Failure probability analysis of high fill levee considering multiple uncertainties and correlated failure modes.

Such complex causative factors in current failure probability models are represented by simply random uncertainty and completely independent or correlation of failure modes, which can often limit the model utility. In this study, we developed a methodology to construct failure probability models for high fill levees, incorporating the identification of uncertainties and an analysis of failure modes. Based on quantification of stochastic-grey-fuzzy uncertainties, probability analysis involved with overtopping, instability and seepage failure modes was implemented combined with probability and non-probability methods. Given that the interaction among failure modes typically exhibits nonlinear behavior, rather than linear correlation or complete independence, a simple methodology for the binary Copula function was established and implemented in MATLAB. This methodology was applied to the high fill segments of a long-distance water transfer project characterized by high population density. It shows that the failure probability of a single failure mode is overestimated when uncertainties are not considered, because of the randomness and fuzziness of some parameters and the greyness of information. Meanwhile, it is found that the magnitude of failure probability related to levee breach is overestimated without respect to failure modes correlation, especially when the probabilities of seepage and instability are both significant and closely aligned.

Implications of Pretreatment Serum Carcinoembryonic Antigen Levels and Perineural Invasion with Staging, Prognosis, and Management in Stage I-III Colon Cancer after Surgery: A Retrospective Cohort Study in the SEER Database.

BACKGROUND: Pretreatment levels of serum carcinoembryonic antigen (CEA) and perineural invasion (PNI) are related to poor prognosis in colon cancer. We analyzed the CEA and PNI (defined as incorporation of carcinoembryonic antigen and perineural invasion (CP)-stage), which are included in the Tumor-Node-Metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), and evaluated the survival prognosis of patients treated with surgery in I-III stage colon carcinoma. MATERIALS AND METHODS: We employed a retrospective study for eligible colon carcinoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Kaplan-Meier curve and Multivariate Cox regression analysis were used to analyze different TNM-CP stages for the cancer-specific survival (CSS) probabilities in colon cancer. RESULT: In our study, CEA levels and PNI were significant prognostic factors (p < 0.05), and the newly proposed CP-stage was an independent prognostic index in stage I-III colon carcinoma after surgery. Multivariate Cox regression analyses indicated that CP1-stage was related to a 63.9% increased risk of cancer-specific mortality (hazard ratio (HR): 1.639, 95% confidence interval (CI): 1.544-1.739, p < 0.001), compared with CP0-stage in colon cancer. In respective TNM stages, the CP0-stage had an advantage over the CP1-stage for CSS (p < 0.001). Moreover, CP1-stage patients with node-negative colon cancer were contacted with similar or worse survival in comparison to CP0-stage patients with node-positive. CONCLUSION: For postoperative patients with stage I-III colon cancer, our study indicated that the CP stage is a significant prognostic factor for CSS, which deserves more clinical attention. It's worth noting that including the CP stage in the AJCC TNM staging system of colon carcinoma is beneficial to the survival prediction and clinical treatment.

Abnormal functional connectivity of the reward circuit associated with early satiety in patients with postprandial distress syndrome.

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

Integration method of compressed sensing with variational mode decomposition based on gray wolf optimization and its denoising effect in mud pulse signal.

The continuous wave mud pulse transmission holds great promise for the future of downhole data communication. However, significant noise interference during the transmission process poses a formidable challenge for decoding. In particular, effectively eliminating random noise with a substantial amplitude that overlaps with the pulse signal spectrum has long been a complex issue. To address this, an enhanced integration algorithm that merges variational mode decomposition (VMD) and compressed sensing (CS) to suppress high-intensity random noise is proposed in this paper. In response to the inadequacy of manually preset parameters in VMD, which often leads to suboptimal decomposition outcomes, the gray wolf optimization algorithm is designed to obtain the optimal penalty factor and decomposition mode number in VMD. Subsequently, the optimized parameter combination decomposes the signal into a series of intrinsic modes. The mode exhibiting a stronger correlation with the original signal is retained to enhance signal sparsity, thereby fulfilling the prerequisite for compressed sensing. The signal is then observed and reconstructed using the compressed sensing method to yield the final signal. The proposed algorithm has been compared with VMD, CS, and CEEMD; the results demonstrate that the method can enhance the signal-noise ratio by up to ∼20.55 dB. Furthermore, it yields higher correlation coefficients and smaller mean square errors. Moreover, the experimental results using real field data show that the useful pulse waveforms can be recognized effectively, assisting surface workers in acquiring precise downhole information, enhancing drilling efficiency, and significantly reducing the risk of engineering accidents.

Efficacy and mechanism of Wuzi Yanzong pill on the prevention and treatment of EAE.

Objective: Studies have shown that Wuzi Yanzong Pill (WYP) can be used to treat neurological diseases, but its mechanisms for multiple sclerosis (MS) remain unclear. This study aims to determine the effect of WYP on MS in an animal model of experimental autoimmune encephalomyelitis (EAE), and explore its mechanism. To provide theoretical basis for the clinical treatment of MS with WYP. Methods: C57BL/6 female mice were randomly divided into Blank control, EAE control, low dose WYP, medium dose WYP, and high dose WYP groups. One week before model generation, the mice were gavaged with saline (50 mL/kg/d) in Blank control and EAE control groups. The treatment groups was gavaged with different doses of WYP solution (4, 8, or 16 g/kg/d respectively) Clinical scores were recorded daily. Sample collection was conducted on the 14th and 28th days, respectively The expressions of IL-10, IL-17, IL-12, TNF-α and IFN-γ in spleen were detected by ELISA. The expressions of ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, CCR2 in spleen, brain and spinal cord were detected by Western Blot. The types of macrophages and the contents of intracellular IL-10 and IL-12 were detected by Flow Cytometry. The contents of TNF-α and TLR4 mRNA in the spleen were detected by RT-PCR. Results: WYP treatment improved the clinical score of EAE mice in a significant dose-dependent manner, with the WYP high-dose group showed the most significant improvement in clinical score. Compared with the EAE control group, WYP high dose group had significantly lower levels of IL-17, IFN-γ, ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, and CCR2 as well as TNF-α and TLR4 mRNA, but increased the number of M2 macrophages and IL-10. Conclusion: WYP treatment relieves clinical symptoms in EAE mice, which may be related to regulate inflammatory pathway and inhibiting expressions of inflammatory cytokines.

Ab Initio Time-Domain Study of Charge Relaxation and Recombination in N-Doped Cu2O.

Cu2O is a good photoelectric material with excellent performance, and its crystal structure, electronic structure, and optical properties have been extensively studied. To further illustrate the charge distribution and the carrier transport in this system, the e-h recombination dynamics was studied. It is found that N doping induced a shallower impurity band above the VBM, leading to significant charge localization around the impurity atom. NAMD simulation reveals that the N doping system possesses a longer e-h nonradiative recombination time scale. Therefore, we demonstrate that the formation of the impurity band and charge localization play an essential role in suppressing e-h recombination in N doping systems. This work is conducive for understanding the carrier transport mechanism in N-doped Cu2O.

Clinical-functional brain connectivity signature predicts longitudinal symptom improvement after acupuncture treatment in patients with functional dyspepsia.

Whilst acupuncture has been shown to be an effective treatment for functional dyspepsia (FD), its efficacy varies significantly among patients. Knowing beforehand how each patient responds to acupuncture treatment will facilitate the ability to produce personalized prescriptions, therefore, improving acupuncture efficacy. The objective of this study was to construct the prediction model, based on the clinical-neuroimaging signature, to forecast the individual symptom improvement of FD patients following a 4-week acupuncture treatment and to identify the critical predictive features that could potentially serve as biomarkers for predicting the efficacy of acupuncture for FD. Clinical-functional brain connectivity signatures were extracted from samples in the training-test set (100 FD patients) and independent validation set (60 FD patients). Based on these signatures and support vector machine algorithms, prediction models were developed in the training test set, followed by model performance evaluation and predictive features extraction. Subsequently, the external robustness of the extracted predictive features in predicting acupuncture efficacy was evaluated by the independent validation set. The developed prediction models possessed an accuracy of 88% in predicting acupuncture responders, as well as an R2 of 0.453 in forecasting symptom relief. Factors that contributed significantly to stronger responsiveness of patients to acupuncture therapy included higher resting-state functional connectivity associated with the orbitofrontal gyrus, caudate, hippocampus, and anterior insula, as well as higher baseline scores of the Symptom Index of Dyspepsia and shorter durations of the condition. Furthermore, the robustness of these features in predicting the efficacy of acupuncture for FD was verified through various machine learning algorithms and independent samples and remained stable in univariate and multivariate analyses. These findings suggest that it is both feasible and reliable to predict the efficacy of acupuncture for FD based on the pre-treatment clinical-neuroimaging signature. The established prediction framework will promote the identification of suitable candidates for acupuncture treatment, thereby improving the efficacy and reducing the cost of acupuncture for FD.

Acupuncture on GB34 for immediate analgesia and regulating pain-related anxiety for patients with biliary colic: a protocol of randomized controlled trial.

BACKGROUND: Biliary colic (BC) is a frequent hepatobiliary disorder encountered in emergency departments. Acupuncture may be effective as an alternative and complementary medicine for BC. Nonetheless, rigorous trials investigating its efficacy are lacking. Therefore, the aim of this study protocol is to determine whether acupuncture provides immediate relief of pain and associated symptoms in BC patients. METHOD: Eighty-six participants who aged from 18 to 60 years with BC will be recruited in the First People's Hospital of Longquanyi District, Chengdu (West China Longquan Hospital Sichuan University). All participants will be allocated into two treatment groups including acupuncture group and sham acupuncture group using a 1:1 ratio. Each group will only receive a single 30-min needle treatment while waiting for their test results after completing the routine examination for BC. The primary outcome of the study is to assess the change in pain intensity after the 30-min acupuncture treatment. The secondary outcomes of the study include the change in pain intensity at various time points, the degree of gastrointestinal symptoms at different time points, the level of anxiety experienced during pain episodes at different time points, the score of Pain Anxiety Symptoms Scale-20 (PASS-20), the score of Fear of Pain Questionnaire-III (FPQ-III), and the score of Pain Catastrophizing Scale (PCS), among others. DISCUSSION: The results of this research will provide substantial evidence regarding the efficacy of acupuncture in alleviating symptoms associated with BC. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2300070661. Registered on 19 April 2023.

Altered resting-state brain activity in functional dyspepsia patients: a coordinate-based meta-analysis.

Background: Neuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear. Methods: Eight databases were systematically searched for literature from inception to October 2022 with the keywords "Functional dyspepsia" and "Neuroimaging." Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients. Results: A total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected. Conclusion: The current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

Nonspecific interactions between Cas12a and dsDNA located downstream of the PAM mediate target search and assist AsCas12a for DNA cleavage.

Cas12a is one of the most commonly used Cas proteins for genome editing and gene regulation. The first key step for Cas12a to fulfill its function is to search for its target among numerous nonspecific and off-target sites. Cas12a utilizes one-dimensional diffusion along the contour of dsDNA to efficiently search for its target. However, due to a lack of structural information of the transient diffusing complex, the residues mediating the one-dimensional diffusion of Cas12a are unknown. Here, combining single-molecule and ensemble assays, we found that nonspecific interactions between Cas12a and dsDNA at the PAM downstream cause asymmetric target search regions of Cas12a flanking the PAM site, which guided us to identify a positive-charge-enriched alpha helix in the REC2 domain serving as a conserved element to facilitate one-dimensional diffusion-driven target search of AsCas12a, LbCas12a and FnCas12a. In addition, this alpha helix assists the target cleavage process of AsCas12a via stabilizing the cleavage states. Thus, neutralizing positive charges within this helix not only significantly slows target search but also enhances the specificity of AsCas12a both in vitro and in living cells. Similar behaviors are detected when residues mediating diffusion of SpCas9 are mutated. Thus, engineering residues mediating diffusion on dsDNA is a new avenue to optimize and enrich the versatile CRISPR-Cas toolbox.

Modulation effects of different treatments on periaqueductal gray resting state functional connectivity in knee osteoarthritis knee pain patients.

BACKGROUND: The analgesic effect of acupuncture is widely recognized, but the mechanical characteristics of acupuncture for pain relief, compared to non-steroidal anti-inflammatory (NSAIDs) and placebo medication, remain unknown. AIMS: To compare the modulation effects of acupuncture treatment with NSAIDs and placebo medication on descending pain modulation system (DPMS) in knee osteoarthritis (KOA) patients. METHODS: This study recruited 180 KOA patients with knee pain and 41 healthy controls (HCs). Individuals with KOA knee pain were divided randomly into groups of verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), and waiting list (WT), with 36 patients in each group. VA and SA groups included ten sessions of puncturing acupoints or puncturing non-acupoints acupuncture treatment for two successive weeks. Celecoxib capsules were continuously given orally to patients in the SC group at a dosage of 200 mg daily for 2 weeks. In the PB group, patients received a placebo capsule once a day for 2 weeks at the same dosage as celecoxib capsules. In the WL group, patients did not receive any treatment. Patients underwent a resting-state BOLD-fMRI scan pre- and post-receiving the therapy, whereas HCs only underwent a baseline scan. Seed (ventrolateral periaqueductal gray, vlPAG, a key node in DPMS) based resting-state functional connectivity (rs-FC) was applied in the data analysis. RESULTS: All groups demonstrated improved knee pain scores relative to the initial state. There was no statistical difference between the VA and SA groups in all clinical outcomes, and vlPAG rs-FC alterations. KOA knee pain individuals reported higher vlPAG rs-FC in the bilateral thalamus than HCs. KOA knee pain patients in the acupuncture group (verum + sham, AG) exhibited increased vlPAG rs-FC with the right dorsolateral prefrontal cortex (DLPFC) and the right angular, which is associated with knee pain improvement. In contrast with the SC and PB group, the AG exhibited significantly increased vlPAG rs-FC with the right DLPFC and angular. Contrary to the WT group, the AG showed greater vlPAG rs-FC with the right DLPFC and precuneus. CONCLUSIONS: Acupuncture treatment, celecoxib, and placebo medication have different modulation effects on vlPAG DPMS in KOA knee pain patients. Acupuncture could modulate vlPAG rs-FC with brain regions associated with cognitive control, attention, and reappraisal for knee pain relief in KOA patients, compared with celecoxib and placebo medication.

Hotspots and trends in fNIRS disease research: A bibliometric analysis.

Objective: To summarize the general information and hotspots of functional near-infrared spectroscopy (fNIRS)-based clinical disease research over the past 10 years and provide some references for future research. Methods: The related literature published between 1 January 2011 and 31 January 2022 was retrieved from the Web of Science core database (WoS). Bibliometric visualization analysis of countries/regions, institutions, authors, journals, keywords and references were conducted by using CiteSpace 6.1.R3. Results: A total of 467 articles were included, and the annual number of articles published over nearly a decade showed an upward trend year-by-year. These articles mainly come from 39 countries/regions and 280 institutions. The representative country and institution were the USA and the University of Tubingen. We identified 266 authors, among which Andreas J Fallgatter and Ann-Christine Ehlis were the influential authors. Neuroimage was the most co-cited journal. The major topics in fNIRS disease research included activation, prefrontal cortex, working memory, cortex, and functional magnetic resonance imaging (fMRI). In recent years, the Frontier topics were executive function, functional connectivity, performance, diagnosis, Alzheimer's disease, children, and adolescents. Based on the burst of co-cited references, gait research has received much attention. Conclusion: This study conducted a comprehensive, objective, and visual analysis of publications, and revealed the status of relevant studies, hot topics, and trends concerning fNIRS disease research from 2011 to 2022. It is hoped that this work would help researchers to identify new perspectives on potential collaborators, important topics, and research Frontiers.

Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. METHODS: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. RESULTS: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01). CONCLUSIONS: WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

Predicting acupuncture efficacy for functional dyspepsia based on functional brain network features: a machine learning study.

Acupuncture is effective in treating functional dyspepsia (FD), while its efficacy varies significantly from different patients. Predicting the responsiveness of different patients to acupuncture treatment based on the objective biomarkers would assist physicians to identify the candidates for acupuncture therapy. One hundred FD patients were enrolled, and their clinical characteristics and functional brain MRI data were collected before and after treatment. Taking the pre-treatment functional brain network as features, we constructed the support vector machine models to predict the responsiveness of FD patients to acupuncture treatment. These features contributing critically to the accurate prediction were identified, and the longitudinal analyses of these features were performed on acupuncture responders and non-responders. Results demonstrated that prediction models achieved an accuracy of 0.76 ± 0.03 in predicting acupuncture responders and non-responders, and a R2 of 0.24 ± 0.02 in predicting dyspeptic symptoms relief. Thirty-eight functional brain network features associated with the orbitofrontal cortex, caudate, hippocampus, and anterior insula were identified as the critical predictive features. Changes in these predictive features were more pronounced in responders than in non-responders. In conclusion, this study provided a promising approach to predicting acupuncture efficacy for FD patients and is expected to facilitate the optimization of personalized acupuncture treatment plans for FD.

Modulation of cerebral cortex activity by acupuncture in patients with prolonged disorder of consciousness: An fNIRS study.

Background and objective: Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods: Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results: Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion: One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

Aberrant resting-state functional connectivity and topological properties of the subcortical network in functional dyspepsia patients.

Functional dyspepsia (FD) is a disorder of gut-brain interaction. Previous studies have demonstrated a wide range of abnormalities in functional brain activity and connectivity patterns in FD. However, the connectivity pattern of the subcortical network (SCN), which is a hub of visceral information transmission and processing, remains unclear in FD patients. The study compared the resting-state functional connectivity (rsFC) and the global and nodal topological properties of SCN between 109 FD patients and 98 healthy controls, and then explored the correlations between the connectivity metrics and clinical symptoms in FD patients. The results demonstrated that FD patients manifested the increased rsFC in seventeen edges among the SCN, decreased small-worldness and local efficiency in SCN, as well as increased nodal efficiency and nodal degree centrality in the anterior thalamus than healthy controls (p < 0.05, false discovery rate corrected). Moreover, the rsFC of the right anterior thalamus-left nucleus accumbens edge was significantly correlated with the NDSI scores (r = 0.255, p = 0.008, uncorrected) and NDLQI scores (r = -0.241, p = 0.013, uncorrected), the nodal efficiency of right anterior thalamus was significantly correlated with NDLQI scores (r = 0.204, p = 0.036, uncorrected) in FD patients. This study indicated the abnormal rsFC pattern, as well as global and nodal topological properties of the SCN, especially the bilateral anterior thalamus in FD patients, which enhanced our understanding of the central pathophysiology of FD and will lay the foundation for the objective diagnosis of FD and the development of new therapies.

Phosphorothioate-Based Site-Specific Labeling of Large RNAs for Structural and Dynamic Studies.

Pulsed electron-electron double resonance (PELDOR) spectroscopy, X-ray scattering interferometry (XSI), and single-molecule Förster resonance energy transfer (smFRET) are molecular rulers that provide inter- or intramolecular pair-wise distance distributions in the nanometer range, thus being ideally suitable for structural and dynamic studies of biomolecules including RNAs. The prerequisite for such applications requires site-specific labeling of biomolecules with spin labels, gold nanoparticles, and fluorescent tags, respectively. Recently, site-specific labeling of large RNAs has been achieved by a combination of transcription of an expanded genetic alphabet containing A-T/G-C base pairs and NaM-TPT3 unnatural base pair (UBP) with post-transcriptional modifications at UBP bases by click chemistry or amine-NHS ester reactions. However, due to the bulky sizes of functional groups or labeling probes used, such strategies might cause structural perturbation and decrease the accuracy of distance measurements. Here, we synthesize an α-thiophosphorylated variant of rTPT3TP (rTPT3αS), which allows for post-transcriptional site-specific labeling of large RNAs at the internal α-phosphate backbone via maleimide-modified probes. Subsequent PELDOR, XSI, and smFRET measurements result in narrower distance distributions than labeling at the TPT3 base. The presented strategy provides a new route to empower the molecular rulers for structural and dynamic studies of large RNA and its complex.

Deqi Sensation to Predict Acupuncture Effect on Functional Dyspepsia: A Machine Learning Study.

Objectives: The aim of the study was to predict the effect of acupuncture for treating functional dyspepsia (FD) using the support vector machine (SVM) techniques based on initial deqi sensations of patients. Methods: This retrospective study involved 90 FD patients who had received four weeks of acupuncture treatment. The support vector classification model was used to distinguish higher responders (patients with Symptom Index of Dyspepsia improvement score ≥ 2) from lower responders (patients with Symptom Index of Dyspepsia improvement score < 2). A support vector regression model was used to predict the change in the Symptom Index of Dyspepsia at the end of acupuncture treatment. Deqi sensations of patients in the first acupuncture treatment of a 20-session acupuncture intervention were defined as features and used to train models. Models were validated by 10-fold cross-validation and evaluated by accuracy, specificity, sensitivity, the area under the receive-operating curve, the coefficient of determination (R 2), and the mean squared error. Results: The two models could predict the efficacy of acupuncture successfully. These models had an accuracy of 0.84 in predicting acupuncture response, and an R 2 of 0.16 in the prediction of symptom improvements, respectively. The presence or absence of deqi sensation, the duration of deqi sensation, distention, and pain were finally selected as significant predicting features. Conclusion: Based on the SVM algorithms and deqi sensation, the current study successfully predicted the acupuncture response as well as clinical symptom improvement in FD patients at the end of treatment. Our prediction models are expected to promote the clinical efficacy of acupuncture treatment for FD, reduce medical expenditures, and optimize the allocation of medical resources.

Acupuncture for emotional disorders in patients with inflammatory bowel disease: a systematic review protocol.

INTRODUCTION: Emotional disorders are often observed in inflammatory bowel disease (IBD). IBD with emotional disorders leads to poor quality of life. This systematic review aims to assess the effectiveness of acupuncture in patients with IBD with emotional disorders. METHODS AND ANALYSIS: Nine electronic databases, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing & Allied Health Literature, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database, will be searched from inception to October 2021 without language restriction. The grey literature containing conference proceedings, as well as systematic reviews listed in the reference of definite publications, will also be retrieved. Randomised controlled trials either in English or Chinese reporting acupuncture therapy for IBD with emotional disorders will be included. The primary outcome is changes of emotional functioning outcomes. The Colitis Activity Index, Crohn's Disease Activity Index, C reactive protein and adverse events will be assessed as the secondary outcomes. More than two assessors will conduct the study retrieval and selection, as well as the data extraction and evaluation of the risk of bias. Data synthesis will be performed using a random-effects model based on the results of heterogeneity. Data analysis will be performed using RevMan software (V.5.4). Moreover, the dichotomous data will be presented as risk ratios, and the continuous data will be calculated using weighted mean difference or standard mean difference. ETHICS AND DISSEMINATION: This systematic review contains no individual patient data; thus, ethical approval is not required. Moreover, this review will be disseminated in a peer-reviewed journal or relevant conference. PROSPERO REGISTRATION NUMBER: CRD42020176340.