[Effects of family dignity intervention on male infertility patients and their spouses].

OBJECTIVE: To investigate the effects of family dignity intervention (FDI) on anxiety, depression, hope level and quality of life (QOL) of male infertility patients and their spouses. METHODS: Using quasi-experimental design, we selected male infertility patients and their spouses undergoing human-assisted reproductive technology (ART) in our Center of Reproductive Medicine from June to December 2022 and divided them into an intervention group (38 couples) and a control group (40 couples). The former underwent a four-stage FDI, including ovulation promotion cycle assessment, family sharing, pre-transplantation interview and post-transplantation follow-up, while the latter received routine nursing. Using Hospital Anxiety and Depression Scale, Herth Hope Index and Fertility Quality of Life Scale, we evaluated the effects of FDI before and after transplantation. RESULTS: After FDI, the anxiety and depression scores were significantly lower (P < 0.05) and the total scores on the hope level and all other dimensions remarkably higher in the intervention group than in the control (P < 0.05). The self-confidence of the couples in the intervention groups in ART treatment was markedly increased in comparison with that of the controls, and their scores on physical and mental health were significantly higher than those of the latter (P < 0.05). CONCLUSION: FDI can effectively relieve the anxiety and depression, raise the hope level and improve the quality of life of both male infertility patients and their spouses.

{BW12O40} Hybrids Modified by in Situ Synthesized Rigid Ligand with Supercapacitance and Photocatalytic Properties.

Organic rigid ligand-modified polyoxometalate-based materials possess complex and diverse structures, promising electrochemical energy storage properties and outstanding photocatalytic capabilities. Hence, two new [BW12O40]5-(abbreviated as {BW12O40})-based inorganic-organic hybrids [{Cu(en)2(H2O)}][{Cu(pdc)(en)}{Cu(en)2}(BW12O40)]·2H2O (1) and [{CuI5(pz)6(H2O)4}(BW12O40)] (2) (pdc = 2-picolinate, en = ethylenediamine, pz = pyrazine) were successfully synthesized through a hydrothermal method. Among them, pdc and pz were obtained by in situ transformation from 2,6-pyridinedicarboxylic acid (H2 pydc) and 2,3-pyrazinedicarboxylic acid (H2pzdc), respectively. In compound 1, the {BW12O40} clusters as an intermediate junction connect with {Cu(pdc)(en)}{Cu(en)2} and {Cu(en)2(H2O)} to form monomers, which in turn form supramolecular chains, sheets, and space network via hydrogen bonding. The {BW12O40} clusters are packed into copper-pyrazine frameworks in compound 2, and a unique polyoxometalate-based metal organic frameworks (POMOFs) structure with a new topology of {12}2{6.123.142}2{62.12.142.18}{62.123.16}{6}6 is formed via covalent bonds. When used as electrode materials for supercapacitors, the values of specific capacitance are 651.56 F g-1 for 1-GCE and 584.43 F g-1 for 2-GCE at a current density of 2.16 A g-1 and good cycling stability (90.94%, 94.81% of the initial capacity after 5000 cycles at 15.12 A g-1, respectively). The kinetic analysis reveals that surface capacitance plays a major role. Furthermore, both compounds can effectively degrade Rhodamine B (RhB) and Methylene blue (MB), showing the outstanding photocatalytic performance.

Characterization of tropane and cinnamamide alkaloids from Scopolia tangutica by high-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

Scopolia tangutica is a traditional Chinese medicine used for antispasmodic, anesthesia, analgesia, and sedation. Its medicinal activity is associated to alkaloid constituents, including tropane and cinnamamide types. Low content of alkaloids in plant makes them difficult to be isolated and identified. The present work developed an effective method to quickly characterize alkaloids from Scopolia tangutica by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Thirteen reference compounds were studied for their fragmentation pathways, including five tropane alkaloids and eight cinnamamide ones. Alkaloid constituent was analyzed by an optimized high-performance liquid chromatography method and mass spectrometry analysis to achieve systematic characterization of alkaloids from Scopolia tangutica. As a result, 53 compounds were identified, including 21 tropane alkaloids (eight new ones), 18 caffeoyl ones (ten new ones) and 14 dicaffeoyl ones (seven new ones). It was important to provide rich information in phytochemical study and structure-guided isolation of important compounds from this plant.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods: This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results: A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Conclusion: Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

Energy metabolism as the target of 3-phenyllactic acid against Rhizopus oryzae.

3-phenyllactic acid (PLA) has broad anti-fungal activity, however, target sites of PLA on fungal cells and its anti-fungal mechanism of action have been poorly studied. In this study, we explored the inhibition mechanism of Rhizopus oryzae (R. oryzae) on rotten lily bulbs by PLA. The minimum inhibitory concentration value of PLA against R. oryzae was 8 mg/mL. We observed the ultrastructure of R. oryzae by scanning electron microscopy and transmission electron microscopy which indicated that PLA did not damage the cell membrane, but destroyed the mitochondria and other organelles. Tandem mass tag proteomes showed that PLA significantly down-regulated (P < 0.05) the expression of hexokinase (HK), phosphofructokinase (PFK), a-ketoglutarate dehydrogenase (a-KGDH), adenylate kinase (ADK1), Cytochrome C oxidase and NADH dehydrogenase, and up-regulated (P < 0.05) the expression of mitochondrial ADP/ATP carrier proteins (AAC) and subunit IV (CCIO IV) in glycolysis, tricarboxylic acid cycle or oxidative phosphorylation metabolism. Following these findings, down-regulated HK and a-KGDH activity of aforementioned pathways was shown by enzyme activity assay, and regulated gene expression of ADK1, AAC, CCIO IV and NADH dehydrogenase was further confirmed by real-time quantitative PCR. Central carbon metabolomics showed that citric acid, cis-Aconitic acid, isocitric acid, alpha-Ketoglutaric acid, succinate, fumarate and malic acid of the tricarboxylic acid cycle metabolites were significantly down-regulated (P < 0.05), and ATP production by oxidative phosphorylation was also significantly reduced (P = 0.02), resulting in insufficient energy production. Thus, ROS levels increased by 141% of the control values and cytochrome C was released, resulting in gradual cell apoptosis. All data indicated that energy metabolism was the target of PLA against R. oryzae. This was the first study to show that energy metabolism could be the target of PLA against R. oryzae, which could provide a theoretical basis to study the mechanism of fungal inhibition.

Water extract of Cayratia albifolia C.L.Li root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization.

BACKGROUND: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)-induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous. PURPOSE: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms. METHODS: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-1ß, IL-6, TNF-α and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-κB transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS. RESULTS: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-1ß, IL-6 and TNF-α rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-1ß, IL-6 and TNF-α, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-κB transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4-guanidinobutyric acid and kynurenic acid were the most abundant. CONCLUSION: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components.

Small molecular compounds that inhibit hepatitis C virus replication through destabilizing heat shock cognate 70 messenger RNA.

UNLABELLED: Host heat shock cognate 70 (Hsc70) protein is packaged into hepatitis C viral (HCV) particles as a structural component of the virus in the assembly process. It helps HCV RNA release into the cytoplasm in the next infection cycle. The goal of this study is to investigate whether chemically down-regulating host Hsc70 expression could be a novel strategy to interrupt HCV replication. Compounds were screened with an Hsc70 messenger RNA (mRNA) assay. IMB-DM122 was found to be an effective and safe inhibitor for Hsc70 mRNA/protein expression in human hepatocytes. IMB-DM122 inhibited HCV replication through destabilization of Hsc70 mRNA, and the half-life of host Hsc70 mRNA was reduced by 78% after the compound treatment. The Hsc70 mRNA 3' untranslated region sequence is the element responsible for the effect of IMB-DM122 on Hsc70 mRNA. The compound appears to be highly efficient in inhibiting Hsc70-related HCV replication. Treatment of the HCV-infected hepatocytes with IMB-DM122 reduced the virion encapsidation of Hsc70, and therefore disrupted HCV replication and the infection cycle. IMB-DM122 showed considerable good safety in vitro as well as in vivo with no indication of harmful effect on liver and kidney functions. CONCLUSION: Hsc70 might be a new drug target and mechanism to inhibit HCV proliferation.

Synthesis and in vitro antitubercular evaluation of novel sansanmycin derivatives.

Tuberculosis (TB) is a major health problem worldwide. A series of novel sansanmycin derivatives were designed, semi-synthesized and evaluated for their activity against drug-susceptible Mycobacterium tuberculosis strain H(37)Rv with sansanmycin A (SSA) as the lead. Among these analogs tested, compound 1d possessing an isopropyl group at the amino terminal afforded an increased antimycobacterial activity with a MIC value of 8 µg/mL in comparison with SSA. Importantly, it was active for rifampicin- and isoniazid-resistant M. tuberculosis strain isolated from patients in China. These promising results offer an opportunity for further exploration of this novel class of analogs as antitubercular agents.

Synthesis, structure-activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators.

Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate.

Synthesis, structure-activity relationship and biological evaluation of anticancer activity for novel N-substituted sophoridinic acid derivatives.

Sophoridine (1), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1. We consider 6b promising for further anticancer investigation.

N-(2,4-Dinitro-phen-yl)-1,3-dimeth-oxy-isoindolin-2-amine.

In the title compound, C(16)H(16)N(4)O(6), the planes of the isoindole and dinitro-benzene groups make a dihedral angle between of 84.15 (8)°. The N atom of the isoindole group is displaced by 0.2937 (3) Šfrom the plane through the remaining atoms. An intra-molecular N-H⋯O inter-action occurs. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur.

(E)-3-[(2-Hy-droxy-naphthalen-1-yl)methyl-idene-amino]-5-(morpholin-4-yl-meth-yl)-1,3-oxazolidin-2-one.

The title compound, C(19)H(21)N(3)O(4), crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, there is an intra-molecular O-H⋯N hydrogen bond, which correlates with the fact that each mol-ecule adopts an E configuration with respect to the C=N bond. In the crystal, there are C-H⋯O and C-H⋯π inter-actions present.

Methyl 3-[(E)-(2-hy-droxy-1-naphth-yl)methyl-idene]carbazate.

The title compound, C(13)H(12)N(2)O(3), has an E configuration with respect to the C=N bond: the conformation is stabilized by an intramolecular O-H⋯N hydrogen bond. In the crystal, an N-H⋯O interaction links the molecules into a C(4) chain along [100].

(E)-1-[(2-Hy-droxy-1-naphth-yl)methyl-idene-amino]-imidazolidine-2,4-dione.

The title compound, C(14)H(11)N(3)O(3), adopts an E or trans configuration with respect to the C=N bond. In the mol-ecule there is an intra-molecular O-H⋯N hydrogen bond involving the hy-droxy substituent at the 2-positon of the naphthalene ring and the adjacent methyl-ene-amino N atom. The mol-ecule is roughly planar, the dihedral angle between the naphthalene and imidazolidine-2,4-dione mean planes being 8.4 (1)°. In the crystal, pairs of N-H⋯O hydrogen bonds link mol-ecules into inversion dimers. These dimers are futher linked via C-H⋯O inter-actions, forming a three-dimensional network.

Scocycamides, a Pair of Macrocyclic Dicaffeoylspermidines with Butyrylcholinesterase Inhibition and Antioxidation Activity from the Roots of Scopolia tangutica.

A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.

Synthesis and activity evaluation of benzoylurea derivatives as potential antiproliferative agents.

3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands that kill cancer cells through mitotic arrest. In exploring the structure-activity relationship (SAR), 17 analogues defined through variations of formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis revealed that (i) the p-pi conjugation between the aromatic ring and formylurea was essential; (ii) suitable aryl substitutions at the N'-end increased anticancer activity with a mechanism different from that of parent compounds; and (iii) introduction of pyridyl at the N'-end provided an opportunity of making soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5-trimethoxyphenyl and 16g bearing 2-pyridyl at the N'-end showed an enhanced activity and were active in hepatoma cells that were resistant to tubulin ligands including the parent compounds. Furthermore, 16c and 16g killed cancer cells with a mechanism independent of mitotic arrest, indicating a change of action mode.

Synthesis and activity evaluation of phenylurea derivatives as potent antitumor agents.

We have discovered several tubulin-active compounds in our previous studies. In the establishment of a compound library of small molecule weight tubulin ligands, 14 new N-3-haloacylaminophenyl-N'-(alkyl/aryl) urea analogs were designed and synthesized. The structure-activity relationship (SAR) analysis revealed that (i) the order of anticancer potency for the 3-haloacylamino chain was following -CH(2)Br>-CHBrCH(3); (ii) the N'-substituent moiety was not essential for the anticancer activity, and a proper alkyl substitution might enhance the anticancer activity. Among these analogs, the compounds 16j bearing bromoacetyl at the N'-end exhibited a potent activity against eight human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), DND-1A (melanoma), LOVO (colon cancer) and MIA Paca (pancreatic cancer), with the IC(50) values between 0.38 and 4.07 microM. Interestingly, compound 16j killed cancer cells with a mechanism independent of the tubulin-based mechanism, indicating a significant change of the action mode after the structure modification.

(E)-2-Hydroxy-naphthalene-1-carb-al-de-hyde semicarbazone.

The title compound, C(12)H(11)N(3)O(2), adopts an E or trans configuration with respect to the C=N bond. There is an intra-molecular O-H⋯N hydrogen bond involving the hydroxyl H atom and an N atom of the hydrazine group. In the crystal structure, mol-ecules are connected via N-H⋯O hydrogen bonds, forming a three-dimensional network.

Strong electrostatic repulsive interaction used for fast and effective alkaloid enrichment from plants.

Since the content of alkaloids is usually low in plants and they are easily co-eluted with other constituents, enrichment of alkaloids is essential in the discovery of bioactive lead compounds from natural products. In this paper, an easy SPE enrichment method was developed in a buffer-free solvent system based on electrostatic repulsion mechanism. The feasibility of the new method was verified by successful enrichment of alkaloids from Scopolia tangutica (S. tangutica) with an optimized eluting condition. Then this developed method was applied to other representative plants in different families, including Przewalskia tangutica and Peganum harmala L, Lycoris radiata and Menispermum dauricum DC, which enlarged the scope of applicability. Additionally, the new SPE procedure avoided possible structural change destruction caused by pH change. Simple solvent system, including formic acid (FA) and methanol, would benefit subsequent mass analysis, quantity determination and bioactivity screening, and so on.

Benzoylurea derivatives as a novel class of antimitotic agents: synthesis, anticancer activity, and structure-activity relationships.

Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC 50 values between 0.01 and 0.30 microM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.