Phe250 and Phe252 interact with P5 Val of Ac-VDVAD-Cho, and enclose the substrate-binding site by conformational change. The kinetic importance of hydrophobic P5 residues was confirmed by more efficient hydrolysis of caspase-3 substrates Ac-VDVAD-pNA and Ac-LDVAD-pNA compared with Ac-DVAD-pNA. In contrast, caspase-7 showed less efficient hydrolysis of the substrates with P5 Val or Leu compared with Ac-DVAD-pNA. Caspase-3 and caspase-2 share similar hydrophobic S5 sites, while caspases 1, 7, 8 and 9 do not have structurally equivalent hydrophobic residues; these caspases are likely to differ in their selectivity for the P5 position of substrates. The distinct selectivity for P5 will help define the particular substrates and signaling pathways associated with each caspase.

Amino Acid Sequence↗
PubMed2006

Elastic registration for retinal images based on reconstructed vascular trees.

The vascular tree of the retina is likely the most representative and stable feature for eye fundus images in registration. Based on the reconstructed vascular tree, we propose an elastic matching algorithm to register pairs of fundus images. The identified vessels are thinned and approximated using short line segments of equal length that results a set of elements. The set of elements corresponding to one vascular tree are elastically deformed to optimally match the set of elements of another vascular tree, with the guide of an energy function to finally establish pixel relationship between both vascular trees. The mapped positions of pixels in the transformed retinal image are computed to be the sum of their original locations and corresponding displacement vectors. For the purpose of performance comparison, a weak affine model based fast chamfer matching technique is proposed and implemented. Experiment results validated the effectiveness of the elastic matching algorithm and its advantage over the weak affine model for registration of retinal fundus images.

Algorithms↗
PubMed2005

Preparation of novel mercury-doped silver nanoparticles film glassy carbon electrode and its application for electrochemical biosensor.

A novel mercury-doped silver nanoparticles film glassy carbon (Ag/MFGC) electrode was prepared in this study. Electrochemical behaviors of cysteine on the Ag/MFGC electrode were investigated by electrochemical impedance spectroscopy and cyclic voltammetry (CV). The results indicated that cysteine could be strongly adsorbed on the surface of the Ag/MFGC electrode to form a thin layer. The doped electrode could catalyze the electrode reaction process of cysteine, and the cysteine displayed a pair of well-defined and nearly reversible CV peaks at the electrode in an acetate buffer solution (pH 5.0). The Ag/MFGC electrode was used for determination of cysteine by differential pulse voltammetry. The linear range was between 4.0x10(-7) and 1.3x10(-5) mol/L, with a detection limit of 1.0x10(-7) mol/L and a signal-to-noise ratio of 3. The relative standard deviation was 2.4% for seven successive determinations of 1.0x10(-5) mol/L cysteine. The determinations of cysteine in synthetic samples and urinal samples were carried out and satisfactory results were obtained. Amperometric application of the Ag/MFGC electrode as biosensors is proposed.

Adsorption↗
PubMed2005

Identification of technology options for reducing nitrogen pollution in cropping systems of Pujiang.

This work analyses the potential role of nitrogen pollution technology of crop systems of Pujiang, County in Eastern China's Zhejiang Province, rice and vegetables are important cropping systems. We used a case study approach involving comparison of farmer practices and improved technologies. This approach allows assessing the impact of technology on pollution, is forward looking, and can yield information on the potential of on-the-shelf technology and provide opportunities for technology development. The approach particularly suits newly developed rice technologies with large potential of reducing nitrogen pollution and for future rice and vegetables technologies. The results showed that substantial reductions in nitrogen pollution are feasible for both types of crops.

Agriculture↗
PubMed2005

[Emergency bedside temporary cardiac pacing through the left subclavicular vein guided by pacemaker impulse].

OBJECTIVE: To investigate the feasibility and merits of emergency bedside temporary cardiac pacing through left subclavicular vein guided by pacemaker impulse. METHODS: The left subclavicular vein was punctured with Seldinger technique for insertion of a cannula. After setting the rate of pacemaker at 20 beat/min above the patients' spontaneous heart rate with output current of 5 mA and sensing voltage of 3 mV, the electrode was inserted through the cannula until the electrocardiograph displaying pulsed signal and pacing rhythm. RESULTS: Good pacing was achieved in 18 patients with one having poor pacing, which was improved 2 h later. The pacing was not satisfactory in two cases. No postoperative complications occurred in the 21 patients. CONCLUSION: Emergency bedside temporary cardiac pacing through the left subclavicular vein guided by pacemaker impulse is rapid and ensures high success rate and safety.

Adolescent↗
PubMed2005

[Experimental study on distraction osteogenesis for reconstruction of maxillary defects with replacement of transplant disk in goats].

PURPOSE: This study was aimed to set up a new method for reconstruction of maxillary defect with distraction osteogenesis through an animal experiment. METHODS: 11 adult goats were randomly divided into 2 groups (9 in the experimental group and 2 in the control group) in this study. 3 subgroups were set up in the experimental group based on the consolidation period. Other 2 goats were chosen as the control group. Maxillary defect was made firstly through partial maxillectomy for the experimental group. Length of the defects was from 12 to 14mm with an average of 12.7mm. A transport disc was then made through anterior Le Fort I osteotomy and it would be shifted backward for the closure of the defect. Only maxillary defect was made for the control group. Distraction was activated after a latency of 7 days at a rate of 0.4mm twice a day for 15-18 days. RESULTS: Bone defects in the maxilla were well repaired when the transport disc was distracted back to its original position. Radiology and histology demonstrated good new bone formation in the distraction gap. CONCLUSIONS: Transport distraction osteogenesis would be a reasonable method for reconstruction of maxillary defect.

Animals↗
PubMed2004

Melanin pigment formation and increased UV resistance in Bacillus thuringiensis following high temperature induction.

The pigment melanin is well known to protect against the damaging effects of UV radiation. In this study, we show that thirty-five of thirty-seven tested Bacillus thuringiensis strains possess the potential to produce melanin in the presence of L-tyrosin at elevated temperature (42 degrees C). These findings offer a method of protecting insecticidal toxins produced by B. thuringiensis from UV degredation and may therefore have important applications in the field of crop protection. Toxicity assays on Heliothis armigera suggested that the insecticidal activity of B. thuringiensis that produced melanin was significantly higher after UV irradiation than when melanin was not produced.

Animals↗
PubMed2004

[Three-dimensional reconstruction on facial soft tissue using three-dimensional grating projection technique].

PURPOSE: The purpose of this study is to establish a method to reconstruct the facial soft tissue three-dimensionally. METHODS: By ATOS three-dimensional opticalmetry, which used in industry, 3D data on facial profile of a patient with mandibular hyperplasia was achieved quickly. RESULTS: Three-dimensional data of facial profile was accurate and the images were reconstructed with verisimilitude. CONCLUSIONS: Traditional device of grating projection was modified by using two CCD cameras to obtain grating images.3D data on facial profile were achieved quickly and accurately.

Adult↗
PubMed2004

[Intensive care and treatment of severe ovarian hyperstimulation syndrome].

OBJECTIVE: To investigate the clinical manifestations, pathogenesis and treatment of severe ovarian hyperstimulation syndrome (OHSS). METHODS: The clinical data of 20 OHSS patients were analyzed retrospectively. RESULTS: Severe OHSS occurred after controlled ovarian hyperstimulation for superovulation. The major manifestations of OHSS included abdominal distension, nausea, ascites, hydrothorax, oliguria, concentrated blood, acid-base and electrolytes, disturbance, azotemia, thrombosis etc., which could be controlled by volume expansion with albumin, low-molecular-weight dextran, 6% Haes, abdominal and thoracic drainages or even early pregnancy termination. CONCLUSION: Preventive measure of OHSS is very important, and the patients must be treated timely and correctly once OHSS occurs.

Adult↗
PubMed2004

Effects of the Chinese drugs for activating blood circulation on plasma TXB2 and 6-keto-PGF1alpha contents in rabbits with glucocorticoid-induced femoral head necrosis.

In the femoral head necrosis model rabbit induced by endotoxin combined with methylprenisolone, the dynamical changes of plasma TXB2 and 6-keto-PGF1alpha contents were observed. As a result, microscopic examination showed that in the model group, bone trabeculae became fine, empty bone lacunae increased, and osteoblasts in number decreased; the ratio of TXB2 and 6-keto-PGF1alpha was out of balance, and these changes worsened gradually with the lapse of time; Compound Sheng Mai Cheng Gu Capsules could reverse femoral head necrosis, protect the vascular endothelial cells, recover the balance of TXB2 and 6-keto-PGF1alpha. It is concluded that the hormone-induced femoral head necrosis is closely related with blood stasis, and that the Chinese drugs for activating blood circulation and removing blood stasis can prevent the femoral head from development of necrosis.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

On the accurate counting of tumor cells.

Quantitative analysis of tumor cells is fundamental to pathological studies. Current practices are mostly manual, time-consuming, and tedious, yielding subjective and imprecise results. To understand the behavior of tumor cells, it is critical to have an objective way to count these cells. In addition, these counts must be reproducible and independent of the person performing the count. In this work, we propose a two-stage tumor cell identification strategy. In the first stage, potential tumor cells are segmented automatically using local adaptive thresholding and dynamic water immersion techniques. Unfortunately, due to histological noise in the images, a large number of false identifications are obtained. To improve the accuracy of the identified tumor cells, a second stage of feature rules mining is initiated. Experiment results show that image processing techniques alone are unable to give accurate results for tumor cell counting. However, with the use of features rules, we are able to achieve an identification accuracy of 94.3%.

Algorithms↗