Molecular dynamics simulations reveal the activation mechanism of mutations G12V and Q61L of Cdc42.

Cell division control protein 42 homolog (Cdc42), which contributes to multiple cellular processes including cell proliferation and migration, is a potential target for cancer therapy, especially in the intervention of tumor migration. Cdc42's mutants G12V and Q61L are discovered constitutively active, and the overexpression of them exhibits oncogenic activities. Here, using molecular dynamics (MD) simulations and dynamic analysis, we illustrated the activation mechanism of Cdc42G12V and Cdc42Q61L . Without GAP, the two mutations differently elicited state transition from the wild-type's open "inactive" state 1 to the closed "active" state 2, induced by the introduction of a newly formed water-mediated T35-γ-phosphate hydrogen bond in G12V system and the additional hydrophobic interactions between L61 and T35 together with the direct T35-γ-phosphate hydrogen bond in Q61L system. When binding with GAP, both mutations weakened the hydrogen bond interactions between Cdc42-GTP and GAP's finger loop, and disturbed the catalytically competent organizations of GAP's catalytic R305/R306 and Cdc42's Q61, thereby impairing the GAP-mediated GTP hydrolysis. Our findings first reveal the activation mechanism of Cdc42's G12V and Q61L mutants on a molecular basis, which provide new insights into the structural and dynamical characteristics of Cdc42 and its mutants and can be exploited in the further development of novel therapies targeting Cdc42-related cancers.

Posterior reversible encephalopathy syndrome secondary to acute post-streptococcal glomerulonephritis in a child: a case report from the Tibetan plateau.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible vasogenic brain oedema with acute neurologic symptoms. It is a rare but serious disease that affects the central nervous system. PRES is a rare complication of acute post-streptococcal glomerulonephritis (APSGN). High altitude can accelerate vasogenic brain oedema by increasing cerebral blood flow (CBF), impairing cerebral autoregulation and promoting vascular inflammation. We report a case of PRES induced by acute post-streptococcal glomerulonephritis in a high-altitude environment. CASE PRESENTATION: A fourteen-year-old Tibetan girl presented with progressive headache with haematuria, facial swelling, dizziness and vomiting for 2 weeks as well as multiple episodes of tonic-clonic seizures for 14 h. She was diagnosed with APSGN based on laboratory tests and clinical symptoms. Brain magnetic resonance imaging (MRI) and computed tomography (CT) revealed bilateral frontal, parietal and occipital lesions that were compatible with the radiological diagnosis of PRES. The treatments included an antibiotic (penicillin), an antiepileptic drug, and hyperbaric oxygen (HBO) therapy. Follow-up MRI obtained 1 week after admission and CT obtained 4 weeks and 6 weeks after admission demonstrated complete resolution of the brain lesions. CONCLUSIONS: The case illustrates a rare occurrence of PRES following APSGN in a 14-year-old child in the Tibetan Plateau. The hypoxic conditions of a high-altitude setting might lower the cerebral autoregulation threshold and amplify the endothelial inflammatory reaction, thus inducing PRES in patients with APSGN. It is important to recognize the clinical and radiologic features of PRES, and adjuvant HBO therapy can promote rapid recovery from this condition in high-altitude areas.

Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway.

BACKGROUND: Semaphorin 3D (SEMA3D) plays an important role in the occurrence and development of multifarious cancers. However, the relationship between SEMA3D and papillary thyroid carcinoma (PTC) remains unclear. This study aimed to investigate the functions and mechanism of SEMA3D in papillary thyroid carcinoma (PTC). METHODS: The expression of SEMA3D in PTC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting and immunohistochemistry (IHC) were used to detect the expression of the related proteins. CCK-8 and colony formation assays and Transwell assays were used to evaluate cell proliferation and migration, respectively. A xenograft model was induced to further verify the effect of SEMA3D in vivo. RESULTS: In this study, we found that SEMA3D was downregulated in PTC tissues and PTC cell lines (TPC-1 and BCPAP). The expression level of SEMA3D was significantly related to age (P < 0.01), extrathyroidal extension (P < 0.01), TNM stage (P < 0.01) and lymph node metastasis (P < 0.01). In vitro experiments showed that overexpression of SEMA3D inhibited the proliferation and migration of TPC-1 and BCPAP cells and that upregulated SEMA3D inhibited the phosphorylation of ERK and the expression of the phenotype-related proteins PCNA and MMP2. In addition, SEMA3D overexpression inhibited tumour growth in vivo. CONCLUSION: In this study, we found that SEMA3D is significantly downregulated in PTC tissues. SEMA3D inhibits the proliferation and migration of PTC cells and suppresses tumour growth in vivo, possibly partially through the MAPK/ERK signalling pathway, suggesting that SEMA3D may be a reliable molecular marker for the diagnosis and treatment of PTC.

Brain Tissue Conductivity in Focal Cerebral Ischemia.

BACKGROUND: Cerebral ischemia leads to oxygen depletion with rapid breakdown of transmembrane transporters and subsequent impaired electrolyte haemostasis. Electric properties tomography (EPT) is a new contrast in MRI which delivers information on tissue electrical conductivity. In the clinical realm it has been mostly used for tumour mapping. Ischemic cerebral stroke is another promising but neglected application. It might deliver additional information on tissue viability and possible response to therapy. AIM: The aim of this study was to demonstrate tissue conductivity in a rodent model of stroke. Further, we aimed to compare electric conductivity in ischemic and non-ischemic cerebral tissue. MATERIALS AND METHODS: Two male Wistar rats were used in this study and were subjected to permanent MCAO. The animals were scanned in a 3 Tesla system (Philips Achieva/Best, the Netherlands) using a dedicated solenoid animal coil (Philips/Hamburg, Germany). In addition to diffusion weighted imaging (DWI), EPT was performed using a steady-state free-precession (SSFP) sequence (repetition time/echo time = 4.5/2.3 ms, measured voxel size = 0.6 × 0.6 × 1.2 mm3, flip angle = 38°, number of excitations = 4). From the transceive phase ϕ of these SSFP scans, conductivity σ was estimated by the equation σ = Δϕ/(2µ0ω) with Δ the Laplacian operator, µ0 the magnetic permeability, and ω the Larmor frequency. Subsequently, a median filter was applied, which was locally restricted to voxels with comparable signal magnitude. RESULTS: The animals exhibited an infarct as demonstrated on DWI. Conductivity within the infarcted region was 60-70 % of the conductivity of not affected contralateral tissue (0.39 ± 0.07 S/m and 0.31 ± 0.14 S/m vs. 0.64 ± 0.15 S/m and 0.66 ± 0.16 S/m, respectively). DISCUSSION: Infarcted tissue exhibited decreased conductivity. Further in-vivo experiments with examination of the influence of reperfusion status and temporal evolution of the infarcted areas should be conducted. Depiction of the ischemic penumbra and possibly subclassification of the DWI lesion still seems to be a fruitful target for further studies.

Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

MSCFS: inferring circRNA functional similarity based on multiple data sources.

BACKGROUND: More and more evidence shows that circRNA plays an important role in various biological processes and human health. Therefore, inferring the circRNA's potential functions and obtaining circRNA functional similarity has become more and more significant. However, there is no effective approach to explore the functional similarity of circRNAs. METHODS: In this paper, we propose a new approach, called MSCFS, to calculate the functional similarity of circRNA by integrating multiple data sources. We combine circRNA-disease association, circRNA-gene-Gene Ontology association, and circRNA sequence information to explore the functional similarity of circRNA. Firstly, we employ different learning representation methods from three data sources to establish three circRNA functional similarity networks. Then we integrate the three networks to obtain the final circRNA functional similarity. RESULTS: We utilize circRNA-miRNA association similarity and circRNA co-expression similarity to evaluate the performance of MSCFS. The results show a positive correlation with miRNA association ([Formula: see text]) and circRNA co-expression similarity ([Formula: see text]). Finally, we construct a circRNA functional similarity network and perform case analysis. The result shows our method can be applied to infer new potential functions of circRNA and other associations. CONCLUSIONS: MSCFS combines multiple data sources related to circRNA functions. Correlation analysis and case analyses prove that MSCFS is a useful method to explore circRNA functional similarity.

PDL and CD insensitive low complexity equalizer for short reach coherent systems.

We propose a polarization dependent loss (PDL) and chromatic dispersion (CD) insensitive, low-complexity adaptive equalizer (AEQ) for short-reach coherent optical transmission systems. The AEQ contains a 1-tap butterfly finite impulse response (FIR) filter and two N-tap FIR filters. It first performs polarization demultiplexing using the 1-tap filter, of which the coefficients are obtained based on Stokes space. Then it mitigates the inter-symbol interference (ISI) using the two N-tap finite impulse response (FIR) filters and adjust the filter's coefficients by utilizing constant modulus algorithm (CMA). Through theoretical and experimental analysis, we verify that this proposed AEQ can perform robust polarization demultiplexing when PDL and CD exists. Besides, our proposed AEQ has faster convergence speed compared with recently proposed AEQs. In addition, it reduces the number of multipliers and thus reduce the computational complexity of conventional butterfly filter structure AEQ. And this proposed AEQ suffers little bit error ratio loss compared with the conventional AEQ. Due to the low-complexity and robustness to PDL and CD, this proposed AEQ is well-suited for future low-cost short-reach optical communication system.

Structural and Functional Changes in the Cerebellum and Brainstem in Patients with Benign Paroxysmal Positional Vertigo.

Benign paroxysmal positional vertigo (BPPV) is one of the most common peripheral vestibular diseases. Since the peripheral vestibular system connects with the cerebellum via the brainstem, repeated episodic vertigo may result in progressive structural and functional changes in the cerebellum and brainstem. In the present work, voxel-based morphometry (VBM) of T1-weighted images and resting-state functional magnetic resonance imaging (fMRI) in 32 patients with BPPV and 32 matched healthy controls were used to assess cerebellar and brainstem anatomical and spontaneous resting-state brain activity alterations associated with BPPV. We used a spatially unbiased infratentorial template toolbox in combination with VBM to analyze cerebellar and brainstem gray matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). Patients with BPPV showed decreased GMV in the right cerebellum posterior lobe/cerebellar tonsil extending to the cerebellum anterior lobe and pons relative to healthy controls. BPPV patients also exhibited significantly higher fALFF values in the right pons and left pons and higher ReHo values in the left cerebellum posterior lobe/Crus2 than the controls. Furthermore, the fALFF z-scores in the pons were positively correlated with the duration of vertigo at baseline and dizziness visual analog scale scores 1 week after canalith repositioning procedures (CRPs). BPPV patients exhibited structural and functional changes in the cerebellum and pons, which may reflect the adaptation and plasticity of these anatomical structures after repeated attacks of episodic vertigo. These results indicate that the changes in pons function may be closely related to residual dizziness after CRPs.

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing.

OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

[Systematic evaluation and sequential Meta-analysis of modified Xuefu Zhuyu Decoction combined with Western medicine in treatment of leiomyoma].

CNKI, PubMed and other databases were retrieved to extract eligible randomized controlled trial(RCT) about modified Xuefu Zhuyu Decoction(MXZD) combined with Western medicine(trial group) versus Western medicine alone(control group) in the treatment of leiomyoma. Therefore, a total of 25 RCTs were included, involving 2 328 patients. Bias risk evaluation tool in Cochrane Handbook 5.1.0 was used for evaluating the quality of these RCTs. Meta-analysis was performed for the reported indicators, including total efficiency, serum hormone level [progesterone(P), luteinizing hormone(LH), estradiol(E_2), follicle stimulating hormone(FSH)], uterine size, fibroids size and adverse reactions by using Stata 14.0 software. Meta-analysis showed that the total efficiency(RR=1.21,95%CI[1.17,1.25],P<0.05) of trial group was better than that of control group. Serum hormone level(WMD_P=-3.86,95%CI[-4.31,-3.41],P<0.05; WMD_(LH)=-3.64,95%CI[-4.47,-2.82],P<0.05; WMD_(E_2)=-39.99,95%CI[-53.45,-26.52],P<0.05; WMD_(FSH)=-3.79,95%CI[-4.86,-2.72],P<0.05), uterine size(WMD=-50.02,95%CI[-55.98,-44.06],P<0.05), fibroids size(WMD=-15.79,95%CI[-18.11,-13.46],P<0.05) and adverse reactions(RR=0.65,95%CI[0.48,0.88],P<0.05) of trial group were all lower than those of control group, with statistical significances. Trial sequential analysis(TSA) was performed by using TSA 0.9 software, and showed a reliable therapeutic effect of the experimental group. In short, our study indicated that modified Xuefu Zhuyu Decoction combined with Western medicine had a better therapeutic effect on leiomyoma than Western medicine alone, but more high-quality studies are needed to verify this conclusion in the future.

Application analysis of clipping and digital resolution enhancer in high-speed direct-detection PAM4 transmission.

In this paper, the application of a clipping and digital resolution enhancer (DRE) is numerically investigated in 56-GBaud direct-detection four-ary pulse amplitude modulation (PAM4) transmission systems. The influence of the tap length and the digital-to-analog converter (DAC) samples per symbol on DRE gain is first studied. After optimizing clipping probability, sampling jitter is introduced. The combination of clipping and DRE can increase jitter tolerance by ∼1.7% sampling time for 4-bit DAC. Then, the required optical signal-to-noise ratio (OSNR) at the hard-decision forward error correction (HD-FEC) threshold of 3.8×10-3 is investigated in back-to-back case and 80-km fiber transmission. It is shown that the combination of clipping and DRE can reduce the required OSNR significantly for 3-bit and 4-bit DAC. Finally, the performance gain introduced by clipping and DRE is analyzed from a perspective of the transmitted average signal power and the received mean-squared quantization error.

Low-complexity storage-reduced digital spectrum-based soft-failure management with Welch's method.

In this paper, we propose a low-complexity storage-reduced digital spectrum-based soft failure management solution including soft failure detection (SFD), identification (SFI) and failure magnitude estimation (FME). Five soft failures are considered. Random fluctuation of key link parameters is introduced in simulations to investigate the robustness of the proposed solution. To reduce computational complexity and storage requirement for digital spectrum calculation, Welch's method is employed instead of applying fast Fourier transform on a long sampling sequence. A false positive rate below 1% and a false negative rate below 3% are achieved for SFD after extensive numerical simulations. Besides, SFI realizes an identification accuracy of 97.4%. The mean square errors of FME for different soft failures are all below 0.4. Finally, with a very small segment length of 25, 46.2% of computational complexity and 99.6% of storage can be reduced for digital spectrum calculation.

Intelligent optical performance monitor using multi-task learning based artificial neural network.

An intelligent optical performance monitor using multi-task learning based artificial neural network (MTL-ANN) is designed for simultaneous OSNR monitoring and modulation format identification (MFI). Signals' amplitude histograms (AHs) after constant module algorithm are selected as the input features for MTL-ANN. The results obtained from simulation and experiment of NRZ-OOK, PAM4 and PAM8 signals demonstrate that MTL-ANN could achieve OSNR monitoring and MFI simultaneously with higher accuracy and stability compared with single-task learning based ANNs (STL-ANNs). The results show an MFI accuracy of 100% for the three modulation formats under consideration. Furthermore, OSNR monitoring with mean-square error (MSE) of 0.12 dB and accuracy of 100% is achieved while regarding it as regression problem and classification problem, respectively. In this intelligent optical performance monitor, only a single MTL-ANN is deployed, which enables reduced-complexity optical performance monitor (OPM) devices for multi-parameters estimation in future heterogeneous optical network.

Loss weight adaptive multi-task learning based optical performance monitor for multiple parameters estimation.

A loss weight adaptive multi-task learning based artificial neural network (MTL-ANN) is applied for joint optical signal-to-noise ratio (OSNR) monitoring and modulation format identification (MFI). We conduct an experiment of polarization division multiplexing (PDM) coherent optical system with 5 km standard single mode fiber (SSMF) transmission to verify this monitor. A group of modulation schemes including nine modulation adaptive M-QAM formats are selected as the transmission signals. Instead of circular constellation, signals' amplitude histograms after constant module algorithm (CMA) based polarization de-multiplexing are selected as input features for our proposed monitor. The experimental results show that the MFI accuracy reaches 100% in the estimated OSNR range. Furthermore, when treated as regression problem and classification problem, OSNR estimation with a root mean-square error (RMSE) of 0.68 dB and an accuracy of 98.7% are achieved, respectively. Unlike loss weight fixed MTL-ANN, loss weight adaptive MTL-ANN could search the optimal loss weight ratio automatically for different link configurations. Besides that, the number of estimated parameters can be easily expanded, which is attractive for multiple parameters estimation in future heterogeneous optical networks.

WoundCareLog APP - A new application to record wound diagnosis and healing.

The incidence of chronic wounds has been increasing over the past 20 years. However, the standardized diagnosis and treatment practice of chronic refractory wounds have not been established. In addition, the properties of the wound are characterized by morphology and thus correct description of the wound in medical history collection plays a vital role, which directly affects the definitive diagnosis. To develop more accurate format of clinical history record which can correctly reflect a patient's course and treatment progress, and to standardize the medical history record of chronic refractory wounds, at the national or regional level, we designed the WoundCareLog APP. It acts as a recording and communication tool for wound healing specialists at all levels of medical institutions in China. The WoundCareLog APP is fully compatible to meet the criteria and requirements of conventional medical records by embedding 9 modules. In addition, the demands for morphological description of wounds in wound healing diagnosis and treatment have been fulfilled by enroll of digital imaging technology to overcome the inadequacies of traditional medical history records.

Nonlinear equalization based on pruned artificial neural networks for 112-Gb/s SSB-PAM4 transmission over 80-km SSMF.

A pruning method of artificial neural network based nonlinear equalizer (ANN-NLE) is proposed and validated for single-sideband 4-ary pulse amplitude modulation (SSB-PAM4) in IM/DD system. As a classifier, ANN is capable to form a complex nonlinear boundary among different classifications, which is considered as an appropriate way to mitigate the nonlinear impairments in optical communication system. In this paper, first, we introduce the operation principle of the traditional linear equalizer (LE) and NLE such as volterra equalizer (VE). Then we make an analogy among the LE, VE and ANN-NLE. After that, a novel pruning method is applied to reduce the complexity of ANN. The BER performance of ANN-NLE outperforms VE after fiber transmission. After 60 km fiber transmission, ANN-NLE decreases the BER by about one order of magnitude compared to VE. By implementing the proposed pruning method, the connections of ANN reduced by a factor of 10x while keeping the BER under the threshold of 3.8x10-3.

Single-photodiode 112-Gbit/s 16-QAM transmission over 960-km SSMF enabled by Kramers-Kronig detection and sparse I/Q Volterra filter.

We have experimentally demonstrated a single-photodiode 112-Gbit/s 16-QAM transmission over 960-km standard single mode fiber with Kramers-Kronig (KK) detection and a sparse I/Q Volterra filter (VF). KK detection is used to mitigate the signal to signal beating interference. A novel I/Q VF based on dual-input real-valued Volterra series is proposed to overcome the constraints of non-linear distortions. Two conventional single-input real-valued VFs are employed as a contrast to prove the necessity of I/Q hybrid structure in I/Q VF when the system suffers from severe I/Q imbalance and crosstalk. The proposed I/Q VF brings nearly two order magnitude improvement in BER performance compared with the conventional linear equalizer for back to back case and doubles the transmission distance from 480 km to 960 km at the hard-decision forward error correction threshold of 3.8 × 10-3. To reduce the complexity of full I/Q VF, a simple ℓ1 regularization-based least mean square (LMS) algorithm is employed to identify the significant kernels and construct a sparse I/Q VF. Compared with full I/Q VF, the sparse I/Q VF reduces up to 58% complexity at 960 km while having the similar BER performance.

Broadband lower-IF RF receiver based on microwave photonic mixer and Kramers-Kronig detection.

A broadband lower- intermediate-frequency (IF) radio frequency (RF) receiver with low cost and complexity based on a microwave photonic mixer and Kramers-Kronig (KK) detection is proposed and experimentally demonstrated. The feasibility of the proposed RF receiver is verified by comparing the error vector magnitude (EVM) performance of a down-converted IF signal with and without KK detection. EVM is measured as a function of IF carrier frequency, input local oscillator (LO) power, input RF power, and the coupling ratio between RF and LO paths. With KK detection, EVM can be improved by more than 9.5% when the IF carrier frequency is close to half of the signal bandwidth. This implies that a lower IF frequency can be down-converted with good EVM and that a low-speed photodetector and a low sampling rate analog to digital converter can be used for wideband RF signal reception.

Metal-Catalyzed Oxa-[4+2] Cyclizations of Quinone Methides with Alkynyl Benzyl Alcohols.

An oxa-[4+2] cyclization of quinone methides with alkynyl benzyl alcohols has been realized in the presence of a metal catalyst, and the reaction afforded spiroacetal products in overall high yields (up to 99%) and good diastereoselectivities (up to >95:5 dr). By carrying out the reaction under gold catalysis and utilizing alkynyl benzyl alcohols as electron-rich reaction partners, this approach provides a useful strategy for settling the challenges in oxa-[4+2] cyclization of para-quinone methide derivatives. This reaction serves as a good example for metal-catalyzed oxa-[4+2] cyclizations of quinone methides. In addition, it also offers a useful method for the construction of spiroacetal skeletons.