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A novel 3D Co(II) coordination polymer (CP) {Co3(IBT)2(H2O)2}n (1) has been synthesized through the reaction of 4,5-Bis(tetrazol-5-yl)imidazole (H3IBT) with Co(NO3)2 in a mixed solvent of N,N-dimethylformamide (DMF) and water. The structural determination results show that complex 1 is a 3D framework with a (3,4)-connected net. Furthermore, its inhibitory activity on endometrial cancer cells was evaluated and the related mechanism was also discussed in the research. The relative expression of the miRNA29 in endometrial cancer cells was measured with real-time PT-PCR. In addition to this, the western blot was performed to detect the endometrial cancer cell apoptosis after compound treatment for the mechanism exploration. The hypothesis that arises from the experimental observation has been further investigated by using molecular docking simulation, where the possible binding interactions between the ligand and Bcl2 protein are studied explicitly. [ABSTRACT FROM AUTHOR]

Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart the anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through the direct interaction of PD-L1 with PD-1 on T lymphocyte surfaces. Recent research focusing on the tumor microenvironment has illuminated the pivotal role of immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated immunosuppression. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. In addition to receiving signals from tumor-derived exosomes that promote PD-L1 expression, TAMs also exert control over PD-L1 expression in tumor cells through the release of exosomes. This paper aims to summarize the mechanisms by which exosomes participate in this process, identify crucial factors that influence these mechanisms, and explore innovative strategies for inhibiting or reversing the tumor-promoting effects of TAMs by targeting exosomes. [ABSTRACT FROM AUTHOR]

Scimitar syndrome (SS) is a rare entity with an incidence of approximately 1–3 in 200 000 people. It is typically characterized by complete or partial anomalous pulmonary venous drainage from the right lung into the systemic venous circulation, most commonly the inferior vena cava (IVC). For the first time, we report the diagnosis of SS in a fetus in utero using four‐dimensional (4D) spatiotemporal image correlation combined with high‐definition live flow rendering mode (STIC‐HD live flow). [ABSTRACT FROM AUTHOR]

Objective: To compare the long‐term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early‐stage cervical adenocarcinoma. Methods: Based on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early‐stage cervical adenocarcinoma were retrospectively reviewed. Long‐term and short‐term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log‐rank method in the whole study population and after propensity score matching. Results: There was no difference in disease‐free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532–1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526–2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk‐adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk‐adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613). Conclusions: LRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early‐stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury. [ABSTRACT FROM AUTHOR]

Background: Interleukin-33 (IL-33) is an effective inducer of pro-inflammatory cytokines regulating innate and adaptive immunity. Inflammation could be a double-edged sword, promoting or inhibiting tumour growth. To date, the roles and mechanisms of IL-33 in tumours remain controversial. Here, we examined the effect of exogenous IL-33 on the biological characteristics of hepatocellular carcinoma (HCC) and the possible mechanism of action.Methods: In this study, IL-33 expression in the tissues of 69 HCC patients was detected and its relationship with prognosis was evaluated. After establishing a mouse HCC model and IL-33 treatment operation, the infiltration of splenic myeloid-derived suppressor (MDSCs), dendritic (DCs), regulatory T, and natural killer (NK) cells was detected by flow cytometry analysis, and the vascular density of the tumour tissues was detected by immunohistochemistry to reveal the mechanism of IL-33 in HCC proliferation. Finally, the Cancer Genome Atlas database was used to analyse Gene Ontology terms the and Kyoto Encyclopaedia of Genes and Genomes pathway. Moreover, the chi-square test, two-tailed unpaired Student's t-test, and multiple t-tests were performed using SPSS version 23.0 and GraphPad Prism 8.0 software.Results: The IL-33 expression level was negatively correlated with the overall survival of HCC patients, suggesting its potential clinical significance in the prognosis of HCC. We found that systemic IL-33 administration significantly promoted the tumour size in vivo. Furthermore, the IL-33-treated mice presented decreased frequencies of tumouricidal NK and CD69+ CD8+ T cells. After IL-33 treatment, the incidence of monocytic MDSCs and conventional DCs increased, while that of granulocytic MDSCs decreased. Moreover, IL-33 promoted the formation of intracellular neovascularization. Therefore, IL-33 accelerated HCC progression by increasing the accumulation of immunosuppressive cells and neovascularization formation. Finally, we found that the transcription of IL-33 was closely related to the PI3K-Akt and MAPK pathways in Gene Set Enrichment Analysis plots, which were involved in the tumourigenesis and pathogenesis of HCC.Conclusions: Taken together, IL-33 may be a key tumour promoter of HCC proliferation and tumourigenicity, an important mediator, and a potential therapeutic target for regulating HCC progression. [ABSTRACT FROM AUTHOR]

Abstract It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against α-syn, and of which only a small part can penetrate the blood-brain barrier, resulting in an extremely low level of effective antibodies in the brain, and limiting the beneficial effect of IVIG on PD mice. Here, we first isolated naturally occurring autoantibodies against α-syn (NAbs-α-syn) from IVIG. Our further investigation results showed that NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-α-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble α-syn, total human α-syn and α-syn oligomers, decreasing the intracellular p-α-synser129 deposits and axonal pathology, inhibiting the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines, increasing the levels of PSD95, synaptophysin and TH in the brain of A53T transgenic mice. These findings suggest that NAbs-α-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD. Highlights • NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. • NAbs-α-syn attenuated the memory and motor deficits in A53T transgenic mice. • NAbs-α-syn reduced the levels of soluble α-syn and α-syn oligomers in the brains of A53T mice. • NAbs-α-syn decreased the intracellular α-syn deposits and axonal pathology. • NAbs-α-syn ameliorated neuroinflammation and synaptic deficiencies in the brains of A53T mice. [ABSTRACT FROM AUTHOR]

Aim: Systemic inflammatory response is closely related to tumor progression. We retrospectively investigated relationships between systemic inflammatory scores, C‐reactive protein/albumin (CRP/Alb) ratio (CAR) and clinical characteristics in advanced non–small‐cell lung cancer (NSCLC) in 436 patients to find better clinical predictors of NSCLC prognosis. Methods: Blood specimens were collected 1 week before treatment to test for systemic inflammatory scores and albumin. Patients' overall survival (OS) was calculated via Kaplan–Meier method. Single‐factor log‐rank and multivariate Cox regression analyses and receiver operating characteristic curves were used to evaluate the prognostic significance of CAR and other systemic inflammatory indexes in predicting OS. Results: Kaplan–Meier method showed that Glasgow prognosis score (GPS), modified GPS (mGPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) were reliable prognostic factors for advanced NSCLC. CAR was positively correlated with GPS, mGPS, NLR, PLR and MLR in these patients. CAR was an independent risk factor for OS in advanced NSCLC, and was more closely associated with prognosis than were GPS, mGPS, NLR, PLR or MLR. Conclusion: In advanced NSCLC patients, CAR may be a better predictor of prognosis compared with other inflammatory markers. A prospective multicenter study is needed to verify these findings. [ABSTRACT FROM AUTHOR]

Two new lanostane triterpenoids (1 and 2), two new ergostane-type steroids (3 and 4) together with two known lanostane triterpenoids (5 and 6) and one known steroid (7) were isolated from the cultured mycelia of Ganoderma capense (CGMCC 5.71). Their structures were determined on the basis of extensive spectroscopic (HRESIMS, 1D NMR, 2D NMR) data analyses. Compound 1 exhibited moderate cytotoxic activity against the human cancer cell line NCI-H1650 with an IC50 value of 22.3 μM, and 7 displayed cytotoxic activity against the human cancer cell line HCT116 with an IC50 value of 17.4 μM. In addition, compounds 2, 3, 5, and 6 displayed weak anti-HIV activity with IC50 values of 23.5, 46.7, 21.6, and 30.1 μM, respectively. [ABSTRACT FROM AUTHOR]

Anhydroicaritin (1a), baohuoside (1b) and icariin (1c) were recognized as major pharmacologically active ingredients of Epimedium plants. Their primary means of acquisition were chemical isolation from plants. However, it suffers from low yield, environmental pollution and shortage of plants. Herein, to remedy these problems, biosynthesis was explored to obtain the three active ingredients. Fortunately, with SfFPT as 8-prenyltransferase, EpPF3RT and Ep7GT as glycosyltransferases, kaempferide (1) was transferred to 1a, 1b and 1c enzymatically. Thus, we report the details of this method. This approach represents a promising environmental friendly alternative for the production of these compounds from an abundant analogue. [ABSTRACT FROM AUTHOR]

The experiment was conducted to study the effect of compound Chinese medicine feed additives on growth performance, slaughter performance, meat quality and immune function of finishing pigs. A total of 120 finishing pigs were randomly divided into four groups, with three replicates in each group and 10 pigs in each replicate. Control group, low-dose group, medium-dose group and high-dose group were supplemented with 0, 0.1%, 0.5% and 1.0% compound traditional Chinese medicine feed additives in the basal diet, respectively. The pre-test lasted for 7 d, and the formal test lasted for 56 d. The results showed that compared with control group, final weight, carcass weight, dressing percentage and carcass skew length of finishing pigs in high-dose group were significantly increased (P<0.05), while back fat thickness was significantly decreased (P<0.05). The average daily gain of finishing pigs in all dose groups was significantly increased (P<0.05). The average daily feed intake of finishing pigs in medium dose group and high dose group was significantly increased (P<0.05), and the feed to gain ratio was significantly decreased (P<0.05). Compared with control group, the pH24 h value of finishing pigs in high-dose group was significantly increased (P<0.05), the shear force and drip loss rate in medium-dose and high-dose groups were significantly decreased (P<0.05), and the cooking loss rate in all dose groups was significantly decreased (P<0.05). Compared with control group, the content of IgA and IL-2 in serum of finishing pigs in medium-dose group and high-dose group were significantly increased (P<0.05), and the content of serum IgG in all dose groups was significantly increased (P<0.05). Compared with control group, spleen index of finishing pigs in highdose group was significantly increased (P<0.05). The study indicates that with the increase of the dosage of compound Chinese medicine feed additive in the diet of finishing pigs, the growth performance, slaughter performance, meat quality and immune function of finishing pigs are gradually enhanced, and the appropriate dosage is 1.0%. [ABSTRACT FROM AUTHOR]

A new steroid glucoside (1), along with nine known steroids (2–10) and four known sorbicillinoids (11–14), were isolated from the endophytic fungusTrichodermasp. Xy24. Their structures were elucidated on the basis of spectroscopic data analyses and by comparison with reported data. Compounds3,5–7,9,10, and13exhibited significant inhibitory effects on HIV-1 virus with IC50values ranging 1.9–9.3 μM; compounds10,13, and14showed potent inhibitory activity on LPS-induced NO production in BV2 microglia cells with inhibitory rates of 108.2, 100, and 75.1% at 10 μM, respectively. In addition, compound10displayed moderate cytotoxicity against BCG823 and HePG2 cell lines with IC50values of 11.1 and 17.7 μM, respectively. [ABSTRACT FROM AUTHOR]

Inspired by the discovery of topological crystalline insulators (TCIs) in three-dimensional materials such as PbSnSe(Te), the classification of topological insulators has been extended to other discrete symmetry classes such as crystal point group symmetries. In this paper, we construct and study a simple model of weak TCIs, which will serve as a more viable project in the experimental probe for such new type of topological phases. [ABSTRACT FROM AUTHOR]

Mutations in the epidermal growth factor receptor (EGFR) have been found in more than 10% of non-small cell lung cancer (NSCLC) patients in North America. The vast majority of these differences are L858R point mutations in Exon 21. Currently, monoclonal antibodies directed against the extracellular domain of EGFR or small molecule/tyrosine kinase inhibitors (TKI) are the stalwarts of NSCLC therapy. Resistance, however, gradually develops because of the T790 mutation towards first and second generation TKIs. The third generation TKI AZD9291 (Osimertinib) has a high affinity for both activating and the acquired resistant mutation (T790 M) in EGFR, with a low affinity towards wild-type EGFR. Recent research, however, suggests that the EGFR (C797S) mutation in the tyrosine kinase domain is a likely cause of resistance to AZD9291. Another significant transformation mechanism associated with this resistance is erbB2 amplification. Our laboratory has developed a small kinase inhibitor, ER121 (MW: ∼500), that inhibits the erbB2/HER2 tyrosine kinases in addition to the EGFR C797S mutations. We have identified a TKI, ER121 targeting the mutant EGFR(T790 M). Using in vitro and in vivo models, examined the efficacy of ER121 on mutant EGFR cell lines. This has enabled us to establish that ER121 is well tolerated when administered orally and produces significant inhibitory activity against human cancers generated by mutant EGFR and amplified ErbB2. • ER121, a dual kinase inhibitor targets both mutant EGFR and activated erbB2. • ER121 inhibits EGFR mutants more effectively than AZD9291. • ER121 exhibits anti-tumor activity against Herceptin resistant breast tumors. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy followed by surgery has been recommended as standard treatment in patients with locally advanced esophageal cancer (LAEC). But the risk of tumor recurrence still remained, and many patients refused or abandoned radiotherapy because of the intolerable adverse effects in China. Neoadjuvant immunochemotherapy (nICT) followed by surgery has become an emerging treatment in patients with esophageal cancer. There was still no consensus on whether nICT was superior to nCT alone in patients with esophageal cancer. Methods: In this retrospective study, patients with resectable esophageal cancer who received surgery after nICT (n=26, 40%) or nCT alone (n=39, 60%) were included. The patients were classified as nICT or nCT arm. The primary endpoints were pathological tumor response (PTR) and event-free survival (EFS). The different clinic-pathological features were compared by the Kruskal-Wallis test for continuous variables and the Chi-square (χ2) test for categorical variables. Kaplan-Meier curves were used to estimate EFS from the date of treatment to recurrence or death. All tests were 2-sided with a significative P-value defined <.05. Results: Three (11.5%) of the 26 patients achieved pathological complete remission (pCR) in the nICT group, and four (10.3%) of the 39 patients achieved pCR in the nCT group, respectively (P=1.000). Six (23.1%) of the 26 patients achieved major pathological response (MPR) in the nICT group, and 11 (28.2%) of the 39 patients achieved MPR in the nCT group, respectively (P=0.645). Downstaging was achieved in 13 (44.8%) patients in the nICT group and 16 (55.2%) patients in the nCT group, respectively (P=0.732). To verify the tumor regression grade (TRG) results, we compared them with MPR and pCR, which showed a significant dependency (P< 0.001). Patients who achieved downgrading showed better MPR and pCR rates (P<0.001 and P =0.010). There was no significant difference in EFS between the nICT and nCT groups (HR=1.011, 95% CI: 0.421–2.425, P = 0.981). Conclusions: Neoadjuvant PD-1 blockade combined with chemotherapy was not superior to chemotherapy alone for patients with resectable locally advanced esophageal carcinoma. However, more studies with long-term follow-up were needed to confirm this result. [ABSTRACT FROM AUTHOR]

CIK cells therapy has been evaluated as an adoptive cell immunotherapy for cancer patients, but there still have not been any standardized systems for evaluating the antitumor efficacy yet. The WHO and RECIST criteria have already been established for a few years but not sufficient to fully characterize the activity of immunotherapy. Based on these two criteria, the irRC was proposed for evaluating the efficacy of immunotherapy. A variety of bioassays for immune monitoring including the specific and non-specific methods, have been established. We recommend detect levels of various immunocytes, immune molecules and soluble molecules to find the correlations among them and clinicopathological characteristics to establish criteria for immunological classification. We also recommend a paradigm shift for the oncologists in the evaluation of immune therapies to ensure assessment of activity based on clinically relevant criteria and time points. [ABSTRACT FROM AUTHOR]

Background: Implants immediately loaded full-arch prosthesis in maxilla is always a challenge, especially when the zone 2 is extremely defected. To achieve a satisfying result, different therapeutic alternatives have been proposed, such as zygomatic implant, pterygoid implant; however, precise surgical skills limited its application. Case presentation: This study reported a case that an edentulous patient was treated with a new technique, two axial implants and four tilted implants supporting an immediate fixed denture, extruding the cortical bone of the anterior wall of the maxillary sinus to establish the primary stability. Conclusions: Two-year follow-up proves that it is a viable choice. Meanwhile, a reliable method for its saving time and money and low level of discomfort for patients is presented. [ABSTRACT FROM AUTHOR]

Background: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro‐environmental distributions. Methods: Immunohistochemical staining was performed for CRC patients' tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan‐Meier analysis and cox analysis. Results: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C‐index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN‐γ was potentially the central molecule at the crossroad between ferroptosis and onco‐immune response. Conclusion: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune‐supportive responses and IFN‐γ was the central molecule for this process. [ABSTRACT FROM AUTHOR]

Background: Mikania micrantha is a vine with strong invasion ability, and its strong sexual reproduction ability is not only the main factor of harm, but also a serious obstacle to control. M. micrantha spreads mainly through seed production. Therefore, inhibiting the flowering and seed production of M. micrantha is an effective strategy to prevent from continuing to spread. Result: The flowering number of M. micrantha is different at different altitudes. A total of 67.01 Gb of clean data were obtained from nine cDNA libraries, and more than 83.47% of the clean reads were mapped to the reference genome. In total, 5878 and 7686 significantly differentially expressed genes (DEGs) were found in E2 vs. E9 and E13 vs. E9, respectively. Based on the background annotation and gene expression, some candidate genes related to the flowering pathway were initially screened, and their expression levels in the three different altitudes in flower bud differentiation showed the same trend. That is, at an altitude of 1300 m, the flower integration gene and flower meristem gene were downregulated (such as SOC1 and AP1), and the flowering inhibition gene was upregulated (such as FRI and SVP). Additionally, the results showed that there were many DEGs involved in the hormone signal transduction pathway in the flower bud differentiation of M. micrantha at different altitudes. Conclusions: Our results provide abundant sequence resources for clarifying the underlying mechanisms of flower bud differentiation and mining the key factors inhibiting the flowering and seed production of M. micrantha to provide technical support for the discovery of an efficient control method. [ABSTRACT FROM AUTHOR]

Three new sesquiterpenoids trichoacorenols B–C and cyclonerodiol B (1–3), along with three known ones (4–6), were isolated from the mangrove plant endophytic fungusTrichodermasp. Xy24 using various column chromatography techniques. The structures of these compounds were determined on the basis of extensive spectroscopic data analyses. Compounds1,2,4, and5were four acorane sesquiterpenes,3and6were two monocyclic sesquiterpenediols. Compounds3and5exhibited significant neural anti-inflammatory activity by inhibiting LPS-induced NO production in BV2 cells with the inhibitory rates of 75.0% and 39.2% at 0.1 μM, respectively, which are more potent than curcumin, a positive control with the inhibitory rate of 21.1% at 0.1 μM. [ABSTRACT FROM PUBLISHER]

Sequence-regulated polymerization is realized upon sequential cross-metathesis polymerization (CMP) and exhaustive hydrogenation to afford precision aliphatic polyesters with alternating sequences. This strategy is particularly suitable for the arrangement of well-known monomer units including glycolic acid, lactic acid, and caprolactic acid on polymer chain in a predetermined sequence. First of all, structurally asymmetric monomers bearing acrylate and α-olefin terminuses are generated in an efficient and straightforward fashion. Subsequently, cross-metathesis (co)polymerization of M1 and M2 using the Hoveyda-Grubbs second-generation catalyst (HG-II) furnishes P1- P3, respectively. Finally, hydrogenation yields the desired saturated polyesters HP1- HP3. It is noteworthy that the ε-caprolactone-derived unit is generated in situ rather than introduced to tailor-made monomers prior to CMP. NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results verify the microstructural periodicity of these precision polyesters. Differential scanning calorimetry (DSC) results reflect that polyesters without methyl side groups exhibit crystallinity, and unsaturated polyester samples show higher glass transition temperatures than their hydrogenated counterparts owing to structural rigidity. [ABSTRACT FROM AUTHOR]

Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance , a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention. [Display omitted] • Ixeris sonchifolia , Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids. • The antitumor activity of terpenoids has become a research hotspot in recent years. • We predicted the anti-liver cancer components of Ixeris sonchifolia and their possible mechanisms, and verified them. • Ixeris sonchifolia inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of β-amyloid (Aβ). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-ε4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against Aβ oligomers (NAbs-Aβo), which were purified by Aβ42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized Aβ42 oligomers or both Aβ40 and 42 oligomers, differently. Both antibodies inhibited Aβ42 aggregation and attenuated Aβ42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric Aβ levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble Aβ levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric Aβ40 or Aβ42 were required, correspondingly, to achieve the optimal effect. NAbs-Aβo could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-Aβo as an extra product of plasma required low cost and the enriched NAbs-Aβo may be more feasible than IVIG for the treatment of AD. [ABSTRACT FROM AUTHOR]

There is an ever-growing demand of construction of large-diameter tunnel in Shanghai, China. How to minimize the environmental impact induced by the tunnel construction has been a hot topic of research over the recent years. The Yingbin San Road tunnel with an external diameter of 13.95 m has been taken as an example to elaborate the controlling of ground surface deformation induced by shield-driven tunneling, in the case of tunnel passing through the settlement sensitive area and adverse geological conditions. Tunneling process of the EPB shield machine was simulated using a three-dimensional finite difference method. Parametric study was performed to optimize the construction parameters. Field measurement was also carried out to validate the numerical model and its applicability in the case of large-diameter tunnels. Both the numerical prediction and field test data show that grouting pressure and quality appear to determine the surface settlement rather than the supporting pressure at workface on the premise of guaranteeing the safety of tunneling process. Both the empirical correlations and field observations demonstrate that the volume loss V i should be controlled below 0.2% to guarantee the maximum surface settlement no more than 10 mm in the airport area. However, the empirical predictions of trough width parameter i do not match the field measurement very well except for the case where such a high volume loss as 0.81% was obtained. [ABSTRACT FROM AUTHOR]

Background: Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, the MET exon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such as EGFR, KRAS, HER-2, BRAF, ALK and ROS1. The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence of MET exon 14 mutations with EGFR exon 20 insertion mutations has never been reported and the management of this subtype is not identified. Case presentation: A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive for MET exon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%), MET amplification (copy number 4.4), and EGFR exon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status. Conclusion: This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carrying MET alterations and EGFR exon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context. [ABSTRACT FROM AUTHOR]

Using chicken feathers as bait, Acremonium globosisporum sp. nov. and Acremonium curvum sp. nov. were collected from the soil of Yuncheng East Garden Wildlife Zoo and Zhengzhou Zoo in China. They were identified by combining the morphological characteristics and the two-locus DNA sequence (LSU and ITS) analyses. In the phylogenetic tree, both new species clustered into separate subclades, respectively. They were different from their allied species in their morphology. The description, illustrations, and phylogenetic tree of the two new species were provided. [ABSTRACT FROM AUTHOR]

Many survival and ecological problems have emerged in Pinus yunnanensis pure pine forest plantations that are usually assumed to be solved by creating mixed plantations. On this basis, we determined the physicochemical properties and enzyme activities of three soil layers in pure and three types of mixed P. yunnanensis plantation stands (admixed species: Alnus nepalensis, Celtis tetrandra, and Quercus acutissima) in Southwest China. We used one-way ANOVA with Tukey's test to analyze the effects of plantation type and depth on the soil's properties and variations among different depths. Principal component analysis combined with cluster analysis was used to evaluate the soil quality of different forest types comprehensively. The results showed that the stand with a mixing proportion of 2:1 of P. yunnanensis and A. nepalensis, C. tetrandra, and Q. acutissima had higher total porosity, moisture content, total nitrogen, available phosphorus, total phosphorus, sucrase, urease, and catalase enzyme activities than other proportions of mixed forest and P. yunnanensis pine pure forest. In general, the mixed P. yunnanensis plantation could improve the soil quality, especially its chemical properties and enzymes. This study provides a basis for creating a mixed-mode of P. yunnanensis and other tree species that can not only improve the economy of forest land but also enhance the ecological value. [ABSTRACT FROM AUTHOR]

The study aims to investigate if low-level laser therapy (LLLT) combined with eccentric exercises could more effectively treat patellar tendinopathy than LLLT alone and eccentric exercises alone. Twenty-one patients with patellar tendinopathy were randomized to three groups: laser alone, exercise alone, or laser plus exercise, with seven in each group. Laser irradiations were administered at the inferior pole of the patella and the two acupoints of Extra 36 (Xiyan) with the intensity of1592 mW/cm². Eccentric training program consisted of three sets of 15 repetitions of unilateral squat on level ground. All patients received six treatments per week for four weeks. Knee pain and function and quadriceps muscle strength and endurance were evaluated at baseline and the end of treatment. After the 4-week intervention, all groups showed significant improvements in all the outcomes (P < 0.01). The laser + exercise group had significantly greater improvements in all the outcomes than the other two groups (P < 0.05), except nonsignificant difference in pain relief between the laser + exercise group and the laser group. In conclusion, LLLT combined with eccentric exercises is superior to LLLT alone and eccentric exercises alone to reduce pain and improve function in patients with patellar tendinopathy. [ABSTRACT FROM AUTHOR]

This paper studied an asset and liability management problem with stochastic interest rate, where interest rate is assumed to be governed by an affine interest rate model, while liability process is driven by the drifted Brownian motion. The investors wish to look for an optimal investment strategy to maximize the expected utility of the terminal surplus under hyperbolic absolute risk aversion (HARA) utility function, which consists of power utility, exponential utility, and logarithm utility as special cases. By applying dynamic programming principle and Legendre transform, the explicit solutions for HARA utility are achieved successfully and some special cases are also discussed. Finally, a numerical example is provided to illustrate our results. [ABSTRACT FROM AUTHOR]

The "Warburg effect" has been developed from the discovery that hypoxia-inducible factor 1α (HIF-1α) could promote the conversion of pyruvate to lactate. However, no studies have linked hypoxia and lactate metabolism to uterine corpus endometrial carcinoma (UCEC). Sequencing and clinical data of patients with UCEC were extracted from The Cancer Genome Atlas (TCGA) database. Hypoxia-related lactate metabolism genes (HRLGs) were screened using Spearman's correlation analysis. A prognostic signature based on HRLGs was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. A comprehensive analysis was conducted on the molecular features, immune environment, mutation patterns, and response to drugs between different risk groups. In vitro and in vivo experiments were performed to verify the function of KIF23. A five HRLG-based prognostic signature was identified. The prognostic outcome was unfavorable for the high-risk subgroup. Observation of increased pathway activities associated with cell proliferation and DNA damage repair was noted in the high-risk subgroup. Additionally, notable correlations were observed between risk score and immune microenvironment, mutational features, and drug responsiveness. Further, we confirmed KIF23 as a novel oncogene in UCEC, whose silencing decreased proliferation and promoted apoptosis of cancer cells. KIF23 knockdown reduced tumor growth in nude mice. We demonstrated that KIF23 was upregulated under hypoxic stress in a HIF-1α dependent manner. Moreover, KIF23 regulated lactate dehydrogenase A expression. The developed HRLG-related signature was associated with prognosis, immune microenvironment, and drug sensitivity in UCEC. We also revealed KIF23 as a hypoxia-regulated lactate metabolism-related oncogene. [Display omitted] • This is the first study to link two cancer hallmarks–hypoxia and lactate metabolism–to UCEC. • Patients in the high-risk group showed high activities of DNA damage repair, impaired immunity, and drug resistance. • We identified KIF23 as a novel oncogene in UCEC, which was upregulated under hypoxic stress in a HIF-1α dependent manner. • KIF23 could participate in lactate metabolism by regulating the expression of lactate dehydrogenase A. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis is to evaluate the effect of marital status on the stage at diagnosis and survival of female patients with breast and gynecologic cancers. A systematic literature search was conducted on electronic databases (PubMed, Cochrane and EMBASE) till December 31, 2020. Publications investigating the association of marital status with stage at diagnosis and/or cancer-specific mortality (CSM) and/or overall survival (OS) in female patients with breast or gynecologic cancers were retrieved. After studies were selected according to inclusion criteria, data extraction, quality assessment and data analysis were performed. 55 articles were eligible for inclusion, consisting of 1,195,773 female cancer patients with breast, vulvar, cervical, endometrial and ovarian cancers. Unmarried female cancer patients had higher odds of being diagnosed at later stage [odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.22–1.36)] and worse survival outcomes in CSM [hazard ratio (HR) = 1.22, 95% CI: 1.16–1.28] and OS (HR = 1.20, 95% CI: 1.14–1.25). This estimate did not vary by level of social support, number of adjustment factors, or between America and Europe. Being married is associated with timely diagnosis and favorable prognosis in most women's cancers. Unmarried female cancer patients have a higher risk of late-stage diagnosis and worse survival outcomes than the married. Greater concern shall be demonstrated towards unmarried female cancer patients. Furthermore, the impact of lacking economic and emotional support on survival outcomes in unmarried female cancer patients deserves particular attention. • Marital status of female cancer patients has an impact on diagnostic timeliness and prognosis • The unmarried female cancer patients are associated with late stage at diagnosis and worse prognosis • Among female cancer patients with high level of social support, the unmarried had worse survival outcomes than the married • From the perspective of public health, more health attention should be paid to unmarried women with cancer [ABSTRACT FROM AUTHOR]

Background: The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods: Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results: A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01–1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions: In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. Trial registration: ChiCTR2000033313. [ABSTRACT FROM AUTHOR]

Background: KRN/I-A (KxB/N) is a mouse model of inflammatory arthritis, which resembles human rheumatoid arthritis. Arthritis in these animals is caused by autoreactivity to a ubiquitously expressed autoantigen, glucose-6 phosphate isomerase. Tolerance is broken at both the T cell and B cell level. The sera from KRN/I-A mice can induce mouse arthritis in healthy mice. Complement components of the alternative complement pathway, including C3, have been shown to be required in induction of mouse arthritis by serum transfer. Methods: We have bred KRN/I-A mice onto a C3-deficient background and followed cohorts for the spontaneous appearance of arthritis. We have also transferred KxB/N serum to B6. I-A recipients. Results: C3-deficient KRN/I-A mice spontaneously developed severe, destructive arthritis, comparable to that seen in C3-intact KRN/I-A mice. However, serum transfer experiments confirmed the strong requirement for C3 in the passive model. Conclusion: The pathogenesis of spontaneous KRN/I-A arthritis can largely proceed by complement-independent pathways and must have pathology effector mechanisms in addition to those seen in the passive serum transfer model. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive and rapid method was developed for quantification of olprinone in human plasma utilizing liquid chromatography tandem mass spectrometry (LC–MS/MS). An aliquot of 1mL plasma sample was extracted with ethyl acetate–dichloromethane. Separation of olprinone and the milrinone (internal standard, IS) from the interferences was achieved on a C18 column followed by MS/MS detection. The analytes were monitored in the positive ionization mode. Multiple reaction monitoring using the transition of m/z 251→ m/z 155 and m/z 212→ m/z 140 was performed to quantify olprinone and IS, respectively. The method had a total chromatographic run time of 3min and linear calibration curves over the concentration range of 0.5–60ng/mL. The lower limit of quantification (LLOQ) was 0.5ng/mL. The intra- and inter-day precisions were less than 16.3% for low QC level, and 7.1% for other QC levels, respectively. The intra- and inter-day relative errors were ranged between −12.2% and 3.7% for three QC concentration levels. The validated method was successfully applied to the quantification of olprinone concentration in human plasma after intravenous (i.v.) administration of olprinone at a constant rate of infusion of 2μg/(kgmin) for 5min in order to evaluate the pharmacokinetics. [ABSTRACT FROM AUTHOR]

Abstract: Restoration and reconstruction of the degraded Tarim River ecosystem is an important challenge. A goal of an ecological water conveyance project is to protect and restore the natural vegetation in the lower reaches of Tarim River by transferring water from Bosten Lake, through the river channel, to the lower reaches. This study describes the changes in groundwater depth during the water transfer and the respondence of riparian vegetation to alterations in groundwater levels. The results indicate that groundwater depth along the Tarim River channel has a significant spatial-temporal component. Groundwater levels closest to the river channel show the most immediate and pronounced changes as a response to water transfer while those further away respond more slowly, although the observed change appears to be longer in duration. With a rise in the groundwater level, natural vegetation responded with higher growth rates, biomass and biodiversity. These favorable changes show that it is feasible to protect and restore the degraded natural vegetation by raising the groundwater depth. Plant communities are likely to reflect the hysteresis phenomenon, requiring higher water levels to initiate and stimulate desired growth than what may be needed to maintain the plant community. Because different species have different ecologies, including different root depths and densities and water needs, their response to increasing water availability will be spatially and temporally heterogenous. The response of vegetation is also influenced by microtopography and watering style. This paper discusses strategies for the protection and restoration of the degraded vegetation in the lower reaches of the Tarim River and provides information to complement ongoing theoretical research into ecological restoration in arid or semi-arid ecosystems. [Copyright &y& Elsevier]

Four new monoterpene esters, 2α,5β-dihydroxybornane-2-cinnamate (1), 2α,5β-dihydroxybornane-5-acetyl-2-cinnamate (2), 2α,5β-dihydroxybornane-2- p -hydroxycinnamate (3) and 2α,5β-dihydroxy-bornane-2- cis - p -hydroxycinnamate (4), together with a known compound 3,4-dimethoxystyrene (5) were isolated from Chinese liverwort Conocephalum conicum and six known compounds, 5,7-dihydroxycalamenene (6), 7-hydroxycalamenene (7), lunularin (8), riccardin C (9), marchantin C (10) and riccardin D (11) were isolated from Dumortiera hirsuta . Their structures were elucidated by extensive spectral analysis and chemical correlations. Compounds 1 and 8 showed moderate cytotoxicity against human HepG2 cells with IC 50 4.5 μg/ml and 7.4 μg/ml, respectively, while compound 8 also showed antimicrobacterial activity against Pseudomonas aeruginosa with minimum inhibitory concentration at 64 μg/ml. [ABSTRACT FROM AUTHOR]

Effective and complete control of the invasive weed Mikania micrantha is required to avoid increasing damages. We exogenously applied indole 3-acetic acid (IAA), gibberellin (GA), and N -(2-Chloro-4-pyridyl)- N′ -phenylurea (CPPU), and their combinations i.e. IAA + CPPU (IC), GA + CPPU (GC), and GA + IAA + CPPU (GIC), at 5, 10, 25, 50, and 75 ppm against distilled water as a control (CK), to examine their effects on the weed. The increasing concentrations of these hormones when applied alone or in combination were fatal to M. micrantha and led towards the death of inflorescences and/or florets. CPPU and GIC were found as the most effective phytohormones. Transcriptome analysis revealed differential regulation of genes in auxin, cytokinin, gibberellin and abscisic acid signaling pathways, suggesting their role in the prohibition of axillary bud differentiation. Collectively, CPPU and GIC at a high concentration (75 ppm) could be used as a control measure to protect forests and other lands from the invasion of M. micrantha. • Investigation on an environment friendly approach to control Mikania micrantha. • CPPU and GIC (75 ppm) were the most effective phytohormones against Mikania micrantha. • Alterations in phytohormone signaling pathways affect Mikania micrantha reproduction. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the feasibility, safety, and clinical effect of modified unicaval drainage for thoracoscopic reoperative isolated tricuspid valve repair, compared with conventional bicaval drainage. Methods: A total of 45 consecutive cases of patients who underwent thoracoscopic reoperative isolated tricuspid valve repair on beating-heart were enrolled and divided into two groups according to the different venous drainage (Group A: modified unicaval drainage, Group B: conventional bicaval drainage). A retrospective analysis of perioperative data and clinical outcomes were performed and all the surviving cases were followed up. Re-evaluation of echocardiography and electrocardiogram was performed prior to discharge, and at first month, sixth month, and every year follow-up. Results: The overall postoperative 30-day mortality was 4.5% in Group A and 8.7% in Group B. The postoperative tricuspid valve regurgitation grade of both groups decreased significantly from preoperative regurgitation grade, p < 0.001, without intergroup significant difference, p = 0.815. Follow-up duration ranged from 6 to 38 months, there was one death at 24 months in Group A, and another at 9 months in Group B, respectively. Nobody from both groups experienced reintervention for residual tricuspid regurgitation. No significant difference could be identified about the incidence of postoperative morbidities and follow-up adverse events. Conclusion: Both strategies of caval venous drainage can provide satisfactory exposure for thoracoscopic reoperative isolated tricuspid valve repair and equivalent favorable postoperative outcome. And the modified unicaval drainage group may even preserve the anesthetic time and decrease the risk of iatrogenic jugular injury, achieving a more simplified procedure with better cosmetic outcome. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention. [ABSTRACT FROM AUTHOR]

Malignant solid tumors are the leading cause of death in humans, and epigenetic regulation plays a significant role in studying the mechanism of human solid tumors. Recently, histone lysine methylation has been demonstrated to be involved in the development of human solid tumors due to its epigenetic stability and some other advantages. The 90-kb protein methyltransferase nuclear receptor SET domain-containing 2 (NSD2) is a member of nuclear receptor SET domain-containing (NSD) protein lysine methyltransferase (KMT) family, which can cause epigenomic aberrations via altering the methylation states. Studies have shown that NSD2 is frequently over-expressed in multiple types of aggressive solid tumors, including breast cancer, renal cancer, prostate cancer, cervical cancer, and osteosarcoma, and such up-regulation has been linked to poor prognosis and recurrence. Further studies have identified that over-expression of NSD2 promotes cell proliferation, migration, invasion, and epithelial–mesenchymal transformation (EMT), suggesting its potential oncogenic role in solid tumors. Moreover, Gene Expression Profiling Interactive Analysis (GEPIA) was searched for validation of prognostic value of NSD2 in human solid tumors. However, the underlying specific mechanism remains unclear. In our present work, we summarized the latest advances in NSD2 expression and clinical applications in solid tumors, and our findings provided valuable insights into the targeted therapeutic regimens of solid tumors. [ABSTRACT FROM AUTHOR]

Bistachybotrysin K (1), one new phenylspirodrimane dimer with a central 6/7 oxygen heterocycle core, was isolated from the fungus Stachybotrys chartarum CGMCC 3.5365. Its structure was elucidated by extensive spectroscopic data and single-crystal X-ray diffraction. Compound 1 showed significant cytotoxicity against human tumor cell lines HCT116, NCI-H460, BGC823, Daoy, and HepG2 with IC50 values in the range of 1.1–4.7 µM. [ABSTRACT FROM AUTHOR]

Various bioactive polyketides have been found in Aloe barbadensis. However, the polyketide synthases (PKSs), which participate in biosynthesis of polyketides in A. barbadensis remain unknown. In this study, two type III PKSs (AbPKS1 and AbPKS2) were identified from A. barbadensis. AbPKS1 and AbPKS2 were able to utilize malonyl-CoA to yield heptaketides (TW93a and aloesone) and octaketides (SEK4 and SEK4b), respectively. AbPKS1 also exhibited catalytic promiscuity in recognizing CoA thioesters of aromatics to produce unusual polyketides. What Is more, a whole cell biocatalysis system with the capability of producing 26.4 mg/L of SEK4/SEK4b and 2.1 mg/L of aloesone was successfully established. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the molecular mechanisms underlying the roles of metformin (MET) and Sorafenib (SOR) in the treatment of endometrial hyperplasia (EH) in polycystic ovary syndrome (PCOS). Effects of MET and SOR on the area of endometrium and myometrium were detected. Western blot analysis and immunohistochemistry assays were carried out to detect the levels of mammalian target of rapamycin complex 1 (mTORC1), mTORC2, LC3‐II, P62, and Caspase‐3 in rats and cultured cells. Furthermore, cell counting kit‐8 assay and flow cytometry analysis was carried out to determine the apoptotic profiles of treated cells. MET and SOR could apparently decrease the areas of endometrium and myometrium in PCOS. MET notably enhanced the expression of LC3‐II and Caspase‐3 in PCOS while substantially reducing the level of mTORC1 and P62. Similarly, SOR also enhanced the expression of LC3‐II and Caspase‐3 in PCOS while substantially reducing the level of mTORC2 and P62. Treatment with MET and SOR significantly inhibited the proliferation of HCC‐94 and HEC‐1‐A cells while promoting their apoptosis by upregulating the expression of Caspase‐3. In cells treated with MET, the expression of mTORC1 and LC3‐II was upregulated while the expression of P62 was downregulated. Similarly, in cells treated with SOR, the expression of mTORC2 and LC3‐II was also upregulated while the expression of P62 was also downregulated. Furthermore, MET showed no effect on mTORC2 expression, while SOR showed no effect on mTORC1 expression. In this study, we suggested that MET and SOR alleviated the risk of EH in PCOS via the mTORC1/autophagy/apoptosis axis and mTORC2/autophagy/apoptosis axis, respectively. [ABSTRACT FROM AUTHOR]

Three new phenylspirodrimanes derivatives named stachybotrysins H and I (1 and 2) and stachybotrin E (3), together with one known compound stachybotrylactam (4), were isolated from Stachybotrys chartarum CGMCC 3.5365. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Compounds 1 and 2 showed inhibitory effect towards potassium channel Kv1.3 with IC50 values of 13.4 and 10.9 μM, respectively. [ABSTRACT FROM AUTHOR]

Glucuronidation is an important and popular metabolic reaction in vivo of drugs. The further evaluation of biological activity and toxicity of glucuronides is necessary in the course of the drug research and development. However, the synthesis of glucuronides is limited by the lack of efficient approach. Herein, we have developed a new glucuronide synthesis method using plant uridine diphosphate-dependent glucuronosyltransferases (UGTs), UGT88D4, UGT88D7, and EpGT8, enabling the convenient preparation for corresponding O-glucuronide metabolites (1a, 2a, 3a, and 3b) in milligram scale of two neurological active agents, IMM-H004 (1) and FLZ (2). Their structures were characterized by spectroscopic data analyses. [ABSTRACT FROM AUTHOR]

Rapid metastasis contributes significantly to the high mortality rates in lung adenocarcinoma. The present study reports a rare case of primary lung adenocarcinoma with concomitant gastric, duodenal, bone, and mediastinal lymph node metastases. A large gene panel based on the next-generation sequencing was used to detect gene mutations in different metastatic sites and blood. The results showed that the gene mutation spectrums among different metastatic foci were roughly similar. The mutation abundance was highest in mediastinal lymph nodes. Unique mutation sites were detected only in mediastinal lymph nodes, bone, and gastric metastatic foci. Despite partial heterogeneity, there are currently no applicable targeted drugs to adopt. In addition, tumor mutation burden (TMB) showed that blood, gastric, bone, and mediastinal lymph node metastases were all TMB-High, while the duodenal metastasis was TMB-Low. This study is the first to report a rare case of newly diagnosed lung adenocarcinoma with concomitant gastrointestinal metastases and to perform mutation analyses on all metastatic foci. Large sample sizes with similar cases are required to gain deeper insights. [ABSTRACT FROM AUTHOR]

Purpose: Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases. Materials and methods: From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Results: Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30 d after ablation. The mean hospital stay was 3 d (range, 2-7 d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31 months (95% CI: 15.4-46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p = .007, p = .022 and p = .030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p = .017). Conclusion: CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases. [ABSTRACT FROM AUTHOR]