Differential effects of clopidogrel and/or aspirin on the healing of tooth extraction wound bone tissue.

Introduction: A multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines. Methods: 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1 week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10 mg/kg/d), aspirin (15 mg/kg/d), clopidogrel (10 mg/kg/d)+aspirin (15 mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28 days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin). Results: MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05). Conclusion: Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

Pulsed Airstream-Driven Hierarchical Micro-Nano Pore Structured Triboelectric Nanogenerator for Wireless Self-Powered Formaldehyde Sensing.

Formaldehyde (HCHO), as a common volatile organic compound, has a serious impact on human health in the daily lives and industrial production scenarios. Given the security issue of HCHO detection and danger warning, a ZIF-8/copper foam based pulsed airstream-driven triboelectric nanogenerator (ZCP-TENG) is designed to develop the self-powered HCHO sensors. By combining contact electrification and electrostatic induction, the ZCP-TENG can be utilized for airflow energy harvesting and HCHO concentration detection. The short-circuit current and output power of the ZCP-TENG can reach 2.0 µA and 81 µW (20 ppm). With the high surface area, abundant micro-nano pores, and excellent permeation flux, the ZCP-TENGs exhibit excellent HCHO sensing response (61.3% at 100 ppm), low detection limit (≈2 ppm), and rapid response/recovery time (14/15 s), which can be served as a highly sensitive and selective HCHO sensor. By connecting an intelligent wireless alarm, the ZCP-TENGs are designed to construct a self-powered warning system to monitor and remind the HCHO of exceedance situations. Moreover, by combining a support vector machine model, the difference concentrations can be quickly identified with an average prediction accuracy of 100%. This study illustrates that ZCP-TENGs have broad application prospects and provide guidance for HCHO monitoring and danger warnings.

A feasibility study of tumor motion monitoring for SBRT of lung cancer based on 3D point cloud detection and stacking ensemble learning.

PURPOSE: To construct a tumor motion monitoring model for stereotactic body radiation therapy (SBRT) of lung cancer from a feasibility perspective. METHODS: A total of 32 treatment plans for 22 patients were collected, whose planning CT and the centroid position of the planning target volume (PTV) were used as the reference. Images of different respiratory phases in 4DCT were acquired to redefine the targets and obtain the floating PTV centroid positions. In accordance with the planning CT and CBCT registration parameters, data augmentation was accomplished, yielding 2130 experimental recordings for analysis. We employed a stacking multi-learning ensemble approach to fit the 3D point cloud variations of body surface and the change of target position to construct the tumor motion monitoring model, and the prediction accuracy was assess using root mean squared error (RMSE) and R-Square (R2). RESULTS: The prediction displacement of the stacking ensemble model shows a high degree of agreement with the reference value in each direction. In the first layer of model, the X direction (RMSE =0.019 ∼ 0.145mm, R2 =0.9793∼0.9996) and the Z direction (RMSE = 0.051 ∼ 0.168 mm, R2 = 0.9736∼0.9976) show the best results, while the Y direction ranked behind (RMSE = 0.088 ∼ 0.224 mm, R2 = 0.9553∼ 0.9933). The second layer model summarizes the advantages of unit models of first layer, and RMSE of 0.015 mm, 0.083 mm, 0.041 mm, and R2 of 0.9998, 0.9931, 0.9984 respectively for X, Y, Z were obtained. CONCLUSIONS: The tumor motion monitoring method for SBRT of lung cancer has potential application of non-ionization, non-invasive, markerless, and real-time.

Establishment and validation of a risk prediction model for delayed neurocognitive recovery associated with cerebral oxygen saturation monitoring.

BACKGROUND: Delayed neurocognitive recovery (DNR) is a common complication in patients undergoing laparoscopic surgery, and there are currently no effective therapies. It is vital to provide a reliable basis for clinical prediction. This study tried to analyse the risk factors for DNR in patients undergoing laparoscopic colorectal surgery and to establish a risk prediction model. METHODS: A retrospective analysis of the clinical data and DNR status of patients undergoing laparoscopic colorectal surgery at Xiangya Hospital of Central South University from March 2018 to July 2020 was conducted. Logistic regression was performed to analyse the related risk factors for DNR post-operatively, and the predictive model of DNR post-operatively was constructed and validated internally. Patients who underwent laparoscopic colorectal surgery between January and July 2021 were also selected for external validation of the predictive model, to ultimately investigate the risk factors for DNR in patients undergoing laparoscopic colorectal surgery. RESULTS: The incidence of DNR in patients undergoing laparoscopic colorectal surgery was 15.2% (31/204). The maximum variability of cerebral oxygen, age, education, and pre-existing diabetes was related to the incidence of DNR (p < 0.05). The risk prediction model of DNR after laparoscopic colorectal surgery was established. The internal and external validation showed that the discrimination was good (the AUCs were 0.751 and 0.694, respectively). CONCLUSIONS: The risk prediction model of DNR related to cerebral oxygen saturation monitoring shows good predictive performance and clinical value, providing a basis for postoperative DNR prevention.

Attention-guided context asymmetric fusion networks for the liver tumor segmentation of computed tomography images.

Background: Liver tumor segmentation based on medical imaging is playing an increasingly important role in liver tumor research and individualized therapeutic decision-making. However, it remains a challenging in terms of the accuracy of automatic segmentation of liver tumors. Therefore, we aimed to develop a novel deep neural network for improving the results from the automatic segmentation of liver tumors. Methods: This paper proposes the attention-guided context asymmetric fusion network (AGCAF-Net), combining attention guidance and fusion context modules on the basis of a residual neural network for the automatic segmentation of liver tumors. According to the attention-guided context block (AGCB), the feature map is first divided into multiple small blocks, the local correlation between features is calculated, and then the global nonlocal fusion module (GNFM) is used to obtain the global information between pixels. Additionally, the context pyramid module (CPM) and asymmetric semantic fusion module (AFM) are used to obtain multiscale features and resolve the feature mismatch during feature fusion, respectively. Finally, we used the liver tumor segmentation benchmark (LiTS) dataset to verify the efficiency of our designed network. Results: Our results showed that AGCAF-Net with AFM and CPM is effective in improving the accuracy of liver tumor segmentation, with the Dice coefficient increasing from 82.5% to 84.1%. The segmentation results of liver tumors by AGCAF-Net were superior to those of several state-of-the-art U-net methods, with a Dice coefficient of 84.1%, a sensitivity of 91.7%, and an average symmetric surface distance of 3.52. Conclusions: AGCAF-Net can obtain better matched and accurate segmentation in liver tumor segmentation, thus effectively improving the accuracy of liver tumor segmentation.

Mirror Syndrome Combined with Postpartum Hemolytic Uremic Syndrome.

BACKGROUND: Mirror syndrome is a rare disease characterized by "triple edema", while Hemolytic Uremic Syndrome (PHUS) is a serious disease that occurs within a short period of time after the end of pregnancy, with a low prevalence and poor prognosis, and it is even rarer for both to occur in the same patient. METHODS: We report a case of mirror syndrome combined with PHUS and analyze the clinical data to improve the understanding of the disease. RESULTS: The patient presented clinically with "triple edema" and was diagnosed with mirror image syndrome. After cesarean section, the patient developed cardiac insufficiency, renal insufficiency, hemolysis, and other symptoms and was diagnosed as PHUS. After active treatment, the maternal prognosis was good. CONCLUSIONS: Mirror syndrome and PHUS are both clinically rare diseases with poor long-term prognosis if not diagnosed and treated in a timely manner; therefore, awareness of the diseases, early and accurate diagnosis and timely and correct treatment should be improved.

Intentional replantation for a Class 4/Stage C cemental tear: Etiology, choice and outcomes of treatment.

Cemental tears, root cracks, and associated periapical-periodontal lesions may occur simultaneously in one tooth, and can be effectively managed by intentional replantation and etiological control. A durable splint, along with occlusal and periodontal monitoring, is required as healing progresses slowly and may be insufficient.

Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis.

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.

Ethnic and national identification of minority youth in China: The mediating role of intergroup orientation.

This study examined the mediating role of intergroup orientation in the relationship between ethnic and national identification. Our participants were 1320 Yi minority youths from a secondary school located in the Yi ethnic autonomous prefecture of southwest China. The participants completed three self-report questionnaires measuring ethnic and national identification, and intergroup orientation, respectively. Structural equation modeling was employed to determine the relationships between ethnic and national identification and intergroup orientation, and to explore the mechanism underlying the association between ethnic and national identification. The results showed that Yi minority youths with a stronger sense of ethnic identity had a stronger sense of national identity. The results further indicated that stronger ethnic identity led to a more positive intergroup orientation, which in turn predicted a stronger national identity. Our findings may facilitate the cultivation of positive attitudes between national subgroups in multiethnic countries and help ethnic minority youth develop a stronger awareness of national identity while retaining their ethnic identity.

A highly specific and ultrasensitive approach to detect Prymnesium parvum based on RPA-CRISPR-LbaCas12a-LFD system.

BACKGROUND: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance. RESULTS: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL). SIGNIFICANCE: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs.

Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

Electroacupuncture and carbamazepine for patients with trigeminal neuralgia: a randomized, controlled, 2 × 2 factorial trial.

BACKGROUND: Trigeminal neuralgia (TN) is difficult to treat due to its severe pain intensity and recurring episodes, which significantly impact quality of life. OBJECTIVES: We aimed to assess the effectiveness of electroacupuncture (EA) in alleviating the pain intensity in TN, and to determine whether EA combined with low-dosage carbamazepine (CBZ) has a synergistic effect. METHODS: A multi-centre, randomized, 2 × 2 factorial trial was conducted. Participants who met the inclusion criteria received active EA or sham EA for 60 min, three times a week for four weeks; CBZ (300 mg per day) or placebo for four weeks. The primary outcome was the change in visual analog scale (VAS) score from baseline to weeks 2, 4, 16, and 28. Secondary outcomes included quality of life and adverse events. RESULTS: A total of 120 participants (75 females and 45 males; mean (SD) age, 58.5 (15.3) years) were included. The main effects of EA and CBZ were significant (P < 0.001), and there was a significant interaction was identified between the interventions (P = 0.041). Participants who received EA (mean difference [MD], -0.3 [95% CI, -0.40 to -0.20] at week 2; -1.6 [-1.70 to -1.50] at week 4; -1.1 [-1.31 to -0.89] at week 16; -0.8 [-1.01 to -0.59] at week 28), CBZ (MD, -0.6 [95% CI, -0.70 to -0.50] at week 2; -0.9 [-1.03 to -0.77] at week 4, -0.2 [-0.41 to 0.01] at week 16, 0.2 [-0.01 to 0.41] at week 28), and the combination of both (MD, -1.8 [95% CI, -1.90 to -1.70] at week 2; -3.7 [-3.83 to -3.57] at week 4, -3.4 [-3.61 to -3.19] at week 16, -2.9 [-3.11 to -2.69] at week 28) had a greater reduction in VAS score over the treatment phase than their respective control groups (sham EA, placebo, and sham EA plus placebo). EA-related adverse events (6/59, 10.17%) were lower than that of CBZ (15/59, 25.42%) during the whole phases. CONCLUSIONS: EA or CBZ alone are effective treatments for TN, while the combination of EA and low-dosage CBZ exerts a greater benefit. These findings in this trial demonstrate that the combination of EA and low-dosage CBZ may be clinically effective under certain circumstances. TRIAL REGISTRATION: NCT03580317.

Experimental Study on Calcination of Portland Cement Clinker Using Different Contents of Stainless Steel Slag.

In order to increase the utilization rate of stainless steel slag, reduce storage needs, and mitigate environmental impacts, this study replaces a portion of limestone with varying amounts of stainless steel slag in the calcination of Portland cement clinker. The study primarily examines the influence of stainless steel slag on the phase composition, microstructure, compressive strength, and free calcium oxide (ƒ-CaO) content of Portland cement clinker. The results show the following: (1) Using stainless steel slag to calcine Portland cement clinker can lower the calcination temperature, reducing industrial production costs and energy consumption. (2) With an increase in the amount of stainless steel slag, the dicalcium silicate (C2S) and tricalcium silicate (C3S) phases in Portland cement clinker initially increase and then decrease; the C3S crystals gradually transform into continuous hexagonal plate-shaped distributions, while the tricalcium aluminate (C3A) and tetracalcium aluminoferrite (C4AF) crystal structures become denser. When the stainless steel slag content is 15%, the dicalcium silicate and tricalcium silicate phases are at their peak; the C3S crystals are continuously distributed with a relatively dense structure, and C3A and C4AF crystals melt and sinter together, becoming distributed around C3S. (3) As stainless steel slag content increases, the compressive strength of Portland cement clinker at 3 days, 7 days, and 28 days increases and then decreases, while ƒ-CaO content decreases and then increases. When the stainless steel slag content is 15%, the compressive strength at 28 days is at its highest, 64.4 MPa, with the lowest ƒ-CaO content, 0.78%. The test results provide a basis for the utilization of stainless steel slag in the calcination of Portland cement clinker.

Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer.

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. RESULTS: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3-61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). CONCLUSIONS: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. TRIAL REGISTRATION: NCT04766320, Jan 04, 2021.

The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.

Nematicidal glycosylated resorcylic acid lactones from the fungus Pochonia chlamydosporia PC-170 and their key biosynthetic genes.

Chemical study of the nematicidal biocontrol fungus Pochonia chlamydosporia PC-170 led to discovery of six resorcylic acid lactones (RALs), including three nematicidal glycosylated RALs, monocillin VI glycoside (1), colletogloeolactone A (2) and monocillin II glycoside (3), and three antibacterial non-glycosylated RALs, monocillin VI (4), monocillin IV (5) and monocillin II (6). The planar structure of the new compound monocillin VI glycoside (1) was elucidated using HRESIMS and NMR data, and its monosaccharide configuration was further determined through sugar hydrolysis experiment and GC-MS analysis method. Furthermore, their two biosynthetic-related PKS genes, pchE and pchI, were identified through the gene knockout experiment. The glycosylated RALs 1-3 exhibited nematicidal activity against Meloidogyne incognita, with LC50 values of 94, 152 and 64 µg/mL, respectively, and thus had great potential in the development of new nematicidal natural products to control M. incognita in the future.

A novel LINC02321 promotes cell proliferation and decreases cisplatin sensitivity in bladder cancer by regulating RUVBL2.

Bladder cancer (BC) has a high incidence and is prone to recurrence. In most instances, the low 5-year survival rate of advanced BC patients results from postoperative recurrence and drug resistance. Long noncoding RNAs (lncRNAs) can participate in numerous biological functions by regulating the expression of genes to affect tumorigenesis. Our previous work had demonstrated that a novel lncRNA, LINC02321, was associated with BC prognosis. In this study, A high expression of LINC02321 was found in BC tissues, which was associated with poor prognosis in patients. LINC02321 promoted both proliferation and G1-G0 progression in BC cells, while also inhibited sensitivity to cisplatin. Mechanistically, LINC02321 can bind to RUVBL2 and regulate the expression levels of RUVBL2 protein by affecting its half-life. RUVBL2 is involved in the DNA damage response. The potential of DNA damage repair pathways to exert chemosensitization has been demonstrated in vivo. The rescue experiment demonstrated that RUVBL2 overexpression can markedly abolish the decreased cell proliferation and the increased sensitivity of BC cells to cisplatin caused by LINC02321 knockdown. The results indicate that LINC02321 functions as an oncogene in BC, and may serve as a novel potential target for controlling BC progression and addressing cisplatin resistance in BC therapy.

The efficacy and safety of electroacupuncture for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN. METHODS: To find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses. DISCUSSION: This protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.

An electrochemical immunosensor based on hybrid self-assembled monolayers for rapid detection of Bombyx mori nucleopolyhedrovirus.

Bombyx mori nucleopolyhedrovirus (BmNPV) is highly contagious and poses a serious threat to sericulture production. Because there are currently no effective treatments for BmNPV, a rapid and simple detection method is urgently needed. This paper describes an electrochemical immunosensor for the detection of BmNPV. The immunosensor was fabricated by covalently immobilizing anti-BmNPV, a biorecognition element, onto the surface of the working gold electrode via 11-mercaptoundecanoic acid (MUA)/ß-mercaptoethanol (ME) hybrid self-assembled monolayers. Electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM) were used to characterize the electrochemical performance and morphology of the immunosensor, respectively. Under optimum conditions, the developed immunosensor exhibited a linear response to BmNPV polyhedrin in the range of 1 × 102-1 × 108 fg/mL, with a low detection limit of 14.54 fg/mL. The immunosensor also exhibited remarkable repeatability, reproducibility, specificity, accuracy, and regeneration. Normal silkworm blood was mixed with BmNPV polyhedrin and analyzed quantitatively using this sensor, and the recovery was 92.31 %-100.61 %. Additionally, the sensor was used to analyze silkworm blood samples at different time points after BmNPV infection, and an obvious antigen signal was detected at 12 h post infection. Although this result agreed with that provided by the conventional polymerase chain reaction (PCR) method, the electroanalysis method established in this study was simpler, shorter in detection period, and lower in material cost. Furthermore, this innovative electrochemical immunosensor, developed for the ultra-sensitive and rapid detection of BmNPV, can be used for the early detection of virus-infected silkworms.