Comparison of Type I Error Rates of Siegel-Tukey and Savage Tests among Non-Parametric Tests

This study aimed to examine the performance of the Siegel-Tukey and Savage tests on data sets with heterogeneous variances. The analysis, considering Normal, Platykurtic, and Skewed distributions and a standard deviation ratio of 1, was conducted for both small and large sample sizes. For small sample sizes, two main categories were established: equal and different sample sizes. Analyses were performed using Monte Carlo simulations with 20,000 repetitions for each scenario, and the simulations were evaluated using SAS software. For small sample sizes, the I. type error rate of the Siegel-Tukey test generally ranged from 0.045 to 0.055, while the I. type error rate of the Savage test was observed to range from 0.016 to 0.041. Similar trends were observed for Platykurtic and Skewed distributions. In scenarios with different sample sizes, the Savage test generally exhibited lower I. type error rates. For large sample sizes, two main categories were established: equal and different sample sizes. For large sample sizes, the I. type error rate of the Siegel-Tukey test ranged from 0.047 to 0.052, while the I. type error rate of the Savage test ranged from 0.043 to 0.051. In cases of equal sample sizes, both tests generally had lower error rates, with the Savage test providing more consistent results for large sample sizes. In conclusion, it was determined that the Savage test provides lower I. type error rates for small sample sizes and that both tests have similar error rates for large sample sizes. These findings suggest that the Savage test could be a more reliable option when analyzing variance differences.

氧化苦参碱对皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的影响

目的探讨氧化苦参碱对小鼠皮肤创面愈合中血清增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)及细胞Ⅰ型胶原蛋白(Type Ⅰ collagen)的影响。方法昆明小鼠背部手术制备1.5 cm×1.5 cm全层皮肤缺损创面模型。自第1 d始,除对照组给予等量生理盐水外,余各组分别按20、40、80 mg/kg给予氧化苦参碱。Van Gieson纤维胶原染色法观察小鼠背部皮肤创面组织胶原纤维的表达;免疫组学法评价创面组织中PCNA、α-SMA及Type Ⅰ collagen的表达。结果Van Gieson纤维胶原染色显示,氧化苦参碱可促进新生肉芽组织、毛细血管及新生纤维胶原生长。免疫组学研究显示,在第7 d时,氧化苦参碱20、40、80 mg/kg使小鼠皮肤创面组织中PCNA表达明显升高(P<0.05);在第9 d、11 d时,氧化苦参碱20 mg/kg使小鼠皮肤创面组织中α-SMA显著增加;氧化苦参碱20 mg/kg在第3 d、11 d,氧化苦参碱40 mg/kg在第3 d,氧化苦参碱80 mg/kg在第3 d、7 d引起Type Ⅰ collagen的表达显著升高(P<0.05)。结论氧化苦参碱能增加皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的表达。

辽东兰花岭地区古元古代Ⅰ型花岗岩类与辽吉A型花岗岩对比研究

辽东半岛是华北克拉通胶-辽-吉古元古代活动带的重要组成部分,古元古代经历了复杂的构造演化过程,并记录了多期岩浆-变质作用,约2.2 Ga的辽吉A型花岗岩和1.89~1.85 Ga的巨斑状花岗岩、正长岩分别标志着辽东古元古代造山作用的开端和结束。最新研究显示,2.20~2.15 Ga的岩浆作用形成了2种不同类型的花岗岩,它们可能具有不同的岩石成因和构造意义。在青城子铅锌矿集区北部采集的兰花岭、白砬子花岗闪长岩和黄泊辉绿岩,锆石U-Pb年龄分别为2177±19 Ma、2129±36 Ma、1876±29 Ma。花岗闪长岩的岩石成因类型、地球化学特征与典型的约2.2 Ga的辽吉A型花岗岩明显不同,属于弱过铝质、低钾钙碱性—碱性岩石,Zr、Hf、Nb、Rb含量较低,K_(2)O/Na_(2)O值、稀土元素总量极低,为典型的Ⅰ型花岗岩类。根据锆石Lu-Hf同位素分析,ε_(Hf)(t)值为-5.1~9.0,二阶段Hf模式年龄t_(DM2)为2089~2817 Ma,岩浆源区为约2.5 Ga的太古宙地壳物质和少量软流圈地幔物质。兰花岭地区花岗闪长岩具备岛弧或活动大陆边缘的地球化学亲缘属性,可能形成于弧岩浆俯冲挤压环境;结合形成于伸展环境的A型条痕状花岗岩特征,认为约2.2 Ga辽东地区古元古代活动带呈现总体伸展、局部挤压的构造环境,为洋壳板块向龙岗地块俯冲碰撞过程中或碰撞后的弧后盆地。

Comparison of the SchirmerⅠtest with and without topical anesthesia for diagnosing dry eye

·AIM:To determine the value of Schirmer Ⅰtest (SⅠt) without anesthesia and with topical anesthesia for diagnosing dry eye (DE). ·METHODS:Totally 220 eyes in 110 patients, male (44) and female (66), (39.56±12.67) years old diagnosed with DE were examined. SⅠt without anesthesia was performed firstly, and 15 minutes later, it was applied again in the same person after topical anesthesia with 0.5% proparacaine hydrochloride eye drops. The wetting strips counted <10mm per 5 minutes were defined positive, while ≤5mm per 5 minutes were defined strong positive. ·RESULTS:The wetting length in SⅠt after topical anesthesia was significantly lower than that in SⅠt without anesthesia(P < 0.001). The positive rate and strong positive rate of SⅠt after topical anesthesia were significantly higher than that of SⅠt without anesthesia (P <0.001). The positive rate and strong positive rate of SⅠt without anesthesia and the strong positive rate of SⅠt after topical anesthesia in patients with aqueous-deficiency dry eye (ADDE) were significantly higher than those in total patients whereas those in patients with evaporative dry eye (EDE) were significantly lower than those in total patients (P <0.001). ·CONCLUSION:SⅠt after topical anesthesia with 0.5% proparacaine hydrochloride eye drops is more objective and reliable than that without anesthesia in reflecting the status of DE, and its diagnostic value in patients with ADDE was even higher, making itself a meaningful evidence for the diagnosis and treatment of DE.

TESTING THE ADEQUACY OF GARCH-TYPE MODELS IN TIME SERIES

In this article a new approach for checking the adequacy of GARCH-type models in time series was proposed. The resulted tests involve weight functions, which provide them with the flexibility in choosing scores to enhance power performance. The choice of weight functions and the power properties of the tests are studied. For a large number of alternatives, asymptotically distribution-free maximin test is constructed. The tests are asymptotically chi-squared under the null hypothesis and easy to implement. Simulation results indicate that the tests perform well.

Evaluation and diagnostic testing of erectile dysfunction in the era of phosphodiesterase type 5 inhibitors

The diagnosis and treatment of erectile dysfunction has changed dramatically since the availability of safe and effective oral therapies. Unfortunately, not all men can be adequately treated in this way, and might require more invasive testing to diagnose and treat the specific cause of their dysfunction. This review looks at the tests and strategies available for men who cannot be treated by oral therapy alone.

Effects of Icariin on Expression of OPN mRNA and Type ⅠCollagen in Rat Osteoblasts in Vitro

To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

Features and imbibition mechanisms of Winsor Ⅰ type surfactant solution in oil-wet porous media

The relationship between NaCl concentration and the phase change behavior of microemulsion of anionic surfactant was characterized by the salinity scan experiments.The wettability of WinsorⅠtype surfactant solution(WⅠsolution)and the effect of NaCL concentration on phase change behavior of WⅠsolution and imbibition in oil-wet porous media were investigated by microfluidic experiments in this study.The WⅠsolution and WinsorⅠtype microemulsion are similar in wetting phase with stronger wettability than other phases.Two main mechanisms of WⅠsolution enhancing imbibitions recovery in oil wet porous media are the wetting phase drive and residual oil solubilization.Under the salinity condition of WinsorⅠtype microemulsion,the NaCl concentration has strong impact on the imbibition mechanism of WⅠsolution,the higher the NaCl concentration,the complex the imbibition process and the higher the imbibition efficiency will be.The NaCl concentration has strong impact on the solubilization ability to oil of the WⅠsolution,the higher the NaCl concentration,the stronger the solubility of the WⅠsolution to residual oil will be.

TypeⅠinositol 1, 4, 5-triphosphate receptors increase in kidney of mice with fulminant hepatic failure

AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.

Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving story

Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the oncosuppressor gene MEN1, in 1997, genetic testing has revealed an important approach for the early and differential diagnosis of the disease. The finding of a MEN1 mutation in a patient has important clinical implications for relatives since it allows very early disease diagnosis and identification of carriers, even before biochemical and/or clinical manifestation, permitting their inclusion in a specific program of surveillance and subsequent praecox therapy. Currently, genetic testing for MEN1 consists principally of the sequencing of coding regions and intron-exon junctions of the MEN1 gene. However, the recent acquisition of novel high throughput technologies will allow the design of innovative, accurate, complete and rapid genetic diagnosis. These new tools are able to increase the strength of the analysis and almost completely eliminate the possibility of false negative results. This review aims to give an overview on genetic testing of MEN1 syndrome, reporting the positive aspects of performing the analysis and the future perspectives for improving the performance of the test, as well as its application in clinical practice.

Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.

Lentinula edodes extract inhibits matrix metalloproteinase expression and increases typeⅠprocollagen expression via the p38 MAPK/c-Fos signaling pathway in ultraviolet A and B-irradiated HaCaT keratinocytes

Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.

Synthesis and high temperature thermoelectric transport properties of Si-based type-Ⅰ clathrates

N-type Si-based type-Ⅰ clathrates with different Ga content were synthesized by combining the solid-state reaction method,melting method and spark plasma sintering （SPS） method.The effects of Ga composition on high temperature thermoelectric transport properties were investigated.The results show that at room temperature,the carrier concentration decreases, while the carrier mobility increases slightly with increasing Ga content.The Seebeck coefficient increases with increasing Ga content. Among all the samples,Ba7.93Ga17.13Si28.72exhibits higher Seebeck coefficient than the others and reaches -135μV·K^-1 at 1000 K.The sample prepared by this method exhibits very high electrical conductivity,and reaches 1.95x 10^5 S·m^-1 for Ba8.01Ga16.61Si28.93 at room temperature.The thermal conductivity of all samples is almost temperature independent in the temperature range of 300-1000 K,indicating the behaviour of a typical metal.The maximum ZT value of 0.75 is obtained at 1000 K for the compound Ba7.93Ga17.13Si28.72.

一类广义Type Ⅰ函数的多目标优化问题

对于非光滑多目标优化的模型,定义了几种广义Type Ⅰ函数,研究了广义Type Ⅰ函数的多目标优化问题,得到了有效解的最优性条件.

Tensile and tear-type fracture toughness of gypsum material:Direct and indirect testing methods

In this context,four specimens,i.e.(i)circumferentially notched cylindrical torsion(CNCT),(ii)circum-ferentially notched cylindrical direct tension(CNCDT),(iii)edge notch disc bend(ENDB)and(iv)three-point bend beam(3PBB),were utilized to measure the modesⅠandⅢfracture toughness values of gypsum.While the CNCT specimen provides pure modeⅢloading in a direct manner,this pure mode condition is indirectly produced by the ENDB specimen.The ENDB specimen provided lower KⅢc and a non-coplanar(i.e.twisted)fracture surface compared with the CNCT specimen,which showed a planar modeⅢfracture surface.The ENDB specimen is also employed for conducting pure modeⅠ(with different crack depths)and mixed modeⅠ/Ⅲtests.KIc value was independent of the notch depth,and it was consistent with the RILEM and ASTM standard methods.But the modeⅢfracture results were highly sensitive to the notch depth.While the fracture resistance against modeⅢwas significantly lower than that of modeⅠ,the greater work of fracture under modeⅢwas noticeable.

Type Ⅰ kerogen-rich oil shale from the Democratic Republic of the Congo: mineralogical description and pyrolysis kinetics

The Democratic Republic of the Congo holds important reserves of oil shale which is still under geological status.Herein,the characterization and pyrolysis kinetics of typeⅠkerogen-rich oil shale of the western Central Kongo(CK)were investigated.X-ray diffraction,Fourier-transform infrared spectroscopy and thermal analysis(TG/DTA)showed that CK oil shale exhibits a siliceous mineral matrix with a consistent organic matter rich in aliphatic chains.The pyrolysis behavior of kerogen revealed the presence of a single mass loss between 300 and 550°C,estimated at 12.5%and attributed to the oil production stage.Non-isothermal kinetics was performed by determining the activation energy using the iterative isoconversional model-free methods and exhibits a constant value with E=211.5±4.7 kJ mol.1.The most probable kinetic model describing the kerogen pyrolysis mechanism was obtained using the Coats–Redfern and Arrhenius plot methods.The results showed a unique kinetic triplet confirming the nature of kerogen,predominantly typeⅠand reinforcing the previously reported geochemical characteristics of the CK oil shale.Besides,the calculation of thermodynamic parameters(ΔH~*,ΔS~*andΔG~*)corresponding to the pyrolysis of typeⅠkerogen revealed that the process is non-spontaneous,in agreement with DTA experiments.

Type Ⅰ neurofibromatosis with spindle cell sarcoma: A case report

BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder presentations. In addition, the incidence of tumors is much higher in patients with neurofibromatosis type Ⅰ. However, there are very few reports at home and abroad on this topic. Here, we present a case of NF1 with spindle cell sarcoma.CASE SUMMARY A 50-year-old male was found to have a right axillary mass for 20 years.Specialist examination found cafe-au-lait spots on many parts of the skin,rounded nodules in the skin, a bulge in the right armpit, touching a lump(10 cm× 6 cm, hard, unclear boundary, poor mobility, local tenderness). The anterior side of the thigh felt weakened on the opposite side;in the right groin a swollen lymph node(hard, clear border, good mobility, local tenderness). According to the results of positron emission tomography/computed tomography, puncture pathology and immunohistochemistry, genetic testing, a diagnosis of NF1 with spindle cell sarcoma was confirmed. According to the genetic testing result, the patient was given a targeted treatment with crizotinib.CONCLUSION Surgery, chemotherapy and radiotherapy are the main treatment methods of NF1. However, with the continuous progress of molecular biology research,molecular targeted therapy may bring benefits for patients.

Significance of elevated serum concentration of type Ⅰ collagen metabolites and its correlation with serum interleukin 6 activities in multiple myeloma

In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradation of type Ⅰ collagen, were determined by radioimmunoassay in 56 patients with multiple myeloma (MM) and 22 healthy controls. It was discovered that serum concentrations of both PICP and ICTP were higher in MM than those in healthy controls (P<0. 01 ). With the disease progressing and the number of bone lesions increasing,serum concentration of ICTP elevated while serum concentration of PICP showed no significant change. Neither serum PICP nor ICTP concentration was related to M-component classes. Our results indicated that serum ICTP concentration was a good serological marker to reflect severity of bone lesions in MM and elevated serum PICP concentration might be due to compensatory increase in type Ⅰ collagen synthesis. Moreover, we also found that serum ICTP concentrations in MM correlated with serum interleukin-6 (IL-6) activities (r= 0. 610, P< 0. 01),which confirms the effectiveness of IL-6 as an osteoclast activating factor.

An Immunochromatographic Strip Test for Rapid Detection of Antibodies against Porcine Circovirus Type 2

Porcine cimovirus type 2 (PCV2) infection causes huge economic losses, but no serological method is available for batch detection of field samples. The aim of the study was to develop a method for large-batch detection of PCV2 infection. Colloidal gold-labeled staphylococcal protein A (SPA) was sprayed on glass fibers to prepare a conjugate pad. The recombinant ORF2 protein of PCV2 was blotted on the test line of the nitrocellulose (NC) membrane, and pig IgG was streaked on the control line of the NC membrane. Then, the immunochromatographic strip was used for detection of antibodies against PCV2. The results show that the strip test was simple and the results could be determined within 10 min with naked eyes. The test strip was highly specific for pig serum against PCV2 and no cross-reaction with pig serum against other pathogens was observed. The test strip had close similarity with ELISA. Storage at RT for 6 months did not affect the specificity and sensitivity obviously. A total of 324 clinical pig sera were detected by both ELISA and the developed test strip, and the coincidence was 98.77%. Therefore, the developed immunochromatographic strip is specific, sensitive, stable, fast and simple, and it is suitable for on-site detection of antibodies against PCV2.

Protein Flexibility and Multiple Docking in Ligand Docking and Virtual Screening to the BRAF(TypeⅠ1/2)Inhibitors

BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.