Inferring gene regulatory network via fusing gene expression image and RNA-seq data.

MOTIVATION: Recently, with the development of high-throughput experimental technology, reconstruction of gene regulatory network (GRN) has ushered in new opportunities and challenges. Some previous methods mainly extract gene expression information based on RNA-seq data, but the associated information is very limited. With the establishment of gene expression image database, it is possible to infer GRN from image data with rich spatial information. RESULTS: First, we propose a new convolutional neural network (called SDINet), which can extract gene expression information from images and identify the interaction between genes. SDINet can obtain the detailed information and high-level semantic information from the images well. And it can achieve satisfying performance on image data (Acc: 0.7196, F1: 0.7374). Second, we apply the idea of our SDINet to build an RNA-model, which also achieves good results on RNA-seq data (Acc: 0.8962, F1: 0.8950). Finally, we combine image data and RNA-seq data, and design a new fusion network to explore the potential relationship between them. Experiments show that our proposed network fusing two modalities can obtain satisfying performance (Acc: 0.9116, F1: 0.9118) than any single data. AVAILABILITY AND IMPLEMENTATION: Data and code are available from https://github.com/guofei-tju/Combine-Gene-Expression-images-and-RNA-seq-data-For-infering-GRN.

Green Halogenation of Indoles with Oxone-Halide.

Oxidative functionalization of indoles is one of the most widely used approaches to exploit the synthetic utility of indoles. In continuation of our research interest in the green oxidation of indoles, we further explore the oxidation of indoles with oxone-halide and discover that the protecting group on the nitrogen of indoles plays a decisive role in controlling the pathways of indole oxidation with oxone-halide. An electron-withdrawing group on the nitrogen of indoles (N-EWG) enables C2 halogenation with stoichiometric halide, while C3 halogenation could be selectively achieved by using stoichiometric halide without dependence on the electronic property of the protecting group on the indole nitrogen. Different from our previous results obtained by using catalytic halide, these findings lead to the development of an environmentally friendly, efficient, and mild protocol for access to 2- or 3-haloindoles (chloro and bromo). As compared to the previous synthetic methods for 2-/3-haloindoles, our method exploits the in situ-generated reactive halogenating species from oxone-halide for halogenation of indoles and thus eliminates the use of stoichiometric halogenating agents and the production of toxic and hazardous organic byproducts derived from oxidants.

BiBr3 -Mediated Intramolecular Aza-Prins Cyclization of Aza-Achmatowicz Rearrangement Products: Asymmetric Total Synthesis of Suaveoline and Sarpagine Alkaloids.

An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed in which bismuth tribromide (BiBr3 ) plays a dual role as an efficient Lewis acid and source of the bromide nucleophile. This approach enables the facile construction of highly functionalized 9-azabicyclo[3.3.1]nonanes (9-ABNs), which are valuable synthetic building blocks and a powerful platform for the synthesis of a variety of alkaloid natural products and drug molecules. Suitable substrates for the aza-Prins cyclization include 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, alkynes, and allenes, with good to excellent yields observed. Finally, we showcase the application of this new approach to the enantioselective total synthesis of six indole alkaloids: (-)-suaveoline (1), (-)-norsuaveoline (2), (-)-macrophylline (3), (+)-normacusine B (4), (+)-Na -methyl-16-epipericyclivine (5) and (+)-affinisine (6) in a total of 9-14 steps. This study significantly expands the synthetic utility of the aza-Achmatowicz rearrangement, and the strategy (aza-Achmatowicz/aza-Prins) is expected to be applicable to the total synthesis of other members of the big family of macroline and sarpagine indole alkaloids.

Rapid construction of indole-fused 8-10 membered lactones via a tandem reaction.

An intramolecular anaerobic Mukaiyama hydration-initiated tandem reduction/condensation/acyl migration/aromatization reaction was developed, which enabled the rapid construction of indole-fused 8-10 membered lactones starting from cyclic 2-allyl-2-(2-nitrophenyl)-1,3-diketones. A nitro substituent in the substrates acted as both an oxygen source in the Mukaiyama hydration step and a nitrogen source in a tandem indole ring construction step. Our reaction features mild conditions, atom economy, and inexpensive reagents and it can be conveniently scaled up to a gram scale in modest yields. A rational reaction mechanism was also proposed based on previous reports and control experiments.

Self-administered acupressure and exercise for patients with osteoarthritis: A randomized controlled trial.

OBJECTIVE: Knee osteoarthritis is a prevalent degenerative joint disease and seriously affects the athletic abilities of middle-aged and elderly patients. Acupressure is a traditional non-pharmacological intervention that promotes blood circulation and muscle activity. Self-administrated acupressure and exercise can be potential management for knee osteoarthritis. DESIGN: It is a randomized and controlled trial for knee osteoarthritis self-treatment. SETTINGS: Cangzhou Hospital. INTERVENTIONS: 221 patients with knee osteoarthritis were recruited and randomly divided into 4 groups: control group (n = 55), exercise group (n = 56), acupressure group (n = 55) and exercise & acupressure group (n = 55). In the first eight weeks, corresponding training courses were provided to different groups of patients. The patients were asked to carry out their own corresponding interventions for 16 weeks. The patient's condition was evaluated in the sixteenth week. MAIN MEASURES: The Western Ontario and McMaster Universities global scores of knee osteoarthritis patients were assessed at the 8th and 16th week of our trial. RESULTS: Self-administered acupressure and exercise significantly decreased visual analogue scale (3.75 ± 1.89 versus 2.93 ± 1.73, p < 0.05), pain (7.6 ± 2.8 versus 4.8 ± 2.7, p < 0.05), stiffness (3.75 ± 1.89 versus 2.93 ± 1.73, p < 0.05) at the 16th week (p < 0.05) in patients with knee osteoarthritis compared to other intervention. The combination of acupressure and exercise also improved the range of motion (114.4 ± 11.5 versus 120.4 ± 11.9, p < 0.05) and walk speed (1.48 ± 0.48 versus 1.76 ± 0.50, p < 0.05) of osteoarthritis patients (p < 0.05). CONCLUSION: Self-administrated exercise and acupressure alleviate the arthritic symptoms (swelling, pain, joint dysfunction and joint deformities) and improve the joint functions, supporting its potential use in the clinical management for osteoarthritis.

A Strategy to Construct cis-Hydrocarbazole via Nickel/Lewis Acid Dual-Catalyzed Arylcyanation.

A strategy for the synthesis of cis-hydrocarbazole with a C3 quaternary carbon center has been developed through nickel/Lewis acid dual-catalyzed arylcyanation. A wide array of cis-hydrocarbazoles was accessed with high diastereoselectivities and atom economies in a good yield. The rich chemistry of the installed nitrile group was demonstrated in the preparation of tryptamine- and tryptophol-derived cis-hydrocarbazoles.

Asymmetric Total Synthesis of (+)-Winchinine B.

The first asymmetric total synthesis of aspidosperma alkaloid (+)-winchinine B was achieved in 12 steps from commercially available materials. A new synthetic strategy which features an efficient aza-Michael addition, a ruthenium-catalyzed transfer dehydrogenation, and an intramolecular palladium-catalyzed oxidative coupling was adopted to install the ABC tricycle system. A one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition developed by our group was utilized to construct the D ring moiety.

CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression.

Chromobox (CBX) 2, a member of the CBX protein family and a crucial component of the polycomb repressive complex (PRC), exerts significant influence on the epigenetic regulation of tumorigenesis, including glioma. However, the precise role of CBX2 in glioma has remained elusive. In our study, we observed a substantial upregulation of CBX2 expression in glioma, which displayed a strong correlation with pathological grade, chemoresistance, and unfavorable prognosis. Through a series of in vivo and in vitro experiments, we established that heightened CBX2 expression facilitated glioma cell proliferation and bolstered resistance to chemotherapy. Conversely, CBX2 knockdown led to a significant inhibition of glioma cell growth and a reduction in chemoresistance. Notably, our investigation uncovered the underlying mechanism by which CBX2 operates, primarily by inhibiting PTEN transcription and activating the AKT/mTOR signalling pathway. Conversely, silencing CBX2 curtailed cell proliferation and attenuated chemoresistance by impeding the activation of the PTEN/AKT/mTOR signalling pathway. Delving deeper into the molecular intricacies, we discovered that CBX2 can recruit EZH2 and modulate the trimethylation of histone H3 lysine 27 (H3K27me3) levels on the PTEN promoter, effectively suppressing PTEN transcription. Our research unveils a comprehensive understanding of how CBX2 impacts the tumorigenesis, progression, chemoresistance, and prognosis of glioma. Furthermore, it presents CBX2 as a promising therapeutic target for drug development and clinical management of glioma.

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review).

Chromobox (CBX) proteins are important epigenetic regulatory proteins and are widely involved in biological processes, such as embryonic development, the maintenance of stem cell characteristics and the regulation of cell proliferation and apoptosis. Disorder and dysfunction of CBXs in cancer usually lead to the blockade or ectoptic activation of developmental pathways, promoting the occurrence, development and progression of cancer. In the present review, the characteristics and functions of CBXs were first introduced. Subsequently, the expression of CBXs in cancers and the relationship between CBXs and clinical characteristics (mainly cancer grade, stage, metastasis and relapse) and prognosis were discussed. Finally, it was described how CBXs regulate cell proliferation and self­renewal, apoptosis and the acquisition of malignant phenotypes, such as invasion, migration and chemoresistance, through mechanisms involving epigenetic modification, nuclear translocation, noncoding RNA interactions, transcriptional regulation, posttranslational modifications, protein­protein interactions, signal transduction and metabolic reprogramming. The study also focused on cancer therapies targeting CBXs. The present review provides new insight and a comprehensive basis for follow­up research on CBXs and cancer.

Application of 3D-printed osteotomy guides in periacetabular osteotomy: A short-term clinical study.

OBJECTIVE: To compare the clinical efficacy between personalised 3-dimensional (3D) printed osteotomy and traditional osteotomy in periacetabular osteotomy (PAO). METHODS: Twenty-two patients with acetabular dysplasia were randomly divided into a personalised 3D-printed osteotomy group and a traditional osteotomy group without 3D printing assistance. The operation time, intraoperative blood loss, X-ray frequency, quantity of postoperative drainage, postoperative transfusion rate, hip angle and Harris hip score of 6 months postoperative were studied and compared to evaluate the surgical efficacy between personalised 3D-printed osteotomy and traditional osteotomy in periacetabular osteotomy. RESULTS: The operation time, intraoperative blood loss, X-ray frequency, postoperative 24 h drainage volume in the personalised 3D-printed osteotomy group (114.70 ± 2.21 min, 639.70 ± 5.00 mL, 11.82 ± 0.42 times, 231.20 ± 3.86 mL) was superior to the traditional group (150.40 ± 2.45 min, 850.50 ± 5.34 mL, 17.09 ± 0.39 times, 324.30 ± 4.06 mL). There was a statistically significant difference between the 3D-printed osteotomy group and the traditional osteotomy group in terms of the operation time, intraoperative blood loss, X-ray frequency and postoperative 24 h drainage volume (p < 0.05). And there were no substantial differences in the hip angle and the 6-month postoperative Harris hip score between the two groups (p > 0.05). CONCLUSION: The 3D-printed osteotomy template for PAO is a valid method and its short-term clinical effect is superior to that of traditional osteotomy.

Identification and characterization of extrachromosomal circular DNA in alcohol induced osteonecrosis of femoral head.

Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples (n = 7) and fracture of femoral neck samples as a control (n = 7) were purified by removing linear DNA and rolling circle amplification. High-throughput sequencing and bioinformatics analysis were performed to study the characterization and biofunction of eccDNAs. We identified more than 600,000 unique eccDNAs. The number of detected eccDNAs in AIONFH was less than that in the control, and eccDNA formation may be related to transcription or other characteristics of coding genes. The eccDNA lengths are mainly distributed between 0.1 kb and 1 kb, with a major peak in 0.358 kb. The bioinformatic analysis showed that 25 significant genes were detected, including MAP3K1, ADCY1, CACNA1S, and MACF1, which contributed to regulating bone formation. GO and KEGG analyses suggested that the related genes derived from exons mainly affected metabolic processes and signal transduction, and bone metabolism-related pathways, such as the MAPK pathway and TGF-ß pathway, were enriched. EccDNAs in AIONFH are common and may play an important role in pathogenesis by regulating bone metabolism.

Total Hip Arthroplasty with Robotic Arm Assistance for Precise Cup Positioning: A Case-Control Study.

OBJECTIVE: To determine whether more precise cup positioning can be achieved with robot-assisted total hip arthroplasty (THA) as compared to conventional THA. METHODS: In this study, between July 2019 and May 2021, 93 patients aged 23-75 years with osteonecrosis of the femoral head (ONFH) and adult developmental dysplasia of hip who underwent first hip surgery were included in the study. They were randomly assigned to either the robotic-assisted THA group (n = 45) or the conventional THA group (n = 48). After the operation, all patients were given routine rapid rehabilitation guidance. The duration of operation was recorded to estimate the learning curve through cumulative summation analysis. We compared the demographics, duration of operation, cup positioning, leg length discrepancy, hip offset, and Harris Hip Score between robot-assisted THA and manual THA. Precision in the positioning of the acetabular prosthesis using the MAKO system was also compared between the two groups. RESULTS: The mean duration of operation for the robot-assisted THA group was 91.37 ± 17.34 min (range: 63 to 135 min), which was significantly higher than that for the conventional THA group. When the number of procedures was increased to 13, the duration of operation in the robot-assisted group decreased significantly and gradually became stable. In terms of duration of operation, robot-assisted THA was associated with a learning curve of 13 cases. The mean amount of bleeding in the robot-assisted THA group was not significantly different from that in conventional THA group (328 ± 210 ml vs 315 ± 205 ml) (p = 0.741). There was no significant difference in the proportion of prostheses located within Lewinnek's safe zone between robot-assisted THA group and conventional THA group (69.81% vs 64.41%). The leg length discrepancy (LLD) was significantly smaller in the robot-assisted THA group than in the conventional THA group (p < 0.001), but both were within acceptable limits (10 mm). The inclination and anteversion angles of the acetabular prosthesis planned before operations were correlated with the actual measurement (r = 0.857 p < 0.001, r = 0.830, p < 0.001). After surgery, none of the patients experienced hip dislocation, aseptic loosening, or periprosthetic infection during the 3 months of follow-up. CONCLUSION: The proportion of acetabular prostheses in the Lewinnek's safety zone was higher and the extent of LLD was significantly lower in the robot-assisted THA group, as compared to the same metrics in the conventional THA group. The MAKO robot improved the accuracy of implant placement in THA.

Construction of the Skeleton of Lucidumone.

The skeleton of lucidumone was constructed through oxidative dearomatization/intramolecular Diels-Alder reaction, Cu-mediated remote C-H hydroxylation, allyl oxidation, acid-promoted dynamic kinetic resolution cyclization, and benzylic oxidation.

Multi-Task Deep Supervision on Attention R2U-Net for Brain Tumor Segmentation.

Accurate automatic medical image segmentation technology plays an important role for the diagnosis and treatment of brain tumor. However, simple deep learning models are difficult to locate the tumor area and obtain accurate segmentation boundaries. In order to solve the problems above, we propose a 2D end-to-end model of attention R2U-Net with multi-task deep supervision (MTDS). MTDS can extract rich semantic information from images, obtain accurate segmentation boundaries, and prevent overfitting problems in deep learning. Furthermore, we propose the attention pre-activation residual module (APR), which is an attention mechanism based on multi-scale fusion methods. APR is suitable for a deep learning model to help the network locate the tumor area accurately. Finally, we evaluate our proposed model on the public BraTS 2020 validation dataset which consists of 125 cases, and got a competitive brain tumor segmentation result. Compared with the state-of-the-art brain tumor segmentation methods, our method has the characteristics of a small parameter and low computational cost.

Palladium-Promoted Neutral 1,4-Brook Rearrangement/Intramolecular Allylic Cyclization Cascade Reaction: A Strategy for the Construction of Vinyl Cyclobutanols.

A cascade reaction to build vinyl cyclobutanol rings through activation of vinyl epoxides by palladium, followed by 1,4-Brook rearrangement and intramolecular cyclization with a palladium complex of the resulting carbon anion, is described. Through this cascade reaction, several highly substituted cyclobutanol substrates were achieved in good yields with high stereoselectivities.

[Application of tibial mechanical axis locator in tibial extra-articular deformity in total knee arthroplasty].

OBJECTIVE: To explore the application value of self-made tibial mechanical axis locator in tibial extra-articular deformity in total knee arthroplasty (TKA) for improving the lower extremity force line. METHODS: Between January and August 2012, 13 cases (21 knees) of osteoarthritis with tibial extra-articular deformity were treated, including 5 males (8 knees) and 8 females (13 knees) with an average age of 66.5 years (range, 58-78 years). The disease duration was 2-5 years (mean, 3.5 years). The knee society score (KSS) was 45.5 +/- 15.5. Extra-articular deformities included 1 case of knee valgus (2 knees) and 12 cases of knee varus (19 knees). Preoperative full-length X-ray films of lower extremities showed 10-21 degrees valgus or varus deformity of tibial extra joint. Self-made tibial mechanical axis locator was used to determine and mark coronal tibial mechanical axis under X-ray before TKA, and then osteotomy was performed with extramedullary positioning device according to the mechanical axis marker.' RESULTS: All incisions healed by first intention, without related complications of infection and joint instability. All patients were followed up 5-12 months (mean, 8.3 months). The X-ray examination showed < 2 degrees knee deviation angle in the others except 1 case of 2.9 degrees knee deviation angle at 3 days after operation, and the accurate rate was 95.2%. No loosening or instability of prosthesis occurred during follow-up. KSS score was 85.5 +/- 15.0 at last follow-up, showing significant difference when compared with preoperative score (t=12.82, P=0.00). CONCLUSION: The seft-made tibial mechanical axis locator can improve the accurate rate of the lower extremity force line in TKA for tibia extra-articular deformity.