A Disconnection for Rapid Access to Heterocyclic Benzylic Amines with Fully Substituted α-Carbons.

2- or 4-Pyridyl benzylic amines represent a privileged motif in drug discovery. However, the formation of heterocyclic benzylic amines with fully substituted α-carbons can require the execution of lengthy synthetic routes, which limit their application. Addition of various nucleophilic agents to Ellman's imines has been well established; however, there is no precedented literature reported for pyridyl-type nucleophiles, which are very important for medicinal chemistry. In this letter, we disclose the development of a one-step synthesis of heterocyclic benzylic amines with fully substituted α-carbons from heteroaryl halides and sulfinyl imines. Starting from 2,4-dibromopyridine, regioselective synthesis of 2- or 4-pyridyl benzylic amines could be achieved by choosing toluene or MTBE as a solvent.

Enhancing Diagnostic Accuracy for Gastric Cancer: Integration of Multi-Slice Spiral CT and Gastrointestinal Angiography.

Objective: This study aimed to assess the clinical efficacy of combining multi-slice spiral CT with gastrointestinal angiography for diagnosing gastric cancer. Methods: We conducted a retrospective analysis of clinical data from 151 patients with suspected gastric cancer admitted to our hospital between January 2014 and January 2022. Among them, 70 patients underwent multi-slice spiral CT alone (control group), while the remaining 81 patients underwent multi-slice spiral CT in combination with gastrointestinal barium contrast (combination group). Finally, pathological examination confirmed gastric cancer in 81 patients. We analyzed the diagnostic efficacy of multi-slice spiral CT combined with gastrointestinal angiography for staging gastric cancer and detecting lymph node metastasis. Results: The sensitivity and accuracy of diagnosing gastric cancer using multi-slice spiral CT combined with gastrointestinal angiography were significantly superior to CT alone (P < .05). This combined approach exhibited substantial advancements in detecting stage I and II tumors compared to a single CT, although the difference in stage III detection rate was marginal (P < .05). Furthermore, among the 81 gastric cancer cases, 67 were confirmed to have lymph node metastasis through surgical and pathological examination. The lymph node detection rate with multi-slice spiral CT combined with gastrointestinal angiography was significantly higher than that achieved with single CT (P < .05). Conclusions: Combining multi-slice spiral CT with gastrointestinal angiography proved to be an effective diagnostic strategy for gastric cancer.

Dual-Functional Tetrahedron Multivalent Aptamer Assisted Amplification-Free CRISPR/Cas12a Assay for Sensitive Detection of Salmonella.

Salmonellosis continues to impose a significant economic burden globally. Rapid and sensitive detection of Salmonella is crucial to preventing the outbreaks of foodborne illnesses, yet it remains a formidable challenge. Herein, a dual-functional tetrahedron multivalent aptamer assisted amplification-free CRISPR/Cas12a assay was developed for Salmonella detection. In the system, the aptamer was programmatically assembled on the tetrahedral DNA nanostructure to fabricate a multivalent aptamer (TDN-multiApt), which displayed a 3.5-fold enhanced avidity over the monovalent aptamer and possessed four CRISPR/Cas12a targeting fragments to amplify signal. Therefore, TDN-multiApt could directly activate Cas12a to achieve the second signal amplification without any nucleic acid amplification. By virtue of the synergism of high avidity and cascaded signal amplifications, the proposed method allowed the ultrasensitive detection of Salmonella as low as 7 cfu mL-1. Meanwhile, this novel platform also exhibited excellent specificity against target bacteria and performed well in the detection of various samples, indicating its potential application in real samples.

Exploring the impact of TGF-ß family gene mutations and expression on skin wound healing and tissue repair.

Transforming Growth Factor-Beta (TGF-ß) signalling pathway is of paramount importance in the processes of wound healing, epidermal integrity maintenance and development of skin cancer. The objective of this research endeavour was to clarify the impact of gene mutations and variations in expression within TGF-ß family on mechanisms of tissue repair, as well as to identify potential targets for therapeutic purposes in non-melanoma skin cancer (NMSC). The methods utilized in this study involved obtaining RNA-seq data from 224 NMSC patients and paired normal skin tissues from the PRJNA320473 and PRJEB27606 databases. The purpose of the differential gene expression analysis was to identify genes whose expression had changed significantly. In order to evaluate the effects and interrelationships of identified gene variants, structural analysis with AlphaFold and PDB data and network analysis with the STRING database were both utilized. Critical gene expression was externally validated through the utilization of the GEPIA database. Tumour tissues exhibited a notable upregulation of genes associated with the TGF-ß pathway, specifically MMP1, MMP3, MMP9, EGF, COL3A1 and COL1A2, in comparison with normal tissues. As indicated by the central node status of these genes in the network analysis, they play a crucial role in the progression of NMSCs. The results of the structural analysis suggested that mutations might cause functional disruptions. External validation of the upregulation confirmed the expression trends and emphasized the biomarker potential of the upregulated genes. In conclusion, this research offered thorough examination of molecular modifications that occur in TGF-ß family genes, which are linked to cutaneous wound healing and NMSC. The modified expression of the identified hub genes may represent innovative targets for therapeutic intervention.

Highly sensitive detection of Salmonella based on dual-functional HCR-mediated multivalent aptamer and amplification-free CRISPR/Cas12a system.

BACKGROUND: Salmonella infection severely threatens human health and causes substantial medical and financial concerns. Sensitive and specific detection of Salmonella in food samples is crucial but remains challenging. While some traditional assays for S. typhimurium are reliable, they suffer from various limitations, such as being time-consuming (culture-based methods), involving intricate nucleic molecular extraction (polymerization chain reaction, PCR), and exhibiting inadequate sensitivity (enzyme-linked immunosorbent assay, ELISA). In this case, it is essential to establish a rapid, simple-operation, and sensitive method for monitoring S. typhimurium to preserve food quality and prevent contamination. RESULT: Herein, an amplification-free detection method for Salmonella was developed by coupling the aptamer magnetic separation with dual-functional HCR (hybridization chain reaction)-scaffold multivalent aptamer and the activity of CRISPR/Cas12a. In the detection system, the dual-functional HCR-scaffold multivalent aptamer with high binding affinity and specificity was fabricated in advance by assembling numerous Salmonella specific aptamers on the long HCR products. In addition to the enhanced affinity, the HCR-multiApt also contains a massive amount of repeated CRISPR-targetable DNA units in its HCR scaffold, which could trigger the trans-cleavage activity of Cas12a. In the presence of target bacteria, the HCR-scaffold multivalent aptamer could attach on the surface of bacteria effectively and amplified the signal of bacteria into CRISPR/Cas12a based fluorescent readout. The proposed detection system allowed for ultrasensitive detection of Salmonella in a linear range from 100 to 107 cfu mL-1 with a LOD (limit of detection) of 2 cfu mL-1. SIGNIFICANCE: The novel dual-functional HCR-multiApt presents a simple and powerful strategy for improving the aptamer binding affinity toward Salmonella. Simultaneously, integrating this dual-functional HCR-multiApt with the CRISPR/Cas12a system significantly enhances the sensitivity by cascade signal amplification in a nucleic acids amplification-free way. Finally, leveraging the versatility of the aptamer, this highly sensitive method can be further extended for application in the detection of other bacteria, food safety monitoring, or clinical diagnostics.

A Colorimetric/Fluorescent Dual-Mode Aptasensor for Salmonella Based on the Magnetic Separation of Aptamers and a DNA-Nanotriangle Programmed Multivalent Aptamer.

Salmonella infection has emerged as a global health threat, causing death, disability, and socioeconomic disruption worldwide. The rapid and sensitive detection of Salmonella is of great significance in guaranteeing food safety. Herein, we developed a colorimetric/fluorescent dual-mode method based on a DNA-nanotriangle programmed multivalent aptamer for the sensitive detection of Salmonella. In this system, aptamers are precisely controlled and assembled on a DNA nanotriangle structure to fabricate a multivalent aptamer (NTri-Multi-Apt) with enhanced binding affinity and specificity toward Salmonella. The NTri-Multi-Apt was designed to carry many streptavidin-HRPs for colorimetric read-outs and a large load of Sybr green I in the dsDNA scaffold for the output of a fluorescent signal. Therefore, combined with the magnetic separation of aptamers and the prefabricated NTri-Multi-Apt, the dual-mode approach achieved simple and sensitive detection, with LODs of 316 and 60 CFU/mL for colorimetric and fluorescent detection, respectively. Notably, the fluorescent mode provided a self-calibrated and fivefold-improved sensitivity over colorimetric detection. Systematic results also revealed that the proposed dual-mode method exhibited high specificity and applicability for milk, egg white, and chicken meat samples, serving as a promising tool for real bacterial sample testing. As a result, the innovative dual-mode detection method showed new insights for the detection of other pathogens.

Application Value of Gastroenterography Combined With CT in the Evaluation of Short-Term Efficacy and Prognosis in Patients With Esophageal Cancer Radiotherapy.

Purpose: To observe the application value of gastroenterography combined with CT in the evaluation of short-term efficacy and prognosis in patients with esophageal cancer radiotherapy. Methods: From January 2013 to December 2020, the clinical data of 207 patients with esophageal cancer treated by radiotherapy in our hospital were collected retrospectively. All patients received gastroenterography and CT examination before and after radiotherapy, and the patients were followed-up for 1 year, and the evaluation value of their short-term efficacy and prognosis was observed. Results: After radiotherapy, the length diameter, short diameter, and volume of the lymph node were lower than those before radiotherapy (p < 0.05), but the maximum tube wall thickness had no significant difference (p > 0.05). The length diameter, short diameter, and volume of the lymph node, and the maximum tube wall thickness in the good efficacy group and the good prognosis group were lower, and the objective response rate in the good prognosis group was higher (p < 0.05). The area under the curve (AUC) of the length diameter, short diameter, and volume of the lymph node to evaluate the short-term efficacy of patients with esophageal cancer was 0.738, 0.705, and 0.748, respectively, and the AUC to evaluate the prognosis of patients with esophageal cancer was 0.751, 0.776, and 0.791, respectively. Conclusion: Gastroenterography combined with CT has a good application value in the evaluation of short-term efficacy and prognosis in patients with esophageal cancer radiotherapy.

Formation of texture quality of raspberry snack under microwave puffing.

Raspberry snack, as a novel berry product, has rich favor and high crisp taste, where controllable texture quality is conducive to the palatability of the snack. Determinative factors of microwave puffing in microwave intensity and duration and key property of material in Young's modulus were introduced to investigate the formation of texture quality of berry snack under microwave puffing. The results indicate that the microwave intensity has negative correlation with Young's modulus of raspberry chips, which causes the more porosity inside under microwave puffing. Reasonable Young's modulus of raspberry chips enhances the interior porosity and exterior expansion volume of raspberry snack due to the water vapor wrapped other than escaped. The greater microwave intensity results in the higher volume expansion of raspberry chips, in which the great volume expansion from porous pores structure confers moderate hardness. In microwave puffing, the formation of hardness and crispness of raspberry snack depend on microwave puffing parameters, leading to high temperature and great dehydration rate in quick puffing duration, in addition to Young's modulus of raspberry chips, where high dehydration rate accelerates water removal inside raspberry chips to form a harder texture with decreasing springiness, whereas low dehydration rate leads to the gentle change of springiness. Raspberry snack with uniform internal pores and regular shape forming desirable texture may be achieved under the microwave intensity of 7.5 W/g and the puffing duration of 6 min. This study indicates that high-quality raspberry snack may be achieved via controlling heating rate in microwave puffing.

Effect of Tongluozhitong Prescription-Assisted Intra-Articular Injection of Sodium Hyaluronate on VAS Score and Knee Lysholm Score in Patients with Knee Osteoarthritis.

Knee osteoarthritis (KOA) has become one of the leading causes of workforce loss in the middle-aged and elderly population and a global public health problem second only to cardiovascular disease, so we need to find more effective treatments for this disease. In this study, we selected 120 patients with KOA admitted to our hospital from June 2018 to December 2020 and divided them into treatment group 1, treatment group 2, and joint group according to the random number table method, with 40 patients in each group. Treatment group 1 was treated with Tongluozhitong prescription dip-soaking therapy, treatment 2 group was treated with intra-articular injection of sodium hyaluronate, and the joint group was treated with a combination of both modalities for 4 weeks in all three groups. Clinical efficacy, visual analogue scale (VAS), Lysholm knee score (LKS), activity of daily living score (ADL), the levels of bone metabolic markers such as cartilage oligomeric matrix protein (COMP), type II collagen degradation maker (CTX-II), and matrix metalloproteinase-3 (MMP-3), and the levels of inflammatory mediators such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and hypersensitive C-reactive protein (hs-CRP) were used as observations to compare and analyze the therapeutic effects of the three treatment regimens in KOA patients. The results showed that the clinical excellence rates of the joint group, treatment group 1, and treatment group 2 were 72.50%, 50.00%, and 90.00%, respectively, with statistically significant differences between any two comparisons. After treatment, VAS scores, serum COMP, CTX-II, MMP-3, IL-1ß, TNF-α, and hs-CRP levels decreased in all three groups, and the levels of each index were as follows: joint group < treatment group 1 < treatment group 2, and the difference between any two comparisons was statistically significant. The LKS score and ADL score increased in all three groups, and the levels of each index were as follows: joint group > treatment group 1 > treatment group 2, with statistically significant differences in any two groups compared. None of the patients in the three groups experienced any significant adverse effects during treatment. This suggests that the dip-soaking therapy of Tongluozhitong prescription is more advantageous than intra-articular sodium hyaluronate injection treatment in suppressing the level of serum bone metabolic markers and inflammatory mediators, reducing pathological joint damage, relieving symptoms of pain, alleviating degenerative joint symptoms, and improving knee function in KOA patients. The combination of the two in KOA patients can significantly improve the efficacy and has a good safety profile.