Molecular network mechanism in cerebral ischemia-reperfusion rats treated with human urine stem cells.

Objective: To explore the effect of human urine-derived stem cells (husc) in improving the neurological function of rats with cerebral ischemia-reperfusion (CIR), and report new molecular network by bioinformatics, combined with experiment validation. Methods: After CIR model was established, and husc were transplanted into the lateral ventricle of rats，neurological severe score (NSS) andgene network analysis were performed. Firstly, we input the keywords "Cerebral reperfusion" and "human urine stem cells" into Genecard database and merged data with findings from PubMed so as to get their targets genes, and downloaded them to make Venny intersection plot. Then, Gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) were performed to construct molecular network of core genes. Lastly, the expressional level of core genes was validated via quantitative real-time polymerase chain reaction (qRT-PCR), and localized by immunofluorescence. Results: Compared with the Sham group, the neurological function of CIR rats was significantly improved after the injection of husc into the lateral ventricle; at 14 days, P = 0.028, which was statistically significant. There were 258 overlapping genes between CIR and husc, and integrated with 252 genes screened from PubMed and CNKI. GO enrichment analysis were mainly involved neutrophil degranulation, neutrophil activation in immune response and platelet positive regulation of degranulation, Hemostasis, blood coagulation, coagulation, etc. KEGG pathway analysis was mainly involved in complement and coagulation cascades, ECM-receptor. Hub genes screened by Cytoscape consist ofCD44, ACTB, FN1, ITGB1, PLG, CASP3, ALB, HSP90AA1, EGF, GAPDH. Lastly, qRT-PCR results showed statistic significance (P < 0.05) in ALB, CD44 and EGF before and after treatment, and EGF immunostaining was localized in neuron of cortex. Conclusion: husc transplantation showed a positive effect in improving neural function of CIR rats, and underlying mechanism is involved in CD44, ALB, and EGF network.

Biocontrol activity of an endophytic Alternaria alternata Aa-Lcht against apple Valsa canker.

Apple Valsa canker (AVC), caused by Valsa mali, is the most serious branch disease for apples in East Asia. Biocontrol constitutes a desirable alternative strategy to alleviate the problems of orchard environment pollution and pathogen resistance risk. It is particularly important to explore efficient biocontrol microorganism resources to develop new biocontrol technologies and products. In this study, an endophytic fungus, which results in the specific inhibition of the growth of V. mali, was isolated from the twig tissue of Malus micromalus with a good tolerance to AVC. The fungus was identified as Alternaria alternata, based on morphological observations and phylogenetic analysis, and was named Aa-Lcht. Aa-Lcht showed a strong preventive effect against AVC, as determined with an in vitro twig evaluation method. When V. mali was inhibited by Aa-Lcht, according to morphological and cytological observations, the hyphae was deformed and it had more branches, a degradation in protoplasm, breakages in cell walls, and then finally died completely due to mycelium cells. Transcriptome analysis indicated that Aa-Lcht could suppress the growth of V. mali by inhibiting the activity of various hydrolases, destroying carbohydrate metabolic processes, and damaging the pathogen membrane system. It was further demonstrated that Aa-Lcht could colonize apple twig tissues without damaging the tissue's integrity. More importantly, Aa-Lcht could also stimulate the up-regulated expression of defense-related genes in apples together with the accumulation of reactive oxygen species and callose deposition in apple leaf cells. Summarizing the above, one endophytic biocontrol resource was isolated, and it can colonize apple twig tissue and play a biocontrol role through both pathogen inhibition and resistance inducement.

Tunable C-H functionalization and dearomatization enabled by an organic photocatalyst.

C-H functionalization and dearomatization constitute fundamental transformations of aromatic compounds, which find wide applications in various research areas. However, achieving both transformations from the same substrates with a single catalyst by operating a distinct mechanism remains challenging. Here, we report a photocatalytic strategy to modulate the reaction pathways that can be directed toward either C-H functionalization or dearomatization under redox-neutral or net-reductive conditions, respectively. Two sets of indoles and indolines bearing tertiary alcohols are divergently furnished with good yields and high selectivity. The key to success is the introduction of isoazatruxene ITN-2 as a novel photocatalyst (PC), which outperforms the commonly used PCs. The ready synthesis and high modulability of isoazatruxene type PCs indicate their great application potential.

Role of Qufeng Tongqiao Prescription in the protection of cerebral ischemia and associated molecular network mechanism.

To explore the of Qufeng Tongqiao Prescription in the treatment of cerebral ischemia-reperfusion (CIR) and associated molecular network mechanism. Venny diagram, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis, protein-protein interaction (PPI), hub genes mining, molecular docking, combined with animal experiments and Nissl stain were performed to determine the molecular network mechanism of Qufeng Tongqiao Prescription for CIR treatment. Fifty three intersecting genes between Qufeng Tongqiao Prescription and cerebral ischemia reperfusion were acquired from Venny analysis. GO analysis showed that the main biological process (BP) was response to lipopolysaccharide, and the main cell localization (CC) process was membrane raft, while the most important molecular function (MF) process is Cytokine receptor binding. Moreover, AGE-RAGE signaling pathway in diabetic complications is the most important signaling pathway in KEGG pathway. Through molecular docking, it was found that Astragalus membranaceus was docked with MAPK14, IL4, FOS, IL6, and JUN; pueraria membranaceus was directly docked with JUN and IL4; Acorus acorus was linked to JUN and MAPK14; Ganoderma ganoderma and human were involved in JUN docking, and Ligusticum chuanqi and pueraria could not be docked with MAPK14, respectively. The results of animal experiments showed that Qufeng Tongqiao Prescription significantly improved behavioral performance and reduced the number of neuronal deaths in rats subjected to CIR, and molecular mechanisms are associated with FOS, IL-6, IL4, JUN, and MAPK14, of there, IL-6, as a vital candidator, which has been confirmed by immunostaining detection. Together, Qufeng Tongqiao Prescription has positive therapeutic effect on CIR, and the underlying mechanism is involved MAPK14, FOS, IL4, and JUN network, while IL-6 may be as a vital target.

Case report: Treatment of two cases of recurrent/refractory early T-cell precursor acute lymphoblastic leukemia with venetoclax combined with the CAG regimen.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a highly aggressive subtype of T-ALL. No standard chemotherapy regimen exists for patients with recurrent/refractory (R/R) ETP-ALL; in these patients, the primary goal of salvage therapy is to achieve remission as a foundation for consolidation and intensification treatments. This study reports cases of two patients with R/R ETP-ALL who underwent salvage therapy of venetoclax combined with the CAG regimen and achieved complete remission in the bone marrow. Flow cytometry results were negative for minimal residual disease. Both patients were bridged to allogeneic hematopoietic stem cell transplantation (HSCT) and in complete remission over a 3-year follow-up period. These cases show that the use of venetoclax combined with the CAG regimen may offer patients with R/R ETP-ALL an opportunity for allogeneic HSCT.

[Effect of Kümmell's disease with kyphosis on spinal-pelvic sagittal parameters].

OBJECTIVE: To explore the effect of Kümmell's disease with kyphosis on the sagittal morphology of the spine-pelvis. METHODS: A retrospective analysis of 34 patients of Kümmell's disease with kyphosis （Kümmell group） admitted from August 2015 to September 2022, including 10 males and 24 females with an average age of （71.1±8.5） years old. A control group of 37 asymptomatic population aged （69.3±6.7） years old was matched. Spinal-pelvic sagittal parameters were measured on the anterior-posterior and lateral X-rays of the whole spine in the standing position, including segmental kyphosis（SK） or thoracolumbar kyphosis（TLK）, thoracic kyphosis（TK）, lumbar lordosis（LL）, pelvic incidence（PI）, pelvic tilt（PT）, sacral slope（SS）, sagittal vertical axis（SVA）, T1 pelvic angle（TPA） and PI-LL. Vertebral wedge angle（WA） in Kümmell was measured and differences in parameters among groups were analyzed and the relationship between spino-pelvic parameters and WA, SK were also investigated. RESULTS: TK, SK, PT, SVA, TPA and PI-LL in Kümmell group were significantly larger than those in control group （P<0.05）, LL and SS in Kümmell group were significantly decreased than those in control group （P<0.05）, and there was no significant difference in PI between two groups （P>0.05）. In Kümmell group, WA（30.8±5.9）° showed a positive correlation with SK and TK（r=0.366, 0.597, P<0.05）, and SK was significantly correlated with LL and SS（r=0.539, -0.591, P<0.05）. Strong positive correlation between LL and PI, SS, SVA, TPA, PI-LL were also confirmed in patients with Kümmell with kyphosis（r=0.559, 0.741, -0.273, -0.356, -0.882, P<0.05）. CONCLUSION: Patients with Kümmell with kyphosis not only have segmental kyphosis, but also changes the overall spinal-pelvic sagittal parameters, including loss of lumbar lordosis, pelvic retrorotation, trunk forward tilt. The surgical treatment of Kümmell disease should not only pay attention to the recovery of the height of the collapsed vertebra, but also focus on the overall balance of the spine-pelvic sagittal plane for patients with kyphosis.

Effect of electroacupuncture of "Jiaji" (EX-B2) on NOD-like receptor protein 3 mediated pyroptosis in spinal cord tissue of rats with acute spinal cord injury. / å¤¹è„Šç”µé’ˆå¯¹æ€¥æ€§è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡NODæ ·å—ä½“çƒ­è›‹ç™½ç»“æž„åŸŸç›¸å ³è›‹ç™½3介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.

S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway.

Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.

[Repairing partial suprahyoid epiglottis-preserved circumferential defect in near total laryngectomy with anterior medial thigh flap in advanced laryngeal cancer].

Objective: To explore the feasibility to restore pronunciation function by repairing partial suprahyoid epiglottis-preserved circumferential defect in near total laryngectomy with anterior medial thigh flap in advanced laryngeal cancer. Methods: A retrospective study of 5 male patients with advanced laryngeal cancer between August 2019 and October 2022, aged 56-73 years, with an average age of 65 years were reviewed. The disease duration ranged from 3 to 24 months, with an average of 8 months. Tumor classification by location: 2 cases of glottic type, 2 cases of supraglottic type, and 1 case of subglottic type; TNM staging: 3 cases of T 4N 0M 0 stage, 1 case of T 4N 1M 0 stage, and 1 case of T 4N 2M 0 stage; American Joint Committee on Cancer (AJCC) staging (2017): stage Ⅳ. Near total laryngectomy with partial suprahyoid epiglottis-preserved and selective bilateral neck dissection were performed before the anterior medial thigh flap was used to repair the circumferential defects. The flap size ranged from 6 cm×5 cm to 8 cm×6 cm. Four patients underwent adjuvant radiotherapy and chemotherapy after operation, while 1 patient did not receive any other adjuvant treatment such as radiochemotherapy. Results: The flaps of all 5 patients survived without obvious neck infection. One patient developed a slight pharyngeal fistula after oral feeding at 1 month after operation, which healed after another week of gastric feeding. Primary healing also achieved in the thigh donor area. One patient had bilateral cervical lymph node metastasis, and 1 patient had lymph node metastasis on one side. The remaining 3 patients had no cervical nodes metastasis on both sides. All 5 patients were followed up 12-36 months, with an average of 27.6 months. Four patients had clear, audible, and hoarse voice while 1 patient (case 3) had pronunciation similar to whispering. Laryngoscopy showed that the reconstructed laryngeal inlet was fissure-shape and the reconstructed laryngo-trachea canal below the laryngeal inlet was gradually enlarged. At 1 month after operation, the gastric tube was withdrawn and the food was taken orally. There was no obvious aspiration pneumonia. The tracheostomy tube could be blocked in 4 patients for from 30 seconds to 3 minutes. Among them, 3 patients were able to make a noticeable pronunciation even when the tube was not blocked, and they were able to engage in barrier-free language communication; the tracheostomy tube could not be blocked in 1 patient who had a pronunciation similar to whispering. Preliminary voice analysis showed that the patients have a relaxed and natural pronunciation, without obvious breath-holding or air-swallowing movement, compared to patients with esophageal pronunciation. Decannulation did not achieved until the last follow-up in all 5 patients. Conclusion: The anterior medial thigh flap can repair circumferential defects after near total laryngectomy in advanced laryngeal cancer patients and achieve satisfactory pronunciation, thus can serve as an effective pronunciation rehabilitation method. The preserved part of epiglottis may play a role to prevent postoperative aspiration.

Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication with no known cure. In this study, we evaluated the combination of ultrasound-targeted microbubble destruction (UTMD) and cationic microbubbles (CMBs) for cardiac S-adenosyl homocysteine hydrolase (SAHH) gene transfection as potential DCM therapy. Models of high glucose/fat (HG/HF)-induced H9C2 cells and streptozotocin-induced DCM rats were established. Ultrasound-mediated SAHH delivery using CMBs was a safe and noninvasive approach for spatially localized drug administration both in vitro and in vivo. Notably, SAHH overexpression increased cell viability and antioxidative stress and inhibited apoptosis of HG/HF-induced H9C2 cells. Likewise, UTMD-mediated SAHH delivery attenuated apoptosis, oxidative stress, cardiac fibrosis, and myocardial dysfunction in DCM rats. Activation of the AMPK/FOXO3/SIRT3 signaling pathway may be a key mechanism mediating the role of SAHH in regulating myocardial injury. Thus, UTMD-mediated SAHH transfection may be an important advancement in cardiac gene therapy for restoring ventricular function after DCM.

Salidroside protects RGC from pyroptosis in diabetes-induced retinopathy associated with NLRP3, NFEZL2 and NGKB1, revealed by network pharmacology analysis and experimental validation.

OBJECTIVE: To investigate the effect of salidroside (SAL) in protecting retinal ganglion cell (RGC) from pyroptosis and explore associated molecular network mechanism in diabetic retinapathy (DR) rats. METHODS: HE, Nissl and immunofluorescence staining were used to observe the retinal morphological change, and the related target genes for salidroside, DR and pyroptosis were downloaded from GeneCard database. Then Venny, PPI, GO, KEGG analysis and molecular docking were used to reveal molecular network mechanism of SAL in inhibiting the pyroptosis of RGC. Lastly, all hub genes were confirmed by using qPCR. RESULTS: HE and Nissl staining showed that SAL could improve the pathological structure known as pyroptosis in diabetic retina, and the fluorescence detection of pyroptosis marker in DM group was the strongest, while they decreased in the SAL group(P < 0.05)). Network pharmacological analysis showed 6 intersecting genes were obtained by venny analysis. GO and KEGG analysis showed 9 biological process, 3 molecular function and 3 signaling pathways were involved. Importantly, molecular docking showed that NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1 could combine with salidroside, and qPCR validates the convincible change of CASP3, NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1. CONCLUSION: Salidroside can significantly improve diabetes-inducedRGC pyrotosis in retina, in which, the underlying mechanism is associated with the NLRP3, NFEZL2 and NGKB1 regulation.

Feast/famine ratio regulates the succession of heterotrophic nitrification-aerobic denitrification and autotrophic ammonia oxidizing bacteria in halophilic aerobic granular sludge treating saline wastewater.

Heterotrophic nitrification-aerobic denitrification (HN-AD) shows innovation potential of wastewater treatment process in a single tank. However, how to enrich HN-AD bacteria in activated sludge to enhance their contribution remained unknown. This study explored the impact of the feast/famine (F/F) ratio on the succession of autotrophic ammonia oxidizing bacteria (AOB) and HN-AD bacteria in a halophilic aerobic granular sludge (HAGS) system. As the F/F ratio decreased from 1/9 to 1/15, the total inorganic nitrogen (TIN) removal performance significantly decreased. The proportion of heterotrophic bacteria was dropped from 79.0 % to 33 %. Accordingly, the relative abundance of Paracoccus decreased from 70.8 % to 25.4 %, and the copy number of the napA gene was reduced from 2.2 × 1010 copies/g HAGS to 8.1 × 109 copies/g HAGS. It found the F/F ratio regulated the population succession of autotrophic AOB and HN-AD bacteria, thereby providing a solution to achieve the enrichment of HN-AD bacteria in HAGS.

Comparison of the characteristics of the CF-H290I and PCF-Q260JI colonoscopes in non-sedated patients with a history of abdominal or pelvic surgery: a randomized controlled study.

BACKGROUND AND AIM: The purpose of this randomized controlled study was to compare the characteristics of the CF-H290I (high-definition) colonoscope with those of the PCF-Q260JI (high-resolution) colonoscope in non-sedated patients with a history of abdominal or pelvic surgery in an effort to help endoscopists to select more effectively and objectively between the various colonoscopes. METHODS: A total of 397 patients who underwent colonoscopy at the Affiliated Wuxi People's Hospital of Nanjing Medical University, between August 2022 and October 2022 were randomized to a CF-H290I group (n = 198) or a PCF-Q260JI group (n = 199) using a computer-generated allocation method. We compared the adenoma detection rate (ADR), patient satisfaction with the examination, discomfort associated with colonoscopy including abdominal distension and pain, cecal intubation time, and patient willingness to undergo colonoscopy in the future between the CF-H290I and PCF-Q260JI groups. RESULTS: There was no statistically significant difference in the overall ADR between the CF-H290I and PCF-Q260JI groups (81 [40.9%] vs 63 [31.7%], Z = 3.674, P = 0.055). However, the ADRs in the transverse colon and left colon were significantly higher in the CF-H290I group (22 [11.1%] vs 6 [3.0%], Z = 9.588, P = 0.002 and 57 [28.8%] vs 37 [18.6%], Z = 5.212, P = 0.017, respectively). More sessile serrated lesions were detected in the CF-H290I group (52 [26.3] vs 30 [15.1%], Z = 7.579, P = 0.006). Patient satisfaction with colonoscopy was better in the PCF-Q260JI group (8.91 ± 1.09 vs 8.51 ± 1.44, t = -3.158, P < 0.01) with less likelihood of discomfort (23 [11.6%] vs 41 [20.7%], Z = 6.144, P = 0.013), The number of patients willing to undergo colonoscopy in the future was significantly greater in the PCF-Q260JI group (168 [84.4%] vs 149 [75.3%], Z = 5.186, P = 0.023). The cecal intubation time was significantly shorter in the CF-H290I group (256.09 ± 155.70 s vs 315.64 ± 171.64 s, P = 0.004). There were no complications such as perforation or bleeding in either group. CONCLUSION: The CF-H290I and PCF-Q260JI colonoscopes each have advantages when used in patients with a history of abdominal or pelvic surgery. The CF-H290I has higher ADRs in the transverse and left colon whereas the PCF-Q260JI is less painful and better accepted by patients. This study was approved by the Clinical Research Ethics Committee of Wuxi People's Hospital and was registered in the Chinese Clinical Trial Registry (ChiCTR2200063092).

Differential Gene Analysis of Ferroptosis in the Treatment of Allergic Rhinitis with Bu-Zhong-Yi-Qi-Decoction Based on GEO Using Network Pharmacology and Molecular Docking.

Objective: The differential gene analysis of ferroptosis inreating allergic rhinitis with Bu-Zhong-Yi-Qi-Decoction based on GEO using network pharmacology and molecular docking . Method: This study used databases such as TCMSP to search for traditional Chinese herbal medicine's active ingredients and targets in Bu-Zhong-Yi-Qi-Decoction in treating allergic rhinitis. GeneCards, OMIM, TTD, and PharmaGkb were used to obtain disease targets for allergic rhinitis, and R language was used to screen Bu-Zhong-Yi-Qi-Decoction as the main target for treating allergic rhinitis. Retrieve the gene dataset of allergic rhinitis using the GEO database, analyze ferroptosis-related genes, and select the intersection of effective targets of Bu-Zhong-Yi-Qi-Decoction for treating allergic rhinitis and ferroptosis-related genes of allergic rhinitis, draw protein interaction networks using the STRING database, use Cytoscape software to construct the target regulatory network of Bu-Zhong-Yi-Qi-Decoction for treating allergic rhinitis and ferroptosis related genes, and then use the CytoNCA plugin to screen key targets. Using R language, Gene ontology, and the biological pathway enrichment analysis were performed on the predicted targets related to the treatment of allergic rhinitis and ferroptosis with Bu-Zhong-Yi-Qi-Decoction. Selecting key targets and active ingredients for molecular docking to explore the potential mechanism of Bu-Zhong-Yi-Qi-Decoction in treating ferroptosis in allergic rhinitis. Result: After searching the TCMSP database, a total of 182 active ingredients were obtained from 8 traditional Chinese medicines of Bu-Zhong-Yi-Qi-Decoction, such as naringenin, kaempferol, Isorhamnetin, corresponding to 3023 targets and 2025 targets related to allergic rhinitis. There are 30 remarkably enriched Go analyses for biological function of potential target genes of Bu-Zhong-Yi-Qi-Decoction in allergic rhinitis, such as regulation of apoptotic signaling pathway, cellular response to peptide, wound healing, etc. Among them, there are 7 key genes related to the treatment of allergic rhinitis and ferroptosis with Bu-Zhong-Yi-Qi-Decoction, namely TP53, MAPK1, MAPK14, HIF1A, AR, CAV1, GSK3B. Conclusion: The treatment of allergic rhinitis with Bu-Zhong-Yi-Qi-Decoction is a process involving multiple divisions, targets, and pathways. These results indicated that oral Bu-Zhong-Yi-Qi-Decoction may effectively treat allergic rhinitis in clinical practice.

Implantation of human urine stem cells promotes neural repair in spinal cord injury rats associated cadeharin-1 and integrin subunit beta 1 expression.

BACKGROUND: The aim of this study was to determine the effect of human urine-derived stem cells (HUSCs) for the treatment of spinal cord injury (SCI) and investigate associated the molecular network mechanism by using bioinformatics combined with experimental validation. METHODS: After the contusive SCI model was established, the HUSC-expressed specific antigen marker was implanted into the injury site immediately, and the Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was utilized to evaluate motor function so as to determine the effect of HUSCs for the neural repair after SCI. Then, the geneCards database was used to collect related gene targets for both HUSCs and SCI, and cross genes were merged with the findings of PubMed screen. Subsequently, protein-protein interaction (PPI) network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as core network construction, were performed using Cytoscape software. Lastly, real-time quantitative polymerase chain reaction (PCR) and immunofluorescence were employed to validate the mRNA expression and localization of 10 hub genes, and two of the most important, designated as cadherin 1 (CDH1) and integrin subunit beta 1 (ITGB1), were identified successfully. RESULTS: The immunophenotypes of HUSCs were marked by CD90+ and CD44+ but not CD45, and flow cytometry confirmed their character. The expression rates of CD90, CD73, CD44 and CD105 in HUSCs were 99.49, 99.77, 99.82 and 99.51%, respectively, while the expression rates of CD43, CD45, CD11b and HLA-DR were 0.08, 0.30, 1.34 and 0.02%, respectively. After SCI, all rats appeared to have severe motor dysfunction, but the BBB score was increased in HUSC-transplanted rats compared with control rats at 28 days. By using bioinformatics, we obtained 6668 targets for SCI and 1095 targets for HUSCs and identified a total of 645 cross targets between HUSCs and SCI. Based on the PPI and Cytoscape analysis, CD44, ACTB, FN1, ITGB1, HSPA8, CDH1, ALB, HSP90AA1 and GAPDH were identified as possible therapeutic targets. Enrichment analysis revealed that the involved signal pathways included complement and coagulation cascades, lysosome, systemic lupus erythematosus, etc. Lastly, quantificational real-time (qRT)-PCR confirmed the mRNA differential expression of CDH1/ITGB1 after HUSC therapy, and glial fibrillary acidic protein (GFAP) immunofluorescence staining showed that the astrocyte proliferation at the injured site could be reduced significantly after HUSC treatment. CONCLUSIONS: We validated that HUSC implantation is effective for the treatment of SCI, and the underlying mechanisms associated with the multiple molecular network. Of these, CDH1 and ITGB1 may be considered as important candidate targets. Those findings therefore provided the crucial evidence for the potential use of HUSCs in SCI treatment in future clinic trials.

Interplay between lncRNA RP11-367G18.1 variant 2 and YY1 plays a vital role in hypoxia-mediated gene expression and tumorigenesis.

BACKGROUND: The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood. METHODS: RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2-YY1 complex on tumor progression. RESULTS: In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2-YY1 complex contributes to hypoxia-induced epithelial-mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2. CONCLUSIONS: RP11-367G18.1 variant 2-YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment.

Self-Trapped, Thermally Equilibrated Delayed Fluorescence Enables Low-Reabsorption Luminescent Solar Concentrators Based on Gold-Doped Silver Nanoclusters.

Reabsorption-free luminescent solar concentrators (LSCs) are crucial ingredients for photovoltaic windows. Atomically precise metal nanoclusters (NCs) with large Stokes-shifted photoluminescence (PL) hold great promise for applications in LSCs. However, a fundamental understanding of the PL mechanism, particularly on the excited-state interaction and exciton kinetics, is still lacking. Herein, we studied the exciton-phonon coupling and singlet/triplet exciton dynamics for gold-doped silver NCs in a solid matrix. Following photoexcitation, the excitons can be self-trapped via strong exciton-phonon coupling. Subsequently, rapid thermal equilibration between the singlet and triplet states occurs due to the coexistence of small energy splitting and spin-orbit coupling. Finally, broadband delayed fluorescence with a large Stokes shift can be generated, namely, self-trapped, thermally equilibrated delayed fluorescence (ST-TEDF). Benefiting from superior ST-TEDF, we demonstrated efficient LSCs with minimized reabsorption.

Effect of transverse colostomy versus ileostomy in colorectal anastomosis on post-operative wound complications: A meta-analysis.

A meta-analysis was conducted to evaluate the effect of colostomy or ileostomy on post-operative wound complications. The research was tested using Embase, PubMed and Cochrane Library databases. Included were randomized, controlled clinical trials (RCTs). A sensitivity analysis and a meta-analysis were carried out. The results indicated that there were no statistically significant differences in the reduction of wound infection between LC and LI. Out of 268 related studies, 5 publications were chosen and examined for compliance. Literature quality was evaluated throughout the trial. Studies with poor literature were excluded. The data were analysed with RevMan 5.3, and a decision was taken to analyse the data with either a stochastic or a fixed-effects model. There were no significant differences in the incidence of post-operative infection in patients with LC (OR, 0.79; 95% CI, 0.34, 1.81; p = 0.57), and the incidence of post-operative anastomotic fistulae (OR, 0.98; 95% CI, 0.30, 3.15; p = 0.97) was not significantly different from that with LI. These meta-analyses indicate that no significant reduction in the incidence of post-operative infections or anastomotic fistulae was observed by either LC or LI.

cDCBLD2 mediates sorafenib resistance in hepatocellular carcinoma by sponging miR-345-5p binding to the TOP2A coding sequence.

Sorafenib is a first-line chemotherapy drug for treating advanced hepatocellular carcinoma (HCC). However, its therapeutic effect has been seriously affected by the emergence of sorafenib resistance in HCC patients. The underlying mechanism of sorafenib resistance is unclear. Here, we report a circular RNA, cDCBLD2, which plays an important role in sorafenib resistance in HCC. We found that cDCBLD2 was upregulated in sorafenib-resistant (SR) HCC cells, and knocking down cDCBLD2 expression could significantly increase sorafenib-related cytotoxicity. Further evidence showed that cDCBLD2 can bind to microRNA (miR)-345-5p through a competing endogenous RNA mechanism, increase type IIA topoisomerase (TOP2A) mRNA stability through a miRNA sponge mechanism, and reduce the effects of sorafenib treatment on HCC by inhibiting apoptosis. Our findings also suggest that miR-345-5p can negatively regulate TOP2A levels by binding to the coding sequence region of its mRNA. Additionally, targeting cDCBLD2 by injecting a specific small interfering RNA (siRNA) could significantly overcome sorafenib resistance in a patient-derived xenograft (PDX) mouse model of HCC. Taken together, our study provides a proof-of-concept for a potential strategy to overcome sorafenib resistance in HCC patients by targeting cDCBLD2 or TOP2A.

The evolution of hot Jupiters revealed by the age distribution of their host stars.

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.